Search results for: squamous intraepithelial lesion

Authors: Ahmed Gonnah, Omar Masoud, Mohamed Abdel-Wahab, Ahmed ElMosalamy, Abdulrahman Al-Naseem

Abstract:

Introduction: Fibroadenomas are solid, mobile, and non-tender benign breast lumps, with the highest prevalence amongst young women aged between 15 and 35. Symptoms can include discomfort, and they can become problematic, particularly when they enlarge, resulting in many referrals for biopsies, with fibroadenomas accounting for 30-75% of the cases. Diagnosis is based on triple assessment that involves a clinical examination, ultrasound imaging and mammography, as well as core needle biopsies. Current management includes observation for 6-12 months, with the indication of definitive surgery, in cases that are older than 35 years or with fibroadenoma persistence. Serious adverse effects of surgery might include nipple-areolar distortion, scarring and damage to the breast tissue, as well as the risks associated with surgery and anesthesia, making it a non-feasible option. Methods: A literature search was performed on the databases EMBASE. MEDLINE/PubMed, Google scholar and Ovid, for English language papers published between 1st of January 2000 and 17th of March 2021. A structured protocol was employed to devise a comprehensive search strategy with keywords and Boolean operators defined by the research question. The keywords used for the search were ‘HIFU’, ‘High-Intensity Focused Ultrasound’, ‘Fibroadenoma’, ‘Breast’, ‘Lesion’. This review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Recently, a thermal ablative technique, High Intensity Focused Ultrasound (HIFU), was found to be a safe, non-invasive, and technically successful alternative, having displayed promising outcomes in reducing the volume of fibroadenomas, pain experienced by patients, and the length of hospitalization. Quality of life improvement was also evidenced, exhibited by the disappearance of symptoms, and enhanced physical activity post-intervention, in addition to patients’ satisfaction with the cosmetic results and future recommendation of the procedure to other patients. Conclusion: Overall, HIFU is a well-tolerated treatment associated with a low risk of complications that can potentially include erythema, skin discoloration and bruising, with the majority of this self-resolving shortly after the procedure.

Keywords: ultrasound, HIFU, breast, efficacy, side effects, fibroadenoma

Procedia PDF Downloads 183

Authors: Anjali Roy, Mirza S. Baig

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Atherosclerosis is a chronic inflammatory disease characterized by the formation of lipid rich plaque enriched with necrotic core, modified lipid accumulation, smooth muscle cells, endothelial cells, leucocytes and macrophages. Macrophage foam cells play a critical role in the occurrence and development of inflammatory atherosclerotic plaque. Foam cells are the fat-laden macrophages in the initial stage atherosclerotic lesion formation. Foam cells are an indication of plaque build-up, or atherosclerosis, which is commonly associated with increased risk of heart attack and stroke as a result of arterial narrowing and hardening. The mechanisms that drive atherosclerotic plaque progression remain largely unknown. Dissecting the molecular mechanism involved in process of macrophage foam cell formation will help to develop therapeutic interventions for atherosclerosis. To investigate the mechanism, we studied the role of nitric oxide synthase 1(NOS1)-mediated nitric oxide (NO) on low-density lipoprotein (LDL) uptake by bone marrow derived macrophages (BMDM). Using confocal microscopy, we found that incubation of macrophages with NOS1 inhibitor, TRIM (1-(2-Trifluoromethylphenyl) imidazole) or L-NAME (N omega-nitro-L-arginine methyl ester) prior to LDL treatment significantly reduces the LDL uptake by BMDM. Further, addition of NO donor (DEA NONOate) in NOS1 inhibitor treated macrophages recovers the LDL uptake. Our data strongly suggest that NOS1 derived NO regulates LDL uptake by macrophages and foam cell formation. Moreover, we also checked proinflammatory cytokine mRNA expression through real time PCR in BMDM treated with LDL and copper oxidized LDL (OxLDL) in presences and absences of inhibitor. Normal LDL does not evoke cytokine expression whereas OxLDL induced proinflammatory cytokine expression which significantly reduced in presences of NOS1 inhibitor. Rapid NOS-1-derived NO and its stable derivative formation act as signaling agents for inducible NOS-2 expression in endothelial cells, leading to endothelial vascular wall lining disruption and dysfunctioning. This study highlights the role of NOS1 as critical players of foam cell formation and would reveal much about the key molecular proteins involved in atherosclerosis. Thus, targeting NOS1 would be a useful strategy in reducing LDL uptake by macrophages at early stage of disease and hence dampening the atherosclerosis progression.

Keywords: atherosclerosis, NOS1, inflammation, oxidized LDL

Procedia PDF Downloads 96

Authors: Grace C. Kuroki, Yixin Hu, Bailey Surtees, Rebecca Krimins, Nicholas J. Durr, Dara L. Kraitchman

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The purpose of this study was to perform a Phase I veterinary clinical trial with a low-cost, carbon-dioxide-based, passive thaw cryoablation device as proof-of-principle for application in pets and translation to third-world treatment of breast cancer. This study was approved by the institutional animal care and use committee. Client-owned dogs with subcutaneous masses, primarily lipomas or mammary cancers, were recruited for the study. Inclusion was based on clinical history, lesion location, preanesthetic blood work, and fine needle aspirate or biopsy confirmation of mass. Informed consent was obtained from the owners for dogs that met inclusion criteria. Ultrasound assessment of mass extent was performed immediately prior to mass cryoablation. Dogs were placed under general anesthesia and sterilely prepared. A stab incision was created to insert a custom 4.19 OD x 55.9 mm length cryoablation probe (Kubanda Cryotherapy) into the mass. Originally designed for treating breast cancer in low resource settings, this device has demonstrated potential in effectively necrosing subcutaneous masses. A dose escalation study of increasing freeze-thaw cycles (5/4/5, 7/5/7, and 10/7/10 min) was performed to assess the size of the iceball/necrotic extent of cryoablation. Each dog was allowed to recover for ~1-2 weeks before surgical removal of the mass. A single mass was treated in seven dogs (2 mammary masses, a sarcoma, 4 lipomas, and 1 adnexal mass) with most masses exceeding 2 cm in any dimension. Mass involution was most evident in the malignant mammary and adnexal mass. Lipomas showed minimal shrinkage prior to surgical removal, but an area of necrosis was evident along the cryoablation probe path. Gross assessment indicated a clear margin of cryoablation along the cryoprobe independent of tumor type. Detailed histopathology is pending, but complete involution of large lipomas appeared to be unlikely with a 10/7/10 protocol. The low-cost, carbon dioxide-based cryotherapy device permits a minimally invasive technique that may be useful for veterinary applications but is also informative of the unlikely resolution of benign adipose breast masses that may be encountered in third world countries.

Keywords: cryoablation, cryotherapy, interventional oncology, veterinary technology

Procedia PDF Downloads 101

Authors: Hernando Santamaría-García, Sandra Báez, Pablo Reyes, José Santamaría-García, Diana Matallana, Adolfo García, Agustín Ibañez

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The study of moral emotions (i.e., Schadenfreude and envy) is critical to understand the ecological complexity of everyday interactions between cognitive, affective, and social cognition processes. Most previous studies in this area have used correlational imaging techniques and framed Schadenfreude and envy as monolithic domains. Here, we profit from a relevant neurodegeneration model to disentangle the brain regions engaged in three dimensions of Schadenfreude and envy: deservingness, morality, and legality. We tested 20 patients with behavioral variant frontotemporal dementia (bvFTD), 24 patients with Alzheimer’s disease (AD), as a contrastive neurodegeneration model, and 20 healthy controls on a novel task highlighting each of these dimensions in scenarios eliciting Schadenfreude and envy. Compared with the AD and control groups, bvFTD patients obtained significantly higher scores on all dimensions for both emotions. Interestingly, the legal dimension for both envy and Schadenfreude elicited higher emotional scores than the deservingness and moral dimensions. Furthermore, correlational analyses in bvFTD showed that higher envy and Schadenfreude scores were associated with greater deficits in social cognition, inhibitory control, and behavior. Brain anatomy findings (restricted to bvFTD and controls) confirmed differences in how these groups process each dimension. Schadenfreude was associated with the ventral striatum in all subjects. Also, in bvFTD patients, increased Schadenfreude across dimensions was negatively correlated with regions supporting social-value rewards, mentalizing, and social cognition (frontal pole, temporal pole, angular gyrus and precuneus). In all subjects, all dimensions of envy positively correlated with the volume of the anterior cingulate cortex, a region involved in processing unfair social comparisons. By contrast, in bvFTD patients, the intensified experience of envy across all dimensions was negatively correlated with a set of areas subserving social cognition, including the prefrontal cortex, the parahippocampus, and the amygdala. Together, the present results provide the first lesion-based evidence for the multidimensional nature of the emotional experiences of envy and Schadenfreude. Moreover, this is the first demonstration of a selective exacerbation of envy and Schadenfreude in bvFTD patients, probably triggered by atrophy to social cognition networks. Our results offer new insights into the mechanisms subserving complex emotions and moral cognition in neurodegeneration, paving the way for groundbreaking research on their interaction with other cognitive, social, and emotional processes.

Keywords: social cognition, moral emotions, neuroimaging, frontotemporal dementia

Procedia PDF Downloads 246

Authors: Mei Chen, Yingping Hou, Michelle Hao, Soheil Aghamohammadzadeh, Esteban Terzo, Roger Clark, Vijay Modur

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Background: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genetic skin condition characterized by skin tearing and unremitting blistering upon minimal trauma. Repeated blistering, fibrosis, and scarring lead to aggressive squamous cell carcinoma later in life. RDEB is caused by mutations in the COL7A1 gene encoding collagen type VII (C7), the major component of anchoring fibrils mediating epidermis-dermis adherence. Nonsense mutations in the COL7A1 gene of a subset of RDEB patients leads to premature termination codons (PTC). Similarly, most Junctional Epidermolysis Bullosa (JEB) cases are caused by nonsense mutations in the LAMB3 gene encoding the β3 subunit of laminin 332. Currently, there is an unmet need for the treatment of RDEB and JEB. Zikani Therapeutics has discovered an array of macrocyclic compounds with ring structures similar to macrolide antibiotics that can facilitate readthrough activity of nonsense mutations in the COL7A1 and LAMB3 genes by acting as Ribosome Modulating Agents (RMAs). The medicinal chemistry synthetic advancements of these macrocyclic compounds have allowed targeting the human ribosome while preserving the structural elements responsible for the safety and pharmacokinetic profile of clinically used macrolide antibiotics. Methods: C7 expression was used as a measure of readthrough activity by immunoblot assays in two primary human fibroblasts from RDEB patients (R578X/R578X and R163X/R1683X-COL7A1). Similarly, immunoblot assays in C325X/c.629-12T > A-LAMB3 keratinocytes were used to measure readthrough activity for JEB. The relative readthrough activity of each compound was measured relative to Gentamicin. An imaging-based fibroblast migration assay was used as an assessment of C7 functionality in RDEB-fibroblasts over 16-20 hrs. The incubation period for the above experiments was 48 hrs for RDEB fibroblasts and 72 hours for JEB keratinocytes. Results: 9 RMAs demonstrated increased protein expression in both patient RDEB fibroblasts. The highest readthrough activity at tested concentrations without cytotoxicities increased protein expression up to 179% of Gentamicin (400 µg/ml), with favored readthrough activity in R163X/R1683X-COL7A1 fibroblasts. Concurrent with protein expression, fibroblast hypermotility phenotype observed in RDEB was rescued by reducing motility by ~35% to WT levels (the same level as 690 µM Gentamicin treated cells). Laminin β3 expression was also shown to be increased by 6 RMAs in keratinocytes to 33-83% of (400 µg/ml) Gentamicin. Conclusions: To date, 9 RMAs have been identified that enhance the expression of functional C7 in a mutation-dependent manner in two different RDEB patient fibroblast backgrounds (R578X/R578X and R163X/R1683X-COL7A1). A further 6 RMAs have been identified that enhance the readthrough of C325X-LAMB3 in JEB patient keratinocytes. Based on the clinical trial conducted by us with topical gentamycin in 2017, Zikani’s RMAs achieve clinically significant levels of read-through for the treatment of recessive dystrophic and Junctional Epidermolysis Bullosa.

Keywords: epidermolysis bullosa, nonsense mutation, readthrough, ribosome modulation

Procedia PDF Downloads 76

Authors: Palak V. Patel, Jessica Pixley, Steven R. Feldman

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Introduction: Basal cell carcinoma (BCC) is the most common skin cancer worldwide and requires substantial resources to treat. When choosing between indicated therapies, providers consider their associated adverse effects, efficacy, cosmesis, and function preservation. The patient’s tumor burden, infiltrative risk, and risk of tumor recurrence are also considered. Treatment cost is often left out of these discussions. This can lead to financial toxicity, which describes the harm and quality of life reductions inflicted by high care costs. Methods: We studied the guidelines set forth by the American Academy of Dermatology for the treatment of BCC. A PubMed literature search was conducted to identify the costs of each recommended therapy. We discuss costs alongside treatment efficacy and side-effect profile. Results: Surgical treatment for BCC can be cost-effective if the appropriate treatment is selected for the presenting tumor. Curettage and electrodesiccation can be used in low-grade, low-recurrence tumors in aesthetically unimportant areas. The benefits of cost-conscious care are not likely to be outweighed by the risks of poor cosmesis or tumor return ($471 BCC of the cheek). When tumor burden is limited, MMS offers better cure rates and lower recurrence rates than surgical excision, and with comparable costs (MMS $1263; SE $949). Surgical excision with permanent sections may be indicated when tumor burden is more extensive or if molecular testing is necessary. The utility of surgical excision with frozen sections, which costs substantially more than MMS without comparable outcomes, is less clear (SE with frozen sections $2334-$3085). Less data exists on non-surgical treatments for BCC. These techniques cost less, but recurrence-risk is high. Side-effects of nonsurgical treatment are limited to local skin reactions, and cosmesis is good. Cryotherapy, 5-FU, and MAL-PDT are all more affordable than surgery, but high recurrence rates increase risk of secondary financial and psychosocial burden (recurrence rates 21-39%; cost $100-270). Radiation therapy offers better clearance rates than other nonsurgical treatments but is associated with similar recurrence rates and a significantly larger financial burden ($2591-$3460 BCC of the cheek). Treatments for advanced or metastatic BCC are extremely costly, but few patients require their use, and the societal cost burden remains low. Vismodegib and sonidegib have good response rates but substantial side effects, and therapy should be combined with multidisciplinary care and palliative measures. Expert-review has found sonidegib to be the less expensive and more efficacious option (vismodegib $128,358; sonidegib $122,579). Platinum therapy, while not FDA-approved, is also effective but expensive (~91,435). Immunotherapy offers a new line of treatment in patients intolerant of hedgehog inhibitors ($683,061). Conclusion: Dermatologists working within resource-compressed practices and with resource-limited patients must prudently manage the healthcare dollar. Surgical therapies for BCC offer the lowest risk of recurrence at the most reasonable cost. Non-surgical therapies are more affordable, but high recurrence rates increase the risk of secondary financial and psychosocial burdens. Treatments for advanced BCC are incredibly costly, but the low incidence means the overall cost to the system is low.

Keywords: nonmelanoma skin cancer, basal cell skin cancer, squamous cell skin cancer, cost of care

Procedia PDF Downloads 83

Authors: Katie Dolaghan, Christina Tran, Kim Hamilton, Amanda Beresford, Vicky Adams, Jamie Toole, John Marley

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During the Covid 19 pandemic routine outpatient appointments were not possible face to face. That resulted in many branches of healthcare starting virtual clinics. These clinics have continued following the return to face to face patient appointments. With these new types of clinic it is important to ensure that a high standard of patient care is maintained. In order to improve patient and clinician experience of the telephone clinics a quality improvement project was carried out to ensure the patient and clinician experience of these clinics was enhanced whilst remaining a safe, effective and an efficient use of resources. The project began by developing a process map for the consultation process and agreed on the design of a driver diagram and tests of change. In plan do study act (PDSA) cycle1 a single consultant completed an online survey after every patient encounter over a 5 week period. Baseline patient responses were collected using a follow-up telephone survey for each patient. Piloting led to several iterations of both survey designs. Salient results of PDSA1 included; patients not receiving appointment letters, patients feeling more anxious about a virtual appointment and many would prefer a face to face appointment. The initial clinician data showed a positive response with a provisional diagnosis being reached in 96.4% of encounters. PDSA cycle 2 included provision of a patient information sheet and information leaflets relevant to the patients’ conditions were developed and sent following new patient telephone clinics with follow-up survey analysis as before to monitor for signals of change. We also introduced the ability for patients to send an images of their lesion prior to the consultation. Following the changes implemented we noted an improvement in patient satisfaction and, in fact, many patients preferring virtual clinics as it lead to less disruption of their working lives. The extra reading material both before and after the appointments eased patients’ anxiety around virtual clinics and helped them to prepare for their appointment. Following the patient feedback virtual clinics are now used for review patients as well, with all four consultants within the department continuing to utilise virtual clinics. During this presentation the progression of these clinics and the reasons that these clinics are still operating following the return to face to face appointments will be explored. The lessons that have been gained using a QI approach have helped to deliver an optimal service that is valid and reliable as well as being safe, effective and efficient for the patient along with helping reduce the pressures from ever increasing waiting lists. In summary our work in improving the quality of virtual clinics has resulted in improved patient satisfaction along with reduced pressures on the facilities of the health trust.

Keywords: clinic, satisfaction, telephone, virtual

Procedia PDF Downloads 37

Authors: E. Locatelli, I. Monaco, R. C. Martin, Y. Li, R. Pini, M. Chiariello, M. Comes Franchini

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Despite the many advantages of application of nanomaterials in the field of nanomedicine, increasing concerns have been expressed on their potential adverse effects on human health. There is urgency for novel green strategies toward novel materials with enhanced biocompatibility using safe reagents. Photothermal ablation therapy, which exploits localized heat increase of a few degrees to kill cancer cells, has appeared recently as a non-invasive and highly efficient therapy against various cancer types; anyway new agents able to generate hyperthermia when irradiated are needed and must have precise biocompatibility in order to avoid damage to healthy tissues and prevent toxicity. Recently, there has been increasing interest in magnesium as a biomaterial: it is the fourth most abundant cation in the human body, and it is essential for human metabolism. However magnesium nanoparticles (Mg NPs) have had limited diffusion due to the high reduction potential of magnesium cations, which makes NPs synthesis challenging. Herein, we report the synthesis of Mg NPs and their surface functionalization for the obtainment of a stable and biocompatible nanomaterial suitable for photothermal ablation therapy against cancer. We synthesized the Mg crystals by reducing MgCl2 with metallic lithium and exploiting naphthalene as an electron carrier: the lithium–naphthalene complex acts as the real reducing agent. Firstly, the nanocrystal particles were coated with the ligand 12-ethoxy ester dodecanehydroxamic acid, and then entrapped into water-dispersible polymeric micelles (PMs) made of the FDA-approved PLGA-b-PEG-COOH copolymer using the oil-in-water emulsion technique. Lately, we developed a more straightforward methodology by introducing chitosan, a highly biocompatible natural product, at the beginning of the process, simultaneously using lithium–naphthalene complex, thus having a one-pot procedure for the formation and surface modification of MgNPs. The obtained MgNPs were purified and fully characterized, showing diameters in the range of 50-300 nm. Notably, when coated with chitosan the particles remained stable as dry powder for more than 10 months. We proved the possibility of generating a temperature rise of a few to several degrees once MgNPs were illuminated using a 810 nm diode laser operating in continuous wave mode: the temperature rise resulted significant (0-15 °C) and concentration dependent. We then investigated potential cytotoxicity of the MgNPs: we used HN13 epithelial cells, derived from a head and neck squamous cell carcinoma and the hepa1-6 cell line, derived from hepatocellular carcinoma and very low toxicity was observed for both nanosystems. Finally, in vivo photothermal therapy was performed on xenograft hepa1-6 tumor bearing mice: the animals were treated with MgNPs coated with chitosan and showed no sign of suffering after the injection. After 12 hours the tumor was exposed to near-infrared laser light. The results clearly showed an extensive damage to tumor tissue after only 2 minutes of laser irradiation at 3Wcm-1, while no damage was reported when the tumor was treated with the laser and saline alone in control group. Despite the lower photothermal efficiency of Mg with respect to Au NPs, we consider MgNPs a promising, safe and green candidate for future clinical translations.

Keywords: chitosan, magnesium nanoparticles, nanomedicine, photothermal therapy

Procedia PDF Downloads 242

Authors: Kakali Roy, Sahana P. Raju, Subhra Dhar, Sandipan Dhar

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Introduction: Xeroderma pigmentosa (XP) is a rare inherited (autosomal recessive) disease resulting from impairment in DNA repair that involves recognition and repair of ultraviolet radiation (UVR) induced DNA damage in the nucleotide excision repair pathway. Which results in increased photosensitivity, UVR induced damage to skin and eye, increased susceptibility of skin and ocular cancer, and progressive neurodegeneration in some patients. XP is present worldwide, with higher incidence in areas having frequent consanguinity. Being extremely rare, there is limited literature on XP and associated complications. Here, the clinico-pathological experience (spectrum of clinical presentation, histopathological findings of malignant skin lesions, and progression) of managing 8 cases of XP is presented. Methodology: A retrospective study was conducted in a pediatric tertiary care hospital in eastern India during a ten-year period from 2013 to 2022. A clinical diagnosis was made based on severe sun burn or premature photo-aging and/or onset of cutaneous malignancies at early age (1st decade) in background of consanguinity and autosomal recessive inheritance pattern in family. Results: The mean age of presentation was 1.2 years (range of 7month-3years), while three children presented during their infancy. Male to female ratio was 5:3, and all were born of consanguineous marriage. They presented with dermatological manifestations (100%) followed by ophthalmic (75%) and/or neurological symptoms (25%). Patients had normal skin at birth but soon developed extreme sensitivity to UVR in the form of exaggerated sun tanning, burning, and blistering on minimal sun exposure, followed by abnormal skin pigmentation like freckles and lentiginosis. Subsequently, over time there was progressive xerosis, atrophy, wrinkling, and poikiloderma. Six patients had varied degree of ocular involvement, while three of them had severe manifestation, including madarosis, tylosis, ectropion, Lagopthalmos, Pthysis bulbi, clouding and scarring of the cornea with complete or partial loss of vision, and ophthalmic malignancies. 50% (n=4) cases had skin and ocular pre-malignant (actinic keratosis) and malignant lesions, including melanoma and non melanoma skin cancer (NMSC) like squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in their early childhood. One patient had simultaneous occurrence of multiple malignancies together (SCC, BCC, and melanoma). Subnormal intelligence was noticed as neurological feature, and none had sensory neural hearing loss, microcephaly, neuroregression, or neurdeficit. All the patients had been being managed by a multidisciplinary team of pediatricians, dermatologists, ophthalmologists, neurologists and psychiatrists. Conclusion: Although till date there is no complete cure for XP and the disease is ultimately fatal. But increased awareness, early diagnosis followed by persistent vigorous protection from UVR, and regular screening for early detection of malignancies along with psychological support can drastically improve patients’ quality of life and life expectancy. Further research is required on formulating optimal management of XP, specifically the role and possibilities of gene therapy in XP.

Keywords: childhood malignancies, dermato-pathological findings, eastern India, Xeroderma pigmentosa

Procedia PDF Downloads 48

Authors: Shiva Naidoo, Kristena Yossef, Grimm Jimm, Mirza Wasique, Eric Kemmerer, Joshua Obuch, Anand Mahadevan

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Background: Fiducial markers effectively enhance tumor target visibility prior to Stereotactic Body Radiation Therapy or Proton therapy. To streamline clinical practice, fiducial placement guidelines from a robotic radiosurgery vendor were examined with the goals of optimizing and standardizing feasible geometries for each treatment indication. Clinical examples of prostate, renal, and pancreatic cases are presented. Methods: Vendor guidelines (Accuray, Sunnyvale, Ca) suggest implantation of 4–6 fiducials at least 20 mm apart, with at least a 15-degree angular difference between fiducials, within 50 mm or less from the target centroid, to ensure that any potential fiducial motion (e.g., from respiration or abdominal/pelvic pressures) will mimic target motion. Also recommended is that all fiducials can be seen in 45-degree oblique views with no overlap to coincide with the robotic radiosurgery imaging planes. For the prostate, a standardized geometry that meets all these objectives is a 2 cm-by-2 cm square in the coronal plane. The transperineal implant of two pairs of preloaded tandem fiducials makes the 2 cm-by-2 cm square geometry clinically feasible. This technique may be applied for renal cancer, except repositioned in a sagittal plane, with the retroperitoneal placement of the fiducials into the tumor. Pancreatic fiducial placement via endoscopic ultrasound (EUS) is technically more challenging, as fiducial placement is operator-dependent, and lesion access may be limited by adjacent vasculature, tumor location, or restricted mobility of the EUS probe in the duodenum. Fluoroscopically assisted fiducial placement during EUS can help ensure fiducial markers are deployed with optimal geometry and visualization. Results: Among the first 22 fiducial cases on a newly installed robotic radiosurgery system, live x-ray images for all nine prostatic cases had excellent fiducial visualization at the treatment console. Renal and pancreatic fiducials were not as clearly visible due to difficult target access and smaller caliber insertion needle/fiducial usage. The geometry of the first prostate case was used to ensure accurate geometric marker placement for the remaining 8 cases. Initially, some of the renal and pancreatic fiducials were closer than the 20 mm recommendation, and interactive feedback with the proceduralists led to subsequent fiducials being too far to the edge of the tumor. Further feedback and discussion of all cases are being used to help guide standardized geometries and achieve ideal fiducial placement. Conclusion: The ideal tradeoffs of fiducial visibility versus the thinnest possible gauge needle to avoid complications needs to be systematically optimized among all patients, particularly in regards to body habitus. Multidisciplinary collaboration among proceduralists and radiation oncologists can lead to improved outcomes.

Keywords: fiducial, prostate cancer, renal cancer, pancreatic cancer, radiotherapy

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Authors: Jaspinder Kaur, Jatinder Pal Singh

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Introduction- Delusional parasitosis is a rare psychotic illness characterized by a fixed belief of manifesting a parasite in a body when in reality, it was not. Also known as Ekbom syndrome or delusional infestations, or acarophobia. Although the patient has no primary skin pathology, but all skin findings were secondary to skin manipulation by the patient itself, which is why up to 90% of patients first seek consultation from a dermatologist. Most commonly, it was seen in older people with female to male ratio is 2:1. For treatment, the patient first need to be investigated to rule all other possible causes, as Delusional parasitosis can be caused by Vitamin B12 deficiency, pellagra, hepatic and renal disease, diabetes mellitus, multiple sclerosis, and leprosy. When all possible causes ruled out, psychiatric referral to be done. Rule out other psychiatric comorbidities, and treatment should be done accordingly. Patient with delusional parasitosis responds well to second generation antipsychotics and need to continuous medication over years, and relapse is likely if treatment is stopped. Case Presentation- A 79-year-old female, belonging to lower socio-economic status, presented with complaints of itching sensation with erythematous patches over the scalp and multiple scratch excoriations lesion over the scalp, face and neck from the past 7-8 months. She had a feeling of small insect crawling under her skin and scalp area. To reduce the itching and kill the insect, she would scratch and squeeze her skin repeatedly. When the family tried to give her explanation that there was no insect in her body, she would not get convinced, rather got angry and abuse family members for not believing her. Gradually, her sleep would remain disturbed, she would be seen awake at night, seen to be scratching her skin, pull her scalp hair, even squeeze out her healed lesions. She collected her skin debris, scalp hairs and look out for insect. Because of her continuous illness, the patient started to remain sad and had crying spells. Her appetite decreased. She became socially isolated and stopped doing her activities of daily living. Family member’s first consulted dermatologist, investigated thoroughly with routine investigations, autoimmune and malignancy workup. As all investigations were normal, following which patient was referred for psychiatric evaluation. The patient was started on Tablet Olanzapine 2.5 mg, gradually increased to 7.5 mg. Over 1 month, there was reduction in itching, skin pricking. Lesions were gradually healed, and the patient continued to take other dermatological medications and ointment and was in regular follow up with psychiatric liaison from past 2 months with 70-80 % improvement in her symptoms. Conclusion- Delusional parasitosis is a psychiatric disorder of insidious onset, seen commonly in middle and old age people. Both psychiatric and dermatology consultation liaison will help the patient for an early diagnosis and adequate treatment. If a primary psychiatric diagnosis, the patient respond well to second generation antipsychotics but always require a further evaluation and treatment management if it is secondary to some physical or other psychiatric comorbidity.

Keywords: delusional parasitosis, delusional infestations, rare, primary psychiatric diagnosis, antipsychotic agents

Procedia PDF Downloads 51

Authors: Premalatha B. S., Shenoy A. M.

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Background: Rehabilitation of swallowing is as vital as speech in surgically treated head and neck cancer patients to maintain nutritional support, enhance wound healing and improve quality of life. Aspiration following supraglottic laryngectomy is very common, and rehabilitation of the same is crucial which requires involvement of speech therapist in close contact with head and neck surgeon. Objectives: To examine the functions of swallowing outcomes after intensive therapy in supraglottic laryngectomy. Materials: Thirty-nine supra glottic laryngectomees were participated in the study. Of them, 36 subjects were males and 3 were females, in the age range of 32-68 years. Eighteen subjects had undergone standard supra glottis laryngectomy (Group1) for supraglottic lesions where as 21 of them for extended supraglottic laryngectomy (Group 2) for base tongue and lateral pharyngeal wall lesion. Prior to surgery visit by speech pathologist was mandatory to assess the sutability for surgery and rehabilitation. Dysphagia rehabilitation started after decannulation of tracheostoma by focusing on orientation about anatomy, physiological variation before and after surgery, which was tailor made for each individual based on their type and extent of surgery. Supraglottic diet - Soft solid with supraglottic swallow method was advocated to prevent aspiration. The success of intervention was documented as number of sessions taken to swallow different food consistency and also percentage of subjects who achieved satisfactory swallow in terms of number of weeks in both the groups. Results: Statistical data was computed in two ways in both the groups 1) to calculate percentage (%) of subjects who swallowed satisfactorily in the time frame of less than 3 weeks to more than 6 weeks, 2) number of sessions taken to swallow without aspiration as far as food consistency was concerned. The study indicated that in group 1 subjects of standard supraglottic laryngectomy, 61% (n=11) of them were successfully rehabilitated but their swallowing normalcy was delayed by an average 29th post operative day (3-6 weeks). Thirty three percentages (33%) (n=6) of the subjects could swallow satisfactorily without aspiration even before 3 weeks and only 5 % (n=1) of the needed more than 6 weeks to achieve normal swallowing ability. Group 2 subjects of extended SGL only 47 %( n=10) of them could achieved satisfactory swallow by 3-6 weeks and 24% (n=5) of them of them achieved normal swallowing ability before 3 weeks. Around 4% (n=1) needed more than 6 weeks and as high as 24 % (n=5) of them continued to be supplemented with naso gastric feeding even after 8-10 months post operative as they exhibited severe aspiration. As far as type of food consistencies were concerned group 1 subject could able to swallow all types without aspiration much earlier than group 2 subjects. Group 1 needed only 8 swallowing therapy sessions for thickened soft solid and 15 sessions for liquids whereas group 2 required 14 sessions for soft solid and 17 sessions for liquids to achieve swallowing normalcy without aspiration. Conclusion: The study highlights the importance of dysphagia intervention in supraglottic laryngectomees by speech pathologist.

Keywords: dysphagia management, supraglotic diet, supraglottic laryngectomy, supraglottic swallow

Procedia PDF Downloads 209

Authors: Abdulaziz Bashir Kutawa1, 2, *, Khairulmazmi Ahmad 1, 3, Mohd Zobir Hussein 4, Asgar Ali 5, * Mohd Aswad Abdul Wahab1, Amara Rafi3, Mahesh Tiran Gunasena1, 6, Muhammad Ziaur Rahman1, 7, Md Imam Hossain1, And Syazwan Afif Mohd Zobir1

Abstract:

Various abiotic and biotic stresses have an impact on rice production all around the world. The most serious and prevalent disease in rice plants, known as rice blast, is one of the major obstacles to the production of rice. It is one of the diseases that has the greatest negative effects on rice farming globally, the disease is caused by a fungus called Magnaporthe grisae. Since nanoparticles were shown to have an inhibitory impact on certain types of fungus, nanotechnology is a novel notion to enhance agriculture by battling plant diseases. Utilizing nanocarrier systems enables the active chemicals to be absorbed, attached, and encapsulated to produce efficient nanodelivery formulations. The objectives of this research work were to determine the efficacy and mode of action of the nanofungicides (in-vitro) and in field conditions (in-vivo). Ionic gelation method was used in the development of the nanofungicides. Using the poisoned media method, the synthesized agronanofungicides' in-vitro antifungal activity was assessed against M. grisae. The potato dextrose agar (PDA) was amended in several concentrations; 0.001, 0.005, 0.01, 0.025, 0.05, 0.1, 0.15, 0.20, 0.25, 0.30, and 0.35 ppm for the nanofungicides. Medium with the only solvent served as a control. Every day, mycelial growth was measured, and PIRG (percentage inhibition of radial growth) was also computed. Every day, mycelial growth was measured, and PIRG (percentage inhibition of radial growth) was also computed. Based on the results of the zone of inhibition, the chitosan-hexaconazole agronanofungicide (2g/mL) was the most effective fungicide to inhibit the growth of the fungus with 100% inhibition at 0.2, 0.25, 0.30, and 0.35 ppm, respectively. Then followed by carbendazim analytical fungicide that inhibited the growth of the fungus (100%) at 5, 10, 25, 50, and 100 ppm, respectively. The least were found to be propiconazole and basamid fungicides with 100% inhibition only at 100 ppm. The scanning electron microscope (SEM), confocal laser scanning microscope (CLSM), and transmission electron microscope (TEM) were used to study the mechanisms of action of the M. grisae fungal cells. The results showed that both carbendazim, chitosan-hexaconazole, and HXE were found to be the most effective fungicides in disrupting the mycelia of the fungus, and internal structures of the fungal cells. The results of the field assessment showed that the CHDEN treatment (5g/L, double dosage) was found to be the most effective fungicide to reduce the intensity of the rice blast disease with DSI of 17.56%, lesion length (0.43 cm), DR of 82.44%, AUDPC of 260.54 Unit2, and PI of 65.33%, respectively. The least treatment was found to be chitosan-hexaconazole-dazomet (2.5g/L, MIC). The usage of CHDEN and CHEN nanofungicides will significantly assist in lessening the severity of rice blast in the fields, increasing output and profit for rice farmers.

Keywords: chitosan, hexaconazole, disease incidence, and magnaporthe grisae

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Authors: Hansraj Bookun, Rachel Xuan, Angela Tan, Kejia Wang, Animesh Singla, David Kim, Christopher Loupos, Jim Iliopoulos

Abstract:

Introduction: Complex endovascular aortic aneursymal repairs with fenestrated and branched endografts require customised devices to exclude the pathology while reducing morbidity and mortality, which was historically associated with open repair of complex aneurysms. Such endovascular procedures have predominantly been performed in a large volume dedicated tertiary centres. We present here our nine year multidisciplinary experience with this technology in an Australian tertiary centre. Method: This was a cross-sectional, single-centre observational study of 670 patients who had undergone complex endovascular aortic aneurysmal repairs with conventional endografts, fenestrated endografts, and iliac-branched devices from January 2010 to July 2019. Descriptive statistics were used to characterise our sample with regards to demographic and perioperative variables. Homogeneity of the sample was tested using multivariant regression, which did not identify any statistically significant confounding variables. Results: 670 patients of mean age 74, were included (592 males) and the comorbid burden was as follows: ischemic heart disease (55%), diabetes (18%), hypertension (90%), stage four or greater kidney impairment (8%) and current or ex-smoking (78%). The main indications for surgery were elective aneurysms (86%), symptomatic aneurysms (5%), and rupture aneurysms (5%). 106 patients (16%) underwent fenestrated or branched endograft repairs. The mean length of stay was 7.6 days. 2 patients experienced reactionary bleeds, 11 patients had access wound complications (6 lymph fistulae, 5 haematoms), 11 patients had cardiac complications (5 arrhythmias, 3 acute myocadial infarctions, 3 exacerbation of congestive cardiac failure), 10 patients had respiratory complications, 8 patients had renal impairment, 4 patients had gastrointestinal complications, 2 patients suffered from paraplegia, 1 major stroke, 1 minor stroke, and 1 acute brain syndrome. There were 4 vascular occlusions requiring further arterial surgery, 4 type I endoleaks, 4 type II endoleaks, 3 episodes of thromboembolism, and 2 patients who required further arterial operations in the setting of patient vessels. There were 9 unplanned returns to the theatre. Discussion: Our numbers of 10 years suggest that we are not a dedicated high volume centre focusing on aortic repairs. However, we have achieved significantly low complication rates. This can be attributed to our multidisciplinary approach with the intraoperative involvement of skilled interventional radiologists and vascular surgeons as well as postoperative protocols with particular attention to spinal cord protection. Additionally, we have a ratified perioperative pathway that involves multidisciplinary team discussions of patient-related factors and lesion-centered characteristics, which allows for holistic, patient-centered care.

Keywords: aneurysm, aortic, endovascular, fenestrated

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Authors: Mrunal Phatak, Suvarna Raut

Abstract:

Introduction: Thyroid hormone is important for the normal function of the auditory system. Hearing impairment can occur insidiously in subclinical hypothyroidism. The present study was undertaken with the aims of evaluating audiological tests like tuning fork tests, pure tone audiometry, brainstem evoked auditory potentials (BAEPs), and auditory reaction time (ART) in hypothyroid women and in age and sex matched controls so as to evaluate the effect of thyroid hormone on hearing. The objective of the study was to investigate hearing status by the audiological profile in hypothyroidism (group 1) and healthy controls ( group 2) to compare the audiological profile between these groups and find the correlation of levels of TSH, T3, and T4 with the above parameters. Material and methods: A total sample size of 124 women in the age group of 30 to 50 years was recruited and divided into the Cases group comprising of 62 newly diagnosed hypothyroid women and the Control group having 62 women with normal thyroid profile. Otoscopic examination, tuning fork tests, Pure tone audiometry tests (PTA). Brain Stem Auditory Evoked Potential (BAEP) and Auditory Reaction Time (ART) were done in both ears, i.e. total 248 ears of all subjects. Results: By BAEPs, hearing impairment was detected in total 64 ears (51.61%). A significant increase was seen in Wave V latency, IPL I-V, and IPL III-V, and the decrease was seen in the amplitude of Wave I and V in both the ears in cases. Positive correlation of Wave V latency of Right and Left ears is seen with TSH levels (p < 0.001) and a negative correlation with T3 (>0.05) and with T4 (p < 0.01). Negative correlation of wave V amplitude of Right and Left ears is seen with TSH levels (p < 0.001), and a significant positive correlation is seen with T3 and T4. Pure tone audiometry parameters showed hearing impairment of conductive (31.29%), sensorineural (36.29%), as well as the mixed type (15.32%). Hearing loss was mild in 65.32% of ears and moderate in 17.74% of ears. Pure tone averages (PTA) were significantly increased in cases than in controls in both the ears. Significant positive correlation of PTA of Right and Left ears is seen with TSH levels (p<0.05). Negative correlation with T3 and T4 is seen. A significant increase in HF ART and LF ART is seen in cases as compared to controls. Positive correlation of ART of high frequency and low frequency is seen with TSH levels and a negative correlation with T3 and T4 (p > 0.05). Conclusion: The abnormal BAEPs in hypothyroid women suggest an impaired central auditory pathway. BAEP abnormalities are indicative of a nonspecific injury in the bulbo-ponto-mesencephalic centres. The results of auditory investigations suggest a causal relationship between hypothyroidism and hearing loss. The site of lesion in the auditory pathway is probably at several levels, namely, in the middle ear and at cochlear and retrocochlear sites. Prolonged ART also suggests the impairment in central processing mechanisms. The results of the present study conclude that the probable reason for hearing impairment in hypothyroidism may be delayed impulse conduction in acoustic nerve up to the level of the midbrain (IPL I-V, III-V), particularly inferior colliculus (wave V). There is also impairment in central processing mechanisms, as shown by prolonged ART.

Keywords: deafness, pure tone audiometry, brain stem auditory evoked potential, hyopothyroidism

Procedia PDF Downloads 90

Authors: Megan L. Srinivas

Abstract:

Individuals with underlying rheumatologic diseases such as dermatomyositis may not adequately respond to tuberculin (PPD) skin tests, creating false negative results. These illnesses are frequently treated with immunosuppressive therapy making proper identification of TB infection imperative. A 59-year-old Filipino man was diagnosed with dermatomyositis on the basis of rash, electromyography, and muscle biopsy. He was initially treated with IVIG infusions and transitioned to oral prednisone and mycophenolate. The patient’s symptoms improved on this regimen. Six months after starting mycophenolate, the patient began having fevers, night sweats, and productive cough without hemoptysis. He moved from the Philippines 5 years prior to dermatomyositis diagnosis, denied sick contacts, and was PPD negative both at immigration and immediately prior to starting mycophenolate treatment. A third PPD was negative following the onset of these new symptoms. He was treated for community-acquired pneumonia, but symptoms worsened over 10 days and he developed watery diarrhea and a growing non-tender, non-mobile mass on the left side of his neck. A chest x-ray demonstrated a cavitary lesion in right upper lobe suspicious for TB that had not been present one month earlier. Chest CT corroborated this finding also exhibiting necrotic hilar and paratracheal lymphadenopathy. Neck CT demonstrated the left-sided mass as cervical chain lymphadenopathy. Expectorated sputum and stool samples contained acid-fast bacilli (AFB), cultures showing TB bacteria. Fine-needle biopsy of the neck mass (scrofula) also exhibited AFB. An MRI brain showed nodular enhancement suspected to be a tuberculoma. Mycophenolate was discontinued and dermatomyositis treatment was switched to oral prednisone with a 3-day course of IVIG. The patient’s infection showed sensitivity to standard RIPE (rifampin, isoniazid, pyrazinamide, and ethambutol) treatment. Within a week of starting RIPE, the patient’s diarrhea subsided, scrofula diminished, and symptoms significantly improved. By the end of treatment week 3, the patient’s sputum no longer contained AFB; he was removed from isolation, and was discharged to continue RIPE at home. He was discharged on oral prednisone, which effectively addressed his dermatomyositis. This case illustrates the unreliability of PPD tests in patients with long-term inflammatory diseases such as dermatomyositis. Other immunosuppressive therapies (adalimumab, etanercept, and infliximab) have been affiliated with conversion of latent TB to disseminated TB. Mycophenolate is another immunosuppressive agent with similar mechanistic properties. Thus, it is imperative that patients with long-term inflammatory diseases and high-risk TB factors initiating immunosuppressive therapy receive a TB blood test (such as a quantiferon gold assay) prior to the initiation of therapy to ensure that latent TB is unmasked before it can evolve into a disseminated form of the disease.

Keywords: dermatomyositis, immunosuppressant medications, mycophenolate, disseminated tuberculosis

Procedia PDF Downloads 179

Authors: Akintade O. Adeboyejo, Edwin O. Clarke, Oluwatoyin Aderinola

Abstract:

The present study is on the sub-lethal toxicity of industrial effluents (IE) from the environment of Ologe Lagoon, Lagos, Nigeria on the African catfish fingerlings Clarias gariepinus. The fish were cultured in varying concentrations of industrial effluents: 0% (control), 5%, 15%, 25%, and 35%. Trials were carried out in triplicates for twelve (12) weeks. The culture system was a static renewable bioassay and was carried out in the fisheries laboratory of the Lagos State University, Ojo-Lagos. Weekly physico-chemical parameters: Temperature (0C), pH, Conductivity (ppm) and Dissolved Oxygen (DO in mg/l) were measured in each treatment tank. Length (cm) and weight (g) data were obtained weekly and used to calculate various growth parameters: mean weight gain (MWG), percentage weight gain (PWG), daily weight gain (DWG), specific growth rate (SGR) and survival. Haematological (Packed Cell Volume (PCV), Red blood cells (RBC), White Blood Cell (WBC), Neutrophil and Lymphocytes etc) and histological alterations were measured after 12 weeks. The physico-chemical parameters showed that the pH ranged from 7.82±0.25–8.07±0.02. DO range from 1.92±0.66-4.43±1.24 mg/l. The conductivity values increased with increase in concentration of I.E. While the temperature remained stable with mean value range between 26.08±2.14–26.38±2.28. The DO showed significant differences at P<0.05. There was progressive increase in length and weight of fish during the culture period. The fish placed in the control had highest increase in both weight and length while fish in 35% had the least. MWG ranged from 16.59–35.96, DWG is from 0.3–0.48, SGR varied from 1.0–1.86 and survival was 100%. Haematological results showed that C. gariepinus had PCV ranging from 13.0±1.7-27.7±0.6, RBC ranged from 4.7±0.6–9.1±0.1, and Neutrophil ranged from 26.7±4.6–61.0±1.0 amongst others. The highest values of these parameters were obtained in the control and lowest at 35%. While the reverse effects were observed for WBC and lymphocytes. This study has shown that effluents may affect the health status of the test organism and impair vital processes if exposure continues for a long period of time. The histological examination revealed several lesions as expressed by the gills and livers. The histopathology of the gills in the control tanks had normal tissues with no visible lesion, but at higher concentrations, there were: lifting of epithelium, swollen lamellae and gill arch infiltration, necrosis and gill arch destruction. While in the liver: control (0%) show normal liver cells, at higher toxic level, there were: vacoulation, destruction of the hepatic parenchyma, tissue becoming eosinophilic (i.e. tending towards Carcinogenicity) and severe disruption of the hepatic cord architecture. The study has shown that industrial effluents from the study area may affect fish health status and impair vital processes if exposure continues for a long period of time even at lower concentrations (Sublethal).

Keywords: sublethal toxicity, industrial effluents, clarias gariepinus, ologe lagoon

Procedia PDF Downloads 577

Authors: Magdalena Chrabąszcz, Teresa Wolniewicz, Cezary Maciejewski, Joanna Czuwara

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BACKGROUND: Dermoscopy is a clinical tool known to improve the early detection of melanoma and other malignancies of the skin. Over the past few years melanoma has grown into a disease of socio-economic importance due to the increasing incidence and persistently high mortality rates. Early diagnosis remains the best method to reduce melanoma and non-melanoma skin cancer– related mortality and morbidity. Dermoscopy is a noninvasive technique that consists of viewing pigmented skin lesions through a hand-held lens. This simple procedure increases melanoma diagnostic accuracy by up to 35%. Dermoscopy is currently the standard for clinical differential diagnosis of cutaneous melanoma and for qualifying lesion for the excision biopsy. Like any clinical tool, training is required for effective use. The introduction of small and handy dermoscopes contributed significantly to the switch of dermatoscopy toward a first-level useful tool. Non-dermatologist physicians are well positioned for opportunistic melanoma detection; however, education in the skin cancer examination is limited during medical school and traditionally lecture-based. AIM: The aim of this randomized study was to determine whether the adjunct of dermoscopy to the standard fourth year medical curriculum improves the ability of medical students to distinguish between benign and malignant lesions and assess acceptability and satisfaction with the intervention. METHODS: We performed a prospective study in 2 cohorts of fourth-year medical students at Medical University of Warsaw. Groups having dermatology course, were randomly assigned to:  cohort A: with limited access to dermatoscopy from their teacher only – 1 dermatoscope for 15 people  Cohort B: with a full access to use dermatoscopy during their clinical classes:1 dermatoscope for 4 people available constantly plus 15-minute dermoscopy tutorial. Students in both study arms got an image-based test of 10 lesions to assess ability to differentiate benign from malignant lesions and postintervention survey collecting minimal background information, attitudes about the skin cancer examination and course satisfaction. RESULTS: The cohort B had higher scores than the cohort A in recognition of nonmelanocytic (P < 0.05) and melanocytic (P <0.05) lesions. Medical students who have a possibility to use dermatoscope by themselves have also a higher satisfaction rates after the dermatology course than the group with limited access to this diagnostic tool. Moreover according to our results they were more motivated to learn dermatoscopy and use it in their future everyday clinical practice. LIMITATIONS: There were limited participants. Further study of the application on clinical practice is still needed. CONCLUSION: Although the use of dermatoscope in dermatology as a specialty is widely accepted, sufficiently validated clinical tools for the examination of potentially malignant skin lesions are lacking in general practice. Introducing medical students to dermoscopy in their fourth year curricula of medical school may improve their ability to differentiate benign from malignant lesions. It can can also encourage students to use dermatoscopy in their future practice which can significantly improve early recognition of malignant lesions and thus decrease melanoma mortality.

Keywords: dermatoscopy, early detection of melanoma, medical education, skin cancer

Procedia PDF Downloads 93

Authors: Wanvipa Thongborisute, Punyaphat Sirithanabadeekul, Pichit Suvanprakorn, Anan Jiraviroon

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Background: Acne vulgaris is one of the most common dermatologic problems, and can have a significant psychological and physical effect on patients. Propionibacterium acnes' roles in acne vulgaris involve the activation of toll-like receptor 4 (TLR4), and toll-like receptor 2 (TLR2) pathways. By activating these pathways, inflammatory events of acne lesions, comedogenesis and sebaceous lipogenesis can occur. Currently, there are several topical agents commonly use in treating acne vulgaris that are known to have an effect on TLRs, such as retinoic acid and adapalene, but these drugs still have some irritating effects. At present, there is an alarming increase in rate of bacterial resistance due to irrational used of antibiotics both orally and topically. For this reason, acne treatments should contain bioactive molecules targeting at the site of action for the most effective therapeutic effect with the least side effects. Sparganium stoloniferumis a Chinese aquatic herb containing a compound called Sparstolonin B (SsnB), which has been reported to selectively blocks Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4)-mediated inflammatory signals. Therefore, this topical TLR2 and TLR4 antagonist, in a form of Sparganium stoloniferum-derived compound containing SsnB, should give a benefit in reducing inflammation of acne vulgaris lesions and providing an alternative treatments for patients with this condition. Materials and Methods: The objectives of this randomized double blinded split faced placebo controlled trial is to study the safety and efficacy of the Sparganium stoloniferum-derived compound. 32 volunteered patients with mild to moderate degree of acne vulgaris according to global acne grading system were included in the study. After being informed and consented the subjects were given 2 topical treatments for acne vulgaris, one being topical 2.40% Sparganium stoloniferum extraction (containing Sparstolonin B) and the other, placebo. The subjects were asked to apply each treatment to either half of the face daily morning and night by randomization for 8 weeks, and come in for a weekly follow up. For each visit, the patients went through a procedure of lesion counting, including comedones, papules, nodules, pustules, and cystic lesions. Results: During 8 weeks of experimentation, the result shows a reduction in total lesions number between the placebo and the treatment side show statistical significance starting at week 4, where the 95% confidence interval begin to no longer overlap, and shows a trend of continuing to be further apart. The decrease in the amount of total lesions between week 0 and week 8 of the placebo side shows no statistical significant at P value >0.05. While the decrease in the amount of total lesions of acne vulgaris of the treatment side comparing between week 0 and week 8 shows statistical significant at P value <0.001. Conclusion: The data demonstrates that 2.40% Sparganium stoloniferum extraction (containing Sparstolonin B) is more effective in treating acne vulgaris comparing to topical placebo in treating acne vulgaris, by showing significant reduction in the total numbers of acne lesions. Therefore, this topical Sparganium stoloniferum extraction could become a potential alternative treatment for acne vulgaris.

Keywords: acne vulgaris, sparganium stoloniferum, sparstolonin B, toll-like receptor 2, toll-like receptor 4

Procedia PDF Downloads 152

Authors: Jatinder Pal Singh, Harpreet Singh, Gagandeep Singh Digra, Mandeep Kaur Sidhu, Pawan Kumar

Abstract:

Introduction: Ganglion cyst is a benign condition in which there is a cystic lesion in relation to a joint or a tendon sheath arising from myxoid degeneration of fibrous connective tissue. These can be unilocular or multilocular. In rare cases, there may be multiple ganglion cysts, known as cystic ganglionosis. They can occur at any age but are commonly seen in adults. Clinically they may be asymptomatic or present as swelling or mass effect in adjacent structures. These are common in extremities such as hands and feet. Case Presentation: 11-year-old female child presented with slowly progressive painless swelling of her right hand since the age of 4. Antenatal and perinatal history was unremarkable. Her family history was negative. She denies fever, malaise, morning stiffness, weight loss, fatigue, restriction of joint movements, or any sensory and motor deficit. Lab parameters were negative for inflammatory or infectious etiology. No other joint or extremity involvement was present. On physical examination, the swelling was present on the dorsum and palmer aspect of the right hand and wrist. They were non-tender on palpation without any motor or sensory deficit. MRI hand revealed multiple well-defined fluid signal intensity cystic appearing lesions in periarticular/intraarticular locations in relation to distal radio-ulnar, radio-carpal, intercarpal, carpometacarpal, metacarpophalangeal and interphalangeal joints as well as peritendinous location around flexor tendons more so in the region of wrist, palm, 1st and 5th digit and along extensor tendons in the region of wrist, largest one noted along flexor pollicis longus tendon in thenar region and along 1st digit measuring approx. 4.6 x 1.2 x 1.2 centimeter. Pressure erosions and bone remodelling were noted in the bases of the 2nd to 5th metacarpals, capitate, trapezoid, the distal shaft of 1st metacarpal, and proximal phalanx of 1st digit. Marrow edema was noted in the base and proximal shaft of the 4th metacarpal and proximal shaft of the 3rd metacarpal – likely stress or pressure related. The patient was advised of aspiration, but the family refused the procedure. Therefore the patient was kept on conservative treatment. Conclusion: Cystic ganglionosis is a rare condition with very few cases reported in the medical literature. Its prevalence and association are not known because of the rarity of this condition. It should be considered as an important differential in patients presenting with soft tissue swelling in extremities. Treatment option includes conservative management, aspiration, and surgery. Aspiration has a high recurrence rate. Although surgery has a low recurrence rate, it carries a high rate of complications. Imaging with MRI is essential for confirmation of the cystic nature of lesions and their relation with the joint capsules or tendons. This helps in differentiating from other soft tissue lesions and presurgical planning.

Keywords: radiology, rare, cystic ganglionosis, child

Procedia PDF Downloads 48

Authors: Pedro Felgueiras, Ana Miguel, Nélson Almeida, Raquel Silva

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Objective: Through the study of a clinical case of delusional somatic disorder secondary to phantogeusia, we aim to highlight the importance of considering psychosomatic conditions in differential diagnosis, as well as to emphasize the complexity of its comprehension, treatment, and respective impact on patients’ functioning. Methods: Bearing this in mind, we conducted a critical analysis of a case series based on patient observations, clinical data, and complementary diagnostic methods, as well as a non-systematic review of the literature on the subject. Results: A 61-year-old female patient with no history of psychiatric conditions. Family psychiatric history of mood disorder (depression), with psychotic features found in her mother. Medical history of many comorbidities affecting different organ systems (endocrine, gastrointestinal, genitourinary, ophthalmological). Documented neuroticism traits of personality. The patient’s family described a persistent concern about several physical symptoms across her life, with a continuous effort to obtain explanations about any sensation out of her normal perception. Since being subjected to endoscopy in 2018, she started complaints of persistent phantogeusia (acid taste) and developed excessive thoughts, feelings, and behaviors associated with this somatic symptom. The patient was evaluated by several medical specialties, and an extensive panel of medical exams was carried out, excluding any disease. Besides all the investigation and with no evidence of disease signs, acute anxiety, time, and energy dispended to this symptom culminated in severe psychosocial impairment. The patient was admitted to a psychiatric ward for investigation and treatment of this clinical picture, leading to the diagnosis of the delusional somatic disorder. In order to exclude the acute organic etiology of this psychotic disorder, an analytic panel was carried out with no abnormal results. In the context of a psychotic clinical picture, a CT scan was performed, which revealed a right cortical vascular lesion. Neuropsychological evaluation was made, with the description of cognitive functioning being globally normative. During treatment with an antipsychotic (pimozide), a complete remission of the somatic delusion was associated with the disappearance of gustative perception disturbance. In follow-up, a relapse of gustative sensation was documented, and her thoughts and speech were dominated by concerns about multiple somatic symptoms. Conclusion: In terms of abnormal bodily sensations, the oral cavity is one of the frequent sites of delusional disorder. Patients with these gustatory perception distortions complain about unusual sensations without corresponding abnormal findings in the oral area. Its pathophysiology has not been fully elucidated yet. In terms of its comprehensive psychopathology, this case was hypothesized as a paranoid development of a delusional somatic disorder triggered by a post-invasive procedure phantogeusia (which is described as a possible side effect of an endoscopy) in a patient with an anankastic personality. This case presents interesting psychopathology, reinforcing the complexity of psychosomatic disorders in terms of their etiopathogenesis, clinical treatment, and long-term prognosis.

Keywords: psychosomatics, delusional somatic disorder, phantogeusia, paranoid development

Procedia PDF Downloads 96

Authors: Maryam Mohammad Hadi, Heather Nesbitt, Hamzah Masood, Hashim Ahmed, Mark Emberton, John Callan, Alexander MacRobert, Anthony McHale, Nikolitsa Nomikou

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Sonodynamic therapy (SDT) utilises ultrasound in combination with sensitizers, such as porphyrins, for the production of cytotoxic reactive oxygen species (ROS) and the confined ablation of tumours. Ultrasound can be applied locally, and the acoustic waves, at frequencies between 0.5-2 MHz, are transmitted efficiently through tissue. SDT does not require highly toxic agents, and the cytotoxic effect only occurs upon ultrasound exposure at the site of the lesion. Therefore, this approach is not associated with adverse side effects. Further highlighting the benefits of SDT, no cancer cell population has shown resistance to therapy-triggered ROS production or their cytotoxic effects. This is particularly important, given the as yet unresolved issues of radiation and chemo-resistance, to the authors’ best knowledge. Another potential future benefit of this approach – considering its non-thermal mechanism of action – is its possible role as an adjuvant to immunotherapy. Substantial pre-clinical studies have demonstrated the efficacy and targeting capability of this therapeutic approach. However, SDT has yet to be fully characterised and appropriately exploited for the treatment of cancer. In this study, a formulation based on multistimulus-responsive sensitizer-containing nanoparticles that can accumulate in advanced prostate tumours and increase the therapeutic efficacy of SDT has been developed. The formulation is based on a polyglutamate-tyrosine (PGATyr) co-polymer carrying hematoporphyrin. The efficacy of SDT in this study was demonstrated using prostate cancer as the translational exemplar. The formulation was designed to respond to the microenvironment of advanced prostate tumours, such as the overexpression of the proteolytic enzymes, cathepsin-B and prostate-specific membrane antigen (PSMA), that can degrade the nanoparticles, reduce their size, improving both diffusions throughout the tumour mass and cellular uptake. The therapeutic modality was initially tested in vitro using LNCaP and PC3 cells as target cell lines. The SDT efficacy was also examined in vivo, using male SCID mice bearing LNCaP subcutaneous tumours. We have demonstrated that the PGATyr co-polymer is digested by cathepsin B and that digestion of the formulation by cathepsin-B, at tumour-mimicking conditions (acidic pH), leads to decreased nanoparticle size and subsequent increased cellular uptake. Sonodynamic treatment, at both normoxic and hypoxic conditions, demonstrated ultrasound-induced cytotoxic effects only for the nanoparticle-treated prostate cancer cells, while the toxicity of the formulation in the absence of ultrasound was minimal. Our in vivo studies in immunodeficient mice, using the hematoporphyrin-containing PGATyr nanoparticles for SDT, showed a 50% decrease in LNCaP tumour volumes within 24h, following IV administration of a single dose. No adverse effects were recorded, and body weight was stable. The results described in this study clearly demonstrate the promise of SDT to revolutionize cancer treatment. It emphasizes the potential of this therapeutic modality as a fist line treatment or in combination treatment for the elimination or downstaging of difficult to treat cancers, such as prostate, pancreatic, and advanced colorectal cancer.

Keywords: sonodynamic therapy, nanoparticles, tumour ablation, ultrasound

Procedia PDF Downloads 117

Authors: Kartik Gupta, Virendra Kumar, Sanjeev Sinha, N. Jagannathan

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Introduction: A significant number of patients having human immunodeficiency virus (HIV) infection show a neurocognitive decline (NCD) ranging from minor cognitive impairment to severe dementia. The possible causes of NCD in HIV-infected patients include brain injury by HIV before cART, neurotoxic viral proteins and metabolic abnormalities. In the present study, we compared the level of NCD in asymptomatic HIV-infected patients with changes in brain metabolites measured by using magnetic resonance spectroscopy (MRS). Methods: 43 HIV-positive patients (30 males and 13 females) coming to ART center of the hospital and HIV-seronegative healthy subjects were recruited for the study. All the participants completed MRI and MRS examination, detailed clinical assessments and a battery of neuropsychological tests. All the MR investigations were carried out at 3.0T MRI scanner (Ingenia/Achieva, Philips, Netherlands). MRI examination protocol included the acquisition of T2-weighted imaging in axial, coronal and sagittal planes, T1-weighted, FLAIR, and DWI images in the axial plane. Patients who showed any apparent lesion on MRI were excluded from the study. T2-weighted images in three orthogonal planes were used to localize the voxel in left frontal lobe white matter (FWM) and left basal ganglia (BG) for single voxel MRS. Single voxel MRS spectra were acquired with a point resolved spectroscopy (PRESS) localization pulse sequence at an echo time (TE) of 35 ms and a repetition time (TR) of 2000 ms with 64 or 128 scans. Automated preprocessing and determination of absolute concentrations of metabolites were estimated using LCModel by water scaling method and the Cramer-Rao lower bounds for all metabolites analyzed in the study were below 15\%. Levels of total N-acetyl aspartate (tNAA), total choline (tCho), glutamate + glutamine (Glx), total creatine (tCr), were measured. Cognition was tested using a battery of tests validated for Indian population. The cognitive domains tested were the memory, attention-information processing, abstraction-executive, simple and complex perceptual motor skills. Z-scores normalized according to age, sex and education standard were used to calculate dysfunction in these individual domains. The NCD was defined as dysfunction with Z-score ≤ 2 in at least two domains. One-way ANOVA was used to compare the difference in brain metabolites between the patients and healthy subjects. Results: NCD was found in 23 (53%) patients. There was no significant difference in age, CD4 count and viral load between the two groups. Maximum impairment was found in the domains of memory and simple motor skills i.e., 19/43 (44%). The prevalence of deficit in attention-information processing, complex perceptual motor skills and abstraction-executive function was 37%, 35%, 33% respectively. Subjects with NCD had a higher level of Glutamate in the Frontal region (8.03 ± 2.30 v/s. 10.26 ± 5.24, p-value 0.001). Conclusion: Among newly diagnosed, ART-naïve retroviral disease patients from India, cognitive decline was found in 53\% patients using tests validated for this population. Those with neurocognitive decline had a significantly higher level of Glutamate in the left frontal region. There was no significant difference in age, CD4 count and viral load at initiation of ART between the two groups.

Keywords: HIV, neurocognitive decline, neurometabolites, magnetic resonance spectroscopy

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Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

Abstract:

Kawasaki disease (KD) is the primary cause of acquired pediatric heart disease as an acute vasculitis. In children with prolonged fever, rash, and inflammation of the mucosa KD must be considered as a clinical diagnosis. There is a persuasive suggestion of immune-mediated damage as the pathophysiologic cascade of KD. For example, the invasion of cytotoxic T-cells supports a viral etiology and the inflammasome of the innate immune system is a critical component in the vasculitis formation in KD. Animal models of KD propose the cytokine profiles, such as increased IL-1 and GM-CSF, which cause vascular damage. CRP and IFN-γ elevated expression and the upregulation of IL-6, and IL-10 production are also described in previous studies. Untreated KD is a critical risk factor for coronary artery diseases and myocardial infarction. Vascular damage may encompass amplified T-cell activity. SMAD3 is an essential molecule in down-regulating T-cells and increasing expression of FoxP3. It has a critical effect in the differentiation of regulatory T-cells. The discrepancy of regulatory T-cells and pro-inflammatory Th17 has been studied in acute coronary syndrome during KD. However in the coronary artery damaged lymphocytes and IgA plasma cells are seen at the lesion locations, the major immune cells in the coronary lesions are monocytes/macrophages and neutrophils. These cells secrete TNF-α, and activates matrix metalloprotease (MMP)-9, reducing the integrity of vessels and prompting patients to arise aneurysm. MMPs can break down the components of the extracellular matrix and assist immune cell movement. IVIG as an effective form of treatment clarified the role of the immune system, which may target pathogenic antigens and regulate cytokine production. Several reports have revealed that in the coronary arteries, high expression of MMP-9 in monocyte/macrophage results in pathologic cascades. Curcumin is a potent antioxidant and anti-inflammatory molecule. Curcumin decreases the production of reactive oxygen and nitrogen species and inhibits transcription factors like AP-1 and NF-κB. Curcumin also contains the characteristics of inhibitory effects on MMPs, especially MMP-9. The upregulation of MMP-9 is an important cellular response. Curcumin treatment caused a reverse effect and down-regulates MMP-9 gene expression which may fund the anti-inflammatory effect. Curcumin inhibits MMP-9 expression via PKC and AMPK-dependent pathways in Human monocytes cells. Elevated expression and activity of MMP-9 are correlated with advanced vascular lesions. AMPK controls lipid metabolism and oxidation, and protein synthesis. AMPK is also necessary for the MMP-9 activity and THP-1 cell adhesion to endothelial cells. Curcumin was shown to inhibit the activation of AMPKα. Compound C (AMPK inhibitor) inhibits MMP-9 expression level. Therefore, through inactivating AMPKs and PKC, curcumin decreases the MMP-9 level, which results in inhibiting monocyte/macrophage differentiation. Compound C also suppress the phosphorylation of three major classes of MAP kinase signaling, suggesting that curcumin may suppress MMP-9 level by inactivation of MAPK pathways. MAPK cascades are activated to induce the expression of MMP-9. Curcumin inhibits MAPKs phosphorylation, which contributes to the down-regulation of MMP-9. This study demonstrated that the potential inhibitory properties of curcumin over MMP-9 lead to a therapeutic strategy to reduce the risk of coronary artery involvement during KD.

Keywords: MMP-9, coronary artery aneurysm, Kawasaki’s disease, curcumin, AMPK, immune system, NF-κB, MAPK

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Authors: Carlos Amnael Orozco-Diaz, Robert David Moorehead, Gwendolen Reilly, Fiona Gilchrist, Cheryl Ann Miller

Abstract:

The current gold-standard for maxillofacial reconstruction surgery (MRS) utilizes auto-grafted cancellous bone as a filler. This study was aimed towards developing a polylactic-acid/hydroxyapatite (PLA-HA) composite suitable for fused-deposition 3D printing. Functionalization of the polymer through the addition of HA was directed to promoting bone-regeneration properties so that the material can rival the performance of cancellous bone grafts in terms of bone-lesion repair. This kind of composite enables the production of MRS implants based off 3D-reconstructions from image studies – namely computed tomography – for anatomically-correct fitting. The present study encompassed in-vitro degradation and in-vitro biocompatibility profiling for 3D-printed PLA and PLA-HA composites. PLA filament (Verbatim Co.) and Captal S hydroxyapatite micro-scale HA powder (Plasma Biotal Ltd) were used to produce PLA-HA composites at 5, 10, and 20%-by-weight HA concentration. These were extruded into 3D-printing filament, and processed in a BFB-3000 3D-Printer (3D Systems Co.) into tensile specimens, and were mechanically challenged as per ASTM D638-03. Furthermore, tensile specimens were subjected to accelerated degradation in phosphate-buffered saline solution at 70°C for 23 days, as per ISO-10993-13-2010. This included monitoring of mass loss (through dry-weighing), crystallinity (through thermogravimetric analysis/differential thermal analysis), molecular weight (through gel-permeation chromatography), and tensile strength. In-vitro biocompatibility analysis included cell-viability and extracellular matrix deposition, which were performed both on flat surfaces and on 3D-constructs – both produced through 3D-printing. Discs of 1 cm in diameter and cubic 3D-meshes of 1 cm3 were 3D printed in PLA and PLA-HA composites (n = 6). The samples were seeded with 5000 MG-63 osteosarcoma-like cells, with cell viability extrapolated throughout 21 days via resazurin reduction assays. As evidence of osteogenicity, collagen and calcium deposition were indirectly estimated through Sirius Red staining and Alizarin Red staining respectively. Results have shown that 3D printed PLA loses structural integrity as early as the first day of accelerated degradation, which was significantly faster than the literature suggests. This was reflected in the loss of tensile strength down to untestable brittleness. During degradation, mass loss, molecular weight, and crystallinity behaved similarly to results found in similar studies for PLA. All composite versions and pure PLA were found to perform equivalent to tissue-culture plastic (TCP) in supporting the seeded-cell population. Significant differences (p = 0.05) were found on collagen deposition for higher HA concentrations, with composite samples performing better than pure PLA and TCP. Additionally, per-cell-calcium deposition on the 3D-meshes was significantly lower when comparing 3D-meshes to discs of the same material (p = 0.05). These results support the idea that 3D-printable PLA-HA composites are a viable resorbable material for artificial grafts for bone-regeneration. Degradation data suggests that 3D-printing of these materials – as opposed to other manufacturing methods – might result in faster resorption than currently-used PLA implants.

Keywords: bone regeneration implants, 3D-printing, in vitro testing, biocompatibility, polymer degradation, polymer-ceramic composites

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Authors: Joseph M. Rich, Vinay A. Duddalwar, Assad A. Oberai

Abstract:

Prostate adenocarcinoma is the most common cancer in males, with osseous metastases as the commonest site of metastatic prostate carcinoma (mPC). Treatment monitoring is based on the evaluation and characterization of lesions on multiple imaging studies, including Computed Tomography (CT). Monitoring of the osseous disease burden, including follow-up of lesions and identification and characterization of new lesions, is a laborious task for radiologists. Deep learning algorithms are increasingly used to perform tasks such as identification and segmentation for osseous metastatic disease and provide accurate information regarding metastatic burden. Here, nnUNet was used to produce a model which can segment CT scan images of prostate adenocarcinoma vertebral bone metastatic lesions. nnUNet is an open-source Python package that adds optimizations to deep learning-based UNet architecture but has not been extensively combined with transfer learning techniques due to the absence of a readily available functionality of this method. The IRB-approved study data set includes imaging studies from patients with mPC who were enrolled in clinical trials at the University of Southern California (USC) Health Science Campus and Los Angeles County (LAC)/USC medical center. Manual segmentation of metastatic lesions was completed by an expert radiologist Dr. Vinay Duddalwar (20+ years in radiology and oncologic imaging), to serve as ground truths for the automated segmentation. Despite nnUNet’s success on some medical segmentation tasks, it only produced an average Dice Similarity Coefficient (DSC) of 0.31 on the USC dataset. DSC results fell in a bimodal distribution, with most scores falling either over 0.66 (reasonably accurate) or at 0 (no lesion detected). Applying more aggressive data augmentation techniques dropped the DSC to 0.15, and reducing the number of epochs reduced the DSC to below 0.1. Datasets have been identified for transfer learning, which involve balancing between size and similarity of the dataset. Identified datasets include the Pancreas data from the Medical Segmentation Decathlon, Pelvic Reference Data, and CT volumes with multiple organ segmentations (CT-ORG). Some of the challenges of producing an accurate model from the USC dataset include small dataset size (115 images), 2D data (as nnUNet generally performs better on 3D data), and the limited amount of public data capturing annotated CT images of bone lesions. Optimizations and improvements will be made by applying transfer learning and generative methods, including incorporating generative adversarial networks and diffusion models in order to augment the dataset. Performance with different libraries, including MONAI and custom architectures with Pytorch, will be compared. In the future, molecular correlations will be tracked with radiologic features for the purpose of multimodal composite biomarker identification. Once validated, these models will be incorporated into evaluation workflows to optimize radiologist evaluation. Our work demonstrates the challenges of applying automated image segmentation to small medical datasets and lays a foundation for techniques to improve performance. As machine learning models become increasingly incorporated into the workflow of radiologists, these findings will help improve the speed and accuracy of vertebral metastatic lesions detection.

Keywords: deep learning, image segmentation, medicine, nnUNet, prostate carcinoma, radiomics

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Authors: Wissam Saliba, Mandy Nicholson

Abstract:

Secretory carcinoma (SC) is a rare type of salivary gland cancer. It was first realized as a distinct type of malignancy in 2010and wasinitially termed “mammary analogue secretory carcinoma” because of similarities with secretory breast cancer. The name was later changed to SC. Most SCs originate in parotid glands, and most harbour a rare gene mutation: ETV6-NTRK3. This mutation is rare in common cancers and common in rare cancers; it is present in most secretory carcinomas. Disease outcomes for SC are usually described as favourable as many cases of SC are lowgrade (LG), and cancer growth is slow. In early stages, localized therapy is usually indicated (surgery and/or radiation). Despitea favourable prognosis, a sub-set of casescan be much more aggressive.These cases tend to be of high-grade(HG).HG casesare associated with a poorer prognosis.Management of such cases can be challenging due to limited evidence for effective systemic therapy options. This case report describes the clinical management of a 46-year-oldmale patient with a unique case of SC. He was initially diagnosed with a low/intermediate grade carcinoma of the left parotid gland in 2009; he was treated with surgery and adjuvant radiation. Surgical pathology favoured primary salivary adenocarcinoma, and 2 lymph nodes were positive for malignancy. SC was not yet realized as a distinct type of cancerat the time of diagnosis, and the pathology reportvalidated this gap by stating that the specimen lacked features of the defined types of salivary carcinoma.Slow-growing pulmonary nodules were identified in 2017. In 2020, approximately 11 years after the initial diagnosis, the patient presented with malignant pleural effusion. Pathology from a pleural biopsy was consistent with metastatic poorly differentiated cancer of likely parotid origin, likely mammary analogue secretory carcinoma. The specimen was sent for Next Generation Sequencing (NGS); ETV6-NTRK3 gene fusion was confirmed, and systemic therapy was initiated.One cycle ofcarboplatin/paclitaxel was given in June 2020. He was switched to Larotrectinib (NTRK inhibitor (NTRKi)) later that month. Larotrectinib continued for approximately 9 months, with discontinuation in March 2021 due to disease progression. A second-generation NTRKi (Selitrectinib) was accessed and prescribedthrough a single patient study. Selitrectinib was well tolerated. The patient experienced a complete radiological response within~4 months. Disease progression occurred once again in October 2021. Progression was slow, and Selitrectinib continuedwhile the medical team performed a thorough search for additional treatment options. In January 2022, a liver lesion biopsy was performed, and NGS showed an NTRKG623R solvent-front resistance mutation. Various treatment pathways were considered. The patient pursuedanother investigational NTRKi through a clinical trial, and Selitrectinib was discontinued in July 2022. Excellent performance status was maintained throughout the entire course of treatment.It can be concluded that NTRK inhibitors provided satisfactory treatment efficacy and tolerance for this patient with high-grade transformation and NTRK gene fusion cancer. In the future, more clinical research is needed on systemic treatment options for high-grade transformations in NTRK gene fusion SCs.

Keywords: secretory carcinoma, high-grade transformations, NTRK gene fusion, NTRK inhibitor

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Authors: Mohamed Abdelmongy

Abstract:

Autologous Blood for Conjunctival Autograft Fixation in Primary Pterygium Surgery: A Systematic Review and Meta-analysis Hossam Zein1,2, Ammar Ismail1,3, Mohamed Abdelmongy1,4, Sherif Elsherif1,5,6, Ahmad Hassanen1,4, Basma Muhammad2, Fathy Assaf1,3, Ahmed Elsehili1,7, Ahmed Negida1,7, Shin Yamane9, Mohamed M. Abdel-Daim8,9 and Kazuaki Kadonosono9 https://www.ncbi.nlm.nih.gov/pubmed/30277146 BACKGROUND: Pterygium is a benign ocular lesion characterized by triangular fibrovascular growth of conjunctival tissue over the cornea. Patients complain of the bad cosmetic appearance, ocular surface irritation and decreased visual acuity if the pterygium is large enough to cause astigmatism or encroach on the pupil. The definitive treatment of pterygium is surgical removal. However, outcomes are compromised by recurrence . The aim of the current study is to systematically review the current literature to explore the efficacy and safety of fibrin glue, suture and autologous blood coagulum for conjunctivalautograft fixation in primary pterygium surgery. OBJECTIVES: To assess the effectiveness of fibrin glue compared to sutures and autologous blood coagulum in conjunctival autografting for the surgical treatment of pterygium. METHODS: During preparing this manuscript, we followed the steps adequately illustrated in the Cochrane Handbook for Systematic Reviews of Interventions version 5.3, and reported it according to the preferred reporting of systematic review and meta-analysis (PRISMA) statement guidelines. We searched PubMed, Ovid (both through Medline), ISI Web of Science, and Cochrane Central Register of Controlled Trials (Central) through January 2017, using the following keywords “Pterygium AND (blood OR glue OR suture)” SELECTION CRITERIA: We included all randomized controlled trials (RCTs) that met the following criteria: 1) comparing autologous blood vs fibrin glue for conjunctivalautograft fixation in primary pterygium surgery 2) comparing autologous blood vs sutures for conjunctivalautograft fixation in primary pterygium surgery DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results, assessed trial quality, and extracted data using standard methodological procedures expected by Cochrane. The extracted data included A) study design, sample size, and main findings, B) Baseline characteristics of patients included in this review including their age, sex, pterygium site and grade, and graft size. C) Study outcomes comprising 1) primary outcomes: recurrence rate 2) secondary outcomes: graft stability outcomes (graft retraction, graft displacement), operation time (min) and postoperative symptoms (pain, discomfort, foreign body sensation, tearing) MAIN RESULTS: We included 7 RCTs and The review included662eyes (Blood: 293; Glue: 198; Suture: 171). we assess the 1) primary outcomes: recurrence rate 2) secondary outcomes: graft stability outcomes (graft retraction, graft displacement), operation time (min) and postoperative symptoms (pain, discomfort, foreign body sensation, tearing) CONCLUSIONS: Autologous blood for conjunctivalautograft fixation in pterygium surgery is associated with lower graft stability than fibrin glue or sutures. It was not inferior to fibrin glue or sutures regarding recurrence rate. The overall quality of evidence is low. Further well designed RCTs are needed to fully explore the efficacy of this new technique.

Keywords: pterygium, autograft, ophthalmology, cornea

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Authors: Hilary Modir, Kyle Dutton, Michelle Swab, Shabnam Asghari

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Since its emergence, the cutaneous manifestations of COVID-19 have been documented in the literature. However, the majority are case reports with significant limitations in appraisal quality, thus leaving the role of dermatological manifestations of COVID-19 erroneously underexplored. The primary aim of this review was to systematically examine clinical patterns of dermatological manifestations as reported in the literature. This study was designed as a systematic review of case reports. The inclusion criteria consisted of all published reports and articles regarding COVID-19 in English, from September 1st, 2019, until June 22nd, 2020. The population consisted of confirmed cases of COVID-19 with associated cutaneous signs and symptoms. Exclusion criteria included research in planning stages, protocols, book reviews, news articles, review studies, and policy analyses. With the collaboration of a librarian, a search strategy was created consisting of a mixture of keyword terms and controlled vocabulary. Electronic databases searched were MEDLINE via PubMed, EMBASE, CINAHL, Web of Science, LILACS, PsycINFO, WHO Global Literature on Coronavirus Disease, Cochrane Library, Campbell Collaboration, Prospero, WHO International Clinical Trials Registry Platform, Australian and New Zealand Clinical Trials Registry, U.S. Institutes of Health Ongoing Trials Register, AAD Registry, OSF preprints, SSRN, MedRxiV and BioRxiV. The study selection featured an initial pre-screening of titles and abstracts by one independent reviewer. Results were verified by re-examining a random sample of 1% of excluded articles. Eligible studies progressed for full-text review by two calibrated independent reviewers. Covidence was used to store and extract data, such as citation information and findings pertaining to COVID-19 and cutaneous signs and symptoms. Data analysis and summarization methodology reflect the framework proposed by PRISMA and recommendations set out by Cochrane and Joanna Brigg’s Institute for conducting systematic reviews. The Oxford Centre for Evidence-Based Medicine’s level of evidence was used to appraise the quality of individual studies. The literature search revealed a total of 1221 articles. After the abstract and full-text screening, only 95 studies met the eligibility criteria, proceeding to data extraction. Studies were divided into 58% case reports and 42% series. A total of 833 manifestations were reported in 723 confirmed COVID-19 cases. The most frequent lesions were 23% maculopapular, 15% urticarial and 13% pseudo-chilblains, with 46% of lesions reporting pruritus, 16% erythema, 14% pain, 12% burning sensation, and 4% edema. The most common lesion locations were 20% trunk, 19.5% lower limbs, and 17.7% upper limbs. The time to resolution of lesions was between one and twenty-one days. In conclusion, over half of the reported cutaneous presentations in COVID-19 positive patients were maculopapular, urticarial and pseudo-chilblains, with the majority of lesions distributed to the extremities and trunk. As this review’s sample size only contained COVID-19 confirmed cases with skin presentations, it becomes difficult to deduce the direct relationship between skin findings and COVID-19. However, it can be correlated that acute onset of skin lesions, such as chilblains-like, may be associated with or may warrant consideration of COVID-19 as part of the differential diagnosis.

Keywords: COVID-19, cutaneous manifestations, cutaneous signs, general dermatology, medical dermatology, Sars-Cov-2, skin and infectious disease, skin findings, skin manifestations

Procedia PDF Downloads 156

Authors: Anisa Suraya Ab Razak, Izza Hayat

Abstract:

Introduction: The diagnosis and management of severe hyponatremia in neuropsychiatric patients present a significant challenge to physicians. Several factors contribute, including diagnostic shadowing and attributing abnormal behavior to intellectual disability or psychiatric conditions. Hyponatraemia is the commonest electrolyte abnormality in the inpatient population, ranging from mild/asymptomatic, moderate to severe levels with life-threatening symptoms such as seizures, coma and death. There are several documented fatal case reports in the literature of severe hyponatremia secondary to psychogenic polydipsia, often diagnosed only in autopsy. This paper presents a case study of acute severe hyponatremia in a neuropsychiatric patient with early diagnosis and admission to intensive care. Case study: A 21-year old Caucasian male with known epilepsy and learning disability was admitted from residential living with generalized tonic-clonic self-terminating seizures after refusing medications for several weeks. Evidence of superficial head injury was detected on physical examination. His laboratory data demonstrated mild hyponatremia (125 mmol/L). Computed tomography imaging of his brain demonstrated no acute bleed or space-occupying lesion. He exhibited abnormal behavior - restlessness, drinking water from bathroom taps, inability to engage, paranoia, and hypersexuality. No collateral history was available to establish his baseline behavior. He was loaded with intravenous sodium valproate and leveritircaetam. Three hours later, he developed vomiting and a generalized tonic-clonic seizure lasting forty seconds. He remained drowsy for several hours and regained minimal recovery of consciousness. A repeat set of blood tests demonstrated profound hyponatremia (117 mmol/L). Outcomes: He was referred to intensive care for peripheral intravenous infusion of 2.7% sodium chloride solution with two-hourly laboratory monitoring of sodium concentration. Laboratory monitoring identified dangerously rapid correction of serum sodium concentration, and hypertonic saline was switched to a 5% dextrose solution to reduce the risk of acute large-volume fluid shifts from the cerebral intracellular compartment to the extracellular compartment. He underwent urethral catheterization and produced 8 liters of urine over 24 hours. Serum sodium concentration remained stable after 24 hours of correction fluids. His GCS recovered to baseline after 48 hours with improvement in behavior -he engaged with healthcare professionals, understood the importance of taking medications, admitted to illicit drug use and drinking massive amounts of water. He was transferred from high-dependency care to ward level and was initiated on multiple trials of anti-epileptics before achieving seizure-free days two weeks after resolution of acute hyponatremia. Conclusion: Psychogenic polydipsia is often found in young patients with intellectual disability or psychiatric disorders. Patients drink large volumes of water daily ranging from ten to forty liters, resulting in acute severe hyponatremia with mortality rates as high as 20%. Poor outcomes are due to challenges faced by physicians in making an early diagnosis and treating acute hyponatremia safely. A low index of suspicion of water intoxication is required in this population, including patients with known epilepsy. Monitoring urine output proved to be clinically effective in aiding diagnosis. Early referral and admission to intensive care should be considered for safe correction of sodium concentration while minimizing risk of fatal complications e.g. central pontine myelinolysis.

Keywords: epilepsy, psychogenic polydipsia, seizure, severe hyponatremia

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