Search results for: elderly hip fracture patients

Authors: Michael R. Shurin, Galina Shurin, Vladimir A. Kirichenko

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Background. Visibility of hepatic malignancies is poor on non-contrast imaging for daily verification of liver malignancies prior to radiation therapy on MRI-guided Linear Accelerators (MR-Linac). Ferumoxytol® (Feraheme, AMAG Pharmaceuticals, Waltham, MA) is a SPION agent that is increasingly utilized off-label as hepatic MRI contrast. This agent has the advantage of providing a functional assessment of the liver based upon its uptake by hepatic Kupffer cells proportionate to vascular perfusion, resulting in strong T1, T2 and T2* relaxation effects and enhanced contrast of malignant tumors, which lack Kupffer cells. The latter characteristic has been recently utilized for MRI-guided radiotherapy planning with precision targeting of liver malignancies. However potential radiotoxicity of SPION has never been addressed for its safe use as an MRI-contrast agent during liver radiotherapy on MRI-Linac. This study defines the radiomodulating properties of SPIONs in vitro on human monocyte and macrophage cell lines exposed to 60Go gamma-rays within clinical radiotherapy dose range. Methods. Human monocyte and macrophages cell line in cultures were loaded with a clinically relevant concentration of Ferumoxytol (30µg/ml) for 2 and 24 h and irradiated to 3Gy, 5Gy and 10Gy. Cells were washed and cultured for additional 24 and 48 h prior to assessing their phenotypic activation by flow cytometry and function, including viability (Annexin V/PI assay), proliferation (MTT assay) and cytokine expression (Luminex assay). Results. Our results reveled that SPION affected both human monocytes and macrophages in vitro. Specifically, iron oxide nanoparticles decreased radiation-induced apoptosis and prevented radiation-induced inhibition of human monocyte proliferative activity. Furthermore, Ferumoxytol protected monocytes from radiation-induced modulation of phenotype. For instance, while irradiation decreased polarization of monocytes to CD11b+CD14+ and CD11bnegCD14neg phenotype, Ferumoxytol prevented these effects. In macrophages, Ferumoxytol counteracted the ability of radiation to up-regulate cell polarization to CD11b+CD14+ phenotype and prevented radiation-induced down-regulation of expression of HLA-DR and CD86 molecules. Finally, Ferumoxytol uptake by human monocytes down-regulated expression of pro-inflammatory chemokines MIP-1α (Macrophage inflammatory protein 1α), MIP-1β (CCL4) and RANTES (CCL5). In macrophages, Ferumoxytol reversed the expression of IL-1RA, IL-8, IP-10 (CXCL10) and TNF-α, and up-regulates expression of MCP-1 (CCL2) and MIP-1α in irradiated macrophages. Conclusion. SPION agent Ferumoxytol increases resistance of human monocytes to radiation-induced cell death in vitro and supports anti-inflammatory phenotype of human macrophages under radiation. The effect is radiation dose-dependent and depends on the duration of Feraheme uptake. This study also finds strong evidence that SPIONs reversed the effect of radiation on the expression of pro-inflammatory cytokines involved in initiation and development of radiation-induced liver damage. Correlative translational work at our institution will directly assess the cyto-protective effects of Ferumoxytol on human Kupfer cells in vitro and ex vivo analysis of explanted liver specimens in a subset of patients receiving Feraheme-enhanced MRI-guided radiotherapy to the primary liver tumors as a bridge to liver transplant.

Keywords: superparamagnetic iron oxide nanoparticles, radioprotection, magnetic resonance imaging, liver

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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

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Authors: Kimberly Winnie Achieng Otieno

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The Nairobi Hospital plays a pivotal role in healthcare provision in East and Central Africa, yet it faces challenges in providing accessible dialysis care. This paper explores strategic interventions to enhance dialysis care, improve access and streamline health information management, with an aim of fostering an integrated and patient-centered healthcare system in our region. Challenges at The Nairobi Hospital The Nairobi Hospital currently grapples with insufficient dialysis machines which results in extended turn around times. This issue stems from both staffing bottle necks and infrastructural limitations given our growing demand for renal care services. Our Paper-based record keeping system and fragmented flow of information downstream hinders the hospital’s ability to manage health data effectively. There is also a need for investment in expanding The Nairobi Hospital dialysis facilities to far reaching communities. Setting up satellite clinics that are closer to people who live in areas far from the main hospital will ensure better access to underserved areas. Community Outreach and Education Implementing education programs on kidney health within local communities is vital for early detection and prevention. Collaborating with local leaders and organizations can establish a proactive approach to renal health hence reducing the demand for acute dialysis interventions. We can amplify this effort by expanding The Nairobi Hospital’s corporate social responsibility outreach program with weekend engagement activities such as walks, awareness classes and fund drives. Enhancing Efficiency in Dialysis Care Demand for dialysis services continues to rise due to an aging Kenyan population and the increasing prevalence of chronic kidney disease (CKD). Present at this years International Nursing Conference are a diverse group of caregivers from around the world who can share with us their process optimization strategies, patient engagement techniques and resource utilization efficiencies to catapult The Nairobi Hospital to the 21st century and beyond. Plans are underway to offer ongoing education opportunities to keep staff updated on best practices and emerging technologies in addition to utilizing a patient feedback mechanisms to identify areas for improvement and enhance satisfaction. Staff empowerment and suggestion boxes address The Nairobi Hospital’s organizational challenges. Current financial constraints may limit a leapfrog in technology integration such as the acquisition of new dialysis machines and an investment in predictive analytics to forecast patient needs and optimize resource allocation. Streamlining Health Information Management Fully embracing a shift to 100% Electronic Health Records (EHRs) is a transformative step toward efficient health information management. Shared information promotes a holistic understanding of patients’ medical history, minimizing redundancies and enhancing overall care quality. To manage the transition to community-based care and EHRs effectively, a phased implementation approach is recommended. Conclusion By strategically enhancing dialysis care access and streamlining health information management, The Nairobi Hospital can strengthen its position as a leading healthcare institution in both East and Central Africa. This comprehensive approach aligns with the hospital’s commitment to providing high-quality, accessible, and patient-centered care in an evolving landscape of healthcare delivery.

Keywords: Africa, urology, diaylsis, healthcare

Procedia PDF Downloads 58

Authors: Roseanne Sharon Borromeo, Mariana Carvalho, Mariia Karizhenskaia

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Healthcare providers need to comprehend cultural diversity for optimal patient-centered care, especially near the end of life. Although a universal method for navigating cultural differences would be ideal, culture’s high complexity makes this strategy impossible. Adding cultural humility, a process of self-reflection to understand personal and systemic biases and humbly acknowledging oneself as a learner when it comes to understanding another's experience leads to a meaningful process in palliative care generating respectful, honest, and trustworthy relationships. This study is a systematic review of the literature on cultural humility in palliative care research and best practices. Race, religion, language, values, and beliefs can affect an individual’s access to palliative care, underscoring the importance of culture in palliative care. Cultural influences affect end-of-life care perceptions, impacting bereavement rituals, decision-making, and attitudes toward death. Cultural factors affecting the delivery of care identified in a scoping review of Canadian literature include cultural competency, cultural sensitivity, and cultural accessibility. As the different parts of the world become exponentially diverse and multicultural, healthcare providers have been encouraged to give culturally competent care at the bedside. Therefore, many organizations have made cultural competence training required to expose professionals to the special needs and vulnerability of diverse populations. Cultural competence is easily standardized, taught, and implemented; however, this theoretically finite form of knowledge can dangerously lead to false assumptions or stereotyping, generating poor communication, loss of bonds and trust, and poor healthcare provider-patient relationship. In contrast, Cultural humility is a dynamic process that includes self-reflection, personal critique, and growth, allowing healthcare providers to respond to these differences with an open mind, curiosity, and awareness that one is never truly a “cultural” expert and requires life-long learning to overcome common biases and ingrained societal influences. Cultural humility concepts include self-awareness and power imbalances. While being culturally competent requires being skilled and knowledgeable in one’s culture, being culturally humble involves the sometimes-uncomfortable position of healthcare providers as students of the patient. Incorporating cultural humility emphasizes the need to approach end-of-life care with openness and responsiveness to various cultural perspectives. Thus, healthcare workers need to embrace lifelong learning in individual beliefs and values on suffering, death, and dying. There have been different approaches to this as well. Some adopt strategies for cultural humility, addressing conflicts and challenges through relational and health system approaches. In practice and research, clinicians and researchers must embrace cultural humility to advance palliative care practices, using qualitative methods to capture culturally nuanced experiences. Cultural diversity significantly impacts patient-centered care, particularly in end-of-life contexts. Cultural factors also shape end-of-life perceptions, impacting rituals, decision-making, and attitudes toward death. Cultural humility encourages openness and acknowledges the limitations of expertise in one’s culture. A consistent self-awareness and a desire to understand patients’ beliefs drive the practice of cultural humility. This dynamic process requires practitioners to learn continuously, fostering empathy and understanding. Cultural humility enhances palliative care, ensuring it resonates genuinely across cultural backgrounds and enriches patient-provider interactions.

Keywords: cultural competency, cultural diversity, cultural humility, palliative care, self-awareness

Procedia PDF Downloads 62

Authors: Richa Jaiswal, Vidisha Sharma, Amulya Rattan, Sushma Sagar, Subodh Kumar, Amit Gupta, Biplab Mishra, Maneesh Singhal

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Background: Adequate nutritional support and daily patient monitoring have an independent therapeutic role in the successful management of high output fistulae and early recovery after abdominal trauma. Case presentation: An 18-year-old girl was brought to AIIMS emergency with alleged history of fall of a heavy weight (electric motor) over abdomen. She was evaluated as per Advanced Trauma Life Support(ATLS) protocols and diagnosed to have significant abdominal trauma. After stabilization, she was referred to Trauma center. Abdomen was guarded and focused assessment with sonography for trauma(FAST) was found positive. Complete duodenojejunal(DJ) junction transection was found at laparotomy, and end-to-end repair was done. However, patient was re-explored in view of biliary peritonitis on post-operative day3, and anastomotic leak was found with sloughing of duodenal end. Resection of non-viable segments was done followed by side-to-side anastomosis. Unfortunately, the anastomosis leaked again, this time due to a post-anastomotic kink, diagnosed on dye study. Due to hostile abdomen, the patient was planned for supportive care, with plan of build-up and delayed definitive surgery. Percutaneous transheptic biliary drainage (PTBD) and STSG were required in the course as well. Nutrition: In intensive care unit (ICU), major goals of nutritional therapy were to improve wound healing, optimize nutrition, minimize enteral feed associated complications, reduce biliary fistula output, and prepare the patient for definitive surgeries. Feeding jejunostomy (FJ) was started from day 4 at the rate of 30ml/h along with total parenteral nutrition (TPN) and intra-venous (IV) micronutrients support. Due to high bile output, bile refeed started from day 13.After 23 days of ICU stay, patient was transferred to general ward with body mass index (BMI)<11kg/m2 and serum albumin –1.5gm%. Patient was received in the ward in catabolic phase with high risk of refeeding syndrome. Patient was kept on FJ bolus feed at the rate of 30–50 ml/h. After 3–4 days, while maintaining patient diet book log it was observed that patient use to refuse feed at night and started becoming less responsive with every passing day. After few minutes of conversation with the patient for a couple of days, she complained about enteral feed discharge in urine, mild pain and sign of dumping syndrome. Dye study was done, which ruled out any enterovesical fistula and conservative management were planned. At this time, decision was taken for continuous slow rate feeding through commercial feeding pump at the rate of 2–3ml/min. Drastic improvement was observed from the second day in gastro-intestinal symptoms and general condition of the patient. Nutritional composition of feed, TPN and diet ranged between 800 and 2100 kcal and 50–95 g protein. After STSG, TPN was stopped. Periodic diet counselling was given to improve oral intake. At the time of discharge, serum albumin level was 2.1g%, weight – 38.6, BMI – 15.19 kg/m2. Patient got discharge on an oral diet. Conclusion: Successful management of post-traumatic proximal high output fistulae is a challenging task, due to impaired nutrient absorption and enteral feed associated complications. Strategic- and goal-based nutrition support can salvage such critically ill patients, as demonstrated in the present case.

Keywords: nutritional monitoring, nutritional support, duodenal fistula, abdominal trauma

Procedia PDF Downloads 261

Authors: Liane J. Ioannou, Jonathan Serpell, Cino Bendinelli, David Walters, Jenny Gough, Dean Lisewski, Win Meyer-Rochow, Julie Miller, Duncan Topliss, Bill Fleming, Stephen Farrell, Andrew Kiu, James Kollias, Mark Sywak, Adam Aniss, Linda Fenton, Danielle Ghusn, Simon Harper, Aleksandra Popadich, Kate Stringer, David Watters, Susannah Ahern

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BACKGROUND: There are significant variations in the management, treatment and outcomes of thyroid cancer, particularly in the role of: diagnostic investigation and pre-treatment scanning; optimal extent of surgery (total or hemi-thyroidectomy); use of active surveillance for small low-risk cancers; central lymph node dissections (therapeutic or prophylactic); outcomes following surgery (e.g. recurrent laryngeal nerve palsy, hypocalcaemia, hypoparathyroidism); post-surgical hormone, calcium and vitamin D therapy; and provision and dosage of radioactive iodine treatment. A proven strategy to reduce variations in the outcome and to improve survival is to measure and compare it using high-quality clinical registry data. Clinical registries provide the most effective means of collecting high-quality data and are a tool for quality improvement. Where they have been introduced at a state or national level, registries have become one of the most clinically valued tools for quality improvement. To benchmark clinical care, clinical quality registries require systematic measurement at predefined intervals and the capacity to report back information to participating clinical units. OBJECTIVE: The aim of this study was to develop a core set clinical indicators that enable measurement and reporting of quality of care for patients with thyroid cancer. We hypothesise that measuring clinical quality indicators, developed to identify differences in quality of care across sites, will reduce variation and improve patient outcomes and survival, thereby lessening costs and healthcare burden to the Australian community. METHOD: Preparatory work and scoping was conducted to identify existing high quality, clinical guidelines and best practice for thyroid cancer both nationally and internationally, as well as relevant literature. A bi-national panel was invited to participate in a modified Delphi process. Panelists were asked to rate each proposed indicator on a Likert scale of 1–9 in a three-round iterative process. RESULTS: A total of 236 potential quality indicators were identified. One hundred and ninety-two indicators were removed to reflect the data capture by the Australian and New Zealand Thyroid Cancer Registry (ANZTCR) (from diagnosis to 90-days post-surgery). The remaining 44 indicators were presented to the panelists for voting. A further 21 indicators were later added by the panelists bringing the total potential quality indicators to 65. Of these, 21 were considered the most important and feasible indicators to measure quality of care in thyroid cancer, of which 12 were recommended for inclusion in the final set. The consensus indicator set spans the spectrum of care, including: preoperative; surgery; surgical complications; staging and post-surgical treatment planning; and post-surgical treatment. CONCLUSIONS: This study provides a core set of quality indicators to measure quality of care in thyroid cancer. This indicator set can be applied as a tool for internal quality improvement, comparative quality reporting, public reporting and research. Inclusion of these quality indicators into monitoring databases such as clinical quality registries will enable opportunities for benchmarking and feedback on best practice care to clinicians involved in the management of thyroid cancer.

Keywords: clinical registry, Delphi survey, quality indicators, quality of care

Procedia PDF Downloads 180

Authors: Aastha Arora, Vikas Bhuria, Saurabh Singh, Uma Pathak, Shweta Mathur, Puja P. Hazari, Rajat Sandhir, Ravi Soni, Anant N. Bhatt, Bilikere S. Dwarakanath

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Radiotherapy is an effective curative and palliative option for patients with thoracic malignancies. However, lung injury, comprising of pneumonitis and fibrosis, remains a significant clin¬ical complication of thoracic radiation, thus making it a dose-limiting factor. Also, injury to the lung is often reported as part of multi-organ failure in victims of accidental radiation exposures. Radiation induced inflammatory response in the lung, characterized by leukocyte infiltration and vascular changes, is an important contributing factor for the injury. Therefore, countermeasure agents to attenuate radiation induced inflammatory response are considered as an important approach to prevent chronic lung damage. Although Amifostine, the widely used, FDA approved radio-protector, has been found to reduce the radiation induced pneumonitis during radiation therapy of non-small cell lung carcinoma, its application during mass and field exposure is limited due to associated toxicity and ineffectiveness with the oral administration. The amifostine analogue (DRDE-30) overcomes this limitation as it is orally effective in reducing the mortality of whole body irradiated mice. The current study was undertaken to investigate the potential of DRDE-30 to ameliorate radiation induced lung damage. DRDE-30 was administered intra-peritoneally, 30 minutes prior to 13.5 Gy thoracic (60Co-gamma) radiation in C57BL/6 mice. Broncheo- alveolar lavage fluid (BALF) and lung tissues were harvested at 12 and 24 weeks post irradiation for studying inflammatory and fibrotic markers. Lactate dehydrogenase (LDH) leakage, leukocyte count and protein content in BALF were used as parameters to evaluate lung vascular permeability. Inflammatory cell signaling (p38 phosphorylation) and anti-oxidant status (MnSOD and Catalase level) was assessed by Western blot, while X-ray CT scan, H & E staining and trichrome staining were done to study the lung architecture and collagen deposition. Irradiation of the lung increased the total protein content, LDH leakage and total leukocyte count in the BALF, reflecting endothelial barrier dysfunction. These disruptive effects were significantly abolished by DRDE-30, which appear to be linked to the DRDE-30 mediated abrogation of activation of the redox-sensitive pro- inflammatory signaling cascade, the MAPK pathway. Concurrent administration of DRDE-30 with radiation inhibited radiation-induced oxidative stress by strengthening the anti-oxidant defense system and abrogated p38 mitogen-activated protein kinase activation, which was associated with reduced vascular leak and macrophage recruitment to the lungs. Histopathological examination (by H & E staining) of the lung showed radiation-induced inflammation of the lungs, characterized by cellular infiltration, interstitial oedema, alveolar wall thickening, perivascular fibrosis and obstruction of alveolar spaces, which were all reduced by pre-administration of DRDE-30. Structural analysis with X-ray CT indicated lung architecture (linked to the degree of opacity) comparable to un-irradiated mice that correlated well with the lung morphology and reduced collagen deposition. Reduction in the radiation-induced inflammation and fibrosis brought about by DRDE-30 resulted in a profound increase in animal survival (72 % in the combination vs 24% with radiation) observed at the end of 24 weeks following irradiation. These findings establish the potential of the Amifostine analogue, DRDE-30, in reducing radiation induced pulmonary injury by attenuating the inflammatory and fibrotic responses.

Keywords: amifostine, fibrosis, inflammation, lung injury radiation

Procedia PDF Downloads 510

Authors: Kyriaki Hatziagapiou, Eleni Kakouri, Konstantinos Bethanis, Alexandra Nikola, Eleni Koniari, Charalabos Kanakis, Elias Christoforides, George Lambrou, Petros Tarantilis

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Medulloblastoma is a highly invasive tumour, as it tends to disseminate throughout the central nervous system early in its course. Despite the high 5-year-survival rate, a significant number of patients demonstrate serious long- or short-term sequelae (e.g., myelosuppression, endocrine dysfunction, cardiotoxicity, neurological deficits and cognitive impairment) and higher mortality rates, unrelated to the initial malignancy itself but rather to the aggressive treatment. A strong rationale exists for the use of Crocus sativus L (saffron) and its bioactive constituents (crocin, crocetin, safranal) as pharmaceutical agents, as they exert significant health-promoting properties. Crocins are water soluble carotenoids. Unlike other carotenoids, crocins are highly water-soluble compounds, with relatively low toxicity as they are not stored in adipose and liver tissues. Crocins have attracted wide attention as promising anti-cancer agents, due to their antioxidant, anti-inflammatory, and immunomodulatory effects, interference with transduction pathways implicated in tumorigenesis, angiogenesis, and metastasis (disruption of mitotic spindle assembly, inhibition of DNA topoisomerases, cell-cycle arrest, apoptosis or cell differentiation) and sensitization of cancer cells to radiotherapy and chemotherapy. The current research aimed to study the potential cytotoxic effect of crocins on TE671 medulloblastoma cell line, which may be useful in the optimization of existing and development of new therapeutic strategies. Crocins were extracted from stigmas of saffron in ultrasonic bath, using petroleum-ether, diethylether and methanol 70%v/v as solvents and the final extract was lyophilized. Identification of crocins according to high-performance liquid chromatography (HPLC) analysis was determined comparing the UV-vis spectra and the retention time (tR) of the peaks with literature data. For the biological assays crocin was diluted to nuclease and protease free water. TE671 cells were incubated with a range of concentrations of crocins (16, 8, 4, 2, 1, 0.5 and 0.25 mg/ml) for 24, 48, 72 and 96 hours. Analysis of cell viability after incubation with crocins was performed with Alamar Blue viability assay. The active ingredient of Alamar Blue, resazurin, is a blue, nontoxic, cell permeable compound virtually nonfluorescent. Upon entering cells, resazurin is reduced to a pink and fluorescent molecule, resorufin. Viable cells continuously convert resazurin to resorufin, generating a quantitative measure of viability. The colour of resorufin was quantified by measuring the absorbance of the solution at 600 nm with a spectrophotometer. HPLC analysis indicated that the most abundant crocins in our extract were trans-crocin-4 and trans-crocin-3. Crocins exerted significant cytotoxicity in a dose and time-dependent manner (p < 0.005 for exposed cells to any concentration at 48, 72 and 96 hours versus cells not exposed); as their concentration and time of exposure increased, the reduction of resazurin to resofurin decreased, indicating reduction in cell viability. IC50 values for each time point were calculated ~3.738, 1.725, 0.878 and 0.7566 mg/ml at 24, 48, 72 and 96 hours, respectively. The results of our study could afford the basis of research regarding the use of natural carotenoids as anticancer agents and the shift to targeted therapy with higher efficacy and limited toxicity. Acknowledgements: The research was funded by Fellowships of Excellence for Postgraduate Studies IKY-Siemens Programme.

Keywords: crocetin, crocin, medulloblastoma, saffron

Procedia PDF Downloads 216

Authors: Z. S. Haidar

Abstract:

Millions of teeth are removed annually, and dental extraction is one of the most commonly performed surgical procedures globally. Whether due to caries, periodontal disease, or trauma, exodontia and the ensuing wound healing and bone remodeling processes of the resultant socket (hole in the jaw bone) usually result in serious deformities of the residual alveolar osseous ridge and surrounding soft tissues (reduced height/width). Such voluminous changes render the placement of a proper conventional bridge, denture, or even an implant-supported prosthesis extremely challenging. Further, most extractions continue to be performed with no regard for preventing the onset of alveolar osteitis (also known as dry socket, a painful and difficult-to-treat/-manage condition post-exodontia). Hence, such serious resorptive morphological changes often result in significant facial deformities and a negative impact on the overall Quality of Life (QoL) of patients (and oral health-related QoL); alarming, particularly for the geriatric with compromised healing and in light of the thriving longevity statistics. Despite advances in tissue/wound grafting, serious limitations continue to exist, including efficacy and clinical outcome predictability, cost, treatment time, expertise, and risk of immune reactions. For cases of dry socket, specifically, the commercially available and often-prescribed home remedies are highly-lacking. Indeed, most are not recommended for use anymore. Alveogyl is a fine example. Hence, there is a great market demand and need for alternative solutions. Herein, SockGEL/PLUG (patent pending), an innovative, all-natural, drug-free, and injectable thermo-responsive hydrogel, was designed, formulated, characterized, and evaluated as an osteogenic, angiogenic, anti-microbial, and pain-soothing suture-free intra-alveolar dressing, safe and efficacious for use in fresh extraction sockets, immediately post-exodontia. It is composed of FDA-approved, biocompatible and biodegradable polymers, self-assembled electro-statically to formulate a scaffolding matrix to (1) prevent the on-set of alveolar osteitis via securing the fibrin-clot in situ and protecting/sealing the socket from contamination/infection; and (2) endogenously promote/accelerate wound healing and bone remodeling to preserve the volume of the alveolus. The intrinsic properties of the SockGEL/PLUG hydrogel were evaluated physical-chemical-mechanically for safety (cell viability), viscosity, rheology, bio-distribution, and essentially, capacity to induce wound healing and osteogenesis (small defect, in vivo) without any signaling cues from exogenous cells, growth factors or drugs. The proposed animal model of cranial critical-sized and non-vascularized bone defects shall provide new and critical insights into the role and mechanism of the employed natural bio-polymer blend and gel product in endogenous reparative regeneration of soft tissues and bone morphogenesis. Alongside, the fine-tuning of our modified formulation method will further tackle appropriateness, reproducibility, scalability, ease, and speed in producing stable, biodegradable, and sterilizable thermo-sensitive matrices (3-dimensional interpenetrating yet porous polymeric network) suitable for the intra-socket application. Findings are anticipated to provide sufficient evidence to translate into pilot clinical trials and validate the innovation before engaging the market for feasibility, acceptance, and cost-effectiveness studies.

Keywords: hydrogel, nanotechnology, bioengineering, bone regeneration, nanogel, drug delivery

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Authors: Ziyad S. Haidar

Abstract:

Background: Saliva plays a major role in maintaining oral, dental, and general health and well-being; where it normally bathes the oral cavity acting as a clearing agent. This becomes more apparent when the amount and quality of saliva are significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the 5th most common malignancy worldwide, during which the salivary glands are included within the radiation field/zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely as they become malnourished and experience a significant decrease in their QoL. Accordingly, the formulation of a radio-protection/-prevention modality and development of an alternative Rx to restore damaged salivary gland tissue is eagerly awaited and highly desirable. Objectives: Assess the pre-clinical radio-protective effect and reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs, followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: cancer, head and neck, oncology, drug development, drug delivery systems, nanotechnology, nanoncology

Procedia PDF Downloads 79

Authors: Ziyad S. Haidar

Abstract:

Millions of teeth are removed annually, and dental extraction is one of the most commonly performed surgical procedures globally. Whether due to caries, periodontal disease or trauma, exodontia and the ensuing wound healing and bone remodeling processes of the resultant socket (hole in the jaw bone) usually result in serious deformities of the residual alveolar osseous ridge and surrounding soft tissues (reduced height/width). Such voluminous changes render the placement of a proper conventional bridge, denture or even an implant-supported prosthesis extremely challenging. Further, most extractions continue to be performed with no regard for preventing the onset of alveolar osteitis (also known as dry socket, a painful and difficult-to-treat/-manage condition post-exodontia). Hence, such serious resorptive morphological changes often result in significant facial deformities and a negative impact on the overall Quality of Life (QoL) of patients (and oral health-related QoL), alarming, particularly for the geriatric with compromised healing and in light of the thriving longevity statistics. Opportunity: Despite advances in tissue/wound grafting, serious limitations continue to exist, including efficacy and clinical outcome predictability, cost, treatment time, expertise and risk of immune reactions. For cases of dry sockets, specifically, the commercially-available and often-prescribed home remedies are highly lacking. Indeed, most are not recommended for use anymore. Alveogyl is a fine example. Hence, there is a great market demand and need for alternative solutions. Solution: Herein, SockGEL/PLUG (patent pending), an all-natural, drug-free and injectable stimuli-responsive hydrogel, was designed, formulated, characterized and evaluated as an osteogenic, angiogenic, anti-microbial and pain-soothing suture-free intra-alveolar dressing, safe and efficacious for use in several oro-dental and cranio-maxillo-facial interventional applications; for example: in fresh dental extraction sockets, immediately post-exodontia. It is composed of FDA-approved, biocompatible and biodegradable polymers, self-assembled electro-statically to formulate a scaffolding matrix to (a) prevent the onset of alveolar osteitis via securing the fibrin-clot in situ and protecting/sealing the socket from contamination/infection; and (b) endogenously promote/accelerate wound healing and bone remodeling to preserve the volume of the alveolus. Findings: The intrinsic properties of the SockGEL/PLUG hydrogel were evaluated physico-chemico-mechanically for safety (cell viability), viscosity, rheology, bio-distribution and essentially, capacity to induce wound healing and osteogenesis (small defect, in vivo) without any signaling cues from exogenous cells, growth factors or drugs. The performed animal model of cranial critical-sized and non-vascularized bone defects shall provide vitally critical insights into the role and mechanism of the employed natural bio-polymer blend and gel product in endogenous reparative regeneration of soft tissues and bone morphogenesis. Alongside, the fine-tuning of our modified formulation method will further tackle appropriateness, reproducibility, scalability, ease and speed in producing stable, biodegradable and sterilizable stimuli (thermo-sensitive and photo-responsive) matrices (3-dimensional interpenetrating yet porous polymeric network) suitable for an intra-socket application, and beyond. Conclusions and Perspective: Findings are anticipated to provide sufficient evidence to translate into pilot clinical trials and validate the bionanomaterial before engaging the market for feasibility, acceptance and cost-effectiveness studies. The SockGEL/PLUG platform is patent pending: SockGEL is a bio-inspired drug-free hydrogel; SockPLUG is a drug-loaded hydrogel designed for complex indications.

Keywords: hydrogel, injectable, dentistry, craniomaxillofacial complex, bioinspired, nanobiotechnology, biopolymer, sol-gel, stimuli-responsive, matrix, tissue engineering, regenerative medicine

Procedia PDF Downloads 72

Authors: Ziyad S. Haidar

Abstract:

Background: Saliva plays a major role in maintaining oral and dental health (consequently, general health and well-being). Where it normally bathes the oral cavity and acts as a clearing agent. This becomes more apparent when the amount and quality of salivare significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the fifth most common malignancy worldwide, during which the salivary glands are included within the radiation field or zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely because they become malnourished and experience a significant decrease in their quality of life. Accordingly, the development of an alternative treatment to restore or regenerate damaged salivary gland tissue is eagerly awaited. Likewise, the formulation of a radioprotection modality and early damage prevention strategy is also highly desirable. Objectives: To assess the pre-clinical radio-protective effect as well as the reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned in this experimental work for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs (in solution and powder formats), followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy (revised from our previous 15Gy model) was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: saliva, head and neck cancer, nanotechnology, controlled drug delivery, xerostomia, mucositis, biopolymers, innovation

Procedia PDF Downloads 88