Plasma fibrinogen degradation products with salivary coagulopathy in OSMF among Indians.

Oral submucous fibrosis (OSMF) produces changes localized to oral cavity. Hence, it is reasonable to assume that saliva may have an important role in its etiology. This prospective case control study included 37 patients with OSMF which were compared with age and gender matched healthy controls. Salivary coagulopathy procedures as described by Chatuvedi et al. and quantification of plasma fibrinogen degradation products using a commercially available kit were carried out. The obtained data was analyzed using Chi-square tests and Tukey HSD test. The salivary coagulopathy was strongly indicated in saliva of OSMF patients and was dependent on the severity of disease. There were also increased levels of plasma fibrinogen degradation products compared to the controls and were found to have a statistically significant correlation with increasing clinical grades of oral submucous fibrosis (p≤ 0.05).

Primary tumor lymphangiogenesis in oral squamous cell carcinoma with N0 neck is the key determinant of its therapeutics.

BACKGROUND: Vascular Endothelial Growth Factor-C (VEGF-C) plays a critical role in tumor growth and invasion through lymphangiogenesis and helps to identify the variability of lymphatic potential of oral squamous cell carcinoma (OSCC) cases with or without lymph node metastasis. MATERIALS AND METHODS: A total of 65 cases of OSCC were included. The clinical details were obtained from patient records. The cases were grouped as N0 versus any N categories. All the cases were immunohistochemically evaluated for VEGF-C within the primary tumor using a standard protocol. An average of 5 lymph nodes were dissected from all neck dissection specimens and were evaluated histopathologically. The data obtained were statistically evaluated at 95% confidence interval and P ≤ 0.05. RESULTS: 100% cases in our study showed VEGF-C immunopositivity. The immunoreactivity increased linearly with advancing grades. A total of 31 out of 40 N0 OSCC revealed score 2 (26%-50%) of VEGF-C immunoreactivity. Eighteen cases were false negative clinically. CONCLUSION: Recognition of locoregional spread may empower clinicians for correct therapeutic decisions in N0 versus any N case.

Neuroectodermal influence in odontogenic cyst and tumor: evidence through CD56 immunoexpression.

BACKGROUND AND OBJECTIVES: CD56, associated with neuroectodermal differentiation of the embryonal cells, is often considered a marker of neural lineage. Odontogenic keratocysts (OKCs) are of particular interest because of their characteristic histopathologic features, high recurrence rate, and aggressive behavior. CD56 immunoreactivity in these lesions has been reported with very high frequency. The present study analyzes the immunoexpression of CD56 in ameloblastoma (AM) and OKC to infer neuroectodermal influence in the pathogenesis of odontogenic lesions and its correlation with clinicopathologic parameters. MATERIALS AND METHODS: Fifty histopathologically confirmed cases of OKC and AM, 25 from tooth-bearing (TB) and molar-ramus (MR) regions each, and 5 dental follicular tissues as control were collected from the department archives and immunohistochemical analysis with CD56 was carried out. RESULTS: CD56 immunopositivity was seen in 64% AM and 36% OKC cases. The majority of AM cases showed cytoplasmic expression in the peripheral cells of odontogenic islands; similarly, OKC cases showed continuous and uniform cytoplasmic expression in the basal and parabasal cells of the cystic lining. CD56 immunopositivity was found in more AM cases as compared to OKC cases in both the TB and MR regions. INTERPRETATION AND CONCLUSIONS: The assessment of CD56 immunoexpression in odontogenic cyst and tumor (AM) may aid in understanding the role of neuroectodermal influence in the etiopathogenetic pathways and a possible influence of CD56 on the clinical behavior and aggressiveness of the odontogenic lesions. A correlation of CD56 expression with the clinical outcome of the disease (site, perforation, root resorption, and tooth displacement) can help envisage possible prognostic assessment for these lesions.

Odontogenic myxoma of the mandible: An update on pathogenesis and differential diagnosis.

Odontogenic myxomas (OMs) represent asymptomatic, slowly expanding gnathic lesions with aggressive biological behaviour. Though the spectrum of OMs remains classical with multilocular radiolucency and presentation of stellate-shaped cells embedded in a mucoid stroma, they may mimic many other lesions radiographically or histopathologically. We hereby discuss a case of OM in a 28-year-old woman with special emphasis on pathogenesis and differential diagnosis.

Student psychological well-being in higher education: The role of internal team environment, institutional, friends and family support and academic engagement.

Psychological well-being of students is an area of concern in higher education institutes across the world. Although several studies have explored the factors associated with students' psychological well-being, limited research has focused on the relation between the overall support for students and psychological well-being. Students of higher education may get formal support, in the form of team environment and institutional support; and informal support, in the form of family and friends' support. The purpose of this study is to examine the relation of these four kinds of support with psychological well-being of management students. We also examine the intervening role of academic engagement in this relationship. Analysis using structural equation modeling and hierarchical regression on data collected from 309 management students from Indian universities, shows that positive internal team environment, and institutional and family support positively relate to students' psychological well-being. Academic engagement partially mediates the relation between positive internal team environment and psychological well-being, and family support and psychological well-being. Also, academic engagement fully mediates the relation between institutional support and psychological well-being. The study highlights the significance of internal team environment and institutional support for students' academic engagement and psychological well-being, and the role of academic engagement in determining well-being. Based on these findings, we suggest interventions that can be undertaken by educational institutions to enhance psychological well-being of students. Theoretical implications and research avenues are discussed.

Research Landscape of Lymphovascular Invasion in Oral Squamous Cell Carcinoma: A Bibliometric Analysis From 1994 to 2023.

The primary factor affecting tumor biology is neo-lymphangiogenesis in solid epithelial malignancies like oral squamous cell carcinoma (OSCC). Determining the impact of lymphovascular invasion is critical in order to determine OSCC's locoregional and global dissemination. Bibliometric landscapes are vital to learning about the most recent advancements in the aforementioned topic because the ongoing research in OSCC is multifaceted. This analysis can reveal the progressions that might modernize OSCC diagnosis and treatment. The present analysis has been therefore undertaken to study the relevance and effects of lymphovascular invasion in OSCC utilizing co-occurrence of keywords analysis and co-authorship analysis in the PubMed database. The keywords included "lymphovascular invasion in oral squamous cell carcinoma" using the Boolean operator (AND). A cross-sectional bibliometric analysis of full-text articles from 1994 to 2023 using VOSviewer (Version 1.6.19; Centre for Science and Technology Studies, Leiden University, The Netherlands) was performed. The data obtained was analyzed for co-occurrence and co-authorship analysis using the VOSviewer standard protocol. The query revealed 296 searches in the PubMed database. Seven clusters were found with default colors in the representation of the entire term co-occurrence network, which also displayed a total link strength of 22,262. The items were categorized into clusters based on their commonalities. The labels' weights, as determined by links and occurrences, did not depend on one another, and the co-occurrence of keywords does not imply a causal association. In the item density visualization, item labels represented individual things. The number of items from a cluster that was close to the point was represented by the weight given to its color, which was formed by combining the colors of other clusters. A network of 57 authors who matched the search parameters was discovered by the co-authorship analysis. The network visualization map displayed three clusters with a total link strength of 184. The quantity of co-authorship relationships and the number of publications did not appear to be significantly correlated. In conclusion, this investigation uncovered a sizable body of bibliometric data that emphasizes key trends and advancements in the aforementioned theme. The observed variances may be a result of the various objectives of the researchers and journals, who collaborate to provide the best possible literature dissemination.

Diagnostic utility of special stains in defining the spectrum of maxillofacial pathologies.

Background: The Fine needle aspiration cytology (FNAC) is considered as a valuable and distinguished diagnostic test in the initial assessment of the patients presenting with a mass in the head and neck region or when a recurrence is suspected after previous treatment. Aims: This study was therefore designed to elucidate the efficacy of FNAC as an alternate diagnostic tool to histopathology in head and neck swellings and evaluation of staining efficacy of PAP and MGG stain over Haematoxylin and eosin (H and E) in routine cytopathological smears. Settings and Design: The study was conducted in the Department of Oral and Maxillofacial Pathology, where FNAC samples were collected from 150 patients with head and neck swellings. Materials and Methods: All the slides were stained with H and E, Papanicolaou (PAP), and May Grunewald Giemsa (MGG) stains. The cytopathological diagnosis was compared with histopathological diagnosis based on H and E stained sections obtained from paraffin-embedded formalin-fixed biopsy specimen of benign and malignant neoplasms. Statistical Analysis Used: The resulting data were analyzed using SPSS software version 19. Differences between the variables were analyzed using Pearson Chi-square test and Kruskal-Wallis test wherever applicable. Results: The FNAC as a diagnostic tool has sensitivity of 84.8%, 72.72%, and 78.78%, specificity of 62.5%, 75%, and 75%, and accuracy of 80.48%, 73.14%, and 78.04% in H and E, MGG, and PAP stain, respectively. PAP stain was the most efficient stain when all qualitative parameters are taken into consideration with maximum sensitivity and specificity for achieving definitive cytodiagnosis. Conclusions: The FNAC is an inexpensive and minimally invasive technique to diagnose different types of head and neck swellings and complement histopathological diagnosis.

Histopathological prognosticators and their clinicopathological correlation in oral squamous cell carcinomas of the tongue.

Background: Tongue carcinomas account for 25%-40% of intraoral squamous cell carcinomas (OSCCs). Although TNM staging systems is an international standard for cancer reporting, prognosis evaluation, and treatment planning, multiple histopathological risk assessment predictors such as tumor thickness (TT), tumor shape, tumor growth pattern, and invasive malignancy grading scoring systems have been studied and should form a basis for prediction and prognostication of such aggressive carcinomas. Aim: To evaluate and characterize the histomorphological prognostic indicators in OSCCs of tongue and compare it with OSCCs of other anatomic sites within the oral cavity. Furthermore, to elucidate the significance of histopathological indicators in predicting prognosis of tongue squamous cell carcinomas (SCCs). Materials and Methods: Forty SCC cases with 20 each of tongue and 20 from other intraoral sites were retrieved from department archives. Clinical data and staging were obtained for each case. Histomorphological parameters including pattern of invasion (POI), tumor budding (TB), depth of invasion (DOI), TT, lymphocytic host response, tumor-associated tissue eosinophilia (TATE), vascular invasion, perineural invasion (PNI), and muscular invasion were assessed. The results were statistically evaluated. Results: TB, DOI, and sarcolemmal spread were significant histologic predictors in tongue SCC. Upon correlation of histomorphological parameters with clinical staging, TT, POI, and TATE were observed to be significantly correlated (P ≤ 0.05). Conclusion: The histomorphological risk assessment model may serve as important addition to the existing prognosticators and may be used as a prognostic index to help plan and individualize treatment protocol in cases with aggressive high-risk disease for whom the use of multimodality treatment seems beneficial.

Outcomes with adjuvant anti-PD-1 therapy in patients with sentinel lymph node-positive melanoma without completion lymph node dissection.

Until recently, most patients with sentinel lymph node-positive (SLN+) melanoma underwent a completion lymph node dissection (CLND), as mandated in published trials of adjuvant systemic therapies. Following multicenter selective lymphadenectomy trial-II, most patients with SLN+ melanoma no longer undergo a CLND prior to adjuvant systemic therapy. A retrospective analysis of clinical outcomes in SLN+ melanoma patients treated with adjuvant systemic therapy after July 2017 was performed in 21 international cancer centers. Of 462 patients who received systemic adjuvant therapy, 326 patients received adjuvant anti-PD-1 without prior immediate (IM) CLND, while 60 underwent IM CLND. With median follow-up of 21 months, 24-month relapse-free survival (RFS) was 67% (95% CI 62% to 73%) in the 326 patients. When the patient subgroups who would have been eligible for the two adjuvant anti-PD-1 clinical trials mandating IM CLND were analyzed separately, 24-month RFS rates were 64%, very similar to the RFS rates from those studies. Of these no-CLND patients, those with SLN tumor deposit >1 mm, stage IIIC/D and ulcerated primary had worse RFS. Of the patients who relapsed on adjuvant anti-PD-1, those without IM CLND had a higher rate of relapse in the regional nodal basin than those with IM CLND (46% vs 11%). Therefore, 55% of patients who relapsed without prior CLND underwent surgery including therapeutic lymph node dissection (TLND), with 30% relapsing a second time; there was no difference in subsequent relapse between patients who received observation vs secondary adjuvant therapy. Despite the increased frequency of nodal relapses, adjuvant anti-PD-1 therapy may be as effective in SLN+ pts who forego IM CLND and salvage surgery with TLND at relapse may be a viable option for these patients.

Prognostic Relevance of Lymphatic Vessel Density in Squamous Cell Carcinomas of the Oral Cavity: A Systematic Review and Meta-Analysis.

BACKGROUND: Oral Squamous Cell Carcinoma (OSCC), a major debilitating illness demands focus in recent times due to a constant upsurge in cases and poor prognostic implications. An urgent mandate upon finding evidence of relevant prognostic markers is the need of the hour. This systematic review and meta-analysis, therefore, elect an objective assessment of Lymphatic Vessel Density (LVD) as a pertinent parameter governing OSCC prognosis. METHODS: The study protocol was registered at the International Prospective Register Of Systematic Reviews (PROSPERO). Databases were searched using the MeSH keywords for all study types following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The exposure under consideration was the evaluation of LVD in patients of OSCC. The outcome was measured as pooled Hazard/Odd's/Risk ratios in survived versus non-survived OSCC population. The risk of bias assessment was performed using the QUIPS tool. Heterogeneity was assessed by Chi-square and I2 statistics whereas publication bias was investigated using Egger's test of significance. All the statistical analysis was conducted using STATA version 13.0. RESULTS: The initial search of 226 records were screened and filtered through the inclusion and exclusion criteria to achieve an outcome of 15 studies for qualitative synthesis out of which seven studies were eligible for meta-analysis. Pooled Hazard of enhanced Lymphatic Vessel Density was not found to be statistically significant (HR = 1.98, p = 0.553); contrary to the pooled Odd's/Risk for patient survival which was statistically significant (RR = 1.33, p = 0.046). The I2 test of heterogeneity was also significant (58.8%, p = 0.046). CONCLUSIONS: This meta-analysis helps to generate pathfinding evidence for a noteworthy role of Lymphatic Vessel Density evaluation in suggesting OSCC prognosis.

Motivating Women to Travel in India: Embodying Safety as an Organizational Purpose.

Safety concerns are a key factor that demotivate women from traveling. Tourism organizations are yet to develop approaches to address this comprehensively. Employing the case study design, this study describes how an Indian tourism organization adopted safe women travel as its purpose to reduce women's safety risk perceptions and motivated them to travel. Nine qualitative interviews were conducted with key stakeholders including co-founders, employees, customers, and vendors. Data were analyzed using thematic analysis resulting in the identification of purpose as a pull factor. Themes of defining, communicating, embodying purpose, and its resulting influence were identified. Through this process, the organization was able to positively impact perceptions of safety, enhance women's travel motivation, and develop long-term associations with all stakeholders. An actionable framework for implementing purpose was developed that can be used to align tourism organizations' practices and activities.

CD44 related stemness maneuvers oral squamous cell carcinoma biology.

Introduction: Despite the commendable advancements in oral squamous cell carcinoma (OSCC) diagnostics and therapeutics, it remains a considerable medical challenge. Recent evidence suggests that small populations of stem-like cancer cells are responsible for tumor initiation, progression and metastasis. These cancer stem cells (CSCs) have been identified and characterized in various types of cancers, including OSCCs. CSC hypothesis has been supported by the expression of CD44, CD133, ALDH1 and ABCG2. Amongst them, CD44 (a transmembrane glycoprotein), is the most reported CSC marker in OSCCs. The increasing incidence of OSCC combined with its poor survival rates motivates a need for research into the expression of adhesion molecules and may play a pivotal role in studying tumor biology related to invasion and distant metastasis. Objective: To quantify the expression of CD44 in the different grades of OSCC and to correlate the expression of CD44 with clinicopathological parameters. Method: A total of 20 formalin-fixed paraffin-embedded tissues of OSCC were retrieved from department archives. Immunohistochemical staining was performed using anti-CD44 antibody (Biogenex). The expression was assessed semi-quantitatively in varying histopathological grades of OSCC and were correlated with tumor, node, metastasis (TNM) staging which were obtained from the department records. The results were statistically evaluated. Result: Overexpression of CD44 was detected in 48% of well-differentiated OSCCs followed by a linear decrease in moderately differentiated and poorly differentiated OSCCs and the expression correlated with the tumor size (T) in 23% cases and with lymph node metastases (N) in 42% of cases (P ≤0.05). Conclusion: The results of the present study suggested an altered expression of CD44 in OSCC. This depicts an association of CD44 with tumor aggressiveness and Epithelial Mesenchymal Transition (EMT) related to loss of cell adhesion in a subset of OSCC-clearly stating tumor cell stemness as a key factor in malignant potential of OSCC.

Outcomes Following Intolerance to Tacrolimus/Sirolimus Graft-versus-Host Disease Prophylaxis for Allogeneic Hematopoietic Cell Transplantation.

Although tacrolimus and sirolimus (TAC/SIR) is an accepted graft-versus-host disease (GVHD) prophylaxis regimen following allogeneic hematopoietic cell transplantation (HCT), toxicity from this regimen can lead to premature discontinuation of immunosuppression. There are limited studies reporting outcomes and subsequent treatment of patients with TAC/SIR intolerance. This study was conducted to assess the outcomes of patients with TAC/SIR intolerance and guide their subsequent management. We retrospectively analyzed transplantation outcomes of consecutive adult patients at Moffitt Cancer Center who underwent allogeneic HCT with TAC/SIR as GVHD prophylaxis between 2009 and 2018. TAC/SIR intolerance was defined as discontinuation of either TAC or SIR due to toxicity before post-transplantation day +100. A total of 777 patients met the inclusion criteria. The median duration of follow-up was 22 months (range, 0.2 to 125 months). Intolerance occurred in 13% (n = 104) of the patients at a median of 30 days (range, 5 to 90 days). The most common causes of intolerance were acute kidney injury (n = 53; 51%), thrombotic microangiopathy (n = 31; 28%), and veno-occlusive disease (n = 23; 22%). The cumulative incidence of grade II-IV acute GVHD at 100 days was 50% (95% CI, 39% to 64%) in the TAC/SIR-intolerant patients and 25% (95% CI, 22% to 29%) in patients tolerant to this regimen (P < .0001). In multivariate analyses, the incidence of grade II-IV 4 acute GVHD was significantly higher in the TAC/SIR-intolerant patients (hazard ratio [HR], 2.40; 95% CI, 1.59 to 3.61; P < .0001). Similarly, in multivariate analyses, the TAC/SIR-intolerant patients had a higher incidence of chronic GVHD (HR, 1.48; 95% CI, 1.03 to 2.12; P = .03). The nonrelapse mortality (NRM) at 1 year was 47% (95% CI, 38% to 59%) in the TAC/SIR-intolerant patients and 12% (95% CI, 10% to 15%) in those tolerant to the regimen (P < .0001). The 2-year relapse-free survival was 35% (95% CI, 25% to 44%) in the TAC/SIR-intolerant patients and 60% (95% CI, 57% to 65%) in the TAC/SIR-tolerant patients (HR, 2.30; 95% CI, 1.61 to 3.28; P < .0001). Intolerance stratified by early (≤30 days) versus late (31 to 100 days) significantly affected the cumulative incidence of acute GVHD at 75% (early; 95% CI, 59% to 94%) versus 33% (late; 95% CI, 21% to 50%) (P = .001), as well as the cumulative incidence of NRM at 61% (early; 95% CI, 48% to 77%) versus 35% (late; 95% CI, 24% to 51%) (P = .006). Most patients who developed TAC/SIR intolerance were switched to an alternative 2-drug regimen (71 of 104; 68%), most commonly mycophenolate mofetil in addition to continuing TAC or SIR (68 of 71; 96%). Overall, TAC/SIR intolerance was associated with poorer outcomes. Early intolerance contributed to a higher risk of acute GVHD, increased NRM, and inferior survival. Patients with early intolerance were often switched to an alternative agent, and patients with late intolerance tended to be continued on single-drug therapy without substitution. The use of single-drug versus 2-drug regimens after intolerance did not appear to affect outcomes. Management strategies to mitigate the risks of intolerance are warranted.

Assessment of Risk of Malignancy of Fine-needle Aspiration Cytology in Salivary Gland Lesions Using the Milan System for Reporting Salivary Gland Cytopathology Categorization: A Systematic Review and Meta-analysis.

BACKGROUND: Fine-needle aspiration cytology (FNAC) of the salivary gland is crucial in the identification of salivary gland lesions, but the variation in morphological pattern and the overlap of morphological traits can result in erroneous interpretation and affect treatment, making FNAC of the salivary gland problematic. The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was created to address these problems. OBJECTIVES: To ascertain whether the FNAC method using MSRSGC was reliable in predicting the risk of malignancy (ROM) in each category of salivary gland lesions. MATERIALS AND METHODS: The databases PubMed-MEDLINE, Web of Science, Cochrane, Scopus, and Google Scholar were all searched using pertinent keywords, reference searches, and citation searches. A fixed effect model was used to determine the pooled proportion with a 95% confidence interval (CI). All statistical analyses were performed using Meta Disc and R version 4.0.2 (R Foundation for Statistical Computing). RESULTS: After reviewing the submissions' abstracts and titles, 58 documents that satisfied the necessary inclusion and exclusion criteria were ultimately selected. A total of 19,652 samples from 19,408 individuals was analyzed, out of which 9,958 samples were available for histopathological follow-up. The pooled ROM for category I was 10%, category II was 5%, category III was 28%, category IV A was 2%, Category IV B was 34%, category V was 91%, and category VI was 99%. CONCLUSION: Milan System for Reporting Salivary Gland Cytopathology is useful for risk stratification and quality control, confirming its validity and diagnostic utility. Widespread use of MSRSGC would improve the accuracy of salivary gland cytology and lead to better patient care and improved treatment strategies. The results of this study are in consonance with reported values as per MSRSGC except for category V. CLINICAL SIGNIFICANCE: The MSRSGC which was first reported in 2018 is a very useful tool for proper stratification of ROM in salivary gland FNAC. This study allowed us to validate the ROM values in different categories as reported in MSRSGC.

Markers of cytotoxicity and oxidative DNA damage in Diabesity: A new age illness.

Background: The oral mucous membrane is particularly sensitive to certain types of systemic disorders such as anemia, vitamin deficiencies, infectious diseases, hormonal disturbances and can be objectively reproduced through definite measurements using cytomorphometry. Objectives: The objective of the study is to evaluate the quantitative and qualitative changes in cytological buccal smears of obese individuals with type II diabetes (Group 1 = 20), obese individuals without type II diabetes (Group 2 = 20), individuals with type II diabetes without obesity (Group 3 = 20) by comparing with controls (individuals without obesity and without type II diabetes) (Group 4 = 20). Materials and Methods: Buccal mucosal cells were scraped from study participants and were subjected to morphometric analysis (Magnus Pro software). Clinical history, hemoglobin A1c, heights and weights of participants were measured and consequently, their body mass index was calculated. Quantitative parameters (nuclear area, cytoplasmic area, nucleo-cytoplasmic ratio) and qualitative parameters (micronuclei [MN], nuclear budding, nuclear disintegration, apoptosis, necrosis) were assessed among the groups. The data were statistically interpreted using SPSS software version 20.0. Results: There is an increase in nuclear diameter and nuclear: cytoplasmic ratio of Groups 1 and 3 relative to Group 2. The qualitative assessment revealed MN and nuclear disintegration in Group 1 and 3 individuals. In addition, other qualitative changes such as nuclear budding and apoptotic bodies were evident in patients with type II diabetes. Conclusion: The aforementioned qualitative and quantitative parameters facilitate early diagnosis and identification of individuals at risk of developing new age systemic illnesses such as diabetes and obesity.

Outcomes of metastatic urothelial carcinoma following discontinuation of enfortumab-vedotin.

BACKGROUND: Enfortumab vedotin (EV) is approved to treat metastatic urothelial carcinoma (mUC) following platinum and PD1/L1 inhibitors. Since the outcomes and patterns of therapy of patients following discontinuation of EV are unknown, we conducted a retrospective study to assess this issue. METHODS: Data were retrospectively obtained from patients with mUC following discontinuation of EV after prior platinum-based chemotherapy and PD1/L1 inhibitors. Objective response rate (ORR) was evaluated in those who received therapy post-EV. Statistical analyses were performed to describe the overall survival (OS) and compare patient characteristics and outcomes of those who did or did not receive treatment post-EV. RESULTS: Data were available for 63 patients from 6 institutions: 46 (73%) were male and median age was 68 years (range 43-83). The median OS was 32 weeks. Thirty-two patients (51%) received therapy after EV. The OS of those who did vs. did not receive post-EV therapy was significantly different (median 43.1 vs. 16.9 weeks, P = .015). Longer duration of prior EV therapy was associated with receipt of post-EV therapy (P = .0437) as well as OS in both the treated (P = .045) and untreated groups (P = .012). Objective response was observed in 3 of 32 patients (9.4%) who received therapy post-EV. CONCLUSION: Outcomes of patients with mUC following discontinuation of EV are dismal and only 51% received therapy after discontinuation of EV. This study identifies benchmarks for the interpretation of activity of new agents following EV and raises the hypothesis for duration of EV as a potential prognostic factor following discontinuation of EV.

Cardiovascular Adverse Events Reported from COVID-19 Vaccines: A Study Based on WHO Database.

BACKGROUND: Thirteen COVID-19 vaccines are granted emergency approval. It is crucial to monitor their adverse events post vaccination. The present study focuses on cardiovascular adverse events post-COVID-19 vaccination and aims to determine adverse events with the administered vaccine. METHODOLOGY: The cardiovascular (CVS) adverse events were extracted for three broad headings (SOCs) - cardiac disorders, vascular disorders, and investigations. Descriptive statistics were reported in the form of percentage and frequency, and the disproportionality analysis was conducted. RESULTS: For the cardiovascular system, 4863 adverse events (AEs) were reported from BNT162b2 Pfizer, 1222 AstraZeneca, Moderna, and other COVID-19 vaccines. Common adverse events observed with vaccines under study were tachycardia (16.41%), flushing (12.17%), hypertension (5.82%), hypotension (3.60%) and peripheral coldness (2.41%). Based on disproportionality analysis (IC025 values), acute myocardial infarction, cardiac arrest, and circulatory collapse were linked to the vaccines in the age group >75 years. Hypertension, severe hypertension, supraventricular tachycardia, sinus tachycardia, and palpitations were associated across all age groups and either gender. Amongst the investigations, abnormal ECG findings raised C-reactive protein, elevated D dimer, and troponin were reported in specific age groups or gender or all subjects. CONCLUSION: Although cardiovascular events have been reported with the COVID-19 vaccines, the causality is yet to be established because such CVS AEs are also usually associated with the general public even without intervention. Hence, people should be administered these vaccines, and sustained monitoring of these AEs should be done.

Integrating Somatic and Germline Next-Generation Sequencing Into Routine Clinical Oncology Practice.

Next-generation sequencing (NGS) is rapidly expanding into routine oncology practice. Genetic variations in both the cancer and inherited genomes are informative for hereditary cancer risk, prognosis, and treatment strategies. Herein, we focus on the clinical perspective of integrating NGS results into patient care to assist with therapeutic decision making. Five key considerations are addressed for operationalization of NGS testing and application of results to patient care as follows: (1) NGS test ordering and workflow design; (2) result reporting, curation, and storage; (3) clinical consultation services that provide test interpretations and identify opportunities for molecularly guided therapy; (4) presentation of genetic information within the electronic health record; and (5) education of providers and patients. Several of these key considerations center on informatics tools that support NGS test ordering and referencing back to the results for therapeutic purposes. Clinical decision support tools embedded within the electronic health record can assist with NGS test utilization and identifying opportunities for targeted therapy including clinical trial eligibility. Challenges for project and change management in operationalizing NGS-supported, evidence-based patient care in the context of current information technology systems with appropriate clinical data standards are discussed, and solutions for overcoming barriers are provided.

Concurrent dentigerous cyst with ossifying fibroma of the mandible.

Dentigerous cyst (DC) and ossifying fibroma (OF) are intraosseous lesions of the jaw. Both are varied pathological entities with a wide spectrum of clinical and histological features along with distinct treatment plan and prognosis. While OF comes under fibro-osseous lesions of the jaws, DC is a developmental odontogenic cyst which is formed by the accumulation of fluid between reduced enamel epithelium and enamel or between layers of the enamel organ. This case report presents a rare display of two distinct pathologies synchronously and aims to discuss the possible histogenesis for the same.

Large granular lymphocytic leukemia - A retrospective study of 319 cases.

Large granular lymphocytic leukemia (LGLL) is a rare hematological malignancy that arises from cytotoxic T lymphocytes (T-LGLL) in 85% of cases and natural killer (NK) cells in the rest. A significant knowledge gap exists regarding the pathogenesis, treatment choices, and prognostic factors of LGLL. We report a cohort of 319 consecutive LGLL patients who presented to our cancer center between 2001 and 2020. A total of 295 patients with T-LGLL and 24 with chronic NK-cell lymphoproliferative disorder (CLPD-NK) were identified. The median age was 65 years (range, 17-90 years). Eighty-three patients (26.0%) had autoimmune diseases. A total of 119 patients (37.3%) had coexisting malignancies, 66 (20.7%) had solid tumors, and 59 (18.5%) had hematological malignancies. Most coexisting malignancies were diagnosed before the diagnosis of LGLL. Treatment was needed for 57% of patients. Methotrexate (MTX), cyclophosphamide (Cy), and cyclosporine A (CSA) were most used and had similar response rates between 61.5%-74.4%. Cy produced more complete responses (32.3%) compared to MTX and CSA (15.7% and 23.1%, respectively). Thrombocytopenia, splenomegaly, and female gender (after controlling for autoimmune diseases) were associated with decreased response rates to MTX, CSA, or Cy. Autoimmune diseases were associated with increased response rates. Thrombocytopenia was an independent risk factor for worse survival.