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  • Fibromatoses of Head and Neck: Case Series and Literature Review

    Objective: The objective of this study was to retrospectively review clinical data, management protocols, and clinical outcomes of patients with fibromatoses of head and neck region treated at our tertiary care center. Methods: We retrospectively reviewed the medical records of 11 patients with confirmed histopathological diagnosis of fibromatosis registered in the Department of Head and Neck Surgery at Tata Memorial Centre, India, between 2009 and 2019. Various clinical and pathological features and treatment modalities were evaluated. Results: Age at diagnosis ranged between 18 and 74 years, with a median age of 36 years. The female-to-male ratio was 5:6. Supraclavicular fossa (n=4) was the most common subsite of origin in the neck (n=8). The lateral (n=2) and posterior cervical regions (n=2) were other common neck subsites. Less commonly involved sites were the mandible (n=1), maxilla (n=1), and thyroid (n=1). A total of eight patients underwent surgery at other centers before being referred to us for further management. Out of a total 11 patients, nine patients had unresectable disease at presentation. Six of the patients with unresectable disease received a combination of weekly doses of vinblastine 6 mg/m2 and methotrexate 30 mg/m2 for a median duration of 6 months (range 6–18 months) followed by hormonal therapy with tamoxifen. Three patients received metronomic chemotherapy followed by hormonal therapy. One treatment-naive patient with fibromatosis of posterior cervical (suboccipital) region underwent R2 resection (excision of bulk of the tumor with preservation of critical structures) at our center along with adjuvant radiotherapy. One pregnant patient reported to us after undergoing surgery outside and defaulting radiotherapy. During median follow-up of 29 months (range 1–77 months), six patients had stable disease, and four patients had disease reduction. Disease progression was seen in one patient. The two-year progression-free survival (PFS) was 90% (95% CI 70%–100%). Conclusion: Gross residual resection (R2) was the mainstay of surgical treatment in our series as obtaining clear surgical margins is seldom possible in these locally aggressive tumors. Radiotherapy, chemotherapy, and hormonal therapy are the other preferred and more conservative treatment modalities. The goal of surgery should be preserving function with minimal or no morbidity. As fibromatoses in the head and neck region are extremely rare, their treatment awaits the development of standard treatment protocols.
  • Loneliness, Depression, and Anxiety Experienced by the Israeli Population During the First COVID-19 Lockdown: A Cross-sectional Survey

    This research letter presents our study, which sought to evaluate the differences in the prevalence of self-reported symptoms of depression, anxiety, and loneliness between younger and older generations at the time of the COVID-19 pandemic. Since the younger generation is generally less accustomed to facing and dealing with adversity and illness, we hypothesized that adolescents and younger adults would have a higher prevalence of depression, anxiety, and loneliness as compared to the older generation. It must be emphasized that this survey was conducted during the first COVID-19 lockdown that occurred in Israel from mid-March 2020 to early-May 2020. This was a time when businesses were closed, individuals and families were isolated at home with very limited social contact, and feelings of fear and panic were fueled by the electronic media.
  • Human Papilloma Virus and Cancer Stem Cell markers in Oral Epithelial Dysplasia—An Immunohistochemical Study

    Objectives: To study the correlation between the putative cancer stem cell (CSC) markers aldehyde dehydrogenase 1 (ALDH1), cluster of differentiation 44 (CD44), sex-determining region Y-box 2 (SOX2), and octamer-binding protein 4 (OCT4) and human papilloma virus (HPV) infection using p16, the surrogate marker of HPV in oral epithelial dysplasia (OED) and normal mucosa. Methods: Five sections each from 40 histopathologically diagnosed cases of different grades of OED and 10 cases of normal oral mucosa without dysplasia were immunohistochemically stained with p16, ALDH1, CD44, SOX2, and OCT4, respectively. Results: Expression of ALDH1 and SOX2 was significantly increased in OED cases, whereas CD44 and OCT4 expression was increased in normal mucosa. P16-positive OED cases showed upregulation of ALDH1 and OCT4 expression as compared to p16-negative cases, while CD44 and SOX2 expression was downregulated in p16-positive OED cases; however, the results were not statistically significant. Conclusion: The present study indicated a suggestive link between p16 and cancer stem cell marker expression in HPV-associated OED, and that p16 has a significant role in CSC progression in OED. This is the first study to evaluate the expression of putative CSC markers in HPV-associated OED. However, low study numbers are a potential limiting factor in this study.
  • Population-level Outcomes of Early Thyroid Cancers: A Need to Revisit Current Practice

    Background: Early thyroid cancers have excellent long-term outcomes, yet the word “cancer” draws unnecessary apprehension. This study aimed to define when the recommendations for observation and surveillance may be extended to early thyroid cancers at the population level. Methods: Non-metastasized thyroid cancers ≤40 mm diameter were identified from the 1975–2016 Surveillance, Epidemiology and End Results (SEER) database. Causes of death were compared across demographic data. Disease-specific outcomes were compared to the age-adjusted healthy United States (US) population. Survival estimates were computed using Kaplan–Meier and compared using the Cox proportional hazard model. Dynamic benchmarks impacting disease-specific overall survival were determined by decision tree modeling and tested by the Cox model. Results: Of the 28,728 thyroid cancers included in this study, 98.4% underwent some form of thyroid-specific treatment and were followed for a maximum of 10.9 years. This group had a 4.3% mortality rate at the end of follow-up (10.9 years maximum), with 13 times more deaths attributed to competing risks rather than thyroid cancer (stage T1a versus stage T1b, P=1.000; T1 versus T2, P<0.001). Among the untreated T1a or T1b tumors, the risk of disease-specific death was 21 times lower than death due to other causes. There was no significant difference between T1a and T1b tumors nor across sex. The age-adjusted risk of death for the healthy US population was higher than the population with thyroid cancer. Dynamic categorization demonstrated worsening outcomes up to 73 years, uninfluenced by sex or tumor size. For patients over 73 years of age, only tumors >26 mm impacted outcomes. Conclusion: Based on the current data, T1a and T1b nodules have similar survival outcomes and are not significantly impacted even when left untreated. Multi-institutional prospective studies are needed to confirm these findings so that current observation and surveillance recommendations can be extended to certain T1 thyroid nodules.
  • Factors Associated with Liver Enzyme Abnormalities in HIV–HBV and/or HCV Co-infected Patients in Kinshasa, Democratic Republic of the Congo: Multicenter Cross-sectional Study

    Background and Objective: Liver enzyme abnormalities (LEA) are extremely common and sometimes severe in individuals infected with human immunodeficiency virus (HIV), but data for this disorder are lacking in the developing countries. The objective of this study was to identify factors associated with LEA in HIV–hepatitis B virus (HBV)/hepatitis C virus (HCV) co-infected patients in Kinshasa, Democratic Republic of the Congo. Methods: This cross-sectional analytical study included 180 people living with HIV (PLWHIV) mono-infected or co-infected with HBV/HCV between November 10, 2013 and January 10, 2014 in Kinshasa. Sociodemographic, clinical, biological, serological, and immunological data were analyzed. Levels of serum glutamate oxaloacetate transferase (SGOT) and serum glutamate pyruvate transaminase (SGPT) were determined. Antibody levels were determined using enzyme-linked immunosorbent assay (ELISA). Results: The mean age of patients was 44.2±11.0 years; female sex was predominant (76.7%). Co-infection, mainly with HBV, but also HCV, was found in 43 (23.9%) patients. Elevated liver enzymes were found in 77 (42.8%) of the patients. No difference was found in the rate of liver enzyme abnormalities between patients with HIV mono-infection or HIV co-infection (46.7% versus 30.2%, respectively; P=0.08). Factors associated with LEA were age ≥50 years (adjusted odds ratio [OR] 2.7; 95% CI 1.4–5.5), duration of HIV infection >3 years (adjusted OR 2.7; 95% CI 1.4–5.5), and CD4 count ≤303 cells/mm³ (adjusted OR 2.2; 95% CI 1.1–4.5). Conclusions: Liver enzyme abnormalities are frequent in patients co-infected with HIV–HBV/HCV as well as in HIV patients without co-infection. Diagnosis is determined based on age, immunodeficiency, and length of illness.
  • Remembering Dr Mark/Meir Dvorjetski: Physician, Survivor, Teacher, Historian, and Pioneer of Shoah Medicine Research

    Meir Dvorjetski was a Holocaust survivor, teacher, and historian. He is best remembered for his descriptions of the medicine practiced by the Nazis during World War II, as well as the diseases, disorders, syndromes, and deaths resulting from such practice—particularly, though not solely, on the Jewish race. Dvorjetski’s contributions to Holocaust research at Bar-Ilan University in Israel, his underground partisan work, his contributions to society, and his testimony at the Eichmann trial have all been well documented. However, his earlier years—including his survival of the Holocaust, and his less-known medical achievements and contributions to historical records regarding the Holocaust—have not been covered as thoroughly. These latter items are the focus of this paper, with a closing commentary on the relevance of his work for the 21st century.
  • Cannabis and Rheumatoid Arthritis: A Scoping Review Evaluating the Benefits, Risks, and Future Research Directions

    Rheumatoid diseases, including rheumatoid arthritis, osteoarthritis, and fibromyalgia, are characterized by progressive inflammation in the musculoskeletal system, predominantly affecting the joints and leading to cartilage and bone damage. The resulting pain and ongoing degradation of the musculoskeletal system contribute to reduced physical activity, ultimately impacting quality of life and imposing a substantial socioeconomic burden. Unfortunately, current therapeutics have limited efficacy in slowing disease progression and managing pain. Thus, the development of novel and alternative therapies is imperative. Cannabinoids possess beneficial properties as potential treatments for rheumatoid diseases due to their anti-inflammatory and analgesic properties. Preclinical studies have demonstrated promising results in halting disease progression and relieving pain. However, there is a scarcity of patient clinical studies, and the available data show mixed results. Consequently, there are currently no established clinical recommendations regarding the utilization of cannabis for treating rheumatoid diseases. In this review, we aim to explore the concept of cannabis use for rheumatoid diseases, including potential adverse effects. We will provide an overview of the data obtained from preclinical and clinical trials and from retrospective studies on the efficacy and safety of cannabis in the treatment of rheumatoid diseases.
  • Integration of Bite Mark Microbiome Analysis with Forensic DNA Profiling: Advancements, Challenges, and Synergistic Approaches

    Bite mark analysis plays a pivotal role in forensic investigations, by helping to identify suspects and establish links between individuals and crime scenes. However, traditional bite mark methodologies face significant challenges due to issues with reliability and subjectivity. Recent advances in microbiome analysis, which involves identifying and characterizing the microbial communities found in bite marks, have led to the emergence of a promising tool for forensic investigations. The integration of microbiome analysis with conventional DNA profiling enables more accurate interpretation of bite mark evidence in forensic investigations. This review provides an in-depth look at the integration of bite mark microbiome analysis with forensic DNA profiling. It also addresses the challenges and strategies involved in microbiome-based bite mark analysis for forensic purposes.
  • Technological Developments and Strategic Management for Overcoming the COVID-19 Challenge within the Hospital Setting in Israel

    The coronavirus disease 2019 (COVID-19) pandemic has remarkably challenged health care organizations and societies. A key strategy for confronting the disease implications on individuals and communities was based on harnessing multidisciplinary efforts to develop technologies for mitigating the disease spread and its deleterious clinical implications. One of the main challenging characteristics of COVID-19 is the provision of medical care to patients with a highly infective disease mandating the use of isolation measures. Such care is complicated by the need for complex critical care, dynamic treatment guidelines, and a vague knowledge regarding the disease’s pathophysiology. A second key component of this challenge was the over¬whelming surge in patient burden and the relative lack of trained staff and medical equipment which required rapid re-organization of large systems and augmenting health care efficiencies to unprecedented levels. In contrast to the risk management strategies employed to mitigate other serious threats and the billions of dollars that are invested in reducing these risks annually by governments around the world, no such preparation has been shown to be of effect during the current COVID-19 pandemic. Unmet needs were identified within the newly opened COVID-19 departments together with the urgent need for reliable information for effective decision-making at the state level. This review article describes the early research and development response in Israel under the scope of in-hospital patient care, such as non-contact sensing of patients’ vital signs, and how it could potentially be weaved into a practical big picture at the hospital or national level using a strategic management system. At this stage, some of the described technologies are still in developmental or clinical evidence generation phases with respect to COVID-19 settings. While waiting for future publications describing the results of the ongoing evidence generation efforts, one should be aware of this trend as these emerging tools have the potential to further benefit patients as well as caregivers and health care systems beyond the scope of the current pandemic as well as confronting future surges in the number of cases.
  • Hydroxychloroquine and Coronavirus Disease 2019: A Systematic Review of a Scientific Failure

    Introduction: Hydroxychloroquine (HCQ) emerged early in the course of the coronavirus disease 2019 (COVID-19) pandemic as a possible drug with potential therapeutic and prophylactic benefits. It was quickly adopted in China, Europe, and the USA. We systematically reviewed the existing clinical evidence of HCQ use for the prevention and treatment of COVID-19. Methods: We screened for clinical studies describing HCQ administration to treat or prevent COVID-19 in PubMed. We included randomized controlled trials (RCTs), non-randomized comparative cohorts, and case series studies that had all undergone peer review. Results: A total of 623 studies were screened; 17 studies evaluating HCQ treatment were included. A total of 13 were observational studies, and 4 were RCTs. In terms of effect on mortality rates, observational studies provided conflicting results. As a whole, RCTs, including one large British RCT that has not yet been published, showed no significant effect of HCQ on mortality rates, clinical cure, and virologic response. The use of HCQ as a post-exposure prophylactic agent was found to be ineffective in one RCT. Conclusion: There is no evidence supporting HCQ for prophylaxis or treatment of COVID-19. Many observational trials were methodologically flawed. Scientific efforts have been disappointingly fragmented, and well-conducted trials have only recently been completed, more than 7 months and 600,000 deaths into the pandemic.