Survival outcomes of patients with concomitant acute variceal bleeding and acute coronary syndrome, and the role of antiplatelet agents: an institutional experience from a lower middle-income Country.

BACKGROUND: There is strong evidence demonstrating the incidence of Acute Coronary Syndrome (ACS) among patients with cirrhosis, with the initiation of antiplatelet therapy being subject to debate due to an increased risk of bleeding. This study aimed to determine mortality among patients presenting with concomitant Acute Variceal Bleeding (AVB) and ACS at Index admission. Furthermore, the recurrence of AVB and ACS among patients discharged with or without antiplatelet therapy was determined. METHODS: This retrospective study was conducted at the Aga Khan University Hospital, Karachi, Pakistan on patients ≥ 18 years of age admitted to our ER with concomitant ACS and AVB between January 2002 to December 2017. Follow-up for 6 months or till death (if < 6 months), was observed, to help determine the incidence of recurrent AVB and ACS. The incidence of AVB and ACS was then compared amongst patient groups based on the usage of anti-platelet drugs on discharge. RESULTS: A total of 29 patients were included, with a mean age of 58.7 ± 11.0 years. Seven patients died on admission, having worse underlying liver disease. No mortality was reported among the remaining 22 patients. All 22 patients underwent surveillance endoscopy with variceal band ligation until obliteration, as needed. Only 7 patients from the surviving cohort received antiplatelet therapy. After 6.05 ± 1.1 months of follow-up, 1/22 (4.5%) developed recurrent AVB and 2/22 (9.1%) developed cardiovascular events. Importantly, there was no significant difference in the incidence of recurrent AVB (P = 1.000) and ACS (P = 0.091), depending on the use of antiplatelet therapy. CONCLUSION: Concomitant AVB and ACS is a severe disorder with increased mortality among cirrhotic patients at presentation. The incidence of AVB does not seem to exacerbate with the use of antiplatelet agents, provided successful obliteration of varices is achieved using elective band ligation.

Quality of life of pediatric patients with craniopharyngioma: A retrospective series from a low-middle-income country with more than 4 years follow-up.

Background: Craniopharyngiomas (CPs) are rare, low-grade tumors characterized by a range of debilitating symptoms. Most of the existing literature reports postoperative outcomes of the different treatment modalities of childhood CP. However, few studies have reported the impact of these different treatment methods on the quality of life (QoL) of survivors of childhood CP. Therefore, we aim to assess the correlation between different surgical modalities on the QoL of patients with childhood CP from a lower-middle-income country. Methods: Twenty-nine survivors who underwent treatment for CP were included in the study. The selected patients had either been managed with complete resection, debulking, or placement of an Ommaya reservoir. QoL was assessed by the pediatric quality of life (PedsQL) questionnaire. The effect of the different treatment modalities on the QoL was assessed. Results: Mean follow-up was 4.4 ± 2.19 years. The type of surgery was significantly related to the mean PedsQL scores for the total score as well as each of the individual domain scores (P < 0.001). Complete resection of the tumor resulted in the lowest mean (standard deviation) PedsQL total score of 56.6 ± 7.12 compared to the Ommaya reservoir with biopsy (83.3 ± 5.69) and debulking (93.8 ± 3.37) (P < 0.001). Conclusion: There was a significant effect of the type of surgical treatment on the QoL of the survivors of childhood CP. It is important to consider the long-term outcomes in addition to immediate postoperative outcomes when deciding on a treatment strategy while managing children with CP.

Knowledge, attitude, and perceptions about cancer genetic testing in clinical practice in Karachi, Pakistan.

Healthcare professionals (HCP) play an important role in the practical application of genetic screening tests but often feel inadequately prepared for cancer genetic testing (CGT) in clinical care. As the complexity of gene-related malignancies increases, it demands HCPs' preparedness to cater to patients' needs. Therefore, the aim of our study is to assess the knowledge, attitude, and practices of HCPs in Pakistan regarding the application of cancer genetics. Our cross-sectional survey was conducted from April 2022 to June 2022 amongst HCPs at a private and a governmental institution in Karachi, Pakistan. Non-probability random convenience sampling was used to select the population; however. non-clinical HCPs, as well as Interns, were excluded from our study. A total of 210 HCPs, 56.7% (119) bearing an experience of over 5 years of clinical experience, were included in this study. Most respondents from both hospitals deemed their knowledge inadequate, with only 2% (2) and 1.8% (2) being extremely knowledgeable, respectively. 68.6% (144) HCPs displayed a positive attitude towards CGT, with 55.2% (116) participants perceiving CGT in a positive light. As compared to the private sector, significantly more HCPs in the public sector dedicated ≥ 5 h/week for CME (P = 0.006), and were better prepared to counsel patients (P = 0.021) and interpret results concerning CGT (P = 0.020). Additionally, screening tests for specific cancer types were popularly considered a worthwhile avenue of investment to improve the current state of CGT in our healthcare system [47.6% (N = 100)]. Demonstrating a lack of knowledge among Pakistani doctors, our results call upon the need for additional training concerning CGT in both the public and private sectors alike. Understanding specific gaps in knowledge may further help enhance post-graduate training programs and eventually lead to effective incorporation of CGT into our healthcare setting.

The Achilles' heel of cancer survivors: fundamentals of accelerated cellular senescence.

Recent improvements in cancer treatment have increased the lifespan of pediatric and adult cancer survivors. However, cancer treatments accelerate aging in survivors, which manifests clinically as the premature onset of chronic diseases, such as endocrinopathies, osteoporosis, cardiac dysfunction, subsequent cancers, and geriatric syndromes of frailty, among others. Therefore, cancer treatment-induced early aging accounts for significant morbidity, mortality, and health expenditures among cancer survivors. One major mechanism driving this accelerated aging is cellular senescence; cancer treatments induce cellular senescence in tumor cells and in normal, nontumor tissue, thereby helping mediate the onset of several chronic diseases. Studies on clinical monitoring and therapeutic targeting of cellular senescence have made considerable progress in recent years. Large-scale clinical trials are currently evaluating senotherapeutic drugs, which inhibit or eliminate senescent cells to ameliorate cancer treatment-related aging. In this article, we survey the recent literature on phenotypes and mechanisms of aging in cancer survivors and provide an up-to-date review of the major preclinical and translational evidence on cellular senescence as a mechanism of accelerated aging in cancer survivors, as well as insight into the potential of senotherapeutic drugs. However, only with time will the clinical effect of senotherapies on cancer survivors be visible.

Pineal cyst apoplexy and memory loss: a novel complication.

An 8-year-old boy presented to our hospital complaining of a bilateral headache associated with episodes of anterograde amnesia. He had a road traffic accident 3 years ago when a computed tomography (CT) scan revealed traumatic brain injury. In addition, a small pineal cyst (PC) was noted with minor intramural calcifications. A follow-up CT a day later demonstrated increased density in the pineal gland of 60 Hounsfield Units, suggestive of apoplectic changes in the PC. However, the patient was lost to follow-up and presented with memory loss a year and a half later, upon which CT and magnetic resonance imaging revealed enlargement of the PC. PC apoplexy is a very rare occurrence usually affecting young adult women; cases in children are rarely reported. Furthermore, PC apoplexy secondary to severe craniofacial trauma manifesting as memory loss has not yet been reported in the literature to the best of our knowledge.

Feasibility and Effectiveness of Mini-Clinical Evaluation Exercise (Mini-CEX) in an Undergraduate Medical Program: A Study From Pakistan.

Background In clinical settings, direct observation (DO) with feedback is an effective method to assess and improve learner performance. One tool used for DO is the mini-clinical evaluation exercise (Mini-CEX). We conducted a study to assess the effectiveness and feasibility of Mini-CEX for medical students at Aga Khan University, Karachi. Methods Utilizing a purposive sampling technique, a total of 199 students in six core clerkships of Years 3 and 4 were selected for this study. Participating faculty underwent training workshops for use of Mini-CEX and feedback strategies. Each student was assessed twice by one faculty, using a modified version of the Mini-CEX, which assessed four domains of clinical skills: Data Gathering, Communication, Diagnosis/Differential, and Management Plan and Organization. Feedback was given after each encounter. Faculty and students also provided detailed feedback regarding the process of DO. Data were analyzed using Statistical Package for Social Sciences (SPSS) version 26 (IBM Corp., Armonk, NY, USA), with categorical variables arranged as frequencies and percentages. The Chi-squared test was used for further statistical analyses, and a P-value of < 0.05 was considered statistically significant. Effectiveness was assessed via a change in student performance between the first and second Mini-CEX, and feasibility was assessed via qualitative feedback. Results We obtained three sets of results: Mini-CEX forms (523), from which we included a total 350 evaluations for analysis, 216 from Year 3 and 134 from Year 4, and feedback on DO: student (70) and faculty (18). Year 3 students performed significantly better in all foci of the Mini-CEX between the first and second assessment (P ≤ 0.001), whereas in Year 4, significant improvement was limited to only two domains of the Mini-CEX [Communication of History/Physical Examination (P = 0.040) and Diagnosis/Differential and Management Plan (P < 0.001)]. Students (65.7%) and faculty (94.4%) felt this exercise improved their interaction. 83.3% faculty recommended its formal implementation compared to 27.1% of students, who reported challenges in implementation of the Mini-CEX such as time constraints, logistics, the subjectivity of assessment, and varying interest by faculty. Conclusion Direct observation using Mini-CEX is effective in improving the clinical and diagnostic skills of medical students and strengthens student-faculty interaction. While challenges exist in its implementation, the strategic placement of Mini-CEX may enhance its utility in measuring student competency.

Mechanistic Insights Into the Immune Pathophysiology of COVID-19; An In-Depth Review.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which causes coronavirus-19 (COVID-19), has caused significant morbidity and mortality globally. In addition to the respiratory manifestations seen in severe cases, multi-organ pathologies also occur, making management a much-debated issue. In addition, the emergence of new variants can potentially render vaccines with a relatively limited utility. Many investigators have attempted to elucidate the precise pathophysiological mechanisms causing COVID-19 respiratory and systemic disease. Spillover of lung-derived cytokines causing a cytokine storm is considered the cause of systemic disease. However, recent studies have provided contradictory evidence, whereby the extent of cytokine storm is insufficient to cause severe illness. These issues are highly relevant, as management approaches considering COVID-19 a classic form of acute respiratory distress syndrome with a cytokine storm could translate to unfounded clinical decisions, detrimental to patient trajectory. Additionally, the precise immune cell signatures that characterize disease of varying severity remain contentious. We provide an up-to-date review on the immune dysregulation caused by COVID-19 and highlight pertinent discussions in the scientific community. The response from the scientific community has been unprecedented regarding the development of highly effective vaccines and cutting-edge research on novel therapies. We hope that this review furthers the conversations held by scientists and informs the aims of future research projects, which will potentially further our understanding of COVID-19 and its immune pathogenesis.

Inflammatory bowel disease causing retroperitoneal varicosity mimicking a renal artery aneurysm: A novel case report and literature review.

A 17-year-old female presented to our hospital complaining of bloody diarrhea 4-6 times per day for the past month. She was a known case of inflammatory bowel disease noncompliant to her medications. Abdominal computed tomography revealed an unusually dilated mass in the retroperitoneum at L2 vertebral level connecting the lumbar and left renal veins. The renal artery was visualized separately, and a diagnosis of communicating vein varicosity was made. This lesion can be misleading on imaging, hence our aim to disseminate our findings to practicing radiologists. The differential diagnosis of these lesions include retroperitoneal lymphadenopathy, renal artery aneurysms, and testicular cancers causing retroperitoneal lymphadenopathy. To our knowledge, this is the first case to be reported in association with inflammatory bowel disease, perhaps providing a novel insight into the pathogenesis of this lesion that has not been considered in the contemporary literature.

Understanding COVID-19 Vaccines Today: Are T-cells Key Players?

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has heavily mutated since the beginning of the coronavirus-2019 (COVID-19) pandemic. In this regard, the so-called variants of concern (VOCs) feature mutations that confer increased transmissibility and evasion of antibody responses. The VOCs have caused significant spikes in COVID-19 cases, raising significant concerns about whether COVID-19 vaccines will protect against current and future variants. In this context, whereas the protection COVID-19 vaccines offer against the acquisition of infection appears compromised, the protection against severe COVID-19 is maintained. From an immunologic standpoint, this is likely underpinned by the maintenance of T-cell responses against VOCs. Therefore, the role of T-cells is essential to understanding the broader adaptive immune response to COVID-19, which has the potential to shape public policies on vaccine protocols and inform future vaccine design. In this review, we survey the literature on the immunology of T-cell responses upon SARS-CoV-2 vaccination with the current FDA-approved and Emergency Use Authorized COVID-19 vaccines.

A Rare Presentation of a True Intra-articular Lipoma: A Case Report and Review of Imaging Findings.

This report describes the unique case of an intra-articular lipoma in a 34-year-old male. The patient presented with a history of chronic knee pain associated with an intermittent sensation of the knee giving way. Physical examination and initial radiographic imaging were unremarkable. Magnetic resonance imaging (MRI) revealed a 9.2 x 6.7 mm ovoid mass posterior to the posterior cruciate ligament (PCL) exhibiting hyperintense signals on T1-weighted images and intermediate-to-high intensity signals on T2. On subsequent proton density fat suppression sequences, the mass demonstrated homogenous signal suppression and was confirmed as being a lipoma. To the best of our knowledge, this is only the second reported case of an intra-articular lipoma arising posterior to the PCL. Intra-articular lipomas, albeit rare, should be considered in the differential diagnosis for chronic knee pain with associated joint motion abnormalities. MRI remains the gold standard in imaging intra-articular soft tissue pathology and should be the study of choice in differentiating intra-articular lipomas from similar conditions such as pigmented villonodular synovitis and lipoma arborescens.

Radiologic Diagnosis of Nasal Gliomas with an Illustrative Case Report.

Nasal gliomas are congenital masses of dysplastic neuroglial and fibrovascular tissue. However, other congenital nasal masses, including encephaloceles, hemangiomas, and dermoid cysts make clinical diagnosis difficult. Radiological examination is imperative to accurate diagnosis of nasal gliomas. We hereby present the diagnostic imaging features of these lesions, which necessitate inclusion into the differential diagnosis of a congenital nasal mass.

SARS-CoV-2 epitopes inform future vaccination strategies.

All currently approved COVID-19 vaccines utilize the spike protein as their immunogen. SARS-CoV-2 variants of concern (VOCs) contain mutations in the spike protein, enabling them to escape infection- and vaccination-induced immune responses to cause reinfection. New vaccines are hence being researched intensively. Studying SARS-CoV-2 epitopes is essential for vaccine design, as identifying targets of broadly neutralizing antibody responses and immunodominant T-cell epitopes reveal candidates for inclusion in next-generation COVID-19 vaccines. We summarize the major studies which have reported on SARS-CoV-2 antibody and T-cell epitopes thus far. These results suggest that a future of pan-coronavirus vaccines, which not only protect against SARS-CoV-2 but numerous other coronaviruses, may be possible. The T-cell epitopes of SARS-CoV-2 have gotten less attention than neutralizing antibody epitopes but may provide new strategies to control SARS-CoV-2 infection. T-cells target many SARS-CoV-2 antigens other than spike, recognizing numerous epitopes within these antigens, thereby limiting the chance of immune escape by VOCs that mainly possess spike protein mutations. Therefore, augmenting vaccination-induced T-cell responses against SARS-CoV-2 may provide adequate protection despite broad antibody escape by VOCs.

Meta-analysis of incidence and outcomes of life-threatening arrhythmias in takotsubo cardiomyopathy.

BACKGROUND: Takotsubo cardiomyopathy (TC) or stress-induced cardiomyopathy is a transient heart condition that clinically resembles an acute coronary syndrome. This study aims to assess the incidence of life-threatening arrhythmias in patients with Takotsubo cardiomyopathy and evaluate the outcomes of patients with life-threatening arrhythmias (LTAs) in Takotsubo cardiomyopathy compared with those without LTA. METHODS: We comprehensively searched the PubMed, Google Scholar, and Embase databases from inception to February 2021. The primary aim of the study was to determine the incidence of LTAs in TC patients. Other outcomes of interest were the odds of in-hospital, long-term mortality, and cardiogenic shock (CS) in TC patients with LTAs versus those without LTAs. For all statistical analyses, ReviewManager and MedCalc were used. RESULTS: Eighteen studies were included in this study involving 55,557 participants (2,185 with LTAs and 53,372 without LTAs). The pooled incidence of LTAs in the patients of TC was found to be 6.29% (CI: 4.70-8.08%; I2 = 94.67%). There was a statistically significant increased risk of in-hospital mortality (OR = 4.74; CI: 2.24-10.04; I2 = 77%, p < 0.0001) and cardiogenic shock (OR = 5.60; CI: 3.51-8.95; I2 = 0%, p < 0.00001) in the LTA group versus the non-LTA group. LTA was not associated with long-term mortality (OR = 2.23; CI: 0.94-5.28; I2 = 53%, p = 0.07). CONCLUSION: The pooled incidence of life-threatening arrhythmias in the patients of TC was found to be 6.29%. In the group of TC patients with LTAs, the odds of in-hospital mortality and CS, was higher than in the TC patients without LTAs.

Role of gene therapy in Fanconi anemia: A systematic and literature review with future directions.

Gene therapy (GT) has been reported to improve bone marrow function in individuals with Fanconi anemia (FA); however, its clinical application is still in the initial stages. We conducted this systematic review, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to assess the long-term safety and clinical outcomes of GT in FA patients. Electronic searches from PubMed, Web of Science, Cochrane Library, and Google Scholar were conducted and full texts of articles meeting our inclusion criteria were reviewed. Three clinical trials were included, with a total of nine patients and mean age of 10.7 ±â€¯5.7 years. All patients had lentiviral-mediated GT. A 1-year follow-up showed stabilization in blood lineages, without any serious adverse effects from GT. A metaregression analysis could not be conducted, as very little long-term follow-up data of patients was observed, and the median survival rate could not be calculated. Thus, we can conclude that GT seems to be a safe procedure in FA; however, further research needs to be conducted on the longitudinal clinical effects of GT in FA, for a better insight into its potential to become a standard form of treatment.

Adenoma detection rate as a quality indicator for colonoscopy: a descriptive cross-sectional study from a tertiary care hospital in Pakistan.

Background and study aims Adenoma detection rate (ADR) is validated for measuring quality of colonoscopy, however there is lack of colorectal cancer (CRC) screening program in South Asia. The purpose of this study is to analyze and review the polyp detection rate (PDR) and ADR and provide insight into the factors that influence them in Pakistan. Patients and methods This retrospective, cross-sectional study was performed at the Aga Khan University Hospital, Karachi, Pakistan, on patients ≥ 18 years, who underwent colonoscopy between January 1, 2017 and June 30, 2018. Results Of 1985 patients, 59 % were male and 41 % female, with mean age of 47.8 ±â€Š16.2 years. The most common indication for colonoscopy was bleeding-per-rectum (28.0 %) and overall PDR and ADR were 17.9 % and 9.9 %, respectively. There was no significant difference between genders for either PDR ( P  = 0.378) or ADR ( P  = 0.574). Significantly higher PDR and ADR were found for patients ≥ 50 years ( P  < 0.001), as well as for suboptimal bowel preparation [PDR (25.7 %; P  = 0.007) and ADR (18.6 %; P  = 0.014)]. Interestingly, endoscopists with < 500 colonoscopy-procedural-experience reported a higher PDR (21.6 %; P  = 0.020) and ADR (14.4 %; P = 0.049), corresponding to a significantly higher PDR (20.6 %; P  = 0.005) and ADR (11.7 %; P  = 0.02) for endoscopists in practice for ≤ 10 years. Conclusions We have noticed low PDR and ADR, which require further investigation and research. In addition, we believe there should be a different baseline ADR and PDR as a quality indicator for colonoscopy in our region, where no internationally recommended colonoscopic screening programs have been implemented.