Toxicities of CAR T-cell therapy: a review of current literature.

The chimeric antigen receptor (CAR) design, first invented by Zelig Eshhar, paved the way for the use of genetically modified T-cells in targeted therapy against cancer cells. Since then, it has gone through many generations, especially with the integration of co-stimulation in the second and third-generation CARs. However, it also mounts a hyperactive immune response named as cytokine release syndrome with the release of several cytokines eventually resulting in multiple end-organ toxicities. The severity of cytokine release syndrome depends upon certain factors such as the tumor burden, choice of co-stimulation, and degree of lymphodepletion, and can manifest as pulmonary edema, vascular leak, renal dysfunction, cardiac problems, hepatic failure, and coagulopathy. Many grading criteria have been used to define these clinical manifestations but they lack harmonization. Neurotoxicity has also been significantly associated with CAR T-cell therapy but it has not been studied much in previous literature. This review aims to provide a comprehensive account of the clinical manifestations, diagnosis, management, and treatment of CAR T-cell associated neurotoxicity.

Acute acalculous cholecystitis as a rare gastroenterological association of COVID-19: a case series and systematic review.

Background and Aim: Acute acalculous cholecystitis (AAC) is an acute inflammatory disease of the gallbladder in the absence of cholecystolithiasis. It is a serious clinicopathologic entity, with a high mortality rate of 30-50%. A number of etiologies have been identified that can potentially trigger AAC. However, clinical evidence on its occurrence following COVID-19 remains scarce. We aim to evaluate the association between COVID-19 and AAC. Methods: We report our clinical experience based on 3 patients who were diagnosed with AAC secondary to COVID-19. A systematic review of the MEDLINE, Google Scholar, Scopus, and Embase databases was conducted for English-only studies. The latest search date was December 20, 2022. Specific search terms were used regarding AAC and COVID-19, with all associated permutations. Articles that fulfilled the inclusion criteria were screened, and 23 studies were selected for a quantitative analysis. Results: A total of 31 case reports (level of clinical evidence: IV) of AAC related to COVID-19 were included. The mean age of patients was 64.7 ± 14.8 years, with a male-to-female ratio of 2.1:1. Major clinical presentations included fever 18 (58.0%), abdominal pain 16 (51.6%), and cough 6 (19.3%). Hypertension 17 (54.8%), diabetes mellitus 5 (16.1%), and cardiac disease 5 (16.1%) were among the common comorbid conditions. COVID-19 pneumonia was encountered before, after, or concurrently with AAC in 17 (54.8%), 10 (32.2%), and 4 (12.9%) patients, respectively. Coagulopathy was noted in 9 (29.0%) patients. Imaging studies for AAC included computed tomography scan and ultrasonography in 21 (67.7%) and 8 (25.8%) cases, respectively. Based on the Tokyo Guidelines 2018 criteria for severity, 22 (70.9%) had grade II and 9 (29.0%) patients had grade I cholecystitis. Treatment included surgical intervention in 17 (54.8%), conservative management alone in 8 (25.8%), and percutaneous transhepatic gallbladder drainage in 6 (19.3%) patients. Clinical recovery was achieved in 29 (93.5%) patients. Gallbladder perforation was encountered as a sequela in 4 (12.9%) patients. The mortality rate in patients with AAC following COVID-19 was 6.5%. Conclusions: We report AAC as an uncommon but important gastroenterological complication following COVID-19. Clinicians should remain vigilant for COVID-19 as a possible trigger of AAC. Early diagnosis and appropriate treatment can potentially save patients from morbidity and mortality. Relevance for Patients: AAC can occur in association with COVID-19. If left undiagnosed, it may adversely impact the clinical course and outcomes of patients. Therefore, it should be considered among the differential diagnoses of the right upper abdominal pain in these patients. Gangrenous cholecystitis can often be encountered in this setting, necessitating an aggressive treatment approach. Our results point out the clinical importance of raising awareness about this biliary complication of COVID-19, which will aid in early diagnosis and appropriate clinical management.

COVID-19 and myasthenia gravis: A review of neurological implications of the SARS-COV-2.

INTRODUCTION: This review highlights the potential mechanisms of neuromuscular manifestation of COVID-19, especially myasthenia gravis (MG). METHODS: An extensive literature search was conducted by two independent investigators using PubMed/MEDLINE and Google Scholar from its inception to December 2020. RESULTS: Exacerbations of clinical symptoms in patients of MG who were treated with some commonly used COVID-19 drugs has been reported, with updated recommendations of management of symptoms of neuromuscular disorders. Severe acute respiratory syndrome coronavirus 2 can induce the immune response to trigger autoimmune neurological disorders. CONCLUSIONS: Further clinical studies are warranted to indicate and rather confirm if MG in the setting of COVID-19 can pre-existent subclinically or develop as a new-onset disease.

Nationwide Assessment of Knowledge and Perception in Reinforcing Telemedicine in the Age of COVID-19 Among Medical Students From Pakistan.

The urgency for telemedicine is felt during the COVID-19 pandemic which has rendered the world shut by enforcing quarantines and lockdowns. Many developing countries including Pakistan have inadequate telehealth care services that limited access to rural and remote areas. A cross-sectional survey was carried out among medical students i.e., both preclinical and clinical enrolled in various medical colleges from all provinces of Pakistan to determine their Knowledge, Attitude and Perception regarding the use of Telemedicine during the COVID-19 Pandemic. A total of 398 respondents were included in this preliminary survey. Knowledgeable scores were calculated, from a maximum obtainable score of 7. The mean knowledge was found to be significantly associated with age, province, and year of study (p-value < 0.05). Attitude scores were calculated from a maximum obtainable score of 10. All the independent variables failed to reach a significant (p < 0.05) association with the mean attitude of respondents about telemedicine. Perception scores were calculated from a maximum obtainable score of 8. Residents of Khyber Pakhtunkhwa are more likely to know about telemedicine than Balochistan (p = 0.022) on univariate regression. We identified, lack of knowledge and training for telemedicine in medical institutes. It is crucial to assess the knowledge of medical students regarding telemedicine to comprehend, and evaluate their attitude as future doctors who can play a significant role in establishing telemedicine services in the health care system.

Artificial intelligence in the diagnosis and detection of heart failure: the past, present, and future.

Artificial Intelligence (AI) performs human intelligence-dependant tasks using tools such as Machine Learning, and its subtype Deep Learning. AI has incorporated itself in the field of cardiovascular medicine, and increasingly employed to revolutionize diagnosis, treatment, risk prediction, clinical care, and drug discovery. Heart failure has a high prevalence, and mortality rate following hospitalization being 10.4% at 30-days, 22% at 1-year, and 42.3% at 5-years. Early detection of heart failure is of vital importance in shaping the medical, and surgical interventions specific to HF patients. This has been accomplished with the advent of Neural Network (NN) model, the accuracy of which has proven to be 85%. AI can be of tremendous help in analyzing raw image data from cardiac imaging techniques (such as echocardiography, computed tomography, cardiac MRI amongst others) and electrocardiogram recordings through incorporation of an algorithm. The use of decision trees by Rough Sets (RS), and logistic regression (LR) methods utilized to construct decision-making model to diagnose congestive heart failure, and role of AI in early detection of future mortality and destabilization episodes has played a vital role in optimizing cardiovascular disease outcomes. The review highlights the major achievements of AI in recent years that has radically changed nearly all areas of HF prevention, diagnosis, and management.