Risks of hypertension and thromboembolism in patients receiving bevacizumab with chemotherapy for colorectal cancer: A systematic review and meta-analysis.

BACKGROUND: Guidelines show that for metastatic colorectal cancer (mCRC), a combination of three-drug regimens, fluorouracil, leucovorin, and oxaliplatin and bevacizumab (BVZ), is one of the first-line standard therapies. BVZ is generally well tolerated; however, it is associated with infrequent, life-threatening side effects such as severe hypertension (HTN) (5%-18%), Grade ≥3 arterial thromboembolism (ATE) (2.6%), Grade ≥3 hemorrhagic events (1.2%-4.6%), and gastrointestinal perforation (0.3%-2.4%). This meta-analysis aims to evaluate the additive risk of BVZ-induced severe HTN and thromboembolism when BVZ is combined with a standard chemotherapy regime in patients with mCRC. METHODS: Our search was conducted from January 29, 2022, to February 22, 2022, through databases of PubMed, clinicaltrial.gov, EMBASE, Web of Science, and Cochrane Library. Data analysis from randomized controlled trials (RCTs) and clinical trials was conducted using Review Manager V.5.4, comparing BVZ-chemotherapy to chemotherapy only, focusing on cardiovascular AE such as HTN and arterial and venous thromboembolism. RESULTS: The analysis from 26 clinical trials and RCTs showed that the odds of HTN were about four times higher, and ATE subgroup analysis of 11 studies showed over two times higher odds of ATE in patients being treated with BVZ compared to the chemotherapy-only group. CONCLUSION: BVZ, when added to the standard chemotherapy regimen for mCRC, was associated with higher odds of developing HTN and thromboembolism, specifically ATE, than the chemotherapy-only group. Our findings are significant as they provide vital information in analyzing the risk-benefit ratio of adding BVZ to the standard chemotherapy regime in patients with mCRC, especially in patients with vascular comorbidities.

"Novel Management of Depression Using Ketamine in the Intensive Care Unit".

BACKGROUND: Ketamine, a dissociative anesthetic, induces improvement in depressive symptoms by antagonizing glutaminergic NMDA receptors. Ketamine has been used previously in outpatient setting for treatment-resistant depression, but we showcase its utility in depression management at the Intensive Care Unit (ICU). Research Question: Can ketamine be used for depression treatment in ICU patients? Study Design and Methods: A retrospective chart review of ICU patients was done at a tertiary center from 2018 to 2021, to assess the ketamine usage. Among the patients reviewed, ketamine was used for depression in 12, and for analgesia & sedation in 2322 patients. Ketamine was administered in doses of 0.5mg/kg & 0.75mg/kg for depression. Each course consisted of 3 doses of ketamine administered over 3 days, and 7 in 12 patients received a single course of ketamine. The rest received 3-4 courses 1 week apart. Results: Ketamine was found to improve mood and affect in most of the patients with depression. 11 in 12 patients had a positive response with better sleep. It has a major advantage over conventional anti-depressants since it takes only a few hours to induce clinical improvement. Patients who were observably withdrawn from care team and family, were administered ketamine. Conclusion: A major drawback of ketamine is that the duration of clinical improvement is short, with the response lasting only up to seven days after a single dose. Hence, all the patients in our study were weaned off ketamine with a supporting antidepressant. Ketamine has been documented to cause cardio-neurotoxicity; however, only one patient had worsening lethargy in our study. To conclude, ketamine has a marked benefit in treating depression in the ICU. Although our study was associated with positive outcomes, there is a need for prospective studies with long-term follow-up assessments.

Impact of colchicine on mortality and morbidity in COVID-19: a systematic review.

INTRODUCTION: Colchicine, because of its anti-inflammatory and possible anti-viral properties, has been proposed as potential therapeutic option for COVID-19. The role of colchicine to mitigate "cytokine storm" and to decrease the severity and mortality associated with COVID-19 has been evaluated in many studies. OBJECTIVE: To evaluate the role of colchicine on morbidity and mortality in COVID-19 patients. METHODS: This systematic review was conducted in accordance with the PRISMA recommendations. The literature search was conducted in 6 medical databases from inception to February 17, 2021 to identify studies evaluating colchicine as a therapeutic agent in COVID-19. All included studies were evaluated for risk of bias (ROB) using the Revised Cochrane ROB tool for randomised controlled trials (RCTs) and Newcastle-Ottawa Scale (NOS) for case-control and cohort studies. RESULTS: Four RCTs and four observational studies were included in the final analysis. One study evaluated colchicine in outpatients, while all others evaluated inpatient use of colchicine. There was significant variability in treatment protocols for colchicine and standard of care in all studies. A statistically significant decrease in all-cause mortality was observed in three observational studies. The risk of mechanical ventilation was significantly reduced only in one observational study. Length of hospitalisation was significantly reduced in two RCTs. Risk for hospitalisation was not significantly decreased in the study evaluating colchicine in outpatients. Very few studies had low risk of bias. CONCLUSION: Based on the available data, colchicine shall not be recommended to treat COVID-19. Further high-quality and multi-center RCTs are required to assess the meaningful impact of this drug in COVID-19.KEY MESSAGESColchicine, an anti-inflammatory agent has demonstrated anti-viral properties in in-vitro studies by degrading the microtubules, as well as by inhibiting the production of pro-inflammatory cytokines.Colchicine has been studied as a potential therapeutic option for COVID-19, with variable results.Until further research can establish the efficacy of colchicine in COVID-19, the use of colchicine in COVID-19 shall be restricted to clinical trials.

Presentation and Spectrum of Male Breast Cancer in a Rural Cancer Center in a Subunit of Tata Memorial Center, India.

This is a retrospective study of the incidence and clinical profile of male breast cancer (MBC) presenting to a rural cancer center in Punjab, India. All MBC cases registered over a period of 4.5 years from January 2015 to July 2019 were included. The study included 34 MBC patients accounting for 1.9% of all breast cancer cases with median age of 62.5 years. All patients were from Punjab except one, with majority from district Sangrur. Family history was present in 7 (20.6%) patients. Mean BMI (n = 23) was 24.8. The median duration of symptoms was 6 months (range 1-60 months). Main complaint was lump in 58.8% of patients followed by lump with ulceration (41.2%). All cases were mostly unilateral, left in 21 (61.8%) and right in 13 (38.2%), and one had bilateral breast cancer. Most tumors were centrally located (70.6%). Infiltrating ductal carcinoma and grade 3 were the commonest histology. ER positivity was high seen in 76.5% cases. In our study, 16 (47.1%) patients presented with distant metastasis at the time of diagnosis, and 10 (39.1%) were locally advance. Bone (41%) followed by lung (17%) were the most common sites of metastasis. Thirteen patients were treated radically, nine were treated with palliative intent, and twelve patients defaulted. Median follow-up period was 16.5 months. MBC constituted 1.9% of all breast cancers registered at our institute, which is higher than worldwide average. Our study population had a longer time to presentation, and majority were metastatic.

Hydroxychloroquine: A review of its safety and efficacy in COVID-19.

SARS-CoV-2 is a novel virus that has infected millions of people across the world. Given the compelling need to develop a therapeutic strategy, hydroxychloroquine has been advocated as an effective drug for the infection. However, multiple clinical trials conducted using hydroxychloroquine have yielded contrasting results. An electronic search using the primary databases from WHO, PubMed and Google Scholar was performed that yielded 21 studies eligible for inclusion. Among a total of 1,350 patients who received hydroxychloroquine, 689 (51.04%) were females. The most commonly reported comorbidities include hypertension (15.18%), diabetes mellitus (8.44%) and pulmonary disease (8.96%). Of the hydroxychloroquine-treated patients, 70% were virologically cured compared to 12.5% of the control group (p = 0.001). A good clinical outcome with virological cure was reported in 973 patients (91%) within 10 days out of 1,061 hydroxychloroquine-treated patients. A total of 29 (65%) renal transplant recipients achieved complete recovery following hydroxychloroquine administration. A total of 37 (2.7%) patients reported QT prolongation. Hydroxychloroquine was found to reduce mortality in healthy, SARS-Cov-2 positive patients and improve clinical recovery in renal transplant recipients. However, a definitive conclusion regarding its effect on viral clearance can only be reached by conducting more clinical trials involving bigger and diverse samples.

COVID-19 Outcomes Amongst Patients With Pre-existing Cardiovascular Disease and Hypertension.

INTRODUCTION:  Coronavirus disease 2019 (COVID-19) has multiorgan involvement and its severity varies with the presence of pre-existing risk factors like cardiovascular disease (CVD) and hypertension (HTN). Therefore, it is important to evaluate their effect on outcomes of COVID-19 patients. The objective of this meta-analysis and meta-regression is to evaluate outcomes of COVID-19 amongst patients with CVD and HTN. METHODS: English full-text observational studies having data on epidemiological characteristics of patients with COVID-19 were identified searching PubMed from December 1, 2019, to July 31, 2020, following Meta-analysis Of Observational Studies in Epidemiology (MOOSE) protocol. Studies having pre-existing CVD and HTN data that described outcomes including mortality and invasive mechanical ventilation (IMV) utilization were selected. Using random-effects models, risk of composite poor outcomes (meta-analysis) and isolated mortality and IMV utilization (meta-regression) were evaluated. Pooled prevalence of CVD and HTN, correlation coefficient (r) and odds ratio (OR) were estimated. The forest plots and correlation plots were created using random-effects models. RESULTS: Out of 29 studies (n=27,950) that met the criteria, 28 and 27 studies had data on CVD and HTN, respectively. Pooled prevalence of CVD was 18.2% and HTN was 32.7%. In meta-analysis, CVD (OR: 3.36; 95% CI: 2.29-4.94) and HTN (OR: 1.94; 95% CI: 1.57-2.40) were associated with composite poor outcome. In age-adjusted meta-regression, pre-existing CVD was having significantly higher correlation of IMV utilization (r: 0.28; OR: 1.3; 95% CI: 1.1-1.6) without having any association with mortality (r: -0.01; OR: 0.9; 95% CI: 0.9-1.1) among COVID-19 hospitalizations. HTN was neither correlated with higher IMV utilization (r: 0.01; OR: 1.0; 95% CI: 0.9-1.1) nor correlated with higher mortality (r: 0.001; OR: 1.0; 95% CI: 0.9-1.1). CONCLUSION: In age-adjusted analysis, though we identified pre-existing CVD as a risk factor for higher utilization of mechanical ventilation, pre-existing CVD and HTN had no independent role in increasing mortality.

Prevalence and Outcomes Associated with Vitamin D Deficiency among Indexed Hospitalizations with Cardiovascular Disease and Cerebrovascular Disorder-A Nationwide Study.

Background: According to past studies, recovery and survival following severe vascular events such as acute myocardial infarction and stroke are negatively impacted by vitamin D deficiency. However, the national estimate on disability-related burden is unclear. We intend to evaluate the prevalence and outcomes of vitamin D deficiency (VDD) among patients with cardiovascular disease (CVD) and cerebrovascular disorder (CeVD). Methods: We performed a cross-sectional study on the Nationwide Inpatient Sample data (2016-2017) of adult (≥18 years) hospitalizations. We identified patients with a secondary diagnosis of VDD and a primary diagnosis of CVD and CeVD using the 9th revision of the International Classification of Diseases, clinical modification code (ICD-10-CM) codes. A univariate and mixed-effect multivariable survey logistic regression analysis was performed to evaluate the prevalence, disability, and discharge disposition of patients with CVD and CeVD in the presence of VDD. Results: Among 58,259,589 USA hospitalizations, 3.44%, 2.15%, 0.06%, 1.28%, 11.49%, 1.71%, 0.38%, 0.23%, and 0.08% had primary admission of IHD, acute MI, angina, AFib, CHF, AIS, TIA, ICeH, and SAH, respectively and 1.82% had VDD. The prevalence of hospitalizations due to CHF (14.66% vs. 11.43%), AIS (1.87% vs. 1.71%), and TIA (0.4% vs. 0.38%) was higher among VDD patients as compared with non-VDD patients (p < 0.0001). In a regression analysis, as compare with non-VDD patients, the VDD patients were associated with higher odds of discharge to non-home facilities with an admission diagnosis of CHF (aOR 1.08, 95% CI 1.07-1.09), IHD (aOR 1.24, 95% CI 1.21-1.28), acute MI (aOR 1.23, 95% CI 1.19-1.28), AFib (aOR 1.21, 95% CI 1.16-1.27), and TIA (aOR 1.19, 95% CI 1.11-1.28). VDD was associated with higher odds of severe or extreme disability among patients hospitalized with AIS (aOR 1.1, 95% CI 1.06-1.14), ICeH (aOR 1.22, 95% CI 1.08-1.38), TIA (aOR 1.36, 95% CI 1.25-1.47), IHD (aOR 1.37, 95% CI 1.33-1.41), acute MI (aOR 1.44, 95% CI 1.38-1.49), AFib (aOR 1.10, 95% CI 1.06-1.15), and CHF (aOR 1.03, 95% CI 1.02-1.05) as compared with non-VDD. Conclusions: CVD and CeVD in the presence of VDD increase the disability and discharge to non-home facilities among USA hospitalizations. Future studies should be planned to evaluate the effect of VDD replacement for improving outcomes.

Epidemiological and Clinical Characteristics of 6635 COVID-19 Patients: a Pooled Analysis.

An unidentified pneumonia outbreak was first observed in Wuhan, the capital of Hubei Province, China, in December 2019. WHO officially named the disease, Coronavirus Disease 2019 (COVID-19), and declared it as pandemic on Mar 11, 2020. Globally, there are more than 3 million confirmed cases with nearly 200,000 deaths. Hence, we aimed to perform a systematic review and pooled analysis of the current published literature on COVID-19 to provide an insight on the epidemiological and clinical characteristics of COVID-19 patients. A systematic search of published peer-reviewed articles that reported cases with demographical and clinical features of real-time reverse transcriptase polymerase chain reaction (rRT-PCR)-confirmed SARS-CoV-2 infection using MOOSE guidelines was conducted from December 1, 2019, to April 27, 2020, and 50 eligible articles were included for the final analysis. Review articles, opinion articles, and letters not presenting original data as well as studies with incomplete information were excluded. We included a total of 6635 patients from 50 articles, with 54.5 % being male. The predominant symptoms were fever (80.3%), cough (64.2%), and fatigue/myalgia (36.5%) and other symptoms including dyspnea, chest pain, and sore throat. We also found patients with GI symptoms like diarrhea (9.2%) and nausea/vomiting (5.2%). Comorbidities were found in 3,435 (51.7%) patients with the most common being hypertension (22.67%) followed by diabetes mellitus (12.78%). COVID-19 pandemic is not only leading a huge burden on health care facilities but significant disruption in the world society. Patients with coexisting comorbidities are at higher risk and need more utilization of health care resources. As this virus is spreading globally, all countries have to join hands and prepare at all levels of human resources, infrastructure, and facilities to combat the COVID-19 disease.