Statin use and clinical outcomes in patients with COVID-19: An updated systematic review and meta-analysis.

PURPOSE: Observations studies have shown that prior use of statins is associated with a reduced risk of adverse clinical outcomes in patients with COVID-19. However, the available data are limited, inconsistent and conflicting. Besides, no randomised controlled trial exists in this regard. Hence, the present meta-analysis was conducted to provide an updated summary and collate the effect of statin use on clinical outcomes in COVID-19 using unadjusted and adjusted risk estimates. METHODS: PubMed, Scopus and Web of Science databases were systematically searched using appropriate keywords till December 18 2020, to identify observational studies reporting clinical outcomes in COVID-19 patients using statins versus those not using statins. Prior and in-hospital use of statins were considered. Study quality was assessed using the Newcastle-Ottawa Scale. Unadjusted and adjusted pooled odds ratio (OR) with 95% CIs were calculated. RESULTS: We included 14 observational studies pooling data retrieved from 19 988 patients with COVID-19. All the studies were of high/moderate quality. Pooled analysis of unadjusted data showed that statin use was not associated with improved clinical outcomes (OR 1.02; 95% CI 0.69 to 1.50, p=0.94, I2=94%, random-effects model). However, on pooling adjusted risk estimates, the use of statin was found to significantly reduce the risk of adverse outcomes (OR 0.51; 95% CI 0.41 to 0.63, p<0.0005, I2=0%, fixed-effects model). CONCLUSIONS: Statin use is associated with improved clinical outcomes in patients with COVID-19. Individuals with multiple comorbidities on statin therapy should be encouraged to continue the drug amid the ongoing pandemic.

Bendamustine-Rituximab in Young CLL: Relevance in the Era of Small Molecule Inhibitors.

Purpose: Chemo-immunotherapies like Fludarabine-Cyclophosphamide-Rituximab (FCR) are used for treatment of chronic lymphocytic leukemia (CLL) in young and fit patients while Bendamustine-Rituximab (BR) is used in older patients. In a resource constrained setting, managing toxicities of FCR chemotherapy is challenging and this study explores the use of upfront BR treatment in young CLL patients (age < 65). Methods: Data of 61 CLL patients treated with the BR regimen between 2016 and 2020 was analysed. Overall-survival and progression-free-survival (OS and PFS) were compared between the two age groups (< / > 65 years) and correlated with the fluorescent-in-situ-hybridization (FISH) data, duration of illness and time to initiation of chemotherapy. Results: Out of 61 patients, 34 (85%) were below 65 years. Five patients had del 17p and were excluded from the analysis. Forty patients had indications for treatment. Twenty-four (70.5%) of the forty patients achieved overall response; 10 developed progressive disease. The median OS and PFS was 1874 days (95% CI 1617-2130 days) and 1226 days (95% CI 1021-1432 days) respectively and were non inferior between the 2 age-groups. There were no correlations with clinical, laboratory or FISH parameters. The OS and PFS were better for patients with longer time to initiation of chemotherapy as compared to those with short duration of illness and short wait-and-watch periods (p < 0.000). Conclusions: Our results show that BR chemotherapy can safely and effectively be used in upfront treatment of young CLL patients and provide durable responses.

Bleeding per rectum during induction chemotherapy: Looking beyond the leukaemia - 2 case reports and review of literature.

Synchronous malignancies involving acute leukemia and a solid organ are rare. Bleeding per rectum is a common manifestation of acute leukemia during induction chemotherapy and might mask the presence of synchronous colorectal adenocarcinoma (CRC). Here we present two rare cases of acute leukemia with synchronous CRC. We also review previously reported synchronous malignancies to investigate demographics, diagnosis, and treatment modalities. Management of these cases requires a multispecialty approach.

Immune Thrombocytopenia Secondary to COVID-19: a Systematic Review.

Immune thrombocytopenia, often known as immune thrombocytopenic purpura (ITP), has emerged as an important complication of COVID-19. A systematic review was done to analyze the clinical profile and outcomes in a total of 45 cases of new-onset ITP in COVID-19 patients described in literature until date. A comprehensive approach is essential for diagnosing COVID-19-associated ITP after excluding several concomitant factors that can cause thrombocytopenia in COVID-19. Majority of ITP cases (71%) were found to be elderly (> 50 years) and 75% cases had moderate-to-severe COVID-19. Three patients (7%) were in the pediatric age group. Reports of ITP in asymptomatic COVID-19 patients (7%) underscore the need for COVID-19 testing in newly diagnosed patients with ITP irrespective of COVID-19 symptoms amid this pandemic. ITP onset occurred in 20% cases 3 weeks after onset of COVID-19 symptoms, with many reports after clinical recovery. SARS-CoV-2-mediated immune thrombocytopenia can be attributed to the underlying immune dysregulation, susceptibility mutations in SOCS 1, and other mechanisms, including molecular mimicry, cryptic antigen expression, and epitope spreading. No bleeding manifestations were reported in 31% cases at diagnosis. Severe life-threatening bleeding was uncommon. One case of mortality was attributed to intracranial hemorrhage. Secondary Evans syndrome was diagnosed in one case. Good initial response to short course of glucocorticoids and intravenous immunoglobulin has been found with the exception of delayed lag response in one case. Thrombopoietin receptor agonist usage as a second-line agent has been noted in few cases for short duration with no adverse events. In the relatively short follow-up period, four relapses of ITP were found.

Clinical profile and outcomes in COVID-19 patients with diabetic ketoacidosis: A systematic review of literature.

BACKGROUND AND AIM: To conduct a systematic literature review and analyze the demographic/biochemical parameters and clinical outcomes of COVID-19 patients with diabetic ketoacidosis (DKA) and combined DKA/HHS (hyperglycemic hyperosmolar syndrome). METHODS: PubMed, Scopus, Embase, and Google Scholar databases were systematically searched till August 3, 2020 to identify studies reporting COVID-19 patients with DKA and combined DKA/HHS. A total of 19 articles reporting 110 patients met the eligibility criteria. RESULTS: Of the 110 patients, 91 (83%) patients had isolated DKA while 19 (17%) had DKA/HHS. The majority of the patients were male (63%) and belonged to black ethnicity (36%). The median age at presentation ranged from 45.5 to 59.0 years. Most of the patients (77%) had pre-existing type 2 diabetes mellitus. Only 10% of the patients had newly diagnosed diabetes mellitus. The median blood glucose at presentation ranged from 486.0 to 568.5 mg/dl, being higher in patients with DKA/HHS compared to isolated DKA. The volume of fluid replaced in the first 24 h was higher in patients with DKA/HHS in contrast to patients with DKA alone. The in-hospital mortality rate was 45%, with higher mortality in the DKA/HHS group than in the isolated DKA group (67% vs. 29%). pH was lower in patients who had died compared to those who were discharged. CONCLUSION: DKA in COVID-19 patients portends a poor prognosis with a mortality rate approaching 50%. Differentiating isolated DKA from combined DKA/HHS is essential as the latter represents nearly one-fifth of the DKA cases and tends to have higher mortality than DKA alone.

COVID-19 Associated Hemophagocytic Lymphohistiocytosis and Coagulopathy: Targeting the Duumvirate.

CONTEXT: Preliminary data on coexistence of secondary hemophagocytic lymphohistiocytosis syndrome (HLH) and disseminated intravascular coagulation (DIC) in critically ill children with novel coronavirus disease (COVID-19) are emerging. Herein, we summarize the available literature and fill-in the gaps in this regard. EVIDENCE ACQUISITION: We have performed a literature search for articles in PubMed, EMBASE and Google Scholar databases till May 12, 2020, with following keywords: "COVID-19", "SARS-CoV-2", "HLH", "HScore", "coagulopathy", "D-dimer", "cytokine storm", "children" and "pediatrics" with interposition of Boolean operator "AND". RESULTS: Children presenting with moderate-severe COVID-19 and Kawasaki disease shock-like syndrome exhibit peripheral blood picture analogous to HLH. HScore, a validated tool to diagnose HLH, has been suggested to screen severe COVID-19 patients for cytokine storm. However, HScore faces certain limitations in this scenario. It may be more pragmatic to use 'high D-dimer' (> 3 µg/mL) instead of 'low fibrinogen' to facilitate early detection of cytokine storm. COVID-19 associated coagulopathy resembles hypercoagulable form of DIC with bleeding being rarely reported. Although the International Society on Thrombosis and Haemostasis (ISTH) interim guidance recommends low molecular weight heparin in all hospitalized patients, data is lacking in population below 14 years of age. However, in the presence of life-threatening thromboembolic event or symptomatic acro-ischemia, unfractionated heparin (UFH) should be used with caution. CONCLUSIONS: HScore can be used as a complement to clinical decision for initiating immunosuppression. Children with moderate-to-severe COVID-19, especially those with documented thrombocytopenia or chilblains, should be regularly monitored for coagulopathy.