The COVID-19 pandemic has resulted in significant morbidity, mortality, and strained healthcare systems worldwide. Thus, a search for modalities that can expedite and improve the diagnosis and management of this entity is underway. Recent data suggested the utility of lung ultrasound (LUS) in the diagnosis of COVID-19 by detecting an interstitial pattern (B-pattern). Hence, we aimed to pool the proportion of various reported lung abnormalities detected by LUS in symptomatic COVID-19 patients. We conducted a systematic review (PubMed, MEDLINE, and EMBASE until April 25, 2020) and a proportion meta-analysis. We included seven studies examining the role of LUS in 122 COVID-19 patients. The pooled proportion (PP) of B-pattern detected by lung ultrasound (US) was 0.97 (95% CI: 0.94-1.00 I 2 0%, Q 4.6). The PP of finding pleural line abnormalities was 0.70 (95% CI: 0.13-1.00 I 2 96%, Q 103.9), of pleural thickening was 0.54 (95% 0.11-0.95 I 2 93%, Q 61.1), of subpleural or pulmonary consolidation was 0.39 (95% CI: 0.21-0.58 I 2 72%, Q 17.8), and of pleural effusion was 0.14 (95% CI: 0.00-0.37 I 2 93%, Q 27.3). Our meta-analysis revealed that almost all SARS-CoV-2-infected patients have abnormal lung US. The most common abnormality is interstitial involvement depicted as B-pattern. The finding from our review highlights the potential role of this modality in the triage, diagnosis, and follow-up of COVID-19 patients. A sizable diagnostic accuracy study comparing LUS, computed tomography scan, and COVID-19-specific tests is warranted to further test this finding and to delineate the diagnostic and prognostic yield of each of these modalities.

Direct oral anticoagulant (DOAC) agents are becoming the anticoagulation strategy of choice. However, their use in the treatment of acute venous thromboembolism (VTE) in morbidly obese patients (bodyweight of > 120 kg or BMI > 40 kg/ m 2) guarded. This is due to the scarce data supporting their use in this population. As a result, the International Society on Thrombosis and Haemostasis recommended against their use in this cohort of patients. New data emerged supporting the use of DOACs in these patients. Hence, we aimed to systematically review the literature exploring the efficacy and safety of these agents compared to warfarin in VTE treatment in morbidly obese patients. A systematic review of PubMed and EMBASE since inception until 01/04/2020. Subsequently, a non-inferiority (NI of 1.75) meta-analysis utilizing the random-effects model. Five observational studies (6585 patients) were included in our meta-analysis. DOAC analogs were non-inferior compared to warfarin in reducing the primary efficacy outcome of VTE recurrence (OR 1.07, 95% CI 0.93-1.23) and the primary safety outcome (major bleeding events) (OR 0.80, 95% CI 0.54-1.17). Our meta-analysis comprising real-world observational data concludes that the use of DOAC analogs in morbidly obese patients (bodyweight of > 120 kg or BMI > 40 kg/m 2) is non-inferior with regards to efficacy and safety compared to warfarin. This finding helps to resolve the uncertainty associated with the use of DOACs in this cohort. Additionally, it invites for a confirmatory non-inferiority randomized controlled trial testing DOAC vs. Warfarin in this group of patients.

The COVID-19 pandemic is caused by the severe acute-respiratory-syndrome-coronavirus-2 that uses ACE2 as its receptor. Drugs that raise serum/tissue ACE2 levels include ACE inhibitors (ACEIs) and angiotensin-II receptor blockers (ARBs) that are commonly used in patients with hypertension, cardiovascular disease and/or diabetes. These comorbidities have adverse outcomes in COVID-19 patients that might result from pharmacotherapy. Increasing ACE2 could potentially increase the risk of infection, severity or mortality in COVID-19 or it might be protective as it forms angiotensin-(1-7) which exhibits anti-inflammatory/anti-oxidative effects and prevents diabetes-and/or hypertension-induced end-organ damage. Thus, there existed clinical uncertainty. Here, we review studies implicating 15 classes of drugs in increasing ACE2 levels in vivo and the available literature on the clinical safety of these drugs in COVID-19 patients. Further, in a re-analysis of clinical data from a meta-analysis of 9 studies, we show that ACEIs/ARBs usage was not associated with an increased risk of all-cause mortality. Literature suggests that ACEIs/ARBs usage generally appears to be clinically safe though their use in severe COVID-19 patients might increase the risk of acute renal injury. For definitive clarity, further clinical and mechanistic studies are needed in assessing the safety of all classes of ACE2 raising medications.

Euglycemic diabetic ketoacidosis (EuDKA) secondary to Sodium-glucose co-transporter-2 inhibitors (SGLT2i) in type 2 diabetes mellitus (T2D) is a rare but increasingly reported phenomenon. Not much is known about the burden of EuDKA in patients on SGLT2i or the associated factors. This retrospective cohort study tries to delineate the differences in factors associated with the development of EuDKA as compared to hyperglycemic DKA. We conducted a multicentre, retrospective study across three tertiary care centers under Weill Cornell affiliated-Hamad Medical Corporation, Qatar. The cohort comprised of T2D patients on SGLT2i who developed DKA between January 2015 to December 2020. The differences between the subjects who developed EuDKA or hyperglycaemic DKA (hDKA) were analyzed. A total of 9940 T2D patients were on SGLT2i during 2015–2020, out of which 43 developed DKA (0.43%). 25 developed EuKDA, whereas 18 had hDKA. The point prevalence of EuDKA in our cohort was 58.1%. EuDKA was most common in patients using canagliflozin, followed by empagliflozin and Dapagliflozin (100%, 77%, and 48.3%, respectively). Overall, infection (32.6%) was the most common trigger for DKA, followed by insulin non-compliance (13.7%). Infection was the only risk factor with a significant point estimate between the two groups, being more common in hDKA patients (p-value 0.006, RR 2.53, 95% CI 1.07–5.98). Canagliflozin had the strongest association with the development of EuDKA and was associated with the highest medical intensive care unit (MICU) admission rates (66.6%). In T2D patients on SGLT2i, infection is probably associated with an increased risk of developing EuDKA. The differential role of individual SGLT2i analogs is less clear and will need exploration by more extensive prospective studies.

Background: Recent studies revealed a high prevalence of venous thromboembolism (VTE) events in coronavirus disease 2019 (COVID-19) patients, especially in those who are critically ill. Available studies report varying prevalence rates. Hence, the exact prevalence remains uncertain. Moreover, there is an ongoing debate regarding the appropriate dosage of thromboprophylaxis.Methods: We performed a systematic review and proportion meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed and EMBASE for studies exploring the prevalence of VTE in critically ill COVID-19 patients till 25/07/2020. We pooled the proportion of VTE. Additionally, in a subgroup analysis, we pooled VTE events detected by systematic screening. Finally, in an exploratory analysis, we compared the odds of VTE in patients on prophylactic compared with therapeutic anticoagulation.Results: The review comprised 24 studies and over 2,500 patients. The pooled proportion of VTE prevalence was 0.31 [95% confidence interval (CI) 0.24, 0.39; I2 94%], of VTE utilizing systematic screening was 0.48 (95% CI 0.33, 0.63; I2 91%), of deep venous thrombosis was 0.23 (95% CI 0.14, 0.32; I2 96%), and of pulmonary embolism was 0.14 (95% CI 0.09, 0.20; I2 90%). Exploratory analysis of few studies, utilizing systematic screening, VTE risk increased significantly with prophylactic, compared with therapeutic anticoagulation [odds ratio (OR) 5.45; 95% CI 1.90, 15.57; I2 0%].Discussion: Our review revealed a high prevalence of VTE in critically ill COVID-19 patients. Almost 50% of patients had VTE detected by systematic screening. Higher thromboprophylaxis dosages may reduce VTE burden in this patient's cohort compared with standard prophylactic anticoagulation; however, this is to be ascertained by ongoing randomized controlled trials.

The converging clinical effectiveness of mineralocorticoid receptor antagonists (MRAs) Spironolactone and Eplerenone has made their safety profiles/cost-effectiveness key determinants of "agents of choice" across a broad range of clinical indications. The clinical biology of the aldosterone molecule and its range of effects in varied organ systems have been well elucidated from recent mechanistic and systematic studies. Clinical experience with Spironolactone is well established, as is its adverse effects profile. The range of adverse effects experienced with Spironolactone subsequently led to its modification and synthesis of Eplerenone. Recent published reports have confirmed lower prevalence rates of sex-related adverse effects attributable to Eplerenone compared to Spironolactone. There is, however, not much to choose between these agents in regards to other adverse effects including hyperkalemia and kidney failure. As was the experience with Spironolactone, as more robust observational data on Eplerenone accrues, it is possible that the real-life experience of its adverse profile may be discordant with that reported by randomized controlled clinical trials (RCTs). In addition, its metabolism by the vulnerable and highly polymorphic cytochrome dependent pathway also makes it susceptible to various drug interactions. The potential implication of the latter (including morbidity and mortality) may take years to evolve.

Background: Recent studies revealed a high prevalence of venous thromboembolism (VTE) events in coronavirus disease 2019 (COVID-19) patients, especially in those who are critically ill. Available studies report varying prevalence rates. Hence, the exact prevalence remains uncertain. Moreover, there is an ongoing debate regarding the appropriate dosage of thromboprophylaxis. Methods: We performed a systematic review and proportion meta-analysis following PRISMA guidelines. We searched PubMed and EMBASE for studies exploring the prevalence of VTE in critically ill COVID-19 patients till 22/07/2020. We pooled the proportion of VTE. Additionally, in a subgroup analysis, we pooled VTE events detected by systematic screening. Finally, we compared the odds of VTE in patients on prophylactic compared to therapeutic anticoagulation. Results: The review comprised of 24 studies and over 2500 patients. The pooled proportion of VTE prevalence was 0.31 (95% CI 0.24, 0.39 I2 94%), of VTE utilizing systematic screening was 0.48 (95% CI 0.33, 0.63 I2 91%), of deep-venous-thrombosis was 0.23 (95% CI 0.14, 0.32 I2 96%), of pulmonary embolism was 0.14 (95% CI 0.09, 0.20 I2 90%). In a subgroup of studies, utilizing systematic screening, VTE risk increased significantly with prophylactic, compared to therapeutic anticoagulation (OR 5.45; 95% CI 1.90, 15.57 I2 0%). Discussion: Our review revealed a high prevalence of VTE in critically ill COVID-19 patients. Almost 50% of patients had VTE detected by systematic screening. Higher thromboprophylaxis dosages seem to reduce VTE burden in this patient's cohort compared to standard prophylactic anticoagulation; ongoing randomized controlled trials will further confirm this.

Background: Drug induced liver injury (DILI) is an increasing cause of acute liver injury especially with increasing need for pharmacotherapy of widening comorbidities amongst our ever-aging population. Uncertainty however remains regarding both acceptable and widely agreeable diagnostic algorithms as well a clear understanding of mechanistic insights that most accurately underpins it. In this review, we have explored the potential role of emerging novel markers of DILI and how they could possibly be integrated into clinical care of patients.Methods: We explored PUBMED and all other relevant databases for scientific studies that explored potential utility of novel biomarkers of DILI, and subsequently carried out a narrative synthesis of this data. As this is a narrative review with no recourse to patient identifiable information, no ethics committee's approval was sought or required.Results: Novel biomarkers such as microRNA-122 (miR-122) profiles, high mobility group box-1 (HMGB1), glutamate dehydrogenase (GLDH), and cytokeratin-18 (K-18), amongst others do have the potential for reducing diagnostic uncertainties associated with DILI. Conclusion:With the increasing validation of some of the novel liver biomarkers such as K-18, mir-122, HMGB-1, and GLDH, there is the potential for improvement in the diagnostic uncertainty commonly associated with cases of DILI.Abbreviations: ALP = alkaline phosphatase, ALT = alanine aminotransferase, AST = aspartate aminotransferase, DILI = drug induced liver injury, EMEA = European medicines agency, FDA = food and drug administration, GLD = glutamate dehydrogenase, HMGB-1 = high mobility group box protein -1, IDILI = idiopathic drug induced liver injury, K-18 = cytokeratin-18, Mir-122 = microrna-122, RUCAM = Roussel-Uclaf Causality Assessment Method, TBL = total bilirubin.