Hydroxychloroquine: A Comprehensive Review and Its Controversial Role in Coronavirus Disease 2019

Hydroxychloroquine, initially used as an antimalarial, is used as an immunomodulatory and anti-inflammatory agent for the management of autoimmune and rheumatic diseases such as systemic lupus erythematosus. Lately, there has been interest in its potential efficacy against severe acute respiratory syndrome coronavirus 2, with several speculated mechanisms. The purpose of this review is to elaborate on the mechanisms surrounding hydroxychloroquine. The review is an in-depth analysis of the antimalarial, immunomodulatory, and antiviral mechanisms of hydroxychloroquine, with detailed and novel pictorial explanations. The mechanisms of hydroxychloroquine are related to potential cardiotoxic manifestations and demonstrate potential adverse effects when used for coronavirus disease 2019 (COVID-19). Finally, current literature associated with hydroxychloroquine and COVID-19 has been analyzed to interrelate the mechanisms, adverse effects, and use of hydroxychloroquine in the current pandemic. Currently, there is insufficient evidence about the efficacy and safety of hydroxychloroquine in COVID-19.KEY MESSAGES HCQ, initially an antimalarial agent, is used as an immunomodulatory agent for managing several autoimmune diseases, for which its efficacy is linked to inhibiting lysosomal antigen processing, MHC-II antigen presentation, and TLR functions. HCQ is generally well-tolerated although severe life-threatening adverse effects including cardiomyopathy and conduction defects have been reported. HCQ use in COVID-19 should be discouraged outside clinical trials under strict medical supervision

Role of Intra-abdominal Pressure in Early Acute Kidney Injury: A Prospective Cohort Study in Critically Ill Obstetric Patients

This prospective cohort study evaluated intra-abdominal pressure (IAP) and its role in causing acute kidney injury (AKI) in critically ill obstetric patients and utility of urinary neutrophil gelatinase-associated lipocalin (NGAL) to predict AKI. A total of 50 eligible obstetric patients admitted to our Intensive Care Unit were enrolled and daily IAP measured using indwelling Foley catheter. Early AKI was diagnosed as per the KDIGO criteria and urine assessed for NGAL using ELISA. AKI was seen in 54% and intra-abdominal hypertension (IAH) in 21% patients. In patients with and without AKI, there was statistically similar IAP on day 1 ( = 0.542) and day 2 ( = 0.907) as well as incidence of IAH (19% vs. 23%) ( = 0.766). Area under receiver operating characteristic curve (AUC) for IAP to predict early AKI was 0.499 (95% confidence interval [CI]: 0.325-0.673) ( = 0.992). Urinary NGAL concentration was significantly greater in patients with early AKI compared to those without ( = 0.006); AUC for urinary NGAL to detect early AKI was 0.734 (95% CI: 0.583-0.884) ( = 0.006) and optimal cutoff was 53.7 ng/ml. IAH and AKI are common in critically ill obstetric patients. While IAP does not correlate with early AKI, NGAL is useful to predict AKI

Risk of early postoperative acute kidney injury with stroke volume variation-guided tetrastarch versus Ringer's lactate

Background: Whether intraoperative use of hydroxyethyl starch (HES) solutions is associated with postoperative acute kidney injury (AKI) continues to be researched. Urinary neutrophil gelatinase-associated lipocalin (NGAL) is validated for early detection of AKI. Previous studies are limited and use empirically predefined volumes of HES solutions with serum creatinine as marker for AKI. Materials and Methods: Adults scheduled for orthopedic surgery under general anesthesia with >200–300 mL blood loss expected were included; 40 were randomized to receive 6% HES 130/0.4 (tetrastarch) (group HES) or Ringer's lactate (group RL) boluses when stroke volume variation (SVV) >10% in supine or lateral position, or >14% in prone position. Incidence of early postoperative AKI using urinary NGAL (>100 ng/mL) was the primary outcome, and using derangement of serum creatinine was the secondary measure. Results: In 38 patients, intervention was completed, and incidence of AKI (postoperative urinary NGAL >100 ng/mL) among them was 0% in both groups. Patients with urinary NGAL >50 ng/mL were insignificantly higher for group RL versus group HES (6/19 vs. 4/19) (P = 0.461), as were those with incidence of AKI as per creatinine values (5/19 vs. 4/19) (P = 1.000). Group RL had significantly higher requirement of fluid (1211 ± 758 mL vs. 689 ± 394 mL) (P = 0.013) and lower cardiac index (P < 0.05) versus group HES. Conclusion: SVV-guided tetrastarch and Ringer's lactate do not result in postoperative AKI diagnosed by urinary NGAL >100 ng/mL; however, an insignificant trend for better renal functions as well as significantly more efficacious volume expansion and hemodynamic stability were seen with tetrastarch instead

In-Hospital Characteristics and 30-Day Readmissions for Acute Myocardial Infarction and Major Bleeding in Patients With Active Cancer

There are limited data on readmission with ischemic and major bleeding events in patients with acute myocardial infarction (AMI) with active cancer. The purpose of our study was to evaluate in-hospital characteristics and 30-day readmission rates for recurrent AMI and major bleeding by cancer type in patients with AMI and active cancer. From 2016 through 2018, patients in the Nationwide Readmission Database admitted with AMI and underlying active colon, lung, breast, prostate, and hematological cancers were included. Thirty-day readmission for recurrent AMI and major bleeding were reported. Of 1,524,677 index hospitalizations for AMI, 35,790 patients (2.2%) had cancer (0.9% hematological; 0.5% lung; 0.4% prostate; 0.2% breast; and 0.1% colon). Compared with patients without cancer, patients with cancer were about 6 to 10 years older and had a higher proportion of atrial fibrillation, valvular heart disease, previous stroke, and a greater co-morbidity burden. Of all cancer types, only active breast cancer (adjusted odds ratios 1.82, 95% CI 1.11 to 2.98) was found to be significantly associated with elevated odds of readmission for major bleeding; no such association was observed for recurrent AMI. In conclusion, AMI in patients with breast cancer is associated with significantly greater odds of readmission for major bleeding within 30 days after discharge. Management of patients with concomitant AMI and cancer is challenging but should be based on a multidisciplinary approach and estimation of an individual patient\u27s risk of major coronary thrombotic and bleeding events

Extracorporeal Membrane Oxygenation in Patients With COVID-19

Coronavirus disease 2019 (COVID-19) is characterized by a clinical spectrum of diseases ranging from asymptomatic or mild cases to severe pneumonia with acute respiratory distress syndrome (ARDS) requiring mechanical ventilation. Extracorporeal membrane oxygenation (ECMO) has been used as rescue therapy in appropriate patients with COVID-19 complicated by ARDS refractory to mechanical ventilation. In this study, we review the indications, challenges, complications, and clinical outcomes of ECMO utilization in critically ill patients with COVID-19-related ARDS. Most of these patients required venovenous ECMO. Although the risk of mortality and complications is very high among patients with COVID-19 requiring ECMO, it is similar to that of non-COVID-19 patients with ARDS requiring ECMO. ECMO is a resource-intensive therapy, with an inherent risk of complications, which makes its availability limited and its use challenging in the midst of a pandemic. Well-maintained data registries, with timely reporting of outcomes and evidence-based clinical guidelines, are necessary for the careful allocation of resources and for the development of standardized utilization protocols

Network meta-analysis comparing the short and long-term outcomes of alternative access for transcatheter aortic valve replacement

BACKGROUND: Several studies have pair-wise compared access sites for transcatheter aortic valve replacement (TAVR) but pooled estimate of overall comparative efficacy and safety outcomes are not well known. We sought to compare short- and long-term outcomes following various alternative access routes for TAVR. METHODS: Thirty-four studies with a pooled sample size of 32,756 patients were selected by searching PubMed and Cochrane library databases from inception through 11th June 2021 for patients undergoing TAVR via 1 of 6 different access sites: Transfemoral (TF), Transaortic (TAO), Transapical (TA), Transcarotid (TC), Transaxillary/Subclavian (TSA), and Transcaval (TCV). Data were extracted to conduct a frequentist network meta-analysis with a random-effects model using TF access as a reference group. RESULTS: Compared with TF, both TAO [RR 1.91, 95% CI (1.46-2.50)] and TA access [RR 2.12, 95% CI (1.84-2.46)] were associated with an increased risk of 30-day mortality. No significant difference was observed for stroke, myocardial infarction, major bleeding, conversion to open surgery, and major adverse cardiovascular or cerebrovascular events at 30 days between different accesses. Major vascular complications were lower in TA [RR 0.43, (95% CI, 0.28-0.67)] and TC [RR 0.51, 95% CI (0.35-0.73)] access compared to TF. The 1-year mortality was higher in TAO [RR of 1.35, (95% CI, 1.01-1.81)] and TA [RR 1.44, (95% CI, 1.14-1.81)] groups. CONCLUSION: Non-thoracic alternative access site utilization for TAVR implantation (TC, TSA and TCV) is associated with outcomes similar to conventional TF access. Thoracic TAVR access (TAO and TA) translates into increased short and long-term mortality