Changes in liver enzymes and association with prognosis in patients with COVID-19: a retrospective case–control study

ObjectiveCOVID-19 has recently emerged as a serious threat to global health. This study examined the laboratory investigations of patients with COVID-19, with an emphasis on liver enzymes.MethodsThis retrospective, single-center study was performed on patients with COVID-19 who were admitted to Imam Reza Hospital, Iran from March 2020 to February 2021. Laboratory tests included a complete blood cell count, white blood cell (WBC) count, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio, and levels of aspartate aminotransferase, alanine aminotransferase (ALT), and alkaline phosphatase. Patient survival was among the outcome measures investigated in association with laboratory findings.ResultsWe enrolled 77 patients with COVID-19 and 63 healthy controls. In comparison with the control group, patients with COVID-19 showed COVID-19 increased ALT, WBC, neutrophils, NLR, and PLR, and decreased platelet counts and lymphocytes.ConclusionAlthough elevated levels of AST, NLR, PLR, and LMR were found in patients with COVID-19, they were not linked to mortality. Given the presence of AST in other tissues, the influence of SARS-CoV-2 on the liver should be interpreted with caution.     

Leveraging Clinical Digitized Data to Understand Temporal Characteristics and Outcomes of Acute Myocardial Infarctions at a Tertiary Care Medical Centre in Pakistan from 1988–2018 – Methods and Results

Background and Objective:Few data exist on trends in acute myocardial infarction (AMI) patterns spanning recent epidemiological shifts in low middle-income countries (LMICs). To understand temporal disease patterns of AMI characteristics and outcomes between 1988–2018, we used digitized legacy clinical data at a large tertiary care centre in Pakistan.Methods:We reviewed digital health information capture systems maintained across the Aga Khan University Hospital and obtained structured elements to create a master dataset. We included index admissions of patients >18 years that were discharged between January 1, 1988, and December 31, 2018, with a primary discharge diagnosis of AMI (using ICD-9 diagnoses). The outcome evaluated was in-hospital mortality.Clinical characteristics derived from the electronic database were validated against chart review in a random sample of cases (k 0.53–1.00).Results:The final population consisted of 14,601 patients of which 30.6% (n = 4,470) were female, 52.4% (n = 7,651) had ST elevation MI and 47.6% (n = 6,950) had non-ST elevation MI. The median (IQR) age at presentation was 61 (52–70) years. Overall unadjusted in-hospital mortality was 10.3%. Across the time period, increasing trends were noted for the following characteristics: age, proportion of women, prevalence of hypertension, diabetes, proportion with NSTEMI (all p_trend < 0.001). In-hospital mortality rates declined significantly between 1988–1997 and 2008–2018 (13.8% to 9.2%, p < 0.001).Conclusions:The patterns of AMI have changed over the last three decades with a concomitant decline in in-hospital mortality at a tertiary care centre in Pakistan. Clinical digitized data presents a unique opportunity for gaining insights into disease patterns in LMICs.     

Proposed model for in vitro interaction between fenitrothion and DNA,by using competitive fluorescence, 31P NMR, 1H NMR,FT-IR,CD and molecular modeling

In this work we proposed a model for in vitro interaction of fenitrothion (FEN) with calf thymus-DNA by combination of multispectroscopic and two dimensional molecular modeling (ONIOM) methods. The circular dichroism results showed that FEN changes the conformation of B-DNA and caused some changes to C-DNA form. The FT-IR results confirmed a partial intercalation between FEN and edges of all base pairs. The competitive fluorescence, using methylene blue as fluorescence probe, in the presence of increasing amounts of FEN, revealed that FEN is able to release the non-intercalated methylene blue from the DNA. The weak chemical shift and peak broadening of ¹H NMR spectrum of FEN in the presence of DNA confirmed a non-intercalation mode. The ³¹P NMR showed that FEN interacts more with DNA via its –NO₂ moiety. The ONIOM, based on the hybridization of QM/MM (DFT, 6.31++G (d,p)/UFF) methodology, was also performed by Gaussian 2003 package. The results revealed that the interaction is base sequence dependent, and FEN interacts more with AT base sequences.     

Therapy of Core Binding Factor Acute Myeloid Leukemia: Incremental Improvements Toward Better Long-Term Results

BackgroundDespite being considered as good prognostic acute myelogenous leukemia (AML), the long-term survival rate in core binding factor (CBF) AML leaves room for substantial improvement.Materials and MethodsWe reviewed relevant English language literature related to treatment of CBF AML available in PubMed. Review also included meeting abstracts.ResultsMulticycle high dose cytarabine in consolidation improves remission duration but larger groups report overall survival in the range of 40% to 50% at 5 years or longer.ConclusionsConcerted effort is needed toward improving outcomes in CBF AML through clinical trials and risk-adapted approach.     

Spironolactone improves angiotensin-induced vascular changes and oxidative stress

Angiotensin II plays an important role in vascular remodeling. We investigated the role of aldosterone, which is stimulated by angiotensin II, as a mediator of angiotensin II-induced vascular structural and functional alterations. Sprague-Dawley rats (n=8 to 12/group) received angiotensin II (120 ng/kg per minute, subcutaneously) for 14 days +/- spironolactone or hydralazine (25 mg/kg per day). An additional group received aldosterone (750 ng/h, subcutaneously) +/- spironolactone. Systolic blood pressure was increased by angiotensin II (P<0.001) and reduced by spironolactone and hydralazine (P<0.001). Aldosterone-induced increase of blood pressure was reduced by spironolactone (P<0.05). In mesenteric small arteries studied on a pressurized myograph, media/lumen ratio was increased (P<0.001) and acetylcholine-mediated relaxation was impaired in angiotensin II-infused rats (P<0.001); both were partially improved by spironolactone (P<0.05) but not by hydralazine. Aldosterone-induced increase of media/lumen ratio (P<0.001) and impaired response to acetylcholine (P<0.001) were normalized by spironolactone. Response to sodium nitroprusside was similar in all groups. Aortic NADPH oxidase activity was increased (P<0.01) by angiotensin II and reduced by spironolactone and hydralazine. Aldosterone also increased (P<0.05) activation of NADPH oxidase, an effect abolished by spironolactone. Plasma thiobarbituric acid-reactive substances (a marker of oxidative stress), higher in angiotensin II and aldosterone rats (P<0.001), were normalized by spironolactone. In conclusion, spironolactone, which inhibited aldosterone actions, partially corrected structural and functional angiotensin II-induced abnormalities. These effects were associated with reduced vascular NADPH oxidase activity and decreased plasma markers of oxidative stress. Our findings suggest that aldosterone may mediate some of angiotensin II-induced vascular effects in hypertension, in part via increased oxidative stress.