Ursodeoxycholic acid as a means of preventing atherosclerosis,steatosis and liver fibrosis in patients with nonalcoholic fatty liver disease

BACKGROUNDAtherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality in patients with nonalcoholic fatty liver disease (NAFLD). Weight loss is a key factor for successful NAFLD and CVD therapy. Ursodeoxycholic acid (UDCA), which is one of the first-line therapeutic agents for treatment of NAFLD, is reported to have a beneficial effect on dyslipidemia and ASCVD risk because of antioxidant properties.AIMTo evaluate the effects of 6 mo of UDCA treatment on hepatic function tests, lipid profile, hepatic steatosis and fibrosis, atherogenesis, and ASCVD risk in men and women with NAFLD, as well as to assess the impact of > 5% weight reduction on these parameters.METHODSAn open-label, multicenter, international noncomparative trial was carried out at primary health care settings and included 174 patients with ultrasound-diagnosed NAFLD who received 15 mg/kg/d UDCA for 6 mo and were prescribed lifestyle modification with diet and exercise. The efficacy criteria were liver enzymes, lipid profile, fatty liver index (FLI), noninvasive liver fibrosis tests (nonalcoholic fatty liver disease fibrosis score and liver fibrosis index), carotid intima-media thickness (CIMT), and ASCVD risk score. To test statistical hypotheses, the Wilcoxon test, paired t-test, Fisher’s exact test, and Pearson''s chi-squared test were used. RESULTSThe alanine aminotransferase (ALT) level changed by -14.1 U/L (-31.0; -5.3) from baseline to 3 mo and by -6.5 U/L (-14.0; 0.1) from 3 to 6 mo. The magnitude of ALT, aspartate transaminase, and glutamyltransferase decrease was greater during the first 3 mo of treatment compared to the subsequent 3 mo (P < 0.001, P < 0.01, P < 0.001, respectively). At 6 mo, in the total sample, we observed a statistically significant decrease in body weight and levels of FLI: 84.9 ± 10.4 vs 72.3 ± 17.6, P < 0.001, total cholesterol: 6.03 ± 1.36 vs 5.76 ± 1.21, Р < 0.001, low-density lipoprotein: 3.86 ± 1.01 vs 3.66 ± 0.91, Р < 0.001, and triglyceride: 3.18 (2.00; 4.29) vs 2.04 (1.40; 3.16), Р < 0.001. No effect on nonalcoholic fatty liver disease fibrosis score or liver fibrosis index was found. The CIMT decreased significantly in the total sample (0.985 ± 0.243 vs 0.968 ± 0.237, P = 0.013), whereas the high-density lipoprotein (Р = 0.036) and 10-year ASCVD risk (Р = 0.003) improved significantly only in women. Fifty-four patients (31%) achieved > 5% weight loss. At the end of the study, the FLI decreased significantly in patients with (88.3 ± 10.2 vs 71.4 ± 19.6, P < 0.001) and without > 5% weight loss (83.5 ± 10.3 vs 72.8 ± 16.7, P < 0.001). The changes in ALT, aspartate transaminase, glutamyltransferase, total cholesterol, and low-density lipoprotein levels were similar between the subgroups.CONCLUSIONUDCA normalizes liver enzymes greatly within the first 3 mo of treatment, improves lipid profile and hepatic steatosis independent of weight loss, and has a positive effect on CIMT in the total sample and 10-year ASCVD risk in women after 6 mo of treatment.     

Evaluation of the Pyruvate Kinase isoenzyme tumor (Tu M2-PK) as a tumor marker for cervical carcinoma

Various isoforms of the glycolytic enzyme pyruvate kinase are expressed in different cell types. One of these isoforms, Tu M2-PK, is over-expressed in tumor cells and released into body fluids. Plasma determination of Tu M2-PK has been shown to discriminate between benign and malignant lesions. Tu M2-PK was quantitated in the plasma of 50 patients with cervical carcinoma, 10 patients with chronic cervicitis and 10 healthy controls. The concentration of Tu M2-PK was determined by commercial kits using a sandwich enzyme linked immunosorbent assay based on two monoclonal antibodies (clone I and II) specific for Tu M2-PK. The sensitivity of the test for discrimination of malignant from non-malignant condition was 82% with a specificity of 60%. Highly significant statistical difference was found in the means of three groups (P = 0.0002). The present results indicate that Tu M2-PK can be used as a tumor marker in follow-up of patients with cervical carcinoma.     

Is Lone Hypertension a Risk Factor for More Severe COVID-19 Outcomes?

Background:Based on current evidence, it is not clear whether lone hypertension increases the risk for severe illness from COVID-19, or if increased risk is mainly associated with age, obesity and diabetes. The objective of the study was to evaluate whether lone hypertension is associated with increase mortality or a more severe course of COVID-19, and if treatment and control of hypertension mitigates this risk.Methods:This is a prospective multi-center observational cohort study with 30-day outcomes of 9,531 consecutive SARS-CoV-2 PCR-positive patients ≥ 18 years old (41.9 ± 9.7 years, 49.2% male), Uzbekistan, June 1-September 30, 2020. Patients were subclassified according to JNC8 criteria into six blood pressure stages. Univariable and multiple logistic regression was conducted to examine how variables predict outcomes.Results:The 30-days all-cause mortality was 1.18% (n = 112) in the whole cohort. After adjusting for age, sex, history of myocardial infarction (MI), type-2 diabetes, and obesity, none of six JNC8 groups showed any significant difference in all-cause mortality. However, age was associated with an increased risk of 30-days all-cause mortality (OR = 1.09, 95%CI [1.07–1.12], p < 0.001), obesity (OR = 7.18, 95% CI [4.18–12.44], p < 0.001), diabetes (OR 4.18, 95% CI [2.58–6.76], p < 0.001), and history of MI (OR = 2.68, 95% CI [1.67–4.31], p < 0.001). In the sensitivity test, being ≥ 65 years old increased mortality 10.56-fold (95% CI [5.89–18.92], p < 0.001). Hospital admission was 12.4% (n = 1,183), ICU admission 1.38% (n = 132). The odds of hospitalization increased having stage-2 untreated hypertension (OR = 4.51, 95%CI [3.21–6.32], p < 0.001), stage-1 untreated hypertension (OR = 1.97, 95%CI [1.52–2.56], p < 0.001), and elevated blood pressure (OR = 1.82, 95% CI [1.42–2.34], p < 0.001). Neither stage-1 nor stage-2 treated hypertension patients were at statistically significant increased risk for hospitalization after adjusting for confounders. Presenting with stage-2 untreated hypertension increased the odds of ICU admission (OR = 3.05, 95 %CI [1.57–5.93], p = 0.001).Conclusions:Lone hypertension did not increase COVID-19 mortality or in treated patients risk of hospitalization.     

A delayed diagnosis: stridor secondary to hypocalcemia

Hypocalcemia with stridor is a well-known condition in the pediatric age group but has rarely been reported in the elderly. We report an elderly patient who presented with dyspnea and laryngeal stridor attack caused by hypocalcemia. The patient had been suffering from stridor and dyspnea episodes for 2 years, and the etiology had not been determined until the evaluation in our department. The cause of stridor was hypocalcemia secondary to thyroidectomy. Complete resolution of stridor was achieved by calcium replacement therapy.     

Extraction of Rhenium and Osmium from Lead Technogenic Raw Materials of Copper Production

Lead sludge from copper production is a source of rare metals, such as rhenium and osmium, whose content reaches 0.06–0.08% and 0.0025–0.0050%, respectively. The base of the sludge consists of lead sulfate. A method of reductive smelting of lead sludge from copper smelting production at 1000–1100 °C has been developed. Coke was used as a reducing agent and sodium sulfate as a slag-forming material. Optimal conditions for selective extraction of rare metals in smelting products were found: osmium in the form of metallic form into raw lead and rhenium in the form of perrhenate compound Na₅ReO₆ into sodium-sulfate slag. The developed technology makes it possible to extract rhenium with a high degree of extraction in the form of water-soluble compounds for the subsequent production of commercial salts of rhenium by the known hydrometallurgical methods. The content of rhenium in the slag phase is 0.18–0.25%, with its initial content in the slime of 0.06–0.08%. The degree of rhenium concentration at the first stage of processing is 3–3.2 times in the form of water-soluble perrhenate. Osmium and lead do not form solid solutions; osmium in crude lead is mainly concentrated in the lower zones of lead. A method of obtaining a concentrate containing 53–67% osmium from raw lead with an initial content of 0.0025–0.0050% in the slurry and a concentration number of 13,000–21,000 times has been proposed.     

KIT mutations in Russian patients with mucosal melanoma

A single institution series of 48 mucosal melanomas (MMs) has been analyzed for the presence of KIT mutations using high-resolution melting and sequencing of abnormally melted DNA fragments. The analysis of exons 9, 11, 13, and 17 has revealed eight of 48 (17%) nonsynonymous alterations, including zero of seven head and neck, six of 24 anorectal, one of 15 genitourinary, one of one gastric, and zero of one mediastinal MMs. Seven of these mutations were potentially associated with the tumor sensitivity to KIT tyrosine kinase inhibitors. One tumor harbored somatically acquired silent nucleotide substitution c.1383A>G (T461T). This study adds to the evidence that a substantial portion of MMs carry a therapeutically relevant mutation in the KIT oncogene.     

The Concomitant Use of Diuretics,Non-Steroidal Anti-Inflammatory Drugs,and Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers (Triple Whammy), Extreme Heat,and In-Hospital Acute Kidney Injury in Older Medical Patients

Introduction

We investigated whether the concomitant use of diuretics, non-steroidal anti-inflammatory drugs, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (triple whammy, TW) predicts in-hospital acute kidney injury (AKI) and whether admission during recorded periods of extreme heat influences this association.

Methods

We retrospectively collected data on patient characteristics and use of TW/non-TW drugs on admission, AKI (increase in serum creatinine ≥ 27 µmol/l either within the first 48 h of admission or throughout hospitalization, primary outcome), length of stay (LOS), and mortality (secondary outcomes) in medical patients ≥65 years admitted (1) during five consecutive heat waves (HWs) between 2007 and 2009 (n = 382) or (2) either before or after each HW, matched for HW period, age, and admission day of the week (non-HW, controls, n = 1339).

Results

Number of TW and non-TW drugs, co-morbidities, number of daily admissions, incidence of in-hospital AKI, LOS, and mortality were similar in the HW and non-HW groups. After adjusting for clinical and demographic confounders, logistic regression showed that TW use did not predict AKI within 48 h of admission either during non-HW periods (OR 0.79, 95% CI 0.34–1.83, P = 0.58) or during HWs (OR 1.02, 95% CI 0.21–2.97, P = 0.97). Similar results were observed when AKI was captured throughout hospitalization. TW use did not predict LOS or mortality irrespective of environmental temperature on admission.

Conclusions

TW use on admission did not predict in-hospital AKI, LOS, or mortality in older medical patients admitted either during periods of normal environmental temperature or during HWs.