Naphthylthiazoles: a class of broad-spectrum antifungals.

Cryptococcal infections remain a major cause of mortality worldwide due to the ability of Cryptococci to pass through the blood-brain barrier (BBB) causing lethal meningitis. The limited number of available therapeutics, which exhibit limited availability, severe toxicity and low tolerability, necessitates the development of new therapeutics. Investigating the antifungal activity of a novel series of naphthylthiazoles provided trans-diaminocyclohexyl derivative 18 with many advantageous attributes as a potential therapeutic for cryptococcal meningitis. Briefly, the antimycotic activity of 18 against cryptococcal strains was highly comparable to that of amphotericin-B and fluconazole with MIC values as low as 1 µg mL-1. Moreover, compound 18 possessed additional advantages over fluconazole; it significantly reduced the intracellular burden of Cryptococci and markedly inhibited cryptococcal biofilm formation. Initial PK assessment of 18 indicated its ability to reach the CNS after oral administration with high permeability, and it maintained therapeutic plasma concentrations for 18 h. Its antifungal activity extended to other clinically relevant strains, such as fluconazole-resistant C. auris.

From past to present: Exploring COVID-19 in Qatar's hemodialysis population across Omicron dominant and pre-Omicron periods.

COVID-19 carries a high risk of morbidity and mortality in dialysis patients. Multiple SARS-CoV-2 variants have been identified since the start of the COVID-19 pandemic. The current study aimed to compare the incidence and outcomes of the COVID-19 Omicron dominant period versus other pre-Omicron period in hemodialysis patients. In this observational, analytical, retrospective, nationwide study, we reviewed adult chronic hemodialysis patients between March 1, 2020, and January 31, 2022. Four hundred twenty-one patients had COVID-19 during the study period. The incidence of COVID-19 due to the Omicron dominant period was significantly higher than other pre-Omicron period (30.3% vs. 18.7%, P<0.001). In contrast, the admission rate to ICU was significantly lower in the Omicron dominant period than in the pre-Omicron period (2.8% vs. 25%, P<0001) but with no significant difference in ICU length of stay. The mortality rate was lower in the Omicron dominant period compared to the pre-Omicron period (2.4% vs. 15.5%, P<0.001). Using multivariate analysis, older age [OR 1.093 (95% CI 1.044-1.145); P<0.0001] and need for mechanical ventilation [OR 70.4 (95% CI 20.39-243.1); P<0.0001] were identified as two independent risk factors for death in hemodialysis patients with COVID-19. In Conclusion, the COVID-19 Omicron variant had a higher incidence and lower morbidity and mortality than pre-Omicron period in our hemodialysis population.

Risk Factors for Unplanned Initiation of Dialysis in Patients with Advanced Chronic Kidney Disease: A Retrospective Cohort Study.

Many patients with advanced chronic kidney disease (CKD) managed in a specialized multidisciplinary clinic start dialysis urgently during hospitalization rather than electively as outpatients. This study aimed to identify risk factors for starting unplanned dialysis among patients with advanced CKD who attended multidisciplinary low-clearance clinics between January 1, 2020, and December 31, 2021. Of these, 175 patients started dialysis: 101 (26.7%) started it urgently, whereas 74 (19.5%) started it electively. Patients with urgent initiation of dialysis received less education, had fewer clinic visits and follow-up and were seen less often in the vascular clinic. In the univariate regression analysis, congestive heart failure significantly increased the risk of acute dialysis. Moreover, the risk increased in patients who did not receive dialysis education. The risk increased in patients who were not seen in a vascular clinic and did not have a vascular access plan. Moreover, high albumin levels at initial presentation to the clinic had a lower risk for elective initiation of dialysis. In the multivariate regression analysis, use of renin-angiotensin-aldosterone system inhibitors and attending a vascular clinic reduced the risk of unplanned dialysis by 73% and 96%, respectively. Acute unplanned initiation of dialysis is common even in CKD patients followed in low-clearance clinics. Early referral to multidisciplinary low clearance clinics, timely education, compliance with timely follow-up periods, and creation of access in patients at risk may reduce hospital admissions, hospital stays, admission to intensive care units, costs, and morbidity in these patients.

Effects of novel anemia nurse manager program on hemodialysis: a retrospective study from Qatar.

INTRODUCTION: Anemia management in dialysis is challenging. Keeping hemoglobin levels within a tight range is difficult. A new program (anemia nurse manager [ANM]) was started for better anemia management. This study aimed to compare traditional anemia management with the new ANM model regarding the achievement of better hemoglobin targets (range, 10-12 g/dL), avoidance of extreme hemoglobin levels ( < 9 or >13 g/dL), and evaluation of the cost-effectiveness of the new model. METHODS: This retrospective observational study compared traditional anemia management with management involving our new ANM model. Patients on hemodialysis in all ambulatory dialysis clinics in Qatar were included. The study included three phases: phase 1 (observation): June 2015 to August 2015, 460 patients; phase 2 (pilot): September 2015 to May 2016, 211 patients; and phase 3 (expansion in two phases): June 2016 to February 2017 and October 2017 to June 2018, 610 patients. Hemoglobin, iron saturation, and ferritin were evaluated according to the protocol. RESULTS: In this study, 55% of the patients achieved the target hemoglobin in phase 1 compared with 75% in phase 2 (p = 0.0007). The hemoglobin level within the target range was sustained at 72% ± 5% of patients in phase 3. The achievement rate of the target hemoglobin level increased from 56% (May 2015) to 72% (July 2018) (p < 0.001). The proportion of patients with extreme hemoglobin declined from 10.7% in phase 1 to 6.4% in phase 2 and sustained at 8% afterward. Reducing the doses of erythropoietin stimulating agents, owing to the use of the ANM model, saved costs by approximately 11%. CONCLUSIONS: The ANM model was able to achieve and maintain hemoglobin levels within the target range and decrease extreme hemoglobin levels. These outcomes improved patient care by avoiding high hemoglobin (increase thrombosis, cancer recurrence, stroke, and death) and low hemoglobin (weakness, poor quality of life, and need for transfusion) levels. The ANM model was cost effective even after including the salaries of nurses. This model can be considered in other aspects of patient care in dialysis.

Design, synthesis, and molecular docking studies of new [1,2,4]triazolo[4,3-a]quinoxaline derivatives as potential A2B receptor antagonists.

Many shreds of evidence have recently correlated A2B receptor antagonism with anticancer activity. Hence, the search for an efficient A2B antagonist may help in the development of a new chemotherapeutic agent. In this article, 23 new derivatives of [1,2,4]triazolo[4,3-a]quinoxaline were designed and synthesized and its structures were confirmed by different spectral data and elemental analyses. The results of cytotoxic evaluation of these compounds showed six promising active derivatives with IC50 values ranging from 1.9 to 6.4 µM on MDA-MB 231 cell line. Additionally, molecular docking for all synthesized compounds was performed to predict their binding affinity toward the homology model of A2B receptor as a proposed mode of their cytotoxic activity. Results of molecular docking were strongly correlated with those of the cytotoxic study. Finally, structure activity relationship analyses of the new compounds were explored.

Bacteriological profiling of diphenylureas as a novel class of antibiotics against methicillin-resistant Staphylococcus aureus.

Bacterial resistance to antibiotics remains an imposing global public health challenge. Of the most serious pathogens, methicillin-resistant Staphylococcus aureus (MRSA) is problematic given strains have emerged that exhibit resistance to several antibiotic classes including ß-lactams and agents of last resort such as vancomycin. New antibacterial agents composed of unique chemical scaffolds are needed to counter this public health challenge. The present study examines two synthetic diphenylurea compounds 1 and 2 that inhibit growth of clinically-relevant isolates of MRSA at concentrations as low as 4 µg/mL and are non-toxic to human colorectal cells at concentrations up to 128 µg/mL. Both compounds exhibit rapid bactericidal activity, completely eliminating a high inoculum of MRSA within four hours. MRSA mutants exhibiting resistance to 1 and 2 could not be isolated, indicating a low likelihood of rapid resistance emerging to these compounds. Bacterial cytological profiling revealed the diphenylureas exert their antibacterial activity by targeting bacterial cell wall synthesis. Both compounds demonstrate the ability to resensitize vancomycin-resistant Staphylococcus aureus to the effect of vancomycin. The present study lays the foundation for further investigation and development of diphenylurea compounds as a new class of antibacterial agents.

Nutritional status and outcomes in hemodialysis patients from the Gulf Cooperation Council countries enrolled in the dialysis outcome and practice patterns study phase 5 (2012-2015).

Nutrition is an important factor in maintaining good health of hemodialysis (HD) patients, affecting their morbidity and mortality. The Dialysis Outcomes and Practice Patterns Study (DOPPS) is an international observational study assessing differences in dialysis practices and outcomes across >20 countries. Here, we present the results for the Gulf Cooperation Council (GCC) countries regarding nutrition data and its relationship with outcomes as a part of the DOPPS Phase 5 study (2012-2015). Data were from Phase 5 of the DOPPS. Main analyses were based on 927 adult chronic HD patients enrolled at the start of the GCC-DOPPS Phase 5 study from each of the 40 randomly selected GCC HD facilities from Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates. Within each participating facility, 20-30 patients were randomly selected, depending on facility size. Analysis showed minor differences across GCC countries in age, albumin levels, nutrition supplement use, and being bothered by the lack of appetite. Elderly (>60 years old) and diabetic HD patients displayed poorer nutritional parameters than young and nondiabetic patients. A low albumin level (<3.2 g/dL) was associated with the highest risk of mortality with a hazard ratio (HR) of 2.47 (P <0.0001) followed by diabetes with HR 1.57 (P <0.04) and older age [HR= 1.27/10 years older (P <0.01)]. Quality of life measures physical component summary and mental component summary correlated negatively with albumin <3.2 g/dL (-2.18 and -5.5, respectively, P <0.05 for each), and with serum creatinine level <7.5 mg/dL (-2.29 and -2.1 respectively, P <0.05 for each. We are presenting the first study of the nutrition status and outcomes for HD patients in the GCC countries in DOPPS. Our results were mostly comparable to findings in previous trials in other countries. Although the data are observational, our study provides good insight into aspects of nutrition in the GCC countries and can be compared to the rest of the world to better understand trends and practice differences.