Effect of Pirfenidone on Risk of Pulmonary Fibrosis in COVID-19 Patients Experiencing Cytokine Storm.

OBJECTIVES: Severe stages of COVID-19 infection have been associated with the excessive discharge of pro-inflammatory mediators such as cytokines, resulting in lung deterioration, which progresses rapidly to lung fibrosis leading to acute respiratory distress syndrome. In this investigation, the efficacy and safety of the novel antifibrotic and anti-inflammatory agent, Pirfenidone, were assessed in COVID-19 patients with pulmonary fibrosis secondary to cytokine storm. In this randomized controlled study, we assigned 100 adult COVID-19 patients cytokine storm and admitted to the intensive care isolation unit into either pirfenidone added to the standard therapy (n = 47), or the standard protocol only (n = 53). High-resolution computed tomography of the chest was performed in all patients to evaluate fibrotic lesions and their progression. The results showed that the percentage of patients who developed pulmonary fibrosis during cytokine storm onset in the pirfenidone group relative to the standard group was 29.8% and 35.8%, respectively, with no significant difference between the two groups; while there was a significant increase in the proportion of patients discharged from the isolation unit with pulmonary fibrosis without progression in fibrotic lesions in the pirfenidone group compared to the standard group (21.3% and 5.7%, respectively). Furthermore, there was a significant difference concerning liver enzyme elevation and GIT disturbance incidences in the studied groups (p = 0.006 and 0.01, respectively). Our findings show that Pirfenidone inhibits fibrosis advancement in COVID-19 patients with pulmonary fibrosis and is associated with hepatotoxicity and GI distress. It may be beneficial in patients with mild to moderate COVID-19-induced pulmonary fibrosis; however, additional research is necessary.

A Battle against COVID-19: Vaccine Hesitancy and Awareness with a Comparative Study between Sinopharm and AstraZeneca.

BACKGROUND: Awareness about the COVID-19 vaccine's adverse effects is crucial for gaining public trust. As we still lack proof of vaccines' safety, this survey aimed to investigate Egyptians' general awareness of the Sinopharm and AstraZeneca vaccines against COVID-19 and provide considerable evidence on their side effects and complications. METHODS: A cross-sectional questionnaire-based study was conducted in Egypt between 20 September and 10 October in 2021, with multiple-choice questions (MCQs) covering all data on vaccine administration confusion, adverse effects or intensity, and complications. RESULTS: Among the 390 participants, 42.3% reported being hesitant before receiving one of the vaccines. About 40.3% of participants were previously infected before getting vaccinated while only 4.6% reported being infected after vaccination. The AstraZeneca vaccine demonstrated higher side effects and symptoms than the Sinopharm vaccine while the Sinopharm vaccine showed a significantly higher rate of COVID-19 infection after vaccination. CONCLUSIONS: People with higher educational levels and chronic respiratory diseases represent an excellent model for accepting COVID-19 vaccination. A booster shot is recommended for people vaccinated with the Sinopharm vaccine due to a significantly higher rate of COVID-19 infection after vaccination; however, the Sinopharm vaccine shows a more acceptable safety profile.

A New Clinical Utility for Tubular Markers to Identify Kidney Responders to Saxagliptin Treatment in Adults With Diabetic Nephropathy.

OBJECTIVES: In recent clinical studies, saxagliptin exhibited nephroprotective potential by lowering albuminuria. In this study, we aimed to determine whether these kidney effects of saxagliptin were mediated by changes in markers of kidney tubular damage, including urinary neutrophil gelatinase-associated protein (uNGAL) and liver-type fatty acid-binding protein (uL-FABP). METHODS: Our study included 80 patients with type 2 diabetes, hypertension and mild to moderate diabetic kidney disease (DKD) with prevalent albuminuria. Patients were either randomly assigned to saxagliptin as add-on therapy or remained unchanged on their stable antidiabetic therapy as a control arm. RESULTS: Saxagliptin significantly reduced uNGAL with a median change of -25.4% (interquartile range [IQR], -35.6% to -12.2%) compared with the control group (median change, -0.91%; IQR, -12% to 11.88%; p<0.001) after 3 months. Similarly, patients given saxagliptin had a highly significant reduction in uL-FABP (median change, -24.4%; IQR, -30.5% to -15.1%) compared with controls (median change, -3.8%; IQR -10% to 12.5%; p<0.001). Median estimated glomerular filtration rate (eGFR) values after 3 months in the saxagliptin arm were significantly higher (76.5 mL/min per 1.73 m2; IQR, 70 to 92.75 mL/min per 1.73 m2) in the low-risk uNGAL group compared with controls (59.8 mL/min per 1.73 m2; IQR, 51 to 76.2 mL/min per 1.73 m2; p=0.002). Also, higher-although not significantly-posttreatment eGFR levels were observed in patients with low risk of uL-FABP (73 mL/min per 1.73 m2; IQR, 58 to 91.3 mL/min per 1.73 m2) compared with controls (57.3 mL/min per 1.73 m2; IQR, 49.5 to 72.6 mL/min per 1.73 m2; p=0.06). No significant increase was observed in high-risk patients for either marker when compared with controls. CONCLUSIONS: The albuminuria-lowering effect of saxagliptin may be due to inhibition of kidney tubular damage. Use of tubular markers may be a promising approach to identifying kidney responders to gliptins.

Effect of mutation and vaccination on spread, severity, and mortality of COVID-19 disease.

Coronavirus disease 2019 (COVID-19) has had different waves within the same country. The spread rate and severity showed different properties within the COVID-19 different waves. The present work aims to compare the spread and the severity of the different waves using the available data of confirmed COVID-19 cases and death cases. Real-data sets collected from the Johns Hopkins University Center for Systems Science were used to perform a comparative study between COVID-19 different waves in 12 countries with the highest total performed tests for severe acute respiratory syndrome coronavirus 2 detection in the world (Italy, Brazil, Japan, Germany, Spain, India, USA, UAE, Poland, Colombia, Turkey, and Switzerland). The total number of confirmed cases and death cases in different waves of COVID-19 were compared to that of the previous one for equivalent periods. The total number of death cases in each wave was presented as a percentage of the total number of confirmed cases for the same periods. In all the selected 12 countries, Wave 2 had a much higher number of confirmed cases than that in Wave 1. However, the death cases increase was not comparable with that of the confirmed cases to the extent that some countries had lower death cases than in Wave 1, UAE, and Spain. The death cases as a percentage of the total number of confirmed cases in Wave 1 were much higher than that in Wave 2. Some countries have had Waves 3 and 4. Waves 3 and 4 have had lower confirmed cases than Wave 2, however, the death cases were variable in different countries. The death cases in Waves 3 and 4 were similar to or higher than Wave 2 in most countries. Wave 2 of COVID-19 had a much higher spread rate but much lower severity resulting in a lower death rate in Wave 2 compared with that of the first wave. Waves 3 and 4 have had lower confirmed cases than Wave 2; that could be due to the presence of appropriate treatment and vaccination. However, that was not reflected in the death cases, which were similar to or higher than Wave 2 in most countries. Further studies are needed to explain these findings.

Recent therapeutic targets in diabetic nephropathy.

BACKGROUND: The prevalence of diabetes mellitus has been increased dramatically which in turn leads to complications including cardiovascular diseases, diabetic kidney disease, and substantially end-stage renal disease. METHODS: We reviewed articles discussing the pathophysiology of diabetic nephropathy with new agents that may be useful in the management of the disease. We used PubMed, Scopus, Google Scholar and the Open-access searching engines. RESULTS: The recent recommendations primarily depend on glycaemic and blood pressure control and the use of standard renin-angiotensin system blockade. Currently, the use of agents with nephroprotective effects beyond the hyperglycaemic lowering effect has been evidenced clinically. CONCLUSIONS: In his review, the pathophysiology, clinical manifestations, and lines of treatment of diabetic nephropathy are discussed. In addition, a focus on the clinical role and nephroprotective effects of the emerging therapeutic class, dipeptidyl peptidase IV (DPP-4) inhibitors, is addressed in detail.

Saxagliptin and vildagliptin lowered albuminuria in patients with diabetes and hypertension independent on glycaemic control.

BACKGROUND: Preclinical data illustrated that the dipeptidyl peptidase-4(DPP-4) inhibitors did lower urinary albumin excretion in diabetes-induced rats. We evaluated the effects of saxagliptin and vildagliptin on albuminuria in patients with diabetic nephropathy on top of the renin-angiotensin-aldosterone system (RAAS) blockade therapy. METHODS: This study included 120 patients with type 2 diabetes (T2D), hypertension, and prevalent albuminuria [defined as urine albumin-to-creatinine ratio (UACR) 30-3000mg/g creatinine] on a stable dose of olmesartan as a standard RAAS blocker for diabetic nephropathy. Patients were assigned to receive either of saxagliptin 5mg/day (n = 40), vildagliptin 100mg/day (n = 40), or traditional antidiabetic therapy as control patients (n = 40) for 12 weeks. RESULTS: Each of saxagliptin and vildagliptin significantly reduced albuminuria after 12 weeks, with mean percentage changes (%) of -57.9% [95% confidence interval (CI) -66.1 to -49.8], and -55.2% (95% CI -64.9 to -45.4); P < .001, respectively, compared with the control group. Significantly, saxagliptin shifted higher proportions of patients towards lower albuminuria categories (P < .001) compared with vildagliptin despite a similar UACR rate of changes. Results of binary logistic models confirmed that the change in UACR because saxagliptin was independent of changes in systolic blood pressure (SBP), glycated hemoglobin (HbA1c ), estimated glomerular filtration rate (eGFR), or body weight (overall regression: P = .002, R2  = 0.398) vs control. Likewise, vildagliptin reduced UACR independently on other confounders (overall regression: P = .002, R2  = 0.388). Furthermore, no significant correlation was observed between the change in UACR and changes in HbA1c, SBP or eGFR with either saxagliptin or vildagliptin (Pearson coefficients: 0.203, 0.143, -0.190; P > .05, and 0.003, 0.241, 0.019; P > .05, respectively). CONCLUSIONS: DPP-4 inhibitors, saxagliptin, and vildagliptin, resulted in substantial reductions in albuminuria in patients with T2D and hypertension on top of RAAS blockade after short term therapy independently on glycaemic or hemodynamic changes. Saxagliptin was superior to vildagliptin in albuminuria-categorical shifting.

Design, green one-pot synthesis and molecular docking study of novel N,N-bis(cyanoacetyl)hydrazines and bis-coumarins as effective inhibitors of DNA gyrase and topoisomerase IV.

A novel, quick, environmentally safe, and one-pot synthesis of a series of N,N-bis(cyanoacetyl)hydrazine derivatives, bis-imino-2H-chromenes and bis-2-oxo-2H-chromene derivatives have been designed. Some selected newly synthesized compounds were investigated in vitro for their antibacterial activity. Compound 5j is the most toxic compound against Staphylococcus aureus with activity index 171%, followed by compound 15b with activity index 136% compared to standard drug ampicillin. Moreover, compound 15a is the most toxic compound against Escherichia coli with activity index 111% compared to standard drug gentamicin. Minimum inhibitory concentration (MIC) was carried out for compounds with high antibacterial activity. Compound 5j has good MIC (7.8 µg/ml) against Staphylococcus aureus while 15a has good MIC (31.25 µg/ml) against Streptococcus mutans which is better than MIC of the standard drug ampicillin (MIC = 62.5 µg/ml). Compounds 5j, 5k, 15a, 15b and 15e which have good MIC values were introduced to enzyme assay against DNA gyrase and topoisomerase IV. The results showed that compound 15a can strongly inhibit DNA gyrase and topoisomerase IV (IC50 = 27.30 and 25.52 µM respectively), compared to methotrexate as the standard drug (IC50 = 29.01 and 23.55 µM respectively). Structure-activity relationships were also discussed based on the biological and docking simulation results.

Effects of Fill Volume and Humidification on Aerosol Delivery During Single-Limb Noninvasive Ventilation.

BACKGROUND: The aim of this work was to determine the effect of fill volume and humidification change on aerosol delivery during single-limb noninvasive ventilation (NIV). METHODS: Four groups were recruited, each consisting of 12 subjects (6 females) with COPD receiving NIV. Groups 1 and 3 received inhaled salbutamol with a vibrating mesh nebulizer, and Groups 2 and 4 received inhaled salbutamol with a jet nebulizer. The in vivo study was carried out on days 1 and 3. In groups 1 and 2, 2 fill-volumes were delivered to each subject; 1 mL 5,000 µg/mL salbutamol respirable solution used as it is or diluted to a total of 2 mL using normal saline. In groups 3 and 4, 1 mL 5,000 µg/mL salbutamol respirable solution diluted to 2 mL total volume using normal saline was delivered to each subject with and without humidification. Unchanged salbutamol in urine at 30 min (USAL0.5) and in pooled urine at 24 h (USAL24) was determined. On day 2, the ex vivo study was carried out on subjects using the same experimental setting with a filter placed proximal to their face mask for collection of total inhaled dose of salbutamol (aerosol emitted). RESULTS: The vibrating mesh nebulizer delivered higher USAL0.5, USAL24, and aerosol emitted compared to the jet nebulizer at all fill volumes and humidification conditions (P < .001). Increasing fill volume from 1 mL to 2 mL resulted in a significant increase in USAL0.5, USAL24, and aerosol emitted from the jet nebulizer (P < .05) with an insignificant effect on the vibrating mesh nebulizer. A 2-mL fill volume with the jet nebulizer delivered USAL24 and aerosol emitted comparable to those of 1 mL with the vibrating mesh nebulizer with significantly longer nebulization times (P < .001). Humidification had an insignificant effect on aerosol delivery. CONCLUSIONS: Increasing the fill volume of a jet nebulizer is essential to increase the amount of inhaled medication reaching a subject. In contrast, there is no need to increase fill volumes when using a vibrating mesh nebulizer. There is no need to switch off the humidifier while delivering aerosol through a single-limb NIV circuit.