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.

Effect of ciprofloxacin vs levofloxacin on QTc-interval and dysglycemia in diabetic and non-diabetic patients.

BACKGROUND: Levofloxacin and ciprofloxacin are more commonly used amongst fluoroquinolone class and the question of cardiac safety and glucose hemostasis of this class has been raised. OBJECTIVE: To compare intravenous levofloxacin and ciprofloxacin regarding their risk on QTc prolongation and dysglycemia in diabetic and non-diabetic patients. METHODS: A randomised prospective study at Beni-Suef university hospital was conducted on 200 adult patients over 6 months. The patients received intravenous levofloxacin 750mg once daily or ciprofloxacin 400mg twice daily. Electrocardiogram and fasting blood glucose were obtained from each patient before starting the antibiotic, 24 hours, 72 hours after the first dose, and 72 hours after antibiotics cessation. RESULTS: The results of the current study showed the relative risk for QTc prolongation with levofloxacin was more than ciprofloxacin by about 4 and 1.5 times in diabetic and non-diabetic patients, respectively. The relative risk for dysglycemia with levofloxacin was 2.28 and 1.39 times more than ciprofloxacin in diabetic and non-diabetic patients, respectively. CONCLUSION: The present study showed that the risk for QTc prolongation and hyperglycemia was greater with levofloxacin than ciprofloxacin in diabetic and non-diabetic patients. In addition, the risk for hypoglycemia was greater with levofloxacin than ciprofloxacin in non-diabetic patients.

The impact of changing patient interfaces on delivering aerosol with titrated oxygen in the high flow system.

INTRODUCTION: Despite the widespread oxygen-culture as more is better in prehospital and hospital settings, the use of titrated oxygen-flow within a high-flow system can be beneficial especially when combined with aerosol-delivery and also save the patient from unnecessary-hyperoxia. METHODS: Forty-five COPD patients were included in this study where they allocated in three-groups (nasal-delivery, oral-delivery, and oronasal-delivery groups). All patients were received their inhaled-salbutamol dose using Aerogen Solo nebuliser by one of the three interfaces, eg, nasal-cannula, mouthpiece, and facemask in two conditions; with oxygen-flow and without any oxygen-flow. Pulmonary and systemic salbutamol deposition was estimated by collecting two urine-samples from the patient; 30 min post-inhalation and cumulatively 24 hr post-inhalation. The quantity of salbutamol in these collected samples was measured by high-performance liquid chromatography. Lung function measurement was performed pre-bronchodilator inhalation and 30 min post-bronchodilator to estimate the change in pulmonary functions post-inhalation regarding all tested interfaces. RESULTS: COPD patients showed the highest salbutamol percentage excreted 30 min post-inhalation of 5.7% (1.4) with mouthpiece interface when combined with oxygen at P < .002. While with the same condition using oxygen, valved-facemask showed the highest salbutamol percentage excreted in 24 hr post inhalation samples but the difference is only significantly compared with nasal cannula (P < .006). Moreover, without oxygen delivery, mouthpiece and valved facemask showed approximately the same salbutamol percentage excreted in 30 min post-inhalation samples, higher than that delivered by nasal cannula (P < .001). Of note, salbutamol delivery is significantly increased with oxygen flow for all interfaces (P < .05) except with nasal cannula. CONCLUSIONS: The nasal cannula is a more comfortable and tolerable interface despite the lower fraction of the delivered drug compared with other tested interfaces. The use of oxygen-flow with aerosol delivery within a high flow system positively affects the delivered drug fraction and the pulmonary deposition of the drug.

In vitro and in vivo performance modelling and optimisation of different dry powder inhalers: A complementary study of neural networks, genetic algorithms and decision trees.

INTRODUCTION: Aerosol delivery from DPIs could be affected by different factors. This study aimed to evaluate and predict the effects of different factors on drug delivery from DPIs. METHODS: Modelling and optimisation for both in vitro and in vivo data of different DPIs (Diskus, Turbohaler and Aerolizer) were carried out using neural networks associated with genetic algorithms and the results are confirmed using a decision tree (DT) and random forest regressor (RFR). All variables (the type of DPI, inhalation flow, inhalation volume, number of inhalations and type of subject) were coded as numbers before using them in the modelling study. RESULTS: The analysis of the in vitro model showed that Turbohaler had the highest emitted dose compared with the Diskus and the Aerolizer. Increasing flow resulted in a gradual increase in the emitted dose. Little differences between the inhalation volumes 2 and 4 litres were shown at fast inhalation flow, and interestingly two inhalations showed somewhat higher emitted doses than one-inhalation mode with Turbohaler and Diskus at slow inhalation flow. Regarding the in vivo model, the percent of drug delivered to the lung was highly increased with Turbohaler and Diskus in healthy subjects where continuous contour lines were observed. The Turbohaler showed increased lung bioavailability with the two-inhalation modes, the Diskus showed a nearly constant level at both one and two inhalations at slow inhalation. The Turbohaler and Aerolizer showed little increasing effect moving from one to two inhalations at slow inhalation. CONCLUSIONS: Modelling of the input data showed a good differentiating and prediction power for both in vitro and in vivo models. The results of the modelling refer to the high efficacy of Diskus followed by Turbohaler for delivering aerosol. With two inhalations, the three DPIs showed an increase in the percent of drug excreted at slow inhalations.

Inhaled salbutamol from aerolizer and diskus at different inhalation flows, inhalation volume and number of inhalations in both healthy subjects and COPD patients.

The aim of the present study was to demonstrate the effect of inhalation-flow, inhalation-volume and number of inhalations on aerosol-delivery of inhaled-salbutamol from two different dry powder inhalers (DPIs) in both healthy-subjects and chronic obstructive pulmonary disease (COPD) patients. Relative pulmonary-bioavailability and systemic-bioavailability of inhaled-salbutamol, delivered by Diskus and Aerolizer, was determined in 24-COPD patients and 24-healthy subjects. The healthy-subjects and the COPD-patients participated in the study for 7 days in which they received 4 study doses of 200 µg salbutamol (one slow-inhalation, two slow-inhalations, one fast-inhalation, and two fast-inhalations) in four alternative days with 24 hr washout period after each dose. Two urine-samples were collected from each study subjects. The first was provided 30 min post inhalation (USAL0.5), as an index of relative pulmonary-bioavailability, and the second was pooled to 24 hr post inhalation (USAL24), as an index of systemic-bioavailability. Fast-inhalation resulted in significantly higher USAL0.5 and USAL24 than slow-inhalation (p˂0.05) after one-inhalation in both healthy-subjects and COPD-patients but there was no significant difference between slow and fast-inhalation after two-inhalations. One-inhalation resulted in significantly higher USAL0.5 and USAL24 in healthy-subjects compared to COPD-patient at both slow and fast-inhalation (p˂0.05) except USAL0.5 with Diskus at slow-inhalation there was no significant difference. Also, two-inhalations resulted in significantly higher USAL0.5 and USAL24 compared to one-inhalation at slow-inhalation only (p˂0.05). No significant difference was found between Aerolizer and Diskus except in USAL0.5 of one slow-inhalation in both health-subjects and COPD-patients (p = 0.048 and 0.047, respectively). Device-formula relation is present at low inhalation-flow since Diskus resulted in significantly higher USAL0.5 and USAL24 in healthy-subjects compared to COPD-patient at slow inhalation than Aerolizer. It is essential to inhale-twice and as hard and deep as possible from each dose when using DPI especially with COPD-patients having poor inspiratory efforts such as elderly patients and children.

Modeling and optimization of nebulizers' performance in non-invasive ventilation using different fill volumes: Comparative study between vibrating mesh and jet nebulizers.

BACKGROUNDS: Substituting nebulisers by another, especially in non-invasive ventilation (NIV), involves many process-variables, e.g. nebulizer-type and fill-volume of respirable-dose, which might affect patient optimum-therapy. The aim of the present work was to use neural-networks and genetic-algorithms to develop performance-models for two different nebulizers. METHODS: In-vitro, ex-vivo and in-vivo models were developed using input-variables including nebulizer-type [jet nebulizer (JN) and vibrating mesh nebulizer (VMN)] fill-volumes of respirable dose placed in the nebulization chamber with an output-variable e.g. average amount reaching NIV patient. Produced models were tested and validated to ensure effective predictivity and validity in further optimization of nebulization process. RESULTS: Data-mining produced models showed excellent training, testing and validation correlation-coefficients. VMN showed high nebulization efficacy than JN. JN was affected more by increasing the fill-volume. The optimization process and contour-lines obtained for in-vivo model showed increase in pulmonary-bioavailability and systemic-absorption with VMN and 2 mL fill-volumes. CONCLUSIONS: Modeling of aerosol-delivery by JN and VMN using different fill-volumes in NIV circuit was successful in demonstrating the effect of different variable on dose-delivery to NIV patient. Artificial neural networks model showed that VMN increased pulmonary-bioavailability and systemic-absorption compared to JN. VMN was less affected by fill-volume change compared to JN which should be diluted to increase delivery.

Total emitted dose of salbutamol sulphate at different inhalation flows and inhalation volumes through different types of dry powder inhalers.

The aim of the present study was to compare the performance of two different dry powder inhalers (DPIs) at different inhalations volumes and inhalation flows. Ventolin Diskus contain blisters of 200µg salbutamol. To test the TED from Aerolizer, salbutamol in Diskus blister was emptied and placed in size 3 capsules suitable for use with Aerolizer. Total emitted dose (TED) delivered by Diskus and Aerolizer was determined using DPI sampling apparatus after one and two inhalations from the same dose. 10-60L/min inhalation flows at 2 and 4L inhalation volume were used in the determination. At inhalation flow ≤30L/min, two inhalations resulted in higher TED than one inhalation (p < 0.05) and Diskus resulted in higher TED than Aerolizer (p < 0.05). The highest TED was at inhalation flow 40L/min above which the effect of the second inhalation and formula device relation were negligible. Device formula relation is present at low inhalation flow but at flow >30L/min Diskus drug formula can be delivered by Aerolizer with no significant difference in TED produced. For the best TED patients are required to inhale as fast as possible (a minimum of 40L/min). At lower inhalation flow two inhalations results in better emitted dose than one inhalation for both DPIs. So, we recommend patients with poor inspiratory efforts to inhale twice and as hard and deep as possible from each dose as they may not receive much benefit from one inhalation even when using DPI with low resistance (Aerolizer) or medium resistance (Diskus). However, further in-vivo study are required to validate this recommendtation.

Cardioprotection by 6-gingerol in diabetic rats.

The current study was conducted to evaluate the effect of 6-gingerol (6G) on cardiac complications in streptozotocin (STZ)-induced diabetic (DM) rats. STZ-induced DM rats (single 50 mg/kg i.p. injection, 15 days prior to drug treatment) or time-matched controls were treated with 6G (75 mg/day route orally). After a further 8 weeks, blood was collected for biochemical analysis and 8-isoprostenol was measured in urine. Cardiac hemodynamics and ECG was assessed. 6G significantly attenuated the increased level of blood glucose in diabetic rats and improved cardiac hemodynamics in including RR interval, max dP/dt, min dP/dt and Tau. In addition, 6G alleviated the elevated ST segment, T amplitude and R amplitude with no significant effect on disturbed levels of adiponectin, TGF-ß or 8-isoprostenol induced by diabetes. The results showed that treatment with 6G has an ameliorative effect on cardiac dysfunction induced by diabetes. Which may be not related to its potential antioxidant effect.

Immunomodulatory effect of red onion (Allium cepa Linn) scale extract on experimentally induced atypical prostatic hyperplasia in Wistar rats.

Red onion scales (ROS) contain large amounts of flavonoids that are responsible for the reported antioxidant activity, immune enhancement, and anticancer property. Atypical prostatic hyperplasia (APH) was induced in adult castrated Wistar rats by both s.c. injection of testosterone (0.5 mg/rat/day) and by smearing citral on shaved skin once every 3 days for 30 days. Saw palmetto (100 mg/kg) as a positive control and ROS suspension at doses of 75, 150, and 300 mg/kg/day were given orally every day for 30 days. All medications were started 7 days after castration and along with testosterone and citral. The HPLC profile of ROS methanolic extract displayed two major peaks identified as quercetin and quercetin-4'-ß-O-D-glucoside. Histopathological examination of APH-induced prostatic rats revealed evidence of hyperplasia and inflammation with cellular proliferation and reduced apoptosis Immunohistochemistry showed increased tissue expressions of IL-6, IL-8, TNF-α, IGF-1, and clusterin, while TGF-ß1 was decreased, which correlates with the presence of inflammation. Both saw palmetto and RO scale treatment have ameliorated these changes. These ameliorative effects were more evident in RO scale groups and were dose dependent. In conclusion, methanolic extract of ROS showed a protective effect against APH induced rats that may be attributed to potential anti-inflammatory and immunomodulatory effects.

Manuka combinations with nigella sativa and hydroxyurea in treating iron overload of pediatric ß-thalassemia major, randomized clinical trial.

Background: ß-thalassemia major is microcytic hypochromic anemia disorder inherited from parents, resulting from a mutation in the ß-globin locus. As a result, a quantitative defective hemoglobin synthesis and relative excess in α-globin is occurred. As such, frequent blood transfusion is required, that leads to iron overload. Iron overload results in several pathological complications, including cell death, tissue injury, organ dysfunction, and liver fibrosis. The present study examined the effectiveness of nigella Sativa and manuka honey combination or manuka honey alone to the conventional therapy (Deferasirox + blood transfusion) used for preventing and managing iron overload in pediatric ß-thalassemia major patients. Methods: One hundred sixty-five patients participated in this randomized, double-blind, standard therapy-controlled, parallel-design multisite trial. The patients were randomly allocated into three groups, receiving either 500 mg nigella sativa oil combined with manuka honey lozenge (344 mg) daily or manuka honey alone plus the conventional therapy for ten treatment months. Ferritin level, serum iron, transferrin saturation, total iron binding capacity, alanine transaminase, and aspartate transaminase were determined at baseline and month 10. Results: Eventually, serum ferritin and iron were decreased significantly in the nigella sativa + manuka honey group as compared with the control group. Other clinical parameters were significantly impacted. The level of alanine transaminase and aspartate transaminase were significantly decreased in the nigella sativa plus manuka honey group compared with the control group. Conclusion: Results showed that nigella sativa plus manuka honey was more effective than manuka alone or the conventional treatment alone in managing iron overload of ß-thalassemia major patients.

Evaluation of applying drug dose adjustment by physicians in patients with renal impairment.

OBJECTIVE: To determine whether appropriate dose adjustment was taken into account or not by the physicians when prescribing drugs in patients with renal impairment. DESIGN: A retrospective chart review was performed and included 98 adult in-patients, diagnosed with renal impairment based on clinical evaluation and laboratory data, in King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia, who was admitted to the hospital from September 2005 to January 2011. Data of the patients were noted and recorded including baseline demographics, clinical data, laboratory data, renal state, treatment data and medications. RESULTS: The initial number of the patients was reduced to 80 where a total of 502 drugs were investigated in the present study with an average of six drugs per patient. Of these 502 studied drugs, 196 (39%) required dose adjustment where 92 (46.9%) were adjusted and 104 (53.1%) were not adjusted. It was found also that most of the drugs requiring dose adjustment were antibiotics (39.8%). CONCLUSION: The current study confirms that physicians still do not take into account sufficiently patients' renal function when prescribing drugs. Continuous medical education and collaboration with clinical pharmacist should be encouraged for quality improvement in patients with renal impairment.

Efficacy and safety of levetiracetam in pediatric epilepsy.

OBJECTIVE: To evaluate the efficacy and tolerability of Levetiracetam (LEV) as an adjunctive therapy in pediatric patients with different generalized epilepsies. DESIGN: Chart review of 22 consecutive children age 4-19 years who were treated with LEV for at least 1 year was observed retrospectively. The mean dose rang of LEV was from 250 to 2000 mg. Data were collected on epilepsy type, seizure frequency, concomitant antiepileptic drug and adverse effect. RESULTS: Of the 22 patient reviewed, 13 (59%) were boys and 9 (41%) were girls. Predominant seizure types were generalized tonic-clonic seizures 13 (59%) and tonic seizure 6 (27%). Other seizure types included myoclonic seizures 2 (9%) and focal seizure 3 (5%). The results showed 10 (45%) had become free of seizure for almost 7 months to 1 year. Eight of these 10 patients (80%) had normalized EEG. Seizure frequency was reduced in 9 (41%) patients and 3 (14%) patients still had seizure. No side effects were reported related to LEV treated patients except for 1 patient. CONCLUSION: Our results confirm that LEV may be an effective adjunctive therapy in treatment of childhood epilepsy, especially tonic-clonic seizure, with possible no evident side effect.

Effect of Amlodipine/Nebivolol combination therapy on central BP and PWV compared to Amlodipine/Valsartan combination therapy.

BACKGROUND: Pulse wave velocity (PWV) and central blood pressure (CBP) have been intoduced into managment of hypertensive patients. PWV is positively correlated with arterial wall stiffness while central aortic pressure becomes better predictor of cardiovascular outcome than peripheral pressure. Reduction in CBP provides protective properties against subclinical organ damage. This work aims to investigate the effect of a new combination therapy of Amlodipine/Nebivolol (A/N) on central BP, peripheral BP and PWV. The results of using this combination will be compared to the well-established fixed-dose combination of Amlodipine/Valsartan (A/V). The study conducted between October 2018 and August 2020. One hundred and two hypertensive patients were assigned for Amlodipine 10 mg/Valsartan 160 mg combination therapy (A/V, n = 52) or Amlodipine 10 mg/Nebivolol 5 mg combination therapy (A/N, n = 50) by simple 1:1 randomization. Office, central blood pressure and PWV were measured on first (0 week), second (4-8 weeks) and third visit (10-12). Difference in BP (in each arm and between arms) was calculated along all visits. RESULTS: No statistical significant difference was found between A/V and A/N regarding age, gender, BMI and CV history. OBP, CBP and PWV were significantly reduced in each arm, but no differences were found when comparing both arm results to each other. Recorded side effects were insignificant. CONCLUSIONS: The new combination therapy Amlodipine/Nebivolol (A/N) affords a significant reduction in CBP, PBP and PWV with minor and tolerable side effects. It has provided comparable results to Amlodipine/Valsartan (A/V) combination therapy.

Perceptions and attitudes of ICU physicians toward antibiotics prescribing and resistance: A cross-sectional study.

BACKGROUND AND AIM: Antibiotic resistance is a major emphasis in intensive care units (ICUs). Better understanding of ICU physicians' perceptions, attitudes, and knowledge about antimicrobial prescribing practices could facilitate more effective interventions in fighting antimicrobial resistance in Egyptian ICUs and establishing a proper Antimicrobial Stewardship Program. METHODS: A cross-sectional questionnaire study was conducted including 92 physicians distributed across the different types of Egyptian healthcare institutions in two cities of Egypt; Cairo and El Monufia. Over a period of three months, started in December 2019 and ended in February 2020. RESULTS: A total of 92 Egyptian physicians were included in the study. Seventy (76.1%) of the surveyed physician strongly agreed and 22 (23.9%) agreed that antibiotic resistance is a worldwide problem. Moreover, 50 (54.3%) strongly agreed and 40 (43.4%) agreed that it is a problem in their hospitals while only 2 (2.1%) disagreed. Poor hand hygiene (67.5%), poor infection control practices by healthcare professionals (63.9%) as well as wrong practices in the management of invasive devices (68.7%), and poor environmental cleaning practices (63.4%) were considered very important causes of AMR by the majority of the surveyed ICU physicians. Almost all of the physicians (95%) rated an advice from a clinical pharmacist as very or moderately helpful intervention, while (52%) declared an advice from a microbiologist or an infectious disease specialist as very helpful. CONCLUSION: The results of the present study showed that the Egyptian ICU physicians have remarkable knowledge regarding antibiotic resistance as a worldwide problem and a high sensibility toward the problem in their hospitals. The study also showed that implementation of proper AMS is an urgent need as physicians answers for the different questions in the survey showed that their attitudes and perceptions regarding antibiotic resistance and their way in prescription could be modified and improved if AMS programs with suitable training programs and local guidelines are provided among different types of Egyptian hospitals.

Effect of pressures and type of ventilation on aerosol delivery to chronic obstructive pulmonary disease patients.

Background: Continuous Positive Airway Pressure (CPAP), BiPhasic Positive Airway Pressure (BiPAP), and high flow nasal cannula (HFNC) show some evidence to have efficacy in COVID-19 patients. Delivery during noninvasive mechanical ventilation (NIV) or HFNC gives faster and more enhanced clinical effects than when aerosols are given without assisted breath. The present work aimed to compare the effect of BiPhasic Positive Airway Pressure (BiPAP) mode at two different pressures; low BiPAP (Inspiratory Positive Airway Pressure (IPAP)/Expiratory Positive Airway Pressure (EPAP) of 10/5 cm water) and high BiPAP (IPAP/EPAP of 20/5 cm water), with HFNC system on pulmonary and systemic drug delivery of salbutamol. On the first day of the experiment, all patients received 2500 µg salbutamol using Aerogen Solo vibrating mesh nebulizer. Urine samples 30 min post-dose and cumulative urinary salbutamol during the next 24 h were collected on the next day. On the third day, the ex-vivo filter was inserted before the patient to collect the delivered dose to the patient of the 2500 µg salbutamol. Salbutamol was quantified using high-performance liquid chromatography (HPLC). Results: Low-pressure BiPAP showed the highest amount delivered to the lung after 30 min followed by HFNC then high-pressure BiPAP. But the significant difference was only observed between low and high-pressure BiPAP modes (p = 0.012). Low-pressure BiPAP showed the highest delivered systemic delivery amount followed by HFNC then high-pressure BiPAP. Low-pressure BiPAP was significantly higher than HFNC (p = 0.017) and high-pressure BiPAP (p = 0.008). No significant difference was reported between HFNC and high-pressure BiPAP. The ex-vivo filter was the greatest in the case of low-pressure BiPAP followed by HFNC then high-pressure BiPAP. Low-pressure BiPAP was significantly higher than HFNC (p = 0.033) and high-pressure BiPAP (p = 0.008). Also, no significant difference was found between HFNC and high-pressure BiPAP. Conclusions: Our results of pulmonary, systemic, and ex-vivo drug delivery were found to be consistent. The low BiPAP delivered the highest amount followed by the HFNC then the high BiPAP with the least amount. However, no significant difference was found between HFNC and high BiPAP.

Comparison of the Treatment Efficacy of Rosuvastatin versus Atorvastatin Loading Prior to Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction.

The aim of this study was to compare the effect of a single high-dose rosuvastatin versus atorvastatin preloading in ST-elevation myocardial infarction (STEMI) patients receiving primary percutaneous coronary intervention (PCI.) Methods: A total of 99 patients presented with STEMI and were randomly divided into three groups­a control group (n = 33) with no statin treatment, an atorvastatin group (n = 33) with a single 80 mg atorvastatin dose and the rosuvastatin group (n = 33) with a single 40 mg rosuvastatin dose in the emergency room (ER) prior to PCI. Post-interventional thrombolysis in myocardial infarction (TIMI) flow grade and corrected TIMI frame count (CTFC) were recorded, and ST-segment resolution was measured. Results: CTFC was significantly lower for the atorvastatin group (p-value < 0.01) than in the control group. A final TIMI flow grade 3 was achieved in 32 (97.0%) patients in the rosuvastatin group and 28 (84.8%) patients in the atorvastatin group compared with only 25 (75.8%) patients in the control group (p = 0.014). Peak CK-MB in the rosuvastatin group (263.2 [207.2−315.6]) and the atorvastatin group (208 [151.0−314.1]) was lower compared to that in the control group (398.4 [303.9−459.3]); p < 0.001. Conclusions: A single extensive dose of lipophilic atorvastatin prior to primary PCI in STEMI patients showed better improvement in microvascular myocardial perfusion compared to hydrophilic rosuvastatin.

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.

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.

The Impact of an SGLT2 Inhibitor versus Ursodeoxycholic Acid on Liver Steatosis in Diabetic Patients.

Non-alcoholic fatty liver disease (NAFLD) is related to metabolic syndrome via insulin resistance, where preventing disease progression is crucial in the management process. The study included 240 NAFLD patients with type 2 diabetes who were randomly allocated into empagliflozin 25 mg (EMPA group), ursodeoxycholic acid 250 mg (UDCA group), or the control group (placebo). The study outcomes included: changes in liver fat content (LFC; %) (utilizing the Dixon-based MRI-PDFF approach), liver enzymes, lipid and glycemic profiles, FIB-4 index, and non-alcoholic fatty liver score (NFS). All endpoints were assessed at baseline and after 6 months. EMPA outperformed UDCA and placebo in decreasing LFC (−8.73% vs. −5.71% vs. −1.99%; p < 0.0001). In post-treatment ultrasound images and MRI-PDFF calculations, more patients had normal fatty liver grade (no steatosis or LFC < 6.5%) with EMPA compared to UDCA. EMPA and UDCA showed significant regression in the FIB-4 index (−0.34 vs. −0.55; p = 0.011) and NFS scores (−1.00 vs. −1.11; p = 0.392), respectively. UDCA achieved higher reductions in insulin resistance than EMPA (p = 0.03); however, only EMPA significantly increased beta-cell function (54.20; p = 0.03). When exploring the differences between the two drugs, EMPA was better in decreasing LFC (%), while UDCA achieved higher reductions in liver fibrosis scores. Both showed a similar safety profile in managing liver steatosis.