Background: Diabetic peripheral neuropathy (DPN) is a vastly common and bothersome disorder with a clinically challenging course of treatment affecting patients with diabetes. This study aimed to evaluate the efficacy and safety of high dose oral N-acetyl cysteine (NAC) as adjuvant therapy on clinical outcome of DPN. Methods: A prospective, randomized, parallel, open label, controlled clinical trial. Ninety eligible DPN patients were randomly assigned to either control group receiving standard of care or NAC group receiving standard of care treatment and NAC at a dose of 2400 mg/day for 12 weeks. Glutathione peroxidase (GPx), nuclear factor erythoid-2 related factor (NRF-2) and tumor necrosis factor (TNF) were measured at baseline and after 12 weeks to assess anti-oxidant and anti-inflammatory properties. Michigan neuropathy screening instrument (MNSI), Toronto clinical neuropathy score (TCNS), Diabetic neuropathy score (DNS), Diabetes-39 quality of life questionnaire (DQOL) and pain score were assessed at baseline and after 12 weeks. Results: NAC group showed a significant increase (p < 0.05) in NRF-2 by 25.3% and GPx by 100% and a decline of 21.45% in TNF-alpha levels versus controls that reported a decline in NRF-2 and GPx and an increase in TNF-alpha. HgbA1C and AST levels significantly decreased in NAC versus controls (7.2 ± 1 vs 8 ± 1.1, p = 0.028 and 29.1 vs 55.4, p = 0.012) respectively. NAC administration resulted in a significant decline in MNSA, TCNS, DNS and pain scores versus controls that showed increase in all scores. The QOL total score and the anxiety and energy and mobility domain scores significantly decreased in the NAC group versus controls, p < 0.001. Conclusion: High dose NAC administered for 12 weeks modulated inflammation by reducing TNF-alpha and increasing GPx and NRF2 versus controls. NAC improved clinical outcomes of DPN reflected by a decline in neuropathy and pain scores and an improvement in QOL. Clinical trial registration number: NCT04766450

Sildenafil citrate, a widely-used oral therapy for erectile dysfunction, is a cytochrome P3A4 (CYP3A4) enzyme substrate. Studies have reported that this substrate has an inhibitory effect on CYP3A4 enzymes in long-term cigarette and cannabis smokers, which predominantly mediate the hepatic elimination of sildenafil. Cigarette and/or cannabis smoking could therefore alter the exposure of sildenafil. The aim of this study was to examine the effect of smoking cigarettes and/or cannabis on the pharmacokinetics, pharmacodynamics, safety and tolerability of sildenafil. Thirty-six healthy human subjects were equally divided into three groups: non-smokers, cigarette smokers and cannabis smokers. Each group was administered a single dose of sildenafil (50 mg tablets). The primary outcome measures included the maximum concentration of sildenafil in plasma (C_max), the elimination half-life (t1/2) and the area under the plasma concentration time curve from zero to time (AUC_0–t). The pharmacodynamics were assessed by the International Index of Erectile Function (IIEF-5). The exposure of sildenafil (AUC_0–t) showed a statistically significant increase in cigarette smokers (1156 ± 542 ng·h/mL) of 61% (p < 0.05) while in cannabis smokers (967 ± 262 ng·h/mL), a non-significant increase in AUC_0–t of 35% (p > 0.05) was observed relative to non-smokers (717 ± 311 ng·h/mL). Moreover, the C_max of sildenafil increased by 63% (p < 0.05) and 22% (p > 0.05) in cigarette smokers and cannabis smokers, respectively. Cigarette smoking increases the exposure of sildenafil to a statistically significant level with no effect on its pharmacodynamics, safety and tolerability.

Background: Pain is a frequent and critical problem in daily hemodialysis practice. The pain experienced during arteriovenous fistula cannulation varies from 12% to even 80% in hemodialysis patients depending on the pain assessment tools used. Pain can lead to sleep problems, decreased compliance with hemodialysis therapy, frequent hospital hospitalizations, a decline in quality of life, and high death rates. Despite utilizing several methods as pain relief, it is still unknown in the literature and practice which method is the most effective. The purpose of the study was to compare the effect of lidocaine spray, cold packs, and flashlights on the pain induced by arteriovenous cannulation in hemodialysis patients. This was a prospective randomized open-label controlled trial. Hundred and eight adult patients on regular hemodialysis were recruited and simply randomized into one of four groups (lidocaine spray, cold packs, flashlights, and control) before cannulation. Results: The mean pain severity using visual analog scale was 4.3 (3.3–5.7) in lidocaine group, 4 (3–5.7) in cold packs group, 4.3 (3.3–5.3) in flashlight group, and 4.7 (3–6) in control group. There was a borderline significant difference between groups using Kruskal–Wallis test (p = 0.054). The post hoc Tukey test showed that only cold packs differ from control group with borderline significance (p = 0.051). Conclusion: The results showed that cold packs were safe and effective than lidocaine spray or flashlights in reducing cannulation pain. It is suggested to implement this method before cannulation in hemodialysis patients to reduce pain and improve quality of life. Future studies are needed to compare different application times of cold packs and its impact on pain scores to recommend the optimum time needed to achieve maximum analgesic effect. Trail registration: Clinical trials.gov NCT05822063, REC #194. Graphical

Neurological injury is a crucial problem that interferes with the therapeutic use of vinca alkaloids as well as the quality of patient life. This study was conducted to assess the impact of using loratadine or diosmin/hesperidin on neuropathy induced by vinca alkaloids. Patients were randomized into one of three groups as follows: group 1 was the control group, group 2 received 450 mg diosmin and 50 mg hesperidin combination orally twice daily, and group 3 received loratadine 10 mg orally once daily. Subjective scores (numeric pain rating scale, douleur neuropathique 4, and functional assessment of cancer therapy/gynecologic oncology group–neurotoxicity (FACT/GOG-Ntx) scores), neuroinflammation biomarkers, adverse drug effects, quality of life, and response to chemotherapy were compared among the three groups. Both diosmin/hesperidin and loratadine improved the results of the neurotoxicity subscale in the FACT/GOG-Ntx score (p < 0.001, p < 0.01 respectively) and ameliorated the upsurge in neuroinflammation serum biomarkers. They also reduced the incidence and timing of paresthesia (p = 0.001 and p < 0.001, respectively) and dysuria occurrence (p = 0.042). Both loratadine and diosmin/hesperidin attenuated the intensity of acute neuropathy triggered by vinca alkaloids. Furthermore, they did not increase the frequency of adverse effects or interfere with the treatment response.

Background: Cardiac remodeling post-myocardial infarction contributes to adverse outcomes and increased mortality. We aimed to evaluate the impact of Dapagliflozin on remodeling markers, clinical outcomes and quality of life of diabetic ST-elevation myocardial infarction (STEMI) patients. This was an open label, single centered, randomized controlled-clinical trial was conducted at the Cardiology department, Ain Shams University. Eligible diabetic STEMI patients (n = 54) were randomly allocated to receive either 10 mg of dapagliflozin plus standard of care (Test group) or standard of care alone (Control group) for 4 weeks. The primary outcome was to assess the changes in suppression of tumorigenicity 2 (sST2) over time. Secondary outcomes included: echocardiographic evaluations (left ventricular ejection fraction (LVEF), End Diastolic Diameter (EDD), End systolic volume (ESV), End diastolic volume (EDV) and quality of life using EQ-5D-5L questionnaire. Results: No change was observed in sST2 levels either between or within groups from baseline to 4 weeks. Echocardiographic and quality of life parameters were comparable between groups after 4 weeks. LVEF was significantly increased in the study group at the end of study (42 vs. 47, P < 0.001). Conclusions: Early administration of dapagliflozin in post-MI diabetic patients had no effect on sST2 and quality of life but improved LVEF after 4 weeks of follow up. More studies are needed with larger sample sizes to further investigate SGLT2-inhibitors potential benefits in such population. ClinicalTrial.gov registration number: NCT05335629