Background: Multiple systematic reviews explore the effect of phosphodiesterase type 5 (PDE5) inhibitors on erectile dysfunction (ED), with each study addressing specific outcomes. However, physicians and policymakers require a holistic approach of this topic.Objective: To summarize the current evidence regarding the efficacy and safety of PDE5 inhibitors for the management of ED through an overview of systematic reviews.Methods: Studies were identified by searching PubMed, Web of Science, Cochrane Library and Scopus databases, as well as sources of grey literature until June 12, 2021 (PROSPERO: CRD42020216754). We considered systematic reviews, meta-analyses or network meta-analyses of randomized trials that provided outcomes about the efficacy and safety of any approved PDE5 inhibitor (avanafil, sildenafil, tadalafil and vardenafil). We constructed forest plots for meta-analytic effects regarding the change in erectile function, adverse events and dropouts after administration of PDE5 inhibitors in the general population and in specific patient groups.Results: We included 23 studies with 154,796 participants and a total of 258 meta-analytic effects. Sildenafil 25 mg [Weighted Mean Difference (WMD): 13.08, 95% Confidence Interval (CI): 10.1-16.06] seemed to be statistically superior to all interventions in improving erectile function compared to placebo, but studies with low-dose sildenafil are lacking. Moreover, comparing among different PDE5 inhibitors, sildenafil 50 mg or sildenafil 100 mg were considered the most effective compounds in the general population. The latter derived, however, predominantly from indirect comparisons among different PDE5 inhibitors. Still, sildenafil 100 mg was associated with more treatment-related adverse events and dropouts. Interestingly, low-dose daily tadalafil may be more effective than high-dose on-demand tadalafil (WMD: 1.24, 95% CI: 0.03-2.44). Furthermore, testosterone and PDE5 inhibitors in patients with ED and hypogonadism seem to further improve symptoms, while the addition of a-blockers in patients with urinary symptoms treated with PDE5 inhibitors does not provide additional benefits (WMD: −0.8, 95% CI: −1.65-0.06).Conclusion: Although the efficacy and safety of PDE5 inhibitors, compared to placebo, is well-documented, the existing evidence comparing different PDE5 inhibitors is low. Therefore, high-quality, head-to-head, trials comparing different PDE5 inhibitors are necessary to determine their ideal dosage and formulation based on their safety and efficacy profile.Systematic Review Registration: PROSPERO, identifier [CRD42020216754].

IntroductionPhosphodiesterase-type 5 inhibitors (PDE5i) are the recommended first-line treatment for erectile dysfunction. Previous systematic reviews and meta-analyses suggest that they are a safe and effective option in many patient groups. Similarly, PDE5i may be effective as part of combination therapy in non-responders to PDE5i. We will generate an overview of systematic reviews, meta-analyses and network meta-analyses aiming to summarise the available knowledge regarding the efficacy and safety of PDE5i in the general population and in multiple subgroups of patients.Methods and analysisThis overview was designed in accordance with the PRIO-harms and Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines and its protocol was registered at PROSPERO. We will systematically search PubMed, Web of Science, Cochrane Library and Scopus databases from inception to November 2020 without any language restrictions. We will include systematic reviews or meta-analyses: (1) comparing the efficacy and safety of any dose of PDE5i with each other, with placebo or with other effective treatments for the management of erectile function; (2) exploring the use of any PDE5i alone or in combination with other treatment modalities in the general male population or in specific subgroups and (3) conducted with systematic procedures. Our overview will employ the AMSTAR 2 tool to evaluate the quality of the included studies and the Grading of Recommendations Assessment, Development and Evaluation approach to assess the strength of evidence for all outcomes. We will construct forest plots of risk estimates with the corresponding CI for all outcomes.Ethics and disseminationIn this overview, we will undertake an extensive literature search in an attempt to evaluate the potential benefits and risks of treatment with one PDE5i versus another or versus placebo and provide recommendations for clinicians and policy-makers. No ethical approval is required.PROSPERO registration numberCRD42020216754.

Background: Abdominal operations may lead to post-operative bowel dysfunction, while administration of probiotics, prebiotics and synbiotics may limit its manifestation. Τhe study aimed to assess the efficacy of probiotics, prebiotics and synbiotics in patients who undergone abdominal operation, in terms of bowel function post-operatively. Methods: PubMed, Scopus, Cochrane Central Register of Controlled Trials (Central), Embase, US Registry of clinical trials, and sources of grey literature were searched. The relative effect sizes were estimated, and we obtained the relative ranking of the interventions using cumulative ranking curves. Results: In total, 30 studies were included in the analysis. For the outcome of post-operative ileus, probiotics was superior to placebo/no intervention (relative risk, RR: 0.38; 95%CI: 0.14–0.98) with the highest SUCRA (surface under the cumulative ranking) value (92.1%). For time to first flatus, probiotics (MD: −0.47; 95%CI: −0.78 to −0.17) and synbiotics (MD: −0.53; 95%CI: −0.96 to −0.09) were superior to placebo/no intervention. For time to first defecation and for post-operative abdominal distension probiotics were superior to placebo/no intervention. For post-operative hospitalization days, synbiotics were superior to placebo/no intervention (MD: −3.07; 95%CI: −4.80 to −1.34). Conclusions: Administration of probiotics in patients who had undergone abdominal surgery reduced the prevalence of post-operative ileus, time to first flatus, time to first defecation, and prevalence of post-operative abdominal distension. Synbiotics reduce time to first flatus and post-operative hospitalization days.

Aims Gestational diabetes mellitus (GDM) is a common medical complication during pregnancy. Endothelial dysfunction is considered an early step in the progression of atherosclerosis that may contribute to subclinical target organ damage. This meta‐analysis aimed to systemically review the existing data regarding endothelial dysfunction between women with and without GDM during pregnancy and post‐partum using flow‐mediated dilation (FMD). Materials and Methods Eligible studies (cohort and observational) published until October 2021 were identified in the MEDLINE, Scopus, Cochrane Library database and grey literature sources were searched. Results The search yielded 2272 studies, of which 17 were fully reviewed and 12 studies (N = 740 pregnant women) were finally included. Pregnant women with GDM exhibited a significantly lower FMD compared to pregnant women without GDM (pooled mean difference −3.12; 95% CI −5.36 to −0.88). Moreover, in the immediate (1–6 months) post‐partum period, women with previous GDM showed lower FMD compared to healthy women without GDM history (pooled mean difference −7.52; 95% CI −9.44 to −5.59), whereas FMD did not differ in the late post‐partum period (more than 4 years). Conclusions Flow‐mediated dilation is decreased in women with GDM during pregnancy and in the immediate post‐partum period, compared to women without GDM, indicating that the endothelial dysfunction noted during the pregnancy in those women persists in the immediate post‐partum period too. Clinical trial registration PROSPERO CRD42021283113 (http://www.ClinicalTrials.gov).

Claudication in the young population is a rare condition derived from varied neurogenic and vascular conditions. We report a case of bilateral claudication of the lower extremities in a young athlete after intense training. Apart from tenderness to deep palpation of the popliteal fossa, physical and laboratory examinations did not reveal any abnormal findings. According to the patient's symptoms, sciatic nerve entrapment to the popliteal fossa was suspected and bilateral surgical exploration of the sciatic nerve was performed. The sciatic nerve was found to be entrapped before its division to the tibial and common peroneal nerves from the terminal branch of the small saphenous vein (SSV) into the popliteal vein (PV). The terminal section of SSV was subsequently ligated and resected to relieve the pressure on the sciatic nerve. One year after surgery, the patient was able to run long distances as well as sprint and train without any restriction. Rare conditions may lead to pseudoclaudication in young individuals and athletes during exercise. Normal physical and laboratory tests must raise the suspicion of sciatic nerve compression from fibrous bands or abnormal anastomotic veins that may also exist bilaterally. Surgical exploration along with sciatic nerve release remains the only treatment solution when conservative treatment fails to alleviate the symptoms.