Cardiovascular Outcomes of Hypogonadal Men Receiving Testosterone Replacement Therapy: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To investigate the impact of testosterone replacement therapy (TRT) on cardiovascular outcomes in hypogonadal men. METHODS: A meta-analysis of 26 randomized controlled trials involving 10 941 participants was conducted. Various clinical outcomes, including all-cause mortality, cardiovascular-related mortality, myocardial infarction, stroke, congestive heart failure, atrial fibrillation, pulmonary embolism, and venous thrombosis, were assessed. RESULTS: No statistically significant differences were observed between the TRT group and the control group in terms of these clinical outcomes. Sensitivity analysis and publication bias assessment supported the robustness of the findings. Meta-regression analysis found no significant associations between clinical outcomes and potential covariates, including age, diabetes, hypertension, dyslipidemia, and smoking. DISCUSSION: Previous research on TRT and cardiovascular events, with comparisons to studies like the Testosterone Trials and the studies conducted by Vigen et al, Finkle et al, Layton et al, and Wallis et al, is provided. The significance of the systematic review and meta-analysis approach is emphasized, particularly its exclusive focus on hypogonadal patients. CONCLUSION: This study offers reassurance that TRT does not increase mortality risk or worsen cardiovascular outcomes in hypogonadal men. However, further research, especially long-term studies involving diverse populations, is essential to strengthen the evidence base and broaden the applicability of these findings.

Preventive Effect of Bone Marrow Mononuclear Cell Transplantation on Acute Myocardial Infarction-Induced Heart Failure: A Meta-analysis of Randomized Controlled Trials.

PURPOSE: Heart failure (HF) is a major complication of acute myocardial infarction (AMI). Transplantation of bone marrow mononuclear cells (BM-MNC) in the setting of AMI has been proposed as a means for myocardial tissue regeneration. Several trials have explored the outcomes of these cells on surrogate end points such as left ventricular ejection fraction (LVEF) in patients with AMI. However, the data regarding the clinical efficacy are infrequent. Here, we performed a meta-analysis investigating the effect of BM-MNCs injection on the rate of hospitalization for HF in the long-term follow-up period. METHODS: PubMed, Scopus, and Cochrane databases were queried with various combinations of keywords through May 2, 2022. A random-effects meta-analysis was performed to calculate risk ratio (RR) and 95% confidence interval (CI) of hospitalization for HF, all-cause mortality, and stroke rate. Subgroup analyses for hospitalization based on time and cell dose were performed. RESULTS: A total of 2150 patients with AMI across 22 trials were included for quantitative synthesis. At long-term follow-up, AMI patients treated with an intracoronary injection of BM-MNCs were less likely to be hospitalized for heart failure compared to the control group receiving standard treatment (RR = 0.54, 95% CI = [0.37; 0.78], p = 0.002). There was no association between BM-MNC therapy and all-cause mortality (RR = 0.69, 95% CI = [0.47; 1.01], p = 0.05) and stroke (RR = 1.12, 95% CI= [0.24; 5.21], p = 0.85). CONCLUSION: Autologous injection of BM-MNC in the setting of AMI may be associated with decreased risk of hospitalization of heart failure in the long term. However, its effect on all-cause mortality and stroke rate is questionable.

Major cardiovascular events after bone marrow mononuclear cell transplantation following acute myocardial infarction: an updated post-BAMI meta-analysis of randomized controlled trials.

BACKGROUND: The effect of bone marrow-derived mononuclear cells (BM-MNCs) after acute myocardial infarction (AMI) on myocardial function indices such as left ventricular ejection fraction has been widely studied. However, the effect of this intervention on major adverse cardiovascular events (MACE) was not the principal purpose of most investigations and its role is unclear. The aim of this study was to investigate the possible long-term clinical efficacy of BM-MNCs on MACE after AMI. METHODS: A comprehensive search was conducted through electronic databases for potentially eligible randomized trials investigating the impact of BM-MNC therapy following acute MI on clinical outcomes. Risk of bias of the eligible studies was assessed using the Cochrane Collaboration's tool. The effect of treatment was displayed by risk ratio (RR) and its 95% confidence interval (CI) using random-effects model. RESULTS: Initial database searching found 1540 records and 23 clinical trials with a total of 2286 participants eligible for meta-analysis. Injection of BM-MNCs was associated with lower risk of composite end points of hospitalization for congestive heart failure (CHF), re-infarction, and cardiac-related mortality (91/1191 vs. 111/812, RR = 0.643, 95% CI = 0.489 to 0.845, p = 0.002). This effect was derived from both reduction of CHF (47/1220 vs. 62/841, RR = 0.568, 95% CI = 0.382 to 0.844, p = 0.005) and re-infarction rate (23/1159 vs. 30/775, RR = 0.583, 95% CI = 0.343 to 0.991, p = 0.046), but not cardiac-related mortality (28/1290 vs. 31/871, RR = 0.722, 95% CI = 0.436 to 1.197, p = 0.207). CONCLUSION: This is the first meta-analysis focused on the cardiovascular outcomes of stem cell therapy after AMI and it revealed that transplantation of BM-MNCs may reduce composite endpoint of hospitalization for CHF, re-infarction, and cardiac related mortality driven mainly by reducing reinfarction and hospitalization for heart failure rates but not cardiovascular mortality.

Global longitudinal strain for detection of cardiac iron overload in patients with thalassemia: a meta-analysis of observational studies with individual-level participant data.

BACKGROUND: Although cardiac magnetic resonance (CMR) is the most reliable tool for assessment of CIO in patients with thalassemia, it is not always readily available. Recent studies have explored the potential of GLS as an alternative for diagnosis of CIO. We aimed to investigate the efficacy of global longitudinal strain (GLS) for detection of cardiac iron level (CIO). METHODS: We searched SCOPUS, MEDLINE, and Embase to identify the studies which used GLS for assessment of CIO. We searched for individual participant data (IPD) in eligible studies to perform ROC curve analysis. CMR with a T2* cut-off value of 20 ms was considered as the gold standard. A meta-analysis was performed and the risk of bias was assessed using the JBI Checklist. RESULTS: A total of 14 studies with 789 thalassemia patients (310 and 430 with and without CIO respectively and 49 with undetermined condition) were considered eligible for meta-analysis. IPDs of 405 participants were available. GLS was significantly lower in patients with CIO (-17.5 ± 2.7%) compared to those without CIO (-19.9 ± 2.3%; WMD = 1.6%, 95% CI = [0.76-2.4], p = 0.001, I2 = 77.1%) and to normal population (-20.61 ± 2.26%; WMD = 2.2%, 95% CI = [0.91-3.5], p = 0.001, I2 = 83.9%). A GLS < -19.5% could predict CIO with 92.8% sensitivity and 34.63% specificity (AUC = 0.659, 95% CI = [0.6-0.72], p-value < 0.0001). A GLS value < -6% has 100% positive predictive and ≥ -24.5% has 100% negative predictive values for detection of CIO. CONCLUSIONS: According to our study, GLS is a strong predictor of CIO and when CMR is not available, it may be a useful screening method for identification of CIO in thalassemia patients.

Occurrence of residual disease in specimens of re-excision surgery in patients with positive margins of primary quadrantectomy.

Performing a re-intervention following a positive margin after primary lumpectomy in patients with breast cancer entails several disadvantages such as additional costs and postponing the follow-up treatments. In the present study, we sought to measure the incidence rate of residual disease in specimens taken from breast cancer patients who had positive margins after quadrantectomy and also compare the clinical and pathological factors between patients with and without a residual disease after the secondary surgery. All of the medical records of patients undergoing quadrantectomy from December 1994 to December 2019 were collected from Shiraz Breast Cancer Registry (SBCR). Patients were divided into two subgroups of patients with and without residual disease from the secondary surgery and also with and without positive margin from the first operation. Two groups were compared in terms of all clinicopathological factors. The records of 4843 patients undergoing quadrantectomy were reviewed, of which 132 (2.3%) had involved margins. Of these, 112 patients underwent a secondary surgery and 28 had residual disease (25%). No clinicopathological factor was correlated with presence of residual cancer. Also, bigger tumor size (p < 0.001) and the presence of in situ component (p < 0.001) were associated with positive margin and hence the need for a re-excision surgery. These results revealed that the significant rate of residual disease in the specimens of the secondary surgery indicates that a re-operation (either re-excision or simple mastectomy) cannot be omitted after obtaining a positive margin from the primary quadrantectomy.

Potential mechanisms of SARS-CoV-2 action on male gonadal function and fertility: Current status and future prospects.

The novel coronavirus was recognised in December 2019 and caught humanity off guard. The virus employs the angiotensin-converting enzyme 2 (ACE2) receptor for entry into human cells. ACE2 is expressed on different organs, which is raising concern as to whether these organs can be infected by the virus or not. The testis appears to be an organ enriched with levels of ACE2, while the possible mechanisms of involvement of the male reproductive system by SARS-CoV-2 are not fully elucidated. The major focus of the present studies is on the short-term complications of the coronavirus and gains importance on studying the long-term effects, including the possible effects of the virus on the male reproductive system. The aim of this review was to provide new insights into different possible mechanisms of involvement of male gonads with SARS-CoV-2 including investigating the ACE2 axis in testis, hormonal alterations in patients with COVID-19, possible formation of anti-sperm antibodies (ASA) and subsequently immunological infertility as a complication of SARS-CoV-2 infection. Finally, we suggest measuring the sperm DNA fragmentation index (DFI) as a determiner of male fertility impairment in patients with COVID-19 along with other options such as sex-related hormones and semen analysis. Invasion of SARS-CoV-2 to the spermatogonia, Leydig cells and Sertoli cells can lead to sex hormonal alteration and impaired gonadal function. Once infected, changes in ACE2 signalling pathways followed by oxidative stress and inflammation could cause spermatogenesis failure, abnormal sperm motility, DNA fragmentation and male infertility.

Ablation versus medical therapy for patients with atrial fibrillation: An updated meta-analysis.

To investigate the effect of ablation compared to medical therapy on clinical outcomes of patients with atrial fibrillation (AF). PubMed, Scopus, Embase, and Web of Science databases were searched using ablation, medical treatment, AF, and related words. The effect of ablation and medical therapy was sought to be gathered on stroke or transitional ischemic attack, mortality, hospitalization, recurrence of AF, progression of AF, and left ventricular ejection fraction. Analyses were performed using R software. 31 studies (the results of 27 randomized controlled trials), compromising an overall 6965 patients (Ablation, n = 3643; Medical treatment, n = 3322) were reviewed in our study, revealed that catheter ablation would result in substantial benefits for patients with AF without significant difference in serious adverse events compared to medical management (Risk Ratio: 0.92, [95% Confidence Interval (CI), 0.64-1.33]). Catheter ablation in patients with AF significantly resulted in a 29% reduction in all-cause mortality (RR: 0.71, [95% CI, 0.57-0.88]), a 57% reduction in hospitalization (RR: 0.43, [95% CI, 0.27-0.67]), a 53% reduction in AF recurrence (RR: 0.47, [95% CI, 0.36-0.61]), and a dramatic reduction, 89%, in progression of paroxysmal to persistent AF (RR: 0.11, [95% CI, 0.02-0.65]); also associated with a remarkable improvement in their left ventricular ejection fraction (LVEF) (Mean Difference, MD: 6.84%, [95% CI, 3.27-10.42]) compared to medical therapy. Our study showed that ablation may be superior to medical therapy in patients with AF regarding AF recurrence, mortality, LVEF improvement, hospitalization, and AF progression outcomes.

Clinical outcomes of optical coherence tomography versus conventional angiography guided percutaneous coronary intervention: A meta-analysis.

BACKGROUND: Performing optical coherence tomography (OCT) as a guide for percutaneous coronary intervention (PCI) compared to conventional coronary angiography has been the subject of the recent cohorts and randomized trials. However, clear evidence demonstrating its superiority is still controversial. METHODS: We performed a thorough search in digital databases to find the relevant observational studies and randomized trials comparing OCT and angiography in patients undergoing PCI. A random-effects meta-analysis was undertaken comparing clinical outcomes to generate an odds ratio (OR) with a corresponding 95% confidence interval (CI). Subgroup analyzes were performed based on study design, underlying cardiac condition, and complexity of cases. RESULTS: A total of 21 studies (10 RCTs and 11 observational studies) with 11,163 participants (5319: OCT and 5844: angiography group) were included for quantitative synthesis. Performing OCT was associated with lower odds of all-cause (OR (95% CI) = 0.56 (0.48; 0.67)) and cardiac mortality (OR (95% CI) = 0.47 (0.35; 0.63)), major adverse cardiovascular events (OR (95% CI) = 0.60 (0.48; 0.76)), myocardial infarction (OR (95% CI) = 0.79 (0.64; 0.97)), and stent thrombosis (OR (95% CI) = 0.61 (0.39; 0.96)) compared to the angiography group. Other clinical outcomes were similar between the studied groups. The outperformance of OCT was more evident in observational studies and the ones with PCI on complex lesions. CONCLUSION: Performing OCT prior to PCI is associated with better clinical outcomes compared to angiography alone based on contemporary evidence. Future well-designed randomized trials are needed to confirm the findings of this meta-analysis.

Hemoglobin A1c levels and 1-year mortality in patients with ST-elevation myocardial infarction undergoing percutaneous coronary intervention.

Background: In this study, we investigated whether different levels of hemoglobin A1c (HbA1c) are associated with different short-term and 1-year mortality rates among diabetic patients undergoing percutaneous coronary intervention. Patients & methods: Clinical events including in-hospital, 1-month and 1-year mortality were compared between three groups based on HbA1c levels of patients (I: ≤5.6%, II: 5.7-6.4%, III: ≥6.5%). Results: Among 165 diabetic individuals, patients with abnormal HbA1c levels (≥6.5%) experienced significantly higher hospitalization days (7.65 ± 1.64 days) compared with those with normal HbA1c (4.94 ± 0.97 days) (p < 0.0001). In-hospital mortality was significantly higher in group III (14.5%) and II (5.5%) compared with group I (0%) (p = 0.008). Conclusion: HbA1c levels may be a reliable predictor of short-term clinical events in diabetic patients.

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Efficacy of exercise training-based cardiac rehabilitation programmes after transcatheter aortic valve implantation: A systematic review and meta-analysis.

Background: The beneficial effects of exercise training-based cardiac rehabilitation (CR) in different cardiac conditions have been previously studied. In this meta-analysis, we focused on the potential impact of CR on patients undergoing transcatheter aortic valve implantation (TAVI). Methods: Multiple databases were searched in a systematic approach to find the eligible studies. All the studies investigating the potential impact of exercise training-based CR programmes on exercise capacity and health-related quality of life in patients undergoing TAVI were retrieved. The primary endpoint of interest was 6-min walk test (6MWT). The pooled standardized mean difference (SMD) and 95 % confidence interval (CI) were measured to compare the improvement or worsening the endpoints using a random- or fixed-effects model, as appropriate. Results: A total of eleven studies (685 patients) were considered eligible for quantitative synthesis. The results showed that performing exercise training-based CR after TAVI is associated with significant improvement in 6MWT (SMD 0.59, 95 % CI (0.48; 0.71), p < 0.01), Barthel index (SMD 0.73, 95 % CI (0.57; 0.89), p < 0.01), 12-item Short Form (SF-12) physical (SMD 0.30, 95 % CI (0.08; 0.52), p < 0.01) and mental (SMD 0.27, 95 % CI (0.05; 0.49), p = 0.02) survey scores, and hospital anxiety and depression scale - depression (HADS-D) score (SMD -0.26, 95 % CI (-0.42; -0.10), p < 0.01). Conclusion: Performing exercise training-based CR following TAVI has significant benefits regarding physical capacity and health-related quality of life irrespective of the programme duration.

Impact of treadmill running on distal femoral cartilage thickness: a cross-sectional study of professional athletes and healthy controls.

PURPOSE: This present study aimed to assess the impact of treadmill running on distal femoral cartilage thickness. METHODS: Professional athletes aged 20 to 40 years with a history of treadmill running (minimum 75 min per week for the past three months or more) and age-, sex-, and body mass index (BMI)-matched healthy controls were recruited. Demographics and clinical features of participants were recorded. Athletes were divided into subgroup 1 with less than 12 months of treadmill running and subgroup 2 with 12 months or more of treadmill running. Distal femoral cartilage thicknesses were measured at the midpoints of the right medial condyle (RMC), right intercondylar area (RIA), right lateral condyle (RLC), left medial condyle (LMC), left intercondylar area (LIA), and left lateral condyle (LLC) via ultrasonography. RESULT: A total of 72 athletes (mean age: 29.6 ± 6.6 years) and 72 controls (mean age: 31.9 ± 6.7 years) were enrolled. Athletes had significantly thinner cartilages in the RLC (2.21 ± 0.38 vs. 2.39 ± 0.31 cm, p = 0.002), LLC (2.28 ± 0.37 vs. 2.46 ± 0.35 cm, p = 0.004), and LMC (2.28 ± 0.42 vs. 2.42 ± 0.36 cm, p = 0.039) compared with the control group. Furthermore, cartilage thickness was significantly thinner in subgroup 2 athletes compared with the control group in the RLC (2.13 ± 0.34 vs. 2.39 ± 0.31 cm, p = 0.001), LLC (2.22 ± 0.31 vs. 2.46 ± 0.35 cm, p = 0.005), and LMC (2.21 ± 0.46 vs. 2.42 ± 0.36 cm, p = 0.027); however, subgroup 1 athletes did not have such differences. There was a weak negative correlation between total months of treadmill running and cartilage thickness in the RLC (r = - 0.0236, p = 0.046) and LLC (r = - 0.0233, p = 0.049). No significant correlation was found between the distal femoral cartilage thickness at different sites and the patients' demographic features, including age, BMI, speed and incline of treadmill running, and minutes of running per session and week (p > 0.05). CONCLUSION: Compared with healthy controls, professional athletes with a history of long-term high-intensity treadmill running had thinner femoral cartilages. The duration (months) of treadmill running was weakly negatively correlated with distal femoral cartilage thickness. Longitudinal studies with prolonged follow-ups are needed to clarify how treadmill running affects femoral cartilage thickness in athletes.

Effect of different reperfusion strategies on recovery of ventricular function after ST-segment elevation myocardial infarction: A longitudinal single-center study.

Background and Aims: Although the clinical benefit of percutaneous coronary intervention (PCI) on cardiovascular outcomes has been widely investigated, the impact of this revascularization strategy compared to other alternatives on the degree of left ventricular function recovery is poorly demonstrated. In this regard, we investigated whether time delays between the presentation of ST-segment elevation myocardial infarction (STEMI) and PCI in reperfusion strategies have different impacts on left ventricular function recovery. Methods: In this single-center study, all the patients who presented with STEMI and a reduced left ventricular ejection fraction (LVEF ≤ 40%) were enrolled. Included patients were subjected to four different treatment groups of primary, rescue (immediate transfer for angioplasty due to failed fibrinolytic therapy), facilitated (fibrinolytic therapy followed by angioplasty within 24 h), and deferred (successful fibrinolytic therapy and PCI after 24 h) PCI based on hospital facilities. Echocardiography was performed for all the patients at the time of hospitalization and 6 months later. Results: A total of 128 patients were included in this study. The LVEF improved by 15.3 ± 6.3%, 11.5 ± 3.61%, 4.0 ± 1.0%, and -1.3 ± 7.0% in primary, rescue, facilitated, and deferred PCI groups, respectively (p < 0.001). Patients undergoing deferred PCI experienced a significantly lower improvement in LVEF compared with primary and rescue PCI (p < 0.001). Conclusion: Primary PCI demonstrated the most promising recovery in left ventricular function following STEMI compared to other alternative strategies. Performing PCI as soon as possible provides better recovery of LVEF.

Glucagon-Like Peptide-1 Receptor Agonists and Major Adverse Cardiovascular Events in Patients With and Without Diabetes: A Meta-Analysis of Randomized-Controlled Trials.

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown encouraging results regarding cardiovascular outcomes mainly in patients with diabetes. In the present study, we compared the efficacy of GLP-1 RAs in cardiovascular events between patients with and without diabetes. METHODS: After finding eligible studies assessing the impact of GLP-1 RAs on cardiovascular events in patients with and without diabetes using a systematic search, we performed a meta-analysis on randomized-controlled trials (RCTs) comparing cardiovascular outcomes between patients taking GLP-1 RAs and placebo stratified by the presence or absence of diabetes. Relative risk (RR) and its 95% confidence interval (CI) were set as the reporting effect size using the random-effects model. RESULTS: A total of 24 RCTs (50 033 with GLP-1 RAs and 44 514 with placebo) were included. Patients on GLP-1 RAs had lower risk of major adverse cardiovascular events (MACE) (RR 0.87, 95% CI 0.82-0.93), cardiovascular death (RR 0.88, 95% CI 0.82-0.94), myocardial infarction (MI) (RR 0.87, 95% CI 0.77-0.97), stroke (RR 0.86, 95% CI 0.80-0.92), and hospitalization for heart failure (RR 0.90, 95% CI 0.83-0.98). Both subgroups were shown to be effective in terms of MACE and mortality. Nondiabetic patients had decreased risk of hospitalization for heart failure and MI, whereas the diabetic subgroup had marginally nonsignificant efficacy. CONCLUSION: The findings of this meta-analysis indicated that patients who are overweight/obese but do not have diabetes have a comparable reduction in the risk of adverse cardiovascular events as those with diabetes. These results need to be confirmed further by large-scale randomized trials in the future.

Calculating torque, back-EMF, inductance, and unbalanced magnetic force for a hybrid electrical vehicle by in-wheel drive application.

To use a Hybrid Excitation Synchronous Machine (HESM) in a hybrid electrical vehicle (HEV), its performance indicators such as back-EMF, inductance and unbalanced magnetic force should be computed preferably by an analytical method. First, the back-EMF is calculated by considering alternate-teeth and all-teeth non-overlapping and overlapping windings. The effects of three types of magnetization patterns including the radial, parallel and Halbach magnetizations on the back-EMF waveform have also been investigated. Then, the self-inductance of the stator and rotor windings, the mutual inductance between the stator and rotor windings, and the mutual inductance between the stator phases are computed. Next, the components of the unbalanced magnetic force (UMF) in the direction of the x and y axes and its amplitude are computed. Moreover, the effects of the magnetization patterns on those magnetic pulls are investigated. To minimize the UMFs, symmetry must be implemented in the excitation sources; therefore, first the stator winding then the permanent magnet and rotor winding are modified in such a way that the UMFs are reduced. Increasing the temperature leads to a weakening of the magnet's residual flux density, which strongly affects the performance characteristics of the electric machine such as Back-EMF and UMF. Finally, the ratio of the permanent magnet flux to the rotor flux is determined in such a way that the average torque is maximized. In this section, the effects of three magnetization patterns will be investigated.

The impact of antihypertensive treatment of mild to moderate hypertension during pregnancy on maternal and neonatal outcomes: An updated meta-analysis of randomized controlled trials.

Currently, there is controversy regarding the treatment of pregnant patients with mild hypertension (blood pressure 140-159/90-109 mm Hg). While guidelines do not recommend this treatment, results from recent clinical trials are supportive of the treatment. This meta-analysis aimed to clarify if active treatment of mild hypertension during pregnancy results in better maternal and fetal outcomes. All of the potentially eligible randomized controlled trials were retrieved through a systematic database search investigating the impact of pharmacological treatment in mild hypertensive patients on maternal, fetal, and neonatal outcomes. Relative risk (RR) and 95% confidence interval (CI) were calculated using a random-effects model. Data from 12 trials comprising 4461 pregnant women diagnosed with mild to moderate hypertension (2395 in the intervention group and 2066 in the control group) were extracted for quantitative synthesis. Antihypertensive treatment was associated with better outcomes in seven out of the 19 analyzed outcomes: Severe hypertension (RR = 0.53; 95% CI = [0.38;0.75]), preeclampsia (RR = 0.71; 95% CI = [0.54; 0.93]), placental abruption (RR = 0.48; 95% CI = [0.26; 0.87]), changes in electrocardiogram (RR = 0.43; 95% CI = [0.25; 0.72]), renal impairment (RR = 0.42; 95% CI = [0.34; 0.51]), pulmonary edema (RR = 0.46; 95% CI = [0.25; 0.84]), and neonatal mortality (RR = 0.72; 95% CI = [0.57; 0.92]). The primary safety outcome of small for gestational age was not different between the treatment group and the control group (RR = 1.12; 95% CI = [0.80; 1.57]). The results of this meta-analysis are in favor of the beneficial impact of pharmacological treatment of mild hypertension on both maternal and neonatal outcomes and without significant adverse events for the fetus.

Are herbal medications, with possible beneficial effects for benign prostatic hyperplasia, better to be continued during the COVID-19 pandemic?

Different strategies have been proposed to treat cytokine storm syndrome (CSS), the final deadly complication of COVID-19. One approach is to target CSS by blocking the interleukin-6 (IL-6) pathway. A promising group of medications blocking the IL-6 pathway is α-blockers, such as prazosin. First, we hypothesized that Panax ginseng, commonly known as ginseng, can be an effective therapeutic agent in preventing CSS due to its blocking activity on alpha-1 adrenergic receptors (α1-AR). Furthermore, we suggested that herbs with 5α-reductase inhibitory effects, such as Saw palmetto, Nettle root, soya, black pepper, and green tea, can have debilitating impacts on pulmonary function since they can lead to impairment of the lung's ability to regenerate. Thus, we encourage the prospective studies to explore the potential effect of herbal medications, with possible beneficial effects for benign prostatic hyperplasia, during the COVID-19 pandemic since they are commonly consumed.

Coronavirus Disease 2019 and Hypertension: How Anti-hypertensive Drugs Affect COVID-19 Medications and Vice Versa.

BACKGROUND: As a medical problem, hypertension is one of the most common disorders in cardiovascular disease. High blood pressure has been identified as one of the most familiar risk factors for the ongoing COVID-19 pandemic. We planned to explore the possible interactions between anti-hypertensive agents and drugs targeting SARS-CoV-2 with broad investigations of these medications' mechanism of action and adverse effects. METHODS: Two co-authors searched the electronic databases (PubMed, Scopus, and Google Scholar) to collect papers relevant to the subject. The keywords searched were angiotensin-converting enzyme inhibitors (ACEI), angiotensin-II receptor blockers (ARBs), sympatholytic drugs (alpha-1 blockers, beta-blockers), vasodilators (calcium channel blockers, nitrates, and hydralazine), diuretics, chloroquine, hydroxychloroquine, lopinavir/ritonavir, remdesivir, favipiravir, interferons, azithromycin, anti-cytokine agents, glucocorticoids, anticoagulant agents, nitric oxide, and epoprostenol. RESULTS: QT prolongation, arrhythmia, hypokalemia, hypertriglyceridemia are the most dangerous adverse effects in the patients on COVID-19 medications and anti-hypertensive drugs. CONCLUSION: This review emphasized the importance of the potential interaction between drugs used against COVID-19 and anti-hypertensive agents. Therefore, caution must be exercised when these medications are being used simultaneously.

Balloon-Expandable Versus Self-Expanding Transcatheter Aortic Valve Implantation in Patients With Small Aortic Annulus: A Meta-Analysis.

Although transcatheter aortic valve implantation (TAVI) is considered a superior option to surgery in patients with small aortic annulus (SAA), it is not clear which type of transcatheter heart valve (THV) has better results in terms of echocardiographic hemodynamics and clinical outcomes. A random-effects meta-analysis was performed comparing balloon-expandable valves (BEVs) and self-expanding valves (SEVs) in patients with SAA who underwent TAVI regarding their impact on hemodynamic and clinical outcomes at short- and midterm follow-up. Relative risk (RR) and mean difference (MD) with 95% confidence interval (95% CI) were measured for the outcomes, as appropriate. Subgroup analyses were performed based on the generation type of devices and study designs. A total of 16 articles comprising 1 randomized trial, 3 propensity-matched studies, and 12 observational studies including 4,341 patients (1,967 in BEV and 2,374 in the SEV group) with SAA were included. The implantation of BEVs correlated with a lower indexed effective orifice area (MD -0.19 [-0.25 to -0.13]) and higher transvalvular mean pressure gradient (MD 3.91, 95% CI 2.96 to 4.87). Compared with SEVs, BEVs had increased risk of prosthesis-patient mismatch (PPM; RR 2.09, 95% CI 1.79 to 2.45) and severe PPM (RR 2.16, 95% CI 1.48 to 3.15). However, BEV had lower moderate and severe paravalvular leak (RR 0.45, 95% CI 0.29 to 0.69), risk of stroke (RR 0.57, 95% CI 0.42 to 0.76), and permanent pacemaker implantation (RR 0.63, 95% CI 0.44 to 0.91). The 1-year all-cause mortality (RR 1.13, 95% CI 0.86 to 1.49) and cardiac-related mortality (RR 1.53, 95% CI 0.24 to 9.81) were not different between the 2 groups. In conclusion, SEVs were associated with larger indexed effective orifice area and lower PPM but higher paravalvular leak. In contrast, patients with SEVs were more likely to develop stroke and required permanent pacemaker implantation. Both THVs did not show difference in terms of early and midterm all-cause and cardiac mortality. Because both types of THVs show similar results regarding mortality data, hemodynamics should be among the factors considered in decision making for patients with SAA who underwent TAVI.

Sex-Specific Differences in Clinical Outcomes in Patients With Coronary Bifurcation Lesions.

Coronary bifurcation lesions are frequent challenging findings during percutaneous coronary intervention (PCI). Contemporary evidence has explored the potential sex-specific differences in patients undergoing PCI. In the present meta-analysis, we compared clinical outcomes of patients undergoing bifurcation PCI between women and men. Using the random-effects method, we compared the clinical outcomes of patients with a coronary bifurcation lesion following PCI between women and men. The results were reported using relative risk (RR) and 95% confidence interval (CI). Baseline comorbidities and mean age were compared between the 2 studied groups. Four observational studies comprising 30,684 patients (8898 women and 21,786 men) were included in the meta-analysis. Women were significantly older than men with a relatively higher prevalence of baseline comorbidities. After using adjusted data from 2 out of 4 available studies, performing PCI for bifurcation lesions in women was not associated with an increased risk of mortality (RR 1.33, 95% CI, 0.78-2.29), myocardial infarction (RR 1.22, 95% CI, 0.41-3.61), target lesion revascularization (RR 1.06, 95% CI, 0.40-2.81), stent thrombosis (RR 0.99, 95% CI, 0.09-10.52), and stroke (RR 1.19, 95% CI, 0.64-2.22). Women were at higher risk of major bleeding compared to male counterparts (RR 2.23, 95% CI, 1.73-2.89). The present study showed no difference in the risk of adverse clinical outcomes except the risk of bleeding between genders with coronary bifurcation lesions. Future studies with adjustment of age and baseline comorbidities are needed to confirm these findings.

Comparing the effect of bone marrow mono-nuclear cells with mesenchymal stem cells after acute myocardial infarction on improvement of left ventricular function: a meta-analysis of clinical trials.

BACKGROUND: The effect of transplantation of bone-marrow mononuclear cells (BM-MNCs) and mesenchymal stem cells (MSCs) on ejection fraction (LVEF) has been studied in patients with acute myocardial infarction (AMI) in clinical trials. This raises the question that which type of cell may help improve LVEF better in AMI patients. No meta-analysis of clinical trials has yet addressed this question. METHODS: Electronic databases were searched thoroughly to find eligible trials on the effects of transplantation of BM-MNCs and MSCs in patients with AMI. The primary outcome was improvement in LVEF. Data were synthesized using random-effects meta-analysis. For maximizing the credibility of subgroup analysis, we used the instrument for assessing the Credibility of Effect Modification of Analyses (ICEMAN) for meta-analyses. RESULTS: A total of 36 trials (26 on BM-MNCs and 10 on MSCs) with 2489 patients (1466 were transplanted [1241 with BM-MNCs and 225 with MSCs] and 1023 as controls) were included. Both types of cells showed significant improvements in ejection fraction in short-term follow-up (BM-MNCs: WMD = 2.13%, 95% CI = 1.23 to 3.04, p < 0.001; MSCs: WMD = 3.71%, 95% CI = 2.32 to 5.09, p < 0.001), and according to ICEMAN criteria, MSCs are more effective. For selected population of patients who received stem cell transplantation in early course after AMI (less than 11 days), this effect was even more pronounced (BM-MNC: WMD = 3.07%, 95% CI = 1.97 to 4.17, p < 0.001, I2 = 40.7%; MSCs: WMD = 5.65%, 95% CI = 3.47 to 7.84, p < 0.001, I2 = 84.6%). CONCLUSION: Our results showed that transplantation of MSCs after AMI might increase LVEF more than BM-MNCs; also, based on ICEMAN, there was likely effect modification between subgroups although uncertainty still remained.