Citations

ABSTRACTBackgroundDespite an increasing number of publications on Peyronie’s disease (PD), evidence-based clinical decision-making remains challenging due to the small number of well-designed clinical trials.AimTo perform a critical analysis of reporting quality in PD systematic reviews (SR) and meta-analyses (MA).MethodsStudy protocol registration was performed on the Open Science Framework platform. In January 2021, a systematic electronic search of the Medline/PubMed, Embase, Ovid, Scopus, Joanne Briggs Institute, and Cochrane databases was performed. Search terms included “Peyronie’s disease” and “systematic review OR meta-analysis OR meta-analysis.” Eligibility criteria were English-language, relevance to PD and specification of “systematic review” or “meta-analysis” in the title or abstract. Oxford Center for Evidence-Based Medicine levels of evidence were used to classify original studies reviewed within each publication. Risk of bias was assessed using the ROBIS tool. Data were tabulated and reported as means with standard deviation, median with interquartile range and t-testing as appropriate. Strength of association between variables was calculated using Pearson correlation coefficient. Statistical analyses were performed on RStudio (version 1.4.1106).OutcomesOutcomes included review type, level of evidence, authorship, journal, publication date, “A MeaSurement Tool to Assess systematic Reviews” (AMSTAR-2) score and “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) score.ResultsFrom 1974 to 2021, 340 articles were identified. After review, 17 full length articles were included. Thirteen were SR, 2 MA and 2 was combined. Significant heterogeneity was seen in evidence level of included studies. There was median 54% adherence to AMSTAR-2 criteria and 74% adherence to PRISMA criteria. Overall AMSTAR-2 confidence rating was Critically Low in 11 of 17 studies. Correlation analysis revealed very high positive association between AMSTAR 2 and PRISMA adherence (+0.95). ROBIS revealed “High” concern regarding methods used to collect data and appraise 12/17 studies (71%), and “High” concern regarding synthesis and findings in 8 of 17 studies (47%).Clinical ImplicationsMany SR include markedly heterogenous levels of evidence and fail to meet accepted methodological criteria for reporting.Strengths and LimitationsMain strengths include extensive literature review and analysis of standardized study reporting. One limitation is that aggregate scoring of AMSTAR-2 and PRISMA is not intended as primary method of quality assessment; however effect was minimized by reporting critical domains, overall quality assessments and specifics on globally poorly reported domains.ConclusionMore high quality randomized controlled PD trials are necessary; SR and MA should focus on these studies alone.

Abstract Aims Mitral valve prolapse (MVP) is a common valvular heart disease with a prevalence of >2% in the general adult population. Despite this high incidence, there is a limited understanding of the molecular mechanism of this disease, and no medical therapy is available for this disease. We aimed to elucidate the genetic basis of MVP in order to better understand this complex disorder. Methods and results We performed a meta-analysis of six genome-wide association studies that included 4884 cases and 434 649 controls. We identified 14 loci associated with MVP in our primary analysis and 2 additional loci associated with a subset of the samples that additionally underwent mitral valve surgery. Integration of epigenetic, transcriptional, and proteomic data identified candidate MVP genes including LMCD1, SPTBN1, LTBP2, TGFB2, NMB, and ALPK3. We created a polygenic risk score (PRS) for MVP and showed an improved MVP risk prediction beyond age, sex, and clinical risk factors. Conclusion We identified 14 genetic loci that are associated with MVP. Multiple analyses identified candidate genes including two transforming growth factor-β signalling molecules and spectrin β. We present the first PRS for MVP that could eventually aid risk stratification of patients for MVP screening in a clinical setting. These findings advance our understanding of this common valvular heart disease and may reveal novel therapeutic targets for intervention.

Abstract Aims Contemporary cardiac intensive care unit (CICU) outcomes remain highly heterogeneous. As such, a risk-stratification tool using readily available lab data at time of CICU admission may help inform clinical decision-making. Methods and results The primary derivation cohort included 4352 consecutive CICU admissions across 25 tertiary care CICUs included in the Critical Care Cardiology Trials Network (CCCTN) Registry. Candidate lab indicators were assessed using multivariable logistic regression. An integer risk score incorporating the top independent lab indicators associated with in-hospital mortality was developed. External validation was performed in a separate CICU cohort of 9716 patients from the Mayo Clinic (Rochester, MN, USA). On multivariable analysis, lower pH [odds ratio (OR) 1.96, 95% confidence interval (CI) 1.72–2.24], higher lactate (OR 1.40, 95% CI 1.22–1.62), lower estimated glomerular filtration rate (OR 1.26, 95% CI 1.10–1.45), and lower platelets (OR 1.18, 95% CI 1.05–1.32) were the top four independent lab indicators associated with higher in-hospital mortality. Incorporated into the CCCTN Lab-Based Risk Score, these four lab indicators identified a 20-fold gradient in mortality risk with very good discrimination (C-index 0.82, 95% CI 0.80–0.84) in the derivation cohort. Validation of the risk score in a separate cohort of 3888 patients from the Registry demonstrated good performance (C-index of 0.82; 95% CI 0.80–0.84). Performance remained consistent in the external validation cohort (C-index 0.79, 95% CI 0.77–0.80). Calibration was very good in both validation cohorts (r = 0.99). Conclusion A simple integer risk score utilizing readily available lab indicators at time of CICU admission may accurately stratify in-hospital mortality risk.

Objective: In a randomized trial, we aimed to evaluate the efficacy of cosyntropin injectable suspension, 1 mg/mL, compared to vigabatrin for infantile spasms syndrome. An additional arm was included to assess the efficacy of combination therapy (cosyntropin and vigabatrin) compared with cosyntropin monotherapy. Methods: Children (2 months to 2 years) with new-onset infantile spasms syndrome and hypsarhythmia were randomized into 3 arms: cosyntropin, vigabatrin, and cosyntropin and vigabatrin combined. Daily seizures and adverse events were recorded, and EEG was repeated at day 14 to assess for resolution of hypsarhythmia. The primary outcome measure was the composite of resolution of hypsarhythmia and absence of clinical spasms at day 14. Fisher exact test was used to compare outcomes. Results: 37 children were enrolled and 34 were included in the final efficacy analysis (1 withdrew prior to treatment and 2 did not return seizure diaries). Resolution of both hypsarhythmia and clinical spasms was achieved in in 9 of 12 participants (75%) treated with cosyntropin, 1/9 (11%) vigabatrin, and 5/13 (38%) cosyntropin and vigabatrin combined. The primary comparison of cosyntropin versus vigabatrin was significant (64% [95% confidence interval 21, 82], P < .01). Adverse events were reported in all 3 treatment arms: 31 (86%) had an adverse event, 7 (19%) had a serious adverse event, and 15 (42%) had an adverse event of special interest with no difference between treatment arms. Significance: This randomized trial was underpowered because of incomplete enrollment, yet it demonstrated that cosyntropin was more effective for short-term outcomes than vigabatrin as initial treatment for infantile spasms.

Abstract The goal of therapy for patients with essential thrombocythemia (ET) and polycythemia vera (PV) is to reduce thrombotic events by normalizing blood counts. Hydroxyurea (HU) and interferon-α (IFN-α) are the most frequently used cytoreductive options for patients with ET and PV at high risk for vascular complications. Myeloproliferative Disorders Research Consortium 112 was an investigator-initiated, phase 3 trial comparing HU to pegylated IFN-α (PEG) in treatment-naïve, high-risk patients with ET/PV. The primary endpoint was complete response (CR) rate at 12 months. A total of 168 patients were treated for a median of 81.0 weeks. CR for HU was 37% and 35% for PEG (P = .80) at 12 months. At 24 to 36 months, CR was 20% to 17% for HU and 29% to 33% for PEG. PEG led to a greater reduction in JAK2V617F at 24 months, but histopathologic responses were more frequent with HU. Thrombotic events and disease progression were infrequent in both arms, whereas grade 3/4 adverse events were more frequent with PEG (46% vs 28%). At 12 months of treatment, there was no significant difference in CR rates between HU and PEG. This study indicates that PEG and HU are both effective treatments for PV and ET. With longer treatment, PEG was more effective in normalizing blood counts and reducing driver mutation burden, whereas HU produced more histopathologic responses. Despite these differences, both agents did not differ in limiting thrombotic events and disease progression in high-risk patients with ET/PV. This trial was registered at www.clinicaltrials.gov as #NCT01259856.

ABSTRACTBackgroundCongenital penile curvature (CPC) is corrected surgically by various corporoplasty or tunica albuginea plication techniques, but the optimal surgical approach is not well-defined.AimTo provide a comprehensive evaluation of the published literature pertaining to outcomes with penile plication and corporoplasty techniques for surgical management of CPC. To determine if plication or corporoplasty offers superior outcomes in surgical correction of CPC.MethodsA systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Checklist. The following databases were queried from inception to March 18, 2020 to search for studies describing surgical treatment of CPC: Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus.OutcomesObjective and subjective postoperative outcomes including penile straightening, shortening, penile sensory changes, and reoperation rates for both corporoplasty and tunica albuginea plication were summarized.ResultsFifty-five articles comprising 2,956 patients with CPC who underwent a plication procedure (n = 1,375) or corporoplasty (n = 1,580) were included. The definition of “treatment success” varied widely and most often involved subjective patient reporting (22 studies; 40%) or objective assessment (15 studies; 27%). We considered curvature correction to be satisfactory if there was self-reported patient satisfaction or residual curvature after correction of &lt;20˚. Reported rates of successful straightening ranged from 75 to 100% and 73 to 100% for plication and corporoplasty, respectively. A comprehensive and accurate assessment of surgical outcomes for CPC correction, such as satisfactory penile straightening, reoperation rates, glans sensory changes, and other complications was limited by significant inter-study heterogeneity with respect to the reporting of treatment outcomes.Clinical ImplicationsWhile both plication and corporoplasty appear to be safe and effective options in the treatment of CPC, definitive conclusions cannot be drawn with respect to treatment superiority due to low-quality study design, methodology flaws, and significant heterogeneity in reporting.Strength & LimitationsThis report represents the most comprehensive review of CPC surgical management. However, there is a significant lack of standardization in the reporting of treatment outcomes for CPC, thereby limiting the reliability of the published data summarization encompassed by our review.ConclusionBoth plication and corporoplasty demonstrate high success rates and relatively low complication rates in the treatment of CPC, albeit with low-level evidence available in most research publications. Robust comparison of the surgical techniques used to correct CPC is limited by significant variation in reporting methods used in the literature.

Abstract Purpose To provide guidance to clinicians regarding therapy for patients with brain metastases from solid tumors. Methods ASCO convened an Expert Panel and conducted a systematic review of the literature. Results Thirty-two randomized trials published in 2008 or later met eligibility criteria and form the primary evidentiary base. Recommendations Surgery is a reasonable option for patients with brain metastases. Patients with large tumors with mass effect are more likely to benefit than those with multiple brain metastases and/or uncontrolled systemic disease. Patients with symptomatic brain metastases should receive local therapy regardless of the systemic therapy used. For patients with asymptomatic brain metastases, local therapy should not be deferred unless deferral is specifically recommended in this guideline. The decision to defer local therapy should be based on a multidisciplinary discussion of the potential benefits and harms that the patient may experience. Several regimens were recommended for non–small-cell lung cancer, breast cancer, and melanoma. For patients with asymptomatic brain metastases and no systemic therapy options, stereotactic radiosurgery (SRS) alone should be offered to patients with one to four unresected brain metastases, excluding small-cell lung carcinoma. SRS alone to the surgical cavity should be offered to patients with one to two resected brain metastases. SRS, whole brain radiation therapy, or their combination are reasonable options for other patients. Memantine and hippocampal avoidance should be offered to patients who receive whole brain radiation therapy and have no hippocampal lesions and 4 months or more expected survival. Patients with asymptomatic brain metastases with either Karnofsky Performance Status ≤ 50 or Karnofsky Performance Status &lt; 70 with no systemic therapy options do not derive benefit from radiation therapy. Additional information is available at www.asco.org/neurooncology-guidelines.

PURPOSE To provide guidance to clinicians regarding therapy for patients with brain metastases from solid tumors. METHODS ASCO convened an Expert Panel and conducted a systematic review of the literature. RESULTS Thirty-two randomized trials published in 2008 or later met eligibility criteria and form the primary evidentiary base. RECOMMENDATIONS Surgery is a reasonable option for patients with brain metastases. Patients with large tumors with mass effect are more likely to benefit than those with multiple brain metastases and/or uncontrolled systemic disease. Patients with symptomatic brain metastases should receive local therapy regardless of the systemic therapy used. For patients with asymptomatic brain metastases, local therapy should not be deferred unless deferral is specifically recommended in this guideline. The decision to defer local therapy should be based on a multidisciplinary discussion of the potential benefits and harms that the patient may experience. Several regimens were recommended for non–small-cell lung cancer, breast cancer, and melanoma. For patients with asymptomatic brain metastases and no systemic therapy options, stereotactic radiosurgery (SRS) alone should be offered to patients with one to four unresected brain metastases, excluding small-cell lung carcinoma. SRS alone to the surgical cavity should be offered to patients with one to two resected brain metastases. SRS, whole brain radiation therapy, or their combination are reasonable options for other patients. Memantine and hippocampal avoidance should be offered to patients who receive whole brain radiation therapy and have no hippocampal lesions and 4 months or more expected survival. Patients with asymptomatic brain metastases with either Karnofsky Performance Status ≤ 50 or Karnofsky Performance Status < 70 with no systemic therapy options do not derive benefit from radiation therapy. Additional information is available at www.asco.org/neurooncology-guidelines .