Vagal dysautonomia in patients with Chagas disease and mortality: 14-year results of a population cohort of the elderly.

INTRODUCTION: Great part of Chagas disease (ChD) mortality occurs due to ventricular arrhythmias, and autonomic function (AF) may predict unfavorable outcomes. We aimed to evaluate the predictive value of AF indexes in ChD patients. METHODS: The Bambuí Study of Aging is a prospective cohort of residents ≥60 years at study onset (1997), in the southeastern Brazilian city of Bambuí (15,000 inhabitants). Consented participants underwent annual follow-up visits, and death certificates were tracked. AF was assessed by the maximum expiration on minimum inspiration (E:I) ratio during ECG acquisition and by heart rate variability indices: SDRR (standard deviation of adjacent RR intervals) and RMSSD (square root of the mean of the sum of squares of the differences between adjacent RR intervals)), calculated using a computer algorithm. Cox proportional hazards regression was performed to access the prognostic value of AF indexes, expressed as terciles, for all-cause mortality, after adjustment for demographic, clinical and ECG variables. RESULTS: From 1742 qualifying residents, 1000 had valid AF tests, being 321 with ChD. Among these, median age was 68 (64-74) years, and 32.5% were men. In Cox survival analyses, only SDRR was associated with all-cause mortality in non-adjusted models: SDRR (hazard ratio (HR): 1.26 (95% CI 1.08-1.47), p < 0.001), E:I ratio (HR: 1.13 (95% CI 0,98-1.31), p = 0.10) and RMSSD (HR: 0.99 (0.86-1.16), p = 0.95). After adjustment for sex and age, none of the indexes remained as independent predictors. CONCLUSION: Among elderly patients with ChD, AF indexes available in this cohort were not independent predictors of 14-year mortality.

Novel Foscan®-derived ring-fused chlorins for photodynamic therapy of cancer.

Photodynamic therapy (PDT) is an established anticancer treatment that combines the use of a photosensitiser (PS) and a light source of a specific wavelength for the generation of reactive oxygen species (ROS) that are toxic to the tumour cells. Foscan® (mTHPC) is a clinically-approved chlorin used for the PDT treatment of advanced head and neck, prostate and pancreatic cancers but is characterized by being photochemically unstable and associated with prolonged skin photosensitivity. Herein, we report the synthesis of new 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused chlorins, having the meso-tetra(3-hydroxyphenyl)macrocycle core of mTHPC, by exploring the [8π + 2π] cycloaddition of a meso-tetra(3-hydroxyphenyl)porphyrin derivative with diazafulvenium methides. These chlorins have photochemical properties similar to Foscan® but are much more photostable. Among the novel compounds, two chlorins with a hydroxymethyl group and its azide derivative present in the 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused system, are promising photodynamic agents with activity in the 100 nM range against triple-negative breast cancer cells and, in the case of azidomethyl chlorin, a safer phototherapeutic index compared to Foscan®.

Early triage echocardiography to predict outcomes in patients admitted with COVID-19: a multicenter study.

INTRODUCTION: Cardiac involvement seems to impact prognosis of COVID-19, especially in critically ill patients. We aimed to assess the prognostic value of right ventricular (RV) and left ventricular (LV) dysfunction, evaluated by bedside triage echocardiography (echo), in patients admitted to emergency departments (ED) in the US with COVID-19. We also assessed the feasibility of using cloud imaging for sharing and interpreting echocardiograms. METHODS: Patients admitted to three reference EDs with confirmed COVID-19 underwent triage echo within 72 h of symptom onset with remote interpretation. Clinical and laboratory data, as well as COVID-19 symptoms, were collected. The association between echo variables, demographics and clinical data with all-cause hospital mortality and intensive care unit (ICU) admission was assessed using logistic regression. RESULTS: Three hundred ninety-nine patients were enrolled, 41% women, with a mean age of 62±16 years. Mean oxygen saturation on presentation was 92.3± 9.2%. Compared to in-hospital survivors, non-survivors were older, had lower oxygen saturation on presentation, were more likely to have a chronic condition and had lower LV ejection fraction (50.3±19.7% vs. 58.0±13.6%) (P < .05). In the cohort, 101 (25%) patients had moderate/severe LV dysfunction, 131 (33%) had moderate/severe RV dysfunction. Advanced age and lower oxygen saturation were independently associated with death and ICU admission. LV and RV function, or other echo variables, were not independent predictors of outcomes. CONCLUSION: In patients admitted with COVID-19 undergoing early echo triage, the independent predictors of death and ICU admission were age and oxygen saturation. The inclusion of echo variables did not improve prediction of unfavorable outcomes.

Influenza vaccination strategy in acute coronary syndromes: the VIP-ACS trial.

AIMS: To evaluate whether a strategy of double-dose influenza vaccination during hospitalization for an acute coronary syndrome (ACS) compared with standard-dose outpatient vaccination (as recommended by current guidelines) would further reduce the risk of major cardiopulmonary events. METHODS AND RESULTS: Vaccination against Influenza to Prevent cardiovascular events after Acute Coronary Syndromes (VIP-ACS) was a pragmatic, randomized, multicentre, active-comparator, open-label trial with blinded outcome adjudication comparing two strategies of influenza vaccination following an ACS: double-dose quadrivalent inactivated vaccine before hospital discharge vs. standard-dose quadrivalent inactivated vaccine administered in the outpatient setting 30 days after randomization. The primary outcome was a hierarchical composite of all-cause death, myocardial infarction, stroke, unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory causes, analysed by the win ratio method. Patients were followed for 12 months. During two influenza seasons, 1801 participants were included at 25 centres in Brazil. The primary outcome was not different between groups, with 12.7% wins in-hospital double-dose vaccine group and 12.3% wins in the standard-dose vaccine group {win ratio: 1.02 [95% confidence interval (CI): 0.79-1.32], P = 0.84}. Results were consistent for the key secondary outcome, a hierarchical composite of cardiovascular death, myocardial infarction and stroke [win ratio: 0.94 (95% CI: 0.66-1.33), P = 0.72]. Time-to-first event analysis for the primary outcome showed results similar to those of the main analysis [hazard ratio 0.97 (95% CI: 0.75-1.24), P = 0.79]. Adverse events were infrequent and did not differ between groups. CONCLUSION: Among patients hospitalized with an ACS, double-dose influenza vaccination before discharge did not reduce cardiopulmonary outcomes compared with standard-dose vaccination in the outpatient setting. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number: NCT04001504.

Different plant compartments, different yeasts: The example of the bromeliad phyllosphere.

The plant phyllosphere is one of the largest sources of microorganisms, including yeasts. In bromeliads, the knowledge of yeasts is dispersed and still incipient. To understand the extent of our knowledge of the subject, this review proposes to compile and synthesize existing knowledge, elucidating possible patterns, biotechnological and taxonomic potentials, bringing to light new knowledge, and identifying information gaps. For such, we systematically review scientific production on yeasts in bromeliads using various databases. The results indicated that the plant compartments flowers, fruits, leaves, and water tank (phytotelma) have been studied when focusing on the yeast community in the bromeliad phyllosphere. More than 180 species of yeasts and yeast-like fungi were recorded from the phyllosphere, 70% were exclusively found in one of these four compartments and only 2% were shared among all. In addition, most of the community had a low frequency of occurrence, and approximately half of the species had a single record. Variables such as bromeliad subfamilies and functional types, as well as plant compartments, were statistically significant, though inconclusive and with low explanatory power. At least 50 yeast species with some biotechnological potentials have been isolated from bromeliads. More than 90% of these species were able to produce extracellular enzymes. In addition, other biotechnological applications have also been recorded. Moreover, new species have been described, though yeasts were only exploited in approximately 1% of the existing bromeliads species, which highlights that there is still much to be explored. Nevertheless, it appears that we are still far from recovering the completeness of the diversity of yeasts in this host. Furthermore, bromeliads proved to be a good ecological model for prospecting new yeasts and for studies on the interaction between plants and yeasts. In addition, the yeast community diverged among plant compartments, establishing bromeliads as a microbiologically complex and heterogeneous mosaic.

Grafting Area Reduction in Peyronie's Disease Surgery: Comparative Assessment Between Double Y Vs iGrafter APP Using 3D-Printed Penile Models.

BACKGROUND: The use of plaque incision and graft techniques (PIG) for the treatment of severe Peyronie's disease (PD), may lead to erectile dysfunction (ED); graft size is 1 of the contributing factors for post-PIG ED. Recently the iGrafter software APP was introduced using a mathematical algorithm to distribute the incisions along the penile length resulting in a smaller grafting area. AIM: Compare 2 PIG techniques, the Double-Y(DY) and iGrafter, in 3 main aspects: (i) Total grafting area; (ii) The variation in calculating the grafting to be used; (iii) time to perform the PIG. METHODS: Six urologists with expertise in sexual medicine performed both techniques twice using four 3-D validated training models for PD with a standard 60° uniplanar dorsal curvature. OUTCOMES: The graft areas and operative partial and total time for each step of the operation were recorded for each procedure. Unpaired t-test and the coefficient of variation for graft area across surgeons was calculated comparing both techniques. RESULTS: For all surgeons, the use of iGrafter resulted in 2 grafts, for the DY technique in 1 graft. Overall, TT for the iGrafter was significantly longer than for DY technique (49.4 ± 11 vs 40.7 ± 5.7 minute; P = .02), The iGrafter grafting area was significantly smaller (11.6 ± 1.2 vs 23.3 ± 5.4 cm2; P: .01), representing a 50.2% area reduction when compared to the DY. The variation of graft area, using the iGrafter also yielded a more consistent graft across all surgeons (CV = 10.56% vs 23.28%). CLINICAL SIGNIFICANCE: The iGrafter, when compared to DY technique, reduced the graft area by 50%, which potentially means less erectile dysfunction. STRENGTHS AND LIMITATIONS: Our study eliminates anatomical variations found in a real clinical case making it possible to compare surgical techniques with the same penile anatomy. However, the 3D-printed model cannot replicate the living human tissue property preventing a simulation close to actual surgery. CONCLUSION: The use of the iGrafter software for PIG surgery has shown to be a promising technique for severe PD management resulting in smaller graft size (about 50% smaller when compared to the DY), although it might be more time-consuming. Tourchi A, Nascimento B, de Freita Miranda A, et al. Grafting Area Reduction in Peyronie's Disease Surgery: Comparative Assessment Between Double Y Vs iGrafter APP Using 3D-Printed Penile Models. J Sex Med 2022;19:669-675.

The Relationship Between PSA and Total Testosterone Levels in Men With Prostate Cancer.

BACKGROUND: Prostate-specific antigen (PSA) secretion is a testosterone (T) dependent process. Published data suggest that a low T level is an independent predictor of higher-grade prostate cancer (PC). AIM: To evaluate the relationship between T and PSA in patients with PC. METHODS: All men diagnosed with PC with a recorded pre-treatment total T level measurement were included in this analysis. We analyzed demographic, clinical, and pathological data. Patients were stratified according to pretreatment PSA levels: <2 ng/mL, 2-4 ng/mL, >4 ng/mL. Low T was defined as total T < 10.4 nmol/L (300 ng/dL), very low T < 6.9 nmol/L (200 ng/dL). OUTCOMES: T levels by PSA groups according to the PC pathology. RESULTS: In this retrospective study, mean patient age was 61 years among 646 men. The distribution by PSA group was: 8% (<2), 17% (2-4), and 76% (>4). The mean T level across the entire cohort was 13 nmol/L (374 ng/dL). Overall, 30% had a T level < 10.4 nmol/L (300 ng/dL). The mean total T level by PSA group was: <2 ng/mL, 7 nmol/L (206 ng/dL); 2-4 ng/mL, 13 nmol/L (362 ng/dL); >4 ng/mL, 14 nmol/L (393 ng/dL), P < .001. PSA <4 ng/mL was a significant predictor of low T in men with PC GS ≥8. PSA <2 ng/mL was a significant predictor of very low T independent of the PC pathology. CLINICAL IMPLICATIONS: These findings suggest that clinicians should consider measuring T levels when a patient diagnosed with PC GS ≥8 and PSA level <4 ng/mL, and for each patient with PSA level <2 ng/mL independent of the PC pathology. STRENGTHS & LIMITATIONS: Our study has several strengths including (i) inclusion of a large population of men, (ii) use of a database which is audited and reviewed for accuracy annually, and (iii) use of an accurate T assay (LCMS). Nonetheless, there are limitations: (i) the subjects of the study are from a single institution, and (ii) we did not measure free T levels. CONCLUSION: In men with PC with GS ≥8, PSA level <4 ng/mL predicts low T. PSA <2 ng/mL predicts very low T independent of the PC pathology. Flores JM, Bernie HL, Miranda E, et al. The Relationship Between PSA and Total Testosterone Levels in Men With Prostate Cancer. J Sex Med 2022;19:471-478.

Predictors of Worsening Erectile Function in Men with Functional Erections Early After Radical Prostatectomy.

BACKGROUND: Prior studies suggest that men with good erectile function shortly after radical prostatectomy (RP) can subsequently have worsened erectile function. AIM: To determine the prevalence and predictors of early erectile function recovery post-RP and of worsening erectile function after initial erectile function recovery. METHODS: We retrospectively queried our institutional database. Men who underwent RP during 2008-2017 and who completed the International Index of Erectile Function erectile function domain both pre-RP and serially post-RP, constituted the population. Functional erections were defined as International Index of Erectile Function (IIEF)-6 erectile function domain scores ≥24. We analyzed factors predicting functional erections at 3 months post-RP as well as factors predicting a decrease in functional erections between 3 and 6 months, defined as ≥2-point drop in the erectile function domain. Multivariable logistic regression models were used to identify predictors of early erectile function recovery and also of subsequent decline. OUTCOMES: Erectile function recovery rates at 3 months post-RP and predictive factors; rates of erectile function decline between 3-6 months and associated predictors. RESULTS: Eligible patients comprised 1,655 men with median age of 62 (IQR 57, 67) years. Bilateral nerve-sparing (NS) surgery was performed in 71% of men, unilateral NS in 19%, and no NS in 10%. Of this population, 224 men (14%; 95% CI 12%, 15%) had functional erections at 3 months post-RP. On multivariable analysis, significant predictors of early erectile function recovery included: younger age (OR 0.93, P < .001), higher baseline erectile function domain score (OR 1.14, P < .001) and bilateral NS (OR 3.81, P = .002). The presence of diabetes (OR 0.43, P = .028) and a former smoking history (OR 0.63, P = .008; reference group: never smoker) was associated with the erectile dysfunction at 3 months post-RP. Of the men with early functional erections, 41% (95% CI 33%, 48%) had a ≥ 2-point decline in erectile function between 3 and 6 months. No factors were identified as predictors for this decline. CLINICAL IMPLICATIONS: Only a small proportion of men have functional erections at 3 months post-RP and a notable number of them will experience a decline in erectile function between 3 and 6 months. STRENGTHS AND LIMITATIONS: Strengths: large patient population and the use of validated questionnaire. LIMITATIONS: single-center retrospective study. CONCLUSION: A minority of men had functional erections 3 months post-RP, about half of whom had a decline in erectile function by month 6. We recommend appropriately counseling post-RP patients on the risk of such a decline in erectile function. Salter CA, Tin AL, Bernie HL, et al. Predictors of Worsening Erectile Function in Men with Functional Erections Early After Radical Prostatectomy. J Sex Med 2022;19:1790-1796.

Predictors of Curvature Improvement in Men With Peyronie's Disease Treated With Intralesional Collagenase Clostridium Histolyticum.

INTRODUCTION: Penile curvature is the most common abnormality that is observed by men with Peyronie's disease (PD). Collagenase Clostridium histolyticum (CCH) has become a standard treatment for PD patients. AIM: To identify predictor factors associated with improvements of penile curvature outcomes in men with PD treated with CCH. METHODS: We retrospectively collected the data of patients with PD treated with CCH up to 8 injections divided into 4 cycles between January 2014 and July 2020. Per protocol, penile curvature was assessed at baseline, and after the second and ford CCH cycle. If after cycle 2, curvature demonstrated no improvement, or penile curvature was significantly improved and the patient was happy, no further treatment was recommended. However, if penile curvature was significantly improved and the patient remained dissatisfied, 4 cycles were completed. Three categories of response were evaluated: improvement (≥10 degrees or ≥20%, either 1 happens), unchanged (±10 degrees or ±20%) or worsened (≥10 degrees or ≥20%, either 1 happens). Logistic regression analyses were performed to evaluate predictive factors associated with penile curvature improvements. OUTCOMES: Degrees of the curvature changes between the baseline and after the cycles of CCH. RESULTS: A total of 114 patients underwent CCH treatment. Median age was 57 years. Median PD duration was 11 months. At baseline, mean curvature was 47 degrees, 65% had dorsal curvature, 53% mid-shaft location, and 15% calcification. After CCH treatment, the mean final curvature was 40 degrees. A total of 44% improved the curvature, 39% had no change while 17% worsened after CCH treatment. Of men who had penile curvature improvement with CCH treatment, the mean curvature decreasing in degrees and percentage were 22 degrees and 41%, respectively. Men with baseline curvature ≤ 30, 31-59, and ≥ 60 degrees, the percentage curvature improvement were 29%, 43%, and 60%, respectively. Baseline curvature was the only significant predictor of penile curvature improvement after CCH (OR 1.33, 95% CI = 1.1, 1.7). CLINICAL IMPLICATIONS: We confirmed baseline penile curvature is the most important predictive factor, and this is the first report describing proportions of penile curvature improvement with CCH treatment. STRENGTHS AND LIMITATIONS: This study has several strengths, including the use of validated instruments. Nonetheless, there are limitations: the retrospective nature of the study, a single institution; and modelling device was not controlled. CONCLUSION: Penile curvature improvement was significantly more common in patients with greater baseline curvature, reaching up to 60% for patients with ≥ 60 degrees. Flores JM, Nascimento B, Punjani N, et al. Predictors of Curvature Improvement in Men With Peyronie's Disease Treated With Intralesional Collagenase Clostridium Histolyticum. J Sex Med 2022;19:1680-1686.

The Burden of Resistant Hypertension Across the World.

PURPOSE OF REVIEW: Resistant hypertension (R-HTN) is related to worse cardiovascular, renal outcomes, and death compared to non R-HTN. We aimed to review the burden of R-HTN across the world, focusing on its prevalence, associated factors and outcomes, and the impact of treatment. RECENT FINDINGS: R-HTN prevalence among hypertensive individuals varies around 10-20%, depending on the population and definition applied. R-HTN consistently relates to older age, chronic kidney disease, obesity, and obstructive sleep apnea - which are increasing in prevalence with global population aging. As such, R-HTN prevalence is also expected to rise. Infrequent use of ambulatory blood pressure monitoring to identify at higher risk individuals and poor adherence to treatment are still barriers in the approach of R-HTN. Available evidence suggests that 10-20% of patients with hypertension have R-HTN. However, the prevalence of true R-HTN using contemporaneous standardized definitions is still unknown. Novel strategies to address clinicians, patients and health system barriers to treatment inertia and adherence are fundamental to reduce the burden of R-HTN.

Racial disparity in excess mortality in Brazil during COVID-19 times.

We evaluated the impact of the COVID-19 pandemic on excess mortality by race/skin colour in Brazil, between epidemiological weeks 12 and 50 of 2020. We compared the 2020 point estimate and the expected point estimate applying 2019 mortality rates to the 2020 population. There was an excess of 187 002 deaths (+20.2%) compared to the expected. Excess mortality was 26.3% (23.3-29.3%) among blacks/browns compared to 15.1% (14.1-16.1%) among whites (58.9% of excess among black/browns). Age-standardized rates increased from 377 to 419/100 000 among blacks/browns compared to 328 to 398/100 000 in whites, resulting in 9% relative risk. Excess mortality in Brazil depicts a considerable gap, with increased mortality in all age groups in the black/brown population.

Cytokine gene functional polymorphisms and phenotypic expression as predictors of evolution from latent to clinical rheumatic heart disease.

INTRODUCTION: Inflammation associated with rheumatic heart disease (RHD) is influenced by gene polymorphisms and inflammatory cytokines. There are currently no immunologic and genetic markers to discriminate latent versus clinical patients, critical to predict disease evolution. Employing machine-learning, we searched for predictors that could discriminate latent versus clinical RHD, and eventually identify latent patients that may progress to clinical disease. METHODS: A total of 212 individuals were included, 77 with latent, 100 with clinical RHD, and 35 healthy controls. Circulating levels of 27 soluble factors were evaluated using Bio-Plex ProTM® Human Cytokine Standard 27-plex assay. Gene polymorphism analyses were performed using RT-PCR for the following genes: IL2, IL4, IL6, IL10, IL17A, TNF and IL23. RESULTS: Serum levels of all cytokines were higher in clinical as compared to latent RHD patients, and in those groups than in controls. IL-4, IL-8, IL-1RA, IL-9, CCL5 and PDGF emerged in the final multivariate model as predictive factors for clinical, compared with latent RHD. IL-4, IL-8 and IL1RA had the greater power to predict clinical RHD. In univariate analysis, polymorphisms in IL2 and IL4 were associated with clinical RHD and in the logistic analysis, IL6 (GG + CG), IL10 (CT + TT), IL2 (CA + AA) and IL4 (CC) genotypes were associated with RHD. CONCLUSION: Despite higher levels of all cytokines in clinical RHD patients, IL-4, IL-8 and IL-1RA were the best predictors of clinical disease. An association of polymorphisms in IL2, IL4, IL6 and IL10 genes and clinical RHD was observed. Gene polymorphism and phenotypic expression of IL-4 accurately discriminate latent versus clinical RHD, potentially instructing clinical management.

Systemic cytokines, chemokines and growth factors reveal specific and shared immunological characteristics in infectious cardiomyopathies.

Heart disease is a major cause of death worldwide. Chronic Chagas cardiomyopathy (CCC) caused by infection with Trypanosoma cruzi leading to high mortality in adults, and rheumatic heart disease (RHD), resulting from infection by Streptococcus pyogenes affecting mainly children and young adults, are amongst the deadliest heart diseases in low-middle income countries. Despite distinct etiology, the pathology associated with both diseases is a consequence of inflammation. Here we compare systemic immune profile in patients with these cardiopathies, to identify particular and common characteristics in these infectious heart diseases. We evaluated the expression of 27 soluble factors, employing single and multivariate analysis combined with machine-learning approaches. We observed that, while RHD and CCC display higher levels of circulating mediators than healthy individuals, CCC is associated with stronger immune activation as compared to RHD. Despite distinct etiologies, univariate analysis showed that expression of TNF, IL-17, IFN-gamma, IL-4, CCL4, CCL3, CXCL8, CCL11, CCL2, PDGF-BB were similar between CCC and RHD, consistent with their inflammatory nature. Network analysis revealed common inflammatory pathways between CCC and RHD, while highlighting the broader reach of the inflammatory response in CCC. The final multivariate model showed a 100% discrimination power for the combination of the cytokines IL-12p70, IL-1Ra, IL-4, and IL-7 between CCC and RHD groups. Thus, while clear immunological distinctions were identified between CCC and RHD, similarities indicate shared inflammatory pathways in these infectious heart diseases. These results contribute to understanding the pathogenesis of CCC and RHD and may impact the design of immune-based therapies for these and other inflammatory cardiopathies that may also share immunological characteristics.

Predictors of Pursuing Intralesional Xiaflex in Peyronie's Disease Patients.

BACKGROUND: Intralesional collagenase such as Xiaflex (ILX) has become a standard treatment for Peyronie's disease (PD). Many robust studies have demonstrated its clear efficacy in the treatment algorithm. AIM: To examine predictors of the patient decision to pursue ILX in PD patients. METHODS: The study included PD patients (i) with stable disease (ii) who had doppler duplex ultrasonography (DUS) at least 6 months prior to analysis date and (iii) did not choose an operation. All patients received a standard discussion regarding treatment options, specifically, observation, ILX and penile reconstructive surgery (plication, plaque incision and grafting, implant surgery). Patients who opted to use ILX were compared to those who opted against it. Comorbidity, demographic and PD characteristics were recorded at the initial PD visit. All patients completed three validated questionnaires including the PD questionnaire (PDQ), Self-Esteem and Relationship (SEAR) questionnaire and a depression questionnaire (CES-D). Logistic regression was used to determine predictors of ILX use. OUTCOMES: Predictors of ILX utilization. RESULTS: Four hundred and fifty stable PD men had DUS completed 6 months before to allow sufficient time for treatment decision. Of these, 111 (24.7%) patients had ILX treatment and 339 (75.3%) did not. Mean age, relationship status and pain occurrence were similar between groups, but ILX patients had less bother defined as PDQ ≥ 9 (46.8% vs 53.7%, P = .02). ILX patients had more complex curves (79.3% vs 47.8%, P < .01) and more severe instability (32.4% vs 15.3%, P = .01). ILX patients also had higher PDQ domain scores (Psychological 11.5 ± 6.4 vs 7.5 ± 6.2, P < .01; Pain 6.2 ± 6.0 vs 4.3 ± 5.6, P = .02; and Bother 9.8 ± 4.7 vs 6.6 ± 4.8, P < .01). On univariable statistics, significant bother (OR 2.41, 95% CI 1.36-4.28, P<0.01), complex curvature (OR 4.18, 95%CI 2.52-6.93, P < .01), moderate and/or severe instability (OR 1.98, 95%CI 1.18-3.30, P < .01) and PDQ-Bother scores (OR 1.15, 95%CI 1.08-1.22 P < .01) predicted ILX use. On multivariable analysis, instability (OR 2.58, 95%CI 1.02-6.57, P = .05) and significant bother (OR 1.23, 95%CI 1.04-1.45, P = .01) predicted ILX use. CLINICAL IMPLICATIONS: Educates providers as to which patients are more likely to choose ILX. STRENGTHS & LIMITATIONS: Our study has a large sample size and all patients received the same standardized treatment discussion. Our study is limited by the absence of insurance data on all patients, and its retrospective single center design. CONCLUSION: ILX was chosen by the minority of stable PD patients. While moderate to severe instability and significant bother is predictive of ILX use, other demographic factors including relationship status, sexual orientation or pain were not. Punjani N, Nascimento B, Salter C, et al. Predictors of Pursuing Intralesional Xiaflex in Peyronie's Disease Patients. J Sex Med 2021;18:1258-1264.

Predictors of Depression in Men With Peyronie's Disease Seeking Evaluation.

BACKGROUND: Peyronie's disease (PD) has negative impacts on the psychosocial status of men including depression warranting clinical evaluation in up to 50% of men. AIM: To examine predictors of depression in patients with early PD seeking evaluation. METHODS: All PD patients at a high-volume PD practice underwent screening and curvature assessment after intracavernosal injection. Complex deformity was defined as any degree of multiplanar curvature, curvature >60 degrees, or presence of hourglass deformity. Men completed the PD questionnaire (PDQ), a validated depression questionnaire (CES-D) as well as the Self-Esteem and Relationship (SEAR) questionnaire. Scores of ≥16 on CES-D were considered indicative of moderate/severe depression. Predictors of the presence of depression were defined using univariable and multivariable logistic regression. OUTCOMES: Demographic, bother and curve related predictors of depression in men with PD. RESULTS: 408 men completed all questionnaires. Mean age was similar between depressed and nondepressed groups (57 ± 10 years overall, P = .60 between groups). Proportions of erectile dysfunction were similar between groups (P = .96). Mean PD duration was similar between groups (19 ± 35 months overall, P = .46 between groups). Mean degree of curvature was 38 ± 2 degrees in the depressed vs 33 ± 1 degrees in the nondepressed groups (P = .03). A complex deformity was seen in 64.5% in the depressed vs 61.5% in the nondepressed (P = .56). A total of 110 (27%) patients had CESD scores ≥16. 74% depressed men were in relationships compared to 84% nondepressed men (P < .01). Other characteristics including bother, pain, duration of disease, curve complexity and instability were similar between the two groups. On univariable analysis, factors protective against depression included being partnered (OR 0.42, 95%CI 0.24-0.75, P < .01) and higher total SEAR scores (OR 0.95, 95%CI 0.94-0.97, P < .01). Elevated PDQ domain scores were associated with depression (Psychologic Symptoms 1.05, 95%CI 1.02-1.10, P < .01; Pain 1.08, 95%CI 1.03-1.12, P < .01; Bother 1.11, 95% CI 1.05-1.68, P < .01) as well as baseline history of depression (OR 2.93, 95%CI 1.67-5.14, P < .001). On multivariable analysis, only total SEAR score remained protective against depression (OR 0.96, 95%CI 0.94-0.97, P < .001). CLINICAL IMPLICATIONS: Providers must recognize that men with PD seeking evaluation have meaningful rates of depression for which early recognition is necessary. STRENGTHS AND LIMITATIONS: Retrospective review of a large prospectively collected dataset from a single center of men with PD utilizing a validated screening tool for depression. CONCLUSION: While no significant demographic, bother or curve related factors predicted depression in early PD men seeking evaluation, it remains a significant problem warranting further prospective evaluation. P. Nahid, N. Bruno, S. Carolyn, et al. Predictors of Depression in Men With Peyronie's Disease Seeking Evaluation. J Sex Med 2021;18:783-788.

Echocardiographic screening of pregnant women by non-physicians with remote interpretation in primary care.

BACKGROUND: Impact of heart disease (HD) on pregnancy is significant. OBJECTIVE: We aimed to evaluate the feasibility of integrating screening echocardiography (echo) into the Brazilian prenatal primary care to assess HD prevalence. METHODS: Over 13 months, 20 healthcare workers acquired simplified echo protocols, utilizing hand-held machines (GE-VSCAN), in 22 primary care centres. Consecutive pregnant women unaware of HD underwent focused echo, remotely interpreted in USA and Brazil. Major HD was defined as structural valve abnormalities, more than mild valve dysfunction, ventricular systolic dysfunction/hypertrophy, or other major abnormalities. Screen-positive women were referred for standard echo. RESULTS: At total, 1 112 women underwent screening. Mean age was 27 ± 8 years, mean gestational age 22 ± 9 weeks. Major HD was found in 100 (9.0%) patients. More than mild mitral regurgitation was observed in 47 (4.2%), tricuspid regurgitation in 11 (1.0%), mild left ventricular dysfunction in 4 (0.4%), left ventricular hypertrophy in 2 (0.2%) and suspected rheumatic heart disease in 36 (3.2%): all, with mitral valve and two with aortic valve (AV) involvement. Other AV disease was observed in 11 (10%). In 56 screen-positive women undergoing standard echo, major HD was confirmed in 45 (80.4%): RHD findings in 12 patients (all with mitral valve and two with AV disease), mitral regurgitation in 40 (14 with morphological changes, 10 suggestive of rheumatic heart disease), other AV disease in two (mild/moderate regurgitation). CONCLUSIONS: Integration of echo screening into primary prenatal care is feasible in Brazil. However, the low prevalence of severe disease urges further investigations about the effectiveness of the strategy.

Impact of incorporating echocardiographic screening into a clinical prediction model to optimise utilisation of echocardiography in primary care.

INTRODUCTION: Access to public subspecialty healthcare is limited in underserved areas of Brazil, including echocardiography (echo). Long waiting lines and lack of a prioritisation system lead to diagnostic lag and may contribute to poor outcomes. We developed a prioritisation tool for use in primary care, aimed at improving resource utilisation, by predicting those at highest risk of having an abnormal echo, and thus in highest need of referral. METHODS: All patients in the existing primary care waiting list for echo were invited for participation and underwent a clinical questionnaire, simplified 7-view echo screening by non-physicians with handheld devices, and standard echo by experts. Two derivation models were developed, one including only clinical variables and a second including clinical variables and findings of major heart disease (HD) on echo screening (cut point for high/low-risk). For validation, patients were risk-classified according to the clinical score. High-risk patients and a sample of low-risk underwent standard echo. Intermediate-risk patients first had screening echo, with a standard echo if HD was suspected. Discrimination and calibration of the two models were assessed to predict HD in standard echo. RESULTS: In derivation (N = 603), clinical variables associated with HD were female gender, body mass index, Chagas disease, prior cardiac surgery, coronary disease, valve disease, hypertension and heart failure, and this model was well calibrated with C-statistic = 0.781. Performance was improved with the addition of echo screening, with C-statistic = 0.871 after cross-validation. For validation (N = 1526), 227 (14.9%) patients were classified as low risk, 1082 (70.9%) as intermediate risk and 217 (14.2%) as high risk by the clinical model. The final model with two categories had high sensitivity (99%) and negative predictive value (97%) for HD in standard echo. Model performance was good with C-statistic = 0.720. CONCLUSION: The addition of screening echo to clinical variables significantly improves the performance of a score to predict major HD.

The Global Impact of Rheumatic Heart Disease.

PURPOSE OF REVIEW: Rheumatic heart disease (RHD) is a neglected disease of poverty, which presents challenges for patients, communities, and health systems. These effects are magnified in low resource countries, which bear the highest disease burden. When considering the impact of RHD, it is imperative that we widen our lens in order to better understand how RHD impacts the over 40 million people currently living with this preventable condition and their communities. We aimed to perform an updated literature review on the global impact of RHD, examining a broad range of aspects from disease burden to impact on healthcare system to socioeconomic implications. RECENT FINDINGS: RHD accounts for 1.6% of all cardiovascular deaths, resulting in 306,000 deaths yearly, with a much higher contribution in low- and middle-income countries, where 82% of the deaths occurred in 2015. RHD can result in severe health adverse outcomes, markedly heart failure, arrhythmias, stroke and embolisms, and ultimately premature death. Thus, preventive, diagnostic and therapeutic interventions are required, although insufficiently available in undersourced settings. As examples, anticoagulation management is poor in endemic regions - and novel oral anticoagulants cannot be recommended - and less than 15% of those in need have access to interventional procedures and valve replacement in Africa. RHD global impact remains high and unequally distributed, with a marked impact on lower resourced populations. This preventable disease negatively affects not only patients, but also the societies and health systems within which they live, presenting broad challenges and high costs along the pathway of prevention, diagnosis, and management.

Neuropsychiatric Syndromes in Childhood-Onset Systemic Lupus Erythematosus: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of this study was to access the prevalence of 19 neuropsychiatric syndromes in childhood-onset systemic lupus erythematosus (cSLE), as defined by the American College of Rheumatology (ACR) in 1999, by performing a systematic review and meta-analysis of relevant publications. METHODS: A literature search from April 1999 to March 2018 identified studies investigating neuropsychiatric syndromes in cSLE patients, applying 1999 ACR Case Definitions, with a sample of at least 20 patients. Case reports, small case series, reviews, articles that did not use 1999 ACR case definitions, and those with adult SLE patients were excluded. The methodological quality of the studies was determined through the Loney quality assessment. Prevalence estimates with a 95% confidence interval were combined using random-effect (DerSimonian-Laird) models. RESULTS: A total of 143 articles were identified and 9 were included. In a population of 1463 cSLE patients, 351 (29.9%) presented 869 neuropsychiatric cSLE events (2.48 events/patient). The results for each syndrome were headache (52.2%), seizure disorders (48.6%), cognitive dysfunction (32.9%), mood disorder (28.3%), psychosis (22.7%), cerebrovascular disease (19.5%), acute confusional state (15.7%), movement disorder (9.4%), anxiety disorder (7.2%), aseptic meningitis (5.1%), mononeuropathy single/multiplex (4.9%), myelopathy (4.2%), demyelinating syndrome (3.2%), cranial neuropathy (2.7%), polyneuropathy (2.6%), Guillain-Barré syndrome (2.5%), autonomic disorder (1.9%), plexopathy (1.3%), and myasthenia gravis (1.3%). CONCLUSIONS: Neuropsychiatric syndromes are prevalent among cSLE patients. The most prevalent were headaches, seizures, cognitive dysfunction, mood disorders, and psychosis. Determining the prevalence of each neuropsychiatric syndrome in cSLE may improve clinical awareness of these potentially fatal and disabling conditions.

Global, Regional, and National Burden of Rheumatic Heart Disease, 1990-2015.

BACKGROUND: Rheumatic heart disease remains an important preventable cause of cardiovascular death and disability, particularly in low-income and middle-income countries. We estimated global, regional, and national trends in the prevalence of and mortality due to rheumatic heart disease as part of the 2015 Global Burden of Disease study. METHODS: We systematically reviewed data on fatal and nonfatal rheumatic heart disease for the period from 1990 through 2015. Two Global Burden of Disease analytic tools, the Cause of Death Ensemble model and DisMod-MR 2.1, were used to produce estimates of mortality and prevalence, including estimates of uncertainty. RESULTS: We estimated that there were 319,400 (95% uncertainty interval, 297,300 to 337,300) deaths due to rheumatic heart disease in 2015. Global age-standardized mortality due to rheumatic heart disease decreased by 47.8% (95% uncertainty interval, 44.7 to 50.9) from 1990 to 2015, but large differences were observed across regions. In 2015, the highest age-standardized mortality due to and prevalence of rheumatic heart disease were observed in Oceania, South Asia, and central sub-Saharan Africa. We estimated that in 2015 there were 33.4 million (95% uncertainty interval, 29.7 million to 43.1 million) cases of rheumatic heart disease and 10.5 million (95% uncertainty interval, 9.6 million to 11.5 million) disability-adjusted life-years due to rheumatic heart disease globally. CONCLUSIONS: We estimated the global disease prevalence of and mortality due to rheumatic heart disease over a 25-year period. The health-related burden of rheumatic heart disease has declined worldwide, but high rates of disease persist in some of the poorest regions in the world. (Funded by the Bill and Melinda Gates Foundation and the Medtronic Foundation.).