Non-Classical Effects of FGF23: Molecular and Clinical Features.

This article reviews the role of fibroblast growth factor 23 (FGF23) protein in phosphate metabolism, highlighting its regulation of vitamin D, parathyroid hormone, and bone metabolism. Although it was traditionally thought that phosphate-calcium homeostasis was controlled exclusively by parathyroid hormone (PTH) and calcitriol, pathophysiological studies revealed the influence of FGF23. This protein, expressed mainly in bone, inhibits the renal reabsorption of phosphate and calcitriol formation, mediated by the α-klotho co-receptor. In addition to its role in phosphate metabolism, FGF23 exhibits pleiotropic effects in non-renal systems such as the cardiovascular, immune, and metabolic systems, including the regulation of gene expression and cardiac fibrosis. Although it has been proposed as a biomarker and therapeutic target, the inhibition of FGF23 poses challenges due to its potential side effects. However, the approval of drugs such as burosumab represents a milestone in the treatment of FGF23-related diseases.

Local contextual factors of child stunting found via shared values of stakeholder groups: an exploratory case study in Kaffrine, Senegal.

OBJECTIVE: This work aims to demonstrate an original approach to identify links between locally situated shared values and contextual factors of stunting. Stunting results from multi-factorial and multi-sectoral determinants, but interventions typically neglect locally situated lived experiences, which contributes to problematic designs that are not meaningful for those concerned and/or relatively ineffective. DESIGN: This case study investigates relevant contextual factors in two steps: by first facilitating local stakeholder groups (n 11) to crystallise their shared-values-in-action using a specialised method from sustainability studies (WeValue_InSitu (WVIS)). Secondly, participants (n 44) have focus group discussions (FGD) about everyday practices around child feeding/food systems, education and/or family life. Because the first step strongly grounds participants in local shared values, the FGD can reveal deep links between contextual factors and potential influences on stunting. SETTING: Kaffrine, Senegal, an 'Action Against Stunting Hub' site. December 2020. PARTICIPANTS: Eleven stakeholder groups of mothers, fathers, grandmothers, pre-school teachers, community health workers, farmers, market traders and public administrators. RESULTS: Local contextual factors of stunting were identified, including traditional beliefs concerning eating and growing practices; fathers as decision-makers; health worker trust; financial non-autonomy for women; insufficient water for preferred crops; merchants' non-access to quality produce; religious teachings and social structures affecting children's food environment. CONCLUSIONS: Local contextual factors were identified. Pre-knowledge of these could significantly improve effectiveness of intervention designs locally, with possible applicability at other sites. The WVIS approach proved efficient and useful for making tangible contextual factors and their potential links to stunting, via a lens of local shared values, showing general promise for intervention research.

Impact of early vs. delayed initiation of dutasteride/tamsulosin combination therapy on the risk of acute urinary retention or BPH-related surgery in LUTS/BPH patients with moderate-to-severe symptoms at risk of disease progression.

PURPOSE: To evaluate the effect of delayed start of combination therapy (CT) with dutasteride 0.5 mg and tamsulosin 0.4 mg on the risk of acute urinary retention or benign prostatic hyperplasia (BPH)-related surgery (AUR/S) in patients with moderate-to-severe lower urinary tract symptoms (LUTS) at risk of disease progression. METHODS: Using a time-to-event model based on pooled data from 10,238 patients from Phase III/IV dutasteride trials, clinical trial simulations (CTS) were performed to assess the risk of AUR/S up to 48 months in moderate-to-severe LUTS/BPH patients following immediate and delayed start of CT for those not responding to tamsulosin monotherapy. Simulation scenarios (1300 subjects/arm) were investigated, including immediate start (reference) and alternative delayed start (six scenarios 1-24 months). AUR/S incidence was described by Kaplan-Meier survival curves and analysed using log-rank test. The cumulative incidence of events as well as the relative and attributable risks were summarised stratified by treatment. RESULTS: Survival curves for patients starting CT at month 1 and 3 did not differ from those who initiated CT immediately. By contrast, significant differences (p < 0.001) were observed when switch to CT occurs ≥ 6 months from the initial treatment. At month 48, AUR/S incidence was 4.6% vs 9.5%, 11.0% and 11.3% in patients receiving immediate CT vs. switchers after 6, 12 and 24 months, respectively. CONCLUSIONS: Start of CT before month 6 appears to significantly reduce the risk of AUR/S compared with delayed start by ≥ 6 months. This has implications for the treatment algorithm for men with LUTS/BPH at risk of disease progression.

Model-based meta-analysis of the time to first acute urinary retention or benign prostatic hyperplasia-related surgery in patients with moderate or severe symptoms.

AIMS: Combination therapy of 5α-reductase inhibitor and α-blocker is a guideline-endorsed therapeutic approach for patients with moderate-to-severe lower urinary tract symptoms or benign prostatic hyperplasia (LUTS/BPH) who are at risk of disease progression. We aimed to disentangle the contribution of clinical and demographic baseline characteristics affecting the risk of acute urinary retention or BPH-related surgery (AUR/S) from the effect of treatment with drugs showing symptomatic and disease-modifying properties. METHODS: A time-to-event model was developed using pooled data from patients (n = 10 238) enrolled into six clinical studies receiving placebo, tamsulosin, dutasteride or tamsulosin-dutasteride combination therapy. A parametric hazard function was used to describe the time to first AUR/S. Covariate model building included the assessment of relevant clinical and demographic factors on baseline hazard. Predictive performance was evaluated by graphical and statistical methods. RESULTS: An exponential hazard model best described the time to first AUR/S in this group of patients. Baseline International Prostate Symptom Score, prostate-specific antigen, prostate volume and maximum urine flow were identified as covariates with hazard ratio estimates of 1.04, 1.08, 1.01 and 0.91, respectively. Dutasteride monotherapy and tamsulosin-dutasteride combination therapy resulted in a significant reduction in the baseline hazard (56.8% and 66.4%, respectively). By contrast, the effect of tamsulosin did not differ from placebo. CONCLUSIONS: Our analysis showed the implications of disease-modifying properties of dutasteride and tamsulosin-dutasteride combination therapy for the risk of AUR/S. It also elucidated the contribution of different baseline characteristics to the risk of these events. The use of tamsulosin monotherapy (symptomatic treatment) has no impact on individual long-term risk.

Real-world therapeutic management and evolution of patients with benign prostatic hyperplasia in primary care and urology in Spain.

OBJECTIVES: This study aimed to describe the real-world therapeutic management of patients with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) (LUTS/BPH) attending primary care and urology clinics in Spain. METHODS: This observational, retrospective, multicentre study included men ≥50 years of age diagnosed with LUTS/BPH (≤8 years prior to study visit) (N = 670). Therapeutic management according to healthcare service (primary care vs. urology clinics) or progression criteria, proportion of patients with treatment change, patient profile according to therapy and evolution of LUTS severity were assessed. RESULTS: Overall differences were noticed in the management of patients between healthcare service (P < .001) and with or without progression criteria (P < .05). Most patients received pharmacological treatment at diagnosis (70.7%; 474/670), which increased at study visit (81.6%; 547/670) with overall similar profiles between primary care and urology clinics for each therapy. α1-Blockers were the most used pharmacological treatment across healthcare settings at diagnosis (61.8%; 293/474) and study visit (51%; 279/547). Only 27.1% (57/210) of patients with progression criteria at diagnosis and 35.6% (99/278) at study visit received 5α-reductase inhibitor (5ARI) alone or in combination with a α1-blocker. Overall, most patients did not change treatment (60%; 402/670) with a trend of more patients worsening in symptoms when not receiving α1-blocker plus 5ARI combination therapy. CONCLUSION: Most patients with LUTS/BPH received pharmacological treatment; however, most men with progression criteria did not receive a 5ARI alone or in combination. These results support the need to reinforce both primary care and urologists existing clinical guideline recommendations for the appropriate medical management of patients with LUTS/BPH.

Impact of disease progression on individual IPSS trajectories and consequences of immediate versus delayed start of treatment in patients with moderate or severe LUTS associated with BPH.

PURPOSE: Despite superiority of tamsulosin-dutasteride combination therapy versus monotherapy for lower urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH), patients at risk of disease progression are often initiated on α-blockers. This study evaluated the impact of initiating tamsulosin monotherapy prior to switching to tamsulosin-dutasteride combination therapy versus immediate combination therapy using a longitudinal model describing International Prostate Symptom Score (IPSS) trajectories in moderate/severe LUTS/BPH patients at risk of disease progression. METHODS: Clinical trial simulations (CTS) were performed using data from 10,238 patients from Phase III/IV dutasteride trials. The effect of varying disease progression rates was explored by comparing profiles on- and off-treatment. CTS scenarios were investigated, including a reference (immediate combination therapy) and six alternative virtual treatment arms (delayed combination therapy of 1-24 months). Clinical response (≥ 25% IPSS reduction relative to baseline) was analysed using log-rank test. Differences in IPSS relative to baseline at various on-treatment time points were assessed by t tests. RESULTS: Delayed combination therapy initiation led to significant (p < 0.01) decreases in clinical response. At month 48, clinical response rate was 79.7% versus 74.1%, 70.3% and 71.0% and IPSS was 6.3 versus 7.6, 8.1 and 8.0 (switchers from tamsulosin monotherapy after 6, 12 and 24 months, respectively) with immediate combination therapy. More patients transitioned from severe/moderate to mild severity scores by month 48. CONCLUSIONS: CTS allows systematic evaluation of immediate versus delayed combination therapy. Immediate response to α-blockers is not predictive of long-term symptom improvement. Observed IPSS differences between immediate and delayed combination therapy (6-24 months) are statistically significant.

Model-based meta-analysis of individual International Prostate Symptom Score trajectories in patients with benign prostatic hyperplasia with moderate or severe symptoms.

AIMS: International Prostate Symptom Score (IPSS) is a marker of lower urinary tract symptoms (LUTS) deterioration or improvement in benign prostate hyperplasia (BPH). Whereas changes in IPSS relative to baseline have been used as endpoints in clinical trials, little attention has been given to the time course of symptoms. The current investigation aimed to develop a drug-disease model to describe individual IPSS trajectories in moderate and severe BPH patients. METHODS: A model-based meta-analytical approach was used including data from 10 238 patients enrolled into Phase III and IV studies receiving placebo, tamsulosin, dutasteride or combination therapy over a period of up to 4 years. Model predictive performance was assessed using statistical and graphical criteria. Subsequently, simulations were performed to illustrate the implications of treatment with drugs showing symptomatic and disease-modifying properties in patients with varying disease progression rates. RESULTS: Improvement and worsening of IPSS could be characterized by a model including a sigmoid function which disentangles drug effects from placebo and varying disease progression rates on IPSS. Mean estimate (95% confidence intervals) for the disease progression rate was 0.319 (0.271-0.411) month-1 . Treatment effect on IPSS (DELTA) was found to be 0.0605, 0.0139 and 0.0310 month-1 for placebo, tamsulosin and combination therapy, respectively. In addition, it appears that individual trajectories can be clustered together into different phenotypes describing the underlying disease progression rate (i.e. slow, moderate and fast progressors). CONCLUSIONS: The availability of a drug-disease model enables the evaluation of interindividual differences in disease progression rate, deterioration of symptoms and treatment effects on LUTS/BPH.

Persistence and adherence to dutasteride/tamsulosin fixed-dose versus free-combination alpha blocker/5ARI therapy in patients with benign prostate hyperplasia in Germany
.

OBJECTIVE: To evaluate real-world persistence and adherence in patients with benign prostate hyperplasia (BPH) receiving a fixed-dose combination of dutasteride plus tamsulosin (DUT-TAM FDC) versus α-blocker plus 5-α reductase inhibitor (AB/5ARI) free-combination therapy. MATERIALS AND METHODS: This retrospective, observational cohort study utilized the German IMS LRx (IQVIA) database. Patients ≥ 45 years old with BPH receiving DUT-TAM FDC or AB/5ARI free-combination therapy from July 1, 2011 to November 30, 2017 were included. Data were analyzed for 48 months from index date (date of first prescription). Persistence, measured as time to discontinuation (defined as a 90-day gap in therapy), was evaluated using Kaplan-Meier curves (log-rank tests). Adherence, measured as medication possession ratio (MPR), was based on a comparison of mean prescribing duration and expected treatment duration. RESULTS: A total of 141,667 patients were included (DUT-TAM FDC, n = 86,057; free AB/5ARI: n = 55,610). Small differences in persistence were observed between treatment arms. At month 12, 41.8% of DUT-TAM FDC-treated and 41.0% of AB/5ARI free-combination therapy-treated patients were persistent; at month 24, 28.2% and 27.1% were persistent, respectively. A higher proportion of DUT-TAM FDC-treated patients had MPR ≥ 0.80, ≥ 0.75 and ≥ 0.70 compared with AB/5ARI free-combination therapy (p < 0.0001). CONCLUSION: Small differences observed in persistence between treatment arms may not translate to meaningful clinical relevance. Adherence was significantly better in the FDC arm, which may be clinically relevant as improved adherence is associated with better outcomes. Persistence and adherence to BPH therapy in Germany is low; further studies exploring the reasons behind this are required.

Immunology and social networks: an approach towards impact assessment.

Scientific journals have changed the mechanisms they use for distribution and dissemination of information. Different approaches towards determining impact have emerged and among these, metrics derived from activity on social media are an emerging trend. This article aims to assess whether a correlation exists between the traditional impact factor and activity on social media. We assessed journals categorized within the area of "immunology" on the SCImago Journal and Country Rank website. Variables reflecting traditional and alternative measures of impact were collected. Differences between journals with and without social networks were assessed using non-parametric Mann-Whitney U tests. Correlation was assessed through Spearman tests. 156 journals were analyzed, 17% had at least one social network. 48.2% of journals with social networks were classified within SJR's quartile 1. An almost perfect correlation was found between the SJR and the number of followers on Twitter, this correlation remained statistically significant after adjusting for time since creation of the account [Spearman's correlation (rs) = 0.83]. We propose the use of Twitter as a mechanism for dissemination of information by immunology journals, as well as other social networks for their potential to increase their audience, as well as the dissemination and impact of their publications.

Men's Sexual Health Questionnaire score changes vs spontaneous sexual adverse event reporting in men treated with dutasteride/tamsulosin combination therapy for lower urinary tract symptoms secondary to benign prostatic hyperplasia: A post hoc analysis of a prospective, randomised, placebo-controlled study.

AIM: To assess the impact of baseline characteristics on Men's Sexual Health Questionnaire (MSHQ) total scores and to evaluate the clinical relevance of MSHQ changes and their association with spontaneously reported sexual adverse events (SexAEs) in patients with benign prostatic hyperplasia. METHODS: This was a post hoc analysis of the Phase 4 FDC116115 study, in which patients aged ≥50 years were randomised 1:1 to receive a fixed-dose combination of dutasteride 0.5 mg and tamsulosin 0.4 mg (DUT-TAM FDC), or placebo. End-points included: change in MSHQ total scores by baseline characteristics and SexAEs; cumulative distribution function for change from baseline to month 12 in MSHQ total score and the ejaculation, erection, satisfaction and sexual desire (libido) domain scores; and relationship between changes in MSHQ scores and SexAEs. RESULTS: The intent-to-treat population comprised 489 patients (DUT-TAM FDC, n = 243; placebo, n = 246). The mean reduction in total MSHQ score was greater in patients with SexAEs across both groups, compared with patients without SexAEs. Most patients reporting any SexAE (86% DUT-TAM FDC, 67% placebo) had a worsening of the MSHQ total score at month 12 compared with baseline. Specifically, 90% (DUT-TAM FDC) and 75% (placebo) of patients reporting an ejaculation SexAE and 73% (DUT-TAM FDC) and 87% (placebo) of patients reporting an erection SexAE had a worsening of MSHQ ejaculation and erection domain scores, respectively, at month 12. A threshold effect for incident SexAE was observed; patients showing a decrease of approximately 6-10 points in the total MSHQ score were more likely to report SexAEs. CONCLUSION: Findings support the clinical utility of the MSHQ tool in assessing the impact of DUT-TAM on sexual function by linking numerical changes in MSHQ scores to spontaneously reported SexAEs for the first time. The threshold effect for incidence of SexAEs warrants further investigation to determine its clinical relevance.

Real-world assessment and characteristics of men with benign prostatic hyperplasia (BPH) in primary care and urology clinics in Spain.

OBJECTIVES: To describe the real-world demographic and clinical characteristics of patients with lower urinary tract symptoms (LUTS) as a result of benign prostatic hyperplasia (BPH) in Spain. METHODOLOGY: This observational, retrospective, multicentre study conducted in primary care and urology clinics in Spain included men aged ≥50 years diagnosed (≤8 years prior to study visit) with LUTS caused by BPH. The primary endpoint was demographic and clinical characteristics; secondary endpoints included disease progression and diagnostic tests across both healthcare settings. RESULTS: A total of 670 patients were included (primary care: n = 435; urology: n = 235). Most patients had moderate/severe LUTS (74.6%) and prostate volume >30 cc (81.7%), with no differences between settings. More patients had prostate-specific antigen (PSA) ≥1.5 ng/mL in primary care (74.5%) versus urology (67.7%). Progression criteria were prevalent (48.9%). Clinical criteria were more commonly used than the International Prostate Symptom Score (IPSS) to evaluate LUTS at diagnosis (primary care: clinical criteria 73.0%; IPSS: 26.9%; urology: clinical criteria 76.5%; IPSS: 23.4%). Proportion of patients with moderate/severe LUTS at diagnosis was lower using clinical criteria than IPSS, and the proportion of patients with 'worsening' LUTS (diagnosis to study visit) was higher when using clinical criteria versus IPSS. In both healthcare settings, the most commonly used diagnostic tests were general and urological clinical history and PSA. CONCLUSION: Demographic and clinical characteristics of patients with BPH in Spain were similar in primary care and urology; however, assessment criteria to evaluate LUTS severity differ and are not completely aligned with clinical guideline recommendations. Increased use of recommended assessments may enhance optimal BPH management.

Comparison of the clinical effect of dutasteride therapy for benign prostatic hyperplasia when initiated at different time points: A multicentre, observational, retrospective chart review study.

AIM: To evaluate the effects of early (≤6 months after starting any medical treatment [baseline] for benign prostatic hyperplasia [BPH]), intermediate (between >6 months and 2 years from baseline) and late (2 years after baseline) initiation of add-on dutasteride therapy on the incidence of acute urinary retention (AUR) and BPH-related surgery in Japanese patients with moderate-to-severe BPH. METHODS: This multicentre, observational, retrospective chart review study used anonymised data from Japanese medical records. Eligible patients (≥50 years) were followed from baseline until first AUR, BPH-related surgery or Year 4. RESULTS: Overall, 1206 patients were included (early initiation: n = 793; intermediate: n = 233; late: n = 180). Early dutasteride initiation was not superior to late initiation in reducing the risk of first AUR or BPH-related surgery from baseline (hazard ratio [HR] 0.733; 95% confidence interval [CI] 0.468-1.150) but was superior in reducing the risk of first AUR alone (HR 3.449; 95% CI 1.796-6.623). One year after initiation, the cumulative incidence of first AUR rose rapidly in the late vs early and intermediate initiation groups. Incidences of all parameters (first AUR/BPH-related surgery, first AUR alone and BPH-related surgery alone) in patients undergoing BPH-related surgery in low incidence sites (ie clinical sites with ≤ 16% incidence of first AUR or BPH-related surgery) were significantly lower in the early vs late initiation groups. CONCLUSION: Early dutasteride initiation reduced the risk of AUR in a Japanese real-world setting. A randomised controlled trial is warranted to evaluate the benefit of early initiation in preventing BPH-related surgery in Japanese patients.

Evaluation of the impact of dutasteride/tamsulosin combination therapy on libido in sexually active men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH): A post hoc analysis of a prospective randomised placebo-controlled study.

AIMS: Five-α reductase inhibitor (5ARI) therapy has been associated with sexual dysfunction in some patients. This study assessed the impact of a fixed-dose combination of the 5ARI dutasteride 0.5 mg and the α1 -adrenoceptor antagonist tamsulosin 0.4 mg (DUT-TAM FDC) on Men's Sexual Health Questionnaire (MSHQ) domain scores in patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH). METHODS: This was a post hoc analysis of a double-blind, randomised, placebo-controlled, parallel-group, multicentre study in sexually active patients, aged ≥50 years, with a confirmed clinical diagnosis of BPH. Sexual activity, sexual desire, and bother domain scores of the MSHQ were assessed at baseline and at Months 1, 3, 6, 9, and 12. Correlation between MSHQ sexual activity/desire scores and ejaculation, erection, and satisfaction domains at baseline was also evaluated. RESULTS: In the intent-to-treat population (N = 489), 243 and 246 patients were randomised to DUT-TAM FDC and placebo groups, respectively. Compared with placebo, DUT-TAM FDC therapy resulted in statistically significant reductions (worsening) from baseline in adjusted mean MSHQ sexual activity and bother domain scores at Months 1, 3, 6, 9, and 12 (all P < 0.05) and in adjusted mean MSHQ sexual desire domain scores at Months 6, 9, and 12 (all P < 0.05). Significant moderate correlations in the expected direction were observed at baseline between the sexual activity/desire domains and the ejaculation, erection, and satisfaction domains (P < 0.0001). CONCLUSIONS: These findings help clarify the degree and impact of libido changes in sexually active men treated with DUT-TAM FDC and may support clinical decision-making.

A prospective randomised placebo-controlled study of the impact of dutasteride/tamsulosin combination therapy on sexual function domains in sexually active men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH).

OBJECTIVE: To prospectively assess the impact of the fixed-dose combination (FDC) of the 5α-reductase inhibitor (5ARI), dutasteride 0.5 mg and the α1 -adrenoceptor antagonist, tamsulosin 0.4 mg (DUT-TAM FDC) therapy on sexual function domain scores in sexually active men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH), using the Men's Sexual Health Questionnaire (MSHQ). PATIENTS AND METHODS: This European and Australian double-blind, placebo-controlled, parallel-group study was conducted at 51 centres. INCLUSION CRITERIA: age ≥50 years, International Prostate Symptom Score ≥12, prostate volume ≥30 cc, prostate-specific antigen 1.5-10 ng/mL. Patients were randomised 1:1 to DUT-TAM FDC therapy or placebo for 12 months. The change from baseline to Month 12 on the total MSHQ (primary endpoint) and MSHQ erection, ejaculation and satisfaction domains (secondary outcome) was assessed, using a mixed model repeated measures analysis. Safety was evaluated. RESULTS: The intention-to-treat population included 489 patients (243 DUT-TAM FDC therapy; 246 placebo). A significant decrease (worsening) was observed with DUT-TAM FDC therapy versus placebo on the total MSHQ score (-8.7 vs -0.7; standard error [se]: 0.81, 0.78; P < 0.001), and the ejaculation (-7.5 vs -0.6; se: 0.56, 0.55; P < 0.001) and satisfaction (-0.6 vs +0.3; se: 0.3, 0.29, P = 0.047) domains, but not the erection domain (-1.0 vs -0.5; se: 0.19, 0.19, P = 0.091). CONCLUSION: This is the first domain-specific quantitative evaluation of DUT-TAM FDC therapy on sexual function in men with LUTS secondary to BPH. The observed changes in the MSHQ with DUT-TAM FDC therapy were mainly driven by changes in the ejaculation domain. These findings will help give context to erectile and ejaculatory dysfunction AEs reported spontaneously in earlier 5ARI studies.

[Ovarian ectopic pregnancy with little common clinical presentation. A case report and bibliographical review]. / Embarazo ectópico ovárico con presentación clínica poco común. Reporte de caso y revisión de la bibliografía.

UNLABELLED: Ovarian ectopic pregnancy is only 3% of all ectopic, with an incidence of 1:7,000-40,000. In the last 10 years, it has been a rise in incidence. Most patients have vaginal bleeding, abdominal pain and shock data. Less than 300-400 cases are reported in the literature. CASE: We present the case of a woman with ovarian ectopic pregnancy of 12 weeks of gestation, who have not suggestive clinical signs and whose diagnosis was incidental despite having a regular prenatal ultrasound. CONCLUSION: Ovarian pregnancy is a rare presentation; diagnosis is difficult and often suggested by clinical data, when clinical data fail, more studies are needed to integrate the diagnosis.

Sex-dependent hypertension and renal changes in aged rats with altered renal development.

Numerous studies have evaluated blood pressure (BP) and renal changes in several models of developmental programming of hypertension. The present study examined to what extent BP, renal hemodynamic, and renal structure are affected at an old age in male and female animals with altered renal development. It also evaluated whether renal damage is associated with changes in cyclooxygenase (COX)-2 and neuronal nitric oxide synthase (NOS1) expression and immunoreactivity. Experiments were carried out in rats at 10-11 and 16-17 mo of age treated with vehicle or an ANG II type 1 receptor antagonist during the nephrogenic period (ARAnp). A progressive increment in BP and a deterioration of renal hemodynamics were found in both sexes of ARAnp-treated rats, with these changes being greater (P < 0.05) in male rats. The decrease in glomerular filtration rate at the oldest age was greater (P < 0.05) in male (74%) than female (32%) ARAnp-treated rats. Sex-dependent deterioration of renal structure was demonstrated in optical and electron microscopic experiments. COX-2 and NOS1 immunoreactivity were enhanced in the macula densa of male but not female ARAnp-treated rats. The present study reports novel findings suggesting that stimuli that induce a decrease of ANG II effects during renal development lead to a progressive increment in BP and renal damage at an old age in both sexes, but these BP and renal changes are greater in males than in females. The renal damage is associated with an increase of COX-2 and NOS1 in the macula densa of males but not females with altered renal development.

Importance of the early diagnosis of incarcerated gravid uterus: Case report and systematic review.

OBJECTIVE: To examine whether the early diagnosis of uterine incarceration before 20 weeks of gestation improves maternal-perinatal prognoses. METHODS: A systematic review of all of the cases published in the past 30 years that met the inclusion and exclusion criteria was performed and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. A comparative analysis of diagnoses before and after 20 weeks of gestation was performed. RESULTS: Eighty-nine studies with a total of 146 cases of uterine incarceration during pregnancy were included. For cases of incarceration diagnosed before 20 weeks of gestation, a higher proportion of clinical symptoms was observed; however, a lower proportion of complications, such as premature delivery, need for cesarean section, and poor perinatal outcomes, were observed (P < 0.05). The proportion of spontaneous resolution and minimally invasive techniques for the treatment of incarceration was significantly higher among patients diagnosed with this pathology before 20 weeks (P < 0.05). CONCLUSION: The literature indicates that uterine incarceration is a rare complication during pregnancy with better maternal-perinatal results if diagnosed earlier than 20 weeks.

Post-myocardial Infarction Ventricular Septal Rupture Complicated by Cardiogenic Shock Stage D: A Successful Case of Extracorporeal Membrane Oxygenation as a Bridge to Delayed Surgical Repair.

Ventricular septal rupture (VSR) after myocardial infarction is often complicated by cardiogenic shock (CS) with high in-hospital mortality rates. Early use of preoperative venoarterial extracorporeal membrane oxygenation (VA ECMO) and delayed surgical repair have demonstrated lower mortality rates; however, the optimal timing of surgical intervention remains controversial. We report the case of a 53-year-old man with CS stage D due to post-myocardial infarction VSR, who was successfully treated with VA ECMO as a bridge to delayed surgical repair. This case highlights the complexity of determining the optimal timing for surgical intervention in these patients and emphasizes the benefits of early use of VA ECMO for preoperative stabilization in patients with CS and multiorgan failure.

Telemedicine screening program for diabetic retinopathy in patients with type 1 diabetes mellitus.

PURPOSE: To analyze the results of the telemedicine screening program for diabetic retinopathy (DR) in patients with type 1 diabetes conducted by the Endocrinology and Nutrition Management Unit of Virgen del Rocío University Hospital. METHODS: This cross-sectional study comprised patients with type 1 diabetes mellitus (DM) in our DR screening program from January 2018 to November 2020. Fundus photographs are performed by trained nurses and reviewed by a trained endocrinologist. Those suggestive of pathology are sent to ophthalmology through a telematic program for review. RESULTS: Of the 995 fundus photographs evaluated, 646 (65.3%) showed no evidence of DR, 327 (33.1%) presented possible DR, and 16 (1.6%) were not gradable. The diagnosis was confirmed in 254 patients after reviewing by ophthalmology, and the screening program achieved a positive predictive value for DR of 77.7%. Seventy-three were excluded by ophthalmology due to the absence of DR (false positive rate - 22.3%). In 92.5% of the cases classified by the ophthalmologist, the degree of DR was mild or very mild. CONCLUSION: Our telemedicine screening program for DR in patients with type 1 DM is consistent with the literature. Effective screening for DR is performed, with patients diagnosed in the early stages. Telemedicine programs facilitate efficient communication among healthcare personnel.

A 25-Year-Old Woman with a High-Risk Large and Occlusive Pulmonary Embolism, Later Diagnosed with Primary Antiphospholipid Syndrome and Hyperhomocysteinemia: A Case Report.

BACKGROUND High-risk pulmonary embolism (PE) occurs when the pulmonary circulation is suddenly occluded by a thrombus and is a life-threatening medical emergency. In young and otherwise healthy individuals, there may be undiagnosed underlying risk factors for PE that require investigation. This report presents the case of a 25-year-old woman admitted as an emergency with a high-risk large and occlusive PE, later diagnosed with primary antiphospholipid syndrome (APS) and hyperhomocysteinemia. CASE REPORT A 25-year-old woman presented with sudden-onset dyspnea after elective cholecystectomy. One year earlier, the patient had lower limb deep vein thrombosis without an identified predisposing cause, and she received anticoagulation for 6 months. On physical examination, she had right leg edema. Laboratory tests revealed elevated levels of troponin, pro-B-type natriuretic peptide, and D-dimer. Computed tomography pulmonary angiography (CTPA) demonstrated a large and occlusive PE, and an echocardiogram showed right ventricular dysfunction. Successful thrombolysis was performed with alteplase. On repeat CTPA, a significant reduction in filling defects in the pulmonary vasculature was observed. The patient evolved uneventfully and was discharged home on a vitamin K antagonist. Due to unprovoked recurrent thrombotic events, suspicion of underlying thrombophilia was raised, and hypercoagulability studies confirmed primary APS and hyperhomocysteinemia. CONCLUSIONS This report presents the case of a life-threatening high-risk PE in a previously healthy young woman and highlights the importance of emergency management followed by investigation and treatment of underlying risk factors for venous thromboembolism, including APS and hyperhomocysteinemia.