Echocardiographic Features of an Evolving Periaortic Valvular Abscess in a Patient with Staphylococcus Epidermidis Prosthetic Valve Endocarditis.

Prosthetic valve endocarditis is a serious complication following valve replacement surgery, with the development of aortic root abscess being a catastrophic manifestation. We present a case of a 71-year-old female with a bioprosthetic aortic valve who presented with shortness of breath. Echocardiographic findings revealed vegetation on the prosthetic aortic valve with a periaortic, annular abscess. Given the patient's comorbidities and high surgical risk, conservative management with antibiotics was chosen. The patient responded well to antibiotic therapy and was discharged with long-term antibiotic treatment. Prosthetic valve endocarditis, particularly with periaortic abscess formation, is associated with significant morbidity and mortality. Early diagnosis and appropriate management are crucial for improving outcomes.

Severe Mitral Valve Regurgitation Secondary to Fulminant Myocarditis in the Setting of a Lupus Flare.

Systemic Lupus Erythematosus represents a chronic autoimmune disorder characterized by multiorgan involvement. Lupus myocarditis is a rare presentation of one of the cardiac complications of lupus with an incidence of 3-9%. It usually presents with non-specific symptoms such as dyspnea, orthopnea, chest pain, pedal edema, fever, diaphoresis, paroxysmal nocturnal dyspnea, nausea, vomiting, or palpitations. Even though endomyocardial biopsy is considered the gold standard diagnostic approach, other non-invasive diagnostic alternatives including cardiac magnetic resonance (CMR) have been studied. Therapeutic interventions may range from high-dose steroids, and IVIG, to the most advanced strategies such as mechanical circulatory support including VenoArterial Extracorporeal Membrane Oxygenation (VA-ECMO), and Impella, among others.

Myocardial Infarction Presenting as Both Left Ventricular Aneurysm and Ventricular Septal Defect.

Acute myocardial infarction can result in various mechanical complications, although they have become rare with the advent of reperfusion therapies. Among these complications, ventricular septal rupture (VSR) and left ventricular aneurysm (LVA) are infrequent but life-threatening conditions associated with high morbidity and mortality. We present a rare case of a 67-year-old male with acute myocardial infarction who developed concomitant apical LVA and ventricular septal rupture. LEARNING POINTS: Mechanical complications of myocardial infarction, such as a ventricular septal rupture (VSR) and left ventricular aneurysm (LVA), are rare but life-threatening.Early diagnosis is critical. A ventricular septal defect (VSD) requires immediate surgical closure, while surgery for LVA is only considered in specific cases such as chest pain or thromboembolism.Diagnostic tools such as echocardiography and left ventriculography play a vital role in identifying and characterising these complications, enabling timely treatment decisions.

Is There a Place for Brachytherapy in Vulvar Cancer? A Narrative Review.

Vulvar cancer is a relatively rare neoplasm. The essential treatment is surgery for the primary tumour. However, postoperative recurrence rates are high, even in early-stage disease when tumour-free surgical margins are achieved or in the absence of associated risk factors (lymph node metastases, deep stromal invasion or invasion of the lymphatic vascular space). Radiotherapy plays an important role in the treatment of vulvar cancer. Adjuvant treatment after surgery as well as primary treatment of locally advanced vulvar cancer (LAVC) is composed of two key radiotherapy treatment scenarios, external beam radiation therapy (EBRT) either combined or not combined with brachytherapy (BT). In a recurrence setting, where surgery is not an option, BT alone or in combination with EBRT can be used. Compared to EBRT, BT has the radiobiological potential to improve dose to the target volume, minimise the dose to organs at risk, and facilitate hypofractionated-accelerated treatment. This narrative review presents recent data on the role of BT in the treatment of primary and/or recurrent vulvar cancer, including radiobiological, clinical, and therapeutic aspects.

Miocardiopatía Hipertrófica en ausencia de criterios de hipertrofia. Serie de casos / Hypertrophic cardiomyopathy in the absence of hypertrophy criteria. Case series

La miocardiopatía hipertrófica (MCH) es la miocardiopatía hereditaria más frecuente, su principal expresión fenotípica consiste en hipertrofia ventricular izquierda (HVI) en ausencia de condiciones de carga que la justifiquen. Cuando existe una variante genética patogénica se denomina MCH sarcomérica. Los criterios diagnósticos más aceptados son HVI ≥ 15 mm en cualquier segmento o ≥ 13 en ciertas condiciones, criterios que tienen tres inconvenientes: 1) La HCM es una patología donde la HVI es evolutiva, existiendo otros elementos más precoces, pero menos precisos, como criptas, bandas musculares y alteraciones de la válvula mitral y músculos papilares; 2) Pacientes de baja estatura pueden no alcanzar estos umbrales; 3) La MCH apical no queda siempre bien representada usando estos grosores, requiriendo indexar por tamaño del paciente y/o considerar la HVI relativa (relación grosor apical / basal que no debe superar 1). Presentamos una serie de casos con genotipo confirmado para MCH que no cumplen los criterios de HVI aceptados para MCH y donde se debe individualizar el diagnóstico considerando los tres elementos señalados.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac condition; its phenotypic expression consists of ventricular hypertrophy (LVH) unrelated to loading conditions. In patients with a genetic pathogenic variant, the condition is termed sarcomeric HCM. Current diagnostic criteria are based on absolute left ventricular thickness, requiring ≥15 mm in any segment or ≥13 mm in particular conditions. These criteria have three pitfalls: 1) HCM is an evolving disease where LVH occurs gradually, with other early -but less precisephenotypic expressions such as myocardial crypts, muscular bands, or mitral and papillary muscle alterations; 2) Patients with short stature tend to have less LVH and do not reach the proposed thickness threshold. 3) Apical HCM is not correctly addressed in this cut-off as the heart tapers from base to apex, warranting indexing wall thickness to body size and using relative LVH in the apex (ratio from apex/base, abnormal,>1). This small case series includes three patients with a pathogenic genetic variant for HCM that doesn't satisfy the current criteria of LVH. For its precise assessment, the aforementioned points must be considered.

Cultura de seguridad del paciente en el personal sanitario del Centro de Salud de Canoa

Fundamento: la calidad y seguridad en la atención de los pacientes es obligación técnica y ética de los prestadores de los servicios a través de la transparencia de los procesos y resultados de las acciones realizadas por los referidos sistemas de salud. Objetivo: determinar la cultura de la seguridad del paciente en el personal sanitario del Centro de Salud Canoa. Métodos: s e realizó un estudio mixto de corte trasversal, descriptivo; la población estuvo compuesta por 19 profesionales de la salud y 379 usuarios que han asistido desde el mes de agosto del 2021 hasta julio del 2022 a la unidad operativa. La técnica utilizada fue una encuesta de nueve preguntas cerradas y la observación con una guía de observación. Resultados: se evidenció que la mayoría de los profesionales de salud cumplen con los protocolos de preparación y administración de medicamentos. Todos los participantes preparan y administran los medicamentos por sí mismos, y el 94,7 % administra el medicamento correcto con la dosis adecuada, verificando la fecha de caducidad y brindando educación al paciente y su familia. Sin embargo, el 42,1 % de los profesionales evaluados no verifica los antecedentes alérgicos antes de administrar un medicamento. Conclusiones: el estudio permitió identificar muchas debilidades en cultura de seguridad del paciente en el personal sanitario del centro de salud de Canoa. Por ello, establecer estrategias de mejora en calidad de atención, en la comunicación, les permitirá reducir los riesgos de eventos adversos y fomentar una cultura de seguridad en el personal sanitario.

Foundation: the quality and safety in patient care is the service providers' technical and ethical obligation through the processes and results transparency of the actions carried out by the aforementioned health systems. Objective: to determine the patient safety's culture in the health staff of the Canoa Health Center Methods: a mixed cross-sectional, descriptive study was carried out, the population was made up of 19 health professionals and 379 users who have attended the operating unit from August 2021 to July 2022. The technique used was a nine closed questions survey and observation with an observation guide. Results: it was evidenced that the health professionals vast majority fulfill with the protocols for the medications preparation and administration. All participants prepare and administer the medications themselves, and 94.7% administer the correct medication with the proper dosage, checking the expiration date and providing education to the patient and the family. However, 42.1% of the evaluated professionals do not verify the allergic history before administering a medication. Conclusions: the study made it possible to identify many weaknesses in the health staff's culture of patient safety of the Canoa health center. Therefore, establishing strategies to improve the quality of care, in communication, will allow them to reduce the risks of adverse events and promote a culture of safety in health staff.

Recidiva de hernias inguinales. Estudio de 52 casos / Recurrence of Inguinal Hernias. Study of 52 cases

Las hernias inguinales son una patología para tratamiento quirúrgico frecuente, afecta entre un 3 a 5 % de toda la población en general, su reparación resulta difícil y peligrosa en caso de recurrencia; un paciente sometido a cirugía tiene entre19 ­ 39 % de probabilidades de recidiva, y esto aumenta con cada nuevo procedimiento. Objetivo: caracterizar la prevalencia de recidivas de hernias inguinales en pacientes intervenidos quirúrgicamente en el Servicio de Cirugía General del Hospital Universitario de Caracas entre los años 2015-2020. Métodos: estudio retrospectivo, descriptivo y analítico. Resultados: se estudiaron 52 casos de recidivas de hernias inguinales, 43 % de un total de 120 pacientes sometidos a hernioplastia inguinal, las técnicas quirúrgicas con mayor número de recidivas fueron: la de Bassini con 14 %, la de Rutkow-Robbins con 10 % y la de Linchtenstein con 9 % de los casos; con un tiempo de recidiva posterior a la primera intervención el cual fue mayor al año de la primera intervención. Conclusiones: la recidiva resultó un poco mayor al promedio, el tiempo en el cual ocurrió es mayor al año de la intervención y las técnicas más involucradas fueron, enorden decreciente: Bassini, Rutkow-Robbins, y Linchtenstein(AU)

Inguinal hernias are a pathology for frequent surgical treatment, affecting between 3 to 5 % of the entire population in general, their repair is difficult and dangerousin case of recurrence; a patient undergoing surgery has a19-39 % chance of recurrence, and this increases with eachnew procedure. Objective: to characterize the prevalence of recurrences of inguinal hernias in patients undergoing surgery at the General Surgery Service of the Hospital Universitario de Caracas between the years 2015-2020. Methods: retrospective, descriptive and analytical study. Results: 52 cases of inguinalhernia recurrences were studied, 43 % of a total of 120 patients undergoing inguinal hernioplasty, the surgical techniques with the highest number of recurrences were: Bassini with 14 %,that of Rutkow-Robbins with 10 % and that of Linchtensteinwith 9 % of the cases; with a recurrence time after the first intervention which was greater than a year after the first intervention. Conclusions: the recurrence was a little high erthan the average, the time in which it occurred is greater than a year othehe intervention and the techniques most involved were,in decreasing order: Bassini, Rutkow-Robbins, and Lichtenstei(AU)

Effectiveness and Safety of Trabectedin and Radiotherapy for Patients With Myxoid Liposarcoma: A Nonrandomized Clinical Trial.

Importance: Preclinical data about the synergistic activity of radiotherapy (RT) and trabectedin have been reported. The combination of trabectedin and RT in treating myxoid liposarcomas appears worth exploring. Objective: To explore the effectiveness and safety of trabectedin combined with RT. Design, Setting, and Participants: This international, open-label, phase 2 nonrandomized clinical trial including 46 patients with myxoid liposarcoma was conducted in 4 centers in Spain, 1 in Italy, and 2 in France from July 1, 2016, to September 30, 2019. Eligible patients had to have a histologic, centrally reviewed diagnosis of localized resectable myxoid liposarcoma arising from an extremity or the trunk wall. Interventions: Trabectedin was administered at the recommended dose stemming from the phase 1 trial (1.5 mg/m2), with intravenous infusion during 24 hours every 21 days for a total of 3 cycles. Radiotherapy was started after completion of the first trabectedin infusion (cycle 1, day 2). Patients received 25 fractions of radiation for a total of 45 Gy. Surgery was planned 3 to 4 weeks after the administration of the last preoperative cycle and not until 4 weeks after the end of preoperative RT. Pathologic specimens were mapped in tumor sections to estimate the histologic changes and the percentage of viable tumor after neoadjuvant treatment. Main Outcomes and Measures: The primary objective of the phase 2 part of the study was overall response. Secondary objectives were effectiveness measured by relapse-free survival and activity measured by functional imaging and pathologic response. Results: A total of 46 patients were enrolled. Four patients were not evaluable. The median age was 43 years (range, 18-77 years), and 31 patients were male (67%). Overall, 9 of 41 patients (22%) achieved a partial response with neoadjuvant treatment with trabectedin and RT, with 5 of 39 patients (13%) achieving a complete pathologic response and 20 of 39 patients (51%) having 10% or less of a viable remaining tumor. Partial responses according to Choi criteria were observed in 24 of 29 evaluable patients (83%), and no patient had disease progression. Treatment was well tolerated. Conclusions and Relevance: Although the primary end point of this phase 2 nonrandomized clinical trial was not met (Response Evaluation Criteria in Solid Tumors response in ≥70% of patients), results suggest this combination was well tolerated and effective in terms of pathologic response. Thus, trabectedin plus RT might be a treatment option regarding tolerability; further evidence should be generated in this setting.

In vitro radiosensitization by eribulin in human cancer cell lines.

Background: The objective was to to determine the radiosensitizing properties of eribulin and the potential mechanisms of radiosensitization in cervical (HeLa) and pharyngeal (FaDu) cancer cell lines. Materials and methods: Cytotoxicity was evaluated by the crystal violet method. The 10% and 50% inhibitory concentration (IC10, IC50) for 24-hour drug exposure were determined. The surviving fraction at 2 Gy (SF2) and the sensitizer enhancement ratio (SER) were calculated from radiation cell survival curves in the presence or absence of eribulin. Combination index (CI) was calculated to determine if there is a true synergistic interaction between eribulin and irradiation. Cell cycle changes were assessed by propidium iodide staining and flow cytometry. Apoptotic cells were detected by annexin V and TUNEL-assay. Results: Mean IC50s and IC10s were 1.58 nM and 0.7 nM and 0.7 nM and 0.27 nM for HeLa and FaDu cells, respectively. Radiosensitization was observed in both lines with a SER up to 2.71 and 2.32 for HeLa and FaDu cells, respectively. A true synergistic effect was showed with a CI of 0.82 and 0.76 for HeLa and FaDu cells, respectively. Eribulin induced significant G2/M cell arrest and marked apoptosis. Irradiation combined with 3 nM eribulin increased the apoptotic response to radiation in Hela cells. Conclusion: Eribulin shows a true in vitro radiosensitizing effect in HeLa and FaDu cells by inducing significant G2/M phase arrest. In HeLa, the enhancement radiation-induced apoptosis could be an additional mechanism of radiosensitization. Further studies are needed to evaluate the clinical benefits of concurrent eribulin and radiotherapy as a novel therapeutic strategy for cancer.

Effect of the combination of bumetanide plus chlorthalidone on hypertension and volume overload in patients with chronic kidney disease stage 4-5 KDIGO without renal replacement therapy: a double-blind randomized HEBE-CKD trial.

BACKGROUND: The co-administration of loop diuretics with thiazide diuretics is a therapeutic strategy in patients with hypertension and volume overload. The aim of this study was to assess the efficacy and safety of treatment with bumetanide plus chlorthalidone in patients with chronic kidney disease (CKD) stage 4-5 KDIGO. METHODS: A double-blind randomized study was conducted. Patients were randomized into two groups: bumetanide plus chlorthalidone group (intervention) and the bumetanide plus placebo group (control) to evaluate differences in TBW, ECW and ECW/TBW between baseline and 30 Days of follow-up. Volume overload was defined as 'bioelectrical impedance analysis as fluid volume above the 90th percentile of a presumed healthy reference population. The study's registration number was NCT03923933. RESULTS: Thirty-two patients with a mean age of 57.2 ± 9.34 years and a median estimated glomerular filtration rate (eGFR) of 16.7 ml/min/1.73 m2 (2.2-29) were included. There was decreased volume overload in the liters of total body water (TBW) on Day 7 (intervention: -2.5 vs. control: -0.59, p = 0.003) and Day 30 (intervention: -5.3 vs. control: -0.07, p = 0.016); and in liters of extracellular water (ECW) on Day 7 (intervention: -1.58 vs. control: -0.43, p < 0.001) and Day 30 (intervention: -3.05 vs. control: -0.15, p < 0.000). There was also a decrease in systolic blood pressure on Day 7 (intervention: -18 vs. control: -7.5, p = 0.073) and Day 30 (intervention: -26.1 vs. control: -10, p = 0.028) and in diastolic blood pressure on Day 7 (intervention: -8.5 vs. control: -2.25, p = 0.059) and Day 30 (intervention: -13.5 vs. control: -3.4, p = 0.018). CONCLUSION: In CKD stage 4-5 KDIGO without renal replacement therapy, bumetanide in combination with chlorthalidone is more effective in treating volume overload and hypertension than bumetanide with placebo.

Ludwig's Angina.

Ludwig's angina is a bacterial infection of the tongue and floor of the mouth. It can be life-threatening if not treated promptly. Treatment includes IV antibiotics and, in some cases, surgical intervention. In this report, we describe a case with an unusual presentation. Early recognition of the condition in such cases is vital to prevent potential complications. LEARNING POINTS: Ludwig's angina, even though a well-established clinical entity, can be hard to recognize clinically.Early recognition of the condition is vital for the prevention of complications.A low threshold for surgical treatment should be maintained when surgery is indicated.

Tricuspid Endocarditis: A Case Report and Comprehensive Literature Review.

Infective endocarditis is a multisystem disease. Tricuspid valve endocarditis is frequently seen in patients with intravenous (IV) drug users. Cavitating lung nodules predominantly in a peripheral location in IV drug users indicate the possibility of septic emboli. Large vegetation and persistent bacteremia with septic embolic phenomena are the most common indication for surgery. We present a case of a 62-year-old male with a history of IV drug use who presented with epigastric abdominal pain, pleuritic chest pain, and shortness of breath. CT chest showed cavitating lung nodules suggestive of septic pulmonary emboli. A transesophageal echocardiogram (TEE) showed tricuspid valve vegetation despite a normal transthoracic echocardiogram. The patient was treated with intravenous antibiotics. He was deemed a poor surgical candidate; therefore, he was transferred to a tertiary center for AngioVAC (AngioDynamics, Latham, New York).

Mirizzi Syndrome: An Unusual Complication of Cholelithiasis.

Mirizzi syndrome is a rare condition caused by the obstruction of the common bile duct or common hepatic duct by external compression from multiple impacted gallstones or a single large impacted gallstone in Hartman's pouch. The condition can easily be confused with choledocholithiasis, bile duct stricture or cholangiocarcinoma due to the presence of obstructive jaundice hence may be overlooked due to the rarity of the condition. The incidence of Mirizzi syndrome among patients with gallstones is reported to range from 0.63 to 5.7%. Furthermore, it poses a differential diagnosis dilemma for the physician as well as radiologists because there are no clinical features or diagnostic procedures that have a 100% specificity and sensitivity. Laparotomy is the preferred surgical technique of choice. For the patients who are poor surgical candidate, mainstay of treatment is biliary stent placement for the restoration of normal biliary drainage. Due to low incidence of the Mirizzi syndrome, an elevated index of suspicion is required to diagnose this condition. At present, there are no well-developed, internationally recognized clinical guidelines for the management of this syndrome. Furthermore, the diagnostic procedures available still pose a barrier in the ability to confirm the diagnosis prior to surgical treatment, even though the diagnostic rate has increased dramatically.

Teaching Urology to Undergraduates: A Prospective Survey of What General Practitioners Need to Know.

BACKGROUND: Higher education training in Medicine has considerably evolved in recent years. One of its main goals has been to ensure the training of students as future adequately qualified general practitioners (GPs). Tools need to be developed to evaluate and improve the teaching of Urology at the undergraduate level. Our objective is to identify the knowledge and skills needed in Urology for the real clinical practice of GPs. METHODS: An anonymous self-administered survey was carried out among GPs of Primary Care and Emergencies which sought to evaluate urological knowledge and necessary urological skills. The results of the survey were exported and descriptive statistics were performed using IBM SPSS Statistics version 19.0. RESULTS AND LIMITATIONS: A total of 127 answers were obtained, in which 'Urological infections', 'Renal colic', 'PSA levels and screening for prostate cancer', 'Benign prostatic hyperplasia', 'Hematuria', 'Scrotal pain', 'Prostate cancer diagnosis', 'Bladder cancer diagnosis', 'Urinary incontinence', and 'Erectile dysfunction' were rated as Very high or High formative requirements (>75%). Regarding urological skills, 'Abdominal examination', 'Interpretation of urinalysis', 'Digital rectal examination', 'Genital examination', and 'Transurethral catheterization' were assessed as needing Very high or High training in more than 80% of the surveys. The relevance of urological pathology in clinical practice was viewed as Very high or High in more than 80% of the responses. CONCLUSIONS: This study has shown helpful results to establish a differentiated prioritization of urological knowledge and skills in Primary Care and Emergencies. Efforts should be aimed at optimizing the teaching in Urology within the Degree of Medicine which consistently ensures patients' proper care by future GPs.

Impact of COVID-19 pandemic on patients and health professionals of a radiation oncology department at a Spanish tertiary hospital.

BACKGROUND: The sanitary emergency created by the COVID-19 pandemic forced us to take exceptional measures that affect decision-making and administration of treatments with radiotherapy. The aim of the study was to analyze the impact of the COVID-19 pandemic on patients and professionals in a radiation oncology department. MATERIALS AND METHODS: We implement a plan with the objectives of maintaining radiotherapy treatment in those patients who need it and, at the same time, reducing the risk of spreading the virus to staff and patients. This plan included measures aimed at limiting the patient's stay in hospital, selecting those patients in whom radiotherapy cannot be delayed and protecting against infection through the use of physical protective measures. RESULTS: Between March 16 and May 31, 2020, 360 patients received radiotherapy in our department. In 14 patients (4.7%) the start of treatment was delayed by an average of 28 days. Four patients had a positive COVID-19 polymerase chain reaction (PCR ) (6.6% and 1.1% of tested and all patients, respectively). Among the professionals, two PCR s were positive (16.6% and 4% of tested and all individuals, respectively). In the serology analysis 4 out of 50 department members were IgG positive (8%). CONCLUSIONS: Despite the fact that our department is located in a region with a high incidence of COVID-19 infection, the impact of the pandemic on our patients and staff has been moderate. The implementation of measures against infection and an adequate selection of patients for treatment allows radiation oncology departments to maintain clinical activity.

Adding value to tumor staging in head and neck cancer: The role of metabolic parameters as prognostic factors.

BACKGROUND: Validated biomarkers in head and neck squamous cell carcinoma (HNSCC) are scarce. METHODS: We retrospectively analyzed 62 patients with HNSCC treated with radiotherapy +/- concurrent chemotherapy. Pretreatment metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured in a 18 F-FDG positron emission tomography using a liver dependent standardized uptake value threshold. Cox regression analyses were performed to find associations with disease-free survival (DFS) and overall survival (OS). RESULTS: High values of MTV (>37 ml) were independently associated with a worse DFS (hazard ratio [HR] = 3.45; 95% confidence interval [CI], 1.52-7.84) and OS (HR = 3.27; 95% CI, 1.41-7.57). Similar results were found for high values of TLG (>247 g) for DFS (HR = 3.32; 95% CI, 1.44-7.65) and OS (HR = 3.42; 95% CI, 1.45-8.07). CONCLUSIONS: MTV and TLG can be considered as independent prognostic factors for DFS and OS in patients with HNSCC. Considering how easily obtainable they are, they may be useful for predicting clinical outcomes in these patients.

Metabolic tumor volume and total lesion glycolysis as prognostic factors in head and neck cancer: Systematic review and meta-analysis.

The role of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in head and neck cancer (HNC) prognosis is not well established. We conducted a systematic review focusing on MTV and TLG measured by 18 F-FDG positron-emission tomography in HNC. Meta-analyses were developed, estimating hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS). Eighteen studies were found with a total of 1512 patients. MTV-adjusted analysis had an HR of 4.65 (95% CI = 2.04-10.6) for DFS and 3.89 (95% CI = 1.47-10.30) for OS. TLG-unadjusted analysis had an HR of 3.19 (95% CI = 2.33-4.37) for DFS and 2.48 (95% CI = 1.82-3.39) for OS. TLG-adjusted analysis for DFS obtained an HR of 2.05 (95% CI = 0.96-4.39). MTV and TLG are good prognostic factors in HNC, as high values predict a worse OS and DFS. Given the important information they provide, these parameters may be considered in clinical practice, as they are easily obtainable with current technology.

Assessment of Safety and Efficacy of Combined Trabectedin and Low-Dose Radiotherapy for Patients With Metastatic Soft-Tissue Sarcomas: A Nonrandomized Phase 1/2 Clinical Trial.

Importance: Active therapeutic combinations, such as trabectedin and radiotherapy, offer potentially higher dimensional response in second-line treatment of advanced soft-tissue sarcomas. Dimensional response can be relevant both for symptom relief and for survival. Objective: To assess the combined use of trabectedin and radiotherapy in treating patients with progressing metastatic soft-tissue sarcomas. Design, Setting, and Participants: Phase 1 of this nonrandomized clinical trial followed the classic 3 + 3 design, with planned radiotherapy at a fixed dose of 30 Gy (3 Gy/d for 10 days) and infusion of trabectedin at 1.3 mg/m2 as the starting dose, 1.5 mg/m2 as dose level +1, and 1.1 mg/m2 as dose level -1. Phase 2 followed the Simon optimal 2-stage design. Allowing for type I and II errors of 10%, treatment success was defined as an overall response rate of 35%. This study was conducted in 9 sarcoma referral centers in Spain, France, and Italy from April 13, 2015, to November 20, 2018. Adult patients with progressing metastatic soft-tissue sarcoma and having undergone at least 1 previous line of systemic therapy were enrolled. In phase 2, patients fitting inclusion criteria and receiving at least 1 cycle of trabectedin and the radiotherapy regimen constituted the per-protocol population; those receiving at least 1 cycle of trabectedin, the safety population. Interventions: Trabectedin was administered every 3 weeks in a 24-hour infusion. Radiotherapy was required to start within 1 hour after completion of the first trabectedin infusion (cycle 1, day 2). Main Outcomes and Measures: The dose-limiting toxic effects of trabectedin (phase 1) and the overall response rate (phase 2) with use of trabectedin plus irradiation in metastatic soft-tissue sarcomas. Results: Eighteen patients (11 of whom were male) were enrolled in phase 1, and 27 other patients (14 of whom were female) were enrolled in phase 2. The median ages of those enrolled in phases 1 and 2 were 42 (range, 23-74) years and 51 (range, 27-73) years, respectively. In phase 1, dose-limiting toxic effects included grade 4 neutropenia lasting more than 5 days in 1 patient at the starting dose level and a grade 4 alanine aminotransferase level increase in 1 of 6 patients at the +1 dose level. In phase 2, among 25 patients with evaluable data, the overall response rate was 72% (95% CI, 53%-91%) for local assessment and 60% (95% CI, 39%-81%) for central assessment. Conclusions and Relevance: The findings of this study suggest that the recommended dose of trabectedin for use in combination with this irradiation regimen is 1.5 mg/m2. The trial met its primary end point, with a high overall response rate that indicates the potential of this combination therapy for achieving substantial tumor shrinkage beyond first-line systemic therapy in patients with metastatic, progressing soft-tissue sarcomas. Trial Registration: ClinicalTrials.gov Identifier: NCT02275286.

The effects of tobacco consumption on paternity rates of adults with a history of cryptorchidism.

OBJECTIVE: To determine the effect of tobacco consumption on paternity rates in men with a history of cryptorchidism. To compare the paternity rates between formerly unilateral, bilateral cryptorchid smokers, and nonsmokers. METHODS: A retrospective cohort study of 153 men who had undergone orchiopexy between 1961 and 1985 at the Miguel Servet University Hospital (116 unilateral and 37 bilateral) and a control group of 100 men were evaluated by review of medical records and a questionnaire. RESULTS: A total of 197 men filled the questionnaire (76.7%). There was no difference in paternity rates between smokers compared to nonsmokers (P = 0.21). In the unilateral cryptorchid men (ULC) group, there is no difference in paternity rates when compared with the controls (P = 0.079) or when comparing ULC smokers to ULC nonsmokers (P = 0.35). In the bilateral cryptorchid men (BLC) group, there is no difference in paternity rates when compared to controls (P = 0.075) or when comparing BLC smokers to BLC nonsmokers (P = 0.36). When comparing according to consumption, there is no difference between mild, moderate or heavy smoker cases and controls. CONCLUSION: There is no difference in paternity rates between men with a history of cryptorchidism that consume tobacco compared to nonsmokers or controls. More studies are needed to determine the impact of tobacco consumption in formerly cryptorchid men.

The Melanocortin 4 Receptor p.Ile269Asn Mutation Is Associated with Childhood and Adult Obesity in Mexicans.

CONTEXT: Rare partial/complete loss-of-function mutations in the melanocortin-4 receptor (MC4R) gene are the most common cause of Mendelian obesity in European populations, but their contribution to obesity in the Mexican population is unclear. OBJECTIVE AND DESIGN: We investigated whether deleterious mutations in MC4R contribute to obesity in Mexican children and adults. RESULTS: We provide evidence that the MC4R p.Ile269Asn (rs79783591) mutation may have arisen in modern human populations from a founder event in native Mexicans. The MC4R Isoleucine 269 is perfectly conserved across 184 species, which suggests a critical role for the amino acid in MC4R activity. Four in silico tools (SIFT, PolyPhen-2, CADD, MutPred2) predicted a deleterious impact of the p.Ile269Asn substitution on MC4R function. The MC4R p.Ile269Asn mutation was associated with childhood (Ncontrols = 952, Ncases = 661, odds ratio (OR) = 3.06, 95% confidence interval (95%CI) [1.94-4.85]) and adult obesity (Ncontrols = 1445, Ncases = 2,487, OR = 2.58, 95%CI [1.52-4.39]). The frequency of the MC4R p.Ile269Asn mutation ranged from 0.52 to 0.59% and 1.53 to 1.59% in children and adults with normal weight and obesity, respectively. The MC4R p.Ile269Asn mutation co-segregated perfectly with obesity in 5 multigenerational Mexican pedigrees. While adults with obesity carrying the p.Ile269Asn mutation had higher BMI values than noncarriers, this trend was not observed in children. The MC4R p.Ile269Asn mutation accounted for a population attributable risk of 1.28% and 0.68% for childhood and adult obesity, respectively, in the Mexican population. CONCLUSION: The MC4R p.Ile269Asn mutation may have emerged as a founder mutation in native Mexicans and is associated with childhood and adult obesity in the modern Mexican population.