Imaging response to immune checkpoint inhibitors in patients with advanced melanoma: a retrospective observational cohort study.

Background: The association between objective imaging response and first line immune checkpoint inhibitor (ICI) therapy regimes in advanced melanoma remains uncharacterized in routine practice. Methods: We conducted a multi-center retrospective cohort analysis of advanced melanoma patients receiving first line ICI therapy from August 2013-May 2020 in Alberta, Canada. The primary outcome was likelihood of RECIST v1.1 assessed objective imaging response between patients receiving anti-programmed cell death protein 1 (anti-PD1) monotherapy and those receiving combination ipilimumab-nivolumab. Secondary outcomes were identification of baseline characteristics associated with non-response and the association of imaging response with overall survival (OS) and time to next treatment (TTNT). Results: 198 patients were included, 41/198 (20.7%) had complete response, 86/198 (43.4%) had partial response, 23/198 (11.6%) had stable disease, and 48/198 (24.2%) had progressive disease. Median OS was not reached (NR) (95% CI 49.0-NR) months for complete responders, NR (95%CI 52.9-NR) months for partial responders, 33.7 (95%CI 15.8-NR) months for stable disease, and 6.4 (95%CI 5.2-10.1) months for progressive disease (log-rank p<0.001). Likelihood of objective imaging response remained similar between anti-PD1 monotherapy and ipilimumab-nivolumab groups (OR 1.95 95%CI 0.85-4.63, p=0.121). Elevated LDH level (OR 0.46; 95%CI 0.21-0.98, p=0.043), mucosal primary site (OR 0.14; 95%CI 0.03-0.48, p=0.003), and BRAF V600E mutation status (OR 0.31; 95%CI 0.13-0.72, p=0.007) were associated with decreased likelihood of response. Conclusion: No significant difference in likelihood of imaging response between anti-PD1 monotherapy and combination ipilimumab-nivolumab was observed. Elevated LDH level, mucosal primary site, and BRAF V600E mutation status were associated with decreased likelihood of response. Given that pivotal clinical trials of ipilimumab-nivolumab did not formally compare ipilimumab-nivolumab with nivolumab monotherapy, this work adds context to differences in outcomes when these agents are used. These results may inform treatment selection, and aid in counseling of patients treated with first-line ICI therapy in routine clinical practice settings.

Changes in substance use among adolescents before and during the COVID-19 pandemic in Guatemala.

Objectives: Due to the COVID-19 pandemic, on March 16th, schools had to be closed in Guatemala and went to online teaching. We sought to analyze the change in substance use among high school students in Guatemala associated with the lockdown. Methods: Data from two surveys (2019, n=2096, and 2020, n=1606) of a student cohort in private high schools in Guatemala City was used. Logistic models for past 30-day cigarette, e-cigarette, marijuana, and alcohol (including binge drinking) were used, regressing these on survey wave, while adjusting for sex, scholastic performance, high school year of student, parental education, substance use, and household member tobacco use. Results: Prevalence declined for smoking (10% to 3%, p<0.001), e-cigarette (31% to 14%, p<0.001), marijuana (4.3% to 1.9%, p<0.001), and alcohol use (47% to 38.5%, p<0.001), and binge drinking (24% to 13%, p<0.001). Adjusted models showed wave 2 associated with lower odds of using cigarettes (AOR=0.44, 95%CI=0.32-0.62), e-cigarettes (AOR=0.41, 95% CI=0.35-0.49, p<0.001), and binge drinking (AOR=0.73, 95%CI=0.59-0.89; p=0.002). Conclusion: Among Guatemalan adolescents, COVID-19 restrictions were associated with a significant decrease in smoking, e-cigarette use, and binge drinking.

A low-cost, DIY tourniquet simulator with built-in self-assessment for prehospital providers in Guatemala city.

BACKGROUND: Hemorrhage is the leading cause of preventable death after trauma. In high-income countries first responders are trained in hemorrhage control techniques but this is not the case for developing countries like Guatemala. We present a low-cost training model for tourniquet application using a combination of virtual and physical components. METHODS: The training program includes a mobile application with didactic materials, videos and a gamified virtual reality environment for learning. Additionally, a physical training model of a bleeding lower extremity is developed allowing learners to practice tourniquet application using inexpensive and accessible materials. Validation of the simulator occurred through content and construct validation. Content validation involved subjective assessments by novices and experts, construct validation compared pre-training novices with experts. Training validation compared pre and post training novices for improvement. RESULTS: Our findings indicate that users found the simulator useful, realistic, and satisfactory. We found significant differences in tourniquet application skills between pre-training novices and experts. When comparing pre- and post-training novices, we found a significantly lower bleeding control time between the groups. CONCLUSION: This study suggests that this training approach can enhance access to life-saving skills for prehospital personnel. The inclusion of self-assessment components enables self-regulated learning and reduces the need for continuous instructor presence. Future improvements involve refining the tourniquet model, validating it with first-responder end users, and expanding the training program to include other skills.

Efficacy and safety of a structured de-escalation from antipseudomonal ß-lactams in bloodstream infections due to Enterobacterales (SIMPLIFY): an open-label, multicentre, randomised trial.

BACKGROUND: De-escalation from broad-spectrum to narrow-spectrum antibiotics is considered an important measure to reduce the selective pressure of antibiotics, but a scarcity of adequate evidence is a barrier to its implementation. We aimed to determine whether de-escalation from an antipseudomonal ß-lactam to a narrower-spectrum drug was non-inferior to continuing the antipseudomonal drug in patients with Enterobacterales bacteraemia. METHODS: An open-label, pragmatic, randomised trial was performed in 21 Spanish hospitals. Patients with bacteraemia caused by Enterobacterales susceptible to one of the de-escalation options and treated empirically with an antipseudomonal ß-lactam were eligible. Patients were randomly assigned (1:1; stratified by urinary source) to de-escalate to ampicillin, trimethoprim-sulfamethoxazole (urinary tract infections only), cefuroxime, cefotaxime or ceftriaxone, amoxicillin-clavulanic acid, ciprofloxacin, or ertapenem in that order according to susceptibility (de-escalation group), or to continue with the empiric antipseudomonal ß-lactam (control group). Oral switching was allowed in both groups. The primary outcome was clinical cure 3-5 days after end of treatment in the modified intention-to-treat (mITT) population, formed of patients who received at least one dose of study drug. Safety was assessed in all participants. Non-inferiority was declared when the lower bound of the 95% CI of the absolute difference in cure rate was above the -10% non-inferiority margin. This trial is registered with EudraCT (2015-004219-19) and ClinicalTrials.gov (NCT02795949) and is complete. FINDINGS: 2030 patients were screened between Oct 5, 2016, and Jan 23, 2020, of whom 171 were randomly assigned to the de-escalation group and 173 to the control group. 164 (50%) patients in the de-escalation group and 167 (50%) in the control group were included in the mITT population. 148 (90%) patients in the de-escalation group and 148 (89%) in the control group had clinical cure (risk difference 1·6 percentage points, 95% CI -5·0 to 8·2). The number of adverse events reported was 219 in the de-escalation group and 175 in the control group, of these, 53 (24%) in the de-escalation group and 56 (32%) in the control group were considered severe. Seven (5%) of 164 patients in the de-escalation group and nine (6%) of 167 patients in the control group died during the 60-day follow-up. There were no treatment-related deaths. INTERPRETATION: De-escalation from an antipseudomonal ß-lactam in Enterobacterales bacteraemia following a predefined rule was non-inferior to continuing the empiric antipseudomonal drug. These results support de-escalation in this setting. FUNDING: Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases; Spanish Clinical Research and Clinical Trials Platform, co-financed by the EU; European Development Regional Fund "A way to achieve Europe", Operative Program Intelligence Growth 2014-2020.

Factors Associated With the Changes in Smoking and Electronic cigarette use in Adolescents During the COVID-19 Pandemic: A Longitudinal Analysis.

PURPOSE: Explore the factors associated with the changes in smoking and electronic cigarette (e-cigarette) use and susceptibility among adolescents during the COVID-19 pandemic. METHODS: We surveyed a cohort of students (7th-12th grade) from private schools in Guatemala. Baseline (May-September 2019) was conducted in-person and follow-up (June-November 2020) online during the lockdown. Separate Generalized Estimating Equations logistic models regressed current smoking (n = 3,729), current e-cigarette use (n = 3,729), smoking susceptibility among never-smokers (n = 2,596), and susceptibility to e-cigarette use among never-users (n = 1,597) on online ad exposure, visiting stores, social network smoking/e-cigarette use, substance use (alcohol, marihuana, and cigarette or e-cigarette), perceived harm of using cigarettes/e-cigarettes, sociodemographic characteristics, and survey wave. Interactions were assessed between time and ad exposures, friends smoking and e-cigarette use. RESULTS: Frequency of store visits, exposure to online ads, and the use of cigarette and e-cigarette lowered at follow-up. Online e-cigarette ads, having family and friends who smoke, and current e-cigarette use increased the likelihood of being a current smoker. Frequent exposure to online e-cigarette ads, having family who use e-cigarettes, and being a current smoker were associated with higher likelihood of current e-cigarette use. Exposure to either online ads or having friends that smoke or use e-cigarettes, increased susceptibility to using either product. Interaction results showed that high exposure to online e-cigarette ads overtime increased the susceptibility to use e-cigarettes. DISCUSSION: Exposure to online ads and friends and family cigarette and e-cigarette use increased adolescent consumption and susceptibility during the pandemic.

Management of Uveal Melanoma: Updated Cancer Care Alberta Clinical Practice Guideline.

OBJECTIVE: The purpose of this guideline update is to reassess and update recommendations in the prior guideline from 2016 on the appropriate management of patients with uveal melanoma. METHODS: In 2021, a multidisciplinary working group from the Provincial Cutaneous Tumour Team, Cancer Care Alberta, Alberta Health Services was convened to update the guideline. A comprehensive review of new research evidence in PubMed as well as new clinical practice guidelines from prominent oncology groups informed the update. An enhancement in methodology included adding levels of evidence and strength of recommendations. The updated guideline was circulated to all members of the Provincial Cutaneous Tumour Team for review and endorsement. RESULTS: New and modified recommendations address provider training requirements, diagnostic imaging for the detection of metastases, neo-adjuvant pre-enucleation radiotherapy, intravitreal anti-vascular endothelial growth factor agents for radiation retinopathy, genetic prognostic testing, surveillance following definitive local therapy, and systemic therapy for patients with metastatic uveal melanoma. DISCUSSION: The recommendations represent evidence-based standards of care agreed to by a large multidisciplinary group of healthcare professionals.

La escala de afluencia familiar en la investigación sobre inequidades sociales en salud en adolescentes latinoamericanos / The family affluence scale for research on social inequities in Latin American adolescents health

Resumen: Objetivo: Evaluar la escala de afluencia familiar (EAF), que consiste en el autorreporte sobre número de computadoras y automóviles del hogar, dormitorio propio y vacaciones, como indicador de nivel socioeconómico (NSE) familiar en adolescentes escolarizados de tres países latinoamericanos. Material y métodos: Fueron encuestados 14 717 estudiantes de secundaria de Argentina, México y Guatemala. Se evaluó la asociación de la EAF con otros indicadores de NSE a nivel familiar (nivel educativo parental, posesión de bienes y servicios tecnológicos) y de entorno escolar (índice de marginación, escuela pública o privada y matrícula escolar). Resultados: La EAF mostró menos datos faltantes que los otros indicadores familiares de NSE. Además, mostró asociaciones en la dirección esperada con los otros indicadores de NSE. Conclusiones: La EAF parece constituir un indicador válido tanto de la riqueza material familiar como del NSE a nivel de la escuela, útil para estudios sobre inequidades en salud en adolescentes latinoamericanos.

Abstract: Objective: To assess the family affluence scale (FAS), which consists of self-reported number of computers and cars in the home, having one's own bedroom and holidays, as a family socioeconomic status (SES) indicator for adolescents in three Latin American countries. Materials and methods: 14 717 secondary students from Argentina, Mexico and Guatemala were surveyed. The association between FAS and other SES indicators at familiar level (parent education and owning of technological goods and services) and school level (marginalization index, public or private school, and school fee) were evaluated. Results: The FAS was associated in the expected direction with all other NSE indicators. Conclusions: The FAS seems to be a valid indicator of the material wealth of adolescent families, as well as of school SES, and it can be used in studies on health inequities in Latin American adolescents.

Carga de enfermedad en el Perú: Estimación de los años de vida saludables perdidos 2012 / Disease burden in Peru: Estimation of healthy life years lost 2012

La publicación constituye el tercer estudio nacional de carga de enfermedad, el mismo que se organiza en cinco secciones. La primera parte hace referencia a los antecedentes que se han sucedido desde las primeras estimaciones mundiales, hasta la experiencia desarrollada en el Perú. La segunda sección, denominada aspectos metodológicos, explica los procedimientos realizados en este estudio para obtener el indicador de AVISA. En la tercera, se presentan los resultados, los cuales se muestran de manera general y luego de manera específica por género y grupos de edad. En cada uno de ellos, se incluye la lista de los principales causas de carga por grupos de enfermedades, categorías y subcategorías. La cuarta sección muestra las conclusiones, resaltando los hallazgos más relevantes identificados durante la elaboración del documento. Finalmente se presentan las recomendaciones con el fin de mejorar los futuros estudios nacionales de carga de enfermedad

Tabaquismo en Guatemala: situación actual / Guatemala smoking: current situation

Según la Organización Mundial de la Salud (OMS), el tabaquismo es una de las principales causas de enfermedad crónica y la principal causa de muerte prevenible a nivel mundial. De no abordarse de manera urgente, para el año 2030 podría llegar a matar a 8 millones de personas anualmente, 80% de estas muertes ocurriendo en países de mediano/bajo ingreso. Los datos sobre la prevalencia de tabaquismo en Guatemala son escasos, según la “Encuesta Global del Tabaco” en el 2008, en los primeros grados de secundaria hay una prevalencia de tabaquismo de 19.7% para hombres y 13.3% para mujeres.

According to the World Health Organization (WHO), smoking is a major cause of chronic disease and the leading cause of preventable death globally. If not addressed urgently, 2030 might get to kill 8 million people annually, 80% of these deaths occurring in middle / low income. Data on smoking prevalence are scarce in Guatemala, according to "Global Survey of Tobacco" in 2008, in the early grades of school is a smoking prevalence of 19.7% for men and 13.3% for women.

Prevalencia de VIH e Infecciones de transmisión sexual y factores de riesgo asociados en mujeres trabajadoras del sexo en Escuintla, Guatemala / Prevalence of HIV and sexually transmitted infections and associated risk factors in Escuintla, Guatemala

Determinar la prevalencia de VIH y otras infecciones de transmisión sexual (ITS) e identificar factores de riesgo asociados entre mujeres trabajadoras del sexo (MTS) de Escuintla, Guatemala, entre junio 2009 y febrero 2010. Se reclutaron 612 MTS de mediana edad de 26 años, que consultaron en clínicas de ITS de centros de atención primaria públicos de Escuintla. Las participantes fueron entrevistadas sobre características sociodemográficas, conductas de riesgo y se tomaron muestras orofaríngeas, ginecológicas, y sanguíneas para ITS/VIH.

Fractura de pene: Estudio de 10 años / Penile fracture: Study of 10 years

INTRODUCCION: La fractura de pene ocurre la mayoría de las veces durante el coito, cuando el órgano, al estar erecto, se flexiona bruscamente. OBJETIVOS: Describir aspectos de la presentación y características de esta entidad, asícomo su diagnóstico y tratamiento. MÉTODOS: Se realizó un estudio descriptivo, a partir de las historias clínicas de 25 pacientes ingresados en el servicio de urología del Hospital Militar Central Dr. Carlos J. Finlay, de enero de 1997 a diciembre de 2006, con el diagnóstico de fractura de pene. Las variables descritas fueron: edad, síntomas y signos, agentes causales, medios diagnósticos utilizados, tratamiento aplicado y complicaciones presentadas. RESULTADOS: Predominó el grupo de edades de 26 a 44 años con el 56 por ciento. El síntoma principal fue el hematoma del pene en el 100 por ciento de los casos y la causa más frecuente fue el traumatismo durante el coito en el 68 por ciento. En el 24 por ciento de los pacientes fue necesario el auxilio de la ecografía peneana, simple o Doppler, para confirmar el diagnóstico; se aplicó el tratamiento quirúrgico en el 72 por ciento de los pacientes. Las complicaciones se presentaron en los casos no operados y consistieron en fibrosis de los cuerpos cavernosos y la disfunción sexual eréctil. CONCLUSIONES: La fractura de pene ocurre fundamentalmente durante el coito. La sintomatología clínica tiene gran valor para el diagnóstico. En caso de dudas, la ecografía simple o Doppler resulta muy útil. El tratamiento quirúrgico es el indicado para evitar secuelas en estos pacientes

INTRODUCTION: The penile fracture is very frequent during the coitus when the organ is in erection undergoes a sudden flexion. OBJECTIVES: To describe the features of presentation and its entity characteristics, as well as its diagnostic and treatment. METHODS: A descriptive study was conducted from the medical records of 25 patients admitted in the Urology Service of the Dr. Carlos J. Finlay Military Hospital from January, 1997 to December, 2006 diagnosed with penile fracture. The variables described were: age, symptoms and signs, causal agents, diagnostic means used, applied treatment and present complications. RESULTS: There was predominance of ages from 26 to 44 years with the 565. The major symptom was a penile hematoma in the 100 percent of cases and the more frequent cause was the trauma during coitus in the 68 percent. In the 24 percent of patients it was necessary the penile single echography or Doppler to verify the diagnosis; surgical treatment was applied in the 72 percent of patients. The complications were present in the non-operated on cases including fibrosis of cavernous bodies and an erectile sexual dysfunction. CONCLUSIONS: The penile fracture occurs mainly during the coitus. The clinical symptomatology is very important for diagnosis. If there are doubts the single echography or Doppler is very useful. The surgical treatment is the more appropriate to avoid sequelae in these patients

Carcinoma suprarrenal gigante / Giant suprarenal carcinoma

OBJETIVO: presentar un caso de carcinoma suprarrenal de gran tamaño, su diagnóstico y tratamiento. DESCRIPSIÓN: se presenta un paciente del sexo masculino, de 69 años de edad, con antecedentes de diabetes mellitus tipo II que refería palparse un tumor abdominal. Al examen físico tenía un tumor palpable en la fosa lumbar y flanco izquierdos de aproximadamente 15 a 16 cm de diámetro. El tumor se corroboró en el ultrasonido, por lo que fue necesario realizar la tomografía axial computadorizada simple y contrastada para establecer el origen suprarrenal de este. Se comprobaron niveles elevados de cortisol en plasma. INTERVENSIÓN: se realizó la suprarrenalectomía más la nefrectomía izquierdas. La evolución posoperatoria resultó satisfactoria. El informe histopatológico de la pieza quirúrgica fue carcinoma suprarrenal con infiltración renal. Se indicó tratamiento de quimioterapia con mitotano con posterioridad a la cirugía. En los controles semestral y anual realizados, el paciente se encontró asintomático y con niveles de cortisol sanguíneo normales. El ultrasonido, la tomografía axial computadorizada del abdomen y la radiografía del tórax no mostraron recidiva tumoral ni metástasis. CONCLUSIONES: los carcinomas suprarrenales pueden evolucionar de forma asintomática hasta alcanzar grandes dimensiones. El tratamiento combinado, quirúrgico y con quimioterapia, mejora el pronóstico de estos pacientes.

OBJECTIVE: this is the presentation of a case of a very large suprarenal carcinoma. DESCRIPTION: a male patient aged 69 with a history of type 2 diabetes mellitus mentioning the palpation of a abdominal tumor. At physical examination we noted the presence of a palpable tumor in lumbar fossa and left flanks of approximately 15 to 16 cm diameter. Ultrasound corroborated the tumor being necessary to perform a single and contrasted computed tomography to establish its suprarenal origin. There were high levels of cortisol in plasma. INTERVENTION: a left suprarenalectomy and nephrectomy were performed. Postoperative course was satisfactory. The histopathology report of the surgical specimen was a suprarenal carcinoma with renal infiltration. Chemotherapy with mitotane was prescribed after surgery. In half-yearly and yearly controls the patient was asymptomatic and with normal blood cortisol levels. Ultrasound, computerized axial tomography of abdomen and thorax X-rays not showed tumor relapse neither metastasis. CONCLUSIONS: suprarenal carcinomas may to evolve in an asymptomatic way and to have bid dimensions. Combined treatment of surgery and chemotherapy, improves the prognosis of these patients.

Divertículo vesical congénito gigante / Giant congenital vesical diverticulum

Los divertículos vesicales congénitos son infrecuentes. En el adulto generalmente se detectan asociados a factores obstructivos a la salida vesical, y se manifiestan por sepsis urinaria recurrente en la mayoría de los casos. Se presenta un paciente del sexo masculino de 67 años de edad, que asistió a consulta por infecciones urinarias bajas a repetición. Al examen físico se constató la presencia de un tumor ovoide de unos 10 cm de diámetro, móvil, no doloroso y con matidez a la percusión, en proyección del hipogastrio y lateralizado hacia la izquierda; la próstata al tacto rectal era de tamaño normal y de consistencia fibroelástica. En el ultrasonido, la uretrocistografía y la tomografía axial computadorizada, se evidenció un divertículo vesical gigante, con su cuello hacia la pared lateral izquierda de la vejiga. Se confirmó mediante la cistoscopia y se procedió a su exéresis por cirugía convencional. El informe histopatológico reveló la existencia de las capas mucosa, muscular y adventicia en su pared, de manera que se corroboró su origen congénito. La evolución del paciente resultó satisfactoria. La exéresis total de los divertículos vesicales congénitos de gran tamaño, constituye la solución definitiva para aquellos pacientes que presentan sepsis urinaria recurrente, en ausencia de factores obstructivos al vaciamiento vesical

Congenital vesical diverticula are infrequent. In adult persons generally are detected in association with obstructive factors for vesical outlet with a recurrent urinary sepsis as manifestation in most cases. This is the case of a male patient aged 67 seen in consultation due to repeated low urinary infections. In physical examination was confirmed the presence of a 10 cm ovoid, mobile and no-painful tumor and with a dull sound to percussion in hypogastrium projection and lateralized to left; at rectal tactus it was of normal size and with a fibroelastic consistency. Ultrasound, urethrocystography and computerized axial tomography evidenced a giant vesical diverticulum with its neck to left lateral wall of bladder confirmed by cystoscopy and exeresis by conventional surgery. Histopathological report showed the presence of mucous and muscular layers, and adventitia in its wall, thus confirming its congenital origin. Patient's course was satisfactory. Total exeresis of big congenital vesical diverticula is the definite solution for those patients presenting with recurrent urinary sepsis in the absence of obstructive factors to vesical voiding