Induction avelumab followed by chemoimmunotherapy and maintenance versus chemotherapy alone as first-line therapy in cis-ineligible metastatic urothelial carcinoma (INDUCOMAIN): a randomized phase II study.

BACKGROUND: Platinum-based chemotherapy (ChT) has been the standard first-line treatment for metastatic urothelial carcinoma (mUC). The purpose of this study was to evaluate the use of induction avelumab followed by avelumab in combination with carboplatin-gemcitabine (carbo/gem) followed by avelumab maintenance. We tested the hypothesis that induction immunotherapy (IO) could enhance the response to ChT and prevent its detrimental effect on immune cells. MATERIALS AND METHODS: INDUCOMAIN is a multicenter, randomized, investigator-initiated, open-label phase II study evaluating the safety and efficacy of induction avelumab before carboplatin-gemcitabine-avelumab, followed by avelumab maintenance (arm A), compared to carbo/gem (arm B). Eligibility criteria included patients with mUC, no prior systemic therapy, and ineligibility for cisplatin by Galsky criteria. Patients were stratified by the presence/absence of visceral metastasis and Eastern Cooperative Oncology Group performance status 0-1 versus 2. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Eighty-five patients were included and randomized to arm A (n = 42) and arm B (n = 43), respectively. ORR was similar between treatment arms: 59.5% in arm A and 53.5% in arm B (P = 0.57). Fourteen patients (33%) in arm A early progressed/died before or at first response assessment, compared to three patients (7%) in arm B. Median OS was 11.1 months in arm A and 13.2 months in arm B [hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.57-1.46, P = 0.69]. Median PFS was 6.9 months in arm A versus 7.4 months in arm B (HR 0.99, 95% CI 0.61-1.60, P = 0.95). Treatment-related adverse events of grade 3-4 occurred in 70.7% of patients in arm A and in 72.1% in arm B. No predictive role of programmed death-ligand 1 expression was found. CONCLUSIONS: The hypothesis that induction avelumab could enhance the efficacy of subsequent ChT was not proven. Administering IO alone as induction before ChT is not an adequate strategy.

Improved LINE-1 Detection through Pattern Matching by Increasing Probe Length.

Long Interspersed Element-1 (LINE-1 or L1) is an autonomous transposable element that accounts for 17% of the human genome. Strong correlations between abnormal L1 expression and diseases, particularly cancer, have been documented by numerous studies. L1PD (LINE-1 Pattern Detection) had been previously created to detect L1s by using a fixed pre-determined set of 50-mer probes and a pattern-matching algorithm. L1PD uses a novel seed-and-pattern-match strategy as opposed to the well-known seed-and-extend strategy employed by other tools. This study discusses an improved version of L1PD that shows how increasing the size of the k-mer probes from 50 to 75 or to 100 yields better results, as evidenced by experiments showing higher precision and recall when compared to the 50-mers. The probe-generation process was updated and the corresponding software is now shared so that users may generate probes for other reference genomes (with certain limitations). Additionally, L1PD was applied to other non-human genomes, such as dogs, horses, and cows, to further validate the pattern-matching strategy. The improved version of L1PD proves to be an efficient and promising approach for L1 detection.

EUS-guided tissue acquisition in patients with solid pseudopapillary neoplasms of the pancreas.

OBJECTIVES: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) has been the most common method used for the preoperative cytopathological diagnosis of solid tumors of the pancreas. There are only a few reported cases about the role of endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) in the pre-operative diagnosis of solid pseudopapillary neoplasms (SPN). This study aimed to evaluate the diagnostic yield of EUS-TA,including endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) andEUS-FNB, in patients with SPN. METHODS: We performed a retrospective analysis of patients with EUS-TA for SPN diagnosis in 2 referral centers. The primary outcome was the diagnostic yield of EUS-TA compared to the surgical specimen. RESULTS: Seventy-four patients with SPN of the pancreas were identified. Eighteen had a EUS-TA (10 EUS-FNB and 8 EUS-FNA). The median age of the patients was 31 years (IQR 21-38), and all patients were women. The most common presenting symptom was abdominal pain. Most of the tumors were in the head of the pancreas (9/18; 50%). The median tumor size by EUS was 4.5 cm (min-max 2-15 cm). The most common appearance on EUS was a solid lesion (n = 8/18, 44.4%). A definitive presurgical cytopathological diagnosis was obtained in 16/18 patients (88.8%) with EUS-TA. The sensitivity and positive predictive value of the EUS-TA were 94% each. One patient in the EUS-FNB group developed mild acute pancreatitis. CONCLUSION: The diagnostic yield of the EUS-TA in SPN is high. In most cases, the diagnosis was obtained with the first procedure. No differences in the diagnostic yield or AEs between EUS-FNA vs. EUS-FNB needles were seen.

Mortality in patients with unresectable gastric cancer complicated with tumor bleeding.

BACKGROUND: gastric cancer (GC) is a gastrointestinal (GI) neoplasia which often complicates with GI bleeding. It is uncertain if bleeding worsens mortality in this group of patients. AIMS: to compare 30- and 90-day mortality in patients with unresectable GC (uGC) and tumor bleeding versus patients with the same neoplasia without bleeding. METHODS: a retrospective analysis of patients with uGC, with and without tumor bleeding was performed. Survival analysis for 30- and 90-days mortality was performed using Cox regression. Logistic regression was used to identify risk factors associated with mortality and first bleeding episode. RESULTS: 202 patients were included in the analysis (105 cases). Mortality at 90 days was 37.14 % for cases and 20.62 % for controls (p = 0.04). There was a significant difference in hazard ratio (HR) at 90 days for cases compared to controls (HR 1.95, 95 % CI 1.14-3.34, p = 0.02). Cases without palliative chemotherapy had the highest 90-days mortality (HR 5.43, 95 % CI 2.12-13.87, p < 0.01), compared to controls treated with chemotherapy. Predictors for first tumor bleeding were clinical stage IV (OR 2.93, 95 % CI 1.04-8.26, p = 0.04), Helicobacter pylori infection (OR 2.80, 95 % CI 1.35-5.80, p < 0.01) and histologic intestinal-subtype (OR 2.14, 95 % CI 1.07-4.30, p = 0.03). CONCLUSIONS: tumor bleeding increases 90-days mortality in patients with uGC. Prevention of the first bleeding episode might improve outcome in these patients and the recognition of high-risk patients might help decision-making.

Does Rectoanal Intussusception Limit Improvements in Clinical Outcome and Quality of Life After Sacral Nerve Stimulation for Fecal Incontinence?

BACKGROUND: Sacral nerve stimulation is a treatment option for severe, medically refractory fecal incontinence, although its use in patients with anatomic abnormalities remains controversial. OBJECTIVE: This study aimed to determine whether patients with rectoanal intussusception achieve similar benefits from device implantation to patients without rectoanal intussusception. DESIGN: Retrospective review of a prospectively maintained database. Demographics and clinical data were collected for each patient, including preoperative pelvic floor testing. Defecographies were reanalyzed in a blinded manner. Preoperative rectoanal intussusception was determined on the basis of the Oxford system (grade III-IV vs not; grade V excluded). SETTINGS: Academic-affiliated pelvic health center. PATIENTS: All patients undergoing sacral nerve stimulation for fecal incontinence between July 2011 and July 2019. MAIN OUTCOME MEASURES: Cleveland Clinic Florida Incontinence/Wexner Scores, Fecal Incontinence Severity Indices, and Fecal Incontinence Quality of Life Indices at 1 year. RESULTS: One hundred sixty-nine patients underwent sacral nerve stimulation for fecal incontinence during the study period. The average age was 60.3 years and 91% were female. Forty-six patients (27.2%) had concomitant rectoanal intussusception (38 patients [22.5%] grade III and 8 patients [4.7%] grade IV). Before surgery, patients reported an average of 10.8 accidents per week and a Wexner score of 15.7, with no difference between patients with and without rectoanal intussusception ( p = 0.22 and 0.95). At 1 year after surgery, the average Wexner score was 9.5. There was no difference in postoperative Wexner scores (10.4 vs 9.2, p = 0.23) or improvement over time between patients with and without rectoanal intussusception (-6.7 vs -5.7, p = 0.40). Similarly, there was no difference in quality of life or frequency of incontinence to liquid or solid stool. LIMITATIONS: Single-institution, moderate sample size, incomplete survey response. CONCLUSIONS: Concomitant rectoanal intussusception does not appear to affect clinical outcomes or quality of life after sacral nerve stimulation for fecal incontinence. Appropriate patients with fecal incontinence and rectoanal intussusception can be considered for sacral nerve stimulation placement. See Video Abstract at http://links.lww.com/DCR/C192 . LA INTUSUSCEPCIN RECTOANAL LIMITA LAS MEJORAS EN EL RESULTADO CLNICO Y LA CALIDAD DE VIDA DESPUS DE LA NEUROESTIMULACION SACRA PARA LA INCONTINENCIA FECAL: ANTECEDENTES:La neuroestimulación sacra es una opción de tratamiento para la incontinencia fecal grave refractaria al tratamiento médico, aunque su uso en pacientes con anomalías anatómicas sigue siendo controvertido.OBJETIVO:Determinar si los pacientes con intususcepción rectoanal logran beneficios similares de la implantación del dispositivo a los pacientes sin intususcepción rectoanal.DISEÑO:Revisión retrospectiva de una base de datos mantenida prospectivamente. Se recopilaron datos demográficos y clínicos de cada paciente, incluidas las pruebas preoperatorias del piso pélvico. Las defecografías se volvieron a analizar de forma ciega. La intususcepción rectoanal preoperatoria se determinó según el sistema de Oxford (grado III-IV vs. no; grado V excluido).ESCENARIO:Centro académico de salud pélvica.PACIENTES:Todos los pacientes sometidos a neuroestimulación sacra por incontinencia fecal entre julio de 2011 y julio de 2019.PRINCIPALES MEDIDAS DE RESULTADO:Cleveland Clinic Florida Incontinence/Wexner Scores, Índices de gravedad de la incontinencia fecal, Índices de calidad de vida de la incontinencia fecal al año.RESULTADOS:169 pacientes se sometieron a neuroestimulación sacra por incontinencia fecal durante el período de estudio. La edad promedio fue de 60.3 años y el 91% eran mujeres. Cuarenta y seis pacientes (27.2%) tenían intususcepción rectoanal concomitante (38 [22.5%] grado III y 8 [4.7%] grado IV). Antes de la cirugía, los pacientes informaron un promedio de 10.8 accidentes por semana y una puntuación de Wexner de 15.7 sin diferencia entre pacientes con y sin intususcepción rectoanal (p = 0.22 y 0.95). Un año después de la cirugía, la puntuación promedio de Wexner fue de 9.5. No hubo diferencia en las puntuaciones de Wexner posoperatorias (10.4 frente a 9.2, p = 0.23) o mejoría con el tiempo entre los pacientes con y sin intususcepción rectoanal (-6.7 frente a -5.7, p = 0.40). De manera similar, no hubo diferencia en la calidad de vida o la frecuencia de incontinencia de heces líquidas o sólidas.LIMITACIONES:Institución única, tamaño de muestra moderado, respuesta de encuesta incompleta.CONCLUSIÓN:La intususcepción rectoanal concomitante no parece afectar los resultados clínicos o la calidad de vida después de la neuroestimulación sacra para la incontinencia fecal. Los pacientes apropiados con incontinencia fecal e intususcepción rectoanal pueden ser considerados para la neuroestimulación sacra. Consulte Video Resumen en http://links.lww.com/DCR/C192(Traducción-Dr. Jorge Silva Velazco ).

Oropouche Virus Glycoprotein Topology and Cellular Requirements for Glycoprotein Secretion.

Oropouche virus (OROV; genus Orthobunyavirus) is the etiological agent of Oropouche fever, a debilitating febrile illness common in South America. We used recombinant expression of the OROV M polyprotein, which encodes the surface glycoproteins Gn and Gc plus the nonstructural protein NSm, to probe the cellular determinants for OROV assembly and budding. Gn and Gc self-assemble and are secreted independently of NSm. Mature OROV Gn has two predicted transmembrane domains that are crucial for glycoprotein translocation to the Golgi complex and glycoprotein secretion, and unlike related orthobunyaviruses, both transmembrane domains are retained during Gn maturation. Disruption of Golgi function using the drugs brefeldin A and monensin inhibits glycoprotein secretion. Infection studies have previously shown that the cellular endosomal sorting complexes required for transport (ESCRT) machinery is recruited to Golgi membranes during OROV assembly and that ESCRT activity is required for virus secretion. A dominant-negative form of the ESCRT-associated ATPase VPS4 significantly reduces recombinant OROV glycoprotein secretion and blocks virus release from infected cells, and VPS4 partly colocalizes with OROV glycoproteins and membranes costained with Golgi markers. Furthermore, immunoprecipitation and fluorescence microscopy experiments demonstrate that OROV glycoproteins interact with the ESCRT-III component CHMP6, with overexpression of a dominant-negative form of CHMP6 significantly reducing OROV glycoprotein secretion. Taken together, our data highlight differences in M polyprotein processing across orthobunyaviruses, indicate that Golgi and ESCRT function are required for glycoprotein secretion, and identify CHMP6 as an ESCRT-III component that interacts with OROV glycoproteins. IMPORTANCE Oropouche virus causes Oropouche fever, a debilitating illness common in South America that is characterized by high fever, headache, myalgia, and vomiting. The tripartite genome of this zoonotic virus is capable of reassortment, and there have been multiple epidemics of Oropouche fever in South America over the last 50 years, making Oropouche virus infection a significant threat to public health. However, the molecular characteristics of this arbovirus are poorly understood. We developed a recombinant protein expression system to investigate the cellular determinants of OROV glycoprotein maturation and secretion. We show that the proteolytic processing of the M polypeptide, which encodes the surface glycoproteins (Gn and Gc) plus a nonstructural protein (NSm), differs between OROV and its close relative Bunyamwera virus. Furthermore, we demonstrate that OROV M glycoprotein secretion requires the cellular endosomal sorting complexes required for transport (ESCRT) membrane-remodeling machinery and identify that the OROV glycoproteins interact with the ESCRT protein CHMP6.

Sistema de gestión de riesgos para reducir el contagio de COVID-19 en el personal de salud / Risk management system to reduce COVID-19 infection in health personnel / Sistema de gestão de riscos para reduzir o contágio de COVID-19 em profissionais de saúde

RESUMEN Objetivo. Evaluar los factores laborales asociados con la ocurrencia de COVID-19 en el personal de salud expuesto a distinta magnitud de riesgo con el uso de la política de gestión de crisis de las Naciones Unidas para COVID-19. Métodos. Encuesta transversal realizada entre abril y mayo del 2021. Se consideraron como grupo de riesgo bajo (GRB) quienes tenían contacto mínimo con pacientes; de riesgo medio (GRM) a quienes tenían contacto con pacientes no-COVID-19 y no realizaban intervención instrumental de vías respiratorias; y de riesgo alto (GRA) a quienes atendían pacientes COVID-19 y realizaban intervención instrumental con generación de aerosoles. Se consideró como desenlace el antecedente de enfermedad diagnosticada de COVID-19 y la presencia de anticuerpos IgG positivos contra el SARS-CoV-2 medida con Elecsys® anti-SARS-CoV-2. Resultados. Desenlace en 43,8% en el GRB; 46,7% en el GRM (razón de momios [RM]: 1,125; intervalo de confianza de 95% [IC95%]: 0,896-1,414; p = 0,311); y 48,6% en el GRA (RM: 1,214; IC95%: 0,964-1,530; p = 0,10). Conclusión. Pertenecer al GRM y al GRA por el grado de exposición a pacientes confirmados de COVID-19 en el área de trabajo no se asoció con mayor ocurrencia de enfermedad o de seroconversión.

ABSTRACT Objective. To assess the occupational factors associated with the occurrence of COVID-19 in health personnel who were exposed to different magnitudes of risk and who followed the United Nations crisis management policy for COVID-19. Methods. Cross-sectional survey conducted between April and May 2021. The low-risk group (LRG) were considered to be those who had minimal contact with patients; the medium-risk group (MRG) had contact with non-COVID-19 patients and did not perform instrumental airway intervention; and the high-risk group (HRG) were those who cared for COVID-19 patients and performed instrumental intervention with aerosol generation. Diagnosed COVID-19 disease and the presence of positive IgG antibodies for SARS-CoV-2 measured with Elecsys® anti-SARS-CoV-2 were considered as outcomes. Results. Outcome recorded in 43.8% of the LRG, versus 46.7% in the MRG (odds ratio [OR]: 1.125; 95% confidence interval [CI 95% ]: 0.896-1.414; p = 0.311), and 48.6% in the HRG (OR: 1,214; CI 95%: 0.964-1.530; p= 0.10). Conclusion. Belonging to the high-risk group and the medium-risk group, based on the degree of exposure to confirmed COVID-19 patients in the work area, was not associated with a higher occurrence of disease or seroconversion.

RESUMO Objetivo. Avaliar os fatores ocupacionais associados à ocorrência de COVID-19 em profissionais de saúde expostos a diferentes níveis de risco utilizando a política de gestão de crises elaborada pelas Nações Unidas para a COVID-19. Métodos. Pesquisa transversal realizada entre abril e maio de 2021. O grupo de risco baixo (GRB) consistia em profissionais que tinham contato mínimo com os pacientes; o grupo de risco médio (GRM) incluía profissionais que tinham contato com pacientes sem COVID-19 e não realizavam intervenções instrumentais nas vias aéreas; e grupo de risco alto (GRA), profissionais que cuidavam de pacientes com COVID-19 e realizavam intervenções instrumentais com geração de aerossóis. Para estabelecer o desfecho, considerou-se a história de COVID-19 do profissional de saúde e a detecção de anticorpos IgG anti- SARS-CoV-2 por Elecsys® Anti-SARS-CoV-2. Resultados. A doença foi diagnosticada em 43,8% dos profissionais no GRB, 46,7% no GRM (razão de chances ajustada: 1,125; intervalo de confiança de 95% [IC95%]: 0,896-1,414; p = 0,311) e 48,6% no GRA (razão de chances: 1,214; IC95%: 0,964-1,530; p = 0,10). Conclusões. Pertencer ao GRM e ao GRA em função do nível de exposição a pacientes confirmados com COVID-19 no ambiente de trabalho não foi associado a um aumento da ocorrência da doença ou da soroconversão.

Polyserositis as a Post-Covid-19 Complication.

INTRODUCTION: Polyserositis is described as inflammation with effusion of more than one serous membrane. There is very little published literature linking it to COVID-19 as a late complication. OBJECTIVE: Present and describe a case of post-COVID-19 polyserositis. METHODS: Data were collected from the medical record of a female patient admitted for fainting spells and marked weakness. The patient underwent a clinical evaluation, additional hematology, imaging and histopathology tests, and a surgical procedure. The new index, called the abdominal adipose deposit index, was obtained by multiplying the subcutaneous fat thickness by visceral fat thickness, both measured by ultrasound. A cutoff point was established that facilitated discernment of an unhealthy phenotype: normal weight but metabolically obese, a cardiometabolic risk factor. RESULTS: We present the case of a 57-year-old female patient admitted to hospital for fainting spells and marked weakness, four months after COVID-19 infection. She also had a history of obesity, asthma, type 2 diabetes mellitus and a cholecystectomy in December 1992 for gallstones. Clinical assessment revealed pericardial effusion and bilateral pleural effusion, in addition to a tumor-like lesion outside the pericardium, proximal to the right ventricular wall. A surgical procedure and findings from additional tests led to diagnoses of thymic remnants and polyserositis. CONCLUSIONS: This is a case of polyserositis in a post-COVID-19 patient. After other causes of polyserositis were ruled out, and since there is a likely physiological and pathogenic mechanism operating between the two diseases, the polyserositis was determined to be a late complication of COVID-19. To date, it is the second case reported in the world and the first reported in Cuba.

Modelo de Integración DIA-Persona para incrementar la calidad de la docencia, investigación y atención médica. Estrategia orientada a la persona / DIA-Person Integration Model to increase the quality of teaching, research and medical care. A person-oriented strategy

Resumen El modelo actual de la medicina ha distanciado la atención médica, la docencia y la investigación, con impacto en el paciente: durante la atención, el médico omite aplicar el método científico, solo atiende la dolencia sin acompañar al paciente; el investigador médico busca respuestas a preguntas alejadas de las dolencias del paciente y, en el mejor de los casos, realiza investigación en especímenes provenientes de este; la díada estudiante-profesor se caracteriza por la transmisión de conocimiento y deja de lado la comprensión del paciente. Pacientes, médicos, investigadores y estudiantes son ajenos a la toma de decisiones y sin cuestionamientos solo siguen procesos. Una manera de abordar el problema es regresar al Modelo de Integración DIA-persona: "la preocupación y el hacer por la persona, acompañados por la integración de docencia, investigación y atención médica", lo que permitiría el traslado del conocimiento, destrezas y beneficios de una actividad a otra. El modelo consiste en contrastar la condición del paciente con el conocimiento, realizar investigación durante y en paralelo al proceso de atención-docencia médica, así como aplicar el modelo arquitectónico de la investigación "descripción estructurada del juicio clínico", como proceso de referencia y reflexión que integra las actividades de docencia-investigación y atención médica orientadas a la persona.

Abstract Current model of medicine has made for medical care, teaching and research to be driven apart, with an impact on the patient: during the process of care, the doctor fails to apply the scientific method, he only treats the ailment without accompanying the patient. The medical researcher looks for answers to questions far removed from patient ailments and, in thebest-case scenario, conducts research on patient specimens. In addition, the student-teacher dyad is characterized by thetransmission of knowledge and leaves aside understanding of the patient. Patients, doctors, researchers and students are oblivious to decision-making and, without questioning, they merely follow processes. One way to address the problem is to return to the DIA-person Integration Model "concern and doing for the person, accompanied by the integration of teaching, research and medical care", which would allow the transfer of knowledge, skills and benefits from one activity to others. The model consists of contrasting the patient condition with knowledge, carrying out research during and parallel to the medical care-teaching process, as well as applying the architecture of research model "clinical judgment structured description", as a reference and reflection process that integrates the activities of teaching-research and person-oriented medical care.

Prevención de desnutrición aguda moderada con un suplemento alimenticio listo para consumir en niños preescolares de comunidades rurales / Moderate acute malnutrition prevention with a ready-to-use therapeutic food in pre-school children from rural communities

Resumen Introducción: La desnutrición infantil en México alcanza prevalencias de 27.5 % en zonas rurales. Objetivo: Evaluar la efectividad de un suplemento alimenticio listo para consumir (SALC) para corregir desnutrición aguda leve y prevenir desnutrición aguda moderada en preescolares de comunidades rurales. Método: Ensayo clínico aleatorizado por grupos: con y sin SALC (g-SALC y g-S/SALC); se incluyeron niños de dos a cinco años, con puntuaciones-Z de peso para la talla (pZ-P/T) mayor de −2 y menor de −1 y nivel socioeconómico bajo. Todos recibieron educación sobre nutrición, salud e higiene dos veces al mes; los niños del g-SALC debieron consumir diariamente una porción del suplemento. Se evaluó pZ-P/T al inicio y a los cuatro, seis y 12 meses. La comparación entre grupos se realizó con el modelo de riesgos proporcionales de Cox. Resultados: Respecto a la recuperación de desnutrición aguda leve, en g-SALC se observó 68.7 versus 52.1% en el grupo control en el análisis de intención para tratar, con una razón de riesgo (HR) = 1.25; en el análisis por protocolo del primer semestre se observó una HR = 1.48 y en el segundo semestre, HR = 1.56. Un paciente progresó a desnutrición aguda moderada. Conclusiones: El g-SALC mostró resolución significativamente mayor de desnutrición aguda leve.

Abstract Introduction: Child malnutrition in Mexico reaches a prevalence as high as 27.5 % in rural areas. Objective: To assess the effectiveness of a ready-to-use supplementary food (RUSF) to correct mild acute malnutrition and prevent moderate acute malnutrition in preschool children from rural communities. Method: Randomized clinical trial, with assignment to two groups: group with RUSF (RUSF-g) or group without it (non-RUSF-g); children aged from two to five years, with weight-for-height Z-scores (WHZ) between -2 and -1 and low socioeconomic status were included. All received education on nutrition, health and hygiene twice monthly; the RUSF-g children had to consume four biscuits of the supplement every day. WHZ was assessed at baseline and at four, six, and 12 months. The comparison between groups was carried out with Cox proportional hazards model. Results: With regard to mild acute malnutrition correction in the RUSF-g, 68.7 versus 52.1 % in the control group was observed in the intent-to-treat analysis, with a hazard ratio (HR) = 1.25; in the per-protocol analysis of first semester, a HR = 1.48 was observed, and in the second semester, HR = 1.56. One patient progressed to moderate acute malnutrition. Conclusions: The RUSF-g showed a significantly higher resolution of mild acute malnutrition.

Sensibilidad y especificidad de la presión de pulso ampliada como prueba diagnóstica de IRC estadio K/DOQI III-b / Sensitivity and specificity of increased pulse pressure as a diagnostic test for K/DOQI III-b

Resumen Introducción: La presión de pulso ampliada (PPA) se asocia a un filtrado glomerular calculado ≤ 60/mL/minuto/1.73 m2, por lo que puede ser útil como prueba diagnóstica para identificar a personas con insuficiencia renal crónica (IRC) estadio K/DOQI III-b. Objetivo: Determinar la utilidad de la PPA como prueba diagnóstica de IRC estadio K/DOQI III-b. Método: Estudio de prueba diagnóstica que incluyó a pacientes adultos sin comorbilidades, registrados en la Cohorte de Trabajadores de la Salud. Se utilizó la fórmula CKD-EPI para calcular la filtración glomerular. Se determinó la presión de pulso restando la presión arterial diastólica a la presión arterial sistólica. Se calculó sensibilidad, especificidad, valor predictivo positivo, valor predictivo negativo y prevalencia. Se elaboró una curva ROC para determinar el área bajo la curva. Resultados: Se incluyeron 6215 pacientes. Se observó que una PPA ≥ 50 mm Hg tuvo sensibilidad de 74 %, especificidad de 70 %, valor predictivo positivo de 1 %, valor predictivo negativo de 100 % y prevalencia de 1 %. El punto de inflexión en la curva ROC para identificar IRC K/DOQI III-b fue de 0.71. Conclusión: La PPA ≥ 50 mm Hg es útil como prueba diagnóstica para identificar a personas con IRC estadio K/DOQI III-b.

Abstract Introduction: Increased pulse pressure (IPP) is associated an estimated glomerular filtration ≤ 60/mL/min/1.73 m2; thus, it can be useful as a diagnostic test to identify people with K/DOQI stage III-b chronic kidney disease (CKD). Objective: To determine the usefulness of IPP as a diagnostic test for K/DOQI stage III-b CKD. Method: Diagnostic test study that included adult patients without comorbidities, registered in the Health Workers Cohort. The CKD-EPI formula was used to calculate glomerular filtration. Pulse pressure was determined by subtracting diastolic from systolic blood pressure. Sensitivity, specificity, positive predictive value, negative predictive value and prevalence were calculated using standard formulas. A ROC curve was generated to determine the area under the curve. Results: A total of 6,215 patients were included. An IPP ≥ 50 mmHg was observed to have a sensitivity of 74 %, specificity of 70 %, positive predictive value of 1 %, negative predictive value of 100 % and a prevalence of 1 %. The inflection point in the ROC curve to identify K/DOQI III-b CKD was 0.71. Conclusion: An IPP ≥ 50 mmHg is useful as a diagnostic test to identify people with K/DOQI stage III-b CKD.

De vuelta a la clínica. Métodos II. Arquitectura de la investigación clínica. Interacción sujeto, maniobras y enfermedad a través del tiempo / Back to the clinic. Methods II. Architecture of clinical research. Subject interaction, maneuvers and disease throughout time

Resumen La medicina se caracteriza por la aplicación del método científico a través del juicio clínico, por la correcta interpretación y el uso del curso clínico o historia natural de la enfermedad; su descripción más lograda la observamos en la arquitectura de la investigación clínica. A través de una secuencia temporal, este modelo explica el fenómeno de causalidad con tres apartados: estado basal, maniobra y desenlace. En el estado basal se evalúa quién es el paciente, de donde proviene, sus condiciones generales, el diagnóstico, el estadio y la agresividad de la patología, las complicaciones, terapias previas, nivel socioeconómico-cultural, hábitos, indicaciones o contraindicaciones terapéuticas y se prevé la evolución esperada. De la maniobra se pueden evaluar los factores de riesgo o pronóstico, tratamiento específico, sintomático y medidas generales. En el desenlace se vigila la evolución temprana y tardía. El modelo también permite determinar las causas de pérdida de seguimiento. Anticipar la evolución del paciente al reconocer su condición, enfermedad y efecto esperado de la decisiones médicas permite actuar anticipadamente, ya que esperar las manifestaciones del proceso evolutivo de la enfermedad resulta en detrimento del paciente.

Abstract Medicine is characterized by the application of the scientific method through clinical judgment, by correct interpretation and use of the clinical course and/or natural history of the disease; its best description is observed in the architecture of clinical research. Through a temporal sequence, this model explains the phenomenon of causality with three sections: baseline status, maneuver, and outcome. The baseline status assesses who the patient is, where does he come from, his general conditions, the diagnosis, stage and aggressiveness of the pathology, complications, previous therapies, socioeconomic-cultural level, habits, therapeutic indications or contraindications and the expected evolution is anticipated. In the maneuver, risk or prognostic factors, specific or symptom treatment, and general measures could be evaluated. In the outcome, early and late evolution are monitored. The model also allows the causes of follow-up loss to be determined. Anticipating patient evolution by recognizing his condition, disease, and expected effect of medical decisions allows acting in advance, since waiting for the manifestations of the evolutionary process of disease results in detriment to the patient.

Surgical and Pharmacological Outcomes in Acromegaly: Real-Life Data From the Mexican Acromegaly Registry.

CONTEXT: Acromegaly registries constitute a valuable source of therapeutic outcome information in real-life. OBJECTIVE: The objective of this work is to analyze surgical and pharmacological outcomes in the Mexican Acromegaly Registry (MAR). DESIGN AND METHODS: Data were extracted from the MAR informatic platform. Surgical remission was defined by a postoperative postglucose (GH) of less than 1 ng/mL and an insulin-like growth factor 1 (IGF-1) of less than 1.2 × upper limit of normal (ULN). Pharmacological remission was defined by a basal GH of less than 1 ng/mL and an IGF-1 of less than 1.2 × ULN. RESULTS: A total of 650 surgical outcomes were analyzed (94.6% transsphenoidal). Surgical remission was achieved in 40.15%, whereas 44.15% remained biochemically active. Persistently active disease after surgery was significantly associated with harboring an invasive macroadenoma, a basal GH of greater than 10 ng/mL, and/or an IGF-1 of greater than 2 × ULN at diagnosis on bivariate and multivariate analysis. The outcome of monotherapy with first-generation somatostatin analogs (SSAs) was evaluated in 267 patients (adjunctive in 65%), of whom 28.4% achieved remission. Persistently active disease was significantly associated with harboring an invasive macroadenoma as well as with pretreatment basal GH and IGF-1 levels of greater than 10 ng/mL and greater than 2 × ULN, respectively, on bivariate and multivariate analysis. Combined therapy with SSA and cabergoline was analyzed in 100 patients, of whom 19% achieved remission and 44% remained active; in this subset of patients, only a pretreatment IGF-1 of greater than 2 × ULN was significantly associated with persistent disease activity. CONCLUSION: Surgical and pharmacological outcomes in acromegaly are highly dependent on tumor size/invasiveness as well as on the degree of hypersomatotropinemia.

Malignant pleural mesothelioma: Treatment patterns and outcomes from the Spanish Lung Cancer Group.

BACKGROUND: Malignant mesothelioma is a rare but aggressive tumor arising from the pleura, typically associated with exposure to asbestos. The purpose of this investigation was to describe mesothelioma patient characteristics, treatment patterns, and outcomes in Spain. MATERIAL AND METHODS: Patients diagnosed with malignant mesothelioma of the pleura were recorded in an anonymous online database (BEMME, Epidemiologic Spanish Malignant Mesothelioma Database) from June 2008 through May 2013. Patient and tumor characteristics at time of diagnosis, as well as subsequent treatments (surgery, radiation, and chemotherapy), were collected. Among patients treated with chemotherapy, we explored type of chemotherapy regimen and outcomes by treatments. RESULTS: A total of 560 malignant pleural mesothelioma (MPM) patients were recorded. The median age at diagnosis was 68 years, mainly with epithelioid histology (62 %), and any asbestos exposure was noted in 45 % of patients. Nearly two-thirds of patients (71 %) received chemotherapy, mainly platinum-pemetrexed combination, as part of their treatment. Surgery and radiotherapy were given in 36 % and 17 % of patients, respectively. The median overall survival (OS) in the whole cohort was 13.0 months (95 % confidence interval (CI), 11.1-14.8 months) with 1-year OS of 53.2 % (95 % CI, 48.7-57.7 %). In patients receiving first-line chemotherapy (N = 315), the median OS was 13.4 months (95 % CI, 10.8-16.0 months), reaching 20.2 months (95 % CI, 17.2-23.2 months) for those 68 patients receiving maintenance chemotherapy. Results of multivariate analyses showed significant association of ECOG-performance status, histology and treatment response with improved OS in MPM patients treated with palliative chemotherapy. CONCLUSIONS: Despite multimodal therapeutic intervention, survival of patients with mesothelioma in Spain remains poor. Although it did not reach significance in the multivariate analysis, a meaningful additional survival benefit was observed among those patients receiving maintenance chemotherapy.

Progresión de talla y peso en niños y niñas entre 6 y 12 años y su diferencia con las tablas de Ramos Galván 40 años después / Height and weight progression patterns in Mexican children aged between 6 and 12 years and differences with Ramos-Galvan growth charts 40 years later

Resumen Introducción: El peso y la talla de niños y adolescentes son un reflejo del estado de salud y desarrollo socioeconómico de la población. Objetivo: Evaluar las progresiones de talla y peso de niños y niñas mexicanos y compararlas con las tablas del doctor Ramos Galván a 40 años de distancia. Método: Encuesta transversal realizada en población del Programa Nacional de Activación Física Ponte al 100, que incluye niños y niñas de seis a 12 años. Resultados: Se evaluaron 43 670 niños y 44 103 niñas, que se estratificaron por sexo y edad. La progresión de talla entre los seis y 12 años fue de 21 cm en hombres y de 22 cm en mujeres; la progresión de peso fue de 9.86 y 10.05 kg, respectivamente para hombres y mujeres. La proporción de niños de seis y 12 años con sobrepeso fue de 11.2 y 9 % y con obesidad, de 14.7 y 15 %. La proporción de niñas de seis y 12 años con sobrepeso fue de 8.2 y 9.1 % y con obesidad, de 21.7 y 13.3 %, respectivamente. Al comparar los valores obtenidos con los de las tablas del doctor Ramos Galván para niños y niñas, el promedio de diferencia fue de 2 cm. Conclusiones: No se documentó un incremento secular de la talla ni del peso en los últimos 40 años.

Abstract Introduction: Children and adolescents weight and height are a reflection of the health status and socioeconomic development of a population. Objective: To evaluate height and weight progression patterns of Mexican children and compare them with Dr. Ramos-Galván growth charts 40 years later. Method: Cross-sectional survey conducted on the population of the National Physical Activation Program Ponte al 100, which includes boys and girls aged 6-12 years. Results: 43,670 boys and 44,103 girls were assessed, stratified by gender and age. The height progression pattern between six and 12 years was 21 cm in males and 22 cm in females, whereas the weight progression pattern was 9.86 and 10.05 kg, respectively, for males and females. The proportion of 6- and 12-year-old boys who were overweight was 11.2 and 9%, while 14.7 and 15% were obese. The proportion of 6- and 12-year-old girls who were overweight was 8.2 and 9.1%, whereas 21.7 and 13.3%, respectively, were obese. When the obtained values were compared with those of Dr. Ramos Galván growth charts for boys and girls, the average difference was 2 cm. Conclusions: No secular height or weight increase within the last 40 years was documented.

De vuelta a la clínica. Métodos I. Diseños de investigación. Mayor calidad de información, mayor certeza a la respuesta / Back to the clinic. Methods I. Research designs. Higher quality of information, greater certainty to the answer

Resumen Los diseños de investigación se refieren a la forma como se obtiene la información y están limitados por viabilidad ética, económica y temporal. Son estrategias estandarizadas para disminuir los sesgos que en el modelo arquitectónico de la investigación se identifican en el estado basal, maniobra y desenlace; de ahí que no hay diseños específicos para cada pregunta. El diseño con menor probabilidad de sesgos es el ensayo clínico, seguido de la cohorte, el estudio de casos y controles y, finalmente, la encuesta transversal. Entre las principales características que dan mérito a los diseños están las siguientes: la pesquisa de la población, que se refiere a la ubicación de la población en relación con el curso clínico o historia natural de la enfermedad; la maniobra, o acción que se espera modifique la condición basal, que puede ser observacional o experimental; el seguimiento, o monitoreo documentado que se le da a cada sujeto, que puede ser longitudinal o transversal; y la direccionalidad, prolectiva o retrolectiva, que alude al tiempo de recopilación de la información con fines de investigación. Siempre será mejor tener una pregunta valiosa, incluso cuando se responda con un diseño con mayor riesgo de sesgos, que una pregunta irrelevante o sin aplicabilidad.

Abstract Research designs refer to the way information is obtained and are limited by ethical, economic and temporal viability. Research designs are standardized strategies to reduce biases, which in the architectural model of research are identified in the baseline state, the maneuver and the outcome; hence, there are no specific designs for each question. The design with the lowest probability of bias is the clinical trial, followed by cohort and case-control studies and, finally, by cross-sectional surveys. Among the main characteristics that give merit to research designs are the following: population inquiry, which refers to the situation of the population in relation to the clinical course/natural history of the disease; the maneuver, or action that is expected to modify the baseline state, which can be observational or experimental; follow-up, or documented monitoring that is given to each subject, which can be longitudinal or cross-sectional; and directionality, which can prolective or retrolective and refers to the timing of data collection for research purposes. It will always be better having a valuable question, even when answered with a design with higher risk of bias, than a question that is irrelevant or has no applicability.

De vuelta a la clínica: sin justificación no existe pregunta de investigación que valga / Back to the clinic: without justification there is no worthwhile research question

Resumen La formulación de una pregunta de investigación clínica requiere la concurrencia de experiencia clínica y conocimiento en metodología y estadística. Inicialmente, la pregunta de investigación debe contar con una estructura que deje claro qué se busca (consecuencia o desenlace), en quién (estado basal) y por acción de qué (maniobra). Posteriormente, su argumentación debe explorar cuatro aspectos: factibilidad y sensatez del cuestionamiento, ausencia de respuesta previa, relevancia de la respuesta a obtener y aplicabilidad. Una vez que estos aspectos han sido cubiertos en forma satisfactoria puede considerarse que la pregunta es "clínicamente relevante", que es diferente a significancia estadística (la probabilidad de que el resultado se deba al azar y que no refleja la relevancia de la pregunta ni de los resultados). Nunca se debe olvidar que toda maniobra conlleva eventos adversos, que cuando son graves demeritan los buenos resultados. Es imperativo estimar la posible respuesta desde la estructura de la pregunta; la función de la investigación clínica es corroborar o rechazar una hipótesis, no probar empíricamente para ver qué resulta.

Abstract A clinical research question requires the concurrence of clinical experience and knowledge on methodology and statistics in that who formulates it. Initially, a research question should have a structure that clearly establishes what is that which is being sought (consequence or outcome), in whom (baseline status), and by action of what (maneuver). Subsequently, its reasoning must explore four aspects: feasibility and reasonableness of the questioning, lack of a prior answer, relevance of the answer to be obtained, and applicability. Once these aspects are satisfactorily covered, the question can be regarded as being "clinically relevant", which is different from being statistically significant, which refers to the probability of the result being driven by chance, which does not reflect the relevance of the question or the outcome. One should never forget that every maneuver entails adverse events that, when serious, discredit good results. It is imperative to have the possible answer estimated from within the structure of the question. The function of clinical research is to corroborate or reject a hypothesis, rather than to empirically test to find out what the outcome is.

Obesity Is Associated with Changes in Iron Nutrition Status and Its Homeostatic Regulation in Pregnancy.

The influence of obesity on maternal iron homeostasis and nutrition status during pregnancy remains only partially clarified. Our study objectives were (1) to describe how obesity influences broad iron nutrition spectrum biomarkers such as available or circulating iron (serum transferrin receptor (sTfr) and serum iron), iron reserves (ferritin), and functional iron (hemoglobin); and (2) to depict the regulating role of hepcidin. The above was carried out while considering influential factors such as initial iron nutrition status, iron intake, and the presence of inflammation. Ninety three non-anemic pregnant adult women were included, 40 with obesity (Ob) and 53 with adequate weight (AW); all took ≈30 mg/day of supplementary iron. Information on iron intake and blood samples were obtained at gestational weeks 13, 20, 27, and 35. A series of repeated measure analyses were performed using General Linear Models to discern the effect of obesity on each iron indicator; iron intake, hepcidin, and C-reactive protein were successively introduced as covariates. Available and circulating iron was lower in obese women: sTfr was higher (p = 0.07) and serum iron was lower (p = 0.01); and ferritin and hemoglobin were not different between groups. Hepcidin was higher in the Ob group (p = 0.01) and was a significant predictor variable for all biomarkers. Obesity during pregnancy dysregulates iron homeostasis, resembling "obesity hypoferremia".

SEOM clinical guidelines for the treatment of non-small cell lung cancer (2018).

Non-small cell lung cancer (NSCLC) accounts for up to 85% of all lung cancers. The last few years have seen the development of a new staging system, diagnostic procedures such as liquid biopsy, treatments like immunotherapy, as well as deeper molecular knowledge; so, more options can be offered to patients with driver mutations. Groups with specific treatments account for around 25% and demonstrate significant increases in overall survival, and in some subgroups, it is important to evaluate each treatment alternative in accordance with scientific evidence, and even more so with immunotherapy. New treatments similarly mean that we must reconsider what should be done in oligometastatic disease where local treatment attains greater value.

Degradation of L-Ascorbic Acid in the Amorphous Solid State.

Ascorbic acid degradation in amorphous solid dispersions was compared to its degradation in the crystalline state. Physical blends and lyophiles of ascorbic acid and polymers (pectins and polyvinylpyrrolidone [PVP]) were prepared initially at 50:50 (w/w), with further studies using the polymer that best inhibited ascorbic acid crystallization in the lyophiles in 14 vitamin : PVP ratios. Samples were stored in controlled environments (25 to 60 °C, 0% to 23% RH) for 1 mo and analyzed periodically to track the physical appearance, change in moisture content, physical state (powder x-ray diffraction and polarized light microscopy), and vitamin loss (high performance liquid chromatography) over time. The glass transition temperatures of select samples were determined using differential scanning calorimetry, and moisture sorption profiles were generated. Ascorbic acid in the amorphous form, even in the glassy amorphous state, was more labile than in the crystalline form in some formulations at the highest storage temperature. Lyophiles stored at 25 and 40 °C and those in which ascorbic acid had crystallized at 60 °C (≥70% ascorbic acid : PVP) had no significant difference in vitamin loss (P > 0.05) relative to physical blend controls, and the length of storage had little effect. At 60 °C, amorphous ascorbic acid lyophiles (≤60% ascorbic acid : PVP) lost significantly more vitamin (P < 0.05) relative to physical blend controls after 1 wk, and vitamin loss significantly increased over time. In these lyophiles, vitamin degradation also significantly increased (P < 0.05) at lower proportions of ascorbic acid, a scenario likely encountered in foods wherein vitamins are naturally present or added at low concentrations and production practices may promote amorphization of the vitamin. PRACTICAL APPLICATION: Vitamin C is one of the most unstable vitamins in foods. This study documents that amorphous ascorbic acid is less stable than crystalline ascorbic acid in some environments (for example, higher temperatures within 1 wk), especially when the vitamin is present at low concentrations in a product. These findings increase the understanding of how material science properties influence the stability of vitamin C.