Characteristics and Surgical Outcomes in Very Elderly Patients (≥75 years) with Renal Cell Carcinoma: Data from the Latin American Renal Cancer Group

Background: The incidence of renal cell carcinoma (RCC) is increasing globally due to an aging population and widespread use of imaging studies. Objective: The aim of this study was to describe the characteristics and perioperative outcomes of RCC surgery in very elderly patients (VEP), ≥75 years of age. Methods: This is a retrospective comparative study of 3656 patients who underwent the treatment for RCC from 1990 to 2015 in 28 centers from eight Latin American countries. We compared baseline characteristics as well as clinical and perioperative outcomes according to age groups (<75 vs.≥ 75 years). Surgical complications were classified with the Clavien-Dindo score. We performed logistic regression analysis to identify factors associated with perioperative complications. Results: There were 410 VEP patients (11.2%). On bivariate analysis, VEP had a lower body mass index (p < 0.01) and higher ASA score (ASA >2 in 26.3% vs. 12.4%, p < 0.01). There was no difference in performance status and clinical stage between the study groups. There were no differences in surgical margins, estimated blood loss (EBL), complication, and mortality rates (1.3% vs. 0.4%, p = 0.17). On multivariate regression analysis, age ≥75 years (odds ratio [OR] 2.33, p < 0.01), EBL ≥ 500 cc (OR 3.34, p < 0.01), and > pT2 stage (OR 1.63, p = 0.04) were independently associated with perioperative complications. Conclusions: Surgical resection of RCC was safe and successful in VEP. Age ≥75 years was independently associated with 30-day perioperative complications. However, the vast majority were low-grade complications. Age alone should not guide decision-making in these patients, and treatment must be tailored according to performance status and severity of comorbidities. (REV INVEST CLIN. 2020;72(5):308-15)

Survey on hypoglycemia among insulin-treated patients with diabetes: The Colombian International Operations Hypoglycemia Assessment Tool population / Encuesta sobre hipoglucemia en pacientes con diabetes tratados con insulina: la población colombiana del International Operations Hypoglycemia Assessment Tool

Abstract Introduction: The non-interventional International Operations Hypoglycemia Assessment Tool (IO-HAT) study assessed the incidence of hypoglycemia in patients with insulin-treated diabetes across nine countries, including a cohort of patients in Colombia. Materials and methods: Hypoglycemia incidence among patients with insulin-treated diabetes was assessed across 26 sites in Colombia. Hypoglycaemic events (any, nocturnal or severe) were reported in self-assessment questionnaires (SAQ) and patient diaries based on capillary blood glucose measurement or symptoms. Retrospective events (severe events 6 months before baseline and any event 4 weeks before baseline) were recorded in SAQ, Part 1, and prospective events (4 weeks from baseline) were recorded in SAQ, Part 2, and patient diaries. Differences in hypoglycemia incidence reported in the retrospective and prospective periods were assessed using two-sided tests. Results: Of the 664 patients assessed, 213 had type 1 diabetes (T1D) and 451 had type 2 diabetes (T2D). Nearly all patients experienced at least one hypoglycaemic event in the prospective period (97.1% T1D; 93.3% T2D). Rates of hypoglycemia (events per person- year, PPY) were higher prospectively than retrospectively for any hypoglycemia (T1 D: 121.6 vs. 83.2, p<0.001; T2D: 28.1 vs. 24.6, p=0.127) and severe hypoglycemia (T 1D: 15.3 vs. 9.2, p=0.605; T 2 D: 9.5 vs. 3.5 p=0.040). Conclusion: These results, the first from a patient-reported dataset on hypoglycemia in insulin-treated patients with diabetes in Colombia, show that patients reported higher rates of any hypoglycemia during the prospective period.

Resumen Introducción. En el estudio no intervencionista International Operations Hypoglycemia Assessment Tool (IO-HAT), se evalúo la incidencia de hipoglucemia en pacientes diabéticos tratados con insulina en nueve países, incluido Colombia. Materiales y métodos. La incidencia de hipoglucemia entre pacientes diabéticos tratados con insulina se evaluó en 26 centros médicos en Colombia. Los episodios de hipoglucemia determinados con base en la medición de la glucemia capilar o en los síntomas se reportaron en el cuestionario de autoevaluación (Self-Assessment Questionnaire, SAQ) y en el diario del paciente. Los episodios retrospectivos (episodios graves y cualquiera ocurrido 6 meses y 4 semanas antes del inicio del estudio, respectivamente) se registraron en el SAQ, parte 1, y los eventos prospectivos (4 semanas desde el inicio), en el SAQ, parte 2, y en el diario del paciente. Las diferencias en la incidencia de la hipoglucemia entre los períodos retrospectivo y prospectivo se evaluaron mediante una prueba de dos colas. Resultados. De los 664 pacientes evaluados, 213 tenían diabetes de tipo 1 y 451 tenían diabetes de tipo 2. Casi todos los pacientes experimentaron al menos un episodio de hipoglucemia en el período prospectivo (97,1 %, diabetes de tipo 1, y 93,3 %, diabetes de tipo 2). Los índices de hipoglucemia (episodios año-persona) fueron mayores prospectivamente que retrospectivamente para cualquier tipo de hipoglucemia (diabetes de tipo 1: 121,6 Vs. 83,2; p<0,001; la diabetes de tipo 2: 28,1 Vs. 24,6; p=0,127) y para la hipoglucemia grave (diabetes de tipo 1: 15,3 Vs. 9,2; p=0,605; diabetes de tipo 2: 9,5 Vs. 3,5; p=0,040). Conclusión. Estos resultados, que constituyen el primer conjunto de datos sobre hipoglucemia informados por pacientes diabéticos colombianos tratados con insulina, evidenciaron tasas más altas para ambos tipos de hipoglucemia durante el período prospectivo.

Mosaic trisomy 8 detected by fibroblasts cultured of skin / Mosaico trisomía 8 detectada por los cultivos de fibroblastos de la piel

Introduction: Mosaic trisomy 8 or "Warkany's Syndrome" is a chromosomopathy with an estimated prevalance of 1:25,000 to 1:50,000, whose clinical presentation has a wide phenotypic variability. Case Description: Patient aged 14 years old with antecedents of global retardation of development, moderate cognitive deficit and hypothyroidism of possible congenital origin. Clinical Findings: Physical examination revealed palpebral ptosis, small corneas and corectopia, hypoplasia of the upper maxilla and prognathism, dental crowding, high-arched palate, anomalies of the extremities such as digitalization of the thumbs, clinodactyly and bilateral shortening of the fifth finger, shortening of the right femur, columnar deviation and linear brown blotches that followed Blaschko's lines. Cerebral nuclear magnetic resonance revealed type 1 Chiari's malformation and ventriculomegaly. Although the karyotype was normal in peripheral blood (46,XY), based on the finding of cutaneous mosaicism the lesions were biopsied and cytogenetic analysis demonstrated mosaic trisomy 8: mos 47,XY,+8[7]/46,XY[93]. Clinical Relevance: Trisomy 8 is clinically presented as a mosaic, universal cases being unfailingly lethal. In this particular case, cutaneous lesions identified the mosaic in tissue, although the karyotype was normal in peripheral blood. The cutaneous mosaicism represented by brown linear blotches which follow Blaschko's lines is a clinical finding that has not previously been described in Warkany's syndrome.

Introducción: La trisomía 8 en mosaico o Síndrome de Warkany, es una cromosomopatía con una prevalencia estimada de 1:25,000 a 1:50,000, que se presenta clínicamente con una amplia variabilidad fenotípica. Descripción del Caso: Paciente de 14 años con antecedente de retardo global del desarrollo, déficit cognitivo moderado e hipotiroidismo de posible origen congénito. Hallazgos Clínicos: Al examen físico presenta ptosis palpebral, corneas pequeñas y corectopia, hipoplasia de maxilar superior y prognatismo, apiñamiento dental, paladar alto ojival, anomalías en extremidades como digitalización de pulgares, clinodactilia y acortamiento bilateral del quinto dedo en manos, acortamiento de fémur derecho, desviación de columna y máculas lineales pardas que siguen las líneas de Blaschko. En la resonancia nuclear magnética cerebral se aprecia malformación de Chiari tipo 1 y ventriculomegalia. El cariotipo en sangre periférica fue normal (46,XY) sin embargo, ante el hallazgo de mosaicismo cutáneo, se realizó biopsia de las lesiones y su análisis citogenético demostró trisomía 8 en mosaico: mos47,XY,+8[7]/46,XY[93]. Relevancia Clínica: La trisomía 8 se presenta clínicamente en mosaico, los casos universales son indefectiblemente letales. En este caso particular, las lesiones cutáneas identificaron el mosaico en tejido, frente al cariotipo normal en sangre periférica. El mosaicismo cutáneo representado por las máculas lineales pardas (que siguen las líneas de Blaschko) es un hallazgo clínico que no se había descrito en el síndrome de Warkany.

Regulation of cardiac excitation-contraction coupling by sorcin, a novel modulator of ryanodine receptors

Activation of Ca2+ release channels/ryanodine receptors (RyR) by the inward Ca2+ current (ICa) gives rise to Ca2+-induced Ca2+ release (CICR), the amplifying Ca2+ signaling mechanism that triggers contraction of the heart. CICR, in theory, is a high-gain, self-regenerating process, but an unidentified mechanism stabilizes it in vivo. Sorcin, a 21.6 kDa Ca2+-binding protein, binds to cardiac RyRs with high affinity and completely inhibits channel activity. Sorcin significantly inhibits both the spontaneous activity of RyRs in quiescent cells (visualized as Ca2+ sparks) and the ICa-triggered activity of RyRs that gives rise to [Ca2+]i transients. Since sorcin decreases the amplitude of the [Ca2+]i transient without affecting the amplitude of ICa, the overall effect of sorcin is to reduce the "gain" of excitation-contraction coupling. Immunocytochemical staining shows that sorcin localizes to the dyadic space of ventricular cardiac myocytes. Ca2+ induces conformational changes and promotes translocation of sorcin between soluble and membranous compartments, but the [Ca2+] required for the latter process (ED50 = ~200 mM) appears to be reached only within the dyadic space. Thus, sorcin is a potent inhibitor of both spontaneous and ICa-triggered RyR activity and may play a role in helping terminate the positive feedback loop of CICR.