Combining germline, tissue and liquid biopsy analysis by comprehensive genomic profiling to improve the yield of actionable variants in a real-world cancer cohort.

BACKGROUND: Comprehensive next-generation sequencing is widely used for precision oncology and precision prevention approaches. We aimed to determine the yield of actionable gene variants, the capacity to uncover hereditary predisposition and liquid biopsy appropriateness instead of, or in addition to, tumor tissue analysis, in a real-world cohort of cancer patients, who may benefit the most from comprehensive genomic profiling. METHODS: Seventy-eight matched germline/tumor tissue/liquid biopsy DNA and RNA samples were profiled using the Hereditary Cancer Panel (germline) and the TruSight Oncology 500 panel (tumor tissue/cfDNA) from 23 patients consecutively enrolled at our center according to at least one of the following criteria: no available therapeutic options; long responding patients potentially fit for other therapies; rare tumor; suspected hereditary cancer; primary cancer with high metastatic potential; tumor of unknown primary origin. Variants were annotated for OncoKB and AMP/ASCO/CAP classification. RESULTS: The overall yield of actionable somatic and germline variants was 57% (13/23 patients), and 43.5%, excluding variants previously identified by somatic or germline routine testing. The accuracy of tumor/cfDNA germline-focused analysis was demonstrated by overlapping results of germline testing. Five germline variants in BRCA1, VHL, CHEK1, ATM genes would have been missed without extended genomic profiling. A previously undetected BRAF p.V600E mutation was emblematic of the clinical utility of this approach in a patient with a liver undifferentiated embryonal sarcoma responsive to BRAF/MEK inhibition. CONCLUSIONS: Our study confirms the clinical relevance of performing extended parallel tumor DNA and cfDNA testing to broaden therapeutic options, to longitudinally monitor cfDNA during patient treatment, and to uncover possible hereditary predisposition following tumor sequencing in patient care.

Preoperative infection risk assessment in hip arthroplasty a matched-pair study of the reliability of 3 validated risk scales.

Peri-prosthetic infection (PJI) represents one of the most devastating complications of total hip arthroplasty (THA). The aim of this study is to assess the reliability of different PJI risk assessment scales between two matched pairs of THA groups. This study included 37 patients with PJI following THA performed between 2012 and 2020 (Group A). Each patient in this group was matched, based on sex, age, and follow-up duration, with a control patient who underwent the same surgical procedure without any septic complications (Group B) during the same period. Each patient's assessment included the American Society of Anesthesiologists (ASA) score and a retrospective evaluation using three different preoperative, specific PJI risk assessment scales: the International Consensus Meeting (ICM) Preoperative Risk Calculator for PJI, the Mayo PJI Risk Score, and the KLIC-score. The two groups were statistically compared using descriptive analyses, both for binomial data and numerical variables. Statistically significant higher values were observed in the preoperative ASA score and surgical time in Group A. Statistically different higher scores were determined only with the ICM risk calculator score in Group A. No significant differences were found using the KLIC score and Mayo score between the two groups. We emphasize the reliability of the ASA score as a nonspecific preoperative assessment scale for PJI. The ICM risk calculator was confirmed as a reliable, specific preoperative assessment scale for PJI, suggesting its routine adoption in THA clinical practice.

Changes, functional disorders, and diseases in the gastrointestinal tract of elderly / Cambios, dolencias funcionales y enfermedades en el sistema gastrointestinal en personas mayores

This article describes changes in the basic digestive functions (motility, secretion, intraluminal digestion, absorption) that occur during aging. Elderly individuals frequently have oropharyngeal muscle dysmotility and altered swallowing of food. Reductions in esophageal peristalsis and lower esophageal sphincter (LES) pressures are also more common in the aged and may cause gastroesophageal reflux. Gastric motility and emptying and small bowel motility are generally normal in elderly subjects, although delayed motility and gastric emptying have been reported in some cases. The propulsive motility of the colon is also decreased, and this alteration is associated with neurological and endocrine-paracrine changes in the colonic wall. Decreased gastric secretions (acid, pepsin) and impairment of the mucous-bicarbonate barrier are frequently described in the elderly and may lead to gastric ulcer. Exocrine pancreatic secretion is often decreased, as is the bile salt content of bile. These changes represent the underlying mechanisms of symptomatic gastrointestinal dysfunctions in the elderly, such as dysphagia, gastroesophageal reflux disease, primary dyspepsia, irritable bowel syndrome, primary constipation, maldigestion, and reduced absorption of nutrients. Therapeutic management of these conditions is also described. The authors also review the gastrointestinal diseases that are more common in the elderly, such as atrophic gastritis, gastric ulcer, colon diverticulosis, malignant tumors, gallstones, chronic hepatitis, liver cirrhosis, Hepato Cellular Carcinoma (HCC), and chronic pancreatitis (AU)

Este artículo describe los cambios en las funciones digestivas básicas (motilidad, secreción, digestión intraluminal, absorción) que ocurren en el envejecimiento. Los individuos ancianos a menudo presentan una dismotilidad de la musculatura orofaríngea y una alteración de la deglución de los alimentos. Las reducciones en el peristaltismo esofágico y de las presiones del esfínter esofágico inferior (EEI) también son más frecuentes en las personas mayores y pueden causar un reflujo gastroesofágico. La motilidad y el vaciamiento gástricos así como la motilidad intestinal son, por lo general, normales en los individuos ancianos, si bien se han notificado en algunos casos una motilidad y vaciamiento gástricos retardados. La motilidad propulsora del colon también está disminuida y esta alteración se asocia con cambios neurológicos y endocrinos-paracrinos de la pared colónica. En el anciano se describen frecuentemente disminución de las secreciones gástricas (ácido, pepsina) y alteración de la barrera mucosa-bicarbonato, lo cual puede favorecer la úlcera gástrica. A menudo la secreción pancreática exocrina está disminuida, así como el contenido en sales biliares de la bilis. Estos cambios representan mecanismos subyacentes de las disfunciones gastrointestinales sintomáticas del anciano tales como disfagia, enfermedad por reflujo gastroesofágico, dispepsia primaria, síndrome del intestino irritable, estreñimiento primario, maladigestión y disminución de la absorción de nutrientes. También se describe el manejo terapéutico de estos trastornos. Los autores también revisan las enfermedades gastrointestinales que son más frecuentes en el anciano, tales como las gastritis atrófica, la úlcera gástrica, la diverticulosis colónica, los tumores malignos, los cálculos biliares, la hepatitis crónica, la cirrosis hepática, el carcinoma hepatocelular (CHC) y la pancreatitis crónica (AU)