Dermatitis herpetiforme como manifestación de enfermedad celiaca: estudio de factores epidemiológicos, genéticos, clínicos, diagnósticos y terapéuticos

La Dermatitis herpetiforme (DH) es una enfermedad autoinmune poco frecuente, con una incidencia en Europa del Norte que varía entre 11.5 y 75 personas de cada 100.000. La enfermedad celiaca (EC) es más frecuente, con una incidencia en Europa de aproximadamente 1%. La DH está infra diagnosticada. El motivo puede deberse a varios factores. Por un lado, la apariencia vesiculosa y el prurito pueden hacer que se confunda con enfermedades dermatológicas más frecuentes. Además debido al rascado predominan las excoriaciones y erosiones. Por otro lado al ser una enfermedad que cursa en brotes a veces el paciente cuando acude al especialista no presenta lesiones típicas. Como los síntomas gastrointestinales solo están presentes en cerca del 20% de los pacientes eso hace que además la enfermedad celiaca subyacente pase desapercibida. La mayoría de los casos de DH tienen EC, de manera que se considera la DH una manifestación de EC. El tratamiento de la DH es la dieta sin gluten (DSG) y la dapsona hasta que la DSG controle la enfermedad. Pacientes y métodos Estudio de casos y controles observacional. Los casos son pacientes con Dermatitis herpetiforme (grupo DH) y los controles pacientes celiacos sin dermatitis herpetiforme (grupo EC) y pacientes sanos sin dermatitis herpetiforme ni enfermedad celiaca conocida (grupo SANOS). La Asociación de Celiacos y Sensibles al Gluten de Madrid comunicó el estudio. Los voluntarios fueron todos revisados en consulta por la Dra. Paloma Borregón en el Departamento de Dermatología de la Clínica Universidad de Navarra en Madrid, aportando los resultados de las pruebas requeridas

Peripheral T-cell lymphoma: Molecular profiling recognizes subclasses and identifies prognostic markers

Peripheral T-cell lymphoma (PTCL) is a clinically aggressive disease, with a poor response to therapy and a low overall survival rate of approximately 30% after 5 years. We have analyzed a series of 105 cases with a diagnosis of PTCL using a customized NanoString platform (NanoString Technologies, Seattle, WA) that includes 208 genes associated with T-cell differentiation, oncogenes and tumor suppressor genes, deregulated pathways, and stromal cell subpopulations. A comparative analysis of the various histological types of PTCL (angioimmunoblastic T-cell lymphoma [AITL]; PTCL with T follicular helper [TFH] phenotype; PTCL not otherwise specified [NOS]) showed that specific sets of genes were associated with each of the diagnoses. These included TFH markers, cytotoxic markers, and genes whose expression was a surrogate for specific cellular subpopulations, including follicular dendritic cells, mast cells, and genes belonging to precise survival (NF-κB) and other pathways. Furthermore, the mutational profile was analyzed using a custom panel that targeted 62 genes in 76 cases distributed in AITL, PTCL-TFH, and PTCL-NOS. The main differences among the 3 nodal PTCL classes involved the RHOAG17V mutations (P < .0001), which were approximately twice as frequent in AITL (34.09%) as in PTCL-TFH (16.66%) cases but were not detected in PTCL-NOS. A multivariate analysis identified gene sets that allowed the series of cases to be stratified into different risk groups. This study supports and validates the current division of PTCL into these 3 categories, identifies sets of markers that can be used for a more precise diagnosis, and recognizes the expression of B-cell genes as an IPI-independent prognostic factor for AITL

Dermatitis herpetiforme como manifestación de enfermedad celiaca : estudio de factores epidemiológicos, genéticos, clínicos, diagnósticos y terapéuticos

La Dermatitis herpetiforme (DH) es una enfermedad autoinmune poco frecuente, con una incidencia en Europa del Norte que varía entre 11.5 y 75 personas de cada 100.000. La enfermedad celiaca (EC) es más frecuente, con una incidencia en Europa de aproximadamente 1\%. La DH está infra diagnosticada. El motivo puede deberse a varios factores. Por un lado, la apariencia vesiculosa y el prurito pueden hacer que se confunda con enfermedades dermatológicas más frecuentes. Además debido al rascado predominan las excoriaciones y erosiones. Por otro lado al ser una enfermedad que cursa en brotes a veces el paciente cuando acude al especialista no presenta lesiones típicas. Como los síntomas gastrointestinales solo están presentes en cerca del 20\% de los pacientes eso hace que además la enfermedad celiaca subyacente pase desapercibida. La mayoría de los casos de DH tienen EC, de manera que se considera la DH una manifestación de EC. El tratamiento de la DH es la dieta sin gluten (DSG) y la dapsona hasta que la DSG controle la enfermedad. Pacientes y métodos Estudio de casos y controles observacional. Los casos son pacientes con Dermatitis herpetiforme (grupo DH) y los controles pacientes celiacos sin dermatitis herpetiforme (grupo EC) y pacientes sanos sin dermatitis herpetiforme ni enfermedad celiaca conocida (grupo SANOS). La Asociación de Celiacos y Sensibles al Gluten de Madrid comunicó el estudio. Los voluntarios fueron todos revisados en consulta por la Dra. Paloma Borregón en el Departamento de Dermatología de la Clínica Universidad de Navarra en Madrid, aportando los resultados de las pruebas requeridas

An integrated prognostic model for diffuse large B‐cell lymphoma treated with immunochemotherapy

Abstract Diffuse large B‐cell lymphoma (DLBCL), the most frequent non‐Hodgkin's lymphoma subtype, is characterized by strong biological, morphological, and clinical heterogeneity, but patients are treated with immunochemotherapy in a relatively homogeneous way. Here, we have used a customized NanoString platform to analyze a series of 197 homogeneously treated DLBCL cases. The platform includes the most relevant genes or signatures known to be useful for predicting response to R‐CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) in DLBCL cases. We generated a risk score that combines the International Prognostic Index with cell of origin and double expression of MYC/BCL2, and stratified the series into three groups, yielding hazard ratios from 0.15 to 5.49 for overall survival, and from 0.17 to 5.04 for progression‐free survival. Group differences were highly significant (p < 0.0001), and the scoring system was applicable to younger patients (<60 years of age) and patients with advanced or localized stages of the disease. Results were validated in an independent dataset from 166 DLBCL patients treated in two distinct clinical trials. This risk score combines clinical and biological data in a model that can be used to integrate biological variables into the prognostic models for DLBCL cases

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit