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Acute severe ulcerative colitis management: unanswered questions and latest insights.
No full textAcute severe ulcerative colitis (ASUC) is a distinctive ulcerative colitis flare presentation characterised by the presence of systemic inflammation as well as bloody diarrhoea, and occurs at least once in 25% of patients with ulcerative colitis during their disease course. Each episode carries a risk of complications, need for colectomy, and mortality. Little is known about ASUC pathogenesis, although impaired host-microbiota crosstalk involving pathobionts is suspected. In this Review, we discuss unanswered questions and results from the latest research on the medical-first-line, second-line, and potential third-line therapies-and surgical management of ASUC. We detail promising options for management, such as the use of enteral nutrition in combination with intravenous steroids, the ability to predict early failure of first-line or second-line therapies, and the emerging role of JAK inhibitors. An optimal framework to personalise therapy on the basis of multiomics tools is yet to be developed
Comprehensive molecular profiling of multiple myeloma identifies refined copy number and expression subtypes.
No full text20.500.12530/87871Multiple myeloma is a treatable, but currently incurable, hematological malignancy of plasma cells characterized by diverse and complex tumor genetics for which precision medicine approaches to treatment are lacking. The Multiple Myeloma Research Foundation's Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile study ( NCT01454297 ) is a longitudinal, observational clinical study of newly diagnosed patients with multiple myeloma (n = 1,143) where tumor samples are characterized using whole-genome sequencing, whole-exome sequencing and RNA sequencing at diagnosis and progression, and clinical data are collected every 3 months. Analyses of the baseline cohort identified genes that are the target of recurrent gain-of-function and loss-of-function events. Consensus clustering identified 8 and 12 unique copy number and expression subtypes of myeloma, respectively, identifying high-risk genetic subtypes and elucidating many of the molecular underpinnings of these unique biological groups. Analysis of serial samples showed that 25.5% of patients transition to a high-risk expression subtype at progression. We observed robust expression of immunotherapy targets in this subtype, suggesting a potential therapeutic option
Impact of Chronic Disease Self-Management Program on the Self-Perceived Health of People in Areas of Social Vulnerability in Asturias, Spain.
No full text20.500.12530/87909The Chronic Disease Self-Management Program (CDSMP) focuses on a health promotion perspective with a salutogenic approach, reinforcing the pillars of self-efficacy. The aim of this study was to assess the impact of the CDSMP on Self-perceived Health (SPH) in disadvantaged areas of Asturias, España. The study included vulnerable adults with experience of chronic diseases for over six months, along with their caregivers. The intervention consisted of a six-session workshop led by two trained peers. SPH was evaluated by administering the initial item of the SF-12 questionnaire at both baseline and six months post-intervention. To evaluate the variable "Change in SPH" [improvement; remained well; worsening/no improvement (reference category)], global and disaggregated by sex multivariate multinomial logistic regression models were applied. There were 332 participants (mean = 60.5 years; 33.6% were at risk of social vulnerability; 66.8% had low incomes). Among the participants, 22.9% reported an improvement in their SPH, without statistically significant sex-based differences, while 38.9% remained in good health. The global model showed age was linked to decreased "improvement" probability (RRRa = 0.96), and the "remaining well" likelihood drops with social risk (RRRa = 0.42). In men, the probability of "remaining well" decreased by having secondary/higher education (RRRa = 0.25) and increased by cohabitation (RRRa = 5.11). Women at social risk were less likely to report "remaining well" (RRRa = 0.36). In conclusion, six months after the intervention, 22.9% of the participants had improved SPH. Age consistently decreased the improvement in the different models
FIGO 2023 staging for endometrial cancer, when, if it is not now?
No full text20.500.12530/87908Incorporation of pathological and (not mandatory) molecular features into the new FIGO 2023 staging system has generated some controversy. Several validations have been published recently that demonstrated the higher prognostic precision of FIGO 2023 compared to the previous FIGO 2009 scheme. In the present article, the authors want to respond to some concerns that were raised by some pathologists and clinicians
Recovery of uninvolved heavy/light chain pair immunoparesis in newly diagnosed transplant-eligible myeloma patients complements the prognostic value of minimal residual disease detection.
No full text20.500.12530/87858Immunoparesis (IP) in multiple myeloma (MM) patients can be measured by classic assessment of immunoglobulin (Ig) levels or by analysis of the uninvolved heavy/light chain pair of the same immunoglobulin (uHLC) by the Hevylite® assay. In this study we evaluate the prognostic value of recovery from IP measured by classic total Ig and uHLC assessment in newly diagnosed MM transplant-eligible (NDMM-TE) patients with intensive treatment and its association with minimal residual disease (MRD). Patients were enrolled and treated in the PETHEMA/GEM2012MENOS65 trial and continued in the PETHEMA /GEM2014MAIN trial. Total Ig (IgG, IgA and IgM) and uHLC were analyzed in a central laboratory at diagnosis, after consolidation treatment and after the first year of maintenance. MRD was analyzed by next-generation flow cytometry after consolidation (sensitivity level 2x10-6). We found no differences in progression-free survival (PFS) between patients who recovered and patients who didn't recover from IP after consolidation when examining classic total Ig and uHLC. However, after the first year of maintenance, in contrast to patients with classic IP, patients with recovery from uHLC IP had longer PFS than patients without recovery, with hazard ratio of 0.42 (95% confidence interval [CI]: 0.21-0.81; P=0.008). Multivariate analysis with Cox proportional-hazards regression models confirmed recovery from uHLC IP after the first year of maintenance as an independent prognostic factor for PFS, with an increase in C-statistic of 0.05 (95% CI: -0.04 to 0.14;
Emerging biomarkers for improving pregnancy planning in multiple sclerosis.
No full textPatient disability, relapse rate, and age are used for family planning in multiple sclerosis (MS). However, the need for more accurate biomarkers is widely recognized. We aimed to explore the influence of age on neurofilament light chain (sNfL), which reflects acute inflammation; glial fibrillary acidic protein (GFAP), associated with disability progression independent of relapses; and anti-Müllerian hormone (AMH), reflecting ovarian reserve, to provide a tailored family planning strategy. This case-control study included 95 MS patients and 61 healthy control women (HCW). sNfL and GFAP levels were measured using a sensitive single-molecule array assay. AMH levels were measured by the automated Elecsys® Anti-Müllerian Hormone Assay. We observed no significant differences in AMH values between MS patients and the control group within any of the age-matched categories. Age exhibited a negative correlation with AMH values in both groups, as expected. Nevertheless, our findings suggest a slight tendency toward reduced ovarian reserve in MS patients (rho MS patients = -0.67, p We found no significant differences in AMH, sNfL or GFAP values between MS patients and the control group within any of the age-matched categories. The assessment of AMH, sNFL and GFAP levels at MS onset facilitates personalized therapeutic and family planning strategies for childbearing-age women
The Gastroscopy RAte of Cleanliness Evaluation (GRACE) Scale: an international reliability and validation study.
No full text20.500.12530/87908 Mucosal visualization during upper gastrointestinal (UGI) endoscopy can be impaired by the presence of foam, bubbles, and mucus. Some UGI endoscopy visibility scales have been proposed but have not undergone multicenter validation. This study aimed to develop and validate the Gastroscopy RAte of Cleanliness Evaluation (GRACE) scale. A multicenter, international, cross-sectional study was conducted. The GRACE scale is based on a score from 0 (worst) to 3 (excellent) for esophagus, stomach, and duodenum, for a total ranging from 0 to 9. In phase 1, four expert endoscopists evaluated 60 images twice, with a 2-week interval between rounds; in phase 2, the same 60 images were scored twice by one expert and one nonexpert endoscopist from 27 endoscopy departments worldwide. For reproducibility assessment and real-time validation, the scale was applied to consecutive patients undergoing gastroscopy at each center. On internal validation, interobserver agreement was 0.81 (95 %CI 0.73-0.87) and 0.80 (95 %CI 0.72-0.86), with reliability of 0.73 (95 %CI 0.63-0.82) and 0.72 (95 %CI 0.63-0.81), in the two rounds, respectively. On external validation, overall interobserver agreement was 0.85 (95 %CI 0.82-0.88) and reliability was 0.79 (95 %CI 0.73-0.84). In real-time evaluation, the overall proportion of correct classifications was 0.80 (95 %CI 0.77-0.82). The GRACE scale showed good interobserver agreement, reliability, and validity. The widespread use of this scale could enhance quality and standardize the assessment of mucosal cleanliness during UGI endoscopy, pushing endoscopists to strive for excellent visibility and reducing the risk of missed lesions
Analyzing public discourse of dementia from Spanish and English tweets: a comparative analysis with other neurological disorders.
No full textDementia comprise a broad spectrum of cognitive declines affecting 47 million people worldwide, with numbers projected to reach 131 million by 2050. Predominantly associated with older adults, dementia can also impact younger individuals, having a significant impact on daily functioning of the affected patients, relatives, caregivers and the socioeconomic system. Recent research underscores the utility of social media, particularly X (previously designed as Twitter), in understanding public perceptions and sentiments related to neurological disorders. Despite some initial studies have explored social perceptions of dementia in X, broader and deeper analysis of this condition is still warranted. In this retrospective study, we collected and examined all tweets posted in English or Spanish from 2007 to 2023 that mentioned dementia and compare the information with other highly representative neurological disorders like migraines, epilepsy, multiple sclerosis, spinal cord injury, or Parkinson's disease. We developed a codebook to analyze tweets, classifying them by themes such as trivialization, treatment perceptions, and etiopathogenesis. Manually categorized tweets trained machine learning models, BERTWEET for English and BETO for Spanish, which then classified larger datasets with high accuracy. Statistical analysis, including ANOVA, Kruskal-Wallis, and chi-square tests, was conducted to explore linguistic and cultural differences in perceptions of neurological disorders, with results visualized. Our study reveals that dementia is by far the most frequently discussed neurological disorder on X. Likewise, this condition appears to be the most trivialized neurological disorder in Spanish tweets and the second most trivialized in English tweets, with notable differences in geolocation data. Additionally, we found significant differences in perceptions of dementia treatment and associated sentiments between Spanish and English tweets. Furthermore, our study identified varying perceptions of medical content (etiology) and non-medical content (positive/negative experiences and aid requests) related to dementia and other neurological disorders, unveiling a complex landscape of these topics on X. This study explores the importance of X as a social platform for addressing various critical issues related to dementia, comparing it with other neurological disorders in English and Spanish tweets. Future research could further investigate the valuable role of social media in understanding public perceptions and needs regarding dementia and neurological disorders among X users
Development and validation of the post-CAR prognostic index for large B-cell lymphoma patients after CAR-T progression in third or later line treatment.
No full textChimeric antigen receptor (CAR) T-cell therapy fails to achieve durable responses in over 60% of relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients in the third or later line setting. After CAR-T failure, survival outcomes are heterogeneous and a prognostic model in this patient population is lacking. A training cohort of 216 patients with progressive disease (PD) after CAR-T from 12 Spanish centers was used to develop the Post-CAR Prognostic Index (PC-PI); primary endpoint was overall survival (OS) from CAR-T progression. Validation was performed in an external cohort from three different European centers (n = 204). The prognostic score incorporated five variables, assessed at time of PD to CAR-T: ECOG (> 0), hemoglobin ( 0), hemoglobin ( 1) and time from CAR-T to PD
Integrative clinical, hormonal, and molecular data associate with invasiveness in acromegaly: REMAH study.
No full text20.500.12530/87887Growth hormone (GH)-secreting pituitary tumors (GHomas) are the most common acromegaly cause. At diagnosis, most of them are macroadenomas, and up to 56% display cavernous sinus invasion. Biomarker assessment associated with tumor growth and invasion is important to optimize their management. The study aims to identify clinical/hormonal/molecular biomarkers associated with tumor size and invasiveness in GHomas and to analyze the influence of pre-treatment with somatostatin analogs (SSAs) or dopamine agonists (DAs) in key molecular biomarker expression. Clinical/analytical/radiological variables were evaluated in 192 patients from the REMAH study (ambispective multicenter post-surgery study of the Spanish Society of Endocrinology and Nutrition). The expression of somatostatin/ghrelin/dopamine system components and key pituitary/proliferation markers was evaluated in GHomas after the first surgery. Univariate/multivariate regression studies were performed to identify association between variables. Eighty percent of patients harbor macroadenomas (63.8% with extrasellar growth). Associations between larger and more invasive GHomas with younger age, visual abnormalities, higher IGF1 levels, extrasellar/suprasellar growth, and/or cavernous sinus invasion were found. Higher GH1 and lower PRL/POMC/CGA/AVPR1B/DRD2T/DRD2L expression levels (P A specific combination of clinical/analytical/molecular variables was found to be associated with tumor invasiveness and growth capacity in GHomas. Pre-treatment with first-line drugs for acromegaly did not significantly modify the expression of the most relevant biomarkers in our association model. These findings provide valuable insights for risk stratification and personalized management of GHomas