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Abstract: A phase 2, international, open-label, nonrandomized, single-arm trial was conducted to evaluate the efficacy and safety of tipifarnib, a farnesyltransferase inhibitor, as monotherapy for relapsed/refractory peripheral T-cell lymphoma (PTCL) and to evaluate tumor mutation profile as a biomarker of response. Adults with relapsed/refractory PTCL received tipifarnib 300 mg orally twice daily for 21 days in a 28-day cycle. The primary end point was objective response rate (ORR); secondary end points included ORR, progression-free survival (PFS), duration of response (DOR), and adverse events (AEs) in specific subtypes. Sixty-five patients with PTCL were enrolled: n = 38 angioimmunoblastic T-cell lymphoma (AITL), n = 25 PTCL not otherwise specified, and n = 2 other T-cell lymphomas. The ORR was 39.7% (95% confidence interval [CI], 28.1-52.5) in all patients and 56.3% (95% CI, 39.3-71.8) for AITL. Median PFS was 3.5 months overall (954% CI, 2.1-4.4), and 3.6 months (95% CI, 1.9-8.3) for AITL. Median DOR was 3.7 months (95% CI, 2.0-15.3), and greatest in patients with AITL (7.8 months; 95% CI, 2.0-16.3). The median overall survival was 32.8 months (95% CI, 14.4 to not applicable). Tipifarnib-related hematologic AEs were manageable and included neutropenia (43.1%), thrombocytopenia (36.9%), and anemia (30.8%); other tipifarnib-related AEs included nausea (29.2%) and diarrhea (27.7%). One treatment-related death occurred. Mutations in RhoA, DNMT3A, and IDH2 were seen in 60%, 33%, and 27%, respectively, in the AITL tipifarnib responder group vs 36%, 9%, and 9% in the nonresponder group. Tipifarnib monotherapy demonstrated encouraging clinical activity in heavily pretreated relapsed/refractory PTCL, especially in AITL, with a manageable safety profile. This trial was registered at www.ClinicalTrials.gov as #NCT02464228., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: The COVID-19 pandemic has resulted in great incertitude and overwhelming changes in healthcare that have had a direct impact on antibiotic prescription. However, the influence of this pandemic on antibiotic consumption in patients undergoing surgery has not yet been analysed. The goal of this study was to analyse antimicrobial consumption and prescription in the same period of 2019 (pre-COVID-19), 2020 (beginning of the COVID-19 pandemic) and 2021 (established COVID-19) according to the DDD system in surgical patients at a tertiary-level hospital., Methods: A prospectively maintained database was analysed. All patients who underwent elective or emergency gastrointestinal surgery during the same period (2019, 2020 and 2021) were included. Those who received at least 1 of the 10 most frequently prescribed antimicrobials during those periods were analysed., Results: A total of 2975 patients were included in this study. In 2020, the number of procedures performed decreased significantly (653 versus 1154 and 1168 in 2020 versus 2019 and 2021, respectively; P = 0.005). Of all patients who underwent surgery during these periods, 45.08% received at least one of the antimicrobials studied (45.8% in 2020 versus 22.9% and 22.97% in 2019 and 2021, respectively; P = 0.005). Of these, 22.97% of the patients received a combination of these antimicrobials, with ceftriaxone/metronidazole being the most frequent. Hepato-Pancreato-Biliary and Liver Transplant, Emergency Surgery and Colorectal Surgery units had higher antibiotic consumption., Conclusions: The COVID-19 pandemic has resulted in a significant decrease in surgical activity and higher post-operative antimicrobial prescription compared with previous and subsequent years., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Cytomegalovirus (CMV) infection is a common complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and in patients receiving novel hematological therapies. Its impact on morbidity and mortality necessitates effective management strategies. Despite recent advances in diagnostics and treatment, unresolved questions persist regarding monitoring and treatment, prompting the need for updated recommendations., Methods: A consensus was reached among a panel of experts selected for their expertise in CMV research and clinical practice. Key clinical areas and questions were identified based on previous surveys and literature reviews. Recommendations were formulated through consensus and graded using established guidelines., Results: Recommendations were provided for virological monitoring, including the timing and frequency of CMV DNAemia surveillance, especially during letermovir (LMV) prophylaxis. We evaluated the role of CMV DNA load quantification in diagnosing CMV disease, particularly pneumonia and gastrointestinal involvement, along with the utility of specific CMV immune monitoring in identifying at-risk patients. Strategies for tailoring LMV prophylaxis, managing breakthrough DNAemia, and implementing secondary prophylaxis in refractory cases were outlined. Additionally, criteria for initiating early antiviral treatment based on viral load dynamics were discussed., Conclusion: The consensus provides updated recommendations for managing CMV infection in hematological patients, focusing on unresolved issues in monitoring, prophylaxis, treatment, and resistance. These recommendations aim to guide clinical practice and improve outcomes in this high-risk population. Further research is warranted to validate these recommendations and address ongoing challenges in CMV management with emerging antiviral combinations, particularly in pediatric populations., Competing Interests: Competing interests: The authors declare no conflict of Interest.

In recent years, the meaning of adequacy in peritoneal dialysis has changed. We have witnessed a transition from an exclusive achievement of specific objectives -namely solute clearances and ultrafiltration- to a more holistic approach more focused to on the quality of life of these patients. The purpose of this document is to provide recommendations, updated and oriented to social and health environment, for the adequacy and prescription of peritoneal dialysis. The document has been divided into three main sections: adequacy, residual kidney function and prescription of continuous ambulatory peritoneal dialysis and automated peritoneal dialysis. Recently, a guide on the same topic has been published by a Committee of Experts of the International Society of Peritoneal Dialysis (ISPD 2020). In consideration of the contributions of the group of experts and the quasi-simultaneity of the two projects, references are made to this guide in the relevant sections. We have used a systematic methodology (GRADE), which specifies the level of evidence and the strength of the proposed suggestions and recommendations, facilitating future updates of the document., (Copyright © 2024.)

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., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: The aim of this study was to determine the agreement between three observers with different levels of experience using the PSMA-RADS 2.0 criteria and the miTNM system for the interpretation of PET-PSMA with [ 18 F]DCFPyL in males with prostate cancer., Materials and Methods: PET-PSMA images from 114 prostate cancer patients were blindly reported twice by three different observers at intervals of 8 weeks. The evaluations were performed according to the molecular imaging TNM (miTNM) and PSMA-RADS 2.0 criteria. We used Fleiss' Kappa to analyse inter and intraobserver agreements., Results: Moderate overall agreement was obtained in the assessment of the PET-PSMA results (Fleiss'k = 0.53; 95% CI 0.45-0.62; p < 0.001), with significant agreement in the miT, miN and miM reports. There was a substantial level of agreement in the reporting of prostatic disease and lymphatic involvement (Fleiss'k = 0.66 and 0.65), being lower than that observed in the reporting of metastatic disease (Fleiss'k = 0.86), especially in the M0 group (Fleiss'k = 0.99). Upon re-evaluation of the images, observer 1 had moderate overall agreement for miT (Fleiss'k = 0.51) and substantial agreement for miN and miM (Fleiss'k 0.75 and 0.63, respectively)., Conclusions: The use of a structured scoring system such as PSMA-RADS 2.0, as well as the miTNM classification system in the interpretation of PET-PSMA images in prostate cancer patients, provides a highly reproducible report format. High levels of interobserver and intraobserver agreement are found, especially when ruling out disease, which supports its use in routine clinical practice., (Copyright © 2024 Sociedad Española de Medicina Nuclear e Imagen Molecular. Published by Elsevier España, S.L.U. All rights reserved.)

Competing Interests: Declaration of competing interest None declared.

Background: In addition to stent retrievers, direct aspiration has become a reasonable thrombectomy strategy., Objectives: We carried out the thrombectomy by guiding the aspiration catheter fully over the clot and performing immediate manual aspiration; we call this procedure "embed aspiration"., Methods: In this prospective, non-randomised, single-centre study, we included all patients treated at a high volume-of-care stroke centre between 2017 and 2018 for the TRIANA (Thrombectomy in Andalusia using Aspiration) registry. Thrombectomy was carried out by embed aspiration. Patients were classified according to the success (eTICI 2b67-2c-3) or failure (eTICI 0-1-2a-2b50) of the procedure. Baseline clinical data and outcomes were compared, and multivariate analysis was performed., Results: The embed aspiration technique was used in 370 patients. Treatment was successful in 90.3% of patients. Mean puncture-to-recanalisation time was 25 minutes. The overall rate of good outcomes (mRS 0-2) at 3 months was 64%., Conclusions: This study supports real-life evidence that standardised embed aspiration may be an alternative to stent retrievers for thrombectomy., (Copyright © 2021 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Objectives: Patients with haematologic malignancies (HM) COVID-19 have more severe disease, with increased risk of mortality. Therefore, this study aimed to evaluate the effect of SARS-CoV-2 RNAemia and the specific humoral immune responses on the clinical outcomes of patients with HM and COVID-19., Methods: Interferon-α/γ (IFN-α/IFN-γ) serum levels, neutralizing antibodies and RNAemia at COVID-19 diagnosis, and persistent RNAemia during the follow-up were evaluated., Results: Overall, 63 (58.9%) out of 107 patients had RNAemia, which was persistent in 26 (41.3%) patients. RNAemia at diagnosis and persistent RNAemia were associated with the need for high-flow nasal oxygen therapy during admission. Persistent RNAemia, age >70 years, and CURB-65 score ≥2 in patients with pneumonia were associated with increased 90-day mortality (P = 0.009, P = 0.030 and P = 0.001, respectively). The 90-day overall survival was lower (P = 0.006) in patients with persistent RNAemia. In addition, dexamethasone administration was associated with a COVID-19 episode with persistent RNAemia., Conclusion: Our results suggest that in patients with HM, RNAemia at the time of COVID-19 diagnosis and during the follow-up can be used to stratify patients with HM according to their clinical evolution and to guide clinical decisions tailored to the specific needs of each patient., Competing Interests: Declarations of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: Alcohol relapse after surviving an episode of alcohol-associated hepatitis (AH) is common. However, the clinical features, risk factors, and prognostic implications of recurrent alcohol-associated hepatitis (RAH) are not well described., Approach and Results: A registry-based study was done of patients admitted to 28 Spanish hospitals for an episode of AH between 2014 and 2021. Baseline demographics and laboratory variables were collected. Risk factors for RAH were investigated using Cox regression analysis. We analyzed the severity of the index episodes of AH and compared it to that of RAH. Long-term survival was assessed by Kaplan-Meier curves and log-rank tests. A total of 1118 patients were included in the analysis, 125 (11%) of whom developed RAH during follow-up (median: 17 [7-36] months). The incidence of RAH in patients resuming alcohol use was 22%. The median time to recurrence was 14 (8-29) months. Patients with RAH had more psychiatric comorbidities. Risk factors for developing RAH included age <50 years, alcohol use >10 U/d, and history of liver decompensation. RAH was clinically more severe compared to the first AH (higher MELD, more frequent ACLF, and HE). Moreover, alcohol abstinence during follow-up was less common after RAH (18% vs. 45%, p <0.001). Most importantly, long-term mortality was higher in patients who developed RAH (39% vs. 21%, p = 0.026), and presenting with RAH independently predicted high mortality (HR: 1.55 [1.11-2.18])., Conclusions: RAH is common and has a more aggressive clinical course, including increased mortality. Patients surviving an episode of AH should undergo intense alcohol use disorder therapy to prevent RAH., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Objective: This study aimed to assess the influence of age, period, and cohort (A-P-C) factors on kidney cancer (KC) incidence trends in Spain from 1990 to 2019., Methods: Employing data from the Global Burden of Disease Study 2019, we employed joinpoint analysis to determine long-term patterns and A-P-C modelling to quantify net drift, local drift, longitudinal age curves, and rate ratios (RRs) of period and cohort effects., Results: Over the period 1990-2019, an estimated 142,811 cases of KC were diagnosed in Spain. A consistent upward trend in KC incidence was observed for both men and women, with the male-to-female ratio remaining stable at 2.6. Joinpoint analysis identified three distinct periods for men: An initial period (1990-1995) characterised by a significant increase in rates, a subsequent period (1995-2016) characterised by a slowdown in the rate of increase, and a final period (2016-2019) in which rates have plateaued. In women, 2 time periods were observed: an initial period (1990-2007) in which rates increased significantly, followed by a period of stabilization (2007-2019). Men born in the early-mid 20th century had a rising KC risk, peaking in the 1960s. Women's risk rose steadily, peaking in the late 1990s., Conclusion: A-P-C analysis reveals steady KC incidence increase in both genders over three decades. This highlights the need for targeted public health policies and effective prevention strategies., (Copyright © 2024 AEU. Published by Elsevier España, S.L.U. All rights reserved.)

Objectives: Lung Cancer (LC) is a multifactorial disease for which the role of genetic susceptibility has become increasingly relevant. Our aim was to use artificial intelligence (AI) to analyze differences between patients with LC based on family history of cancer (FHC)., Materials and Methods: From August 2016 to June 2020 clinical information was obtained from Thoracic Tumors Registry (TTR), a nationwide database sponsored by the Spanish Lung Cancer Group. In addition to descriptive statistical analysis, an AI-assisted analysis was performed. The German Technical Information Library supported the merging of data from the electronic medical records and database of the TTR. The results of the AI-assisted analysis were reported using Knowledge Graph, Unified Schema and descriptive and predictive analyses., Results: Analyses were performed in two phases: first, conventional statistical analysis including 11,684 patients of those 5,806 had FHC. Median overall survival (OS) for the global population was 23 months (CI 95 %: 21.39-24.61) in patients with FHC versus 21 months (CI 95 %: 19.53-22.48) in patients without FHC (NFHC), p < 0.001. The second AI-assisted analysis included 5,788 patients of those 939 had FHC. 58.48 % of women with FHC had LC. 9.53 % of patients had an EGFR or HER2 mutation or ALK translocation and at least one relative with cancer. A family history of LC was associated with an increased risk of smoking-related LC. Non-smokers with a family history of LC were more likely to have an EGFR mutation in NSCLC. In Bayesian network analysis, 55 % of patients with a family history of LC and never-smokers had an EGFR mutation., Conclusion: In our population, the incidence of LC in patients with a FHC is higher in women and younger patients. FHC is a risk factor and predictor of LC development, especially in people ≤ 50 years. These results were confirmed by conventional statistics and AI-assisted analysis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Calvo reported receiving personal fees from Roche, Bristol Myers Squibb, Merck Sharp & Dohme, AstraZeneca, Takeda, Pfizer, Sanofi and AMGEN outside the submitted work; being a consultant or advisor and speakerś bureau for Roche, Bristol Myers Squibb/Celgene, Merck Sharp & Dohme, AstraZeneca, Takeda Sanofi and AMGEN and receiving travel, accommodations, and expenses from Takeda, Roche, Bristol Myers Squibb and Merck Sharp & Dohme. Dr. Carcereny reported receiving consulting fees from AstraZeneca, Novartis, Boehringer Ingelheim, Roche, Bristol Myers Squibb, Merck Sharp & Dohme; payment or honoraria from AstraZeneca, Roche, Boehringer Ingelheim, Bristol Myers Squibb, Pfizer and receiving travel, accommodations, and expenses from Roche, Merck Sharp & Dohme, Takeda, Bristol Myers Squibb and Pfizer. Dr. Cobo reported receiving consulting fees from Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Lilly, Takeda, Pfizer, Kyowa, Sanofi, Jansen; payment or honoraria from Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Lilly, Takeda, Kyowa, Pierre-Fabre, Novocure, Sanofi, Jansen and receiving travel, accommodations, and expenses from AstraZeneca, Boehringer-Ingelheim, Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Lilly, Pierre-Fabre and being advisor for Gilead. Dr. López-Castro reported receiving consulting fees from Takeda, Roche, Pfizer, Novartis, Pierre-Fabre, Bristol Myers Squibb; payment or honoraria from Pfizer, Pierre-Fabre, Takeda, Roche, Novartis Jansen and receiving travel, accommodations, and expenses from Roche, Takeda, Novartis and Merck Sharp & Dohme. Dr. Bernabé reported receiving grant from Roche; payment or honoraria from Roche, Merck Sharp & Dohme, Pfizer, AMGEN, Takeda, Astrazeneca and receiving travel, accommodations, and expenses from Roche, Bristol Myers Squibb and being advisor for Takeda, Roche, Bristol Myers Squibb and Astrazeneca. Dr. Garcia-Campelo reported receiving consulting fees from AMGEN, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Roche, Janssen, Lilly, Merck Sharp & Dohme, Pfizer, Sanofi, Takeda, Pfizer; payment or honoraria from AMGEN, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Roche, Janssen, Lilly, Merck Sharp & Dohme, Pfizer, Sanofi, Takeda and receiving travel, accommodations, and expenses from AstraZeneca, Roche, Pfizer and being advisor for AstraZeneca. Dr. del Barco reported receiving travel, accommodations and expenses from Merck Sharp & Dohme. Dr. Bosch-Barrera reported receiving grants from Pfizer and Roche outside the submitted work; payment or honoraria from Astrazeneca, Pfizer, Merck Sharp & Dohme, Bristol Myers Squibb, Roche, Sanofi and receiving travel, accommodations, and expenses from Merck Sharp & Dohme, Roche and Takeda. Dr. Provencio reported receiving grants from Bristol Myers Squibb, Takeda, Roche, Pfizer, and Merck Sharp & Dohme outside the submitted work; being a consultant or advisor for Bristol Myers Squibb, Roche, Merck Sharp & Dohme, AstraZeneca, and Takeda; being on the speakers’ bureau for Bristol Myers Squibb, Roche, AstraZeneca, and Merck Sharp & Dohme; receiving research funds from Pierre Fabre, Roche, Boehringer Ingelheim, and Bristol Myers Squibb; and receiving travel, accommodations, and expenses from Roche, Bristol Myers Squibb, and AstraZeneca. The remaining authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Introduction and Objectives: The current evaluation of acute heart failure (HF) does not allow an adequate prediction of its evolution. The electrical bioimpedance (BI) allows knowing the state of blood volume, until now only with fixed equipment. We have developed and validated a portable and wireless device to measure BI at the ankle (IVOL). The objective of the study is to know the long-term prognostic value of the point measurement of BI with IVOL in patients with acute HF., Methods: A prospective cohort study of unselected patients admitted for acute HF in a tertiary hospital. The association between BI and different clinical, analytical and echocardiographic variables on admission and clinical evolution were analyzed., Results: 76 patients were included (mean age 66.1 years, 71.1% men, 68.4% hypertensive, 34.2% diabetic, mean NT-ProBNP: 7,103 pg / ml). Of these, 52.6% with non-preserved left ventricular ejection fraction (LVEF) (<50%) and 56.6% with right ventricular (RV) dysfunction. 26.3% died during a mean follow-up of 35.8 months. Survival in patients with BI≤21,8Ω was lower, globally and in the subgroups of patients without preserved LVEF and with RV dysfunction, P<.008). In the multivariate analysis, a BI≥21.8Ω was an independent survival factor (HR: 0.242; 95% CI: 0.86-0.681; P=.007)., Conclusions: BI values measured with IVOL may be an independent predictor of long-term mortality in patients hospitalized for acute HF. This prognostic value is maintained in patients without preserved LVEF function and with RV dysfunction., (Copyright © 2024 The Authors. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: In patients with acute ischemic stroke (AIS) secondary to intracranial large vessel occlusion, optimal blood pressure (BP) management following endovascular treatment (EVT) has not yet been established. The randomized trial on Hemodynamic Optimization of Cerebral Perfusion after Successful Endovascular Therapy in Patients with Acute Ischemic Stroke (HOPE) (clinicaltrials.gov id: NCT04892511) aims to demonstrate whether hemodynamic optimization using different systolic BP targets following EVT according to the degree of final recanalization, is more effective than currently recommended BP management in improving functional outcomes of patients with AIS., Methods: HOPE is an investigator-initiated multicenter clinical trial with randomized allocation, open-label treatment, and blinded endpoint evaluation (PROBE). Patients with an anterior circulation AIS within 24 h of symptom onset, treated with EVT, and showing successful recanalization (mTICI ≥2b) at the end of the procedure, are equally allocated (1:1) to hemodynamic optimization according to the study protocol versus BP management according to current guidelines (≤180/105 mm Hg). The protocol includes two different targets of systolic BP depending on the recanalization status (mTICI = 2b: 140-160 mm Hg; mTICI = 2c/3: 100-140 mm Hg). The protocol is applied within the first 72 h and includes BP lowering as well as vasopressor therapies when needed. The primary outcome is the proportion of favorable outcome (modified Rankin Scale [mRS] 0-2) at 90 days. Secondary outcomes include the shift on the mRS score, neurological deterioration, symptomatic intracerebral hemorrhage, and mortality., Conclusion: The HOPE trial will provide new information on the safety and efficacy of different BP targets following EVT according to the degree of final recanalization in patients with AIS., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Purpose: CAR therapy targeting BCMA is under investigation as treatment for multiple myeloma. However, given the lack of plateau in most studies, pursuing more effective alternatives is imperative. We present the preclinical and clinical validation of a new optimized anti-BCMA CAR (CARTemis-1). In addition, we explored how the manufacturing process could impact CAR-T cell product quality and fitness., Methods: CARTemis-1 optimizations were evaluated at the preclinical level both, in vitro and in vivo. CARTemis-1 generation was validated under GMP conditions, studying the dynamics of the immunophenotype from leukapheresis to final product. Here, we studied the impact of the manufacturing process on CAR-T cells to define optimal cell culture protocol and expansion time to increase product fitness., Results: Two different versions of CARTemis-1 with different spacers were compared. The longer version showed increased cytotoxicity. The incorporation of the safety-gene EGFRt into the CARTemis-1 structure can be used as a monitoring marker. CARTemis-1 showed no inhibition by soluble BCMA and presents potent antitumor effects both in vitro and in vivo. Expansion with IL-2 or IL-7/IL-15 was compared, revealing greater proliferation, less differentiation, and less exhaustion with IL-7/IL-15. Three consecutive batches of CARTemis-1 were produced under GMP guidelines meeting all the required specifications. CARTemis-1 cells manufactured under GMP conditions showed increased memory subpopulations, reduced exhaustion markers and selective antitumor efficacy against MM cell lines and primary myeloma cells. The optimal release time points for obtaining the best fit product were > 6 and < 10 days (days 8-10)., Conclusions: CARTemis-1 has been rationally designed to increase antitumor efficacy, overcome sBCMA inhibition, and incorporate the expression of a safety-gene. The generation of CARTemis-1 was successfully validated under GMP standards. A phase I/II clinical trial for patients with multiple myeloma will be conducted (EuCT number 2022-503063-15-00)., (© 2024. The Author(s).)

Ewing sarcoma is a small round-cell sarcoma characterized by gene fusion involving EWSR1 (or another TET family protein like FUS) and an ETS family transcription factor. The estimated incidence of this rare bone tumor, which occurs most frequently in adolescents and young adults, is 0.3 per 100,000/year. Although only 25% of patients with Ewing sarcoma are diagnosed with metastatic disease, historical series show that this is a systemic disease. Patient management requires multimodal therapies-including intensive chemotherapy-in addition to local treatments (surgery and/or radiotherapy). In the recurrent/refractory disease setting, different approaches involving systemic treatments and local therapies are also recommended as well as patient inclusion in clinical trials whenever possible. Because of the complexity of Ewing sarcoma diagnosis and treatment, it should be carried out in specialized centers and treatment plans should be designed upfront by a multidisciplinary tumor board. These guidelines provide recommendations for diagnosis, staging, and multimodal treatment of Ewing sarcoma., (© 2024. The Author(s).)

The concept of "remission" in asthma has been around for a long time and it has been a controversial topic. Despite the attempts of some studies to characterize this entity, the discussion continues. In the case of asthma there is still no clear definition, either in terms of its meaning or the parameters that should be included or whether it should be divided into clinical or complete remission. To help defining these controversial concepts, SEPAR has advocated the multidisciplinary working group REMAS (REMission in ASthma). Following the Delphi methodology and with the involvement of more than 120 specialists in asthma management, this group has arrived at a consensus on the definitions of remission in asthma and establishing the criteria and characteristics that will be of use in future studies evaluating the efficacy or effectiveness of treatments., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: Granulocyte-monocyte apheresis (GMA) has shown to be safe and effective in treating ulcerative colitis (UC), also in combination with biologics. The objective of this study is to evaluate the efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to tofacitinib (TOFA) in patients with UC., Patients and Methods: Retrospective study including all patients with refractory UC who received GMA plus TOFA. Efficacy was assessed 1 and 6 months after finishing GMA by partial Mayo score, C-reactive protein (CRP) and fecal calprotectin (FC). Descriptive statistics and non-parametric tests were used in the statistical analysis., Results: Twelve patients were included (median 46 years [IQR, 37-58]; 67% female; 67% E3). Patients were mostly receiving TOFA 10mg bid (75%), and 33% also concomitant steroids at baseline. Median partial Mayo score at baseline was 7 (IQR, 5-7), and it decreased to a median of 2 (IQR, 0-3) and 0 (IQR, 0-3) after 1 and 6 months (p=0.027 and 0.020, respectively), while no differences were found in CRP and FC. Clinical remission was achieved by 6 patients both at 1 (50%) and 6 months (67%). CF values<250mg/kg were achieved by 2 and 4 patients at 1 and 6 months (data available in 5 and 7 patients, respectively). No patient required dose-escalation of TOFA, and one patient was able to de-escalate the drug. No patient required colectomy and all patients under steroids were able to stop them., Conclusion: The combination of GMA and TOFA can be effective in selected cases of UC after PNR or LOR to this drug., (Copyright © 2024 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: The treatment landscape for neuromyelitis optica spectrum disorder (NMOSD) has changed in recent years with the approval of therapies with different efficacy, safety and administration profiles., Objective: The aim of this study was to assess neurologists' preferences for different NMOSD treatment attributes using conjoint analysis (CA)., Methods: We conducted an online, non-interventional, cross-sectional study in collaboration with the Spanish Society of Neurology. Our CA assessed five drugs' attributes: prevention of relapse, prevention of disability accumulation, safety risk, management during pregnancy, and route and frequency of administration. Participants were presented with eight hypothetical treatment scenarios to rank based on their preferences from the most preferred to the least. An ordinary least squares method was selected to estimate weighted preferences., Results: A total of 104 neurologists were included. Mean age (standard deviation-SD) was 37.7 (10.3) years, 52.9 % were male, and median time (interquartile range) of experience managing NMOSD was 5.0 (2.9, 10.8) years. Neurologists placed the greatest importance on efficacy attributes, time to relapse (44.1 %) being the most important, followed by preventing disability accumulation (36.8 %). In contrast, route and frequency of administration (4.6 %) was the least important characteristic. Participants who prioritised efficacy attributes felt more comfortable in decision-making, had fewer past experiences of care-related regret and a lower attitude to risk taking than their counterparts., Conclusion: Neurologists' treatment preferences in NMOSD were mainly driven by efficacy attributes. These results may be useful to design policy decisions and treatment guidelines for this condition., Competing Interests: Declaration of competing interest R.G-B, P.L-L, and J.M are employees of Roche Farma Spain. P.R is an employee of IQVIA Spain. N.T-L received compensation for consulting services, advisory activities and speaking honoraria from Bayer Schering Pharma, Biogen Idec, MerckSerono, Novartis, Sanofi-Aventis, Teva Pharmaceuticals, Roche Pharma and Bristol Myers Squibb. M.S received speaking honoraria from Roche, Biogen and UCB Pharma, and travel reimbursement from Biogen, Sanofi, Merck and Roche for national and international meetings. A.O received research grants, travel support or honoraria for speaking engagements from Almirall, Biogen, Bristol Myers Squibb, Merck, Mylan, Novartis, Roche, Sanofi-Genzyme, and Teva. M.D-S received speaking honoraria from Roche, Biogen, Novartis, Sanofi and Janssen; and travel reimbursement from Biogen for international meeting. SB received research grants, travel support or honoraria for speaking engagements from Biogen, Bristol Myers Squibb, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. M.A-V received speaking honoraria from Roche, Biogen, Novartis, Sanofi and Janssen. A.CC has received grant from Instituto de Salud Carlos III, Spain; JR19/00,007. A preliminary report of this data was presented as an eposter at the 9th Congress of the European Academy of Neurology (EPV-505, Budapest, Hungary; July 1–4, 2023)., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The EPICO (Spanish general registry of COVID-19 in children)-SEHOP (Spanish Society of Pediatric Hematology and Oncology) platform gathers data from children with SARS-CoV-2 in Spain, allowing comparison between children with cancer or allogeneic hematopoietic stem cell transplantation (alloHSCT) and those without. The infection is milder in the cancer/alloHSCT group than in children without comorbidities (7.1% vs. 14.7%), except in children with recent alloHSCT (less than 300 days), of which 35.7% experienced severe COVID-19. These data have been shared with the SEHOP members to support treatment and isolation policies akin to those for children without cancer, except for those with recent alloHSCT or additional comorbidities. This highlights the collaborative registries potential in managing pandemic emergencies., (© 2024 Wiley Periodicals LLC.)

Background and Aims: Spontaneous ruptured hepatocellular carcinoma is an uncommon complication, and there are scarce data about non-cirrhotic patients. Tumor treatment is not standardized and the risk of peritoneal dissemination is unclear., Aim: we analyzed the treatment and survival in patients with rHCC on non-cirrhotic liver., Methods: One hundred and forty-one non-cirrhotic patients with hepatocellular carcinoma diagnosed by histology were included in a multicenter prospective registry (2018-2022). Seven of them (5%) presented with hemoperitoneum due to spontaneous rupture., Results: Liver disease was associated in three patients (42.9%). A single nodule was detected in three cases (42.9%). One patient had vascular invasion and none extrahepatic spread. Initial hemostatic therapy and sequential treatment was individualized. Patients with single nodule were treated: resection (one case) with recurrence at 4 months treated with TACE and sorafenib. TACE/TAE followed by surgery (two cases) one in remission 43 months later, the other had liver recurrence at 18 months and was transplanted. Patients with multiple lesions were treated: TAE/emergency surgery and subsequent systemic therapy (two cases), one received lenvatinib (1-year survival) and the other sorafenib (5-month survival). TAE and surgery with subsequent systemic therapy (one case). Initial hemostatic surgery, dying on admission (one case). No patient developed intraperitoneal metastasis. All patients with multiple lesions died by tumor. The 3-year survival rate was 42.9%., Conclusions: Initial hemostasis was achieved in all patients by TAE/TACE or surgery. Subsequent treatment was individualized, based on tumor characteristics, regardless of rupture. Long-time remission could be achieved in single nodule patients., (Copyright © 2023 Elsevier España, S.L.U. All rights reserved.)

Aims: To compare glycemic control and maternal-fetal outcomes of women with type 1 diabetes (T1D) using hybrid closed loop (HCL) versus multiple daily insulin injections (MDI) plus continuous glucose monitoring. Methods: Multicenter prospective cohort study of pregnant women with T1D in Spain. We evaluated HbA1c and time spent within (TIR), below (TBR), and above (TAR) the pregnancy-specific glucose range of 3.5-7.8 mmol/L. Adjusted models were performed for adverse pregnancy outcomes, including baseline maternal characteristics and center. Results: One hundred twelve women were included (HCL n  = 59). Women in the HCL group had a longer duration of diabetes and higher rates of prepregnancy care. There was no between-group difference in HbA1c in any trimester. However, in the second trimester, MDI users had a greater decrease in HbA1c (-6.12 ± 9.06 vs. -2.16 ± 7.42 mmol/mol, P  = 0.031). No difference in TIR (3.5-7.8 mmol/L) and TAR was observed between HCL and MDI users, but with a higher total insulin dose in the second trimester [+0.13 IU/kg·day)]. HCL therapy was associated with increased maternal weight gain during pregnancy (β adjusted  = 3.20 kg, 95% confidence interval [CI] 0.90-5.50). Regarding neonatal outcomes, newborns of HCL users were more likely to have higher birthweight (β adjusted  = 279.0 g, 95% CI 39.5-518.5) and macrosomia (OR adjusted  = 3.18, 95% CI 1.05-9.67) compared to MDI users. These associations disappeared when maternal weight gain or third trimester HbA1c was included in the models. Conclusions: In a real-world setting, HCL users gained more weight during pregnancy and had larger newborns than MDI users, while achieving similar glycemic control in terms of HbA1c and TIR.

Introduction: Peritoneal sarcomatosis is a rare disease, with multiple histological origins and poor overall prognosis. The option of radical cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is controversial. The results of a surgical team experienced in these procedures are analyzed and discussed based on the available evidence., Methods: Study on a prospective database of patients with peritoneal sarcomatosis who underwent CRS and HIPEC, from 2016 to 2022, in a national reference center for sarcomas and peritoneal oncological surgery, who met the established inclusion/exclusion criteria., Results: 23 patients were included in the study, with a median age of 53 years (6-68). Recurrent/persistent clinical presentation predominated (78.3%). Visceral origin (including GIST and non-GIST peritoneal) accounted for 47.8% of patients, compared to 43.5% uterine and 8.7% retroperitoneal. The median PCI was 17 (3-36), with CC0 cytoreduction of 87%. Postoperative morbidity (Dindo Clavien III-IV) of 13%, with no postoperative mortality in the series. Overall survival and disease-free survival at 5 years were 64% and 34%, respectively. Histological grade was the most influential prognostic factor for survival., Conclusions: The results of the series, with low morbidity, support the benefit of radical peritoneal oncological surgery in patients with peritoneal sarcomatosis after adequate selection, as long as it is performed in high-volume centers, experienced surgeons and expert multidisciplinary teams. However, the role of HIPEC remains to be demonstrated and pending future studies., (Copyright © 2024 AEC. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Two-stage exchange is the gold standard in the surgical management of prosthetic joint infection (PJI). However, perioperative reinfections (RePJI) can occur to newly inserted prosthesis, which highlights the importance of an adequate antibiotic prophylaxis, although there is scarce evidence in this field. Our objective was to evaluate the characteristics of RePJI, its prognosis and the antibiotic prophylaxis that is commonly used in second-stage surgery., Methods: Multicentric retrospective observational study in Spanish hospitals including patients with RePJI between 2009 and 2018., Results: We included 92 patients with RePJI from 12 hospitals. The most frequent isolated microorganism was Staphylococcus epidermidis in 35 cases (38.5%); 61.1% of staphylococci were methiciliin-resistant. In 12 cases (13%), the same microoganism causing the primary PJI was isolated in RePJI. When comparing with the microbiology of primary PJI, there were more cases caused by Gram-negative bacteria (the most frequent was Pseudomonas spp.) and less by Gram-positive bacteria. Failure occured in 69 cases (75%). There were 43 different courses of antibiotic prophylaxis after the second-stage surgery; the most frequent was a unique preoperative cefazolin dose, but most patients received prophylaxis before and after the second-stage surgery (61 cases)., Conclusions: The most frequent microorganisms in RePJI are coagulase-negative staphylococci, although Gram-negative bacteria, especially Pseudomonas spp. are also common. There is a significant heterogeneity in antibiotic prophylaxis for a second-stage surgery. ReIPJI treatment has a high failure rate., (Copyright © 2023 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Published by Elsevier España, S.L.U. All rights reserved.)

Primary aldosteronism (PA) is the most frequent cause of secondary hypertension and is associated with a higher cardiometabolic risk than essential hypertension. The aim of this consensus is to provide practical clinical recommendations for its surgical and medical treatment, pathology study and biochemical and clinical follow-up, as well as for the approach in special situations like advanced age, pregnancy and chronic kidney disease, from a multidisciplinary perspective, in a nominal group consensus approach of experts from the Spanish Society of Endocrinology and Nutrition (SEEN), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN), Spanish Society of Internal Medicine (SEMI), Spanish Radiology Society (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Society of Laboratory Medicine (SEQC(ML)), Spanish Society of Anatomic-Pathology and Spanish Association of Surgeons (AEC)., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We investigated the use patterns and indications of intraoperative neural monitoring (IONM) among endocrine surgeons in Spain. We sent an anonymous web-based survey to endocrine surgeons' members of the Spanish Association of Surgery by email. We analysed 79/ 269 surveys. Respondents had a median age of 52 years and 13 years of surgical experience. Only 32% of respondents performed routinely preoperative laryngoscopy in all thyroidectomies and 19% in all parathyroidectomies. Seventy-five percent of respondents used the intermittent-IONM, and 9.7% used the continuous-IONM. All respondents identified recurrent laryngeal nerve during surgery, and 40% of surgeons routinely identified external branch superior laryngeal nerve (EBSLN) during thyroidectomy. Seventy-eight percent of respondents used IONM always for all thyroidectomies. Only 11% stimulated EBSLN in all cases. Forty-nine percent used IONM always for all parathyroidectomies. The most frequent reasons for not using IONM were the unavailability of IONM, the high cost, and the lack of adding value to their clinical practice. Almost 10% declared not having IONM. The IONM is a reality in Spain, especially the intermittent mode. Its use is superior in thyroid surgery than in parathyroid. Its standardized use is not yet fully established, and routine adherence to standardized guidelines should increase., (© 2024. The Author(s).)

Background: Carboplatin and paclitaxel (CP) have been the standard of care for advanced/recurrent endometrial cancer (EC) for many years. However, this chemotherapy combination shows limited efficacy and recurrences often occur in less than 12 months. ABTL0812 is a novel drug that selectively kill cancer cells by cytotoxic autophagy and has shown anticancer efficacy in preclinical models of EC in combination with CP., Methods: ENDOLUNG was an open-label, phase 1/2 clinical trial designed to determine the safety and efficacy of Ibrilatazar (ABTL0812) with CP in patients with advanced/recurrent EC and non-irradiable stage III and IV squamous non-small cell lung cancer (sq-NSCLC). The phase 1 part consisted of a 3 + 3 de-escalation design followed by an expansion cohort with 12 patients. The primary endpoint was safety. ABTL0812 starting dose was 1300 mg tid combined with carboplatin at area under the curve (AUC) 5 and paclitaxel at 175 mg/m 2 both administered every 21 days for up to 8 cycles. The phase 2 part included a total of 51 patients. The primary endpoint was overall response rate (ORR) and the secondary endpoints included duration of response (DOR), progression-free survival (PFS) and overall survival (OS)., Results: During the phase 1 only one dose limiting toxicity (DLT), a grade 4 neutropenia, was observed in 1 out of 6 patients, thus no de-escalation was applied. One additional DLT, a grade 3 febrile neutropenia, was observed in the expansion cohort, thus the recommended phase 2 dose (RP2D) for ABTL0812 was established at 1300 mg tid. Most frequent hematological adverse events (AE) of the combination were neutropenia (52.9%), anemia (37.3%) and thrombocytopenia (19.6%). Nausea (66.7%), asthenia (66.7%), diarrhea (54.9%) and vomiting (54.9%) were the most frequent non-hematological adverse events (AEs). The combination of ABTL0812 plus CP showed an ORR of 65.8% (13.2% complete response and 52.6% partial response) with a median DOR of 7.4 months (95% CI: 6.3-10.8 months). Median PFS was 9.8 months (95% CI: 6.6-10.6) and median OS 23.6 months (95% CI 6.4-ND). Pharmacokinetic parameters were compatible with target engagement observed in preclinical studies, and blood pharmacodynamic biomarkers indicated sustained target regulation during, at least, 28 days after starting the treatment., Conclusions: This study suggests that the combination of ABTL0812 with CP is safe and feasible with an encouraging activity in patients with advanced/recurrent EC. Our data warrant further confirmation in prospective randomized trials., Trial Registration: EU Clinical Trial Register, EudraCT number 2016-001352-21 and National Clinical Trials Number, NCT03366480. Registration on 19 September 2016., (© 2024. The Author(s).)

Competing Interests: Conflicto de intereses: Los autores declaran no tener ningún conflicto de intereses.

Introduction: The indication of preoperative prophylaxis in the insertion of indwelling tunneled central venous catheters (ITCVC) has a low level of evidence. Our objective was to assess risk factors of ITCVC-related early bacteremia in oncological pediatric patients and to determine the need for preoperative prophylaxis., Materials and Methods: A univariate and multivariate retrospective analysis of patients in whom an ITCVC was placed from January 2020 to July 2023, according to whether they had ITCVC-related early bacteremia (EB) in the first 30 postoperative days, was carried out. Demographic variables, leukopenia, neutropenia, use of preoperative antibiotic prophylaxis, and history of central venous catheter (CVC) or bacteremia were collected. Calculations were carried out using the IBM SSPS29® software., Results: 176 patients with a mean age of 7.6 years (SD: 4.82) were analyzed. 7 EB cases were identified, with a greater frequency of neutropenia (p= 0.2), history of CVC in the 48 hours before insertion (p= 0.08), and intraoperative CVC (p= 0.04). The presence of intraoperative CVC increased the risk of EB 9-fold [OR: 9.4 (95%CI: 1.288-69.712) (p= 0.027)]. The lack of preoperative prophylaxis did not increase the risk of EB [OR: 2.2 (CI: 0.383-12.669) (p= 0.3)]. The association with other variables was not significant., Conclusions: The intraoperative presence of CVC was a risk factor of EB in our patients. Preoperative prophylaxis had no impact on the risk of EB, which in our view does not support its use. However, further studies with a larger sample size are required. Leukopenia or neutropenia at diagnosis were not associated with a greater prevalence of infection.

Background: Trabectedin in combination with pegylated liposomal doxorubicin (PLD) is approved for the treatment of patients with platinum-sensitive relapsed ovarian cancer. Nevertheless, there is currently limited information regarding this treatment in elderly patients with ovarian cancer in a real-world setting., Methods: This observational and multicentric study retrospectively evaluated trabectedin plus PLD in a real-world setting treatment of elderly patients diagnosed with platinum-sensitive relapsed ovarian cancer, treated according to the Summary of Product Characteristics (SmPC) from 15 GEICO-associated hospitals. Patients ≥ 70 years old at the time of treatment initiation and platinum-free intervals ≥ 6 months were considered eligible., Results: Forty-three patients with a median age of 74.0 years were treated between January 1st, 2015, and December 31st, 2019 in 15 Spanish centers. Four patients achieved complete response (9.3%), 14 (32.6%) partial response, and 13 (30.2%) stable disease as the best radiological response. In the analysis of biological overall response according to CA125 serum levels (i.e., Rustin criteria), 14 responded to the treatment (32.6%), 11 responded and normalized (25.6%), three patients stabilized (7.0%) and three progressed (7.0%). Median progression-free survival (PFS) and overall survival (OS) in the study population were 7.7 and 19.5 months, respectively. The most common grade 3/4 adverse events were neutropenia (n = 8, 18.7%) and asthenia (n = 5, 11.6%)., Conclusions: This analysis demonstrated that trabectedin combined with PLD is a feasible and effective treatment in elderly patients with platinum-sensitive relapsed ovarian cancer, showing an acceptable safety profile, which is crucial in the palliative treatment of these patients., (© 2024. The Author(s).)

Objective: To develop by consensus a dashboard model to standardize and promote the evaluation of research activity in Spanish Hospital Pharmacy Services., Methods: The study was carried out in 5 phases following the modified Delphi methodology: constitution of the coordinating group, elaboration of a list of scenarios, selection of participating centers, evaluation of the list of scenarios, and analysis of the results. The coordinating group designed a questionnaire with 114 questions. General research questions and different scenarios (indicators) were included to form the dashboard. The Hospital Pharmacy Services with the highest number of publications were identified to participate in the Delphi consultation. Two rounds of consultations were conducted in which the "Need" and/or "Feasibility" of their measurement was evaluated for each of the scenarios, using a numerical scale from 1 (lowest score) to 9 (highest score)., Results: Sixteen Hospital Pharmacy Services, belonging to 8 different autonomous communities, participated in the Delphi consultation. A total of 100% of them responded to all the questions in the 2 rounds of consultations. It was considered that the Hospital Pharmacy Services should have a research dashboard (need = 100%) with a basic structure and a common minimum set of data for all them (need = 87.5%). The consensus was reached on distinguishing research projects led by the Hospital Pharmacy Services from those led by other groups in which the Hospital Pharmacy Services collaborate (need = 87.5%), and a definition was approved on the leadership of these projects according to whether they are single-center or multicenter. A consensus was reached on 40 indicators to form the dashboard, which evaluates publications (13 indicators), human resources (12 indicators), research projects (9 indicators), doctoral theses (4 indicators), and patents and intellectual property registrations (2 indicators)., Conclusions: This is the first consensus dashboard developed to evaluate the research activity of the Hospital Pharmacy Services, which will help to analyze the productivity and impact of research systematically and continuously. In addition, it will allow comparison between them and will help to establish synergies and identify trends, patterns, and challenges., (Copyright © 2024 Sociedad Española de Farmacia Hospitalaria (S.E.F.H). Publicado por Elsevier España, S.L.U. All rights reserved.)

Hereditary ataxia (HA) and hereditary spastic paraplegia (HSP) are rare diseases; as such, they are rarely managed in general neurology consultations. We present a set of brief, practical recommendations for the diagnosis and management of these patients, as well as a standardised procedure for comprehensive evaluation of disability. We provide definitions for HA and "HA plus," and "pure" and "complicated" HSP; describe the clinical assessment of these patients, indicating the main complementary tests and clinical scales for physical and psychological assessment of the patients; and summarise the available treatments. These recommendations are intended to facilitate daily neurological practice and to unify clinical criteria and disability assessment protocols for patients with HA and HSP., (Copyright © 2022 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: Genitourinary (GU) multidisciplinary tumour boards (GUMTBs) are key components of patient care, as they might lead to changes in treatment plan, improved survival, and increased adherence to guidelines. However, there are no guidelines on how GUMTBs should operate or how to assess their quality of performance., Methods: A systematic literature review was conducted to identify criteria and indicators to evaluate quality in GUMTBs. A scientific committee-comprising 12 GU cancer specialists from seven disciplines-proposed a list of criteria and developed indicators, evaluated in two rounds of Delphi method. Appropriateness and utility of indicators were scored using a 9-point Likert scale. Consensus was defined as at least two-thirds of Delphi respondents selecting a score sub-category that encompassed the median score of the group., Results: Forty-five criteria were selected to evaluate the quality of GUMTBs covering five dimensions: organisation, personnel, protocol and documentation, resources, and interaction with patients. Then, 33 indicators were developed and evaluated in the first round of Delphi, leading to a selection of 26 indicators in two dimensions: function, governance and resources, and GUMTB sessions. In the second round, consensus was reached on the appropriateness of all 26 indicators and on the utility of 24 of them. Index cards for criteria and indicators were developed to be used in clinical practice., Conclusions: Criteria and indicators were developed to evaluate the quality of GUMTBs, aiming to serve as a guide to improve quality of care and health outcomes in patients with GU cancer., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Primary aldosteronism (PA) is the most frequent cause of secondary hypertension (HT), and is associated with a higher cardiometabolic risk than essential HT. However, PA remains underdiagnosed, probably due to several difficulties clinicians usually find in performing its diagnosis and subtype classification. The aim of this consensus is to provide practical recommendations focused on the prevalence and the diagnosis of PA and the clinical implications of aldosterone excess, from a multidisciplinary perspective, in a nominal group consensus approach by experts from the Spanish Society of Endocrinology and Nutrition (SEEN), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN), Spanish Society of Internal Medicine (SEMI), Spanish Radiology Society (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Society of Laboratory Medicine (SEQC(ML)), Spanish Society of Anatomic-Pathology, Spanish Association of Surgeons (AEC)., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: To evaluate the impact of haemophilia A without inhibitors on humanistic outcomes in patients and caregivers. Herein, we report a cross-sectional analysis of the baseline data of persons with haemophilia (PWH) participating in the prospective study HEMOLIFE., Methods: These data are part of a prospective, observational, and multicentre study currently being conducted in 20 hospitals in Spain by haematologists. We included subjects 12 years or older diagnosed with haemophilia. The evaluations included the Maladjustment Scale, Haemophilia-Specific Quality of Life Questionnaire for Adults (HaemoQol)/HaemoQol Short Form (Children), haemophilia-specific version of the Work Productivity and Impairment Questionnaire plus the Classroom Impairment Questionnaire (WPAI+CIQ:HS), Haemophilia Activity List (HAL)/Paediatric Haemophilia Activities List (pedHAL), visual analogue scale (VAS) for evaluating pain, Coping Pain Questionnaire-Reduced (CAD-R), and Hospital Anxiety and Depression Scale (HADS)., Results: A total of 81 PWH were recruited at 18 centres; 66 PWH were ≥18 years (i.e., adults), and PWH 15 were <18 years (i.e., paediatric patients). Out of the 79 evaluable subjects, 16 (20%) showed an impact of haemophilia on daily life, and the areas most affected were "leisure time" (58% showed maladjustment) and "work/studies" (47% showed maladjustment). Patients reported a higher impact of haemophilia on quality of life (mean [SD] of the transformed score) in the dimensions of "sport" (49.4 [28.6]), "physical health" (40.5 [25.8]) and "future" (37.7 [28.9]). In adults, according to HAL scores, greater impairment of function was observed in "lying/sitting/kneeling/standing," "function of legs" and "leisure activities and sports," with mean normalized scores of 64.7, 65.1 and 69.0, respectively. Productivity was mostly impacted by presenteeism. The pain was infrequent and moderate. According to the HADS scores, nine (11.5%) patients had clinical anxiety and depression., Conclusion: PWH without inhibitors exhibited impairments in adjustment, quality of life and functionality, especially related to leisure and sports activities, and exhibit relevant levels of anxiety and depression., (© 2024 The Author(s). Haemophilia published by John Wiley & Sons Ltd.)

Background and Objective: Psoriasis often precedes the onset of psoriatic arthritis (PsA), so dermatologists often face the challenge of early identifying signs of PsA in patients with psoriasis. Our aim was to validate the Spanish version of the PURE-4 questionnaire as a screening tool for PsA, evaluate its performance in terms of sensitivity, specificity, feasibility, reliability, and build validity., Methods: This was a cross-sectional, observational, multicenter trial of adult patients with psoriasis. Initially, patients were assessed by a dermatologist and completed 2 self-administered versions (in print and online) of the PURE-4 questionnaire. Afterwards, the rheumatologist, blinded to the PURE-4 results, assessed the presence/absence of PsA, being the reference to determine the performance of the PURE-4 questionnaire., Results: A total of 268 patients were included (115 [42.9%] women; mean age, 47.1±12.6). The prevalence of PsA according to rheumatologist diagnosis was 12.7% (34 patients). The mean PURE-4 score for patients with psoriasis diagnosed with PsA was 2.3±1.1, and 1.3±1.3 for patients without PsA (P<.001). The cutoff value ≥2 demonstrated the best performance for detecting PsA, with a negative predictive value of 95.1% (95% confidence interval, 90.3-97.6)., Conclusions: The PURE-4 questionnaire demonstrated good performance in detecting PsA, with an optimal cutoff point ≥2. This simple tool could facilitate early referral of patients to the rheumatology unit., (Copyright © 2024 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: The methodology used for recording, evaluating and reporting postoperative complications (PC) is unknown. The aim of the present study was to determine how PC are recorded, evaluated, and reported in General and Digestive Surgery Services (GDSS) in Spain, and to assess their stance on morbidity audits., Methods: Using a cross-sectional study design, an anonymous survey of 50 questions was sent to all the heads of GDSS at hospitals in Spain., Results: The survey was answered by 67 out of 222 services (30.2%). These services have a reference population (RP) of 15 715 174 inhabitants, representing 33% of the Spanish population. Only 15 services reported being requested to supply data on morbidity by their hospital administrators. Eighteen GDSS, with a RP of 3 241 000 (20.6%) did not record PC. Among these, 7 were accredited for some area of training. Thirty-six GDSS (RP 8 753 174 (55.7%) did not provide details on all PC in patients' discharge reports. Twenty-four (37%) of the 65 GDSS that had started using a new surgical procedure/technique had not recorded PC in any way. Sixty-five GDSS were not concerned by the prospect of their results being audited, and 65 thought that a more comprehensive knowledge of PC would help them improve their results. Out of the 37 GDSS that reported publishing their results, 27 had consulted only one source of information: medical progress records in 11 cases, and discharge reports in 9., Conclusions: This study reflects serious deficiencies in the recording, evaluation and reporting of PC by GDSS in Spain., (Copyright © 2024. Published by Elsevier España, S.L.U.)

The treatment landscape for multiple myeloma has significantly evolved in the last decade. Notwithstanding, a large proportion of patients continue to relapse and novel combinations continue to be needed. In this phase II study, selinexor, a first-in-class inhibitor of exportin-1 was evaluated in combination with standard daratumumab-bortezomib-dexamethasone (DVd), for the treatment of relapsed and refractory multiple myeloma (RRMM). The aim of the trial was to assess the efficacy and safety of the combination of selinexor with DVd (S-DVd). A total of 57 patients were enrolled in the two parts of the study. Part 1 enrolled a heavily pretreated population with at least three prior lines (PL) of therapy and part 2 enrolled an early relapse population with at least one PL of therapy. The primary endpoint was complete response (CR) rate in part 2 and overall response rate (ORR) in part 1. In the latter, 24 patients were treated with a median of three PL. Overall response rate (ORR) was 50% with two CR. Median progression- free survival (PFS) was 7 months. In part 2, 33 patients were enrolled, with a median of one PL. ORR was 82% and CR or better was 33%. Median PFS was 24 months. In lenalidomide-refractory patients, a median PFS of 22.1 months was observed. Thrombocytopenia was the most common hematological adverse event (69%; grade 3-4: 34%) and nausea, the most frequent non-hematological adverse event (38%; grade 3-4: 6%). Sixty-two percent of the patients required dose modifications. In summary, although the primary endpoint of the study was not met, the combination of S-DVd showed encouraging clinical efficacy with a generally manageable safety profile representing a potential option for the treatment of RRMM patients.

Objective: To develop by consensus a dashboard model to standardise and promote the evaluation of research activity in Spanish Hospital Pharmacy Services., Methods: The study was carried out in 5 phases following the modified Delphi methodology: constitution of the coordinating group, elaboration of a list of scenarios, selection of participating centres, evaluation of the list of scenarios, and analysis of the results. The coordinating group designed a questionnaire with 114 questions. General research questions and different scenarios (indicators) were included to form the dashboard. The Hospital Pharmacy Services with the highest number of publications were identified to participate in the Delphi consultation. Two rounds of consultations were conducted in which the "Need" and/or "Feasibility" of their measurement was evaluated for each of the scenarios, using a numerical scale from 1 (lowest score) to 9 (highest score)., Results: Sixteen Hospital Pharmacy Services, belonging to 8 different Autonomous Communities, participated in the Delphi consultation. A total of 100% of them responded to all the questions in the 2 rounds of consultations. It was considered that the Hospital Pharmacy Services should have a research dashboard (Need=100%) with a basic structure and a common minimum set of data for all them (Need=87.5%). The consensus was reached on distinguishing research projects led by the Hospital Pharmacy Services from those led by other groups in which the Hospital Pharmacy Services collaborate (Need=87.5%), and a definition was approved on the leadership of these projects according to whether they are single-centre or multicentre. A consensus was reached on 40 indicators to form the dashboard, which evaluates publications (13 indicators), human resources (12 indicators), research projects (9 indicators), doctoral theses (4 indicators), and patents and intellectual property registrations (2 indicators)., Conclusions: This is the first consensus dashboard developed to evaluate the research activity of the Hospital Pharmacy Services, which will help to analyse the productivity and impact of research systematically and continuously. In addition, it will allow comparison between them and will help to establish synergies and identify trends, patterns, and challenges., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 Sociedad Española de Farmacia Hospitalaria (S.E.F.H). Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: After two-stage exchange due to prosthetic joint infection (PJI), the new prosthesis carries a high risk of reinfection (RePJI). There isn`t solid evidence regarding the antibiotic prophylaxis in 2nd-stage surgery. The objective of this study is to describe what antibiotic prophylaxis is used in this surgery and evaluate its impact on the risk of developing RePJI., Methods: Retrospective multicenter case-control study in Spanish hospitals. The study included cases of PJI treated with two-stage exchange and subsequently developed a new infection. For each case, two controls were included, matched by prosthesis location, center, and year of surgery. The prophylaxis regimens were grouped based on their antibacterial spectrum, and we calculated the association between the type of regimen and the development of RePJI using conditional logistic regression, adjusted for possible confounding factors., Results: We included 90 cases from 12 centers, which were compared with 172 controls. The most frequent causative microorganism was Staphylococcus epidermidis with 34 cases (37.8%). Staphylococci were responsible for 50 cases (55.6%), 32 of them (64%) methicillin-resistant. Gram-negative bacilli were involved in 30 cases (33.3%), the most common Pseudomonas aeruginosa. In total, 83 different antibiotic prophylaxis regimens were used in 2nd-stage surgery, the most frequent a single preoperative dose of cefazolin (48 occasions; 18.3%); however, it was most common a combination of a glycopeptide and a beta-lactam with activity against Pseudomonas spp (99 cases, 25.2%). In the adjusted analysis, regimens that included antibiotics with activity against methicillin-resistant staphylococci AND Pseudomonas spp were associated with a significantly lower risk of RePJI (adjusted OR = 0.24; 95% IC: 0.09-0.65)., Conclusions: The lack of standardization in 2nd-satge surgery prophylaxis explains the wide diversity of regimens used in this procedure. The results suggest that antibiotic prophylaxis in this surgery should include an antibiotic with activity against methicillin-resistant staphylococci and Pseudomonas., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Mycoplasma pneumoniae (M. pneumoniae) is a bacterium with particular characteristics that give rise to a broad clinical spectrum, being respiratory infection the most frequent presentation. Infection by M. pneumoniae occurs in cyclical epidemics, and paediatricians in Spain have noticed an increase in cases since January 2024, establishing hospital registers to collect surveillance data (as it is not a notifiable disease in Spain). The diagnosis of infection by M. pneumoniae is made through serological testing and/or the detection of genetic material by means of polymerase chain reaction (PCR). Neither methods can differentiate between colonization and active infection, so a precise diagnosis is not possible and testing should only be requested in the case of high clinical suspicion. The role of antibiotherapy in infection by M. pneumoniae in its different clinical variants is not well defined. Most infections are self-limiting and mild, and there is insufficient evidence to support the use of antibiotherapy in these cases. Antibiotic treatment is justified in patients with risk factors for the development of severe disease (Down syndrome, anatomical or functional asplenia, immunosuppression), in hospitalized patients with respiratory infection and in patients with moderate or severe extrapulmonary forms. Taking into account aspects concerning the rational use of antimicrobials, the treatment of choice would be clarithromycin, with azithromycin as an alternative, reserving the use of doxycycline and levofloxacin for cases of antimicrobial resistance and/or infections of the central nervous system., (Copyright © 2024 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Since the end of 2023, an elevated incidence and severity of Mycoplasma pneumoniae infections among children in Asia has been noted. Subsequently, this trend was observed in several European countries although limited data are currently available. We conducted a national study to delineate the ongoing M. pneumoniae outbreak in our country., Methods: A multicenter retrospective observational study was conducted across 32 hospitals in Spain, encompassing patients under 18 years old hospitalized for M. pneumoniae infection from January 2023 to March 2024. Infection was confirmed by positive polymerase chain reaction and/or by 2 serological tests., Results: A total of 623 children were included, with 79% of cases diagnosed in the final 3 months of the study period. Pneumonia was the most common diagnosis (87%). Respiratory symptoms were present in 97% of cases, with 62% requiring oxygen supplementation and 14% requiring admission to the pediatric intensive care unit (PICU). Risk factors for PICU admission included the presence of neurological symptoms, hypoxemia and a history of prematurity. Children admitted to the PICU exhibited significantly higher neutrophil counts upon admission., Conclusions: We have observed a notable increase in hospital admissions, including PICU support by up to 14%, due to M. pneumoniae infection in our country since November 2023, indicative of a more severe clinical course associated with this pathogen., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Rathke's cleft cysts (RCC) are a common type of lesion found in the sellar or suprasellar area. They are usually monitored clinically, but in some cases, surgery may be required. However, their natural progression is not yet well understood, and the outcomes of surgery are uncertain. The objective of this study is to evaluate the natural history of Rathke's cleft cysts in patients who are clinically monitored without treatment, and to determine the outcomes of surgery and the incidence of recurrences over time., Design and Patients: National multicentric study of patients diagnosed of Rathke's cleft cyst (RCC- Spain) from 2000 onwards and followed in 15 tertiary centers of Spain. A total of 177 patients diagnosed of RCC followed for 67.3 months (6-215) and 88 patients who underwent surgery, (81 patients underwent immediate surgery after diagnosis and 7 later for subsequent growth) followed for 68.8 months (3-235)., Results: The cyst size remained stable or decreased in 73.5% (133) of the patients. Only 44 patients (24.3%) experienced a cyst increase and 9 of them (5.1%) experienced an increase greater than 3 mm. In most of the patients who underwent surgery headaches and visual alterations improved, recurrence was observed in 8 (9.1%) after a median time of 96 months, and no predictors of recurrence were discovered., Conclusions: Rathke's cleft cysts without initial compressive symptoms have a low probability of growth, so conservative management is recommended. Patients who undergo transsphenoidal surgery experience rapid clinical improvement, and recurrences are infrequent. However, they can occur after a long period of time, although no predictors of recurrence have been identified., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Menéndez-Torre, Gutiérrez-Hurtado, Ollero, Irigaray, Martín, Parra, González-Molero, Araujo-Castro, Idrobo, Moure, Molina, Biagetti, Iglesias, Paja, Villar-Taibo, Pena, Vicente, Guerrero-Pérez, Cordido, Aulinas, Mateu and Soto.)

Introduction: Growth 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., Objectives: 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., Methods: 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., Results: 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 < .05) were associated with tumor invasiveness. Least Absolute Shrinkage and Selection Operator's penalized regression identified combinations of clinical and molecular features with areas under the curve between 0.67 and 0.82. Pre-operative therapy with DA or SSAs did not alter the expression of any of the markers analyzed except for DRD1/AVPR1B (up-regulated with DA) and FSHB/CRHR1 (down-regulated with SSAs)., Conclusions: 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., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology.)

Pulmonary embolism (PE), the most severe form of presentation of venous thromboembolic disease (VTE), currently represents a foremost healthcare issue due to its high impact in terms of morbidity, mortality, costs, and resource consumption. Early mortality associated with PE is primarily due to hemodynamic instability, exacerbation of pre-existing conditions, or major complications of antithrombotic therapies. Beyond the risk of death, there are relevant complications related to PE, such as bleedings, VTE recurrences, and persistence of residual respiratory symptoms; the latter complication related to PE is mainly characterized by two entities, chronic thromboembolic pulmonary hypertension and chronic thromboembolic disease. Significant scientific advances made in recent years have allowed for the improvement of both diagnostic and therapeutic management of the disease, as outlined in this document through a series of relevant issues about PE that are answered with the most up-to-date scientific evidence., (© 2024 Sociedad Española de Neumología y Cirugía Torácica (SEPAR). Published by Elsevier España, S.L.U.)