Hospital Virgen de la Concha

Deprescribing is a key strategy for optimizing therapeutic plans in multimorbid or complex chronic patients. Despite its long-standing use, further studies are needed to validate health outcomes and support its routine clinical integration. This project aims to assess the impact of applying LESS-CHRON criteria in terms of therapeutic and anticholinergic burden, as well as to describe potentially inappropriate medications (PIMs) more often involved in chronic treatments of patients with multimorbidity or those with complex health needs across two care settings: institutionalized and outpatients. A quasi-experimental, multicenter, pre-post intervention cohort study was conducted in several phases (screening, intervention, and follow-up at 3 and 6 months after inclusion). The study included two cohorts: outpatients and institutionalized patients. The main variable was the percentage reduction in medication use. Additionally, the deprescribing success rate, reasons for non-acceptance (barriers to deprescribing), anticholinergic burden, and non-pharmacological variables were analyzed. Four hundred and sixty patients (229 outpatients, 231 institutionalized) with a mean age of 84.5 (SD: 7.9) years were included. Demographic, clinical, and pharmacological data were collected. Deprescribing opportunities were identified using the LESS-CHRON criteria, and recommendations were assessed by medical teams. Follow-up evaluations were conducted after 3 months. A total of 960 PIMs were identified, of which 542 medications were successfully deprescribed (345 patients), with an acceptance rate of 56.46%, showing no significant differences between cohorts. The overall therapeutic burden was reduced by 10.73% (SD: 10.68). The main barriers to deprescribing were clinical decisions (69.86%) and patient/family refusal (11.72%). After 3 months, at least one deprescribed drug was reintroduced in 61 patients. The mean deprescribing success rate was 87.10%, which was significantly higher in institutionalized patients (p < 0.05), and the anticholinergic burden was significantly reduced (p < 0.001). The LESS-CHRON tool effectively identified deprescribing opportunities, reducing both medication burden and anticholinergic load. Institutionalized patients had a higher deprescribing success rate. However, clinical judgment and patient preferences remain key barriers to successful implementation.

<h3>Background and Importance</h3> Inadequate control of LDL cholesterol persists in a considerable proportion of patients with dyslipidaemia despite intensive treatment with statins and ezetimibe. Inclisiran, a small interfering ribonucleic acid that inhibits hepatic synthesis of PCSK9, represents an innovative therapeutic alternative with a twice-yearly dosing schedule after the initial phase. <h3>Aim and Objectives</h3> To evaluate the effectiveness and safety of inclisiran in patients with primary hypercholesterolaemia or mixed dyslipidaemia in real-world clinical practice. <h3>Material and Methods</h3> A retrospective multicentre observational study including all patients who initiated treatment with inclisiran up to September 2025. Data collected in Excel included demographic variables, cardiovascular diagnosis, reason for initiation, previous use of PCSK9 inhibitors, statin intolerance, concomitant lipid-lowering therapies and adherence. The primary variables were the median and interquartile range (IQR) of percentage reduction from baseline in LDL cholesterol, total cholesterol, non-HDL cholesterol, HDL cholesterol and triglycerides at 90 and 270 days after treatment initiation. Safety was assessed through reported adverse events and treatment discontinuations. Adherence to concomitant lipid-lowering therapies was evaluated according to dispensing records. Data were obtained from electronic medical records and hospital pharmacy databases. <h3>Results</h3> A total of 63 patients were included (mean age 64 ± 11 years; 63% male). At 90 days, the reduction in LDL cholesterol was 36% (IQR 6–62) and at 270 days 39% (IQR 26–51). Total cholesterol decreased by 23% (IQR 0–42) and 24% (IQR 17–34), respectively. Non-HDL cholesterol was reduced by 33% (IQR 1–56) at 90 days and 36% (IQR 19–50) at 270 days. HDL cholesterol remained stable with minimal changes (3% (IQR 0–11) and 0% (IQR 0–9)). Triglycerides showed median reductions of 12% (IQR 0–29) at 90 days and 7% (IQR 0–22) at 270 days. No serious adverse events were reported; however, 8% (5/63) experienced local injection site reactions and 3% (2/63) discontinued treatment due to lack of effectiveness. Adherence to concomitant lipid-lowering therapies was &gt;80% in 82% (52/63) of patients. <h3>Conclusion and Relevance</h3> Inclisiran was associated with reductions in LDL cholesterol and total cholesterol in real-world clinical practice, with an acceptable safety profile. Nevertheless, the magnitude of LDL cholesterol reduction was lower than that reported in pivotal clinical trials. <h3>Conflict of Interest</h3> No conflict of interest

D. Alonso Castronuño, S. Romero Rodríguez, M. J. Terol Castera, and N. C. Gutiérrez equally contributing author. Background: Central nervous system (CNS) infiltration by diffuse large B-cell lymphoma (DLBCL), whether primary (PCNSL) or secondary (SCNSL), is associated with poor prognosis. Bruton’s tyrosine kinase inhibitors (BTKi) have demonstrated efficacy in lymphomas with B-cell receptor and Toll-like receptor signaling alterations pathways, such as lymphomas of immune-privileged sites, including PCNSL. Aims: To assess the real-world efficacy and safety of BTKi in patients with PCNSL and SCNSL. Desing: We conducted a retrospective, observational, multicenter study within the Spanish Lymphoma Group (GELTAMO). Patients diagnosed with PCNSL or SCNSL with DLBCL histology who received BTKi for the treatment of CNS infiltration were included. Prognostic factors and survival were analyzed using Chi-square and Kaplan-Meier models. Results: A total of 65 patients were analyzed. The median age was 60 (range 27–81) years. The diagnosis of PCNSL was more frequent (43/65, 66%) than that of SCNSL (22/65, 34%). Most cases (86%) exhibited a non-germinal center B-cell phenotype (non-GC-Ph). All GC-Ph were SCNSL. Population characteristics are summarized in Table 1. The overall and complete response rates were 54% and 24%, respectively. The diagnosis of PCNSL, a non-GC-Ph, MYD88 mutations and ECOG < 2 were associated with higher response rates (p < 0.05). After a median follow-up for surviving patients of 30 (3 to 93) months, the median progression-free survival (PFS) after BTKi was 3 months and PFS at 2-years was 26%. Median PFS was significantly longer for patients diagnosed with PCNSL compared to those diagnosed with SCNSL (7 vs. 2 months, p = 0.003), and for non-GC-Ph compared to CG-Ph (3 vs. 1 months (p = 0.001). At the time of the last follow-up, 66% of patients had died, 84% due to disease progression. The median overall survival (OS) was 6 months, and OS at 2-years was 36%. Median OS was higher in patients with PCNSL compared to those with SCNSL diagnosis (8 vs. 5 months, p = 0.017), and in patients with non-GC-Ph (6 vs. 1 month, p < 0.001), with normal LDH at the onset of BTKi (8 vs. 2 months, p = 0.009) and with ECOG < 2 at the onset of BTKi (not-reached vs. 6 months, p = 0.002) compared to the opposite alternative. Consolidation therapy (Table 1) after BTKi was associated with longer OS at 5-years with respect to patients without consolidation therapy (90% vs. 16%, p < 0.001). Half of the patients experienced BTKi-related toxicity (Table 1), requiring discontinuation in 22% of cases. The rate of febrile neutropenia was 9% and 12% of patients died due to infection. No fungal infections were reported. Less than 10% of patients presented cardiovascular toxicity. Conclusions: BTKi were effective in treating DLBCL involving CNS, particularly in PCNSL. Ibrutinib yielded a significant response in many patients; however, these responses were not durable. Consolidation treatment following ibrutinib significantly improved outcomes. Safety profile was as expected for this population. Keywords: aggressive B-cell non-Hodgkin lymphoma; molecular targeted therapies; extranodal non-Hodgkin lymphoma No potential sources of conflict of interest.

Obesity poses a global health challenge, demanding a deeper understanding of adipose tissue (AT) and its mitochondria. This study describes the role of the mitochondrial protein Methylation-controlled J protein (MCJ/DnaJC15) in orchestrating brown adipose tissue (BAT) thermogenesis. Here we show how MCJ expression decreases during obesity, as evident in human and mouse adipose tissue samples. MCJKO mice, even without UCP1, a fundamental thermogenic protein, exhibit elevated BAT thermogenesis. Electron microscopy unveils changes in mitochondrial morphology resembling BAT activation. Proteomic analysis confirms these findings and suggests involvement of the eIF2α mediated stress response. The pivotal role of eIF2α is scrutinized by in vivo CRISPR deletion of eIF2α in MCJKO mice, abrogating thermogenesis. These findings uncover the importance of MCJ as a regulator of BAT thermogenesis, presenting it as a promising target for obesity therapy.

Ulcerative proctitis (UP) can have a milder, less aggressive course than left-sided colitis or extensive colitis. Therefore, immunosuppressants tend to be used less in patients with this condition. Evidence, however, is scarce because these patients are excluded from randomised controlled clinical trials. Our aim was to describe the characteristics of patients with refractory UP and their disease-related complications, and to identify the need for immunosuppressive therapies. We identified patients with UP from the prospective ENEIDA registry sponsored by the GETECCU. We evaluated socio-demographic data and complications associated with immunosuppression. We defined immunosuppression as the use of immunomodulators, biologics and/or small molecules. We used logistic regression to identify factors associated with immunosuppressive therapy. From a total of 34,716 patients with ulcerative colitis, we identified 6281 (18.1%) with UP; mean ± SD age 53 ± 15 years, average disease duration of 12 ± 9 years. Immunosuppression was prescribed in 11% of patients, 4.2% needed one biologic agent and 1% needed two; 2% of patients required hospitalisation, and 0.5% underwent panproctocolectomy or subtotal colectomy. We identified 0.2% colorectal tumours and 5% extracolonic tumours. Patients with polyarthritis (OR 3.56, 95% CI 1.86-6.69; p < 0.001) required immunosuppressants. Among patients with refractory UP, 11% required immunosuppressant therapy, and 4.2% required at least one biologic agent.