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Beyond lines of treatment: embracing early high-efficacy disease-modifying treatments for multiple sclerosis management.
No full textRecent advances in multiple sclerosis (MS) management have shifted perspectives on treatment strategies, advocating for the early initiation of high-efficacy disease-modifying therapies (heDMTs). This perspective review discusses the rationale, benefits, and challenges associated with early heDMT initiation, reflecting on the obsolescence of the traditional "first-line" and "second-line" treatment classifications. The article emerges from the last update of the consensus document of the Spanish Society of Neurology on the treatment of MS. During its development, there was a recognized need to further discuss the concept of treatment lines and the early use of heDMTs. Evidence from randomized controlled trials and real-world studies suggests that early heDMT initiation leads to improved clinical outcomes, including reduced relapse rates, slowed disease progression, and decreased radiological activity, especially in younger patients or those in early disease stages. Despite the historical belief that heDMTs involve more risks and adverse events compared to moderate-efficacy DMTs (meDMTs), some studies have reported comparable safety profiles between early heDMTs and meDMTs, though long-term safety data are still lacking. The review also addresses the need for a personalized approach based on patient characteristics, prognostic factors, and preferences, explores the importance of therapeutic inertia, and highlights the evolving landscape of international and national guidelines that increasingly advocate for early intensive treatment approaches. The article also addresses the challenges of ensuring access to these therapies and the importance of further research to establish long-term safety and effectiveness of DMTs in MS
Laryngeal dystonia and vocal tremor response to botulinum toxin injection.
No full text20.500.12530/87913The main objective of this study was to compare laryngeal dystonia (LD) and vocal tremor's (VT) response to botulinum toxin injection. Retrospective study including every patient with LD or VT injected with botulinum toxin guided by electromyography, from January 1, 2010, to September 30, 2022, at a tertiary hospital centre. Improvement was assessed with the VHI-10, grade of dysphonia in a visual analogue scale (VAS; 0-10), GRBAS(I) scale (0-3) and maximum phonation time (MPT). A total of 77 patients were included, 44 patients with LD and 33 with VT. There were no differences between groups on pre-treatment VHI-10, grade of dysphonia in the VAS, MPT and G, R, B, A and I at diagnosis (p > 0.05). S was significantly higher in patients with LD (p 0.05). S was significantly higher in patients with LD (p BTX injection was successful in improving the VHI-10, grade of dysphonia on the VAS and G, S and I in the GRBAS-I scale for both DT and VT. LD seems to have a better response to BTX in comparison to VT
Bone metastasis in differentiated thyroid cancer: Spanish multicenter study of clinical characteristics, survival and prognostic factors.
No full text20.500.12530/87907This study describes the characteristics, survival and prognostic factors in a cohort of patients with bone metastases (BM) from differentiated thyroid carcinoma (DTC). This was a multicenter retrospective observational study conducted in Spain, including patients diagnosed with DTC and BM between 1980 and 2022. A Cox regression analysis was performed to examine prognostic factors for survival. Kaplan-Meier and log-rank tests were performed for survival analysis and comparison between groups. A total of 133 patients were included with a median follow-up of 40 (17-70) months. Seventy patients (52.6%) had BM at the initial diagnosis. Fifty-two (39.1%) had follicular carcinoma. Sixty-six (49.6%) presented multiple BM. The most frequent location was the spine (63.2%). Other metastases were present at diagnosis in 88 (66.2%), mainly lung (60.9%). BM were treated with I131 in 91 (68.4%) patients, with BM uptake in 63 (47.4%). Fifty-six (42.1%) received treatment with multikinase inhibitors. Fifty-three (3.9%) had skeletal-related events. Seventy-two (54.1%) died. The 3-, 5- and 10-year survival was 53.5, 39.5% and 28.5%, respectively. Significant prognostic factors in the multivariate analysis were the presence of lymph node metastases (N1) HR 1.71 (95% CI 1.005-2.098; p=0.048), BM treatment with I131 HR 0.532 (95% CI 0.304-0.931; p=0.027) and age ≥67 years at BM diagnosis HR 1.991 (95% CI 1.142-3.47; p=0.015). Survival of DTC patients with BM treated in a Spanish cohort was 39.5% at 5 years and 28.5% at 10 years. Patients with BM treated with I131 appear to have a better outcome in terms of mortality and the presence of lymph node involvement and age over 67 years were associated with higher mortality
Sodium glucose co-transporter 2 inhibitors in the treatment of glomerular diseases: a CKJ controversy.
No full textIntegrating sodium-glucose co-transporter 2 inhibitors (SGLT2i) into the treatment for chronic kidney disease (CKD) has marked a significant therapeutic advance in nephrology. Clinical trials such as DAPA-CKD and EMPA-KIDNEY have demonstrated the beneficial effects of SGLT2i in slowing CKD progression and reducing proteinuria. However, the applicability of these results to patients with glomerulonephritis is still unresolved due to various limitations. This manuscript combines the evidence supporting the use of SGLT2i in glomerular diseases, highlights the limitations and strikes a conclusive balance on their role in clinical practice
<i>MAML3</i>-fusions modulate vascular and immune tumour microenvironment and confer high metastatic risk in pheochromocytoma and paraganglioma
No full text20.500.12530/87849Pheochromocytomas and paragangliomas are rare neuroendocrine tumours. Around 20-25 % of patients develop metastases, for which there is an urgent need of prognostic markers and therapeutic stratification strategies. The presence of a MAML3-fusion is associated with increased metastatic risk, but neither the processes underlying disease progression, nor targetable vulnerabilities have been addressed. We have compiled a cohort of 850 patients, which has shown a 3.65 % fusion prevalence and represents the largest MAML3- positive series reported to date. While MAML3-fusions mainly cause single pheochromocytomas, we also observed somatic post-zygotic events, resulting in multiple tumours in the same patient. MAML3- tumours show increased expression of neuroendocrine-to-mesenchymal transition markers, MYC-targets, and angiogenesis-related genes, leading to a distinct tumour microenvironment with unique vascular and immune profiles. Importantly, our findings have identified MAML3-tumours specific vulnerabilities beyond Wntpathway dysregulation, such as a rich vascular network, and overexpression of PD-L1 and CD40, suggesting potential therapeutic targets. (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
In vivo reduction of biofilm seeded on orthopaedic implants.
No full text20.500.12530/87913Electromagnetic induction heating has demonstrated in vitro antibacterial efficacy over biofilms on metallic biomaterials, although no in vivo studies have been published. Assessment of side effects, including thermal necrosis of adjacent tissue, would determine transferability into clinical practice. Our goal was to assess bone necrosis and antibacterial efficacy of induction heating on biofilm-infected implants in an in vivo setting. Titanium-aluminium-vanadium (Ti6Al4V) screws were implanted in medial condyle of New Zealand giant rabbit knee. Study intervention consisted of induction heating of the screw head up to 70°C for 3.5 minutes after implantation using a portable device. Both knees were implanted, and induction heating was applied unilaterally keeping contralateral knee as paired control. Sterile screws were implanted in six rabbits, while the other six received screws coated with Staphylococcus aureus biofilm. Sacrifice and sample collection were performed 24, 48, or 96 hours postoperatively. Retrieved screws were sonicated, and adhered bacteria were estimated via drop-plate. Width of bone necrosis in retrieved femora was assessed through microscopic examination. Analysis was performed using non-parametric tests with significance fixed at p ≤ 0.05. The width of necrosis margin in induction heating-treated knees ranged from 0 to 650 μm in the sterile-screw group, and 0 to 517 μm in the biofilm-infected group. No significant differences were found between paired knees. In rabbits implanted with sterile screws, no bacteria were detected. In rabbits implanted with infected screws, a significant bacterial load reduction with median 0.75 Log10 colony-forming units/ml was observed (p = 0.016). Induction heating was not associated with any demonstrable thermal bone necrosis in our rabbit knee model, and might reduce bacterial load in S. aureus biofilms on Ti6Al4V implants
Treatment-Refractory Mycobacterium avium Complex Pulmonary Disease: A Case Report.
No full text20.500.12530/8789
Long-term sequelae and quality of life after childhood-onset craniopharyngioma: Results of a Spanish multicenter study.
No full text20.500.12530/87910We aim to describe the characteristics of patients with childhood-onset craniopharyngioma and to analyze factors that impair quality of life (QoL) in this population. Multicenter national study including patients treated between 2008 and 2022, from 2 to 25 years of age diagnosed with craniopharyngioma. QoL was assessed once during patient's follow-up by age-adapted versions of Pediatric Quality of Life Inventory (PedsQL) questionnaire. Sixty-six patients were included. Median age at diagnosis was 5 years (interquartile range [IQR]: 3-8), while median follow-up was 7.4 years (IQR: 2.8-9.7). Most craniopharyngioma were suprasellar (93.9%), and 59.7% had hypothalamic involvement (HI). All patients underwent surgery, 44.4% received radiotherapy, and 23.6% intracystic therapy. Most frequent long-term complications were visual deficit (72.7%) and endocrine impairment (94.5%). Patients exhibited hypothyroidism requiring hormone replacement (92.4%), hypocortisolism (80.3%), diabetes insipidus (86.4%), and/or growth hormone therapy (50%). When parents evaluated QoL, PedsQL median score was 53.8 points out of 100 (IQR: 41-71.6). Higher scores were noted when patients assessed their own QoL (median score 64.8 [IQR: 57.3-81.8]), observing statistically significant differences (p = .019). QoL was impaired by repeated surgeries (r = -.44; p = .014), HI (median score 51.5 [IQR: 39-63.8] vs. 76.4 [59-84.8]; p = .001), radiotherapy (median score 51.9 [IQR: 38.1-61.3] vs. 63.8 [IQR: 49-82.5]; p = .02) and longer follow-up (r = -.3; p = .01). In our study, most patients had significant comorbidities and low overall QoL scores, which was mainly affected by repeated surgery, radiation, and hypothalamic involvement. This reflects the need for further research and intensified studies of systemic therapy/alternate strategies to broaden the standard-of-care options, so that treatment-related sequalae can be avoided
Diagnosed and undiagnosed cough-related stress urinary incontinence in women with refractory or unexplained chronic cough: Its impact on general health status and quality of life.
No full text20.500.12530/87913Background: Stress urinary incontinence (SUI) is common in women with chronic cough but may be overlooked. Objective: To determine the frequency of underdiagnosis of cough-related SUI and its impact on women's general health status and quality of life (QoL). Methods: Data were analyzed for 147 women with refractory/unexplained chronic cough. Relevant details were collected from clinical charts and a patient-completed survey. General health status was assessed using the EuroQoL visual analogue scale (EQ-VAS) and QoL with the cough-specific Leicester Cough Questionnaire (LCQ). Results: Women were classified into diagnosed (n = 32; 21.8%) or undiagnosed (n = 33; 22.4%) cough-related SUI, and no SUI (n = 82; 55.6%) groups. Women with versus without cough-related SUI perceived poorer health status and greater impact of cough on everyday lives. Mean LCQ scores were significantly lower in cough-related SUI groups versus no SUI group. In multivariate analysis, the presence of cough-related SUI was significantly associated with lower EQ-VAS and LCQ scores. Conclusion: In our cohort, 44% of women had cough-related SUI, and half were undiagnosed. Irrespective of diagnosis, impairment to everyday lives and QoL was similar. Diagnosing cough-related SUI may identify additional patients who can benefit from therapies to suppress cough and improve QoL
Addressing residual risk beyond statin therapy: New targets in the management of dyslipidaemias-A report from the European Society of Cardiology Cardiovascular Round Table.
No full text20.500.12530/87854Cardiovascular (CV) disease is the most common cause of death in Europe. Despite proven benefits, use of lipid-lowering therapy remains suboptimal. Treatment goals are often not achieved, even in patients at high risk with atherosclerotic CV disease (ASCVD). The occurrence of CV events in patients on lipid-lowering drugs is defined as "residual risk", and can result from inadequate control of plasma lipids or blood pressure, inflammation, diabetes, and environmental hazards. Assessment of CV risk factors and vascular imaging can aid in the evaluation and management decisions for individual patients. Lifestyle measures remain the primary intervention for lowering CV risk. Where drug therapies are required to reach lipid treatment targets, their effectiveness increases when they are combined with lifestyle measures delivered through formal programs. However, lipid drug dosage and poor adherence to treatment remain major obstacles to event-free survival. This article discusses guideline-supported treatment algorithms beyond statin therapy that can help reduce residual risk in specific patient profiles while also likely resulting in substantial healthcare savings through better patient management and treatment adherence