Altered tubulin detyrosination due to SVBP malfunction induces cytokinesis failure and senescence, underlying a complex hereditary spastic paraplegia.

Senescence, marked by permanent cell cycle arrest may contribute to the decline in regenerative potential and neuronal function, thereby promoting neurodegenerative disorders. In this study, we employed whole exome sequencing to identify a previously unreported biallelic missense variant in SVBP (p.Leu49Pro) in six patients from three unrelated families.

Reliability and Validity of Ultrasound in Identifying Anatomical Landmarks for Diagnosing A2 Pulley Ruptures: A Cadaveric Study.

: Rock climbing is becoming more popular, leading to an increased focus on diagnosing and treating related injuries. Finger pulley and flexor tendon injuries are common among climbers, with the A2 pulley being the most frequently affected. High-resolution ultrasound (US) is the preferred method for detecting pulley injuries.

New calcimimetics for secondary hyperparathyroidism in CKD G5D: do they offer advantages?

Secondary hyperparathyroidism is one of the most frequent metabolic abnormalities found in patients with chronic kidney disease. The calcium-sensing receptor senses extracellular calcium and is the principal regulator of parathyroid hormone secretion. Cloning of the calcium-sensing receptor led to the development of calcimimetics, drugs that decrease parathyroid hormone secretion through the positive allosteric modulation of this receptor.

Geometric Changes in Mitral Valve Apparatus during Long-term Cardiac Resynchronization Therapy as Assessed with Cardiac CT.

Purpose To assess long-term geometric changes of the mitral valve apparatus using cardiac CT in individuals who underwent cardiac resynchronization therapy (CRT). Materials and Methods Participants from a randomized controlled trial with cardiac CT examinations before CRT implantation and at 6 months follow-up (Clinicaltrials.gov identifier NCT01323686) were invited to undergo an additional long-term follow-up cardiac CT examination.

Standardization through education of molecular pathology: a spotlight on the European Masters in Molecular Pathology.

Despite advancements in precision medicine, many cancer patients globally, particularly those in resource-constrained environments, face significant challenges in accessing high-quality molecular testing and targeted therapies. The considerable heterogeneity in molecular testing highlights the urgent need to harmonize practices across Europe and beyond, establishing a more standardized and consistent approach in MP laboratories. Professionals, especially molecular pathologists, must move beyond traditional education to cope with this heterogeneity.

Multicenter analysis of the surgical management and adjuvant therapy of patients with melanoma and a positive sentinel lymph node biopsy.

Introduction: Complete lymph node dissection (CLND) was the standard practice for patients with melanoma and a positive sentinel lymph node biopsy (SLNB) until the results of 2 clinical trials published in 2016 and 2017 demonstrated that it did not improve melanoma-specific survival (MSS). However, it continues to be performed in some scenarios. No studies have ever been published on lymph node management after a positive SLNB in the routine clinical practice in our setting.

CSF proteomics identifies early changes in autosomal dominant Alzheimer's disease.

In this high-throughput proteomic study of autosomal dominant Alzheimer's disease (ADAD), we sought to identify early biomarkers in cerebrospinal fluid (CSF) for disease monitoring and treatment strategies. We examined CSF proteins in 286 mutation carriers (MCs) and 177 non-carriers (NCs). The developed multi-layer regression model distinguished proteins with different pseudo-trajectories between these groups.

Sex-Stratified Genome-Wide Association Study in the Spanish Population Identifies a Novel Locus for Lacunar Stroke.

Background: Ischemic stroke (IS) represents a significant health burden globally, necessitating a better understanding of its genetic underpinnings to improve prevention and treatment strategies. Despite advances in IS genetics, studies focusing on the Spanish population and sex-stratified analyses are lacking.

Methods: A case-control genome-wide association study was conducted with 9081 individuals (3493 IS cases and 5588 healthy controls).

Indocyanine green in laparoscopic cholecystectomy: utility and correlation with a preoperative risk score.

Background: This study aims to compare the visualization of the cystic duct-common bile duct junction with indocyanine green (ICG) among 3 groups of patients divided according to the difficulty of elective laparoscopic cholecystectomy.

Methods: Conducted at a single center, this non-randomized, prospective, observational study encompassed 168 patients who underwent elective laparoscopic cholecystectomy and were assessed with a preoperative risk score to predict difficult cholecystectomies, including clinical factors and radiological findings. Three groups were identified: low, moderate, and high risk.

Measurable residual disease by mass spectrometry and next-generation flow to assess treatment response in myeloma.

Quantitative immunoprecipitation mass spectrometry (QIP-MS) allows the identification of the M-protein in patients with multiple myeloma (MM) otherwise in complete response, and could be considered suitable for measurable residual disease (MRD) evaluation in peripheral blood. In the context of the GEM2012MENOS65 and GEM2014MAIN trials, we compared the performance of QIP-MS in serum with next-generation flow (NGF) cytometry in bone marrow to assess MRD in paired samples obtained postinduction, transplant, consolidation and after 24 cycles of maintenance. At each time point, both NGF and QIP-MS were able to segregate 2 groups of patients with significantly different progression-free survival; when the evolution of the results obtained with either method was considered, maintaining or converting to MRD negativity was associated with longer survival, significantly better when compared with sustaining or converting to MRD positivity.

High-sensitivity C-reactive protein and risk of clinical outcomes in patients with acute heart failure.

Inflammation is relevant in the pathogenesis and progression of heart failure (HF). Previous studies have shown that elevated high-sensitivity C-reactive protein (hsCRP) are associated with greater severity and may be associated with adverse outcomes. In this study, we sought to evaluate the prognostic role of hsCRP in a non-selected cohort of patients with acute HF.

Addressing residual risk beyond statin therapy: New targets in the management of dyslipidaemias-A report from the European Society of Cardiology Cardiovascular Round Table.

Cardiovascular (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).

Connecting genomic and proteomic signatures of amyloid burden in the brain.

Background: Alzheimer's disease (AD) has a high heritable component characteristic of complex diseases, yet many of the genetic risk factors remain unknown. We combined genome-wide association studies (GWAS) on amyloid endophenotypes measured in cerebrospinal fluid (CSF) and positron emission tomography (PET) as surrogates of amyloid pathology, which may be helpful to understand the underlying biology of the disease.

Methods: We performed a meta-analysis of GWAS of CSF Aβ42 and PET measures combining six independent cohorts (n=2,076).

ctDNA Dynamics and Mechanisms of Acquired Resistance in Patients Treated with Osimertinib with or without Bevacizumab from the Randomized Phase II ETOP-BOOSTER Trial.

Purpose: The ETOP 10-16 BOOSTER study was a randomized phase II trial of osimertinib and bevacizumab therapy versus osimertinib therapy in patients with an acquired EGFR T790M mutation. The mechanisms of acquired resistance to osimertinib and bevacizumab have not been described previously.

Experimental Design: Next-generation sequencing (Guardant360) was conducted in serial plasma samples.

Immunotherapy in first line treatment of adult acute lymphoblastic leukemia.

Purpose Of Review: The use of immunotherapy in recent years has changed the paradigm of treatment in patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL), improving outcomes in the relapsed/refractory setting. New strategies are incorporating immunotherapy into front-line regimens to reduce the toxicity of chemotherapy, prolong survival and increase the possibility of treating older patients. The aim of this review was to describe the new strategies, which have incorporated these drugs into front-line regimens for BCP-ALL patients.