Systematic Localisation Based on History and Clinical Examination.

Localisation in neurology is an important step in determining the location of a neurological lesion based on history taking and clinical examination before confirmation with imaging. Lesions can vary from the cortical to the subcortical, brainstem, and spinal cord levels, in which every presentation and finding from the patient can provide a rough idea of where the pathology is located. A differential diagnosis can later be made according to the duration of the symptoms and the cumulative signs and symptoms presented.

Nivolumab to restore T-cell fitness in CAR-T refractory multiple myeloma.

Efficacy and durability remain central shortcomings of T-cell based therapies in multiple myeloma (MM). Here, we employ blood-based transcriptional T-cell profiling to define impaired T-cell fitness as putative biomarker associated with sensitivity to PD1 inhibition in CAR-T refractory MM patients.

Prevalence of urinary tract infections in women with vulvovaginal atrophy and the impact of vaginal prasterone on the rate of urinary tract infections.

Objective: The aims of this study were to assess the prevalence of urinary tract infections (UTI) in women newly diagnosed with vulvovaginal atrophy (VVA) versus women without VVA and to evaluate the potential of vaginal prasterone to be used in postmenopausal VVA women with UTI as prophylaxis to reduce the future UTI risk. As a first subgroup analysis, women using aromatase inhibitors, medications that stop the production of estrogen were analyzed. As a second subgroup analysis, we looked at women with diabetes to investigate whether the same prophylaxis approach should be considered.

Integration of clinical outcomes and molecular features in extramedullary disease in multiple myeloma.

Multiple myeloma (MM) remains incurable despite novel therapeutics. A major contributor to the development of relapsed/refractory and resistant MM is extraosseous extramedullary disease (EMD), whose molecular biology is still not fully understood. We analyzed 528 MM patients who presented to our institution between 2014 and 2021 and who had undergone molecular testing.

Development and Usability of an Advance Care Planning Website (My Voice) to Empower Patients With Heart Failure and Their Caregivers: Mixed Methods Study.

Background: Web-based advance care planning (ACP) interventions offer a promising solution to improve ACP engagement, but none are specifically designed to meet the needs of patients with heart failure and their caregivers.

Objective: We aimed to develop and assess the usability and acceptability of a web-based ACP decision aid called "My Voice," which is tailored for patients with heart failure and their caregivers.

Methods: This study's team and advisory board codeveloped the content for both patient and caregiver modules in "My Voice.

Elotuzumab in combination with pomalidomide, bortezomib, and dexamethasone in relapsed and refractory multiple myeloma.

Elotuzumab is an approved monoclonal antibody targeting SLAMF7 on plasma and NK cells that enhances the activity of lenalidomide, pomalidomide, and bortezomib in multiple myeloma (MM). The OPTIMISMM study showed improved outcomes with the combination of pomalidomide, bortezomib, and dexamethasone (PVd) in relapsed/refractory MM. We therefore studied adding elotuzumab to PVd (elo-PVd) in relapsed/refractory MM in a multicenter phase 2 trial.

Minimal Clinically Important Differences With the Outcomes of the App-Based Japanese Allergic Conjunctival Diseases Quality of Life Questionnaire: Cross-Sectional Observational Study.

Background: Assessing changes in quality of life in patients with hay fever-related allergic conjunctivitis requires validated and clinically meaningful metrics. A minimal clinically important difference (MCID) that can be applied to assess Domain II of the Japanese Allergic Conjunctival Disease Quality of Life Questionnaire (JACQLQ) in a smartphone app setting has yet to be determined.

Objective: This cross-sectional observational study aimed to determine MCIDs for the app-based JACQLQ in assessing hay fever-related allergic conjunctivitis.

Impact of Robotic Surgery Objective Performance Indicators: A Systematic Review.

Objective intraoperative performance metrics are a new resource for the field of surgical data science. In this study, we conducted a comprehensive review to analyze the existing literature on robotic surgical objective performance indicators (OPIs). OPIs have been used to assess surgical skill and provide automated, objective feedback in multiple settings.

Functional Status and Quality of Life in Light-Chain Amyloidosis: Advanced Imaging, Longitudinal Changes, and Outcomes.

Background: In light-chain (AL) amyloidosis, whether functional status and heart failure-related quality of life (HF-QOL) correlate with cardiomyopathy severity, improve with therapy, and are associated with major adverse cardiac events (MACE) beyond validated scores is not well-known.

Objectives: The authors aimed to: 1) correlate functional status and HF-QOL with cardiomyopathy severity; 2) analyze their longitudinal changes; and 3) assess their independent associations with MACE.

Methods: This study included 106 participants with AL amyloidosis, with 81% having AL cardiomyopathy.

Impact of the Coronavirus Disease 2019 Pandemic on Outpatient Visits for Diabetic Retinopathy in Japan: A Retrospective Cohort Study.

Purpose: Long-term ramifications of the coronavirus disease 2019 pandemic on various care-seeking characteristics of patients with diabetic retinopathy remain unclear. This study aimed to identify risk factors for dropout from regular fundus examinations (RFEs) in patients with diabetic retinopathy in Japan.

Methods: We extracted demographic and health checkup data (April 2018 to March 2021) from the JMDC database.

Targeting Ikaros and Aiolos: reviewing novel protein degraders for the treatment of multiple myeloma, with a focus on iberdomide and mezigdomide.

Introduction: The treatment of multiple myeloma (MM) is evolving rapidly. Quadruplet regimens incorporating proteasome inhibitors, immunomodulatory drugs (IMiDs), and CD38 monoclonal antibodies have emerged as standard-of-care options for newly diagnosed MM, and numerous novel therapies have been approved for relapsed/refractory MM. However, there remains a need for novel options in multiple settings, including refractoriness to frontline standards of care.

The impact of von Willebrand factor on fibrin formation and structure unveiled with type 3 von Willebrand disease plasma.

Normally, von Willebrand factor (VWF) remains inactive unless its A1A2 domains undergo a shear stress-triggered conformational change. We demonstrated the capacity of a recombinant A2 domain of VWF to bind and to affect fibrin formation, altering the fibrin clot structure. The data indicated that VWF contains an additional binding site for fibrin in the A2 domain that plays a role in the incorporation of VWF to the polymerizing fibrin.

A robust CETSA data analysis automation workflow for routine screening.

The Cellular Thermal Shift Assay (CETSA) enables the study of protein-ligand interactions in a cellular context. It provides valuable information on the binding affinity and specificity of both small and large molecule ligands in a relevant physiological context, hence forming a unique tool in drug discovery. Though high-throughput lab protocols exist for scaling up CETSA, subsequent data analysis and quality control remain laborious and limit experimental throughput.

A Case of Primary Lung Adenocarcinoma With Metastasis to Colon Harboring EGFR Exon 19 Deletion.

Lung cancer metastasizing to the colon is exceedingly rare and can present similarly to colorectal cancer. It is crucial to conduct further evaluations using immunohistochemical (IHC) stains and genomic testing to differentiate between the two and provide appropriate treatment without delay. Lung cancer generally has a poor prognosis, especially in cases with distant metastases.

A chemogenetic approach for dopamine imaging with tunable sensitivity.

Genetically-encoded dopamine (DA) sensors enable high-resolution imaging of DA release, but their ability to detect a wide range of extracellular DA levels, especially tonic versus phasic DA release, is limited by their intrinsic affinity. Here we show that a human-selective dopamine receptor positive allosteric modulator (PAM) can be used to boost sensor affinity on-demand. The PAM enhances DA detection sensitivity across experimental preparations (in vitro, ex vivo and in vivo) via one-photon or two-photon imaging.

Mechanisms of left ventricular systolic dysfunction in light chain amyloidosis: a multiparametric cardiac MRI study.

Background: Cardiac systolic dysfunction is a poor prognostic marker in light-chain (AL) cardiomyopathy, a primary interstitial disorder; however, its pathogenesis is poorly understood.

Purpose: This study aims to analyze the effects of extracellular volume (ECV) expansion, a surrogate marker of amyloid burden on myocardial blood flow (MBF), myocardial work efficiency (MWE), and left ventricular (LV) systolic dysfunction in AL amyloidosis.

Methods: Subjects with biopsy-proven AL amyloidosis were prospectively enrolled (April 2016-June 2021; Clinicaltrials.

Longitudinal effects of early exposure to intermittent hypoxia on autonomic cardiovascular control in very preterm infants.

Introduction: Cardiorespiratory control is immature in infants born preterm compared to those born at term. Animal studies have shown that repetitive hypoxia associated with periodic breathing can alter autonomic control. We aimed to elucidate if the amount of time spent with apnoea and periodic breathing in the neonatal unit was associated with longitudinal changes in autonomic control assessed using heart rate variability.

Isatuximab, carfilzomib, lenalidomide, and dexamethasone in patients with newly diagnosed, transplantation-eligible multiple myeloma (SKylaRk): a single-arm, phase 2 trial.

Background: Isatuximab is a CD38 monoclonal antibody approved for relapsed or refractory multiple myeloma. We aimed to evaluate the addition of isatuximab to weekly carfilzomib (K), lenalidomide (R), and dexamethasone (d; Isa-KRd) in transplant-eligible patients with newly diagnosed multiple myeloma and stratified maintenance by cytogenetic risk.

Methods: This single-arm phase 2 trial was done at three cancer centres (two hospitals and a cancer institute) in Boston (MA, USA).