Biomarkers.

Background: The myelin sheath around axons is of fundamental importance for signal transduction. Myelin is reduced in white matter hyperintensities (WMH), which occur in both small vessel disease (SVD) and Alzheimer's disease (AD), giving rise to the question to what extent myelin is reduced in these diseases. Here, we employed an advanced MRI based method to assess myelin independently from a major confounding factor, i.

Alzheimer's Imaging Consortium.

Background: The myelin sheath around axons is of fundamental importance for signal transduction. Myelin is reduced in white matter hyperintensities (WMH), which occur in both small vessel disease (SVD) and Alzheimer's disease (AD), giving rise to the question to what extent myelin is reduced in these diseases. Here, we employed an advanced MRI based method to assess myelin independently from a major confounding factor, i.

Neurofilament Light Chain as a Discriminator of Disease Activity Status in MOG Antibody-Associated Disease.

Background And Objectives: In patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), acute disease activity is generally identified through medical history, neurologic examination, and imaging. However, these may be insufficient for detecting disease activity in specific conditions. This study aimed to investigate the dynamics of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) after clinical attacks and to assess their utility in discriminating attacks from remission in patients with MOGAD.

Tolerability and Preliminary Outcomes of Adjuvant T-DM1 in HER2-Positive Breast Cancer After Neoadjuvant Therapy: The ATD Study.

Background/objectives: HER2-positive breast cancer (HER2BC) is an aggressive subtype, with neoadjuvant treatment (NAT) aiming to achieve a pathological complete response (pCR) to improve long-term outcomes. Trastuzumab emtansine (T-DM1) has been established as the standard of care in the adjuvant setting for HER2BC patients who do not obtain pCR. The ATD study aimed to evaluate the real-world tolerability of T-DM1 in this setting.

The QIBA Profile for Dynamic Susceptibility Contrast MRI Quantitative Imaging Biomarkers for Assessing Gliomas.

The dynamic susceptibility contrast (DSC) MRI measures of relative cerebral blood volume (rCBV) play a central role in monitoring therapeutic response and disease progression in patients with gliomas. Previous investigations have demonstrated promise of using rCBV in classifying tumor grade, elucidating tumor viability after therapy, and differentiating pseudoprogression and pseudoresponse. However, the quantification and reproducibility of rCBV measurements across patients, devices, and software remain a critical barrier to routine or clinical trial use of longitudinal DSC MRI in patients with gliomas.

Ocrelizumab in Early-Stage Relapsing-Remitting Multiple Sclerosis: The Phase IIIb ENSEMBLE 4-Year, Single-Arm, Open-Label Trial.

Background And Objectives: Early treatment of multiple sclerosis (MS) reduces disease activity and the risk of long-term disease progression. Effectiveness of ocrelizumab is established in relapsing MS (RMS); however, data in early RMS are lacking. We evaluated the 4-year effectiveness and safety of ocrelizumab as a first-line therapy in treatment-naive patients with recently diagnosed relapsing-remitting MS (RRMS).

Assessment of Perceived Effort Through On-Field Hydration Monitoring: A Case Analysis.

This case report examines the correlation between hydration, weight variation, and perceived effort in a 43-year-old amateur athlete during a self-supported 81.5 km crossing of Death Valley, completed over 3 days with significant elevation changes. Studies have shown that a body mass loss greater than 2-3% can lead to an increased perception of effort and a decline in performance.

Comparing Lenvatinib/Pembrolizumab with Atezolizumab/Bevacizumab in Unresectable Hepatocellular Carcinoma: A Real-World Experience with Propensity Score Matching Analysis.

Background: The combination of anti-angiogenic therapy and immune checkpoint inhibitors has revolutionized the management of unresectable hepatocellular carcinoma (uHCC). While an early-phase study demonstrated promising outcomes for lenvatinib plus pembrolizumab (L+P) in treating uHCC, the LEAP-002 trial did not meet its primary endpoint. However, the comparative efficacy between L+P and atezolizumab plus bevacizumab (A+B) as first-line treatment remains a topic of uncertainty.

Advances in Targeted Therapy: Addressing Resistance to BTK Inhibition in B-Cell Lymphoid Malignancies.

B-cell lymphoid malignancies are a heterogeneous group of hematologic cancers, where Bruton's tyrosine kinase (BTK) inhibitors have received FDA approval for several subtypes. The first-in-class covalent BTK inhibitor, Ibrutinib, binds to the C481 amino acid residue to block the BTK enzyme and prevent the downstream signaling. Resistance to covalent BTK inhibitors (BTKi) can occur through mutations at the BTK binding site (C481S) but also other BTK sites and the phospholipase C gamma 2 (PLCγ2) resulting in downstream signaling.

Pain Management in Knee Osteoarthritis: Insights from an Exploratory Online Survey of Italian Patients and Physicians.

Background: In Italy, knee osteoarthritis (KOA) accounts for over 5 million prevalent cases and requires long-term multidisciplinary management. The most frequent KOA symptom is pain. The aim of the survey is to provide a national overview of the current management of moderate-to-severe pain associated with KOA from both clinicians' and patients' perspectives.

The epithelial barrier theory and its associated diseases.

The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide.

Prognostic factors for worsening and improvement in multiple sclerosis using a multistate model.

Background: The long-term disease trajectory of people living with multiple sclerosis (MS) can be improved by initiating efficacious treatment early. More quantitative evidence is needed on factors that affect a patient's risk of disability worsening or possibility of improvement to inform timely treatment decisions.

Methods: We developed a multistate model to quantify the influence of demographic, clinical, and imaging factors on disability worsening and disability improvement simultaneously across the disability spectrum as measured by the Expanded Disability Status Scale (EDSS).

Real-Time Fluorescence Monitoring System for Optimal Light Dosage in Cancer Photoimmunotherapy.

: Near-infrared photoimmunotherapy (NIR-PIT) was recently approved for the treatment of unresectable locally advanced or recurrent head and neck cancers in Japan; however, only one clinical dose has been validated in clinical trials, potentially resulting in excessive or insufficient dosing. Moreover, IRDye700X (IR700) fluorescence intensity plateaus during treatment, indicating a particular threshold for the antitumor effects. Therefore, we investigated the NIR laser dose across varying tumor sizes and irradiation methods until the antitumor effects of the fluorescence decay rate plateaued.

An Ultrasonographic Analysis of the Deep Inferior Tendon in the Masseter Muscle: Implications for Botulinum Toxin Injections.

(1) Background: With the increasing aesthetic pursuit of facial features, the clinical use of Botulinum Toxin Type A (BoNT-A) injections for masseter hypertrophy has been on the rise. However, due to variations in masseter muscle structure and differences in clinicians' injection techniques, blind injections may lack precision, potentially compromising treatment accuracy and increasing the risk of complications. (2) Objectives: The study aims to use ultrasonography to detail the deep inferior tendon (DIT) within the masseter muscle in a young Chinese cohort, refine its classification, analyze muscle belly thickness and variations across groups, and propose a customized ultrasound-guided BoNT-A injection protocol.

The Role of Small-Bowel Capsule Endoscopy in the Diagnostic Algorithm of Complicated Perianal Disease.

Introduction: Complicated perianal disease (cPD) may be the sole presentation of Crohn's disease (CD). The role of small-bowel capsule endoscopy (SBCE) in the diagnostic algorithm of cPD is unclear. We aimed to evaluate the role of SBCE as a diagnostic tool, in patients with cPD, after a negative standard workup for CD.

Long-Term Socioeconomic and Neurologic Outcome for Individuals with Childhood-Onset Multiple Sclerosis.

Intorduction: Most studies on the progression of childhood-onset multiple sclerosis (MS) involve relatively short follow-up periods, focusing primarily on neurological outcomes and disability progression. The influence of these and other factors on the health-related quality of life is not known. To gain a comprehensive understanding of early-onset MS, it is crucial to evaluate the effects of treatment and the disease on quality of life.

Prevalence of Enteric Pathogens and Antibiotic Resistance: Results of a Six-Year Active Surveillance Study on Patients Admitted to a Teaching Hospital.

Background: Acute Infectious Diarrhea (AID) and the short- and long-term complications associated with it are major causes of hospitalization worldwide. In Italy, due to a lack of robust surveillance programs, only limited data has been collected on their prevalence and circulation. This study aims to evaluate the resistance pattern of enteric pathogens and their epidemiological trends over a six-year period.

Using AuNPs-DNA Walker with Fluorophores Detects the Hepatitis Virus Rapidly.

Viral hepatitis is a systemic infectious diseases caused by various hepatitis viruses, primarily leading to liver damage. It is widely prevalent worldwide, with hepatitis viruses categorized into five types: hepatitis A, B, C, D, and E, based on their etiology. Currently, the detection of hepatitis viruses relies on methods such as enzyme-linked immunosorbent assay (ELISA), immunoelectron microscopy to observe and identify viral particles, and in situ hybridization to detect viral DNA in tissues.

Novel Flow Cytometry Method Detecting Complement C1q Bound to Blood Type A/B IgG Antibody for Preventing Severe Antibody-Mediated Rejection in ABO-Incompatible Kidney Transplantation.

We aimed to develop a novel method for measuring the complement-binding ability of anti-blood type antibodies (ab-Abs), the flow cytometry method for the complement C1q test (FCM-C1q) for detecting antibody-mediated rejection (AMR) caused by ab-Abs in ABO-incompatible kidney transplantation (ABOI-KTx). FCM-C1q distribution was surveyed in 44 healthy participants and 43 dialysis patients (Cohort A). The relationship between AMR and FCM-C1q levels was examined along with ab-Ab titers by the flow cytometry method for the IgG test (FCM-IgG) in 62 ABOI-KTx patients (Cohort B).

Adjuvant Therapy with Immune Checkpoint Inhibitors after Carbon Ion Radiotherapy for Mucosal Melanoma of the Head and Neck: A Case-Control Study.

The development of new treatment strategies to improve the prognosis of mucosal malignant melanoma of the head and neck (MMHN) after carbon ion radiotherapy (CIRT) is essential because of the risk of distant metastases. Therefore, our objective was to evaluate the outcomes of immune checkpoint inhibitor (ICI) treatment to justify its inclusion in the regimen after CIRT. Thirty-four patients who received CIRT as an initial treatment were included in the analysis and stratified into three groups: those who did not receive ICIs (Group A), those who received ICIs after recurrence or metastasis (Group B), and those who received ICIs as adjuvant therapy after CIRT (Group C).

Real-world usage and effectiveness of recombinant factor VIII/factor IX Fc in hemophilia A/B: final data from the 24-month, prospective, noninterventional PREVENT study in Germany.

Background: Real-world experience with efmoroctocog alfa (a recombinant factor [F]VIII Fc fusion protein [rFVIIIFc]) and eftrenonacog alfa (a recombinant factor IX Fc fusion protein [rFIXFc]) is needed to bridge evidence gaps.

Objectives: To describe rFVIIIFc/rFIXFc usage and effectiveness over a 24-month prospective period.

Methods: PREVENT (NCT03055611), a noninterventional study across 25 German hemophilia treatment centers, enrolled previously treated persons with hemophilia A and B (all ages/severities) on individualized rFVIIIFc/rFIXFc prophylaxis before/at enrollment.