Clinical Activity of Mitogen-Activated Protein Kinase Inhibitors in Patients With MAP2K1 (MEK1)-Mutated Metastatic Cancers.

Purpose: MAP2K1/MEK1 mutations are potentially actionable drivers in cancer. MAP2K1 mutations have been functionally classified into three groups according to their dependency on upstream RAS/RAF signaling. However, the clinical efficacy of mitogen-activated protein kinase (MAPK) pathway inhibitors (MAPKi) for MAP2K1-mutant tumors is not well defined.

The Real-World Clinical Outcomes of Heavily Pretreated HER2+ and HER2-Low Metastatic Breast Cancer Patients Treated with Trastuzumab Deruxtecan at a Single Centre.

Background: Trastuzumab deruxtecan (TDXd) is an antibody-drug conjugate that has demonstrated impressive activity in randomized controlled clinical trials in the context of patients with HER2-amplified and HER2-low metastatic breast cancer. We aimed to review the activity and adverse event profile of TDXd in heavily pretreated breast cancer patients in real practice.

Methods: We describe a single-center retrospective case series of metastatic breast cancer patients who were treated with TDXd.

Cerebral spinal fluid analyses and therapeutic implications for leptomeningeal metastatic disease.

Purpose: To review applications of cerebral spinal fluid (CSF) biomarkers for the diagnosis, monitoring and treatment of leptomeningeal metastatic disease (LMD) among patients with metastatic solid tumors.

Methods: A narrative review identified original research related to CSF biomarkers among patients with metastatic solid tumors and LMD. Pre-clinical research (e.

A comparison between lipid-based vs. glycemic-based insulin sensitivity indices for the association with abnormal ECG findings and 20-year mortality among older adults.

Background: A direct comparison between glycemic-based and lipid-based insulin sensitivity indices (ISIs) for ECG findings and all-cause and cardiovascular mortality is lacking.

Methods: 963 community-dwelling older adults, examined as part of the third phase of the Glucose intolerance, Obesity, and Hypertension study between 1999 and 2008, were followed until December 2016 and December 2019 for cardiovascular and all-cause mortality, respectively. Eleven different ISIs were calculated and evaluated against ECG findings, all-cause, and cardiovascular mortality with multivariable regression models.

The Association Between Delirium Upon Admission to a Rehabilitation Hospital and Motor Rehabilitation Outcomes Among Hip Fracture Surgery Patients: A Historical Cohort Study.

: Delirium is a common neuropsychiatric syndrome characterized by the acute and fluctuating impairment of cognition, attention, and consciousness, which is prevalent in older adults following surgical procedures. Despite the recognized impact of delirium on recovery, its specific effects on motor rehabilitation outcomes in the geriatric population remain underexplored. This historical cohort study aimed to evaluate the association between the presence of delirium upon admission to a rehabilitation hospital and the motor functional gain at discharge among older patients following hip fracture surgery.

Machine learning prediction of brain metastasis invasion pattern on brain magnetic resonance imaging scans.

Background: Brain metastasis invasion pattern (BMIP) is an emerging biomarker associated with recurrence-free and overall survival in patients, and differential response to therapy in preclinical models. Currently, BMIP can only be determined from the histopathological examination of surgical specimens, precluding its use as a biomarker prior to therapy initiation. The aim of this study was to investigate the potential of machine learning (ML) approaches to develop a noninvasive magnetic resonance imaging (MRI)-based biomarker for BMIP determination.

The Contribution of Sustained Attention and Response Inhibition to Reading Comprehension Among Japanese Adolescents.

Previous studies demonstrated the influential role of sustained attention in the reading comprehension of alphabetic writing systems. However, there is limited understanding of how these cognitive functions contribute to reading comprehension in non-alphabetic systems, such as Japanese. This study seeks to explore this gap, focusing on how sustained attention and response inhibition function in a writing system where some of the characters represent meanings rather than sounds, introducing another layer of difficulty in the complex process of reading; Methods: Seventy-five Japanese 9th grade students performed a task to assess sustained attention and response inhibition.

Self-reported physical activity properties and 20-year all-cause and cardiovascular mortality among community-dwelling older adults.

Purpose: Physical activity was previously associated with decreased mortality. Current guidelines recommend >150 min/week or >75 min/week of moderate or high-intensity exercise to maintain a healthy lifestyle; however, exercise properties most strongly associated with low mortality among the elderly may still be explored.

Methods: A total of 1210 community-dwelling older adults, from the third phase (1999-2004) of the Israel Study on Glucose Intolerance, Obesity, and Hypertension, were followed until 2016 and 2019 for cardiovascular and all-cause mortality, respectively.

Methodology and challenges for harmonization of nutritional data from seven historical studies.

Background: Collection of detailed dietary data is labor intensive and expensive, harmonization of existing data sets has been proposed as an effective tool for research questions in which individual studies are underpowered.

Methods: In this paper, we describe the methodology used to retrospectively harmonize nutritional data from multiple sources, based on the individual participant data of all available studies, which collected nutritional data in Israel between 1963 and 2014. This collaboration was established in order to study the association of red and processed meat with colorectal cancer.

A historical cohort study with 27,754 individuals on the association between meat consumption and gastrointestinal tract and colorectal cancer incidence.

In order to explore the association between meat consumption and gastrointestinal/colorectal cancer (CRC) risk and to estimate the Israeli population attributable fraction (PAF), we conducted a collaborative historical cohort study using the individual participant data of seven nutritional studies from the past 6 decades. We included healthy adult men and women who underwent a nutritional interview. Dietary assessment data, using food-frequency or 24-h recall questionnaires, were harmonized.

The association between frailty biomarkers and 20-year all-cause and cardiovascular mortality among community-dwelling older adults.

Objectives: While several biomarkers were previously associated with frailty and mortality, data are still contradicting. We aimed to evaluate the association between novel biomarkers and frailty among community-dwelling older adults to enhance understanding of the pathophysiology of frailty.

Methods: Nine hundred and sixty-three older adults were screened during the third phase (1999-2008) of the Israel study on Glucose Intolerance, Obesity, and Hypertension (GOH).

The Reliability and Validity of the OneStep Smartphone Application for Gait Analysis among Patients Undergoing Rehabilitation for Unilateral Lower Limb Disability.

An easy-to-use and reliable tool is essential for gait assessment of people with gait pathologies. This study aimed to assess the reliability and validity of the OneStep smartphone application compared to the C-Mill-VR+ treadmill (Motek, Nederlands), among patients undergoing rehabilitation for unilateral lower extremity disability. Spatiotemporal gait parameters were extracted from the treadmill and from two smartphones, one on each leg.

Osimertinib is associated with improved outcomes in pre-treated non-small cell lung cancer leptomeningeal metastases: A systematic review and meta-analysiss.

Purpose: Leptomeningeal metastasis (LM) is a severe complication of non-small cell lung cancer (NSCLC). In patients with NSCLC LM harboring epidermal growth factor receptor () mutations, osimertinib is favored over alternative EGFR tyrosine kinase inhibitors (TKIs). However, the efficacy of osimertinib relative to other EGFR-TKIs is not well established for patients with LM.

A historical cohort study on predictors for successful weaning from prolonged mechanical ventilation and up to 3-year survival follow-up in a rehabilitation center.

Background: We followed prolonged mechanically ventilated (PMV) patients for weaning attempts and explored factors associated with successful weaning and long-term survival.

Methods: This historical cohort study included all adult PMV patients admitted to a single rehabilitation hospital during 2015-2018 and followed for survival according to weaning success up to 3 years or the end of 2021.

Results: The study included 223 PMV patients.

Neoadjuvant Chemoimmunotherapy for NSCLC: A Systematic Review and Meta-Analysis.

Importance: To date, no meta-analyses have comprehensively assessed the association of neoadjuvant chemoimmunotherapy with clinical outcomes in non-small cell lung cancer (NSCLC) in randomized and nonrandomized settings. In addition, there exists controversy concerning the efficacy of neoadjuvant chemoimmunotherapy for patients with NSCLC with programmed cell death 1 ligand 1 (PD-L1) levels less than 1%.

Objective: To compare neoadjuvant chemoimmunotherapy with chemotherapy by adverse events and surgical, pathological, and efficacy outcomes using recently published randomized clinical trials and nonrandomized trials.

Emulated Trial for Discharge Prescription of Guideline-Directed Medical Therapy and 15-Year Survival After Coronary Artery Bypass Graft Surgery.

Objectives: To explore admission and discharge prescription rates of guideline-directed medical therapy (GDMT), defined as aggregate antiplatelet agents, statins, and β-blockers, after coronary artery bypass graft (CABG) surgery and to reveal its association with long-term survival.

Patients And Methods: This is a prospective cohort study-based emulated trial of patients undergoing elective or semi-elective isolated CABG surgery in 7 cardiothoracic units in Israel from January 1, 2004, to December 31, 2007, and followed up until December 31, 2020, for all-cause mortality.

Results: Only 59.

The Clinical, Genomic, and Transcriptomic Landscape of BRAF Mutant Cancers.

Background: BRAF mutations are classified into four molecularly distinct groups, and Class 1 (V600) mutant tumors are treated with targeted therapies. Effective treatment has not been established for Class 2/3 or BRAF Fusions. We investigated whether BRAF mutation class differed according to clinical, genomic, and transcriptomic variables in cancer patients.

Invasive growth of brain metastases is linked to CHI3L1 release from pSTAT3-positive astrocytes.

Background: Compared to minimally invasive brain metastases (MI BrM), highly invasive (HI) lesions form abundant contacts with cells in the peritumoral brain parenchyma and are associated with poor prognosis. Reactive astrocytes (RAs) labeled by phosphorylated STAT3 (pSTAT3) have recently emerged as a promising therapeutic target for BrM. Here, we explore whether the BrM invasion pattern is influenced by pSTAT3+ RAs and may serve as a predictive biomarker for STAT3 inhibition.

The role of CRAF in cancer progression: from molecular mechanisms to precision therapies.

The RAF family of kinases includes key activators of the pro-tumourigenic mitogen-activated protein kinase pathway. Hyperactivation of RAF proteins, particularly BRAF and CRAF, drives tumour progression and drug resistance in many types of cancer. Although BRAF is the most studied RAF protein, partially owing to its high mutation incidence in melanoma, the role of CRAF in tumourigenesis and drug resistance is becoming increasingly clinically relevant.

Glucagon-Like Peptide-1 Receptor Agonists and Pancreatic Cancer Risk in Patients With Type 2 Diabetes.

Importance: Concerns have been raised that glucagon-like peptide-1 receptor agonists (GLP-1RA) may increase the risk of pancreatic cancer.

Objective: To investigate the association of GLP-1RA treatment with pancreatic cancer incidence over 9 years of follow-up.

Design, Setting, And Participants: In this population-based historical cohort study, adult patients (aged 21 to 89 years) with type 2 diabetes insured by Clalit Healthcare Services, the largest state-mandated health organization in Israel, were followed up from 2009, when GLP-1RA became available in Israel, until pancreatic cancer diagnosis, death, reaching age 90 years, or end of follow-up (December 2017).

Evaluating the use of a customized digital navigation program to optimize bowel preparation in pediatric colonsocopy.

Introduction: Adequate bowel preparation is essential for optimal colonoscopy diagnosis and/or intervention. However, suboptimal bowel preparation occurs in as many as 1 in 3 pediatric colonoscopies, leading to missed diagnoses, procedural complications, wasted resources, and increased costs. We aimed to evaluate the effect of an automated Pediatric Colonoscopy Digital Navigation Program (PC-DNP) on the quality of colonoscopy preparation among pediatric patients.