Prognostic factors for very early recurrence after neoadjuvant treatment and curative resection in pancreatic ductal adenocarcinoma.

Introduction: Very early recurrence in pancreatic ductal adenocarcinoma has been defined as recurrence ≤3 months after resection. Besides others, neoadjuvant treatment is delivered based on the assumption of preoperative eradication of micrometastasis as well as local downstaging. Prognostic factors of very early recurrence after neoadjuvant treatment remain largely unexplored.

Molecularly matched targeted therapies plus radiotherapy in glioblastoma: the phase 1/2a NM umbrella trial.

Advances in molecular understanding and diagnostic precision of glioblastoma enable the identification of key genetic alterations in a timely manner and, in principle, allow treatments with targeted compounds based on molecular markers. Here we report the results of the phase 1/2 umbrella trial NCT Neuro Master Match (NM), which evaluated targeted treatments in 228 patients with newly diagnosed glioblastoma without O6-methylguanine DNA-methyltransferase promoter hypermethylation. Stratification for treatment was conducted by a trial-specific molecular tumor board across five subtrials, each evaluating a targeted therapy-alectinib, idasanutlin, palbociclib, vismodegib or temsirolimus-selected according to the best-matching molecular alteration.

Kinematic characterization of residual deformities in idiopathic clubfoot initially treated with the Ponseti method: Gait analysis using the Heidelberg Foot Model.

Purpose: This study aimed to investigate foot kinematics during gait in individuals with idiopathic clubfoot initially treated with the Ponseti method, focusing on clubfoot-specific deformities, to improve the understanding of posttreatment functional impairments.

Methods: In this prospective cohort study, 23 patients with treated idiopathic clubfoot (34 feet) were compared with 15 age-matched healthy controls (30 feet). Gait analysis was performed using the Heidelberg Foot Model.

Predictors of health-related quality of life in older adults over a course of twelve years - Results from a large population-based study using a machine learning approach.

Background: The proportion of older people is growing dramatically, implying that predictors of health-related quality of life (HRQoL) in older adults are of major interest within public health research.

Methods: Analyses were based on the ESTHER study, a German population-based cohort study conducted in the federal state of Saarland, Germany. The study was initiated in 2000-2002 and included 9940 community-dwelling older adults recruited via general practioners.

Pre-surgery gut microbial diversity and abundance are associated with post-surgery onset of cachexia in colorectal cancer patients: the ColoCare Study.

Background: Cachexia accounts for about 20% of all cancer-related deaths and it is indicative of poor prognosis and progressive functional impairment. The role of the gut microbiome in the development of cachexia in colorectal cancer (CRC) patients has not been established.

Methods: Pre-surgical stool samples from n = 103 stage I-III CRC patients in the ColoCare Study were analyzed using 16S rRNA gene sequencing (Illumina) to characterize fecal bacteria.

LET measurements in proton and helium-ion beams of therapeutic energies using a silicon pixel detector towards a tool for quality assurance.

Background: As advanced treatment plans increasingly include optimizing both dose and linear energy transfer (LET), there is a growing demand for tools to measure LET in clinical settings. Although various detection systems have been investigated in this pursuit, the scarcity of detectors capable of providing per-ion data for a fast and streamlined verification of LET distributions remains an issue. Silicon pixel detector technology bridges this gap by enabling rapid tracking of single-ion energy deposition.

Selective targeting of TBXT with DARPins identifies regulatory networks and therapeutic vulnerabilities in chordoma.

The embryonic transcription factor TBXT (brachyury) drives chordoma, a spinal neoplasm without effective drug therapies. TBXT's regulatory network is poorly understood, and strategies to disrupt its activity for therapeutic purposes are lacking. We developed designed ankyrin repeat proteins that block TBXT-DNA binding (T-DARPins).

Time-varying impact of established prognostic factors in resected pancreatic ductal adenocarcinoma.

Background: Prognostic factors in resected pancreatic ductal adenocarcinoma (PDAC) have been determined under the assumption that hazard ratios (HRs) remain static. However, PDAC is a dynamic disease with evolving conditional survival. The aim of this study was to determine if the impact of prognostic factors in PDAC is time-varying.

Sex-specific outcomes after transcatheter or surgical treatment of aortic valve stenosis: the DEDICATE-DZHK6 trial.

Background And Aims: Aortic stenosis may be managed differently in women and men, but evidence remains limited. Sex-specific characteristics and outcomes of low- to intermediate-risk patients assigned to transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR) from the DEDICATE-DZHK6 trial are described.

Methods: The DEDICATE-DZHK6 trial demonstrated non-inferiority for the primary outcome of all-cause death or stroke at 1 year.

Dental Implants in Medically Compromised Patients Undergoing or After Receiving Anti-Resorptive or Radiotherapy: Retrospective Clinical and Radiographic Data.

Objective And Aim: A retrospective study to evaluate the clinical and radiological outcomes of dental implants placed in compromised patients who have undergone antiresorptive therapy (AR) or head and neck radiotherapy (IR).

Material And Methods: Dental implant placement was evaluated in compromised patients undergoing or after receiving AR/IR therapy following specific preventive measures: antibiotic prophylaxis (2 days before and 5 days after surgery) and primary wound closure with submerged healing for 4 months. The primary outcome was implant survival during the observation period.

Communication about personal values of patients with advanced lung cancer in the hospital: results of a mixed-methods study.

Background: Guidelines recommend to discuss the treatment and care goals of patients with advanced cancer in alignment with their values and preferences, yet this approach is often not adequately implemented in hospitals. To explore the personal values of patients with metastatic lung cancer and how they communicate them to physicians, a mixed-methods study was conducted at a German University Lung Cancer Center.

Methods: The study included quantitative data from 66 patients with metastatic lung cancer using the Human Values Scale, a group comparison after propensity score matching with the German cohort from the 9th European Social Survey, semi-structured in-depth interviews (n = 17), qualitative content analysis, and integration of the data using side-by-side display.

Effects of mentoring on self-reflection and competence in Final year medical students' internal medicine rotation.

Background: Final year medical students (FYMS) in Germany transfer theoretical knowledge to clinical practice. However, there is a deficiency in structured guidance and feedback and self-reflective practices are often neglected. This study aims to investigate the impact of three mentoring strategies on cultivating self-reflection and introspection in FYMS and to assess competence during routine activities.

Diagnostic value of MRI for posttreatment surveillance of early-stage (I-II) glottic larynx cancer.

Purpose: There is no uniformity across various guidelines in defining the modality and frequency of the follow-up, particularly regarding radiological imaging. The objective is to assess the diagnostic performance of magnetic resonance imaging (MRI)-based posttreatment surveillance for early-stage (I-II) glottic squamous cell carcinoma of the larynx.

Methods: The follow-up of patients diagnosed with glottic squamous cell carcinoma of the larynx, treated with radiotherapy or surgery in curative intent, was analyzed over a period of 2 years posttreatment.

Functional phenotyping of genomic variants using joint multiomic single-cell DNA-RNA sequencing.

Genetic variants (both coding and noncoding) can impact gene function and expression, driving disease mechanisms such as cancer progression. The systematic study of endogenous genetic variants is hindered by inefficient precision editing tools, combined with technical limitations in confidently linking genotypes to gene expression at single-cell resolution. We developed single-cell DNA-RNA sequencing (SDR-seq) to simultaneously profile up to 480 genomic DNA loci and genes in thousands of single cells, enabling accurate determination of coding and noncoding variant zygosity alongside associated gene expression changes.

ATF6 activation alters colonic lipid metabolism causing tumour-associated microbial adaptation.

Endoplasmic reticulum unfolded protein responses contribute to cancer development, with activating transcription factor 6 (ATF6) involved in microbiota-dependent tumorigenesis. Here we show the clinical relevance of ATF6 in individuals with early-onset and late colorectal cancer, and link ATF6 signalling to changes in lipid metabolism and intestinal microbiota. Transcriptional analysis in intestinal epithelial cells of ATF6 transgenic mice (nATF6) identifies bacteria-specific changes in cellular metabolism enriched for fatty acid biosynthesis.

Genetic predisposition to persistent fatigue after a diagnosis of colorectal cancer.

Background: Cancer-related fatigue (fatigue) is a common and persistent symptom after cancer treatment, yet the role of genetic susceptibility remains unclear.

Methods: We leveraged data from a prospective cohort study, ColoCare Study (ie, five U.S.

Digital Outcomes of Upper Limb Ataxia Capture Meaningful Longitudinal Change and Treatment Response.

Background: Digital-motor outcomes promise better responsiveness than clinician-reported outcomes in ataxia trials. However, their patient meaningfulness and sensitivity to change remain to be demonstrated, particularly in the upper limb domain.

Objectives: Validation of quantitative motor (Q-Motor) assessment for upper limb ataxia against patient-reported outcomes and regarding sensitivity to both longitudinal and treatment-induced change, the latter in n-of-1 treatment settings.

cIMPACT-NOW update 11: Proposal on adaptation of diagnostic criteria for IDH- and H3-wildtype diffuse high-grade gliomas and for posterior fossa ependymal tumors.

The Consortium to Inform Molecular and Practical Approaches to Central Nervous System Tumor Taxonomy (cIMPACT-NOW) updates provide guidelines for the diagnosis of central nervous system (CNS) tumors and suggestions for future World Health Organization (WHO) classification. Following publication of the fifth edition WHO Classification of CNS Tumors (WHO CNS5) in 2021, the cIMPACT-NOW working group "Clarification" reviewed WHO CNS5 and prioritized two topics for further elucidation: (a) distinction of Glioblastoma, IDH-wildtype from Diffuse pediatric-type high-grade glioma, H3-wildtype, and IDH-wildtype and (b) clarification of subgroups of posterior fossa (PF) ependymal tumors. Recommendations regarding the IDH- and H3-wildtype diffuse high-grade gliomas include: (1) use caution assigning CNS WHO grade 4 (diagnosis of Glioblastoma, IDH-wildtype) to a "TERT promoter only", histologically low-grade, IDH-wildtype tumor; (2) EGFR gene amplification and +7/-10 chromosome copy number alterations should not be used as solitary defining features for diagnosing high-grade gliomas as Glioblastoma, IDH-wildtype in patients <40 years of age; (3) Diffuse pediatric-type high-grade glioma, H3-wildtype, and IDH-wildtype should be considered in the differential diagnosis in adults, especially those <40 years of age; (4) PDGFRA alteration, EGFR alteration, or MYCN amplification count as key molecular features of Diffuse pediatric-type high-grade glioma, H3-wildtype, and IDH-wildtype only in patients <25 years.

Targeting alcohol use in high-risk population groups: a US microsimulation study of beverage-specific pricing policies.

Background: Raising retail prices on alcoholic beverages preferred by high-risk groups (males, those of low socioeconomic status, and those with heavy alcohol use) might selectively reduce their alcohol consumption. However, the differential impact of beverage-specific price increases on US population groups has yet to be studied. This study aimed to simulate the effect of beverage-specific price increases on alcohol use within subgroups of the adult US population defined by sex, educational attainment, and alcohol use category.

A novel feedback loop between DYRK2 and USP28 regulates cancer homeostasis and DNA damage signaling.

Posttranslational modifications, such as ubiquitination and phosphorylation, play pivotal roles in regulating protein stability in response to cellular stress. Dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) and ubiquitin-specific peptidase 28 (USP28) are critical regulators of cell cycle progression, DNA damage response, and oncogenic signaling. However, their functional interplay remains largely unexplored.

Heart Failure Therapy in Patients with Advanced Cancer Receiving Specialized Palliative Care (EMPATICC trial).

Background And Aims: Advanced cancer may resemble a heart failure (HF)-like phenotype marked by cardiac wasting, dyspnoea, congestion, and/or physical dysfunction. The trial evaluated safety and efficacy of HF therapy among patients with advanced cancer receiving specialized palliative care to improve patients' self-care ability.

Methods: Patients with stage 4 solid tumours with a life expectancy of 1-6 months receiving specialized palliative care were enrolled.