Medium-Sized Rotator Cuff Tears Repaired With Transosseous-Equivalent Technique Plus Bone Marrow Stimulation Yielded Similar Short-Term Outcomes Regardless of Whether Complete or Incomplete Footprint Coverage Was Achieved.

Purpose: To compare clinical outcomes and retear rates of medium-sized rotator cuff tears repaired with incomplete footprint coverage using the transosseous-equivalent technique versus those with complete footprint coverage plus bone marrow stimulation.

Methods: The retrospective study, conducted from March 2019 to December 2021, included consecutive patients with medium-sized (1-3 cm) posterosuperior rotator cuff tears repaired using the transosseous-equivalent technique and bone marrow stimulation, with a minimum follow-up of 2 years. Patients were divided into 2 groups based on the degree of footprint coverage achieved: group C (complete coverage) and group I (incomplete coverage).

Association between patient medications and postoperative outcomes in early-stage non-small cell lung cancer.

Background: Currently, there is no consensus on how to comprehensively assess comorbidities in lung cancer patients in the clinical setting. Prescription medications may be a preferred comorbidity assessment tool and provide a simple mechanism for predicting postoperative outcomes for lung cancer. We examined the relationship between prescription medications and postoperative outcomes for early-stage non-small cell lung cancer (NSCLC).

Integrated Deep Learning Model for the Detection, Segmentation, and Morphologic Analysis of Intracranial Aneurysms Using CT Angiography.

Purpose To develop a deep learning model for the morphologic measurement of unruptured intracranial aneurysms (UIAs) based on CT angiography (CTA) data and validate its performance using a multicenter dataset. Materials and Methods In this retrospective study, patients with CTA examinations, including those with and without UIAs, in a tertiary referral hospital from February 2018 to February 2021 were included as the training dataset. Patients with UIAs who underwent CTA at multiple centers between April 2021 to December 2022 were included as the multicenter external testing set.

Development of an orally bioavailable CDK12/13 degrader and induction of synthetic lethality with AKT pathway inhibition.

Cyclin-dependent kinases 12/13 play pivotal roles in orchestrating transcription elongation, DNA damage response, and maintenance of genomic stability. Biallelic CDK12 loss has been documented in various malignancies. Here, we develop a selective CDK12/13 PROTAC degrader, YJ9069, which effectively inhibits proliferation in subsets of prostate cancer cells preferentially over benign immortalized cells.

Incidence and Outcomes of Cardiocerebral Infarction: A Cohort Study of 2 National Population-Based Registries.

Background: Cardiocerebral infarction (CCI), which is concomitant with acute myocardial infarction (AMI) and acute ischemic stroke (AIS), is a rare but severe presentation. However, there are few data on CCI, and the treatment options are uncertain. We investigated the characteristics and outcomes of CCI compared with AMI or AIS alone.

IL-13Rα2/TGF-β bispecific CAR-T cells counter TGF-β-mediated immune suppression and potentiate anti-tumor responses in glioblastoma.

Background: Chimeric antigen receptor (CAR)-T cell therapies targeting glioblastoma (GBM)-associated antigens such as interleukin-13 receptor subunit alpha-2 (IL-13Rα2) have achieved limited clinical efficacy to date, in part due to an immunosuppressive tumor microenvironment (TME) characterized by inhibitory molecules such as transforming growth factor-beta (TGF-β). The aim of this study was to engineer more potent GBM-targeting CAR-T cells by countering TGF-β-mediated immune suppression in the TME.

Methods: We engineered a single-chain, bispecific CAR targeting IL-13Rα2 and TGF-β, which programs tumor-specific T cells to convert TGF-β from an immunosuppressant to an immunostimulant.

Optimizing immunofluorescence with high-dynamic-range imaging to enhance PD-L1 expression evaluation for 3D pathology assessment from NSCLC tumor tissue.

Assessing programmed death ligand 1 (PD-L1) expression through immunohistochemistry (IHC) is the golden standard in predicting immunotherapy response of non-small cell lung cancer (NSCLC). However, observation of heterogeneous PD-L1 distribution in tumor space is a challenge using IHC only. Meanwhile, immunofluorescence (IF) could support both planar and three-dimensional (3D) histological analyses by combining tissue optical clearing with confocal microscopy.

Pembrolizumab for advanced urothelial carcinoma: exploratory ctDNA biomarker analyses of the KEYNOTE-361 phase 3 trial.

Circulating tumor DNA (ctDNA) is emerging as a potential biomarker in early-stage urothelial cancer, but its utility in metastatic disease remains unknown. In the phase 3 KEYNOTE-361 study, pembrolizumab with and without chemotherapy was compared with chemotherapy alone in patients with metastatic urothelial cancer. The study did not meet prespecified efficacy thresholds for statistical significance.

Sequential CD7 CAR T-Cell Therapy and Allogeneic HSCT without GVHD Prophylaxis.

Background: Patients with relapsed or refractory hematologic cancers have a poor prognosis. Chimeric antigen receptor (CAR) T-cell therapy as a bridge to allogeneic hematopoietic stem-cell transplantation (HSCT) has the potential for long-term tumor elimination. However, pre-HSCT myeloablation and graft-versus-host disease (GVHD) prophylaxis agents have toxic effects and could eradicate residual CAR T cells and compromise antitumor effects.

Nivolumab Plus 5-Azacitidine in Pediatric Relapsed/Refractory Acute Myeloid Leukemia (AML): Phase I/II Trial Results from the Therapeutic Advances in Childhood Leukemia and Lymphoma (TACL) Consortium.

Improvements in survival have been made over the past two decades for childhood acute myeloid leukemia (AML), but the approximately 40% of patients who relapse continue to have poor outcomes. A combination of checkpoint-inhibitor nivolumab and azacitidine has demonstrated improvements in median survival in adults with AML. This phase I/II study with nivolumab and azacitidine in children with relapsed/refractory AML (NCT03825367) was conducted through the Therapeutic Advances in Childhood Leukemia & Lymphoma consortium.

Abdominal Symptom Improvement During Clinical Trials of Tenapanor in Patients With Irritable Bowel Syndrome With Constipation: A Post Hoc Analysis.

Introduction: This post hoc analysis evaluated the efficacy of tenapanor on abdominal symptoms in patients with irritable bowel syndrome with constipation. Abdominal symptoms assessed included pain, discomfort, bloating, cramping, and fullness.

Methods: The abdominal symptom data were pooled from 3 randomized controlled trials (NCT01923428, T3MPO-1 [NCT02621892], and T3MPO-2 [NCT02686138]).

Inhaled medications for chronic obstructive pulmonary disease predict surgical complications and survival in stage I non-small cell lung cancer.

Background: Lung function is routinely assessed prior to surgical resection for non-small cell lung cancer (NSCLC). Further assessment of chronic obstructive pulmonary disease (COPD) using inhaled COPD medications to determine disease severity, a readily available metric of disease burden, may predict postoperative outcomes and overall survival (OS) in lung cancer patients undergoing surgery.

Methods: We retrospectively evaluated clinical stage I NSCLC patients receiving surgical treatment within the Veterans Health Administration from 2006-2016 to determine the relationship between number and type of inhaled COPD medications (short- and long-acting beta2-agonists, muscarinic antagonists, or corticosteroids prescribed within 1 year before surgery) and postoperative outcomes including OS using multivariable models.

In Vivo Base Editing of Rescues Type 3 Long QT Syndrome in Mice.

Background: Pathogenic variants in can result in long QT syndrome type 3, a life-threatening genetic disease. Adenine base editors can convert targeted A T base pairs to G C base pairs, offering a promising tool to correct pathogenic variants.

Methods: We generated a long QT syndrome type 3 mouse model by introducing the T1307M pathogenic variant into the gene.

Bag-Valve-Mask Ventilation and Survival From Out-of-Hospital Cardiac Arrest: A Multicenter Study.

Background: Few studies have measured ventilation during early cardiopulmonary resuscitation (CPR) before advanced airway placement. Resuscitation guidelines recommend pauses after every 30 chest compressions to deliver ventilations. The effectiveness of bag-valve-mask ventilation delivered during the pause in chest compressions is unknown.

Vepafestinib is a pharmacologically advanced RET-selective inhibitor with high CNS penetration and inhibitory activity against RET solvent front mutations.

RET receptor tyrosine kinase is activated in various cancers (lung, thyroid, colon and pancreatic, among others) through oncogenic fusions or gain-of-function single-nucleotide variants. Small-molecule RET kinase inhibitors became standard-of-care therapy for advanced malignancies driven by RET. The therapeutic benefit of RET inhibitors is limited, however, by acquired mutations in the drug target as well as brain metastasis, presumably due to inadequate brain penetration.

Improved predictability of pancreatic ductal adenocarcinoma diagnosis using a blood immune cell biomarker panel developed from bulk mRNA sequencing and single-cell RNA-sequencing.

Background: Pancreatic ductal adenocarcinoma (PDAC) remains a devastating cancer due to its poor survival rate, early detection, and resectability. This study aimed to determine the peripheral blood mononuclear cell (PBMC) immune biomarkers in patients with PDAC and investigate the PDAC-specific peripheral blood biomarker panel and validate its clinical performance.

Methods: In this prospective, blinded, case-control study, a biomarker panel formula was generated using a development cohort-including healthy controls, patients at high risk of PDAC, and patients with benign pancreatic disease, PDAC, or other gastrointestinal malignancies-and its diagnostic performance was verified using a validation cohort, including patients with ≥ 1 lesion suspected as PDAC on computed tomography (CT).

Intrarenal Renin-Angiotensin System Activation Alters Relationship Between Systolic Blood Pressure and Progression of Chronic Kidney Disease.

Background: Elevated blood pressure and intrarenal renin-angiotensin system activity are closely related to chronic kidney disease (CKD) progression. However, interrelationship between blood pressure and intrarenal renin-angiotensin system activity on the risk of CKD progression is unknown.

Methods: We analyzed 2076 participants from the Korean Cohort Study for Outcomes in Patients With CKD.

Early-Life Cardiovascular Risk Factor Trajectories and Vascular Aging in Midlife: A 30-Year Prospective Cohort Study.

Background: Vascular aging, as assessed by structural and functional arterial properties, is an independent predictor of cardiovascular outcomes. We aimed to explore the associations of individual cardiovascular risk factors from childhood to midlife and their accumulation over a 30-year span with vascular aging in midlife.

Methods: Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, 2180 participants aged 6 to 18 years at baseline were followed for over 30 years.

Reversion mutations in germline BRCA1/2-mutant tumors reveal a BRCA-mediated phenotype in non-canonical histologies.

The association between loss of BRCA1/2 and a homologous recombination deficiency phenotype is lineage dependent. In BRCA-associated cancers such as breast, ovarian, pancreas and prostate, this phenotype confers sensitivity to PARP inhibitors and platinum-therapies. Somatic reversion mutations restoring BRCA1/2 function mediate resistance, and have exclusively been reported in BRCA-associated tumors.