Nivolumab plus ipilimumab versus nivolumab in microsatellite instability-high metastatic colorectal cancer (CheckMate 8HW): a randomised, open-label, phase 3 trial.

Background: CheckMate 8HW prespecified dual primary endpoints, assessed in patients with centrally confirmed microsatellite instability-high or mismatch repair-deficient status: progression-free survival with nivolumab plus ipilimumab compared with chemotherapy as first-line therapy and progression-free survival with nivolumab plus ipilimumab compared with nivolumab alone, regardless of previous systemic treatment for metastatic disease. In our previous report, nivolumab plus ipilimumab showed superior progression-free survival versus chemotherapy in first-line microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer in the CheckMate 8HW trial. Here, we report results from the prespecified interim analysis for the other primary endpoint of progression-free survival for nivolumab plus ipilimumab versus nivolumab across all treatment lines.

Giant Modulation of Magnetoresistance in a Van Der Waals Magnet by In-Plane Current Injection.

Efficient magnetization control is a central issue in magnetism and spintronics. Particularly, there are increasing demands for manipulation of magnetic states in van der Waals (vdW) magnets with unconventional functionalities. However, the electrically induced phase transition between ferromagnetic-to-antiferromagnetic states without external magnetic field is yet to be demonstrated.

Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial.

Encorafenib + cetuximab (EC) is approved for previously treated BRAF V600E-mutant metastatic colorectal cancer (mCRC) based on the BEACON phase 3 study. Historically, first-line treatment of BRAF V600E-mutant mCRC with chemotherapy regimens has had limited efficacy. The phase 3 BREAKWATER study investigated EC+mFOLFOX6 versus standard of care (SOC) in patients with previously untreated BRAF V600E mCRC.

Exploring the Therapeutic Landscape: A Narrative Review on Topical and Oral Phosphodiesterase-4 Inhibitors in Dermatology.

Phosphodiesterase-4 (PDE4) is involved in the synthesis of inflammatory cytokines that mediate several chronic inflammatory disorders, including psoriasis and atopic dermatitis. In recent years, the therapeutic armamentarium in dermatology has expanded with the introduction of PDE4 inhibitors, both in oral and topical formulations. PDE4 inhibitors have gained increasing interest due to their remarkable safety record and ease of prescription, as evidenced by the recent influx of literature detailing its off-label uses.

Liver Elastography for Liver Fibrosis Stratification: A Comparison of Three Techniques in a Biopsy-Controlled MASLD Cohort.

The aim of this study was to investigate the accuracy in fibrosis staging of a novel shear wave elastography (SWE) device (S-Shearwave Imaging by Samsung) and a previously validated 2D-SWE by Supersonic Imagine (SSI) in patients with biopsy proven metabolic dysfunction-associated steatotic liver disease (MASLD). This prospective study included 75 consecutive patients with MASLD who underwent liver biopsy for suspected MASH. All patients underwent S-Shearwave Imaging by Samsung and 2D-SWE with SSI on the same day of liver biopsy.

Construction of a Compound Model to Enhance the Accuracy of Hepatic Fat Fraction Estimation with Quantitative Ultrasound.

we evaluated regression models based on quantitative ultrasound (QUS) parameters and compared them with a vendor-provided method for calculating the ultrasound fat fraction (USFF) in metabolic dysfunction-associated steatotic liver disease (MASLD). We measured the attenuation coefficient (AC) and the backscatter-distribution coefficient (BSC-D) and determined the USFF during a liver ultrasound and calculated the magnetic resonance imaging proton-density fat fraction (MRI-PDFF) and steatosis grade (S0-S4) in a combined retrospective-prospective cohort. We trained multiple models using single or various QUS parameters as independent variables to forecast MRI-PDFF.

Precision Oncology: A Global Perspective on Implementation and Policy Development.

Despite the acknowledged merits of precision oncology (PO) and its increasing global implementation, its full potential for advancing care and prevention remains unrealized. The benefits are currently accessible to only limited patient segments because of multifaceted barriers. Successful implementation hinges on various factors-scientific complexities not limited to technical, clinical, regulatory, economic, administrative, and health care policy-related challenges.

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Pembrolizumab and chemotherapy in high-risk, early-stage, ER/HER2 breast cancer: a randomized phase 3 trial.

Addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab improved outcomes in patients with high-risk, early-stage, triple-negative breast cancer. However, whether the addition of neoadjuvant pembrolizumab to chemotherapy would improve outcomes in high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER/HER2) breast cancer remains unclear. We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER/HER2 grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1-2 or T3-4, cN0-2) were randomly assigned (1:1) to neoadjuvant pembrolizumab 200 mg or placebo Q3W given with paclitaxel QW for 12 weeks, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide Q2W or Q3W.

Timing for a surgically safe and oncologically prompt pancreatoduodenectomy after preoperative biliary drainage in patients with bile duct cancer.

Background: Preoperative biliary drainage (PBD) is commonly performed in patients with bile duct cancer (BDC). However, data regarding the timing of pancreatoduodenectomy (PD) after PBD are insufficient. This study aimed to investigate the optimal timing for surgically and oncologically safe PD after PBD.

Risk Factors for Progressive Disease After Immune Checkpoint Inhibitor Therapy in Head and Neck Squamous Cell Carcinoma.

Background: This study analyzed the clinical features of patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC), who developed progressive disease (PD) after immune checkpoint inhibitor (ICI) therapy.

Methods: We retrospectively analyzed 256 patients with R/M HNSCC treated with ICIs at 11 medical centers. Associations between the treatment outcomes-best response, overall survival, and progression-free survival-and various clinical factors were analyzed.

Mismatch repair (MMR) and microsatellite instability (MSI) phenotypes across solid tumors: A comprehensive cBioPortal study on prevalence and prognostic impact.

Mismatch repair deficiency (MMR-d) and microsatellite instability (MSI) are prognostic and predictive biomarkers in oncology. Current testing for MMR/MSI relies on immunohistochemistry (IHC) for MMR proteins and molecular assays for MSI detection. This combined diagnostic strategy, however, lacks tumor specificity and does not account for gene variants.

Association of pre-surgical circulating tumor DNA detection, use of sublobar resection with risk of recurrence in stage I non-small cell lung cancer.

Background: Sublobar resection is increasingly recognized as an effective treatment for early-stage NSCLC. However, no studies to date have investigated the potential role of preoperative ctDNA detection in guiding surgical decisions, such as opting for sublobar resection, in stage I NSCLC.

Methods: Patients with solid-dominant (CTR>0.

Consensus and guidelines on diagnosis and management of polypoidal choroidal vasculopathy (PCV) from the Asia-Pacific Vitreo-retina Society (APVRS).

A panel of 21 international experts are formed by the Asia-Pacific Vitreo-retina Society to work out the consensus and guidelines on polypoidal choroidal vasculopathy (PCV). PCV is a common subtype of neovascular age-related macular degeneration and is more prevalent in Asian populations. Recent advancement in imaging technology allows greater understanding of the disease process of PCV.

Characterization for the Similarity Assessment Between the Proposed Biosimilar SB17 and Ustekinumab Reference Product Using State-of-the-Art Analytical Methods.

Background: SB17 is being developed as a biosimilar to ustekinumab reference product (RP), a human monoclonal antibody (IgG1 kappa immunoglobulin) that binds to the common p40 subunit of cytokines interleukin (IL)-23 and IL-12. Binding to this subunit prevents interaction with their receptor, resulting in modulation in the immune system responses that play a key role in inflammatory disease.

Objective: The objective of this study was to demonstrate structural, physicochemical, and biological similarity between ustekinumab RP and SB17 using various state-of-the-art analytical methods.

Neoadjuvant atezolizumab in combination with dual HER2 blockade plus epirubicin in women with early HER2-positive breast cancer: the randomized phase 2 ABCSG-52/ATHENE trial.

The role of anthracyclines in the treatment of early breast cancer (EBC) is increasingly being challenged, especially in de-escalation strategies. However, owing to their immunogenic effects, anthracyclines are promising combination partners with immunotherapies. In the randomized phase 2 trial ABCSG-52 (EudraCT no.

Design of an Atomic Layer-Deposited InO/GaO Channel Structure for High-Performance Thin-Film Transistors.

For potential application in advanced memory devices such as dynamic random-access memory (DRAM) or NAND flash, nanolaminated indium oxide (In-O) and gallium oxide (Ga-O) films with five different vertical cation distributions were grown and investigated by using a plasma-enhanced atomic layer deposition (PEALD) process. Specifically, this study provides an in-depth examination of how the control of individual layer thicknesses in the nanolaminated (NL) IGO structure impacts not only the physical and chemical properties of the thin film but also the overall device performance. To eliminate the influence of the cation composition ratio and overall thickness on the IGO thin film, these parameters were held constant across all conditions.

Risankizumab efficacy and safety based on prior inadequate response or intolerance to advanced therapy: post hoc analysis of the INSPIRE and COMMAND phase 3 studies.

Background And Aims: Treating ulcerative colitis (UC) in patients with prior advanced therapy (AT) exposure may be challenging. We report the efficacy and safety of risankizumab, a monoclonal interleukin 23p19 antibody, in patients with UC and prior inadequate response or intolerance to AT (AT-IR).

Methods: In the 12-week phase 3 INSPIRE induction study, patients were randomized to intravenous risankizumab 1200 mg or placebo.

Oral Maintenance Therapy in Early Breast Cancer-How Many Patients Are Potential Candidates?

Background/objectives: This single-center analysis evaluated the number of potential candidates for endocrine-based oral maintenance therapy in a real-world setting, focusing on three therapeutic agents, namely, olaparib, abemaciclib, and ribociclib, for patients with hormone receptor-positive HER2-negative early breast cancer.

Methods: All breast cancer cases from the past 10 years ( = 3230) that underwent treatment at the certified Breast Cancer Center of the Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Lübeck Campus, were analyzed.

Results: Of a total of 2038 patients with HR+ HER2- eBC, 685 patients (33.

Differential Expression of CXCL12 in Human and Mouse Hair: Androgens Induce CXCL12 in Human Dermal Papilla and Dermal Sheath Cup.

We previously demonstrated that C-X-C Motif Chemokine Ligand 12 (CXCL12) is primarily secreted by dermal fibroblasts in response to androgens and induces hair miniaturization in the mouse androgenic alopecia (AGA) model. However, the direct effects of androgen-induced CXCL12 on dermal papilla cells (DPCs) and dermal sheath cup cells (DSCs) have not been demonstrated. First, we compared single-cell RNA sequencing data between mouse and human skin, and the results show that CXCL12 is highly co-expressed with the androgen receptor (AR) in the DPCs and DSCs of only human hair.

[Treatment of severe flares in Crohn's disease and ulcerative colitis].

Background: In chronic inflammatory bowel diseases (IBD), severe flares are characterized by intense inflammatory activity and a high disease burden for patients. Treatment addresses both short-term goals (e.g.

Fractional flow reserve measurement using dynamic CT perfusion imaging in patients with coronary artery disease.

Purposes: The objective was to evaluate the accuracy of a novel CT dynamic angiographic imaging (CT-DAI) algorithm for rapid fractional flow reserve (FFR) measurement in patients with coronary artery disease (CAD).

Materials And Methods: This retrospective study included 14 patients (age 58.5 ± 10.

Talquetamab plus Teclistamab in Relapsed or Refractory Multiple Myeloma.

Background: Talquetamab (anti-G protein-coupled receptor family C group 5 member D) and teclistamab (anti-B-cell maturation antigen) are bispecific antibodies that activate T cells by targeting CD3 and that have been approved for the treatment of triple-class-exposed relapsed or refractory multiple myeloma.

Methods: We conducted a phase 1b-2 study of talquetamab plus teclistamab in patients with relapsed or refractory multiple myeloma. In phase 1, we investigated five dose levels in a dose-escalation study.

Clinical predictors and noninvasive imaging in Fontan-associated liver disease: A systematic review and meta-analysis.

Background: Despite the development of several imaging modalities for diagnosing Fontan-associated liver disease (FALD), there is no optimal protocol for the follow-up of FALD. We conducted a systematic review and meta-analysis to identify factors related to liver fibrosis using biopsy reports and to identify alternative noninvasive modalities that could better reflect liver histological changes in FALD.

Methods: A systematic review and meta-analysis were conducted following the PRISMA guidelines Table S2.