Preoperative pembrolizumab‑induced hemophagocytic lymphohistiocytosis in a patient with breast cancer: A case report.

Recently, the anti-programmed cell death protein 1 antibody pembrolizumab, a type of immune checkpoint inhibitor (ICI), has been used in preoperative systemic chemotherapy for hormone receptor and human epidermal growth factor 2-negative breast cancer, also known as triple-negative breast cancer (TNBC). Chemotherapy with pembrolizumab has demonstrated clinical activity in terms of pathologic complete response and event-free survival. Despite their efficacy, the current understanding of the full spectrum of side effects associated with relatively new ICIs remains incomplete.

A single-arm, phase II study of sotorasib plus carboplatin/pemetrexed in advanced non-squamous non-small cell lung cancer patients with KRAS G12C mutation (WJOG14821L, SCARLET).

Background: The efficacy and safety of sotorasib plus platinum-doublet chemotherapy in KRAS G12C-mutated non-squamous non-small cell lung cancer (non-Sq NSCLC) were previously reported with limited follow-up period.

Method: SCARLET was a single-arm phase II study of chemotherapy-naïve patients with KRAS G12C-mutated non-Sq NSCLC. Participants received sotorasib 960 mg daily plus four cycles of carboplatin (area under the curve, 5)/pemetrexed 500 mg/m, followed by sotorasib/pemetrexed until disease progression.

Impact of low-dose aspirin therapy initiation timing on pregnancy outcomes after frozen-thawed blastocyst transfer.

Clinical effects of low-dose aspirin (LDA) on embryo implantation still remains controversial; therefore, we investigated the appropriate timing for starting LDA in frozen-thawed embryo transfer (ET) cycles. A cross-sectional study was conducted on 885 infertile women who underwent thrombophilia screening between 2020 and 2023. We recruited first frozen-thawed blastocyst transfer cycles in 553 consecutive women aged < 40 years.

Comparative analysis of kidney function prediction: traditional statistical methods vs. deep learning techniques.

Background: Chronic kidney disease (CKD) represents a significant public health challenge, with rates consistently on the rise. Enhancing kidney function prediction could contribute to the early detection, prevention, and management of CKD in clinical practice. We aimed to investigate whether deep learning techniques, especially those suitable for processing missing values, can improve the accuracy of predicting future renal function compared to traditional statistical method, using the Japan Chronic Kidney Disease Database (J-CKD-DB), a nationwide multicenter CKD registry.

Chronic kidney disease is a major risk factor for mortality in triglyceride deposit cardiomyovasculopathy patients.

Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare cardiovascular disorder caused by defective intracellular lipolysis of triglyceride, resulting in heart failure and diffuse narrowing atherosclerosis. Recently, the registry of TGCV patients in Japan revealed that the 3-year overall survival rate was 80.1% and the 5-year overall survival rate was 71.

Impact of hyper- and hypothermia on cellular and whole-body physiology.

The incidence of heat-related illnesses and heatstroke continues to rise amidst global warming. Hyperthermia triggers inflammation, coagulation, and progressive multiorgan dysfunction, and, at levels above 40 °C, can even lead to cell death. Blood cells, particularly granulocytes and platelets, are highly sensitive to heat, which promotes proinflammatory and procoagulant changes.

Mitochondrial dysfunction is a major cause of thromboinflammation and inflammatory cell death in critical illnesses.

Background: Mitochondria generate the adenosine triphosphate (ATP) necessary for eukaryotic cells, serving as their primary energy suppliers, and contribute to host defense by producing reactive oxygen species. In many critical illnesses, including sepsis, major trauma, and heatstroke, the vicious cycle between activated coagulation and inflammation results in tissue hypoxia-induced mitochondrial dysfunction, and impaired mitochondrial function contributes to thromboinflammation and cell death.

Methods: A computer-based online search was performed using the PubMed and Web of Science databases for published articles concerning sepsis, trauma, critical illnesses, cell death, mitochondria, inflammation, coagulopathy, and organ dysfunction.

PARADIGM-PV: a randomized, multicenter phase 4 study to assess the efficacy and safety of ropeginterferon alfa-2b in patients with low- or high-risk polycythemia vera.

Polycythemia vera (PV) is characterized by clonal hematopoietic stem or progenitor cells with constitutively active somatic mutation(s) in the Janus kinase 2 gene. Phlebotomy (Phl) and aspirin are often used alone for low-risk PV patients. However, data from the Low-PV study demonstrated that Phl and aspirin may not be adequate for patients.

Treatment of Crohn's Disease With Infliximab and Subsequent Development of Takayasu's Arteritis.

A 23-year-old man was diagnosed with Crohn's disease (CD) of the large intestine after colonoscopy revealed longitudinal ulcers, and pathology revealed non-caseating epithelioid cell granulomas and anal fistulas. The CD relapsed, and therefore prednisolone (PSL) and infliximab (IFX) treatment was initiated. The PSL was gradually tapered.

Corticosteroid therapy and long-term outcomes in patients with cardiac sarcoidosis stratified by left ventricular ejection fraction.

Aims: This study aimed to investigate the relationship between corticosteroid therapy and long-term outcomes in patients with cardiac sarcoidosis, stratified by left ventricular ejection fraction (LVEF) at diagnosis.

Methods And Results: This study conducted a analysis of the ILLUstration of the Management and prognosIs of JapaNese PATiEnts with Cardiac Sarcoidosis, a retrospective multicentre registry. Cardiac sarcoidosis was diagnosed based on the 2016 Japanese Circulation Society and 2014 Heart Rhythm Society criteria.

Association Between Gastrointestinal-Related Quality of Life and Frailty Using Baseline Data of the Prospective Cohort Study (JUSTICE-TOKYO Study).

To determine the prevalence of frailty and examine its association with gastrointestinal-related quality of life (QOL) among older outpatients in a geriatric hospital. This cross-sectional study involved 1042 outpatients (age: ≥65 years) diagnosed using the revised Japanese version of the cardiovascular health study criteria. Data collection was performed by a multidisciplinary team.

Alpha-synuclein inhibits the secretion of extracellular vesicles through disruptions in YKT6 lipidation.

Parkinson's disease is characterized by the presence of α-synuclein (α-syn) primarily containing Lewy bodies in neurons. Despite decades of extensive research on α-syn accumulation, its molecular mechanisms have remained largely unexplored. Recent studies by us and others have suggested that extracellular vesicles (EVs), especially exosomes, can mediate the release of α-syn from cells, and inhibiting this pathway could result in increased intracellular α-syn levels.

α-Cyclodextrin supplementation improves endurance exercise performance and reduces post-exercise fatigue in human males: a randomized, double-blind, placebo-controlled, parallel-group study.

α-Cyclodextrin (αCD), a cyclic hexasaccharide composed of six glucose units, is not digested in the small intestine but is completely fermented by gut microbes. Recently, we have reported that αCD supplementation for nonathlete men improved their 10 km biking times. However, the beneficial effects of αCD on exercise are not yet fully understood.

Effect of pre-hospital living setting on nutritional intake route upon discharge in older adults with aspiration pneumonia: a prospective cohort study.

Background: Aspiration pneumonia, which often recurs due to dysphagia, worsens as patients move between homes, facilities, and hospitals. The impact of pre-hospital living setting on oral intake at discharge remains unclear. The purpose of this study was to identify the effects of the pre-hospital living setting on the nutritional intake route upon discharge in older patients with aspiration pneumonia.

Nuclear PD-L1 triggers tumour-associated inflammation upon DNA damage.

Immune checkpoint inhibitors against PD-1/PD-L1 are highly effective in immunologically hot tumours such as triple-negative breast cancer, wherein constitutive DNA damage promotes inflammation, while inducing PD-L1 expression to avoid attack by cytotoxic T cells. However, whether and how PD-L1 regulates the DNA damage response and inflammation remains unclear. Here, we show that nuclear PD-L1 activates the ATR-Chk1 pathway and induces proinflammatory chemocytokines upon genotoxic stress.

Evaluating Craniofacial Morphology Ratios as Predictors of Obstructive Sleep Apnea Severity in Non-Obese Adult Males.

: This study aimed to examine the connection between craniofacial morphology, particularly the horizontal and vertical dimensions of the mandible, and the severity of obstructive sleep apnea (OSA) in non-obese adult males by utilizing a cephalometric analysis and introducing a new skeletal ratio index. : A cohort of 44 non-obese adult males with OSA, diagnosed via the apnea-hypopnea index (AHI) from polysomnographic recordings, was evaluated using a lateral cephalometric analysis. OSA severity was classified as mild (5 ≤ AHI < 15) in 19 patients, moderate (15 ≤ AHI < 30) in 15 patients, and severe (AHI ≥ 30) in 10 patients.

Cost-effectiveness of ferric citrate hydrate in patients with iron deficiency anemia.

We investigated the cost-effectiveness of treating iron deficiency anemia (IDA) with ferric citrate hydrate (FC) in Japan. We employed four treatment strategies: switching from sodium ferrous citrate (SF) to FC at (1) 500 mg (approximately 120 mg of iron) per day or (2) 1000 mg (approximately 240 mg of iron) per day in patients with SF-induced nausea/vomiting, or starting treatment with FC at (3) 500 mg/day or (4) 1000 mg/day. We evaluated the cost-effectiveness of these strategies compared with SF 100 mg (100 mg of iron) per day.

Design of buffer property for the new enrichment method of circulating tumor cell based on immunomagnetic-negative separation.

Metastasis is a significant contributor to cancer-related mortality and a critical issue in cancer. Monitoring the changes in circulating tumor cells (CTCs) with metastatic potential is a valuable prognostic and predictive biomarker. CTCs are a rare population in the peripheral blood of patients with cancer.

The transition of the criteria for disseminated intravascular coagulation and the targeted patients in randomized controlled trials over the decades: a scoping review.

Background: Disseminated intravascular coagulation (DIC) is a severe complication in septic patients. The Japanese Ministry of Health and Welfare (JMHW)-DIC criteria, the first DIC criteria, were established in 1983, and several other criteria have been proposed since then, including the International Society on Thrombosis and Haemostasis (ISTH)-overt DIC criteria and the Japanese Association for Acute Medicine (JAAM) DIC criteria. This study aimed to look into the transition of DIC criteria used in randomized controlled trials (RCTs) for sepsis-induced DIC.

Dantrolene inhibition of ryanodine receptor 1 carrying the severe malignant hyperthermia mutation Y522S visualized by cryo-EM.

Mutations in the skeletal isoform of the ryanodine receptor 1 (RyR1) pose grave risks during anesthesia or treatment with succinylcholine muscle relaxants. These can trigger a potentially lethal malignant hyperthermia (MH) episode via intracellular calcium increase mainly from RyR1 channel leakage. Dantrolene is the only known treatment option to prevent death.

Characterization of anti-asialo-GM1 monoclonal antibody.

Asialo-GM1 (ASGM1) has been identified as a cell surface marker of murine NK cells. Although polyclonal anti-asialo-GM1 antibodies (anti-ASGM1 pAb) have been widely used for studying natural killer (NK) cell functions in vivo, the technical challenges have existed in their specificity for NK cell depletion. Furthermore, the exact expression of ASGM1 on the NK cell lineage and other immune cells has not been characterized due to the lack of appropriate reagents.

Comprehensive Gene Expression Analysis Using Human Induced Pluripotent Stem Cells Derived from Patients with Sleep Bruxism: A Preliminary In Vitro Study.

Sleep bruxism (SB) involves involuntary jaw movements during sleep and is potentially caused by motor neuronal hyperexcitability and GABAergic system dysfunction. However, the molecular basis remains unclear. In this study, we aimed to investigate changes in the expression of several genes associated with the pathophysiology of SB.