Toyooka Hospital

Impaired neutrophil function is thought to increase infection risk associated with smoking. We examined the effects of nicotine- and tar-free cigarette smoke extracts (CSEs) from combustible cigarettes (CCs) and heated tobacco products (HTPs) on neutrophil-like HL-60cells. HTP-derived CSEs exhibited lower cytotoxicity and milder impairment of neutrophil functions, including chemotaxis, reactive oxygen species production, phagocytosis, and neutrophil extracellular trap formation, than those of CC-derived CSEs. However, at higher concentrations, HTP-derived CSEs markedly impaired the cell viability and function. These results indicate that HTP emissions impair neutrophil functions at high concentrations, highlighting the need for cautious health risk evaluation.

Cytokine storm syndrome (CSS), commonly associated with hemophagocytic lymphohistiocytosis (HLH), is a fatal hyperinflammatory syndrome. Differentiating the underlying diseases responsible for CSS is essential for timely therapeutic decisions. This study explored the clinical usefulness of serum cytokine profiling in distinguishing underlying diseases in patients with CSS. Serum samples were collected from 143 adult and pediatric patients with CSS and 22 healthy controls. The cohort included patients with various diagnoses of primary and secondary HLH and Kawasaki disease (KD)-like hyperinflammatory syndromes. Serum levels of 48 cytokines were analyzed in 97 patients using a bead-based multiplex immunoassay (Luminex assay). Serum levels of interferon alpha (IFN-α), interleukin-18 (IL-18), IL-6, CXCL9, and soluble tumor necrosis factor receptor II (sTNF-RII) were measured in 165 participants using enzyme-linked immunosorbent assay (ELISA). Luminex assay categorized patients with CSS into five clusters based on serum cytokine patterns. ELISA revealed distinct cytokine patterns, wherein patients with histiocytic necrotizing lymphadenitis-associated HLH and systemic lupus erythematosus-associated macrophage activation syndrome (MAS) showed elevated IFN-α; systemic juvenile idiopathic arthritis-associated and adult-onset Still's disease-associated MAS, X-linked inhibitor of apoptosis protein deficiency with HLH, and NLRC4-associated autoinflammatory disorder exhibited higher IL-18 levels. Additionally, KD shock syndrome had higher IL-6 levels than the other groups. CXCL9 was significantly elevated in patients with virus-associated HLH, familial HLH, malignant lymphoma-associated HLH, and KD-MAS. Multisystem inflammatory syndrome in children and toxic shock syndrome also showed moderate elevations of CXCL9 and IL-6 levels. Serum cytokine profiling effectively differentiates CSS subtypes, facilitating better diagnosis and personalized treatment strategies based on specific disease backgrounds.

BackgroundSepsis is a leading cause of death in intensive care units (ICU). Sepsis survivors are often left with significant morbidity, termed post-intensive care syndrome (PICS), impacting post-sepsis life. The aim was to present detailed data on the prognostic and functional long-term outcomes of ICU patients with sepsis in Japan, which is currently lacking and therefore prevents development of targeted solutions.MethodsA multicenter prospective study, involving 21 ICUs in 20 tertiary hospitals in Japan, included all consecutive adult ICU patients between November 2020 and April 2022, and diagnosed with sepsis at ICU admission (Sepsis 3). Follow-ups were performed at 3, 6, and 12 months after hospital discharge by telephone and mail. Primary outcome was death or incidence of PICS, defined by any of physical dysfunction (Barthel Index ≤ 90), cognitive dysfunction (Short Memory Questionnaire < 40), or mental disorder (any subscales for anxiety or depression of Hospital Anxiety and Depression Scale ≥ 8, or Impact of Event Scale-Revised ≥ 25). Secondary outcomes included Quality of Life (QOL), employment, and use of hospital, emergency, rehabilitation, and psychiatric services. A multivariable analysis investigated independent factors associated with each dysfunction at each follow-up.ResultsA total of 339 patients were included (median age 74 [67–82] years, 60% male, 77% septic shock, and a median SOFA of 9 [6–12]). Mortality was 23% at hospital discharge, increasing to 37% at 12 months. The rate of death or those who met PICS Criteria at hospital discharge was 89%, with a death or PICS incidence of 73%, 64%, and 65% at 3, 6, and 12 months, respectively. Limited improvements in QOL and return to work (44%), high rates of hospital readmissions (40%), frequent emergency service usage (31%), and low utilization of rehabilitation and psychiatric services (15% and 7%) were identified over the first year. The incidence of any PICS-related dysfunction was consistently an independent factor for the incidence of the same dysfunction at the following follow-ups.ConclusionsThis multicenter study identified the distinct realities of post-sepsis life in Japanese ICU patients, highlighting the unique challenges in improving their functions and returning to daily life.Trial RegistrationUniversity Hospital Medical Information Network UMIN000041433

We aimed to elucidate the efficacy of conventional cisplatin-based adjuvant chemotherapy for patients with lung cancers harboring epidermal growth factor receptor (EGFR) mutation. This retrospective cohort study included 110 patients (EGFR mutation group: n = 51; EGFR wild-type group: n = 59) receiving cisplatin-based adjuvant chemotherapy following complete resection of non-small-cell non-squamous-cell lung cancer (2010-2021). Clinicopathological characteristics, recurrence-free survival (RFS), and overall survival (OS) were investigated. The pStage distribution was not statistically different. The EGFR mutation group was characterized by more advanced pN, papillary predominance, and presence of micropapillary components, whereas the EGFR wild-type group exhibited more advanced pT and solid predominant patterns. The median RFS was significantly worse in the EGFR mutation group (23.0 vs. 76.1 months, p = 0.017). Nevertheless, the median OS was not significantly different (85.6 months vs. not reached, p = 0.151). Multivariable analysis demonstrated that EGFR mutation and lymphatic invasion were significant risk factors in RFS; however, no independent factors were identified in OS. Cisplatin-based adjuvant chemotherapy might be less effective in patients with EGFR-mutated lung cancer. The style of progression and histological pattern related with EGFR mutation may be associated with the efficacy of adjuvant chemotherapy and poor RFS.

Superoxide dismutase (SOD) catalyzes the highly reactive superoxide anion to form hydrogen peroxide, which facilitates cell proliferation and death. We investigated whether red cell SOD (R-SOD) activity is associated with an increased risk of cancer in a Japanese general population. We prospectively analyzed data from 1,921 participants (800 men and 1,121 women; age, 58.7 ± 14.7 years) in a Hidaka cohort study. After a median follow-up period of 10.9 years, 160 participants had developed cancer. The Cox proportional hazards model was used to estimate quartile-specific HRs and 95% confidential intervals (CI) for cancer risk. After adjustment for potential cancer risk factors including age, sex, current smoking habit, alcohol use, physical activities, body mass index, plasma immunoreactive insulin, and non–high-density lipoprotein cholesterol levels, we found a significant association between R-SOD activity and an increased risk of cancer (HR, 1.61; 95% CI, 1.03–2.52; P = 0.037). In analyses conducted separately by sex, a significant association was found in men (HR, 2.49; 95% CI, 1.35–4.59; P = 0.003) but not women (HR, 1.46; 95% CI, 0.70–3.05; P = 0.320). After excluding participants who developed cancer within 5 years of the baseline survey, the association was more evident in men (HR, 4.64; 95% CI, 1.88–11.45; P = 0.001). We found no association with cancer risk in women (HR, 1.01; 95% CI, 0.39–2.65; P = 0.983). Increased R-SOD activities were associated with an increased risk of cancer, particularly in men in this population.Significance:Our study is the first to show that increased R-SOD activity is associated with a significantly higher cancer risk in men but not in women. Antioxidative enzymes such as SOD are essential for maintaining cellular redox balance. Their roles in cancer development and prevention are yet to be fully elucidated.

Clinical findings and postoperative follow-up data on remnant gastric cancer (RGC) are limited due to its rarity. Additionally, the preoperative staging, radical surgery, and managing recurrence in RGC present significant clinical challenges. We analyzed the clinicopathological findings, adjuvant chemotherapy, and patterns of postoperative recurrence of 313 consecutive patients who underwent curative surgery for RGC at 17 Japanese institutions. This study investigated the optimal management of RGC and the impact of adjuvant chemotherapy (AC) on recurrence-free survival (RFS). Pathological stages I, II, and III were observed in 55.9% (N = 175), 24.9% (N = 78), and 19.2% (N = 60) of the patients, respectively. The overall concordance rate between clinical and pathological T staging was 58.3%, with a clinical T4 sensitivity of 41.4% for diagnosing pathological T4. During the median follow-up period of 4.6years, disease recurrence occurred in 24.3% of patients. Most recurrences (over 80%) occurred within 2.5years, and 96.1% within 5years after RGC surgery. Peritoneal recurrence was the most common in patients with advanced RGC, accounting for 14.1% in stage II and 28.3% in stage III. Multivariable regression analysis showed that AC was significantly associated with a longer RFS, with a hazard ratio of 0.45 (95% confidence interval: 0.26-0.76). Our study underscores the importance of early detection, accurate preoperative staging, and postoperative surveillance in managing advanced RGC cases. Despite some limitations, our findings indicate that AC may provide survival benefits comparable to those seen in primary gastric cancer.

Although patients who underwent night-time resuscitation for out-of-hospital cardiac arrest (OHCA) had worse clinical outcomes than those who underwent day-time resuscitation, the differences between the outcomes of patients with OHCA who underwent extracorporeal cardiopulmonary resuscitation (ECPR) in the day-time and night-time remain unclear. We analyzed data from the Study of Advanced Life Support for Ventricular Fibrillation with Extracorporeal Circulation in Japan. Patients were categorized according to whether they received treatment during the day-time or night-time. The primary outcomes were survival to hospital discharge and favorable neurological outcome at discharge, and the secondary outcomes were estimated low-flow time, implementation time of ECPR, and complications due to ECPR. A multivariate logistic regression model adjusted for confounders was used for comparison. Among the 1644 patients, the night-time patients had a significantly longer ECMO implementation time and estimated low-flow time than the day-time patients, along with a significantly higher number of complications than the day-time patients. However, the survival and neurologically favorable survival rates did not differ significantly between the groups. Thus, although patients who underwent ECPR at night had an increased risk of longer implementation time and complications, their clinical outcomes did not differ from those who underwent day-time ECPR.

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of aggressive extranodal large B-cell lymphoma characterized by the selective growth of lymphoma cells within the lumina of blood vessels, particularly capillaries. IVLBCL lacks mass formation, and its diagnosis can be challenging. We analyzed the utility of insulin-like growth factor II mRNA-binding protein 3 (IMP3) immunohistochemistry for IVLBCL diagnosis in various organs. Double staining with paired box 5 (PAX5) was performed for validation. Overall, 152 pathological specimens (111 positive and 41 negative for IVLBCL) obtained from 88 patients with a diagnosis of IVLBCL were stained for IMP3 and IMP3/PAX5. As negative controls, 40 pathology specimens from 38 patients with no history of IVLBCL or other B-cell lymphomas were stained for IMP3, which comprised 31 benign pathological specimens from 29 patients in whom malignancy was suspected, 7 cases of appendicitis with intravascular and/or intralymphatic lymphoid proliferations, and 2 cases of intravascular natural killer/T-cell lymphoma. All mononuclear cells with cytoplasmic staining were considered positive for IMP3 expression, but expression restricted to germinal center B cells was excluded from evaluation. All 111 IVLBCL pathological specimens were positive for IMP3 and IMP3/PAX5. In addition, 11 of the 41 specimens originally diagnosed as IVLBCL-negative showed IMP3/PAX5 double-positive cells, raising the suspicion of IVLBCL. However, of the 40 negative control samples, IMP3-positive non-germinal center B cells were detected in only 2 samples ( P = 0.0131) and no intravascular IMP3-positive B cells suspicious for IVLBCL were identified. Altogether, IMP3 immunohistochemistry is a highly sensitive marker of IVLBCL and can be a helpful adjunct for IVLBCL diagnosis.

This study aimed to assess the effects of thienopyridine-class antiplatelet agents (including ticlopidine, clopidogrel, and prasugrel) on bleeding complications in patients who underwent robot-assisted radical prostatectomy. This cohort study used a database for robot-assisted radical prostatectomy at 23 tertiary centers nationwide between 2011 and 2022. Patients who received thienopyridines (thienopyridine group) were compared with those who received aspirin monotherapy (aspirin group). The primary outcome was the incidence of bleeding complications. High-grade complications were defined as Clavien-Dindo grade III or higher. The risks of these outcomes were evaluated using inverse probability of treatment weighted regression models. The study results demonstrated that thienopyridine therapy was associated with a higher risk of overall bleeding complications (OR: 3.62, 95%CI 1.54-8.49). The increased risks of the thienopyridine group were detected for low-grade bleeding complications (OR: 3.20, 95%CI 1.23-8.30) but not for high-grade bleeding complications (OR: 5.23, 95%CI 0.78-34.9). The increased risk of bleeding complications was not observed when thienopyridine was discontinued (OR: 2.52, 95%CI 0.83-7.70); however, it became apparent when it was continued perioperatively (OR: 4.35, 95%CI 1.14-16.61). In conclusion, thienopyridine increased the incidence of bleeding complications, particularly low-grade bleeding complications, following robot-assisted radical prostatectomy. These bleeding effects emerged when thienopyridine was continued perioperatively.