Effects of the Coronavirus disease 2019 pandemic on mortality in patients with lung cancer: A multiple mediation analysis in Japan.

COVID-19 pandemic has had a substantial effect on healthcare systems worldwide, including the care of patients with lung cancer. The impact of healthcare disruptions and behavioral changes on lung cancer mortality is unclear. Patients newly diagnosed with lung cancer during the pandemic period 2020-2021 were compared with those diagnosed in the pre-pandemic 2018-2019. The primary outcome was all-cause mortality within 1 year. Cox proportional hazards regression analyses were conducted to estimate the changes in mortality between pandemic and pre-pandemic. Multiple mediation analyses were performed to determine the factors that accounted for the changes in mortality. In total, 5785 patients with lung cancer were included in this study. The overall mortality rate was significantly higher during the pandemic compared with the pre-pandemic (crude hazard ratio [HR]: 1.19, 95% confidence interval [CI]: 1.05, 1.29). Mediation analyses showed that not receiving tumor-directed treatment, diagnosis at an older age, and decreased diagnosis through cancer screening significantly accounted for 17.5% (95%CI: 4.2, 30.7), 13.9% (95%CI: 0.8, 27.0), and 12.4% (95%CI: 3.0, 21.8) of the increased mortality, respectively. This study revealed a significant increase in mortality risk in patients with lung cancer who have not received tumor-directed treatment or cancer screening, despite potential selection bias for follow-up status. Efforts should be focused on ensuring timely access to healthcare services, optimizing treatment delivery, and addressing the unique challenges faced by patients with lung cancer during the pandemic to mitigate the impact of the pandemic on lung cancer outcomes and provide clinical care to vulnerable populations.

Computed Tomography-guided Drainage with Modified Trocar Technique Using a Drainaway Drainage Kit.

Purpose: Image-guided percutaneous drainage for abscesses is known as a safe and effective treatment. The computed tomography-guided percutaneous drainage kit Drainaway (SB Kawasumi Co., Ltd.), developed on the basis of a modified trocar method, has made it possible to complete the procedure only under computed tomography guidance without radiographic fluoroscopy. This study investigated the feasibility and safety of Drainaway for abscess drainage. Material and Methods: In this retrospective observational study, 28 procedures in 27 patients (18 men and 9 women; age 67.0 ± 12.3 years) who underwent computed tomography-guided drainage using Drainaway between March and December 2021 at seven affiliated hospitals were analyzed. Patients with symptomatic, puncturable on computed tomography and refractory abscesses were included. Technical success (successful drainage with computed tomography alone), primary clinical success (successful drainage with Drainaway alone), secondary clinical success (avoidance of surgery), and complications were evaluated. Results: The sites of the abscesses were the intraperitoneal, retroperitoneal, and thoracic cavities in 19, 5, and 2 patients, respectively, and subcutaneous tissue in 1 patient. The mean size of the abscesses was 7.1 ± 3.4 cm. The technical success rate was 96.4%; the ligament of the puncture route could not be penetrated in one case. The primary clinical success rate was 77.8%, whereas the secondary clinical success rate of catheter upsizing or replacement was 96.3%. Complications included one case of biliary pleurisy that required drainage. Conclusions: Drainaway is a useful device that allows abscess drainage using only computed tomography guidance without radiographic fluoroscopy.

Impact of the COVID-19 pandemic on the mortality among patients with colorectal cancer in Hiroshima, Japan: A large cancer registry study.

BACKGROUND: This retrospective cohort study aimed to evaluate the impact of the COVID-19 pandemic on colorectal cancer care and mortality using a large cancer registry in Hiroshima Prefecture, Japan. The study aimed to estimate the all-cause mortality rates within 1 year of diagnosis among colorectal cancer patients diagnosed during the pandemic period (2020 and 2021) compared to those diagnosed during the pre-pandemic period (2018 and 2019). METHODS: The day of diagnosis was set as Day 0 and Cox regression models were utilized to estimate crude hazard ratios (HRs) and adjusted HRs, accounting for age, sex, cancer stage, and treatment status. Two sensitivity analyses of overall survival were performed with different cutoffs of the pre-pandemic/pandemic periods and year-to-year comparisons. Subgroup analyses were performed using likelihood ratio tests. RESULTS: A total of 15,085 colorectal cancer patients were included, with 6499 eligible for follow-up. A median age of included patients was 72 years old, of which 59% were male. The distribution of cancer stages showed little variation between the pre-pandemic and pandemic periods. With a median follow-up of 177 days, the number of events was 316/3111 (173 events per 1000 person-years [E/1000PY], 95% confidence interval [CI]: 154-192 E/1000PY) in the pre-pandemic period, and 326/2746 (245 E/1000PY, 95% CI: 220-274 E/1000PY) in the pandemic period (crude HR: 1.42, 95% CI: 1.22-1.66; adjusted HR: 1.25, 95% CI: 1.07-1.46). The two sensitivity analyses and subgroup analyses consistently supported these findings. CONCLUSIONS: The study revealed an increased colorectal cancer mortality during the pandemic period, suggesting a continuous impact of the COVID-19 pandemic on the known and unknown risk factors for colorectal cancer for several years. Further studies are necessary to mitigate the adverse effects on patient outcomes.

Systemic therapy for Asian patients with advanced BRAF V600-mutant melanoma in a real-world setting: A multi-center retrospective study in Japan (B-CHECK-RWD study).

BACKGROUND: Anti-PD-1-based immunotherapy is considered a preferred first-line treatment for advanced BRAF V600-mutant melanoma. However, a recent international multi-center study suggested that the efficacy of immunotherapy is poorer in Asian patients in the non-acral cutaneous subtype. We hypothesized that the optimal first-line treatment for Asian patients may be different. METHODS: We retrospectively collected data of Asian patients with advanced BRAF V600-mutant melanoma treated with first-line BRAF/MEK inhibitors (BRAF/MEKi), anti-PD-1 monotherapy (Anti-PD-1), and nivolumab plus ipilimumab (PD-1/CTLA-4) between 2016 and 2021 from 28 institutions in Japan. RESULTS: We identified 336 patients treated with BRAF/MEKi (n = 236), Anti-PD-1 (n = 64) and PD-1/CTLA-4 (n = 36). The median follow-up duration was 19.9 months for all patients and 28.6 months for the 184 pa tients who were alive at their last follow-up. For patients treated with BRAF/MEKi, anti-PD-1, PD-1/CTLA-4, the median ages at baseline were 62, 62, and 53 years (p = 0.03); objective response rates were 69%, 27%, and 28% (p < 0.001); median progression-free survival (PFS) was 14.7, 5.4, and 5.8 months (p = 0.003), and median overall survival (OS) was 34.6, 37.0 months, and not reached, respectively (p = 0.535). In multivariable analysis, hazard ratios (HRs) for PFS of Anti-PD-1 and PD-1/CTLA-4 compared with BRAF/MEKi were 2.30 (p < 0.001) and 1.38 (p = 0.147), and for OS, HRs were 1.37 (p = 0.111) and 0.56 (p = 0.075), respectively. In propensity-score matching, BRAF/MEKi showed a tendency for longer PFS and equivalent OS with PD-1/CTLA-4 (HRs for PD-1/CTLA-4 were 1.78 [p = 0.149]) and 1.03 [p = 0.953], respectively). For patients who received second-line treatment, BRAF/MEKi followed by PD-1/CTLA-4 showed poor survival outcomes. CONCLUSIONS: The superiority of PD-1/CTLA-4 over BRAF/MEKi appears modest in Asian patients. First-line BRAF/MEKi remains feasible, but it is difficult to salvage at progression. Ethnicity should be considered when selecting systemic therapies until personalized biomarkers are available in daily practice. Further studies are needed to establish the optimal treatment sequence for Asian patients.

Skeletal muscle atrophy and short-term mortality in patients with acute exacerbation of idiopathic pulmonary fibrosis: an observational cohort study.

BACKGROUND: Skeletal muscle atrophy, a common complication of idiopathic pulmonary fibrosis (IPF), and its presence upon diagnosis can indicate a poor prognosis. Patients with IPF frequently experience acute exacerbations (AE), which is associated with a high mortality rate. However, the association between skeletal muscle atrophy and short-term mortality remains unknown. METHODS: We performed a retrospective, multicenter cohort study of patients admitted for AE-IPF in Japan. The cross-sectional areas of the erector spinae muscle (ESMCSA) and the pectoralis muscle (PMCSA) were analyzed via single-slice computed tomography (CT). The primary outcome was 90-day mortality. Survival probability was estimated using the Kaplan-Meier method, and the log-rank test was used between the low and high groups of ESMCSA and PMCSA. We used multivariable Cox proportional-hazards models to evaluate the association between ESMCSA and PMCSA and prognosis. RESULTS: Of the 212 patients included, 94 (44%) died during the observation period. The low ESMCSA group (<25.6 cm2) had a significantly worse prognosis than that of the high ESMCSA group (≥25.6 cm2) (hazard ratio (HR) [95% confidence interval (CI)]: 1.52 [1.00-2.33], P = 0.049). Multivariable analyses showed that all-cause mortality was associated with low ESMCSA (model 1, adjusted HR [95% CI]: 1.59 [0.98-2.60]; model 2, 1.55 [0.95-2.56], and model 3, 1.67 [1.00-2.78], respectively). The adjusted HR of low PMCSA (<20.4 cm2) vs. high PMCSA (≥20.4 cm2) was 1.39 (95% CI: 0.88-2.20). CONCLUSIONS: Low ESMCSA on CT images is associated with a high 90-day mortality rate in patients with AE-IPF.

Association between intraoperative end-tidal carbon dioxide and postoperative organ dysfunction in major abdominal surgery: A cohort study.

BACKGROUND: Data on the effects of intraoperative end-tidal carbon dioxide (EtCO2) levels on postoperative organ dysfunction are limited. Thus, this study was designed to investigate the relationship between the intraoperative EtCO2 level and postoperative organ dysfunction in patients who underwent major abdominal surgery under general anesthesia. METHODS: We conducted a cohort study involving patients who underwent major abdominal surgery under general anesthesia at Kyoto University Hospital. We classified those with a mean EtCO2 of less than 35 mmHg as low EtCO2. The time effect was determined as the minutes when the EtCO2 value was below 35 mmHg, whereas the cumulative effect was evaluated by measuring the area below the 35-mmHg threshold. The outcome was postoperative organ dysfunction, defined as a composite of at least one organ dysfunction among acute renal injury, circulatory dysfunction, respiratory dysfunction, coagulation dysfunction, and liver dysfunction within 7 days after surgery. RESULTS: Of the 4,171 patients, 1,195 (28%) had low EtCO2, and 1,428 (34%) had postoperative organ dysfunction. An association was found between low EtCO2 and increased postoperative organ dysfunction (adjusted risk ratio, 1.11; 95% confidence interval [CI], 1.03-1.20; p = 0.006). Additionally, long-term exposure to EtCO2 values of less than 35 mmHg (≥224 min) was associated with postoperative organ dysfunction (adjusted risk ratio, 1.18; 95% CI, 1.06-1.32; p = 0.003) and low EtCO2 severity (area under the threshold) (adjusted risk ratio, 1.13; 95% CI, 1.02-1.26; p = 0.018). CONCLUSIONS: Intraoperative low EtCO2 of below 35 mmHg was associated with increased postoperative organ dysfunction.

Successful azacitidine therapy for myelodysplastic syndrome associated with VEXAS syndrome.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is caused by UBA1 somatic mutations and is characterized by late-onset systemic autoimmune inflammation and blood abnormalities such as cytopenia, vacuolation of myeloid/erythroblastic cells, and myelodysplastic syndrome (MDS). It is often resistant to immunosuppressive therapy, and no treatment strategy has been established. A 65-year-old man presented with palpable erythema, fever, macrocytic anemia, and arthralgia. He was subsequently diagnosed with MDS complicated by Sweet's disease. Treatment with azacitidine was initiated due to suspected skin invasion by MDS cells and resistance of the skin rash to steroid therapy. Next-generation sequencing of bone marrow samples prior to treatment initiation revealed the presence of UBA1 p.M41L (VAF 0.38) and DNMT3A p.L605fs mutations (VAF 0.184). Based on the findings of systemic inflammation, a diagnosis of VEXAS syndrome was made. The fever and skin rash improved with azacitidine therapy. In conclusion, somatic mutations in UBA1 should be explored in patients with MDS exhibiting systemic autoimmune inflammation. Furthermore, azacitidine may be a good treatment option for systemic autoinflammation in MDS associated with VEXAS syndrome.

Early corticosteroid dose tapering in patients with acute exacerbation of idiopathic pulmonary fibrosis.

BACKGROUND: Although corticosteroid therapy with dose tapering is the most commonly used treatment for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF), there is no consensus on the tapering regimen. This study aimed to investigate the association between early corticosteroid dose tapering and in-hospital mortality in patients with AE-IPF. METHODS: In this retrospective cohort study, we analyzed the data of a cohort from eight Japanese tertiary care hospitals and routinely collected administrative data from a cohort from 185 Japanese hospitals. Patients with AE-IPF were classified into the early and non-early tapering groups depending on whether the maintenance dose of corticosteroids was reduced within two weeks of admission. Propensity score analysis with inverse probability weighting (IPW) was performed to estimate the effect of early corticosteroid dose tapering. RESULTS: The multi-center cohort included 153 eligible patients, of whom 47 (31%) died, whereas the administrative cohort included 229 patients, of whom 51 (22%) died. Patients with early tapering tended to have a better prognosis than those without it (unadjusted hazard ratio [95% confidence interval] 0.41 [0.22-0.76] and 0.65 [0.36-1.18] in the multi-center and administrative cohorts, respectively). After IPW, the early tapering group had a better prognosis than the non-early tapering group (IPW-adjusted hazard ratio [95% confidence interval] 0.37 [0.14-0.99] and 0.27 [0.094-0.83] in the multi-center and administrative cohorts, respectively). CONCLUSION: Early corticosteroid dose tapering was associated with a favorable prognosis in patients with AE-IPF. Further studies are warranted to confirm the effects of early corticosteroid dose tapering in patients with AE-IPF.

Association between ICU admission during off-hours and in-hospital mortality: a multicenter registry in Japan.

BACKGROUND: The effect of ICU admission time on patient outcomes has been shown to be controversial in several studies from a number of countries. The imbalance between ICU staffing and medical resources during off-hours possibly influences the outcome for critically ill or injured patients. Here, we aimed to evaluate the association between ICU admission during off-hours and in-hospital mortality in Japan. METHODS: This study was an observational study using a multicenter registry (Japanese Intensive care PAtient Database). From the registry, we enrolled adult patients admitted to ICUs from April 2015 to March 2019. Patients with elective surgery, readmission to ICUs, or ICU admissions only for medical procedures were excluded. We compared in-hospital mortalities between ICU patients admitted during off-hours and office-hours, using a multilevel logistic regression model which allows for the random effect of each hospital. RESULTS: A total of 28,200 patients were enrolled with a median age of 71 years (interquartile range [IQR], 59 to 80). The median APACHE II score was 18 (IQR, 13 to 24) with no significant difference between patients admitted during off-hours and those admitted during office-hours. The in-hospital mortality was 3399/20,403 (16.7%) when admitted during off-hours and 1604/7797 (20.6%) when admitted during office-hours. Thus, off-hours ICU admission was associated with lower in-hospital mortality (adjusted odds ratio 0.91, [95% confidence interval, 0.84-0.99]). CONCLUSIONS: ICU admissions during off-hours were associated with lower in-hospital mortality in Japan. These results were against our expectations and raised some concerns for a possible imbalance between ICU staffing and workload during office-hours. Further studies with a sufficient dataset required for comparing with other countries are warranted in the future.

Enrichment of Cancer Cells Based on Antibody-Free Selective Cell Adhesion.

Blood-compatible and cell-adhering polymer materials are extremely useful for regenerative medicine and disease diagnosis. (Meth)acryl polymers with high hydrophilicity have been widely used in industries, and attempts to apply these polymers in the medical field are frequently reported. We focused on crosslinked polymer films prepared using bifunctional monomers, which are widely used as coating materials, and attempted to alter the cell adhesion behavior while maintaining blood compatibility by changing the chemical structure of the crosslinker. Four bifunctional monomers were studied, three of which were found to be blood-compatible polymers and to suppress platelet adhesion. The adhesion behavior of cancer cells to polymer films varied; moreover, the cancer model cells MCF-7 [EpCAM(+)] and MDA-MB-231 [EpCAM (-)], with different expression levels of epithelial cell adhesion molecule (EpCAM), showed distinct adhesion behavior for each material. We suggest that a combination of these materials has the potential to selectively capture and enrich highly metastatic cancer cells.

Low quality of life in men with chronic prostatitis-like symptoms.

BACKGROUND: Chronic prostatitis (CP) can impair health-related quality of life (QOL), but the full impact of CP, including the impact of CP-like symptoms in men who have no CP diagnosis (CPS), is unknown. We estimated the impact of diagnosed CP (DCP) and CPS on Health-related QOL. METHODS: From a representative nationwide survey of men aged 20-84 in Japan, we determined the prevalence of DCP and also of CPS. For CPS, we used Nickel's criteria, which were used previously to estimate the prevalence of CP and are based on the NIH Chronic Prostatitis Symptom Index. To test the robustness of Nickel's criteria, we used two other definitions of CPS (two sensitivity analyses). We measured QOL with the Short-Form 12-Item Health Survey. We compared the participants' QOL scores with the national-norm scores, and with the scores of men who had benign prostatic hyperplasia (BPH). RESULTS: Among the 5 010 participants, 1.4% had DCP and 3.7% had CPS. The sensitivity analyses resulted in CPS prevalence estimates of 3.1% and 4.5%. CPS was particularly common in younger participants (5.7% of those in their 30 s had CPS). QOL was very low among men with CP: In most areas (domains) of QOL, their scores were more than 0.5 standard deviation below the national-norm mean. Their mental-health scores were lower than those of men with BPH. The lowest scores among all 8 QOL domains were in role-functioning. CONCLUSIONS: CP is common, but it is underdiagnosed, particularly in younger men. Whether diagnosed or only suspected, CP's impact on QOL is large. Because CP is common, and because it substantially impairs individuals' QOL and can also reduce societal productivity, it requires more attention. Specifically, needed now is a simple tool for urologists and for primary care providers, to identify men, particularly young men, whose QOL is impaired by CP.

Development of healthy lifestyle consciousness index for gynecological cancer patients.

PURPOSE: Healthy lifestyle is related to quality of life (QOL) after cancer diagnosis and prognosis. However, there are few reports on patients conscious of healthy lifestyle and patients requiring medical providers' attention regarding healthy lifestyle. We aimed to develop a healthy lifestyle consciousness index (HLCI) for cancer patients and evaluated its validity in gynecological cancer patients. METHODS: The HLCI was designed to assess degree of healthy lifestyle consciousness, including items regarding "diet," "exercise," "body weight," and "sleep." Exploratory factor analysis was performed for dimensionality of the scale; Cronbach's alpha was calculated to assess internal-consistency reliability. For criterion-based validity, we calculated proportions of stage III/IV gynecological malignancies in those with categorized HLCI scores based on tertiles. Concurrent validity was evaluated between HLCI and other quality of life (QOL) scales including European Organization for Research and Treatment of Cancer QLQ-C30 in limited patients. RESULTS: HLCI comprised five 10-point items (0-45); higher values implied improved healthy lifestyle consciousness. Data from 108 gynecological malignancy patients at Kyoto University Hospital were analyzed. The mean age of subjects was 55.8 years; 36.1% of them had uterine corpus cancer; 34.3% were at stage III/IV of gynecological malignancy. The factor analysis revealed HLCI was unidimensional; the reliability based on Cronbach's alpha was satisfactory (0.88). The proportions of stage III/IV gynecological malignancies were 25.7%, 33.3%, and 44.4% in those with first (7-24 points), second (25-30 points), and third (31-46 points) tertiles of HLCI score, respectively. For patients with other QOL scales (n = 25), the mean scores of global health status of QLQ-C30 were 33.3, 50.0, and 83.3 for first, second, and third tertiles of HLCI score, respectively. CONCLUSION: HLCI was successfully validated; thus, patients with advanced stages or higher QOL might have strong consciousness regarding healthy lifestyle. HLCI may be useful in precision care for improved lifestyles and QOL.

Assessment of malignant melanoma lesions using violet-light dermoscopy: A case report.

Malignant melanomas often present with irregular shapes and in multiple shades of brown under white light. Dermoscopy is used to diagnose malignant melanomas; nevertheless, it is often difficult to differentiate malignant melanoma from healthy pigmented skin. The DZ-D100 dermoscope (Casio Computer) is a digital camera equipped with a white light-emitting diode (LED) and a violet LED, which can capture non-polarized/polarized conventional dermoscopy images (CDS) as well as violet-light dermoscopy (VLD) images. Since the absorption wavelength of melanin approaches that of ultraviolet rays, VLD with a wavelength of 405 nm can be used to visualize it. This camera allows three images with the same composition to be captured simultaneously. In this case, we performed dermoscopy with DZ-D100 to determine the surgical resection margins of a melanoma of the heel in a 76-year-old woman. The pale-colored lesions that were difficult to demarcate by CDS were clearly visible by VLD, presenting as dark areas in the grayscale images. Preoperatively determined lesion boundaries with CDS in combination with VLD were histologically more accurate than those with conventional CDS alone. Therefore, the combination of CDS and VLD may reveal the distribution of subtle pigmentation of fine melanin in the skin, making it easier to distinguish between lesions and healthy skin. As one of the limitations, parts of the heel with thick stratum corneum were also observed to be dark gray in the VLD images. Therefore, the evaluation of pigment lesion should be performed by comparing both CDS and VLD.

Association between intraoperative end-tidal carbon dioxide and postoperative nausea and vomiting in gynecologic laparoscopic surgery.

Gynecologic laparoscopic surgery has a high incidence of postoperative nausea and vomiting (PONV). Studies suggest that low intraoperative end-tidal carbon dioxide (EtCO2) is associated with an increased incidence of PONV, but the results have not been consistent among studies. This study investigated the association between intraoperative EtCO2 and PONV in patients undergoing gynecologic laparoscopic surgeries under general anesthesia. This retrospective cohort study involved patients who underwent gynecologic laparoscopic surgeries under general anesthesia at Kyoto University Hospital. We defined low EtCO2 as a mean EtCO2 of < 35 mmHg. Multivariable modified Poisson regression analysis examined the association between low EtCO2 and PONV during postoperative two days and the postoperative length of hospital stay (PLOS). Of the 739 patients, 120 (16%) had low EtCO2, and 430 (58%) developed PONV during postoperative two days. There was no substantial association between low EtCO2 and increased incidence of PONV (adjusted risk ratio: 0.96; 95% confidence interval [CI] 0.80-1.14; p = 0.658). Furthermore, there was no substantial association between low EtCO2 and prolonged PLOS (adjusted difference in PLOS: 0.13; 95% CI - 1.00 to 1.28; p = 0.816). Intraoperative low EtCO2, specifically a mean intraoperative EtCO2 below 35 mmHg, was not substantially associated with either increased incidence of PONV or prolonged PLOS.

Resting respiration rate predicts all-cause mortality in older outpatients.

BACKGROUND: Although respiratory rate has been a sensitive predictor for prognosis in acute settings, resting respiratory rate (RRR) is undervalued in chronic care. The clinical significance of RRR among older people is not well documented. AIM: We investigated the association between RRR and all-cause mortality among older outpatients. METHODS: A retrospective cohort study exhaustively included patients who had undergone medical checkups in a facility between April 2017 and March 2018 and followed up for at least 2 years. We excluded patients who were less than 60 years of age or had not undergone regular outpatient appointments. Sex, age, smoking habits, history of hospitalization, polypharmacy, long-term care insurance certification status, Mazzaglia index, pulse rate, systolic blood pressure, and Charlson Comorbidity Index were measured at the baseline medical checkup. Survival was confirmed by chart review and by contacting physicians in charge. The risk ratios were estimated by converting the odds ratios derived from the multivariable logistic regression models. RESULTS: Of the 853 patients who underwent baseline checkups, 749 were enrolled in the analyses; death occurred in 53 patients (7.1%), with no loss to follow-up. The RRR was independently associated with all-cause mortality after adjusting for covariates [adjusted risk ratio of RRR per 1 bpm = 1.14, 95% confidence interval (CI): 1.06 - 1.22]. DISCUSSION: Given the independent association of RRR for existing predictors, this simple index seems worthy of consideration in further studies aimed at defining its predictive role in older people and in different settings. CONCLUSION: RRR was independently associated with all-cause mortality.

Macrophage-inducible C-type lectin activates B cells to promote T cell reconstitution in heart allograft recipients.

Diminishing homeostatic proliferation of memory T cells is essential for improving the efficacy of lymphoablation in transplant recipients. Our previous studies in a mouse heart transplantation model established that B lymphocytes secreting proinflammatory cytokines are critical for T cell recovery after lymphoablation. The goal of the current study was to identify mediators of B cell activation following lymphoablation in allograft recipients. Transcriptome analysis revealed that macrophage-inducible C-type lectin (Mincle, Clec4e) expression is up-regulated in B cells from heart allograft recipients treated with murine anti-thymocyte globulin (mATG). Recipient Mincle deficiency diminishes B cell production of pro-inflammatory cytokines and impairs T lymphocyte reconstitution. Mixed bone marrow chimeras lacking Mincle only in B lymphocytes have similar defects in T cell recovery. Conversely, treatment with a synthetic Mincle ligand enhances T cell reconstitution after lymphoablation in non-transplanted mice. Treatment with agonistic CD40 mAb facilitates T cell reconstitution in CD4 T cell-depleted, but not in Mincle-deficient, recipients indicating that CD40 signaling induces T cell proliferation via a Mincle-dependent pathway. These findings are the first to identify an important function of B cell Mincle as a sensor of damage-associated molecular patterns released by the graft and demonstrate its role in clinically relevant settings of organ transplantation.

Lower effectiveness of intravenous steroid treatment for moderate-to-severe ulcerative colitis in hospitalised patients with older onset: a multicentre cohort study.

BACKGROUND: The increasing incidence of older-onset ulcerative colitis (UC), which has a higher risk of surgery, is a global health issue. However, data regarding intravenous steroid treatment, one of the important treatment options to avoid surgery, for older-onset UC is lacking. AIMS: To evaluate the association between onset age and effectiveness of intravenous steroids in UC. METHODS: This retrospective multicentre (27 facilities) cohort study included moderate-to-severe hospitalised UC patients who underwent their first intravenous steroids between April 2014 and July 2019. The primary outcome was clinical remission at day 30, using two-item patient-reported outcome scoring. The key secondary outcomes were risks of surgery and adverse events (death, infection and venous thrombosis) within 90 days. A modified Poisson regression model was used for analysis. RESULTS: Overall, 467 UC patients (384 younger-onset and 83 older-onset) were enrolled. Clinical remission at day 30 was observed in 252 (65.6%) among younger-onset patients and 43 (51.8%) among older-onset patients (adjusted risk difference, -21.7% [95% CI, -36.1% to -7.2%]; adjusted risk ratio [ARR], 0.74 [95% CI, 0.59 to 0.93]). The risks of surgery and adverse events were higher in older-onset UC (20.5% vs. 3.1%; ARR, 8.92 [95% CI, 4.13 to 19.27], 25.3% vs. 9.1%; ARR, 2.19 [95% CI, 1.22 to 3.92], respectively). Four deaths occurred, all involving older-onset UC. The risks of infection and venous thrombosis were also higher in older-onset UC (18.1% vs. 8.6%, 7.2% vs. 0.5%, respectively). CONCLUSIONS: Older-onset was associated with a lower effectiveness of intravenous steroids with higher risks of surgery and adverse events in UC.

Influence of anti-coronavirus disease 2019 policies on 10 pediatric infectious diseases.

BACKGROUND: To combat the coronavirus disease 2019 pandemic, many countries, including Japan, implemented policies limiting social activities and encouraging preventive behaviors. This study examines the influence of such policies on the trends of 10 infectious pediatric diseases: pharyngoconjunctival fever; group A streptococcal pharyngitis; infectious gastroenteritis; chickenpox; erythema infectiosum; hand, foot, and mouth disease; herpangina; respiratory syncytial virus; exanthem subitum; and mumps. METHODS: The research adopted a retrospective cohort study design. We collected data from Japan's National Epidemiological Surveillance Program detailing the incidences of the 10 diseases per pediatric sentinel site for a period beginning at 9 weeks before government-ordered school closures and ending at 9 weeks after the end of the state of emergency. We obtained corresponding data for the equivalent weeks in 2015-2019. We estimated the influence of the policies using a difference-in-differences regression model. RESULTS: For seven diseases (pharyngoconjunctival fever; group A streptococcal pharyngitis; infectious gastroenteritis; chickenpox; erythema infectiosum; hand, foot, and mouth disease; and herpangina), the incidence in 2020 decreased significantly during and after the school closures. Sensitivity analysis, in which the focus area was limited to the policy-implementation period or existing trend patterns, replicated these significant decreases for one of the above mentioned seven diseases - infectious gastroenteritis. CONCLUSIONS: Policies such as school closures and encouragement of preventive behaviors were associated with significant decreases in the incidences of most of the 10 diseases, which sensitivity analysis replicated in infectious gastroenteritis. To determine the long-term effects of these policies, prospective cohort studies are needed.

Association of occupational direct radiation exposure to the hands with longitudinal melanonychia and hand eczema in spine surgeons: a survey by the society for minimally invasive spinal treatment (MIST).

PURPOSE: To investigate the association between occupational direct radiation exposure to the hands and longitudinal melanonychia (LM) and hand eczema in spine surgeons. METHODS: A web-based questionnaire survey of the Society for Minimally Invasive Spinal Treatment (MIST) in Japan was conducted. The proportion of LM and hand eczema in hands with high and low-radiation exposure was compared using Fisher's exact test. The odds ratios (ORs) and their 95% confidence intervals (CIs) for the prevalence of LM and hand eczema in the high-radiation exposure hands were calculated using generalized estimating equations for logistic regression as control for the correlation of observations among the same individuals and possible confounders. RESULTS: Among 324 members of the society, responses were received from 229 members (70.7%). A total of 454 hands from 227 participants were analysed. The prevalence of LM and hand eczema was 43% and 29%, respectively. In a hand-by-hand comparison, more hands had LM in the high-radiation exposure group than the low-radiation exposure group (90 [40%] vs. 39 [17%], respectively, p < 0.001). A similar trend was observed for hand eczema (63 [28%] vs. 33 [15%], respectively, p = 0.001). The adjusted OR for high-radiation exposure hands was 3.18 (95% CI: 2.24-4.52). Consistent results were obtained for hand eczema, with an adjusted OR of 2.26 (95% CI: 1.67-3.06). CONCLUSION: The present study suggests that direct radiation exposure to physician's hands is associated with LM and hand eczema. Those with LM and radially biased hand eczema may have had high direct radiation exposure.

Intraoperative end-tidal carbon dioxide and postoperative mortality in major abdominal surgery: a historical cohort study.

PURPOSE: There is a paucity of data on the effect of intraoperative end-tidal carbon dioxide (EtCO2) levels on postoperative mortality. The purpose of this study was to investigate the relationship between intraoperative EtCO2 and 90-day mortality in patients undergoing major abdominal surgery under general anesthesia. METHODS: We conducted a historical cohort study of patients undergoing major abdominal surgery under general anesthesia at Kyoto University Hospital. We measured the intraoperative EtCO2, and patients with a mean EtCO2 value < 35 mm Hg were classified as low EtCO2. The time effect was determined based on minutes below an EtCO2 of 35 mm Hg, and cumulative effects were evaluated by measuring the area under the threshold of 35 mm Hg for each patient. RESULTS: Of 4,710 patients, 1,374 (29%) had low EtCO2 and 55 (1.2%) died within 90 days of surgery. Multivariable Cox regression analysis-adjusted for age, American Society of Anesthesiologists Physical Status classification, sex, laparoscopic surgery, emergency surgery, blood loss, mean arterial pressure, duration of surgery, type of surgery, and chronic obstructive pulmonary disease-revealed an association between low EtCO2 and 90-day mortality (adjusted hazard ratio, 2.2; 95% confidence interval [CI], 1.2 to 3.8; P = 0.006). In addition, severity of low EtCO2 was associated with an increased 90-day mortality (area under the threshold; adjusted hazard ratio; 2.9, 95% CI, 1.2 to 7.4; P =0.02); for long-term exposure to an EtCO2 < 35 mm Hg (≥ 226 min), the adjusted hazard ratio for increased 90-day mortality was 2.3 (95% CI, 0.9 to 6.0; P = 0.08). CONCLUSION: A mean intraoperative EtCO2 < 35 mm Hg was associated with increased postoperative 90-day mortality.

RéSUMé: OBJECTIF: Il n'existe que très peu de données s'intéressant à l'effet du niveau peropératoire télé-expiratoire du dioxyde de carbone (EtCO2) sur la mortalité postopératoire. L'objectif de cette étude était d'examiner la relation entre l'EtCO2 peropératoire et la mortalité à 90 jours chez des patients subissant une chirurgie abdominale majeure sous anesthésie générale. MéTHODE: Nous avons réalisé une étude de cohorte historique portant sur des patients subissant une chirurgie abdominale majeure sous anesthésie générale à l'Hôpital universitaire de Kyoto. Nous avons mesuré l'EtCO2 peropératoire, et les patients avec une valeur moyenne d'EtCO2 < 35 mmHg ont été catégorisés comme EtCO2 faible. L'effet temps a été déterminé en fonction de la durée, en minutes, avec une EtCO2 inférieure à 35 mmHg, et les effets cumulatifs ont été évalués en mesurant l'aire sous le seuil de 35 mmHg pour chaque patient. RéSULTATS: Sur 4710 patients, 1374 (29 %) avaient une EtCO2 faible et 55 (1,2 %) sont décédés dans les 90 jours suivant la chirurgie. Une analyse de régression multivariée de Cox, ajustée pour tenir compte des facteurs suivants : âge, statut physique selon l'American Society of Anesthesiologists, sexe, chirurgie par laparoscopie, chirurgie d'urgence, pertes de sang, tension artérielle moyenne, durée de la chirurgie, type de chirurgie et maladie pulmonaire obstructive chronique, a révélé une association entre une EtCO2 faible et la mortalité à 90 jours (rapport de risque ajusté, 2,2; intervalle de confiance [IC] à 95 %, 1,2 à 3,8; P = 0,006). De plus, la sévérité de l'EtCO2 basse était associée à une augmentation de la mortalité à 90 jours (aire sous le seuil; rapport de risque ajusté; 2,9, IC 95 %, 1,2 à 7,4; P =0,02); pour une exposition à long terme à une EtCO2 < 35 mmHg (≥ 226 minutes), le rapport de risque ajusté pour une mortalité accrue à 90 jours était de 2,3 (IC 95 %, 0,9 à 6,0 ; P = 0,08). CONCLUSION: Une EtCO2 peropératoire moyenne < 35 mmHg était associée à une augmentation de la mortalité postopératoire à 90 jours.