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Abstract Background A recent database study and meta-analysis reported that adjunctive glucocorticoid therapy reduces mortality in patients with non-human immunodeficiency virus-associated (non-HIV) Pneumocystis jirovecii pneumonia (PCP), having hypoxemia. However, the optimal glucocorticoid dose remains unclear. Our study aimed to evaluate the effectiveness of pulse methylprednisolone compared with mild-to-moderate steroid doses in patients with non-HIV PCP. Methods This multicentre retrospective cohort study included adults with non-HIV PCP receiving adjunctive steroids at three Japanese tertiary care hospitals from June 2006 to March 2021. Patients were categorised into pulse methylprednisolone and mild-to-moderate dose groups. Pulse methylprednisolone involved an initial intravenous infusion of 500–1000 mg methylprednisolone daily, while the mild-to-moderate dose was lower. Primary and secondary outcomes were 30-day and 180-day mortality from treatment initiation. Patient characteristics were adjusted using propensity score analysis with overlap weighting. Subgroup analysis focused on patients with respiratory failure. Results The study included 139 patients with non-HIV PCP: 55 in the pulse methylprednisolone group and 84 in the mild-to-moderate dose group. After adjusting for patient background, 30-day mortality (14.2% vs. 15.5%, P = 0.850) and 180-day mortality (33.5% vs. 27.3%, P = 0.516) did not differ significantly between groups. Subgroup analysis revealed no significant associations among patients with respiratory failure. Conclusions After adjusting for patient characteristics, no difference in prognosis was observed between pulse methylprednisolone and mild-to-moderate dose groups in patients with non-HIV PCP. A mild-to-moderate dose of adjunctive corticosteroid may suffice for treating non-HIV PCP.

Abstract Titin, a giant sarcomeric protein, regulates diastolic left ventricular (LV) passive stiffness as a molecular spring and could be a therapeutic target for diastolic dysfunction. Sacubitril/valsartan (Sac/Val), an angiotensin receptor neprilysin inhibitor, has been shown to benefit patients with heart failure with preserved ejection fraction. The effect of Sac/Val is thought to be due to the enhancement of the cGMP/PKG pathway via natriuretic peptide. In this study, the effects of Sac/Val on LV diastolic dysfunction are demonstrated in a mouse diabetic cardiomyopathy model focusing on titin phosphorylation. Sac/Val-treated diabetic mice showed a greater increase in myocardial levels of cGMP-PKG than Val-treated and control mice. Conductance catheter analysis showed a significant reduction in LV stiffness in diabetic mice, but not in non-diabetic mice. Notably, diastolic LV stiffness was significantly reduced in Sac/Val-treated diabetic hearts compared with Val-treated or vehicle-treated diabetic mice. The phosphorylation level of titin (N2B), which determines passive stiffness and modulates active contraction, was higher in Sac/Val-treated hearts compared with Val-treated hearts in diabetic mice. Given that alteration of titin phosphorylation through PKG contributes to myocardial stiffness, the beneficial effects of Sac/Val in heart failure might be partly attributed to the induction of titin phosphorylation.

Abstract Background The micro-axial flow pump Impella, a new mechanical circulatory device for cardiogenic shock, is still only available in a limited number of hospitals, due to the facility certification requirements and insufficient evidence of the benefit of introducing Impella in hospitals. This study aimed to evaluate the impact of introducing Impella in hospitals on in-hospital mortality of patients treated with extracorporeal membrane oxygenation (ECMO). Methods Using a nationwide Japanese inpatient database, we identified patients who received ECMO during hospitalization between 1 April 2014 and 31 March 2021. A hospital-level propensity score–matched cohort was created matching hospitals that introduced Impella (exposure group) to those that did not introduce Impella (control group). The inclusion period in each hospital was divided into two time periods according to the time of Impella introduction in the exposure group and the corresponding hospital in the control group (before and after exposure). The primary outcome was in-hospital mortality. Uncontrolled and controlled interrupted time-series analyses involved before–after exposure comparison and exposure–control comparison. Results Out of 34,379 eligible patients, we created a matched cohort of 8351 patients from 86 hospitals with Impella introduction (exposure group) and 7230 patients from 86 hospitals without Impella introduction (control group). In-hospital mortality before and after exposure was 62.5% and 59.3, respectively, in the exposure group; and 66.8% and 63.7%, respectively, in the control group. Uncontrolled interrupted time-series analysis showed no significant level change or trend change in the before–after exposure comparison in both the exposure and the control groups. Controlled interrupted time-series analysis also showed no significant level change (−0.01%; 95% confidence intervals −5.36% to + 5.33%) or trend change (+ 0.10%, −0.30% to + 0.40%) after exposure in the exposure–control comparison. Conclusions This nationwide inpatient database study showed no association between Impella introduction in hospitals and in-hospital mortality of patients who underwent ECMO. Because this study confined itself to analze of the impact of the introduction of Impella solely at the hospital level, further detailed studies are warranted to assess its efficacy at the patient level.

Abstract Atypical haemolytic uremic syndrome (aHUS) is a rare disorder characterised by complement-mediated thrombotic microangiopathy (TMA). Despite clinical guidelines, the diagnosis and treatment of aHUS in its early stages remains challenging. This study examined the annual trends in aHUS clinical practices in Japan and explored factors influencing early diagnosis and treatment. Using data from the 2011–2020 Diagnosis Procedure Combination database, 3096 cases with the HUS disease code were identified, of which 217 were confirmed as aHUS and treated with eculizumab or plasma exchange. Early initiation, defined as starting eculizumab or plasma exchange within 7 days of admission, was the focus of the study. Our study revealed no significant changes over time in the number of aHUS diagnoses, cases treated with eculizumab, or early initiation cases. Early initiation cases underwent haemodialysis earlier and had ADAMTS13 activity measured earlier, shorter hospital stays, and lower hospitalisation costs than late initiation cases. In conclusion, we found no increase in the number of newly diagnosed aHUS cases or early treatment initiation over time. Early recognition of TMA and differentiation of the causative disease are crucial for identifying potential aHUS cases, which may lead to better patient prognoses.

Background: Legionella pneumonia, a severe form of pneumonia, is caused by Legionella bacteria. The epidemiology of Legionnaires’ disease in Japan, including seasonal trends, risk factors for severe disease, and fatality rates, is unclear. This study examined the epidemiology of Legionella pneumonia in Japan. Methods: This retrospective cohort study included data of adult patients hospitalized for Legionella pneumonia (identified using the International Classification of Diseases, 10th revision code, A481) in the Japanese Diagnosis Procedure Combination inpatient database, from April 2011 to March 2021. We performed multivariable logistic regression analysis to explore the prognostic factors of in-hospital mortality. Results: Of 7,370 enrolled hospitalized patients from 1,140 hospitals (male, 84.4%; aged >50 years, 87.9%), 469 (6.4%) died during hospitalization. The number of hospitalized patients increased yearly, from 658 in 2016 to 975 in 2020. Multivariable logistic regression analysis revealed that higher in-hospital mortality was associated with older age, male sex, lower body mass index, worsened level of consciousness, comorbidities (congestive heart failure, chronic renal diseases, and metastasis), hospitalization from November to May, and ambulance use. However, lower in-hospital mortality was associated with comorbidity (liver diseases), hospitalization after 2013, and hospitalization in hospitals with higher case volume. Conclusion: The characterized epidemiology of Legionella pneumonia in Japan revealed a high mortality rate of 6.4%. To the best of our knowledge, this is the first study to demonstrate a higher mortality rate in winter and in patients with congestive heart failure and metastasis. Further research is needed to understand the complex interplay between the prognostic factors of Legionella pneumonia.

Abstract Background Fluid resuscitation is fundamental in acute pancreatitis (AP) treatment. However, the optimal choice between normal saline (NS) and Ringer's solution (RS), and its impact on mortality in critically ill patients, remains controversial. This retrospective cohort study, utilizing a national Japanese inpatient database, investigates this question. Methods Using the Japanese Diagnosis Procedure Combination database between July 2010 and March 2021, we identified adult patients hospitalized in intensive care units (ICU) or high-dependency care units (HDU) for AP who survived at least three days and received sufficient fluid resuscitation (≥ [10 ml/kg/hr*1 h + 1 ml/kg/hr*71 h] ml) within three days of admission including emergency room infusions. Patients were classified into groups based on the predominant fluid type received: the NS group (> 80% normal saline) and the RS group (> 80% Ringer's solution). Propensity score matching was employed to reduce potential confounding factors and facilitate a balanced comparison of in-hospital mortality between the two groups. Results Our analysis included 8710 patients with AP. Of these, 657 (7.5%) received predominantly NS, and 8053 (92.5%) received predominantly RS. Propensity score matching yielded 578 well-balanced pairs for comparison. The NS group demonstrated significantly higher in-hospital mortality than the RS group (12.8% [474/578] vs. 8.5% [49/578]; risk difference, 4.3%; 95% confidence interval, 0.3% to 8.3%). Conclusions In patients admitted to ICU or HDU with AP receiving adequate fluid resuscitation, RS can be a preferred infusion treatment compared to NS.

Abstract Background Patients who receive invasive mechanical ventilation (IMV) in the intensive care unit (ICU) have exhibited lower in-hospital mortality rates than those who are treated outside. However, the patient-, hospital-, and regional factors influencing the ICU admission of patients with IMV have not been quantitatively examined. Methods This retrospective cohort study used data from the nationwide Japanese inpatient administrative database and medical facility statistics. We included patients aged ≥ 15 years who underwent IMV between April 2018 and March 2019. The primary outcome was ICU admission on the day of IMV initiation. Multilevel logistic regression analyses incorporating patient-, hospital-, or regional-level variables were used to assess cluster effects by calculating the intraclass correlation coefficient (ICC), median odds ratio (MOR), and proportional change in variance (PCV). Results Among 83,346 eligible patients from 546 hospitals across 140 areas, 40.4% were treated in ICUs on their IMV start day. ICU admission rates varied widely between hospitals (median 0.7%, interquartile range 0–44.5%) and regions (median 28.7%, interquartile range 0.9–46.2%). Multilevel analyses revealed significant effects of hospital cluster (ICC 82.2% and MOR 41.4) and regional cluster (ICC 67.3% and MOR 12.0). Including patient-level variables did not change these ICCs and MORs, with a PCV of 2.3% and − 1.0%, respectively. Further adjustment for hospital- and regional-level variables decreased the ICC and MOR, with a PCV of 95.2% and 85.6%, respectively. Among the hospital- and regional-level variables, hospitals with ICU beds and regions with ICU beds had a statistically significant and strong association with ICU admission. Conclusions Our results revealed that primarily hospital and regional factors, rather than patient-related ones, opposed ICU admissions for patients with IMV. This has important implications for healthcare policymakers planning interventions for optimal ICU resource allocation.

Objectives Laboratory experiments have indicated that calcium channel blockers (CCBs) inhibit the entry and replication of influenza A virus in cells. However, no clinical studies have assessed the incidence of influenza among patients receiving CCBs. This study aimed to investigate the association between CCB use and the incidence of influenza among patients with hypertension using administrative claims data in Japan.Design Retrospective cohort study.Setting Administrative health insurance claims database of Kumamoto Prefecture, Japan.Participants 360 515 patients with hypertension (10th edition of the International Classification of Diseases code I10) who were prescribed CCBs and 171 142 patients who were prescribed angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) between 2012 and 2016.Primary outcome We compared the incidence of influenza between the CCB and ACEI/ARB groups using high-dimensional propensity-score (HD-PS) matching.Results A total of 166 814 HD-PS matched pairs were obtained. Before HD-PS matching, the CCB group had a significantly lower influenza incidence than the ACEI/ARB group in the overall analysis (2.4% vs 2.5%, p=0.007; risk ratio 0.95, 95% CI 0.92 to 0.99). However, no significant difference was observed between the two groups after HD-PS matching (2.4% vs 2.5%, p=0.067; risk ratio 0.96, 95% CI 0.92 to 1.00); only in 2012 did the CCB group have a significantly lower likelihood of influenza than the ACEI/ARB group.Conclusions No significant difference was observed in the influenza incidence between the CCB and ACEI/ARB groups. A direct comparative study between background-matched patients with and without CCBs is warranted to confirm the effect of CCBs on reducing the incidence of influenza.

Background: Although neonatal disseminated intravascular coagulation (DIC) is associated with high mortality and severe complications, few studies have reported its clinical course. We aimed to describe the characteristics, treatments, and outcomes of neonatal DIC by using a national inpatient database. Methods: Using the Japanese Diagnosis Procedure Combination database, we identified 5533 patients with neonatal DIC who were admitted to neonatal intensive care units between July 2010 and March 2020. We categorized the patients into those with asphyxia (n = 2911) and those without asphyxia (n = 2622). We investigated the patient characteristics, treatments, and outcomes. We further categorized neonates with asphyxia according to its severity. Results: The gestational age of neonates with asphyxia was significantly lower than that of neonates without asphyxia (P

Background Ectopic pregnancy (EP) can be treated surgically or nonsurgically. In many countries, methotrexate is frequently used as a first-line medical treatment, and its effect is similar to that of surgery in selected patients. We aimed to investigate national trends in the treatment of EP in Japan.Methods We conducted a retrospective observational analysis between 2010 and 2020 using a nationwide claims database that included inpatient data. We identified female inpatients with EP aged 15 to 49 years old. We analysed year-to-year treatment trends for EP, as well as year-to-year trends in methotrexate administration, with a focus on the site of the pregnancy. Patients who received methotrexate were divided into two groups: Those with and those without surgery after methotrexate use. We compared the characteristics of these groups and calculated the methotrexate success rate.Results We identified 53,653 patients with EP. The proportion of patients undergoing surgery increased from 79% in 2010 to 83% in 2020, whereas the proportion of methotrexate therapy decreased from 8.1% in 2010 to 5.1% in 2020. Regarding methotrexate use for the site of the pregnancy, there was a significant downward trend in methotrexate therapy for tubal pregnancies. Notably, the methotrexate success rate was 84% during the study period.Conclusions Surgery showed an increasing tendency over time, whereas methotrexate therapy showed a decreasing tendency for EP treatment in Japan. The efficacy of methotrexate in Japan was comparable to that observed in other countries.

Background The 2014 European Respiratory Society/American Thoracic Society guidelines defined severe asthma based on treatment intensity and estimated the proportion of severe asthma among all asthma cases to be 5–10%. However, data supporting the estimate and comprehensive and sequential data on asthma cases are scarce. We aimed to estimate the national prevalence and proportion of severe asthma during the last decade. Methods Using a Japanese national administrative database, which covers ≥99% of the population, we evaluated the prevalence and proportion of severe asthma in 2013, 2015, 2017 and 2019. Additionally, we elucidated the demographic characteristics, treatments and outcomes of patients with asthma. Results The national prevalence of mild–moderate and severe asthma in 2019 was 800 and 36 per 100 000 persons, respectively. While the prevalence of mild–moderate asthma remained almost constant in the study years, the prevalence of severe asthma decreased, resulting in a reduction in the proportion of severe asthma from 5.6% to 4.3%. Although treatment modalities have evolved, such as the increased use of combination inhalers and asthma biologics, approximately 15% of mild–moderate and 45% of severe asthma cases were still considered “uncontrolled”. The number of deaths from asthma decreased in patients with both mild–moderate and severe asthma. Conclusions This study revealed that the prevalence of severe asthma in Japan decreased during the study period and fell below 5% in the most recent data. Despite treatment evolution, a substantial proportion of patients with both mild–moderate and severe asthma still have poor asthma control.

Objectives: The effectiveness of monotherapy and combination therapy with quinolones and macrolides for treating Legionnaires’ disease remains uncertain; this study aimed to assess the comparative effectiveness of three treatment approaches. Methods: Using a nationwide inpatient database, we analyzed 3560 eligible patients hospitalized for Legionnaires’ disease between April 1, 2014, and March 31, 2021; patients were divided into combination therapy, quinolone monotherapy, and macrolide monotherapy groups according to the antibiotics administered within 2 days of admission. We compared in-hospital mortality, total hospitalization costs, and length of stay across these groups using multiple propensity score analysis with inverse probability of treatment weighting. Results: Of the 3560 patients, there were 564 (15.8%), 2221 (62.4%), and 775 (21.8%) patients in the combination therapy, quinolone monotherapy, and macrolide monotherapy groups, respectively. No significant differences were observed in in-hospital mortality between combination therapy and quinolone monotherapy groups, and between combination therapy and macrolide monotherapy groups. There were no significant differences in total hospitalization costs or length of stay among the three groups. Conclusion: The study suggests that there may not be a significant advantage in using a combination of quinolones and macrolides over monotherapy for the treatment of Legionnaires’ disease. Given the potential for increased side effects, careful consideration is advised when choosing this combination therapy.

Abstract Aim Postoperative ileus (POI) is a common complication after abdominal surgery. However, the risk factors for POI after laparoscopic colorectal resection are unclear. We therefore investigated the risk factors for POI after laparoscopic colorectal surgery. Methods This retrospective study involved 484 patients who underwent laparoscopic surgery for primary colorectal cancer at Hokkaido University Hospital. We categorized the patients into a POI group (n = 19) and non‐POI group (n = 465). We compared sex, age, smoking, chronic obstructive pulmonary disease (COPD), diabetes mellitus, body mass index (BMI), cardiac disorder, serum albumin, American Society of Anesthesiologists‐physical status, tumor location, tumor stage, operative duration, stoma formation, lymph node dissection, operator, and bleeding as potential risk factors for POI between the POI group and non‐POI group by univariate and multivariate analyses. Results The univariate analysis results showed that the POI group had a higher incidence of male sex (P = 0.036), COPD (P = 0.029), and a BMI of

Abstract Background Previous studies have reported conflicting results regarding fresh frozen plasma (FFP)-to-red blood cell (RBC) ratio and platelet-to-RBC ratio on outcomes for massive transfusion for trauma. Moreover, nationwide data on massive transfusion practices for trauma in the real-world clinical setting are scarce. This study aimed to examine the nationwide practice patterns and trends in massive transfusion for trauma in Japan using a national administrative, inpatient database. Method We identified patients who underwent emergency hospitalization for trauma and received massive transfusion, defined as administration of at least 20 units of RBC within the first 2 days of admission, using the nationwide inpatient database, which covers approximately 90% of all tertiary emergency hospitals in Japan, between 2011 and 2020. Trends in the incidence and practice patterns of massive transfusion were described by calendar year. The association of practice patterns with mortality or adverse events was tested. Results A total of 3,530,846 trauma hospitalizations were identified, of which 5247 (0.15%) received massive transfusion. A significant declining trend was observed in the incidence of massive transfusion in trauma hospitalizations from 0.24% in 2011 to 0.10% in 2020 (P for trend

Abstract The aim of this study was to compare in-hospital mortality of three procedures –halo-vest immobilization, anterior spinal fixation (ASF), and posterior spinal fixation (PSF)– in the treatment of elderly patients with isolated C2 odontoid fracture. We extracted data for elderly patients who were admitted with C2 odontoid fracture and treated with at least one of the three procedures (halo-vest immobilization, ASF, or PSF) during hospitalization. We conducted a generalized propensity score-based matching weight analysis to compare in-hospital mortality among the three procedures. We further investigated independent risk factors for in-hospital death. The study involved 891 patients (halo-vest, n = 463; ASF, n = 74; and PSF, n = 354) with a mean age of 78 years. In-hospital death occurred in 45 (5.1%) patients. Treatment type was not significantly associated with in-hospital mortality. Male sex (odds ratio 2.98; 95% confidence interval 1.32–6.73; p = 0.009) and a Charlson comorbidity index of ≥ 3 (odds ratio 9.18; 95% confidence interval 3.25–25.92; p

Abstract Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve heart failure (HF) outcomes across a range of patient characteristics. A hypothesis that SGLT2i induce metabolic change similar to fasting has recently been proposed to explain their profound clinical benefits. However, it remains unclear whether SGLT2i primarily induce this change in physiological settings. Here, we demonstrate that empagliflozin administration under ad libitum feeding did not cause weight loss but did increase transcripts of the key nutrient sensors, AMP-activated protein kinase and nicotinamide phosphoribosyltransferase, and the master regulator of mitochondrial gene expression, PGC-1α, in quadriceps muscle in healthy mice. Expression of these genes correlated with that of PPARα and PPARδ target genes related to mitochondrial metabolism and oxidative stress response, and also correlated with serum ketone body β-hydroxybutyrate. These results were not observed in the heart. Collectively, this study revealed that empagliflozin activates transcriptional programs critical for sensing and adaptation to nutrient availability intrinsic to skeletal muscle rather than the heart even in normocaloric condition. As activation of PGC-1α is sufficient for metabolic switch from fatigable, glycolytic metabolism toward fatigue-resistant, oxidative mechanism in skeletal muscle myofibers, our findings may partly explain the improvement of exercise tolerance in patients with HF receiving empagliflozin.

Abstract Background The prognosis for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is poor, and there is no established treatment. Hence, we aimed to investigate the effectiveness of a polymyxin B-immobilised fibre column (PMX) for the treatment of AE-IPF. Methods Data were retrospectively collected from the Japanese Diagnosis Procedure Combination database from 1 July 2010 to 31 March 2018. We identified adult patients with idiopathic pulmonary fibrosis who received high-dose methylprednisolone (mPSL) therapy and mechanical ventilation upon admission. Eligible patients (n = 5616) were divided into those receiving PMX treatment combined with high-dose mPSL (PMX group, n = 199) and high-dose mPSL alone (mPSL alone group, n = 5417). To compare outcomes between the two groups, we applied a stabilised inverse probability of treatment weighting (IPTW) using propensity scores. The primary outcome was in-hospital mortality, and the secondary outcomes were 14- and 28-day mortality and length of hospital stay. Results The in-hospital mortality rates of the PMX and mPSL alone groups were 79.9% and 76.4%, respectively. The results did not significantly differ between the two groups after performing a stabilised IPTW. The odds ratio of the PMX group compared with the mPSL alone group was 1.56 (95% confidence interval 0.80–3.06; p = 0.19). The 14- and 28-day mortality and length of hospital stay (secondary outcomes) also did not significantly differ between the two groups. Conclusions In AE-IPF patients using mechanical ventilation, the treatment outcome was not significantly better for PMX combined with high-dose mPSL than for high-dose mPSL alone.

Abstract Background Early-stage colorectal cancer (CRC) is often treated endoscopically, but additional surgical resection may be considered depending on pathological findings. Case presentation A 73-year-old man was found to have early-stage sigmoid colon cancer by colonoscopy during a medical examination, and endoscopic mucosal resection (EMR) was performed. The lesion was a 7-mm-sized sessile polyp, and the pathological diagnosis was well-differentiated tubular adenocarcinoma, pT1 (submucosal invasion of 400 μm), with no lymphovascular invasion, low budding grade, and negative horizontal and vertical margins. Therefore, the patient was observed without postoperative treatment. One year later, a computed tomography (CT) scan showed multiple liver metastases. After five courses of preoperative chemotherapy with folinic acid, 5-fluorouracil and oxaliplatin (FOLFOX) and panitumumab, liver metastases were reduced. The patient underwent extended right hepatic lobectomy. The pathological finding was well-to-moderately differentiated tubular adenocarcinoma, and immunohistochemistry findings were consistent with liver metastases from sigmoid colon cancer. Postoperatively, the patient received five courses adjuvant chemotherapy with FOLFOX. Although the patient had been recurrence-free for 5 years after liver resection, a CT scan revealed a nodular lesion in the sigmoid mesentery. Positron emission tomography (PET) showed abnormal accumulation in the same lesion. Therefore, the mesenteric nodules diagnosed as lymph metastasis and recurrence of sigmoid colon cancer and performed laparoscopic sigmoid colon resection with lymph node dissection. The pathological findings showed that the recurrent lesion in the mesentery formed a nodular infiltrate with venous, lymphatic, and neural invasion, but lymph node structures were not found, and it was assumed to be metastasis or recurrence due to lymphovascular invasion. The pathologic specimen of the sigmoid colon had no neoplastic lesions, which are considered to be a local recurrence on the mucosal surface. After sigmoid colectomy, adjuvant chemotherapy with CapeOX was conducted, and the patient has been recurrence-free for 13 months at present. Conclusion Even early-stage CRCs that have no pathological indications for additional resection have risks of metastases and recurrences, and we may need to consider that the criteria for additional resection should not be limited to pathological findings alone.

Abstract Background Pleural infection, an infection of the pleural space, is frequently treated with antibiotics and thoracic tube drainage. In case of insufficient drainage, an intrapleural fibrinolytic agent is considered before surgical intervention. However, the effectiveness of fibrinolytic monotherapy is still controversial. Therefore, we aimed to examine the association between urokinase monotherapy and treatment failure in patients with pleural infection. Methods In this retrospective observational study, patients with pleural infection underwent chest tube insertion were divided into two groups including patients treated with or without intrapleural instillation of urokinase. The propensity score overlap weighting was used to balance the baseline characteristics between the groups. Treatment failure was defined by the composite primary outcome of in-hospital death and referral for surgery. Results Among the 94 patients, 67 and 27 patients were in the urokinase and non-urokinase groups, respectively. Urokinase monotherapy improved the composite outcome between the groups (19.4% vs. 48.1%, p = 0.01). After adjusting using propensity score overlap weighting, urokinase monotherapy improved the composite outcome compared to the non-urokinase group (19.0% vs. 59.5%, p = 0.003). Conclusions Urokinase monotherapy can be an important nonsurgical treatment option for patients with pleural infection. Trial registration The participants were retrospectively registered.

Abstract Background Hepatorenal syndrome (HRS) is a life-threatening complication of end-stage liver disease. This study aimed to clarify the status of HRS in Japan by analyzing the Japanese Diagnosis Procedure Combination database. Methods Patients hospitalized for cirrhosis and HRS from July 2010 to March 2019 were sampled. They were divided into two groups according to their prognosis upon discharge: the transplant-free survival group and the death or liver transplantation group. The two groups’ baseline patient characteristics and treatments were compared. Results The mean age of the 1,412 participants was 67.3 years (standard deviation: 12.3 years), and 65.4% were male. The Child–Pugh grades was B and C in 18.8% and 81.2%, respectively. Hepatocellular carcinoma was present in 27.1% of the patients, and the proportion of spontaneous bacterial peritonitis was 2.3%. Albumin, noradrenaline, and dopamine were administered to 57.9%, 8.0%, and 14.9% of the patients, respectively; 7.0% of the patients underwent renal replacement therapy; and 5.0% were admitted to the intensive care unit. Intravenous antibiotics were administered to 30.8% of the patients. A total of 925 patients (65.5%) died or underwent liver transplantation. In addition to a higher proportion of patients with poor baseline liver function, the death or liver transplantation group included more males, patients with hepatocellular carcinoma, and those with spontaneous bacterial peritonitis. Conclusions HRS in Japan has a high mortality rate. Albumin was administered to over 50% of participants. Although noradrenaline is recommended in Japanese clinical guidelines, dopamine was more frequently used as a vasoconstrictor in clinical practice.

IntroductionProprioceptive function declines with age, leading to falls, pain, and difficulties in performing activities of daily living among older adults. Although individuals with low back pain (LBP) exhibit decreased lumbosacral proprioception in various postures, the mechanism by which reduced proprioceptive function causes LBP remains uncertain. Vibratory stimulation may enhance proprioceptive function; however, its efficacy in treating LBP has not been investigated. Thus, we investigated the feasibility of improving proprioceptive function and its effect on alleviating chronic LBP in older patients through targeted vibratory therapy (TVT) administration.MethodsThis single arm designed trial included older patients aged >65 years with non-specific chronic LBP. TVT involved applying vibratory stimulation, matching the frequency of dysfunctional receptors, for 1 min daily over 14 days to activate proprioceptors; patients performed TVT three times daily at home. In cases of reduced proprioceptive function at multiple sites, TVT was aimed at the lowest frequency band value. LBP and proprioceptive function were evaluated at 2 weeks after TVT and at 2 weeks after the end of TVT in patients with declined proprioception in the trunk or lower extremities.ResultsOverall, 56 patients with chronic LBP were enrolled; 32 patients were recruited for treatment based on a proprioceptive dysfunction diagnosis and 24 patients were recruited with a normal diagnosis with no significant differences observed between the two sets of patients in sarcopenia-related factors and clinical proprioception-related characteristics. No patient had any adverse events. Two weeks after TVT, the numerical pain rating scale score improved to ConclusionsTVT demonstrated efficacy in improving proprioception and alleviating LBP in older patients with impaired proprioceptive function without affecting non-targeted proprioceptors.

Living-donor lobar lung transplantation (LDLLT) is a well-established surgical procedure with favorable outcomes; however, the frequency of readmission and costs in LDLLT are poorly understood. Here, we aimed to compare health care costs and readmissions at 90 days and 1 year after the index discharge in LDLLT and cadaveric lung transplantation (CLT) and evaluate the reasons for readmission and in-hospital mortality. In this retrospective cohort study, we used the Diagnosis Procedure Combination database, a nationwide inpatient database in Japan to obtain initial lung transplantation data for all patients from July 2010 to March 2020. Multivariable Poisson or multiple regression analyses after multiple imputation was performed to compare the cumulative number of readmissions and costs between patients receiving LDLLT and CLT. Among 514 recipients, 115 (22%) underwent LDLLT and 399 (78%) received CLT. Overall, in-hospital mortality after transplantation was 4.5%. The LDLLT group showed a significantly lower crude readmission rate (90 days, 22% vs 37%, p = 0.004; 1 year, 48% vs 62%, p = 0.031) and median readmission cost (90 days, United States dollar (USD) 0 vs 0, p = 0.003; 1 year, USD 1178 vs 4714, p = 0.005) than the CLT group. Multivariable regression analyses showed that the LDLLT group had a lower risk of readmission (incidence rate ratio, 0.59; 95% confidence interval, 0.38-0.92; p = 0.020) and lower costs at 90 days (difference, USD −11,629; 95% confidence interval, −5682 to −17,462; p

Abstract Background Acute kidney injury and chronic kidney disease (CKD) after cardiac surgery are associated with poor renal prognosis and increased mortality. The impact of intraoperative hemodialysis (IHD) on postoperative renal function remains unknown. We aimed to evaluate the utility of IHD during open-heart surgery in patients with severe non-dialysis-dependent chronic kidney disease (CKD-NDD) and its association with clinical outcomes. Methods This was a single-center retrospective cohort study that employed IHD during non-emergency open-heart surgery in patients with CKD stage G4 or G5. Patients who underwent emergent surgery, chronic dialysis, and/or kidney transplantation were excluded. We retrospectively compared the clinical characteristics and outcomes between patients from the IHD and non-IHD groups. The primary outcomes were 90-day mortality and postoperative initiation of renal replacement therapy (RRT). Results Twenty-eight patients were categorized into the IHD group and 33 into the non-IHD group. When comparing the IHD and non-IHD groups, men accounted for 60.7 vs. 50.3% of patients, the mean patient age was 74.5 (standard deviation [SD] 7.0) vs. 72.9 (SD 9.4) years (p = 0.744), and the proportion of patients with CKD G4 was 67.9 vs. 84.9% (p = 0.138). Regarding clinical outcomes, no significant differences were observed in the 90-day mortality (7.1 vs. 3.0%; p = 0.482) and 30-day RRT (17.9 vs. 30.3%; p = 0.373) rates between the groups. Among the patients with CKD G4, the IHD group had significantly lower 30-day RRT rates than the non-IHD group (0 vs. 25.0%; p = 0.032). RRT initiation was less likely for patients with CKD G4 (odds ratio 0.07, 95% confidence interval [CI] 0.01–0.37; p = 0.002); however, IHD did not significantly decrease the incidence of poor clinical outcomes (odds ratio 0.20, 95% CI 0.04–1.07; p = 0.061). Conclusions IHD during open-heart surgery in patients with CKD-NDD did not improve their clinical outcomes with regards to postoperative dialysis. However, for patients with CKD G4, IHD may be useful for postoperative cardiac management.

Abstract Background Children with community-acquired septic shock can rapidly deteriorate and die in acute-care hospitals. This study aimed to describe the mortality, timing, and risk factors in children with community-acquired septic shock. Methods This is a retrospective cohort study using a national inpatient database in Japan. The study population included children (age

Abstract Background Current guidelines recommend systemic thrombolysis as the first-line reperfusion treatment for patients with high-risk pulmonary embolism (PE) who present with cardiogenic shock but do not require venoarterial extracorporeal membrane oxygenation (VA-ECMO). However, little is known about the optimal reperfusion treatment in high-risk PE patients requiring VA-ECMO. We aimed to evaluate whether systemic thrombolysis improved high-risk PE patients’ outcomes who received VA-ECMO. Methods This was a retrospective cohort study using the Japanese Diagnosis Procedure Combination inpatient database from July 2010 to March 2021. We identified patients who were diagnosed with PE and received VA-ECMO on the day of admission. Patients who received systemic thrombolysis with monteplase or urokinase within two days of initiating VA-ECMO were defined as the thrombolysis group and the remaining patients as the control group. The primary outcome was in-hospital mortality and secondary outcomes were favorable neurological outcomes, length of hospital stay, VA-ECMO duration, total hospitalization cost, major bleeding, and blood transfusion volume. Propensity-score inverse probability of treatment weighting (IPTW) was performed to compare the outcomes between the groups. Results Of 1220 eligible patients, 432 (35%) received systemic thrombolysis within two days of initiating VA-ECMO. Among the unweighted cohort, patients in the thrombolysis group were less likely to have poor consciousness at admission, out-of-hospital cardiac arrest, and left heart catheterization. After IPTW, the patient characteristics were well-balanced between the two groups The crude in-hospital mortality was 52% in the thrombolysis group and 61% in the control group. After IPTW, in-hospital mortality did not differ significantly between the two groups (risk difference: − 3.0%, 95% confidence interval: − 9.6% to 3.5%). There were also no significant differences in the secondary outcomes. Sensitivity analyses showed a significant difference in major bleeding between the monteplase and control groups (risk difference: 6.9%, 95% confidence interval: 1.7% to 12.1%), excluding patients who received urokinase. There were no significant differences in the other sensitivity and subgroup analyses except for the total hospitalization cost. Conclusions Systemic thrombolysis was not associated with reduced in-hospital mortality or increased major bleeding in the high-risk PE patients receiving VA-ECMO. However, systemic thrombolysis with monteplase was associated with increased major bleeding.

Background: The guidelines for the requirement of Legionella urinary antigen tests on admission for patients hospitalized with community-acquired pneumonia differ in Japan, the United States, and Europe. We aimed to evaluate the association between the timing of Legionella urinary antigen testing and inhospital mortality in patients with atypical pneumonia. Methods: We identified 654,708 patients with atypical pneumonia from July 2010 to March 2021 using the Japanese national inpatient database. The patients were divided into groups that underwent Legionella urinary antigen tests on the day of admission (test group, n = 229,649) and those that underwent testing after the day of admission or were untested (control group, n = 425,059). A propensity score-stabilized inverse probability of treatment weighting analysis was performed to compare inhospital mortality, length of hospital stay, and total hospitalization costs between the two groups. Odds ratios (ORs) or differences and their 95% confidence intervals (CIs) were calculated using generalized linear models. Results: The tested group had a significantly lower 30-day inhospital mortality than that of the control group (7.7% vs. 9.0%; OR: 0.83 [95% CIs, 0.81–0.86]). The tested group also had a significantly shorter length of stay (difference, −2.3 [−2.6 to − 2.0] days and total hospitalization costs (−396 [−508 to − 285] US dollars) than that of the control group. Conclusions: Legionella urinary antigen testing upon admission is associated with better outcomes in patients with atypical pneumonia. Legionella urinary antigen testing performed on the day of admission is recommended for hospitalized patients with atypical pneumonia.

Abstract Background An increasing number of studies are evaluating the safety of intravenous sedation compared with that of general anesthesia; however, data on bleeding complications after pediatric percutaneous renal biopsy performed under intravenous sedation or general anesthesia are lacking. We aimed to examine differences in bleeding complications between intravenous sedation and general anesthesia in pediatric patients. Methods Data of pediatric patients aged ≤ 15 years undergoing percutaneous kidney biopsy for kidney disease between July 2007 and March 2019 were retrieved from a national inpatient database in Japan. We examined differences in bleeding complications after renal biopsy performed under intravenous sedation, defined by the absence of the record of general anesthesia with intubation but by the presence of intravenous sedation during biopsy, and general anesthesia, defined by the presence of the record of general anesthesia with intubation during biopsy, among pediatric patients admitted for percutaneous renal biopsy. We performed binomial regression using overlap weights based on propensity scores for patients receiving intravenous sedation. Analyses stratified by age or sex, a sensitivity analysis using generalized estimating equations considering cluster effects by hospital among a propensity score-matched cohort, and another sensitivity analysis using the instrumental variable method were performed to confirm the robustness of the results. Results We identified 6,560 biopsies performed in 5,999 children aged 1–15 years from 328 hospitals and 178 events. Only three severe complications and no death were observed. No significant difference in the proportion of bleeding complications was observed between procedures performed under intravenous sedation and those performed under general anesthesia (unadjusted proportions, 2.8% and 2.3%; adjusted proportions, 2.5% and 2.2%), with an unadjusted relative risk of 1.21 (95% confidence interval, 0.80–1.81) and adjusted relative risk of 1.13 (95% confidence interval, 0.74–1.73). Both age- and sex-stratified analyses yielded similar results. The analysis using generalized estimating equation and the instrumental variable method showed relative risks of 0.95 (95% confidence interval, 0.48–1.88) and 1.18 (95% confidence interval, 0.74–1.89), respectively. Conclusion This retrospective cohort study using a national database revealed that the risk of biopsy-related bleeding was comparable between intravenous sedation and general anesthesia during pediatric percutaneous kidney biopsy, suggesting that intravenous sedation alone and general anesthesia may have a similar bleeding risk in pediatric percutaneous kidney biopsies.

Introduction: Recent studies have shown worse post-operative outcomes following several surgeries in underweight or obese patients. However, the association between body mass index (BMI) and short-term outcomes following thyroid cancer surgery remains unclear because of the small number of patients, deficit s in background data known as risk factors (e.g. cancer stage, operative procedure, intraoperative device use and hospital volume) and categorisation of BMI. Methods: We identified patients who underwent thyroidectomy for different iated thyroid cancer from July 2010 to March 2017 using a Japanese nationwide inpatient database. We used restricted cubic spline (RCS) analyses to investigate potential non-linear associations between BMI (without categorisation) and outcomes: post-operative complications (local and general), duration of anaesthesia, post-operative length of hospital stay and hospitalisation costs. The analyses were adjusted for demographic and clinical backgrounds including the above-stated factors. We also performed multivariable regression analyses for the outcomes with categorisation of BMI. Results: Among 59,671 eligible patients, the median BMI was 22.9 kg/m2 (interquartile range (IQR), 20.7–25.6 kg/m2). In total, 3860 patients (6.5%) had local complications and 787 patients (1.3%) had general complications. Although the re were no significant associations with local complications, such as bleeding, recurrent laryngeal nerve paralysis and surgical site infection, the occurrence of general complications was significantly associated with higher BMI. BMI showed a linear as sociation with the duration of anaesthesia and U-shaped associations with post-operative length of stay and hospitalisation costs. The lowest points of the U-shaped curves occurred at a BMI of approximately 24 kg/m2. The multivariate regression analyses showed consistent results with the RCS analyses.

Background: Detailed data on intensive care unit (ICU) occupancy in Japan are lacking. Using a nationwide inpatient database in Japan, we aimed to assess ICU bed occupancy to guide critical care utilization planning. Methods: We identified all ICU patients admitted from January 1, 2015 to December 31, 2018 to ICU-equipped hospitals participating in the Japanese Diagnosis Procedure Combination inpatient database. We assessed the trends in daily occupancy by counting the total number of occupied ICU beds on a given day divided by the total number of licensed ICU beds in the participating hospitals. We also assessed ICU occupancy for patients with mechanical ventilation, patients with extracorporeal membrane oxygenation, and patients without life-supportive therapies. Results: Over the 4 study years, 1,379,618 ICU patients were admitted to 495 hospitals equipped with 5,341 ICU beds, accounting for 75% of all ICU beds in Japan. Mean ICU occupancy on any given day was 60%, with a range of 45.0% to 72.5%. Mean ICU occupancy did not change over the 4 years. Mean ICU occupancy was about 9% higher on weekdays than on weekends and about 5% higher in the coldest season than in the warmest season. For patients with mechanical ventilation, patients with extracorporeal membrane oxygenation, and patients without life-supportive therapies, mean ICU occupancy was 24%, 0.5%, and 30%, respectively. Conclusion: Only one-fourth of ICU beds were occupied by mechanically ventilated patients, suggesting that the critical care system in Japan has substantial surge capacity under normal temporal variation to care for critically ill patients.

Abstract Background The coronavirus disease 2019 (COVID-19) pandemic has disrupted critical care services worldwide. Examining how critical care systems responded to the COVID-19 pandemic on a national level will be useful in setting future critical care plans. The present study aimed to describe the utilization of critical care services before and during the COVID-19 pandemic using a nationwide Japanese inpatient administrative database. Methods All patients admitted to an intensive care unit (ICU) or a high-dependency care unit (HDU) from February 9, 2019, to February 8, 2021, in the Japanese Diagnosis Procedure Combination inpatient database were included. February 9, 2020, was used as the breakpoint separating the periods before and during COVID-19 pandemic. Hospital and patient characteristics were compared before and during the COVID-19 pandemic. Change in ICU and HDU bed occupancy before and during the COVID-19 pandemic was evaluated using interrupted time-series analysis. Results The number of ICU patients before and during the COVID-19 pandemic was 297,679 and 277,799, respectively, and the number of HDU patients was 408,005 and 384,647, respectively. In the participating hospitals (383 ICU-equipped hospitals and 460 HDU-equipped hospitals), the number of hospitals which increased the ICU and HDU beds capacity were 14 (3.7%) and 33 (7.2%), respectively. Patient characteristics and outcomes in ICU and HDU were similar before and during the COVID-19 pandemic except main etiology for admission of COVID-19. The mean ICU bed occupancy before and during the COVID-19 pandemic was 51.5% and 47.5%, respectively. The interrupted time-series analysis showed a downward level change in ICU bed occupancy during the COVID-19 pandemic (− 4.29%, 95% confidence intervals − 5.69 to − 2.88%), and HDU bed occupancy showed similar trends. Of 383 hospitals with ICUs, 232 (60.6%) treated COVID-19 patients in their ICUs. Their annual hospital case volume of COVID-19 ICU patients varied greatly, with a median of 10 (interquartile range 3–25, min 1, max 444). Conclusions The ICU and HDU bed capacity did not increase while their bed occupancy decreased during the COVID-19 pandemic in Japan. There was no change in clinicians’ decision-making to forego ICU/HDU care for selected patients, and there was no progress in the centralization of critically ill COVID-19 patients.

Objectives: This study aim to evaluate the effectiveness of fluoroquinolone (FQ) antimicrobial therapy in combination with tetracyclines (TCs) in patients with Japanese spotted fever (JSF) using a nationwide inpatient database in Japan.Methods: We identified hospitalized patients diagnosed with JSF who were enrolled in the Japanese Diagnosis Procedure Combination inpatient database from July 2010 to March 2021. Patients who received FQ plus TC on the day of admission were compared with patients who received TC alone on the day of admission, using inverse probability of treatment weighting. The primary outcome was in-hospital mortality. Secondary outcomes were in-hospital complications, total hospitalization costs, and length of hospital stay.Results: We identified 1060 eligible patients. Of these, 434 (41%) received FQ plus TC on the day of admission and 626 (59%) received TC alone on the day of admission. Inverse probability of treatment weighting showed no statistically significant differences between the groups in in-hospital mortality, in-hospital complications, total hospitalization costs, and length of hospital stay.Conclusion: This study did not show any significantly improved effectiveness using FQ antimicrobials in combination with TCs for treating JSF. Clinicians may need to be cautious in administering FQ and TC antimicrobials concomitantly in routine practice.

Proprioception is a deep sensation that perceives the position of each part of the body, state of movement and muscle contraction, and resistance and mass applied to the body. Proprioceptive feedback influences movement and positional accuracy, resulting in key somatosensory functions for human postural control. Proprioception encompasses signals received from proprioceptors located in the skin, subcutaneous tissue, muscles, tendons, and joint capsules, commonly known as mechanoreceptors. The muscle spindle, a crucial proprioceptor, is stretched during eccentric contraction of muscle, thus generating an action potential on afferent fibers to convey a proprioceptive information to the sensorimotor cortex in the brain. For exercise therapy in patients with locomotor disease, proprioception serves an essential function for motor control; thus, this should be considered to obtain effective muscle output. As postural control is achieved by proprioceptive function according to the balance between the lower limb and trunk, relative proprioceptive weighting ratio can help clarify proprioceptive control using muscle response to mechanical vibration. The absence of proprioceptive information congruent with motor intention activates cortical center monitoring incongruence of sensation, leading to pathological pain. Therapeutic procedures may aim to restore the integrity of cortical information processing in musculoskeletal chronic pain. Poor proprioception is one of the main causes of decreased postural balance control in elderly patients with low back pain (LBP). It has been hypothesized that proprioception of the lower limbs deteriorates with age-related muscle mass loss (sarcopenia), which increases the proprioceptive burden on the lumbar spine. Accurate diagnosis of the proprioceptive function is important for establishing a treatment procedure for proprioceptive recovery, and further prospective research is required to clarify the relationship between proprioception and LBP improvement.

Abstract Background Pleural infection is an infection of the pleural space that is usually treated with antibiotics and source control. Chest tube insertion is the most popular and widely used drainage technique. We typically attempt to place the tube at the bottom of the thoracic cavity to consider the effects of gravity; however, the effectiveness of this practice is not well-defined. Therefore, we aimed to examine whether the position of the tip of the thoracic tube affects treatment failure in patients with pleural infection. Methods In this retrospective observational study, patients with pleural infection who underwent thoracic tube insertion were divided into two groups: those with the tip of the tube positioned below the 10th thoracic vertebra at the level of the diaphragm (lower position group) and those with the tip placed above the 9th thoracic vertebra (upper position group). We compared whether the position of the tube tip affected treatment failure. Stabilized inverse probability treatment weights (SIPTW) were used to balance the baseline characteristics between the groups. Treatment failure showed a composite outcome of hospital death, referral to surgeons for surgery, and additional chest tube insertion. Results Among the 87 patients, 41 and 46 patients were in the lower and upper groups, respectively. No significant difference was observed in the composite outcomes between the groups (46.3% vs. 54.3%, P = 0.596). There was also no significant difference in the composite outcome between both groups after adjusting for SIPTW (52.3% vs. 68.8%, P = 0.286). Conclusions There were no significant differences in the treatment failure in this study addressing pleural infection treatment, in which the drain tip position was stratified by the 9th and 10th thoracic vertebrae. The position of the tip of the thoracic tube may not be important for pleural infection treatment providing that it is in the thoracic cavity. Trial registration The participants were registered retrospectively.

Background: Psoriasis is a known risk factor for acute myocardial infarction (AMI). However, the associations between psoriasis and short-term outcomes of AMI remain controversial. Objective: To compare the short-term outcomes of AMI patients with and without psoriasis accounting for patient background characteristics and site-specific effects. Methods: We identified patients with AMI between July 2010 and March 2020, using a Japanese national inpatient database. We matched patients with and without psoriasis to generate a 1:10 matched-pair cohort matched for sex, hospital, and fiscal year at admission. Multivariable regression analyses with adjustment for background characteristics including age and Killip class at admission were conducted to compare short-term outcomes of AMI. Results: In this study of AMI patients with psoriasis (n = 455) and without psoriasis (n = 438,534), 30-day in-hospital mortality was 5.6%. Patients with psoriasis had higher proportions of comorbidities than patients without psoriasis. Multivariable regression analyses in the matched-pair cohort revealed that psoriasis was significantly associated with decreased 30-day in-hospital mortality (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.08-0.85). Limitations: Retrospective study design without data on psoriasis severity. Conclusion: The matched-pair cohort analyses with adjustment for patient background characteristics and site-specific effects revealed decreased in-hospital mortality in AMI patients with psoriasis.

Objectives: The prevalence of chronic pain increases with age. It has been reported that chronic pain is associated with sarcopenia and obesity. Age-related skeletal muscle loss and fat gain are known to occur due to chronic inflammation. The aim of this study was to analyze how skeletal muscle and fat, caused by chronic inflammation due to aging, regulate the development of geriatric chronic pain. Methods: The results of skeletal muscle and fat mass, 412 participants aged ≥65 years with non-specific chronic pain lasting ≥6 months, including low back, neck, and knee pain, was compared with the control without chronic pain. Body composition threshold regulating chronic pain was calculated. Results: A significantly lower skeletal muscle mass index and higher body fat percentage were observed in patients with chronic pain than that in the control. The muscle fat ratio (MFR) was significantly lower in the chronic pain group than in the control group. When the MFR threshold related to chronic pain was calculated by sex, it was 2.984 for men and 1.867 for women. Conclusions: Evaluation of the body composition of elderly patients with non-specific chronic pain revealed that the MFR was useful as an index related to chronic pain.

Background The impact of major changes in the treatment practice of pulmonary embolism (PE), such as limited indications for systemic thrombolysis and the introduction of direct oral anticoagulants, is not well documented. This study aimed to describe annual trends in the treatment patterns and outcomes in patients with PE. Methods and Results Using the Japanese Diagnosis Procedure Combination inpatient database from April 2010 to March 2021, we identified hospitalized patients with PE. Patients with high‐risk PE were defined as those admitted for out‐of‐hospital cardiac arrest or who received cardiopulmonary resuscitation, extracorporeal membrane oxygenation, vasopressors, or invasive mechanical ventilation on the day of admission. The remaining patients were defined as patients with non–high‐risk PE. The patient characteristics and outcomes were reported with fiscal year trend analyses. Of 88 966 eligible patients, 8116 (9.1%) had high‐risk PE, and the remaining 80 850 (90.9%) had non–high‐risk PE. Between 2010 and 2020, in patients with high‐risk PE, the annual proportion of extracorporeal membrane oxygenation use significantly increased from 11.0% to 21.3%, whereas that of thrombolysis use significantly decreased from 22.5% to 15.5% (P for trend

Abstract Aim Although major complication rates following percutaneous liver biopsy (PLB) have been reported to be higher in children than in adults, scarce data are available regarding pediatric patients stratified by native and transplanted liver. We aimed to assess the factors associated with major complications after percutaneous biopsy of native or transplanted liver using a nationwide inpatient database. Methods Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified pediatric patients who underwent PLB between 2010 and 2018. We described major complication rates and analyzed factors associated with major complications following PLB, stratified by native and transplanted liver. Results We identified 3584 pediatric PLBs among 1732 patients from 239 hospitals throughout Japan during the study period, including 1310 in the native liver and 2274 in the transplanted liver. Major complications following PLB were observed in 0.5% (n = 18) of the total cases; PLB in the transplanted liver had major complications less frequently than those in the native liver (0.2% vs. 1.0%, p = 0.002). The occurrence of major complications was associated with younger age, liver cancers, unscheduled admission, anemia or coagulation disorders in cases with native liver, while it was associated with younger age alone in cases with transplanted liver. Conclusions The present study, using a nationwide database, found that major complications occurred more frequently in pediatric cases with native liver and identified several factors associated with its major complications.

Abstract Objectives In July 2017, supplementary guidelines on anticoagulants, including direct oral anticoagulants, were published in Japan. We investigated the changes in endoscopic submucosal dissection (ESD) of gastric mucosal lesions after the publication of the supplement, examined the risk factors, and developed a predictive model for post‐ESD bleeding. Methods We included 2272 gastric ESD cases from our hospital between May 2003 and June 2021 and classified them into two groups: 1789 cases before and 483 after the publication of the supplementary guidelines. A predictive model for post‐ESD bleeding was developed using the pre‐publication cohort data. Results The proportion of patients receiving warfarin decreased (5.0% vs. 1.4%) and those receiving direct oral anticoagulants increased (1.2% vs. 6.8%) after the publication of the supplementary guidelines. Post‐ESD bleeding occurred in 61 patients, but there was no significant difference in the bleeding rate between the groups (50 [2.8%] vs. 11 [2.3%] patients, respectively). Five risk factors (number of antithrombotic agents, dialysis, heparin replacement, resection specimen size, and procedure time) were identified for model development. The C‐statistic for the model and post‐publication cohorts were 0.83 and 0.72, respectively. In the model, each risk factor for postoperative bleeding was scored, and the risk was classified into three levels according to the total score. Bleeding rates at low, intermediate, and high risks were 1.6%, 10.3%, and 38.9%, respectively. Conclusion Despite changes in patient characteristics and clinical practice regarding ESD before and after the publication of the supplementary guidelines, we could still develop a simple and useful predictive model.

Abstract Ketone body β-hydroxybutyrate (βOHB) and fibroblast growth factor-21 (FGF21) have been proposed to mediate systemic metabolic response to fasting. However, it remains elusive about the signaling elicited by ketone and FGF21 in the heart. Stimulation of neonatal rat cardiomyocytes with βOHB and FGF21 induced peroxisome proliferator-activated receptor α (PPARα) and PGC1α expression along with the phosphorylation of LKB1 and AMPK. βOHB and FGF21 induced transcription of peroxisome proliferator-activated receptor response element (PPRE)-containing genes through an activation of PPARα. Additionally, βOHB and FGF21 induced the expression of Nrf2, a master regulator for oxidative stress response, and catalase and Ucp2 genes. We evaluated the oxidative stress response gene expression after 24 h fast in global Fgf21-null (Fgf21−/−) mice, cardiomyocyte-specific FGF21-null (cmFgf21−/−) mice, wild-type (WT), and Fgf21fl/fl littermates. Fgf21−/− mice but not cmFgf21−/− mice had unexpectedly higher serum βOHB levels, and higher expression levels of PPARα and oxidative stress response genes than WT mice or Fgf21fl/fl littermates. Notably, expression levels of oxidative stress response genes were significantly correlated with serum βOHB and PGC1α levels in both WT and Fgf21−/− mice. These findings suggest that fasting-induced βOHB and circulating FGF21 coordinately regulate oxidative stress response gene expression in the heart.

Abstract Recently, the Lorentzian path integral formulation using the Picard–Lefschetz theory has attracted much attention in quantum cosmology. In this paper, we analyze the tunneling amplitude in quantum mechanics by using the Lorentzian Picard–Lefschetz formulation and compare it with the WKB analysis of the conventional Schrödinger equation. We show that the Picard–Lefschetz Lorentzian formulation is consistent with the WKB approximation for wave-function and the Euclidean path integral formulation utilizing the solutions of the Euclidean constraint equation. We also consider some problems of this Lorentzian Picard–Lefschetz formulation and discuss a simpler semiclassical approximation of the Lorentzian path integral without integrating the lapse function.

Abstract Background Whether an oxaliplatin- or cisplatin-based regimen is more optimal for treating elderly patients with advanced gastric cancer, in terms of survival and adverse events remains unclear. Methods In this retrospective cohort study, we used stacked claim data of residents in two Japanese prefectures collected between 2012 and 2017 and between 2014 and 2019, respectively. We included patients with advanced gastric cancer who received oxaliplatin-based and cisplatin-based regimens. Propensity score overlap weighting analysis was conducted to compare overall survival and granulocyte colony-stimulating factor use during chemotherapy between the oxaliplatin- and cisplatin-based treatment groups. Results A total of 242 patients were included in the study. After propensity score weighting, Kaplan–Meier analysis showed no significant differences in overall survival between the two groups (hazard ratio: 1.13; 95% confidence interval, 0.60–2.11; p = 0.70). However, the proportion of patients receiving granulocyte colony-stimulating factor was significantly lower in the oxaliplatin group than in the cisplatin group (2.3% vs.22.7%, p = 0.01). Conclusions Survival did not differ significantly between elderly patients with advanced gastric cancer treated with oxaliplatin-based versus cisplatin-based regimens; however, the oxaliplatin-based regimen was associated with less granulocyte colony-stimulating factor use.

Abstract Background Although numerous studies have investigated out-of-hospital cardiac arrest, few studies have been conducted on in-hospital cardiac arrest (IHCA). Knowledge of the nationwide epidemiology of IHCA in Japan, with its super-aging society, is important to understand the current situation of IHCA and to establish evidenced-based medicine in the future. The present study aimed to determine the incidence and outcomes of IHCA and their trends in Japan. Methods This observational cohort study was performed using a national administrative inpatient database for more than 1600 acute-care hospitals covering about 50% of all acute-care hospital beds in Japan from April 2011 to March 2018. We defined cardiac arrest patients who received cardiopulmonary resuscitation (chest compression) during hospitalization as IHCA. We excluded out-of-hospital cardiac arrest patients from the source population. The incidence of IHCA per 1000 hospital admissions and survival to discharge rate was reported with trend analyses by calendar year 2011–2017. Results Among 53,871,101 hospitalized patients without out-of-hospital cardiac arrest patients in 1626 hospitals, 2,136,038 (4.0%) had cardiac arrest. Of them, 274,664 (12.9%) received cardiopulmonary resuscitation at least once during hospitalization and were identified as IHCA, and 1,861,374 (87.1%) did not receive cardiopulmonary resuscitation. The incidence of IHCA per 1000 hospital admissions was 5.1, with a significant decreasing trend from 6.1 in 2011 to 4.6 in 2017 (P for trend = 0.033). Our estimated incidence can be translated to approximately 87,000 IHCA cases in Japan each year. The percentage of IHCA patients among cardiac arrest patients was 12.9%, with a significant decreasing trend from 14.0% in 2011 to 12.2% in 2017 (P for trend = 0.006). The overall rate of survival to discharge was 12.7%, with a significant increasing trend from 10.5% in 2011 to 14.0% in 2017 (P for trend

Abstract Background Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is the leading cause of death among patients with IPF. However, there is no established treatment for this condition. Hence, we aimed to investigate the effectiveness and safety of recombinant human soluble thrombomodulin (rTM) for the treatment of AE-IPF. Methods Data were retrospectively collected from the Japanese Diagnosis Procedure Combination database from 1 January 2014 to 31 March 2018. We identified adult patients with IPF who received high-dose methylprednisolone (mPSL) therapy and mechanical ventilation upon admission. Eligible patients (n = 2814) were divided into those receiving high-dose mPSL alone (mPSL alone group, n = 2602) and rTM combined with high-dose mPSL (rTM group, n = 212). A stabilised inverse probability of treatment weighting (IPTW) using propensity scores was performed to compare outcomes between the two groups. The primary outcome was in-hospital mortality, and the secondary outcomes were 14- and 28-day mortality, bleeding events and length of hospital stay. Results The in-hospital mortality rates of the mPSL alone and rTM groups were 75.9% and 76.9%, respectively. The results did not significantly differ between the two groups after performing a stabilised IPTW. The odds ratio of the rTM group compared to the mPSL alone group was 1.15 (95% confidence interval: 0.71–1.84; p = 0.57). Moreover, the secondary outcomes did not differ significantly between the two groups. Conclusions In patients with AE-IPF who developed severe respiratory failure, rTM in addition to high-dose mPSL was not associated with a better outcome.

Introduction: Nephrologists have recently recognized the heterogeneity of kidney diseases among patients with diabetes and begun to actively perform percutaneous renal biopsies (PRBs). Nevertheless, the association between diabetes and major bleeding complications of PRB remains unclear. Methods: In this retrospective cohort study using the Diagnosis Procedure Combination database in Japan, we identified patients who underwent an elective PRB from July 2010 to March 2018. The primary outcome was the occurrence of major bleeding complications, defined as red blood cell transfusion within 7 days after PRB or invasive hemostasis after PRB. Multivariable regression analysis was performed to analyze the association between diabetes and major bleeding complications with adjustment for patient and hospital characteristics. Results: We identified 76,302 patients, including 8245 with diabetes. The proportion of PRBs performed for patients with diabetes continuously increased over time. Major bleeding complications occurred in 678 patients (0.9%), including 622 (0.8%) with red blood cell (RBC) transfusion and 109 (0.1%) with invasive hemostasis. Diabetes was significantly associated with major bleeding complications (relative risk [RR] = 2.41; 95% CI 2.00–2.90). Among patients with diabetes, multiagent or insulin treatment had significant association with major bleeding complications (RR = 1.57; 95% CI 1.18–2.10), compared with single-agent diabetes treatment. Conclusion: Diabetes is significantly associated with major bleeding complications of PRBs. Moreover, severity of diabetes has association with increases in major bleeding complications. Thus, nephrologists should carefully judge whether the anticipated benefits outweigh the relatively high risk of major bleeding complications when considering PRB for patients with diabetes.

Background: Japan’s historically low immigration rate and monolingual culture makes it a particularly interesting setting for clarifying non-national medical care. Our study objective was to examine disease patterns and outcome differences between Japanese and non-Japanese patients in a rapidly globalizing nation. Methods: A secondary data analysis of 325 non-Japanese and 13,370 Japanese patients requiring tertiary care or intensive-care unit or high-care unit admission to the emergency department at the Tokyo Medical and Dental University medical hospital from 2010 through 2019 was conducted. Multivariable linear and logistic regressions models were applied to examine differences in percentage of diagnosis, mortality rates, and length of stay, stratified by Glasgow Coma Scale (GCS) scores to consider the impact of language barriers. Sex and age were adjusted. Results: Non-Japanese patients had more anaphylaxis, burns, and infectious disease, but less cardiovascular diagnoses prior to adjustment. After adjustment, there were significantly more anaphylaxis (adjusted odds ratio [aOR] 2.7; 95% confidence interval [CI], 1.7–4.4) and infectious disease diagnoses (aOR 2.2; 95% CI, 1.3–3.7), and marginally more burn diagnoses (aOR 2.3; 95% CI, 0.96–5.3) than Japanese patients. Regardless of GCS scores, there were no significant differences between non-Japanese and Japanese patient length of stay for anaphylaxis, burn, and infectious disease after covariate adjustment. Conclusion: There were more non-Japanese patients diagnosed with anaphylaxis, burns, and infectious disease, but no notable patient care differences for length of stay. Further prevention efforts are needed against anaphylaxis, burns, and infectious disease for non-Japanese tourists or residents.

Abstract Background Community-acquired pneumonia (CAP) is the most common cause of acute respiratory distress syndrome (ARDS). Although previous studies have suggested that macrolide therapy is beneficial for ARDS, its benefit for severe CAP-associated ARDS remains uncertain. Previous studies were limited in that they had a small sample size and included patients with non-pulmonary ARDS and those with pulmonary ARDS. This study aimed to investigate the additional effect of azithromycin when used with β-lactam compared with the effect of β-lactam alone in mechanically ventilated patients with CAP-associated ARDS. Methods We identified mechanically ventilated patients with CAP-associated ARDS between July 2010 and March 2015 using data in the Diagnosis Procedure Combination database, a Japanese nationwide inpatient database. We performed propensity score matching analysis to assess 28-day mortality and in-hospital mortality in mechanically ventilated patients with CAP-associated ARDS who received β-lactam with and without azithromycin within hospital 2 days after admission. The inverse probability of treatment weighting analysis was also conducted. Results Eligible patients (n = 1257) were divided into the azithromycin group (n = 226) and the control group (n = 1031). The one-to-four propensity score matching analysis included 139 azithromycin users and 556 non-users. No significant difference was observed between the groups with respect to 28-day mortality (34.5% vs. 37.6%, p = 0.556) or in-hospital mortality (46.0% vs. 49.1%, p = 0.569). The inverse probability of treatment weighting analysis showed similar results. Conclusions Compared with treatment with β-lactam alone, treatment with azithromycin plus β-lactam had no significant additional effect on 28-day mortality or in-hospital mortality in mechanically ventilated patients with CAP-associated ARDS. To the best of our knowledge, this study is the first to determine the effect of azithromycin in mechanically ventilated patients with CAP-associated ARDS.

Abstract A comprehensive analysis of clinical information in patients with chronic low back pain (CLBP) was performed to clarify the clinical characteristics of geriatric LBP from the perspective of body composition, spinal alignment, and blood findings related to senescence. We enrolled 203 patients with an average age of 79.0 years (77 men and 126 women), with non-specific CLBP as a single-center prospective cohort study, the patients were compared with age- and sex-matched controls without CLBP using a propensity score-matching. We performed laboratory analysis, radiographic evaluations for global spinal parameter and lumbar degeneration, and body composition analysis using whole-body dual-energy X-ray absorptiometry. We observed a higher red blood cell distribution width (RDW) (p

Background and study aims Despite the widespread use of direct oral anticoagulants (DOACs), the association between DOAC use and complications (e. g., bleeding) following gastrointestinal endoscopic biopsy remains unclear. This study aimed to evaluate complications after biopsy in patients treated with DOACs in Japan, where biopsies would be generally performed without DOAC withdrawal based on guideline recommendations. Patients and methods Using a Japanese nationwide database, we identified patients taking DOACs who underwent gastrointestinal endoscopic biopsy (n = 2,769, DOAC group) and those not taking DOACs (n = 129,357, control group) from April 2015 to November 2020. We conducted 1:4 propensity score (PS) matching and overlap PS-weighting analyses with adjustment for background characteristics to compare occurrence of post-procedure hemorrhage and stroke within 1 week after biopsy, and thrombin use on the day of biopsy without a diagnosis of hemorrhage. Results In total, 578 patients (0.44 %) developed post-procedure hemorrhage, and 13 patients (0.01 %) developed stroke. The DOAC group had more comorbidities than the control group. The PS matching analysis revealed no significant differences in post-procedure hemorrhage (odds ratio, 1.52 [95 % confidential interval, 0.96–2.41]) or stroke (1.00 [0.21–4.71]), whereas the DOAC group received thrombin more often than the control group (1.60 [1.30–1.95]). The results were equivalent in the overlap PS-weighting analysis. Conclusions The PS analyses showed no significant differences in complications following gastrointestinal endoscopic biopsy between DOAC users and non-users. These results suggest the safety of endoscopic biopsy without DOAC withdrawal although the need for careful hemostasis remains.