Cardiac Reoperation or Transcatheter Mitral Valve Replacement for Patients With Failed Mitral Prostheses.

BACKGROUND: Evidence is limited regarding patient outcomes comparing redo surgical mitral valve replacement (redo SMVR) vs transcatheter mitral valve replacement (TMVR) for failed prostheses. OBJECTIVES: The goal of this study was to compare the outcomes of redo SMVR vs TMVR in patients with failed prostheses, as well as evaluate the association between case volume and outcomes. METHODS: Medicare beneficiaries aged ≥65 years who underwent redo SMVR or TMVR for failed mitral prostheses between 2016 and 2020 were included. The primary endpoint was mid-term (up to 3 years) major adverse cardiovascular events (MACE), including all-cause death, heart failure rehospitalization, stroke, or reintervention. Propensity score-matched analysis was used. RESULTS: A total of 4,293 patients were included (redo SMVR: 64%; TMVR: 36%). TMVR recipients were older, with a higher comorbidity burden. In matched cohort (n = 1,317 in each group), mid-term risk of MACE was similar (adjusted HR: 0.92; 95% CI: 0.80-1.04; P = 0.2). However, landmark analysis revealed a lower risk of MACE with TMVR in the first 6 months (adjusted HR: 0.75; 95% CI: 0.63-0.88; P < 0.001) albeit with a higher risk beyond 6 months (adjusted HR: 1.28; 95% CI: 1.04-1.58; P = 0.02). Increasing procedural volume was associated with decreased risk of mid-term MACE after redo SMVR (P = 0.001) but not after TMVR (P = 0.3). CONCLUSIONS: In this large cohort of Medicare beneficiaries with failed mitral prostheses, outcomes were similar between redo SMVR and TMVR at 3 years, with TMVR showing a lower initial risk but a higher risk of MACE after 6 months. These findings highlight the importance of striking a balance between surgical risk, anticipated longevity, and hospital expertise when selecting interventions.

Patient characteristics and procedural and safety outcomes of percutaneous transesophageal gastro-tubing: A nationwide database study in Japan.

BACKGROUND: Percutaneous transesophageal gastro-tubing (PTEG) is an alternative interventional procedure in cases where gastrostomy is not feasible. However, the safety and complication rates of PTEG have not yet been evaluated. We aimed to describe the characteristics of patients who underwent PTEG and investigate complications using a nationwide Japanese inpatient database. METHODS: In this retrospective cohort study, we used the Diagnosis Procedure Combination database in Japan to identify patients who underwent PTEG from April 2012 to March 2020. The outcomes were the occurrence of complications, invasive treatment within 7 days after PTEG, and tube replacement within 14 days after PTEG. We statistically compared patient background, complication rates, and outcomes using PTEG indications. RESULTS: A total of 3,684 patients underwent PTEG, which was performed in 1,455 patients for decompression and 2,193 patients for feeding. The patients' mean age was 73.1 years, and 62.1% were men. More patients in the decompression group had cancer than those in the feeding group. The overall number of complications was 47 cases (1.3%). The most common treatment administered after PTEG was red blood cell transfusion (3.9%), followed by early tube replacement (3.3%). As invasive treatments for PTEG complications, percutaneous drainage and transcatheter arterial embolization were required in 4 and 1 cases, respectively, and no cases required surgery. CONCLUSION: We performed a descriptive study on PTEG using a nationwide database in Japan. This study also showed a low complication rate after PTEG in the real world. Our findings provide practical information on the safety of PTEG in Japan.

Long-Term Outcomes After Hybrid Coronary Revascularization Versus Coronary Artery Bypass Grafting: Meta-Analysis of Kaplan-Meier-Derived Data.

Hybrid coronary revascularization (HCR) is an alternative option to conventional coronary artery bypass grafting (CABG), but the long-term outcomes of HCR versus CABG remain unclear. We aimed to analyze the long-term outcomes after HCR and CABG for patients with multivessel coronary artery disease using meta-analysis. A systemic literature search of PubMed and EMBASE was performed from inception to March 2023. Studies reporting Kaplan-Meier curves with follow-up ≥1 year were included. The primary outcome was all-cause mortality, and the secondary outcomes were major adverse cardiac and cerebrovascular events (MACCEs) and repeat revascularization. In total, 13 studies (1 randomized controlled trial and 12 propensity-score matched observational studies) were analyzed. The mean follow-up period was 5.1 ± 3.1 years. HCR was associated with similar overall mortality (hazard ratio [HR] 1.09, 95% confidence interval [CI] 0.87 to 1.36), significantly higher incidence of MACCEs (HR 1.49, 95% CI 1.07 to 2.06), and repeat revascularization (HR 2.01, 95% CI 1.53 to 2.64) compared with CABG. In phase-specific analysis, the mortality rate was similar, and the incidence of repeat revascularization was higher in HCR regardless of phases. The incidence of MACCEs was higher in HCR during the mid-term phase (1 to 5 years), but it was similar during the long-term phase (long-term: ≥5 years). In conclusion, despite the higher incidence of MACCEs and repeat revascularization compared with CABG, HCR offered a similar long-term survival. Even longer-term follow-up and randomized controlled trials with a large population are warranted to investigate the role of HCR for multivessel coronary artery disease.

Risk Factors Amenable to Primary Prevention of Type 2 Diabetes Among Disaggregated Racial and Ethnic Subgroups in the U.S.

OBJECTIVE: Race and ethnicity data disaggregated into detailed subgroups may reveal pronounced heterogeneity in diabetes risk factors. We therefore used disaggregated data to examine the prevalence of type 2 diabetes risk factors related to lifestyle behaviors and barriers to preventive care among adults in the U.S. RESEARCH DESIGN AND METHODS: We conducted a pooled cross-sectional study of 3,437,640 adults aged ≥18 years in the U.S. without diagnosed diabetes from the Behavioral Risk Factor Surveillance System (2013-2021). For self-reported race and ethnicity, the following categories were included: Hispanic (Cuban, Mexican, Puerto Rican, Other Hispanic), non-Hispanic (NH) American Indian/Alaska Native, NH Asian (Chinese, Filipino, Indian, Japanese, Korean, Vietnamese, Other Asian), NH Black, NH Pacific Islander (Guamanian/Chamorro, Native Hawaiian, Samoan, Other Pacific Islander), NH White, NH Multiracial, NH Other. Risk factors included current smoking, hypertension, overweight or obesity, physical inactivity, being uninsured, not having a primary care doctor, health care cost concerns, and no physical exam in the past 12 months. RESULTS: Prevalence of hypertension, lifestyle factors, and barriers to preventive care showed substantial heterogeneity among both aggregated, self-identified racial and ethnic groups and disaggregated subgroups. For example, the prevalence of overweight or obesity ranged from 50.8% (95% CI 49.1-52.5) among Chinese adults to 79.8% (73.5-84.9) among Samoan adults. Prevalence of being uninsured among Hispanic subgroups ranged from 11.4% (10.9-11.9) among Puerto Rican adults to 33.0% (32.5-33.5) among Mexican adults. CONCLUSIONS: These findings underscore the importance of using disaggregated race and ethnicity data to accurately characterize disparities in type 2 diabetes risk factors and access to care.

Different Roles of Functional and Structural Renal Markers Measured at Discontinuation of Renal Replacement Therapy for Acute Kidney Injury.

INTRODUCTION: Severe acute kidney injury (AKI) requiring renal replacement therapy (RRT) has been associated with an unacceptably high mortality of 50% or more. Successful discontinuation of RRT is thought to be linked to better outcomes. Although functional and structural renal markers have been evaluated in AKI, little is known about their roles in predicting outcomes at the time of RRT discontinuation. METHODS: In this prospective single-center cohort study, we analyzed patients who received continuous RRT (CRRT) for AKI between August 2016 and March 2018 in the intensive care unit of the University of Tokyo Hospital (Tokyo, Japan). Clinical parameters and urine samples were obtained at CRRT discontinuation. Successful CRRT discontinuation was defined as neither resuming CRRT for 48 h nor receiving intermittent hemodialysis for 7 days from the CRRT termination. Major adverse kidney events (MAKEs) were defined as death, requirement for dialysis, or a decrease in the estimated glomerular filtration rate (eGFR) of more than 25% from the baseline at day 90. RESULTS: Of 73 patients, who received CRRT for AKI, 59 successfully discontinued CRRT and 14 could not. Kinetic eGFR, urine volume, urinary neutrophil gelatinase-associated lipocalin (NGAL), and urinary L-type fatty acid binding protein were predictive for CRRT discontinuation. Of these factors, urine volume had the highest area under the curve (AUC) 0.91 with 95% confidence interval [0.80-0.96] for successful CRRT discontinuation. For predicting MAKEs at day 90, the urinary NGAL showed the highest AUC 0.76 [0.62-0.86], whereas kinetic eGFR and urine volume failed to show statistical significance (AUC 0.49 [0.35-0.63] and AUC 0.59 [0.44-0.73], respectively). CONCLUSIONS: Our prospective study confirmed that urine volume, a functional renal marker, predicted successful discontinuation of RRT and that urinary NGAL, a structural renal marker, predicted long-term renal outcomes. These observations suggest that the functional and structural renal makers play different roles in predicting the outcomes of severe AKI requiring RRT.

Gender Differences in Long-Term Outcomes of Young Patients Who Underwent Percutaneous Coronary Intervention: Long-Term Outcome Analysis from a Multicenter Registry in Japan.

Young patients who underwent percutaneous coronary intervention (PCI) have shown worse long-term outcomes but remain inadequately investigated. We analyzed 1,186 consecutive young patients (aged ≤55 years) from the Keio Cardiovascular PCI registry who were successfully discharged after PCI (2008 to 2019) and compared them to 5,048 older patients (aged 55 to 75 years). The primary outcome was a composite of all-cause death, acute coronary syndrome, heart failure, bleeding, stroke requiring admission, and coronary artery bypass grafting within 2 years after discharge. In the young patients, the mean age was 48.4 ± 5.4 years, acute coronary syndrome cases accounted for 69.6%, and 92 (7.8%) were female. Body mass index; hemoglobin levels; and proportions of smoking, hyperlipidemia, and ST-elevation myocardial infarction were lower and dialysis or active cancer proportions were higher in young female patients than male patients. A higher number of young female than male patients reached the primary end point and all-cause death (15.2% vs 7.1%, p = 0.01; 4.3% vs 1.0%, p = 0.023), mainly because of noncardiac death (4.3% versus 0.5%, p = 0.001). After covariate adjustment, the primary end point rates were higher among young women than men (hazard ratio 2.00, 95% confidence interval 1.03 to 3.89, p = 0.042). Gender did not predict the primary end point among older patients (vs men; hazard ratio 0.84, 95% confidence interval 0.67 to 1.06, p = 0.14). In conclusion, young women showed worse outcomes during the 2-year post-PCI follow-up, but this gender difference was absent in patients aged 55 to 75 years.

Impact of a financial incentive scheme for team-based palliative care in patients with heart failure in Japan: A nationwide database study.

BACKGROUND: Palliative care provided to patients with heart failure (HF) are reported to be inadequate. Herein, we examined the impact of the recently introduced financial incentive scheme for team-based palliative care for patients with HF in acute care hospitals in Japan. METHODS: Using a nationwide inpatient database, we identified patients aged ≥65 years with HF who had died between April 2015 and March 2021. Interrupted time-series analyses were used to compare practice patterns in end-of-life care (symptom management and invasive medical procedures within one week before death) before and after the financial incentive scheme issuance in April 2018. RESULTS: Overall, 53,857 patients in 835 hospitals were eligible. The adoption of the financial incentive was 1.10 to 1.22% after the introduction. There were upward pre-trends in opioid use (+0.11% per month; 95% confidence interval [CI], 0.06 to 0.15) and antidepressant use (+0.06% per month; 95% CI, 0.04 to 0.09). Opioid use showed a downward slope change during the post-period (-0.07% change in trend; 95% CI, -0.13 to -0.01). Intensive care unit stay showed a downward pre-trend (-0.09% per month; 95% CI, -0.14 to -0.04) and upward slope changes during the post-period (+0.12% change in trend; 95% CI, 0.04 to 0.19). Invasive mechanical ventilation showed downward slope changes during the post-period (-0.11% change in trend; 95% CI, -0.18 to -0.04). CONCLUSIONS: The financial incentive scheme for team-based palliative care was rarely adopted and not associated with changes in end-of-life care. Further multifaceted strategies to promote palliative care for HF are warranted.

Subanesthetic-dose propofol infusion for preventing emergence agitation in children: a retrospective observational study.

PURPOSE: Anesthesia maintenance using propofol and a propofol bolus dose at the end of surgery have been shown to prevent emergence agitation (EA). However, the preventive effect of subanesthetic propofol infusion during sevoflurane anesthesia on EA remains unknown. We aimed to evaluate the effect of subanesthetic propofol infusion on EA in children. METHODS: We retrospectively compared the incidences of severe EA requiring pharmacological intervention in children who underwent adenoidectomy, tonsillectomy with or without adenoidectomy, or strabismus surgery between maintenance with sevoflurane alone (sevoflurane group) and maintenance with subanesthetic propofol with sevoflurane (combination group). A multivariable logistic regression model adjusted for confounders was used to assess the association between anesthesia methods and the occurrence of EA. Additionally, we estimated the direct effect of anesthesia methods by a mediation analysis, excluding the indirect effects of intraoperative fentanyl and droperidol administration. RESULTS: Among 244 eligible patients, 132 and 112 were in the sevoflurane and combination groups, respectively. The crude incidence of EA was significantly lower in the combination group (17.0% [n = 19]) than in the sevoflurane group (33.3% [n = 44]) (P = 0.005). After adjusting for confounders, the incidence of EA was still significantly lower in the combination group (adjusted odds ratio [aOR]: 0.48, 95% confidence interval [CI] 0.25-0.91). The mediation analysis revealed a direct association of anesthesia methods with a lower EA incidence in the combination group (aOR: 0.48, 95% CI 0.24-0.93) than in the sevoflurane group. CONCLUSION: Subanesthetic propofol infusion may effectively prevent severe EA requiring the administration of opioids or sedatives.

Crystallization with Nodular Aggregation near the Glass Transition Temperature for Syndiotactic Polypropylene.

The isothermal crystallization from the melt state of syndiotactic polypropylene (sPP) has been studied by wide-angle X-ray diffraction (WAXD), small-angle X-ray scattering (SAXS), and optical microscopy. The WAXD and SAXS results show the crystallization mechanism near the glass transition temperature in which the crystalline and mesomorphic nodules cover the entire sample with the formation of aggregation regions. For the SAXS analysis, the scattering function for the three-component system has been suggested. Furthermore, to analyze the growth kinetics of the aggregation region for sPP, the time-dependent structure factor combined with the homogeneous and inhomogeneous nucleation-and-growth kinetics has been suggested. The analysis shows that the growth kinetics of the aggregation region for sPP is the homogeneous nucleation-and-growth. The growth velocity of the aggregation region is a natural extrapolation of that of spherulite to the high supercooling region. These results might indicate that the crystallization with the nodular aggregation is a fundamental crystallization process near the glass transition temperature for polymers.

Development and validation of genome-wide polygenic risk scores for predicting breast cancer incidence in Japanese females: a population-based case-cohort study.

PURPOSE: This study aimed to develop an ancestry-specific polygenic risk scores (PRSs) for the prediction of breast cancer events in Japanese females and validate it in a longitudinal cohort study. METHODS: Using publicly available summary statistics of female breast cancer genome-wide association study (GWAS) of Japanese and European ancestries, we, respectively, developed 31 candidate genome-wide PRSs using pruning and thresholding (P + T) and LDpred methods with varying parameters. Among the candidate PRS models, the best model was selected using a case-cohort dataset (63 breast cancer cases and 2213 sub-cohorts of Japanese females during a median follow-up of 11.9 years) according to the maximal predictive ability by Harrell's C-statistics. The best-performing PRS for each derivation GWAS was evaluated in another independent case-cohort dataset (260 breast cancer cases and 7845 sub-cohorts of Japanese females during a median follow-up of 16.9 years). RESULTS: For the best PRS model involving 46,861 single nucleotide polymorphisms (SNPs; P + T method with PT = 0.05 and R2 = 0.2) derived from Japanese-ancestry GWAS, the Harrell's C-statistic was 0.598 ± 0.018 in the evaluation dataset. The age-adjusted hazard ratio for breast cancer in females with the highest PRS quintile compared with those in the lowest PRS quintile was 2.47 (95% confidence intervals, 1.64-3.70). The PRS constructed using Japanese-ancestry GWAS demonstrated better predictive performance for breast cancer in Japanese females than that using European-ancestry GWAS (Harrell's C-statistics 0.598 versus 0.586). CONCLUSION: This study developed a breast cancer PRS for Japanese females and demonstrated the usefulness of the PRS for breast cancer risk stratification.

Association of chronic kidney disease with total and site-specific cancer incidence in participants of the Japan Public Health Center-based Prospective Study.

BACKGROUND: Although studies have found an association between chronic kidney disease (CKD) and cancer incidence, the results are inconsistent. METHODS: This study included participants in the Japan Public Health Center-based Prospective Study who had data on serum creatinine measurements. We assessed the association between estimated glomerular filtration rate (eGFR) and the risk of total and site-specific cancer incidence using a systematic survey in Japan. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for participant demographics and lifestyle factors. RESULTS: A total of 21 978 participants who met the inclusion criteria were followed up for a mean period of 12.9 years, during which a total of 2997 incident cancer cases were reported. In the multivariable adjusted models, an eGFR of <45 mL/min/1.73 m2 was not significantly associated with total cancer incidence (adjusted HR 1.22, 95% CI 0.94-1.60), compared with an eGFR of 60-89 mL/min/1.73 m2 (reference). The HR among those with eGFRs of ≥90 mL/min/1.73 m2 was 1.10 (95% CI 1.00-1.22). CONCLUSIONS: In this large prospective study, a low eGFR was not significantly associated with an increased risk of total cancer incidence in patients with CKD, which may be partly due to an underpowered sample size. This finding may be due to the many shared risk factors between CKD and cancer.

No Association of Early Postoperative Heart Rate With Outcomes After Coronary Artery Bypass Grafting.

BACKGROUND: Elevated perioperative heart rate potentially causes perioperative myocardial injury because of imbalance in oxygen supply and demand. However, large multicenter studies evaluating early postoperative heart rate and major adverse cardiac and cerebrovascular events (MACCEs) are lacking. OBJECTIVE: To assess the associations of 4 postoperative heart rate assessment methods with in-hospital MACCEs after elective coronary artery bypass grafting (CABG). METHODS: Using data from the eICU Collaborative Research Database in the United States from 2014 to 2015, the study evaluated postoperative heart rate measured during hospitalization within 24 hours after intensive care unit admission. Four heart rate assessment methods were evaluated: maximum heart rate, duration above heart rate 100/min, area above heart rate 100/min, and time-weighted average heart rate. The outcome was in-hospital MACCEs, defined as a composite of in-hospital death, myocardial infarction, angina, arrhythmia, heart failure, stroke, cardiac arrest, or repeat revascularization. RESULTS: Among 2585 patients, the crude rate of in-hospital MACCEs was 6.2%. In multivariable logistic regression analysis, the adjusted odds ratios (95% CI) for in-hospital MAC-CEs assessed by maximum heart rate in each heart rate category (beats per minute: >100-110, >110-120, >120-130, and >130) were 1.43 (0.95-2.15), 0.98 (0.56-1.64), 1.47 (0.76-2.69), and 1.71 (0.80-3.35), respectively. Similarly, none of the other 3 methods were associated with MACCEs. CONCLUSIONS: More research is needed to assess the usefulness of heart rate measurement in patients after CABG.

Association of Plasma Iron Status with Subsequent Risk of Total and Site-Specific Cancer: A Large Case-Cohort Study within JPHC Study.

It is unclear whether prediagnostic iron-related biomarkers in circulation are associated with cancer risk. We constructed a case-cohort of participants who had plasma samples available from the Japan Public Health Center-based Prospective Study and determined the incidence of cancer in these participants. We measured plasma concentrations of iron, ferritin, and hepcidin, and assessed the association between each biomarker and cancer incidence using a weighted Cox regression model. There were 4,253 participants in the sub-cohort (the randomly selected participants from an eligible, at-risk population) and 3,596 incident cancer cases (499 cases occurred in the sub-cohort). Median follow-up was for 16.5 years. In the multivariable adjusted analysis, iron deficiency (plasma ferritin <30 ng/mL) was associated with a higher risk of total cancer [adjusted HR, 1.23; 95% confidence interval (CI), 1.07-1.42] and the association was weaker after excluding those followed-up for <3 years. Iron overload was not significantly associated with total cancer (HR, 1.04; 95% CI, 0.82-1.33), but was associated with liver cancer (HR, 4.49; 95% CI, 2.71-7.43). Lower plasma levels of hepcidin and ferritin are associated with an increased gastrointestinal cancer risk. Meanwhile, lower plasma hepcidin and higher plasma ferritin levels were associated with an increased liver cancer risk. In conclusion, there was no association between iron overload and cancer risk, besides liver cancer. PREVENTION RELEVANCE: High ferritin and low hepcidin levels in the plasma were associated with increased liver cancer risk. Evaluating iron metabolism including hepcidin levels may help identify people with high liver cancer risk.

Postoperative outcomes of cancer surgery in patients with and without kidney failure with dialysis therapy: a matched-pair cohort study.

Background: The difference in outcomes of cancer surgery between patients with and without kidney failure with dialysis therapy (KFDT) remains uncertain. Methods: Using 2010-18 data in a national inpatient database in Japan, we identified patients who had undergone resection of colorectal, lung, gastric or breast cancer. We matched selected patient characteristics, type of cancer, surgical procedure and hospital of up to four patients without KFDT to each patient with KFDT. We assessed 30-day mortality and postoperative complications. Results: Through matching, we identified 2248 patients with KFDT (807 with colorectal, 579 with lung, 500 with gastric and 362 with breast cancer) and 8210 patients without KFDT (2851 with colorectal, 2216 with lung, 1756 with gastric and 1387 with breast cancer). Postoperative complications occurred in a higher proportion of patients with KFDT than of those without KFDT after colorectal {20.3% versus 14.6%; risk difference (RD): 5.7% [95% confidence interval (95% CI) 2.6%-8.8%]}, lung [18.0% versus 12.9%; RD: 5.1% (95% CI 1.6%-8.4%)], gastric [25.0% versus 13.2%; RD: 11.8% (95% CI 7.6%-16.2%)] and breast cancer surgery [7.5% versus 3.5%; RD: 3.9% (95% CI 1.1%-6.9%)]. Patients with KFDT had a higher 30-day mortality than those without KFDT after gastric cancer surgery [1.6% versus 0.3%; RD: 1.3% (95% CI 0.1%-2.3%)]. Heart failure and ischemic heart disease occurred more frequently in patients with KFDT. Conclusions: Patients with KFDT had higher rates of postoperative complications and 30-day mortality; however, RDs varied between cancer types. The higher rates of postoperative complications in patients with KFDT were mainly attributable to cardiovascular complications.

The Association of Timing of Tracheostomy and Survival of Patients with COVID-19.

Tracheostomy is performed for critically ill patients with prolonged endotracheal intubation including COVID-19 to mitigate the risk of airway complications. We analyzed the difference in mortality of COVID-19 patients undergoing early tracheostomy within 14 days of intubation compared to later tracheostomy than 14 days after intubation. The mortality was not significantly higher in early tracheostomy compared to later tracheostomy.

The association of remdesivir and in-hospital outcomes for COVID-19 patients treated with steroids.

BACKGROUND: Remdesivir has been shown to decrease SARS-CoV-2 viral loads and the duration of COVID-19 symptoms. However, current evidence regarding the association between remdesivir and in-hospital mortality for patients with COVID-19 steroid treatments is limited. We aimed to investigate whether remdesivir reduces in-hospital mortality among patients with COVID-19 treated with steroids. METHODS: In this retrospective multicentre study, we reviewed the medical records of 3372 patients discharged between 1 March 2020 and 30 March 2021, with laboratory confirmed COVID-19 in the Mount Sinai Health System and treated with steroids. We evaluated the effect of remdesivir on the outcomes using propensity score analyses. Subgroup analyses were conducted by stratification of patients by endotracheal intubation and COVID-19 antibody status. Acute kidney injury (AKI) was defined as an absolute serum creatinine increase of 0.3 mg/dL or a relative increase of 50%. RESULTS: Of the 3372 eligible patients, 1336 (39.6%) received remdesivir. After 1:1 propensity score matching (N = 999 pairs), in-hospital mortality was similar between those with and without remdesivir (21.4% versus 21.6%, respectively, P = 0.96). Remdesivir was not significantly associated with in-hospital mortality regardless of endotracheal intubation or COVID-19 antibody status. However, there was a signal that remdesivir was associated with a reduced risk of AKI in the propensity matched analysis (17.5% versus 23.4%, respectively, P = 0.001). CONCLUSIONS: Remdesivir was not associated with reduced risk of in-hospital mortality in patients with COVID-19 treated with steroids but potentially associated with decreased risk of AKI. These findings should be confirmed in prospective studies focusing on COVID-19 patients treated with steroids.

Association between Nafamostat Mesylate and In-Hospital Mortality in Patients with Coronavirus Disease 2019: A Multicenter Observational Study.

Nafamostat mesylate may be effective against coronavirus disease 2019 (COVID-19). However, it is not known whether its use is associated with reduced in-hospital mortality in clinical practice. We conducted a retrospective observational study to evaluate the effect of nafamostat mesylate in patients with COVID-19 using the Medical Data Vision Co. Ltd. hospital-based database in Japan. We compared patients with COVID-19 who were (n = 121) and were not (n = 15,738) administered nafamostat mesylate within 2 days of admission between January and December 2020. We conducted a 1:4 propensity score matching with multiple imputations for smoking status and body mass index and combined the 20 imputed propensity score-matched datasets to obtain the adjusted odds ratio for in-hospital mortality. Crude in-hospital mortality was 13.2% (16/121) and 5.0% (790/15,738), respectively. In the propensity score-matched analysis with multiple imputations, the adjusted odds ratio (use vs. no use of nafamostat mesylate) for in-hospital mortality was 1.27 (95% confidence interval: 0.61-2.64; p = 0.52). Sensitivity analyses showed similar results. The results of this retrospective observational study did not support an association between nafamostat mesylate and improved in-hospital outcomes in patients with COVID-19, although further studies with larger sample sizes are warranted to assess the generalizability of our findings.

Risk of Cancer in Association with Ranitidine and Nizatidine vs Other H2 Blockers: Analysis of the Japan Medical Data Center Claims Database 2005-2018.

INTRODUCTION: In September 2019, ranitidine and nizatidine were suggested to contain N-nitrosodimethylamine, a carcinogenic substance. People have since been concerned about the potential impact of ranitidine/nizatidine use on the risk of cancer. OBJECTIVE: The objective of this study was to investigate the risk of cancer among people receiving ranitidine or nizatidine compared with other histamine 2 receptor antagonists (H2 blockers) [cimetidine, famotidine, roxatidine, and lafutidine]. METHODS: In the Japan Medical Data Center claims database (comprising people aged < 75 years) from 2005 to 2018, we identified new adult users of H2 blockers and classified them into ranitidine/nizatidine users and other H2 blocker users. We estimated the incidence of cancer diagnosis in each group and conducted a multivariable Cox regression analysis. RESULTS: We identified 113,745 new users of ranitidine/nizatidine (median age 41.2 years [interquartile range 31.7-51.1]; 49.1% men; median follow-up 2.4 years [1.1-4.5]) and 503,982 new users of other H2 blockers (median age 40.9 years [31.1-51.2]; 51.0% men; median follow-up 2.3 years [0.9-4.2]). The incidence rate of cancer diagnosis was 6.39 (95% confidence interval 6.13-6.66) cases per 1000 person-years (top three sites: breast 14.8%; colorectal 14.6%; and stomach 11.5%) in the ranitidine/nizatidine group and 6.17 (6.05-6.30) cases per 1000 person-years (colorectal 14.7%; breast 13.5%; and stomach 11.2%) in the other H2 blockers group. The adjusted hazard ratio (ranitidine/nizatidine users vs other H2 blocker users) was 1.02 (0.98-1.07). The results were similar by follow-up length, by cancer site, and when ranitidine and nizatidine users were separately compared with the other H2 blockers group. By cumulative dose, the adjusted hazard ratio (95% confidence interval) was 1.03 (0.98-1.08) from 1 to 180 defined daily doses (DDDs), 1.00 (0.73-1.39) from 181 to 365 DDDs, 0.95 (0.61-1.48) from 366 to 730 DDDs, and 0.83 (0.45-1.55) at > 730 DDDs. CONCLUSIONS: We found no evidence that ranitidine/nizatidine is associated with an increased risk of cancer, although further studies with more accurate measurement of exposure, inclusion of older people, and longer follow-up may be needed.

Temporal change in characteristics and outcomes of acute kidney injury on renal replacement therapy in intensive care units: analysis of a nationwide administrative database in Japan, 2007-2016.

BACKGROUND: We aimed to examine recent trends in patient characteristics and mortality in patients with acute kidney injury (AKI) receiving renal replacement therapy (RRT), including continuous RRT (CRRT) and intermittent RRT (IRRT), in intensive care units (ICUs). METHODS: From the Diagnosis Procedure Combination database in Japan during 6 months (July-December) from 2007 to 2016, we identified patients with AKI who received RRT in ICUs. We restricted the study participants to those admitted to hospitals (in which both CRRT and IRRT were available) that participated in the Diagnosis Procedure Combination database for all 10 years. We examined the trends in patient characteristics and mortality overall, by RRT modality, and by main diagnosis category subgroup. Logistic regression was used to adjust for patient characteristics. RESULTS: We identified 51,758 patients starting RRT in 287 hospitals, including 39,471 (76.3%) and 12,287 (23.7%) patients starting CRRT and IRRT. The crude in-hospital mortality declined from 44.9 to 36.1% (P for trend < 0.001). Compared with 2007, the adjusted odds ratio (aOR) for in-hospital mortality was 0.66 (95% confidence interval (CI) 0.60-0.72) in 2016, and the decreasing trend was observed in both patients starting CRRT (aOR 0.67, 95% CI 0.61-0.75) and IRRT (0.58, 0.45-0.74), and in all subgroups except for coronary artery disease: sepsis aOR 0.68 (95% CI 0.57-0.81); cardiovascular surgery 0.58 (0.45-0.76); coronary artery disease 0.84 (0.60-1.19); non-coronary heart disease 0.78 (0.64-0.94); central nervous system disorders 0.42 (0.28-0.62); trauma 0.39 (0.21-0.72); and other 0.64 (0.50-0.82). CONCLUSIONS: This nationwide study confirmed a consistent decline in mortality among patients with AKI on RRT in ICUs. The adjusted mortality also declined during the study period; however, physiological variables were not measured in this study and it is possible that RRT may have been indicated for patients with less severe AKI in more recent years.