University Hospital In Japan Research Articles

Effect of Vitamin D Supplements on Relapse or Death in a p53-Immunoreactive Subgroup With Digestive Tract Cancer

Recent meta-analyses of randomized clinical trials found that daily vitamin D3 supplementation had beneficial effects on cancer mortality, although the results are still controversial. To examine whether vitamin D supplementation reduces the risk of relapse or death in a supgroup of patients with digestive tract cancer who were p53 immunoreactive. This was a post hoc subgroup analysis of the AMATERASU randomized, double-blind, placebo-controlled clinical trial. This trial included patients at a single university hospital in Japan with digestive tract cancers between January 2010 and February 2018 followed up for a median (IQR) of 3.5 (2.5-5.3) years to compare the effects of vitamin D supplementation with placebo and was reported in 2019. Patients from among 417 participants in the AMATERASU trial whose residual serum samples were available were included. Data were analyzed from October 20 to November 24, 2022. Vitamin D3 (2000 IU/d) supplementation or placebo. The primary outcome was 5-year relapse or death. The subgroup of patients who were p53 immunoreactive was defined by positivity for anti-p53 antibodies in serum and nuclear accumulation of p53 oncosuppressor protein in more than 99% of cancer cells, which is considered a biomarker for p53 missense mutations. Anti-p53 antibody levels were measured using chemiluminescent enzyme immune assay. Immunohistochemical staining data of p53 protein in cancer tissue in pathologic specimens were obtained from a previous study and divided into 4 grades. Among 392 patients with digestive tract cancer (mean [SD] age, 66 [10.7] years; 260 males [66.3%]), there were 37 patients with esophageal cancer (9.4%), 170 patients with gastric cancer (43.4%), 2 patients with small bowel cancer (0.5%), and 183 patients with colorectal cancer (46.7%). Serum anti-p53 antibody was detectable in 142 patients (36.2%), and p53-immunohistochemistry grade showed a positive association with serum anti-p53 antibody levels (coefficient = 0.19; P < .001). In the p53-immunoreactive subgroup (80 patients), relapse or death occurred in 9 of 54 patients (16.7%) in the vitamin D group and 14 of 26 patients (53.8%) in the placebo group; 5-year relapse-free survival (RFS) was significantly higher in the vitamin D group (13 patients [80.9%]) than the placebo group (1 patient [30.6%]; hazard ratio [HR], 0.27; 95% CI, 0.11-0.61; P = .002). This was significantly different from 272 patients in the non-p53 immunoreactive subgroup, in which vitamin D had no effect on 5-year RFS (vitamin D: 35 of 158 patients [22.2%] vs placebo: 24 of 114 patients [21.1%]; HR, 1.09; 95% CI, 0.65-1.84) (P for interaction = .005). This study found that vitamin D supplementation reduced the risk of relapse or death in the subgroup of patients with digestive tract cancer who were p53 immunoreactive. Identifier: UMIN000001977.

Efficacy of Bezlotoxumab Against Clostridioides difficile Infection: A Case-Series Study at a University Hospital in Japan and Literature Review.

Background Clostridioides difficile infection (CDI) recurrence is a public health concern as well as a health economic burden. Bezlotoxumab treatment is one way to prevent recurrence; however, its clinical results have not been reported in Japan. Therefore, we investigated the efficacy and safety of bezlotoxumab in patients with CDI at a university hospital in Japan and compared them with previously reported findings. Methodology We retrospectively examined all patients with some risk factors for recurrent CDI who received bezlotoxumab at the discretion of physicians at the Aichi Medical University Hospital, Aichi, Japan, between July 2018 and July 2022. The primary outcome was the three-month CDI recurrence rate. The secondary outcomes were an initial clinical cure and the six-month CDI recurrence rate. The safety of the administration was also assessed. Results A total of nine patients who received bezlotoxumab were included during the study period. The rate of CDI recurrence within three months was 28.5% (2/9). Two patients died due to other causes before their diarrhea improved. None of the patients experienced CDI recurrence between three and six months after the initial clinical cure of the baseline episode. Patients showed good tolerability to bezlotoxumab with no adverse effects. Two patients with a single episode of CDI recurrence before bezlotoxumab administration showed no recurrence. Conclusions In this Japanese case-series study, the efficacy of bezlotoxumab in preventing CDI recurrence in elderly patients with CDI and multiple underlying diseases was inferior to that reported in previous studies that analyzed real-world data. It is possible that bezlotoxumab may not be fully effective in elderly patients with CDI.

High level of C-reactive protein as a predictive factor for immune-related adverse events of immune checkpoint inhibitors in non-small cell lung cancer: a retrospective study.

Several risk factors for the immune-related adverse events (irAEs) during treatment with immune checkpoint inhibitors (ICIs) have been reported, of which include high levels of C-reactive protein (CRP). In this study, we aim to evaluate CRP levels before ICIs treatments as potential predictive biomarkers of irAEs incidence rate and overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC). Between December 1, 2015 to December 31, 2019, we retrospectively collected all adult patients with NSCLC who received at least one dose of an ICI targeting the PD-1/PD-L1 axis at the Iwate Medical University Hospital in Japan. In this study the patients were categorized into low and high groups with a cut-off value of 10 mg/L as the baseline level of CRP before the ICI treatment. The primary endpoint was relationship between CRP levels at baseline and incidence of irAEs. The secondary endpoints were the relationship of progression-free survival (PFS) and OS. A total of 101 irAEs, and 25 severe irAEs were observed. The incidence of the most irAEs was higher in the high CRP group compared to the low CRP group (54.4% vs. 34.5%, respectively, P=0.003). The most frequent irAEs were skin rush (28.8%), followed by pneumonitis (19.2%), hypothyroidism (15.4%), and hepatotoxicity (9.6%). The most common grade 3 or 4 irAEs was pneumonitis (7.9%), which tended to be more frequent in the high CRP group. In multivariate analysis, patients with high CRP levels had an adjusted OR of 2.41 and were associated with an increased risk of developing irAEs (95% CI: 1.16-4.43, P=0.020). The high CRP group was related with shorter PFS compared to the low CRP group (2.2 vs. 3.3 months, respectively, P=0.006). The high CRP group were also related with shorter OS compared to the low CRP group (8.9 vs. 39.1 months, respectively, P<0.001). The results suggest that higher level of pretreatment CRP is involved in the development of irAE and poor prognosis. Identification of patients at high risk of irAEs would be of great help. Future multicenter prospective studies are needed to expand on this study.

Comparison of Short-term Outcomes Between Esophageal Bypass Surgery and Self-expanding Stent Insertion in Esophageal Cancer: A Propensity Score-matched Analysis Using a Large-scale Inpatient Database.

Advanced esophageal cancer is occasionally accompanied by difficulty swallowing owing to esophageal stenosis or tracheoesophageal fistula formation. Esophageal bypass surgery and stent insertion are considered feasible palliative management options. The aim of this study was to evaluate the short-term outcomes of these palliative treatments. Patient data were obtained from a large-scale inpatient database of 42 National University Hospitals in Japan. Patients with advanced esophageal cancer who underwent esophageal bypass surgery or stent insertion between April 2016 and March 2021 were included in this study. One-to-one propensity score matching of patients who underwent bypass surgery or stent insertion was performed. The primary outcomes were time to diet resumption and length of hospital stay after surgery. The secondary outcome was the incidence of postoperative complications. In 43 propensity score-matched pairs, the incidence of postoperative respiratory complications was significantly higher in the bypass group than in the stent group (32.6% vs. 9.3%, P = 0.008). Postoperative length of hospital stay was longer in the bypass group than in the stent group (24 vs. 10d, P < 0.001). Logistic regression analysis revealed that stent insertion was associated with a decreased risk of respiratory complications (odds ratio 0.077, P < 0.007). Among patients who underwent the interventions (bypass surgery or stent insertion) and subsequently underwent anticancer therapy (chemotherapy/radiotherapy) during hospitalization, the interval between the intervention and anticancer therapy was longer in the bypass group than in the stent group (25 vs. 7d, P = 0.003). Esophageal stent insertion provides better short-term outcomes than bypass surgery in patients with advanced unresectable esophageal cancer.

Impact of the COVID-19 Pandemic on Initiation of Antibiotic Treatment After Performing a Blood Culture and Intervention by the Antimicrobial Stewardship Team.

Whether the coronavirus disease 2019 (COVID-19) pandemic had any effect on the time between blood culture collection and administration of antibiotics in the outpatient Department of Emergency Medicine in a single university hospital in Japan was investigated, and the intervention carried out by the antimicrobial stewardship team (AST) to promote the appropriate use of antibiotics was examined. The monthly percentage of patients who visited the outpatient Department of Emergency Medicine between January 2019 and December 2021 and received an intravenous antibiotic within 3 hours of blood culture collection was calculated. The AST calculated a quality indicator (QI) based on the results of the investigation and started QI monitoring and hospital feedback. From January 2020 to March 2021 (the third COVID-19 wave), the implementation rate of antibiotic administration within 3 hours after blood culture collection decreased as the COVID-19 pandemic spread, and the implementation rate tended to increase as the number of COVID-19-positive patients decreased. However, when the AST started monitoring and feedback from April 2021, although there was a temporary decline in the early stages of the fifth wave when the scale of infection was large, the implementation rate rose and was maintained by AST intervention. (the fourth and the fifth COVID-19 waves) (P<0.01). Also, the implementation rate was significantly lower during the COVID-19 pandemic than during the non- pandemic (P<0.05). The early COVID-19 pandemic may have affected the delay in time from blood culture collection to antibiotic administration. Later, in recurring COVID-19 pandemics, AST intervention eliminated this problem. When a bacterial infection such as sepsis is suspected, delayed treatment can be prevented by promptly collecting a blood culture, irrespective of concerns about COVID-19 infection. Calculating the QI may promote AST activities and the appropriate use of antibiotics.

High prevalence of colistin heteroresistance in specific species and lineages of Enterobacter cloacae complex derived from human clinical specimens

BackgroundColistin (CST) is a last-line drug for multidrug-resistant Gram-negative bacterial infections. CST-heteroresistant Enterobacter cloacae complex (ECC) has been isolated. However, integrated analysis of epidemiology and resistance mechanisms based on the complete ECC species identification has not been performed.MethodsClinical isolates identified as “E. cloacae complex” by MALDI-TOF MS Biotyper Compass in a university hospital in Japan were analyzed. Minimum inhibitory concentrations of CST were determined by the broth microdilution method. The population analysis profiling (PAP) was performed for detecting the heteroresistant phenotype. The heat shock protein 60 (hsp60) cluster was determined from its partial nucleotide sequence. From the data of whole-genome sequencing, average nucleotide identity (ANI) for determining ECC species, multilocus sequence type, core genome single-nucleotide-polymorphism-based phylogenetic analysis were performed. phoPQ-, eptA-, and arnT-deleted mutants were established to evaluate the mechanism underlying colistin heteroresistance. The arnT mRNA expression levels were determined by reverse transcription quantitative PCR.ResultsThirty-eight CST-resistant isolates, all of which exhibited the heteroresistant phenotype by PAP, were found from 138 ECC clinical isolates (27.5%). The prevalence of CST-resistant isolates did not significantly differ among the origin of specimens (29.0%, 27.8%, and 20.2% for respiratory, urine, and blood specimens, respectively). hsp60 clusters, core genome phylogeny, and ANI revealed that the CST-heteroresistant isolates were found in all or most of Enterobacter roggenkampii (hsp60 cluster IV), Enterobacter kobei (cluster II), Enterobacter chuandaensis (clusters III and IX), and Enterobacter cloacae subspecies (clusters XI and XII). No heteroresistant isolates were found in Enterobacter hormaechei subspecies (clusters VIII, VI, and III) and Enterobacter ludwigii (cluster V). CST-induced mRNA upregulation of arnT, which encodes 4-amino-4-deoxy-l-arabinose transferase, was observed in the CST-heteroresistant isolates, and it is mediated by phoPQ pathway. Isolates possessing mcr-9 and mcr-10 (3.6% and 5.6% of total ECC isolates, respectively) exhibited similar CST susceptibility and PAP compared with mcr-negative isolates.ConclusionsSignificant prevalence (approximately 28%) of CST heteroresistance is observed in ECC clinical isolates, and they are accumulated in specific species and lineages. Heteroresistance is occurred by upregulation of arnT mRNA induced by CST. Acquisition of mcr genes contributes less to CST resistance in ECC.

Correlation between antibiotic use and resistance of gram-negative bacteria at a university hospital in Japan from 2013 to 2021: a study using the Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE) system

ObjectivesThe Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE) system aggregates information related to antimicrobial resistance (AMR) measures. We aimed to investigate the correlation between antibiotic use and AMR...

Clinical Outcomes and Genetic Analyses of Restrictive Cardiomyopathy in Children.

Restrictive cardiomyopathy in children is rare and outcomes are very poor. However, little information is available concerning genotype-outcome correlations. We analyzed the clinical characteristics and genetic testing, including whole exome sequencing, of 28 pediatric restrictive cardiomyopathy patients who were diagnosed from 1998 to 2021 at Osaka University Hospital in Japan. The median age at diagnosis (interquartile range) was 6 (2.25-8.5) years. Eighteen patients received heart transplantations and 5 patients were on the waiting list. One patient died while waiting for transplantation. Pathologic or likely-pathogenic variants were identified in 14 of the 28 (50%) patients, including heterozygous TNNI3 missense variants in 8 patients. TNNT2, MYL2, and FLNC missense variants were also identified. No significant differences in clinical manifestations and hemodynamic parameters between positive and negative pathogenic variants were detected. However, 2- and 5-year survival rates were significantly lower in patients with pathogenic variants (50% and 22%) compared with survival in patients without pathogenic variants (62% and 54%; P=0.0496, log-rank test). No significant differences were detected in the ratio of patients diagnosed at nationwide school heart disease screening program between positive and negative pathogenic variants. Patients diagnosed by school screening showed better transplant-free survival compared with patients diagnosed by heart failure symptoms (P=0.0027 in log-rank test). In this study, 50% of pediatric restrictive cardiomyopathy patients had pathogenic or likely-pathogenic gene variants, and TNNI3 missense variants were the most frequent. Patients with pathogenic variants showed significantly lower transplant-free survival compared with patients without pathogenic variants.

The effect of introducing a nurse-practitioner-led peripherally inserted central venous catheter placement program on the utilization of central venous access device: A retrospective study in Japan.

Nurse-led peripherally inserted central venous catheter (PICC) placement teams are common in western hospitals, but they are still in their infancy in Japan. Although implementing a dedicated program may improve ongoing vascular-access management, the direct hospital-level effects of launching a nurse-led PICC team on specific outcomes have not been formally investigated. To evaluate the effect of introducing a nurse practitioner (NP)-led PICC-placement program on subsequent utilization of centrally inserted central catheters (CICCs) and to contrast the quality of PICC placements conducted by physicians and NPs. Patients who underwent central venous access devices (CVADs) between 2014 and 2020 at a university hospital in Japan were evaluated retrospectively using an interrupted time-series analysis on the trend for monthly CVAD utilization and logistic regression and propensity score-based analyses for PICC-related complications. Among 6007 CVAD placements, 2230 PICCs were inserted into 1658 patients (725 by physicians and 1505 by NPs). The monthly number of CICC utilization fell from 58 in April 2014 to 38 in March 2020, while PICC placements by the NP PICC team increased from 0 to 104. The implementation of the NP PICC program reduced the immediate rate (by 35.5; 95% confidence interval [CI]: 24.1-46.9; p < 0.001) and post-intervention trend (by 2.3; 95% CI: 1.1-3.5; p < 0.001) of monthly CICC utilization. Overall immediate complication rates were lower in the NP group than the physician group (1.5% vs 5.1%; adjusted odds ratio = 0.31; 95% CI: 0.17-0.59; p < 0.001). The cumulative incidences of central line-associated bloodstream infections were comparable between the NP and physician groups (5.9% vs 7.2%; adjusted hazard ratio = 0.96; 95% CI: 0.53-1.75; p = .90). This NP-led PICC program reduced CICC utilization without affecting the quality of PICC placement or complication rate.

Oxford Hip Scores, Floor-Sitting Score Trajectories, and Postoperative Satisfaction Rates at 10 Years After Primary Total Hip Arthroplasty

BackgroundAvailable evidence on outcomes at 5 years and beyond for total hip arthroplasty (THA) is mainly limited to patient-reported outcome measures (PROMs). This study documented the trajectory of functional measurement using the Oxford hip score (OHS) and floor-sitting posture in Japan for up to 10 years post-THA and investigated predictors of dissatisfaction at 10 years with THA. MethodsPatients scheduled for primary THA at a university hospital in Japan between 2003 and 2006 were enrolled in this prospective study. Overall, 826 preoperative participants were eligible for follow-up, with response rates ranging from 93.6% to 69.4% at each postoperative survey point. The OHS and floor-sitting scores were calculated using a self-administered questionnaire 6 times up to 10 years postoperatively. Patient satisfaction, including general surgery, walking ability, and activities of daily living (ADL), was assessed in the 10-year survey. ResultsThe linear mixed-effects model demonstrated a postoperative improvement, peaking at 7 years for OHS and 5 years earlier for the floor-sitting score. The postoperative overall surgical dissatisfaction at 10 years with THA was very low (3.2%). No predictors of surgical dissatisfaction were identified in the logistic regression analyses. Predictors of walking ability dissatisfaction were older age, men, and worse OHS at 1 year postoperatively. Predictors of ADL dissatisfaction were poorer preoperative and 1-year postoperative floor-sitting scores and 1-year postoperative OHS. ConclusionThe floor-sitting score is a simple PROM suitable for the Japanese population; other populations would require a scale suitable for their lifestyles.

Clinical Characteristics and Progression of Geographic Atrophy in a Japanese Population

To elucidate the clinical characteristics and progression rate of geographic atrophy (GA) associated with age-related macular degeneration (AMD) in a Japanese population. Retrospective, multicenter, observational study. A total of 173 eyes from 173 patients from six university hospitals in Japan were included. Of 173 study eyes, 101 eyes from 101 patients were included in the follow-up group. All patients were Japanese, aged ≥ 50 years, and had definite GA associated with AMD in at least one eye. The GA area was measured semi-automatically using fundus autofluorescence (FAF) images. In the follow-up group followed for more than six months with FAF images, the GA progression rate was calculated by two methods: mm2/year and mm/year using the square-root transformation (SQRT) strategy. Simple and multiple linear regression analyses were used to identify the baseline factors associated with the GA progression rate. Clinical characteristics of GA and the GA progression rate. The mean age was 76.8 ± 8.8 years and 109 (63.0%) were males. Sixty-two (35.8%) patients had bilateral GA. The mean GA area was 3.06 ± 4.00 mm2 (1.44 ± 1.00 mm [SQRT]). Thirty-eight eyes (22.0%) were classified as having pachychoroid GA. Drusen and reticular pseudodrusen were detected in 115 (66.5%) and 73 eyes (42.2%), respectively. The mean subfoveal choroidal thickness was 194.7 ± 105.5 μm. In the follow-up group (follow-up period: 46.2 ± 28.9 months), the mean GA progression rate was 1.01 ± 1.09 mm2/year (0.23 ± 0.18 mm/year [SQRT]). In the multivariable analysis, baseline GA area [SQRT] (P=0.002) and the presence of reticular pseudodrusen (P<0.001) were significantly associated with a greater GA progression rate [SQRT]. Certain clinical characteristics of GA in Asian populations may differ from those in Caucasians. Asian patients with GA showed male-dominance and relatively thicker choroid than Caucasian patients. There was a group with GA without drusen but with features of pachychoroid. The GA progression rate in this Asian population was relatively lower than that in Caucasians. Large GA and reticular pseudodrusen were associated with a greater GA progression rate.

NURSE-LED proactive rounding and automatic early-warning score systems to prevent resuscitation incidences among Adults in ward-based Hospitalised patients

ObjectivesIn this study, we investigated the impact of critical care outreach implemented to overcome the problem of rapid response system (RRS) activation. The aim was to evaluate the impact of nurse-led proactive rounding on the rate of adverse events in a hospital setting using an automatic early-warning score system, without a call-activated team. MethodsThis observational study was conducted at a university hospital in Japan. Beginning in September 2019, critical care outreach via nurse-led proactive rounding of the general ward was conducted, using an automatic early-warning score system. We retrospectively assessed the computerised records of all inpatient days (N = 497,284) of adult inpatients admitted to the hospital from September 2017 to 2020. We compared the adverse event occurrences before and after implementation of the critical care outreach program. The main outcome measures were: unexpected death in the general ward, code blue (an in-hospital resuscitation request code directed towards all staff via broadcast) for non-intensive care unit inpatients and unexpected intensive care unit admissions from the general ward. The secondary outcome was the proportion of patients who received respiratory rate measurement. ResultsThe incidence rate ratios of the occurrence of unexpected deaths (0.19, 95% confidence interval: 0.04–0.57) and code blue in the general ward (0.15, 95% confidence interval: 0.025–0.50) decreased. There was no change in unexpected intensive care unit admissions from the general ward (1.25, confidence interval: 0.84–1.82). The proportion of patients who received respiratory rate measurement increased (10.2% vs 16.2%). ConclusionOur results suggest that in RRSs, drastic control of the failure of the mechanism to activate a response team may produce positive outcomes. Proactive rounding that bypasses the mechanism to activate a response team component of RRSs may relieve ward nurses of activation failure responsibility and help them overcome the hierarchical hospital structure.

Inhalation adherence for asthma and COPD improved during the COVID-19 pandemic: a questionnaire survey at a university hospital in Japan

Background: Good adherence to an inhaled medication protocol is necessary for the management of asthma and chronic obstructive pulmonary disease (COPD), and several interventions to improve adherence have been reported. However, the impact of patient life changes and psychological aspects on treatment motivation is obscure. Here, we investigated changes in inhaler adherence during the COVID-19 pandemic and how lifestyle and psychological changes affected it. Methods: Seven-hundred sixteen adult patients with asthma and COPD who had visited Nagoya University Hospital between 2015 and 2020 were selected. Among them, 311 patients had received instruction at a pharmacist-managed clinic (PMC). We distributed one-time cross-sectional questionnaires from January 12 to March 31, 2021. The questionnaire covered the status of hospital visits, inhalation adherence before and during the COVID-19 pandemic, lifestyles, medical conditions, and psychological stress. The Adherence Starts with Knowledge-12 (ASK-12) was used to assess adherence barriers. Results: Four-hundred thirty-three patients answered the questionnaire. Inhalation adherence was significantly improved in both diseases during the COVID-19 pandemic. The most common reason for improved adherence was fear of infection. Patients with improved adherence were more likely to believe that controller inhalers could prevent COVID-19 from becoming more severe. Improved adherence was more common in patients with asthma, those not receiving counseling at PMC, and those with poor baseline adherence. Conclusions: Inhalation adherence for asthma and COPD improved in the COVID-19 pandemic. The patients seemed to realize the necessity and benefits of the medication more strongly than before the pandemic, which motivated them to improve adherence.

Pharmacist-led multi-faceted intervention in an antimicrobial stewardship programme at a dental university hospital in Japan

Antimicrobials are commonly prescribed in dentistry. However, inappropriate antimicrobial prescriptions are common in this field. Optimizing antimicrobial prescriptions in dentistry requires an effective strategy for modifying prescribing behaviour. To assess the efficacy of pharmacist-led multi-faceted intervention for the proportion of monthly antimicrobial prescriptions in each drug group per 100 oral antimicrobial prescriptions. A before-after trial was performed at a university hospital outpatient dental clinic. A pharmacist-led, multi-faceted intervention, including immediate and direct feedback to the prescribers, an explanation of the rules of antimicrobial prescriptions for patients with penicillin allergy, tutorials for dentistry students, and a review of hospital-approved antimicrobials, was implemented from April 2017 to March 2022. Antimicrobials were classified into eight groups, namely, penicillins, first- and second-generation cephalosporins, third-generation cephalosporins, fluoroquinolones, macrolides, clindamycin, carbapenem, and others. In total, there were 2,643,988 visits to the outpatient dental clinic during the study period. The monthly mean proportion of prescriptions for penicillins increased from 45.6 to 84.1 per 100 oral antimicrobial prescriptions (P<0.001) while that of third-generation cephalosporins decreased from 43.0 to 7.3 (P<0.001) from the pre-intervention to the intervention period. Moreover, the monthly mean proportion of fluoroquinolones, macrolides, and carbapenems decreased from 11.2 to 7.44 (P<0.001). The intervention modified dentists' antimicrobial prescribing behaviours, leading to an immediate increase in the number of monthly prescriptions for penicillins and a simultaneous decrease in the number of monthly prescriptions for third-generation cephalosporins and other broad-spectrum, oral antimicrobials.

Symptom-based stratification algorithm for heterogeneous symptoms of dry eye disease: a feasibility study.

To test the feasibility of a dry eye disease (DED) symptom stratification algorithm previously established for the general population among patients visiting ophthalmologists. This retrospective cross-sectional study was conducted between December 2015 and October 2021 at a university hospital in Japan; participants who underwent a comprehensive DED examination and completed the Japanese version of the Ocular Surface Disease Index (J-OSDI) were included. Patients diagnosed with DED were stratified into seven clusters using a previously established symptom-based stratification algorithm for DED. Characteristics of the patients in stratified clusters were compared. In total, 426 participants were included (median age [interquartile range]; 63 [48-72] years; 357 (83.8%) women). Among them, 291 (68.3%) participants were diagnosed with DED and successfully stratified into seven clusters. The J-OSDI total score was highest in cluster 1 (61.4 [52.2-75.0]), followed by cluster 5 (44.1 [38.8-47.9]). The tear film breakup time was the shortest in cluster 1 (1.5 [1.1-2.1]), followed by cluster 3 (1.6 [1.0-2.5]). The J-OSDI total scores from the stratified clusters in this study and those from the clusters identified in the previous study showed a significant correlation (r = 0.991, P < 0.001). The patients with DED who visited ophthalmologists were successfully stratified by the previously established algorithm for the general population, uncovering patterns for their seemingly heterogeneous and variable clinical characteristics of DED. The results have important implications for promoting treatment interventions tailored to individual patients and implementing smartphone-based clinical data collection in the future.

Survey of Inpatient Consultations with General Internal Medicine Physicians in a Tertiary Hospital: A Retrospective Observational Study.

The general internal medicine (GIM) department can be an effective diagnostic coordinator for undiagnosed outpatients. We investigated the contribution of GIM consultations to the diagnosis of patients admitted to specialty departments in hospitals in Japan that have not yet adopted a hospitalist system. This single-center, retrospective observational study was conducted at a university hospital in Japan. GIM consultations from other departments on inpatients aged ≥20 years, from April 2016 to March 2021, were included. Data were extracted from electronic medical records, and consultation purposes were categorized into diagnosis, treatment, and diagnosis and treatment. The primary outcome was new diagnosis during hospitalization for patients with consultation purpose of diagnosis or diagnosis and treatment. The secondary outcomes were the purposes of consultation with the Diagnostic and Generalist Medicine department. In total, 342 patients were included in the analysis. The purpose of the consultations was diagnosis for 253 patients (74%), treatment for 60 (17.5%), and diagnosis and treatment for 29 patients (8.5%). In 282 consultations for diagnosis and diagnosis and treatment, 179 new diagnoses were established for 162 patients (57.5%, 95% confidence interval [CI], 51.5-63.3). The GIM department can function as a diagnostic consultant for inpatients with diagnostic problems admitted to other specialty departments in hospitals where hospitalist or other similar systems are not adopted.

A Novel Risk Model for Predicting Dysphagia after Tongue Reconstruction: A Retrospective Multicenter Study in Japan.

There is no consensus on the postoperative outcomes of tongue reconstruction. Therefore, the authors developed a novel risk model for predicting dysphagia after tongue reconstruction. This retrospective study was conducted by the Oral Pharyngeal Esophageal Operation and Reconstruction Analytical, or OPERA, group across 31 cancer centers and university hospitals in Japan. A total of 532 patients [390 (73.3%) men and 142 (26.7%) women; median age at surgery, 60 years (range, 15 to 88 years)] who were diagnosed with oral tongue squamous cell carcinoma and underwent tongue reconstruction following glossectomy between 2009 and 2013 were included. Independent risk factors were identified using univariate regression analysis and converted to a binary format for multivariate analysis. An integer value was assigned to each risk factor to calculate a total score capable of quantifying the risk of feeding tube dependence. Overall, 54 patients (10.2%) required a feeding tube at the time of evaluation. Predictive factors for feeding tube dependence were advanced age, lower American Society of Anesthesiologists physical status, low body mass index, lower serum albumin, comorbid hypertension and diabetes, extended tongue defect, resection beyond the tongue, laryngeal suspension, postoperative radiation therapy, and no functional teeth. In multivariate logistic regression analysis, age greater than or equal to 58.5 years, postoperative radiation therapy, wider tongue defect, and body mass index less than 21.27 kg/m 2 earned 6, 4, 3, and 2 points, respectively, for a maximum total score of 15. The authors' risk model provides a mathematical tool for estimating the individual risk of postoperative feeding tube dependence before tongue reconstruction. Risk, III.

Evaluation of a Previously Developed Predictive Model for Infective Endocarditis in 320 Patients Presenting with Fever at 4 Centers in Japan Between January 2018 and December 2020.

BACKGROUND In our previous single-center study, we developed an infective endocarditis (IE) prediction model among patients with undiagnosed fever (UF) based on 5 factors that can be obtained on admission: ambulance transfer, presence of cardiac murmur or pleural effusion, blood neutrophil percentage, and platelet count. The present study aimed to retrospectively evaluate the prediction model for IE in 320 patients presenting with fever at 4 university hospitals in Japan from January 2018 to December 2020. MATERIAL AND METHODS Patients aged ≥20 years admitted to 4 hospitals with I-330 (IE) or R-50-9 (UF) according to the International Statistical Classification of Diseases and Related Health Problems-10 were enrolled. More than 2 physicians at each hospital reviewed the patient diagnoses using the modified Duke criteria, allocating "definite IE" to IE group (n=119) and "non-definite IE" to UF group (n=201). Five factors on admission were analyzed by multivariate logistic regression. The discriminative ability and calibration of the model were evaluated using the area under the curve (AUC) and the shrinkage coefficient, respectively. RESULTS A total of 320 patients were enrolled. The odds ratios (95% confidence intervals) were as follows: ambulance transfer 1.81 (0.91-3.55); cardiac murmur 13.13 (6.69-27.36); pleural effusion 2.34 (0.62-2.42); blood neutrophil percentage 1.09 (1.06-1.14); and platelet count 0.96 (0.93-0.99). The AUC was 0.783 (0.732-0.834) with a shrinkage coefficient of 0.961. CONCLUSIONS The IE prediction model is useful to estimate the probability of IE immediately after admission for fever in patients aged ≥20 years.

Abstract P5-12-02: Germline variants detected by next-generation sequencing-based multigene panel testing in patients with suspected hereditary breast cancer at a University Hospital in Japan

Abstract Background: The usefulness of prophylactic surgery and surveillance for hereditary breast cancer has been demonstrated, and germline testing for BRCA1 and BRCA2 had been covered by insurance since 2020 in Japan. In addition to BRCA1 and BRCA2, several other genes are also associated with an increased risk of developing breast cancer, such as PALB2, ATM, BARD1, CHEK2, PTEN, and TP53. Next-generation sequencing-enabled multigene panel tensing provides information about these gene variants at the same time, and at a low cost. Although germline testing of BRCA1 and BRCA2 has become widespread in Japan, multi-panel gene testing for germline variants has been conducted only in a limited number of facilities, partly due to the difficulty associated with dealing with the gene variant information obtained from the test. The aim of this study was to clarify the current status of multigene panel testing in our institute, and reveal the characteristics of the variants detected in patients with, or predisposed to, hereditary breast cancer. Methods: This retrospective study included 37 individuals who underwent next-generation sequencing-based multigene panel testing in order to investigate any inherited genetic variants due to a suspicion of hereditary breast cancer. Eighteen patients had a diagnosis of breast cancer with a family history of breast and/or ovarian cancer, nine patients had a diagnosis of breast cancer without family history of breast or ovarian cancer, and 10 patients had a family history of breast cancer but had not developed breast cancer themselves. Results: Utilizing mutigene panel testing, at least one alteration was found in 24 genes, and a total of 39 variants were found in the 37 patients. Of these 37 patients, nine (24.3%) had a pathogenic/likely pathogenic variant with or without other variants of uncertain significance (VUS), 15 (40.5%) had VUS, and 13 (35.1%) had negative genetic test results. Among the nine patients with pathogenic/likely pathogenic variants, seven had variants in either BRCA1 or BRCA2 (one BRCA1 pathogenic variant, five BRCA2 pathogenic variants, and one BRCA2 likely pathogenic variant), while the remaining positive results were attributed to other genes (one MLH1 pathogenic variant, and one SDHB pathogenic variant). VUS included BRCA1 and BRCA2, as well as other breast cancer-associated genes, such as ATM (n=2), CDH1 (n=2), NF1 (n=2), PALB2 (n=1), CHEK2 (n=1), NBN (n=1), and RAD51D (n=1). VUS also included other cancer syndrome-related genes, such as MLH1 (n=2), MUTYH (n=2), APC (n=1), and RET (n=1). Conclusion: Multigene panel tests in our institute revealed pathogenic/likely pathogenic variants in 24.3% of individuals who suspected hereditary breast cancer. As expected, multigene panel tests also revealed more VUS than pathogenic variants and 40.5% individuals were detected with VUS, which included many genes associated with hereditary breast cancer and other cancer syndromes, in addition to BRCA1 and BRCA2. Individuals with VUS will need to cope with new information if the interpretation of the variant changes in the future. We need to be aware of the characteristics and limitations of this type of panel testing, and to properly utilize the test results and information obtained for good quality patient care. Citation Format: Yusa Atake, Masayuki Nagahashi, Haruka Kanaoka, Akira Hattori, Ayako Bun, Reiko Fukui, Hiromi Ozawa, Yukie Fujimoto, Tomoko Higuchi, Michiko Imamura, Keiko Murase, Yuichi Takatsuka, Mina Kashima, Chiho Okada, Chinatsu Kinjo, Mikako Miyata, Ayako Miyazaki, Mako Ueda, Hiroshi Tsubamoto, Hideaki Sawai, Yasuo Miyoshi. Germline variants detected by next-generation sequencing-based multigene panel testing in patients with suspected hereditary breast cancer at a University Hospital in Japan [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-12-02.

The incidence of Jarisch-Herxheimer reactions and associated risk factors in pregnant women and nonpregnant women: A retrospective chart review at a university hospital in Japan.

Jarisch-Herxheimer reactions (JHR) is a transient adverse event that occurs during initial antimicrobial treatment for syphilis patients, and is known to develop uterine contractions and fetal distress in pregnant women complicated with syphilis. The aim of this study is to identify risk factors for JHR in patients with syphilis, and to clarify whether pregnancy status is a risk factor for JHR, and to describe the characteristics of pregnant women who develop JHR. This was a retrospective chart review in a singleton university hospital in Japan. We collected data of syphilis patients who were diagnosed and treated at department of obstetrics and gynecology, dermatology between January 2010 and May 2022. There were no validated diagnostic criteria for JHR, we defined JHR as one or more of the following in addition to raised body temperature (≧38.0°C) within 24 h of initial antibiotic treatment: headache, chills, myalgias, tachycardia (≧110 bpm), new rash. There were 30 syphilis patients. Of whom nine (30%) were pregnant women and all their neonates were not diagnosed with congenital syphilis. Five patients (17%) developed JHR at the time of initial treatment (JHR group, n=5). There was no difference between JHR group and non-JHR group (n=25) in pregnancy status. Secondary syphilis was an only significant risk factor for JHR. Two pregnant women with JHR were both treated for secondary syphilis in the third trimester of pregnancy. Pregnancy status was not a risk factor for JHR in syphilis patients. Further research is needed.