National Hospital Organization Research Articles

Holter Electrocardiographic Approach to Predicting Outcomes of Pediatric Patients With Long QT Syndrome.

This study was performed to clarify the clinical findings of pediatric patients diagnosed with long QT syndrome (LQTS) through electrocardiographic screening programs and to predict their outcome using Holter electrocardiographic approaches.Methods and Results: This retrospective study included pediatric patients with a Schwartz score of ≥3.5 who visited the National Hospital Organization Kagoshima Medical Center between April 2005 and March 2019. Resting 12-lead and Holter electrocardiograms were recorded at every visit. The maximum resting QTc and maximum Holter QTc values among all recordings were used for statistical analyses. To test the prognostic value of QTc for the appearance of cardiac events after the first hospital visit, receiver operating characteristic curves were used to calculate the area under the curve (AUC). Among 207 patients, 181 (87%) were diagnosed through screening programs. The prevalence of cardiac events after the first hospital visit was 4% (8/207). Among QTc at diagnosis, maximum resting QTc, and maximum Holter QTc, only maximum Holter QTc value was a predictor (P=0.02) of cardiac events after the hospital visit in multivariate regression analysis. The AUC of the maximum Holter QTc was significantly superior to that of maximum resting QTc. The maximum Holter QTc value can be used to predict the appearance of symptoms in pediatric patients with LQTS.

Phase II study in children and adults under 40 years with newly diagnosed Langerhans cell histiocytosis: protocol for an LCH-19-MSMFB clinical trial in Japan

IntroductionAlthough the prognosis of Langerhans cell histiocytosis (LCH) is excellent, the high recurrence rate and permanent consequences, such as central diabetes insipidus and LCH-associated neurodegenerative diseases, remain to be resolved....

Safety and efficacy of airway stent placement following bronchial artery embolization: A retrospective study at a single institute

BackgroundAirway stenting is an established procedure for treating oncological emergencies in patients with airway disorders. In patients with airway hemorrhage, respiratory conditions may worsen during stenting. Bronchial artery embolization (BAE) is useful to prevent bleeding from the bronchus. We aimed to evaluate the efficacy and safety of airway stenting after BAE in patients with malignant airway disorders. MethodsThe medical records of all patients who underwent airway stenting following BAE at the National Hospital Organization Okayama Medical Center between 2016 and 2023 were retrospectively reviewed. ResultsThirteen procedures (11 silicone Y stents, one hybrid stent, and one self-expandable metallic stent) were performed. The median duration from BAE to airway stenting was one day (range: 1–5 days). Nine patients experienced tumor shrinkage, and none experienced severe bleeding after BAE during the stent procedure. No other major complications were associated with the stent placement. The median survival time after stenting was 169 days (range; 24–1086). No serious complications caused by BAE, such as spinal cord infarction, were observed. ConclusionsAirway stent placement was safely performed after BAE without severe bleeding or acute respiratory failure. BAE, followed by airway stenting, is useful.

Impact of segmented optical axial length on the performance of intraocular lens power calculation formulas.

To investigate the difference between the segmented axial length (AL) and the composite AL on a swept-source optical coherence tomography biometer and to evaluate the subsequent effects on artificial intelligence intraocular lens (IOL) power calculations: the Kane and Hill-RBF 3.0 formulas compared with established vergence formulas. National Hospital Organization, Tokyo Medical Center, Japan. Retrospective case series. Consecutive patients undergoing cataract surgery with a single-piece IOL were reviewed. The prediction accuracy of the Barrett Universal II, Haigis, Hill-RBF 3.0, Hoffer Q, Holladay 1, Kane, and SRK/T formulas based on 2 ALs were compared for each formula. The heteroscedastic test was used with the SD of prediction errors as the endpoint for formula performance. The study included 145 eyes of 145 patients. The segmented AL (24.83 ± 1.89) was significantly shorter than the composite AL (24.88 ± 1.96, P < .001). Bland-Altman analysis revealed a negative proportional bias for the differences between the segmented AL and the composite AL. The SD values obtained by Hoffer Q, Holladay 1, and SRK/T formulas based on the segmented AL (0.52 diopters [D], 0.54 D, and 0.50 D, respectively) were significantly lower than those based on the composite AL (0.57 D, 0.60 D, and 0.52 D, respectively, P < .01). The segmented ALs were longer in short eyes and shorter in long eyes than the composite ALs. The refractive accuracy can be improved in the Hoffer Q, Holladay 1, and SRK/T formulas by changing the composite ALs to the segmented ALs.

A prospective observational study on hemodynamic risk in cerebral aneurysm growth

Introduction: Hemodynamic factors are thought to play a major role in the development, growth, and rupture of cerebral aneurysms, but the hemodynamics related to enlargement remain unclear. We prospectively enrolled patients with unruptured cerebral aneurysms and performed Computational Fluid Dynamics (CFD) analysis using 3D CT images to investigate differences in hemodynamic environments between aneurysms that grew and those that did not grow over a 3-year period. Methods: This prospective observational study was approved by the National Hospital Organization Central Ethics Review Board. Hemodynamic distributions were examined using ANSYS-CFX software. Patient-specific arterial geometries and inflow velocities were obtained from 3D-CTA and carotid ultrasound Doppler examinations. The distributions of hemodynamic metrics of 17 enlarged and 70 unenlarged aneurysms was compared. In addition, the distributions of hemodynamic metrics of the neck, body, and dome of the aneurysm was also examined in 9 enlarged and 41 non-enlarged cases. A multivariate logistic analysis was performed to investigate the influence of the six hemodynamic metrics, i.e., the time-averaged wall shear stress (TAWSS), time-averaged WSS gradient (TAWSSG), oscillatory shear index (OSI), gradient oscillatory number (GON), transverse WSS (transWSS), and normalized transWSS (NtransWSS) after adjustment forknown risk factors for aneurysm growth, i.e., age, sex, hypertension, smoking history, and aneurysm location, size, and history of subarachnoid hemorrhage. Results: Regarding the distributions of hemodynamic metrics throughout the aneurysm, NtransWSS was significantly higher in the cases with growth than in the cases without growth (odds ratio 2.09, 95% CI 1.02-4.29). the distributions of hemodynamic metrics at each cerebral aneurysm growth site showed that NtransWSS at the dome was significantly higher in the growth cases than in the non-enlargement cases (odds ratio 4.14, 95% CI 1.02-16.80). Conclusion: The data suggest that multidirectional disturbance of wall shear stress is involved in cerebral aneurysm growth, and the disturbance at the dome of the aneurysm may be particularly strongly related. This study was supported by a Grant-in-Aid from the Japanese National Hospital Organization Multi-Center Clinical Research, AMED under grant no. JP15gm0810006h0301 and a JSPS KAKENHI Grant, no. 15K10323. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Usefulness of a pluralistic approach in sentinel surveillance: seasonal influenza activity based on case counts per sentinel site in the National Epidemiological Surveillance of Infectious Diseases Program and test counts, case counts, and test positivity from the National Hospital Organization.

In Japan, based on the National Epidemiological Surveillance of Infectious Diseases (NESID) Program, influenza cases from ~5,000 sentinel sites are monitored weekly as part of influenza surveillance (as number of influenza cases/sentinel site). One limitation is that the number of influenza tests conducted is not reported. Separately, the National Hospital Organization (NHO), with ~140 hospitals, routinely publishes three indicators: number of influenza tests, influenza-positive case counts, and test positivity. We used NESID and NHO data from April 2011 to June 2022 to assess the usefulness of multiple indicators to monitor influenza activity. Temporal trends of the NHO and NESID indicators were similar, and NHO indicator levels well-correlated with those of the NESID indicator. Influenza positivity in the NHO data, however, showed an earlier rise and peak time compared to the NESID indicator. Importantly, through the non-epidemic summer periods and the coronavirus disease 2019 pandemic, a sizable number of influenza tests continued to be done at NHO hospitals, with results showing considerably low case counts and test positivity. These data show that a relatively small number of sentinel sites is sufficient to monitor influenza activity nationally, and, that utilizing multiple indicators can increase our confidence in situational awareness and data interpretations.

Renal function and lipid metabolism in Japanese HIV-1-positive individuals 288 weeks after switching from tenofovir disoproxil fumarate to tenofovir alafenamide fumarate: a single-center, retrospective cohort study

BackgroundContinued use of tenofovir disoproxil fumarate (TDF), an antiretroviral drug, causes renal function decline and tubular damage in individuals with HIV. While tenofovir alafenamide fumarate (TAF) may have less damaging effects, it causes weight gain and abnormal lipid metabolism.MethodsThis single-center, retrospective cohort study used medical records from the National Hospital Organization Sendai Medical Center to investigate renal function of Japanese HIV-1-positive individuals who switched from TDF to antiretroviral therapy including TAF by 2017. The endpoints were: estimated glomerular filtration rate (eGFR), urinary β2 microglobulin (Uβ2MG), weight, and lipid metabolism parameters at 288 weeks after switching. Possible correlation between eGFR and Uβ2MG and factors affecting eGFR decline were examined.ResultsSixty patients switched from TDF to TAF and continued therapy for 288 weeks. eGFR showed a significant decline after 144 weeks, although it was controlled from the time of change until 96 weeks. In the renal impairment group, the decline was suppressed until week 288. Uβ2MG continued to decrease significantly after 48 weeks. However, the suggested correlation between eGFR and Uβ2MG disappeared when patients switched from TDF to TAF. Weight and lipid metabolic parameters increased significantly at 48 weeks and were maintained. Factors associated with decreased eGFR were: history of acquired immune deficiency syndrome (AIDS) and Uβ2MG. However, considering the odds ratio, the switch from TDF to TAF suppressed the eGFR decline in the group with a history of AIDS, and Uβ2MG had no effect on the eGFR decline.ConclusionsSwitching from TDF to TAF for the long term slows eGFR decline, decreases Uβ2MG levels, and reduces worsening of renal function. Weight gain and abnormal lipid metabolism may occur in the short term but are controllable.

Drug effectiveness for COVID-19 inpatients inferred from Japanese medical claim data using propensity score matching

Background Earlier studies and clinical trials of Coronavirus 2019 (COVID-19) showed that drugs such as antiviral drugs, antibody cocktails, and steroids and anti-inflammatory drugs can prevent severe outcomes and death. Methods Observational data in Japan assess drug effectiveness against COVID-19. We applied the average treatment effect model, particularly propensity scoring, which can treat the choice of administered drug as if administration were randomly assigned to inpatients. Data of the Medical Information Analysis Databank, operated by National Hospital Organization in Japan, were used. The outcome was defined as mortality. Subjects were all inpatients, inpatients with oxygen administration, and inpatients using respiratory ventilation, classified by three age classes: all ages, 65 years old or older, and younger than 65 years old. Information about demographic characteristics, underlying disease, administered drug, the proportions of Alpha, Beta and Omicron variant strains, and vaccine coverage were used as explanatory variables for logistic regression. Results Estimated results indicated that only one antibody cocktail (sotrovimab, casirivimab and imdevimab) was associated with raising the probability of survival consistently and significantly. By contrast, other drugs, an antiviral drug (remdesivir), a steroid (dexamethasone), and an anti-inflammatory drug (baricitinib and tocilizumab) were related to reduce the probability of survival. However, propensity score matching method might engender biased results because of a lack of data such as detailed information related to intervention and potential confounders. Therefore, the effectiveness of some drugs might not be evaluated properly in this study. Conclusions Results indicate high likelihood that antibody cocktails were consistently associated with high probability of survival, although low likelihood was found for other drugs for older patients with mild to severe severity and all age patients with moderate severity. Further study is necessary in light of the lack of available data.

Differences in asthma-related outcomes by anti-IL-5 biologics, omalizumab, and dupilumab based on blood eosinophil counts.

Selecting optimal biologics based on type 2 biomarkers has been of interest in severe asthma treatment. However, few direct biomarker stratification-based comparisons have been made. To compare the effectiveness of anti-IL-5 (mepolizumab, benralizumab), omalizumab, and dupilumab in reducing the number of hospitalizations from asthma and exacerbations across all and eosinophil-stratified subgroups. A retrospective cohort study using the National Hospital Organization database (2016-2020) was performed. Asthmatic patients using biologics were selected, and the baseline backgrounds of the groups were balanced using inverse probability treatment weighting for propensity scores. Weighted rate ratios (RRs) were obtained using a Poisson regression model. Among the 320 patients with asthma using biologics, 205 (64.1%), 75 (23.4%), and 40 (12.5%) were categorized into the anti-IL-5, omalizumab, and dupilumab groups, respectively. After weighting, there were 47.1, 30.0, and 62.6 hospitalizations per 100 person-years [omalizumab vs. anti-IL-5: weighted RR, 0.61 (0.34-1.08); dupilumab vs. anti-IL-5: 1.48 (0.81-2.72)], and 117.0, 134.6, and 287.3 exacerbations per 100 person-years [omalizumab vs. anti-IL-5: 1.13 (0.83-1.54); dupilumab vs. anti-IL-5: 2.69 (1.91-3.78)] in these respective groups. In patients with eosinophil of ≥ 300/μL, the dupilumab group had more exacerbations compared with the anti-IL-5 group [weighted RR, 2.85 (1.82-4.46)]. In patients with eosinophil of < 300/μL, the omalizumab group had fewer hospitalizations compared with the anti-IL-5 group [weighted RR, 0.32 (0.13-0.51)]. Anti-IL-5 biologics may be more effective than dupilumab in patients with high blood eosinophil counts, while less effective than omalizumab in patients with low eosinophil counts.

Cancer-Chemotherapy-Related Regimen Checks Performed by Pharmacists of General Hospitals Other than Cancer Treatment Collaborative Base Hospitals: A Multicenter, Prospective Survey.

Although prescription review is an important role for pharmacists in anticancer drug therapy, there are no guidelines in Japan that specify what pharmacists should check for in chemotherapy regimens. This prospective multicenter survey aimed to investigate the implementation of chemotherapy regimen checks by pharmacists in general hospitals by focusing on 19 recommended confirmation items designed to enhance chemotherapy safety. This study involved 14 hospitals within the National Hospital Organization in different regions of Japan. The top five cancers in Japan (gastric, colorectal, lung, breast, and gynecological) were targeted and specific chemotherapy regimens were analyzed. This study assessed the amount of time required for regimen checks, the number of confirmation items completed, the number and the content of inquiries raised regarding prescriptions, and the pharmacists' opinions using a questionnaire that had a maximum score of 10 points. Pharmacists checked 345 and 375 chemotherapies of patients in the control group (CG) and recommended items group (RIG), respectively. The mean time periods required for completing a chemotherapy regimen check were 4 min and 14 s (SD ±1 min and 50 s) and 6 min and 18 s (SD, ±1 min and 7 s) in the CG and RIG, respectively. The mean of the recommended items for the CG = 12.4 and for the RIG = 18.6. The items that the pharmacists did not confirm included urine protein (sixty-nine cases, 18.4%), allergy history (four cases, 1%), previous history (two cases, 0.5%), and a previous history of hepatitis B virus (sixty-nine cases, 18.4%). The number of inquiries for a doctor's prescription order was higher in the RIG than in the CG (41 vs. 27 cases). This multicenter survey demonstrated the potential effectiveness of implementing 19 recommended confirmation items in the regimen checks by pharmacists in general hospitals other than cancer treatment collaborative base hospitals.

An increased relative eosinophil count as a predictive dynamic biomarker in non-small cell lung cancer patients treated with immune checkpoint inhibitors.

An increased relative eosinophil count (REC) has potential as a predictive biomarker for a beneficial clinical response and outcome to cancer immunotherapies. Therefore, the present study investigated the impact of an increased posttreatment REC on the prognosis of non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs). We retrospectively reviewed all 151 patients diagnosed with NSCLC and treated with ICI monotherapy and blood test data between March 2016 and August 2021 at National Hospital Organization Kochi Hospital and Tokushima University. A total of 151 patients with a mean age of 69 years were included. REC after 4 weeks of initial ICI monotherapy was higher than pretreatment REC in 87 patients but not in 64. REC after 4 weeks of the ICI treatment with and without an increased REC were 4.4 and 1.8%, respectively (p < 0.001). Disease control rates (DCR) were significantly higher in patients with than in those without an increased REC (84% vs. 47%, p < 0.001). The median overall survival (OS) of lung cancer patients with or without an increased REC were 674 and 234 days, respectively. A Kaplan-Meier univariate analysis revealed a significant difference in OS between the two groups (p < 0.001). A Cox proportional regression analysis identified an increased REC as an independent predictor of OS (p = 0.003). ICI-treated NSCLC patients with an increased REC after 4 weeks of treatment had a better DCR and prognosis than the other patients examined.

An exploratory pilot study on diffusion MRI measurement of cortical microstructural neurodegeneration for the assessment of dementia in a Japanese hospital setting

AbstractBackgroundThe use of diffusion MRI (dMRI) to assess cortical microstructure has demonstrated promise for measuring neurodegeneration in Alzheimer’s disease (PMID:33174658, PMID:36281682) and frontotemporal dementia (PMID:32641807, PMID:34686217) using retrospective research datasets. The ultimate translation of research findings to clinical practice requires prospective studies in hospital settings. A pilot study at the National Hospital Organization, Niigata, was designed and successfully delivered.MethodThe study was registered on Oct 5th 2021 (jRCT1032210367). Scanning took place between Oct 13th 2021 and June 30th 2022, on a 1.5T Philips Ingenia. MRI data was transferred using a secure cloud gateway (Cimar). A total of 10 healthy controls (HC), 10 Alzheimer’s disease (AD) patients, and 5 frontotemporal dementia (FTD) patients were recruited.Structural (3D T1‐weighted) and dMRI (2mm isotropic, 32 directions at b = 1000 s/mm2) scans were used to calculate cortical mean diffusivity and three neuropathologically‐inspired cortical diffusivity measures: the angle between the radial minicolumnar direction and the principal diffusion direction (AngleR); the principal diffusion component parallel with the minicolumns (ParlPD), and the diffusion components perpendicular to the minicolumns (PerpPD+). Metrics were also summarized over AD signature regions (Ridgway et al., CTAD 2022).ResultOf the n = 25 cases, 18 had clear clinical diagnoses after neurological and radiological assessment, while 7 were more complex (including focal bleeding, focal ischemia, meningioma, supra‐sellar tumour). Characteristics are given in Table 1.Figure 1 plots two whole‐brain measures: PerpPD+ and AngleR. A threshold of PerpPD+ &gt; 1.325 has 100% sensitivity to the 8 clear AD cases, with 86% specificity for 7 controls vs AD. Results were less clear for FTD using whole‐brain measures alone.The Cohen’s d effect size for clear AD versus clear HC was 2.82 using whole‐brain PerpPD+. Using signature regions (Figure 2b) improved separation to d = 3.08 for PerpPD+, compared to d = 1.87 for the cortical thickness signature (Figure 2a).ConclusionThe pilot study demonstrated practical feasibility and good performance for distinguishing AD from HC using cortical diffusivity measures acquired at the 1.5T field‐strength common in hospitals in Japan. Future work will investigate FTD signature regions. A larger multicentre study assessing diagnostic accuracy using additional AD biomarkers is warranted.

An exploratory pilot study on diffusion MRI measurement of cortical microstructural neurodegeneration for the assessment of dementia in a Japanese hospital setting

AbstractBackgroundThe use of diffusion MRI (dMRI) to assess cortical microstructure has demonstrated promise for measuring neurodegeneration in Alzheimer’s disease (PMID:33174658, PMID:36281682) and frontotemporal dementia (PMID:32641807, PMID:34686217) using retrospective research datasets. The ultimate translation of research findings to clinical practice requires prospective studies in hospital settings. A pilot study at the National Hospital Organization, Niigata, was designed and successfully delivered.MethodThe study was registered on Oct 5th 2021 (jRCT1032210367). Scanning took place between Oct 13th 2021 and June 30th 2022, on a 1.5T Philips Ingenia. MRI data was transferred using a secure cloud gateway (Cimar). A total of 10 healthy controls (HC), 10 Alzheimer’s disease (AD) patients, and 5 frontotemporal dementia (FTD) patients were recruited. Structural (3D T1‐weighted) and dMRI (2mm isotropic, 32 directions at b = 1000 s/mm2) scans were used to calculate cortical mean diffusivity and three neuropathologically‐inspired cortical diffusivity measures: the angle between the radial minicolumnar direction and the principal diffusion direction (AngleR); the principal diffusion component parallel with the minicolumns (ParlPD), and the diffusion components perpendicular to the minicolumns (PerpPD+). Metrics were also summarized over AD signature regions (Ridgway et al., CTAD 2022).ResultOf the n = 25 cases, 18 had clear clinical diagnoses after neurological and radiological assessment, while 7 were more complex (including focal bleeding, focal ischemia, meningioma, supra‐sellar tumour). Characteristics are given in Table 1. Figure 1 plots two whole‐brain measures: PerpPD+ and AngleR. A threshold of PerpPD+ &gt; 1.325 has 100% sensitivity to the 8 clear AD cases, with 86% specificity for 7 controls vs AD. Results were less clear for FTD using whole‐brain measures alone. The Cohen’s d effect size for clear AD versus clear HC was 2.82 using whole‐brain PerpPD+. Using signature regions (Figure 2b) improved separation to d = 3.08 for PerpPD+, compared to d = 1.87 for the cortical thickness signature (Figure 2a).ConclusionThe pilot study demonstrated practical feasibility and good performance for distinguishing AD from HC using cortical diffusivity measures acquired at the 1.5T field‐strength common in hospitals in Japan. Future work will investigate FTD signature regions. A larger multicentre study assessing diagnostic accuracy using additional AD biomarkers is warranted.

Predictors of 2-Year Mortality in Patients Receiving Long-Term Oxygen Therapy: A Prospective Observational Study.

Background: Patients receiving long-term oxygen therapy are in a state of progressive respiratory dysfunction and have high mortality. However, the predictors of mortality in these patients have not yet been established. Objectives: This prospective observational study aimed to identify the predictors of two-year mortality in patients receiving long-term oxygen therapy. Design, Setting/Subjects: This two-year prospective observational study included 96 patients who received long-term oxygen therapy in the outpatient department of the National Hospital Organization Nishiniigata Chuo Hospital in Japan. Measurements: The updated Charlson Comorbidity Index, body mass index, handgrip strength, modified British Medical Research Council scale (mMRC), Barthel Index (BI), and Montreal Cognitive Assessment (MoCA) were collected in 2019 as a baseline. Outcome was defined as mortality due to chronic respiratory disease during the two-year follow-up period, and predictors were estimated using age- and sex-adjusted Cox proportional hazards model. Results: The 83 patients that were followed up, 30 (36%) died. The Cox proportional hazards model estimated handgrip strength (adjusted hazard ratio [HR]: 0.89; 95% confidence interval [CI]: 0.84-0.94; p < 0.01; Wald: 14.38.), mMRC (adjusted HR: 1.96; 95% CI: 1.36-2.83; p < 0.01; Wald: 13.16.), BI (adjusted HR: 0.95; 95% CI: 0.93-0.98; p < 0.01; Wald: 17.07.), and MoCA (adjusted HR: 2.17; 95% CI: 1.31-3.59; p < 0.01; Wald: 9.06) as predictors. Conclusions: This study indicated that handgrip strength, dyspnea, activities of daily living, and cognitive function were predictors of two-year mortality in patients receiving long-term oxygen therapy.

Microbiological findings in patients with community-acquired pneumonia: An analysis using the National Hospital Organization Clinical Data Archives

Although large-scale administrative databases may be useful for studies of infectious diseases, conventional databases lack microbiological data. To illustrate the applicability of the National Hospital Organization Clinical Data Archives, a novel database of electronic medical records in Japan, we conducted a descriptive study of the microbiological findings in patients with community-acquired pneumonia using the database. We identified patients aged ≥18 years who were hospitalized for community-acquired bacterial pneumonia between April 2016 and March 2019. We evaluated the results of bacterial culture and antibacterial susceptibility of specimens obtained on the first day of hospitalization, in addition to patient characteristics, diagnosis codes, and intravenous antibiotics administered. The analysis identified 2200 eligible patients from 15 hospitals. Sulbactam–ampicillin was the most frequently used initial antibiotic (32 %), followed by ceftriaxone (22 %) and tazobactam–piperacillin (19 %). Overall, 56 %, 95 %, 56 %, and 73 % of patients with pathogen-specific diagnosis codes in the database for Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae, and Pseudomonas aeruginosa, respectively, also tested positive for the corresponding pathogen in their sputum or blood cultures. Antibacterial susceptibilities were consistent with a previous report from Japan; 81 % of S. pneumoniae cases were resistant to azithromycin, and 48 % of H. influenzae cases were resistant to ampicillin. These microbiological characteristics warrant the future use of this database for detailed real-world research on infectious diseases.

Pretreatment eosinophil counts as a predictive biomarker in non-small cell lung cancer patients treated with immune checkpoint inhibitors.

The peripheral blood eosinophil count prior to treatment has potential as a predictive biomarker for a beneficial clinical response to cancer immunotherapies. Therefore, the present study investigated the impact of the eosinophil count on overall survival (OS) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICI). We retrospectively reviewed all patients diagnosed with NSCLC and treated with ICI monotherapy between March 2016 and August 2021 at National Hospital Organization Kochi Hospital and Tokushima University. A total of 166 patients were included. Fifty-five patients had an eosinophil count of less than 100 cells/μL (Eo < 100). Nighty-eight patients had an eosinophil count of 100 cells/μL or more, but less than 500 cells/μL (100 ≤ Eo < 500). Thirteen patients had an eosinophil count of 500 cells/μL or more (Eo ≥500). The median OS of all lung cancer patients was 476 days. The median OS of lung cancer patients with Eo <100, 100 ≤ Eo <500, and Eo ≥500 was 339, 667, and 143 days, respectively. A Kaplan-Meier univariate analysis showed a significant difference in OS between these three groups (p < 0.001). A Cox proportional regression analysis identified 100 ≤ Eo <500 (p = 0.04), ECOG PS score ≥ 2 (p = 0.02), tumor size ≥5 cm (p = 0.02), and PD-L1 ≥ 1% (p = 0.01) as independent predictors of OS. OS was significantly longer in ICI-treated NSCLC patients with a pretreatment eosinophil count of 100 ≤ Eo <500 than in the other patients and, thus, has potential as a new predictive biomarker.

Respiratory pathogen trends in patients with Kawasaki disease during the COVID-19 pandemic and respiratory syncytial virus epidemic in Japan.

Although the etiology of Kawasaki disease (KD) remains unknown, the most common view is that an infectious agent triggers the activation of the inflammatory cascade in predisposed children. The coronavirus disease 2019 (COVID-19) pandemic has led to the establishment of infection control measures, which reduced the overall incidence of respiratory infections; however, a resurgence of respiratory syncytial virus (RSV) infection occurred in the summer of 2021. This study aimed to examine the relationship between respiratory pathogens and KD during the COVID-19 pandemic and the RSV epidemic in Japan between 2020 and 2021. We retrospectively reviewed the medical charts of pediatric patients with KD or respiratory tract infection (RTI) admitted to National Hospital Organization Okayama Medical Center between December 1, 2020, and August 31, 2021. All patients with KD and RTI underwent multiplex polymerase chain reaction testing upon admission. We classified patients with KD into the three subgroups-pathogen-negative, single pathogen-positive, and multi-pathogen-positive-and compared their laboratory data and clinical features. This study enrolled 48 patients with KD and 269 with RTI. Rhinovirus and enterovirus were the most prevalent pathogens in both patients with KD and RTI (13 [27.1%] and 132 patients [49.1%], respectively). The clinical characteristics of the pathogen-negative KD group and the pathogen-positive KD group at diagnosis were similar; however, the pathogen-negative group tended to receive additional treatment, such as multiple courses of intravenous immunoglobulin, intravenous methylprednisolone, infliximab, cyclosporine A, and plasmapheresis, more frequently. The number of patients with KD remained stable when RTI was not prevalent but increased following the surge in RTI with RSV. An epidemic of respiratory infections led to an increase in the incidence of KD. Patients with respiratory pathogen-negative KD could have greater recalcitrance to intravenous immunoglobulin than those with respiratory pathogen-positive KD.

Utility of a loop-mediated isothermal amplification detection kit to diagnose chronic pulmonary aspergillosis

BackgroundDiagnosing chronic pulmonary aspergillosis (CPA) is still challenging, and infection with Aspergillus spp. must be detected early. The aim of this study was to evaluate, for the first time, the usefulness of a new loop-mediated isothermal amplification (LAMP) test kit in diagnosing CPA. MethodsThis cross-sectional study was performed at the National Hospital Organization Kinki-Chuo Chest Medical Center. We prospectively enrolled patients with and without CPA. The primary outcomes of this study were the sensitivity and specificity of LAMP for the diagnosis of CPA. ResultsIn total, 34 patients with CPA and 21 without CPA (the control group) were enrolled between October 2019 and December 2021. Among the 34 patients with CPA, cultures were positive for CPA in 16 and negative for 18. The majority of fungi isolated in sputum were A. fumigatus in 15 specimens; Aspergillus flavus was isolated in 1) LAMP demonstrated 55.9% sensitivity (95% confidence interval [CI] 37.9–72.8) and 100.0% specificity (95% CI 77.2–100.0). ConclusionLAMP is an acceptable tool for diagnosing CPA, and its application in clinical practice necessitates more studies.

Re-immunotherapy with nivolumab plus ipilimumab in advanced non-small cell lung cancer patients previously treated with anti-programmed death-1 and/or anti-programmed death ligand-1 antibodies

BackgroundThe role of re-immunotherapy in advanced non-small cell lung cancer (NSCLC) remains unclear. No studies have evaluated the re-immunotherapy regimen including anti-cytotoxic T-lymphocyte antigen-4 antibody for lung cancer treatment. This study aimed to investigate the efficacy and safety of re-immunotherapy with nivolumab plus ipilimumab in patients with advanced NSCLC previously treated with anti-programmed death-1 (PD-1) and/or anti-programmed death ligand-1 (PD-L1) antibodies.MethodsWe retrospectively reviewed patients with advanced or recurrent NSCLC who received immunotherapy with nivolumab plus ipilimumab (without concomitant cytotoxic chemotherapy) between November 2020 and November 2022 at the National Hospital Organization Kyoto Medical Center, Kyoto, Japan. Data were extracted from patients who had previously received immunotherapies with anti-PD-1 and/or anti-PD-L1 antibodies. Treatment responses and adverse events were evaluated.ResultsOf the 67 patients who received immunotherapy with nivolumab plus ipilimumab, 23 were included in final analysis. The objective response rate was 17%, and the disease control rate was 48% for nivolumab plus ipilimumab therapy. The highest grade of immune-related adverse events was grade 3, occurring in 11% of cases.ConclusionRe-immunotherapy with nivolumab plus ipilimumab after anti-PD-1 and/or anti-PD-L1 immunotherapy may be feasible and provide clinical benefit in selected patients. Further prospective studies are warranted to identify the patient population that may benefit from re-immunotherapy.

Low placental weight may be involved in the etiology of congenital cryptorchidism in neonatal boys

IntroductionSeveral factors have been reported to be associated with the etiology of cryptorchidism; however, clear evidence regarding the risk factors for cryptorchidism is elusive. In the present study, we evaluated the clinical characteristics of cryptorchidism using the common neonatal intensive-care unit (NICU) database of the National Hospital Organization and explored one of possible factors associated with the development of cryptorchidism. MethodsA total of 7882 male neonates were included in this study. We separated them into two groups: those without cryptorchidism (n = 7852) and those with cryptorchidism (n = 30) at the time of discharge from the NICU. Cryptorchidism was defined as a condition in which the testis was located out of the scrotum on the route of descent at the time of NICU discharge.The associations between cryptorchidism and the maternal, placental, and neonatal information were analyzed. Analyses were performed statistically to compare nominal variables between the groups using Fisher's direct establishment calculation method and logistic regression analyses. ResultsUnivariate analyses showed the placental weight <10% tile (odds ratio 3.31, 95% confidence interval [CI] 1.18–8.64), birth height <−2 standard deviations (SD) (odds ratio 3.65, 95% CI 0.92–10.6), birth weight <−2SD (odds ratio 4.06, 95% CI 1.55–9.51), and small for gestational age (odds ratio 3.82, 95% CI 1.46–8.97) were significantly associated with the development of cryptorchidism. Multivariate analyses showed that placental weight <10th percentile (odds ratio 2.86, 95% CI 1.11–7.44) was significantly associated with the development of cryptorchidism. DiscussionAlthough, this study population was limited to infants admitted to the ICU, the data indicated a possible association between low placental weight and the development of cryptorchidism in neonatal boys.