Association between hospital case volume and mortality in non-elderly pneumonia patients stratified by severity: a retrospective cohort study

Background: The characteristics and aetiology of pneumonia in the non-elderly population is distinct from that in the elderly population. While a few studies have reported an inverse association between hospital case volume and clinical outcome in elderly pneumonia patients, the evidence is lacking in a younger population. In addition, the relationship between volume and outcome may be different in severe pneumonia cases than in mild cases. In this context, we tested two hypotheses: 1) non-elderly pneumonia patients treated at hospitals with larger case volume have better clinical outcome compared with those treated at lower case volume hospitals; 2) the volume-outcome relationship differs by the severity of the pneumonia. Methods: We conducted the study using the Japanese Diagnosis Procedure Combination database. Patients aged 18–64 years discharged from the participating hospitals between July to December 2010 were included. The hospitals were categorized into four groups (very-low, low, medium, high) based on volume quartiles. The association between hospital case volume and in-hospital mortality was evaluated using multivariate logistic regression with generalized estimating equations adjusting for pneumonia severity, patient demographics and comorbidity score, and hospital academic status. We further analyzed the relationship by modified A-DROP pneumonia severity score calculated using the four severity indices: dehydration, low oxygen saturation, orientation disturbance, and decreased systolic blood pressure. Results: We identified 8,293 cases of pneumonia at 896 hospitals across Japan, with 273 in-hospital deaths (3.3%). In the overall population, no significant association between hospital volume and in-hospital mortality was observed. However, when stratified by pneumonia severity score, higher hospital volume was associated with lower in-hospital mortality at the intermediate severity level (modified A-DROP score = 2) (odds ratio (OR) of very low vs. high: 2.70; 95% confidence interval (CI): 1.12–6.55, OR of low vs. high: 2.40; 95% CI:0.99–5.83). No significant association was observed for other severity strata. Conclusions: Hospital case volume was inversely associated with in-hospital mortality in non-elderly pneumonia patients with intermediate pneumonia severity. Our result suggests room for potential improvement in the quality of care in hospitals with lower volume, to improve treatment outcomes particularly in patients admitted with intermediate pneumonia severity

Nuclear Localization of COX-2 in relation to the Expression of Stemness Markers in Urinary Bladder Cancer

Inflammation may activate stem cells via prostaglandin E2 (PGE2) production mediated by cyclooxygenase-2 (COX-2) expression. We performed an immunohistochemical analysis of the expression of stemness markers (Oct3/4 and CD44v6) and COX-2 in urinary bladder tissues obtained from cystitis and cancer patients with and without Schistosoma haematobium infections. Immunoreactivity to Oct3/4 was significantly higher in S. haematobium-associated cystitis and cancer tissues than in normal tissues. CD44v6 expression was significantly higher in bladder cancer without S. haematobium than in normal tissues. COX-2 was located in the cytoplasmic membrane, cytoplasm, and nucleus of the cancer cells. Interestingly, the nuclear localization of COX-2, which was reported to function as a transcription factor, was significantly associated with the upregulation of Oct3/4 and CD44v6 in bladder cancer tissues with and without S. haematobium infection, respectively. COX-2 activation may be involved in inflammation-mediated stem cell proliferation/differentiation in urinary bladder carcinogenesis

Independent calculation-based verification of volumetric-modulated arc therapy–stereotactic body radiotherapy plans for lung cancer

This study aimed to investigate the feasibility of independent calculation‐based verification of volumetric‐modulated arc therapy (VMAT)–stereotactic body radiotherapy (SBRT) for patients with lung cancer using a secondary treatment planning system (sTPS). In all, 50 patients with lung cancer who underwent VMAT‐SBRT between April 2018 and May 2019 were included in this study. VMAT‐SBRT plans were devised using the Collapsed‐Cone Convolution in RayStation (primary TPS: pTPS). DICOM files were transferred to Eclipse software (sTPS), which utilized the Eclipse software, and the dose distribution was then recalculated using Acuros XB. For the verification of dose distribution in homogeneous phantoms, the differences among pTPS, sTPS, and measurements were evaluated using passing rates of a dose difference of 5% (DD5%) and gamma index of 3%/2 mm (γ3%/2 mm). The ArcCHECK cylindrical diode array was used for measurements. For independent verification of dose‐volume parameters per the patient’s geometry, dose‐volume indices for the planning target volume (PTV) including D95% and the isocenter dose were evaluated. The mean differences (± standard deviations) between the pTPS and sTPS were then calculated. The gamma passing rates of DD5% and γ3%/2 mm criteria were 99.2 ± 2.4% and 98.6 ± 3.2% for pTPS vs. sTPS, 92.9 ± 4.0% and 94.1 ± 3.3% for pTPS vs. measurement, and 93.0 ± 4.4% and 94.3 ± 4.1% for sTPS vs. measurement, respectively. The differences between pTPS and sTPS for the PTVs of D95% and the isocenter dose were −3.1 ± 2.0% and −2.3 ± 1.8%, respectively. Our investigation of VMAT‐SBRT plans for lung cancer revealed that independent calculation‐based verification is a time‐efficient method for patient‐specific quality assurance

Trk-fused gene (TFG) regulates pancreatic beta cell mass and insulin secretory activity

The Trk-fused gene (TFG) is reportedly involved in the process of COPII-mediated vesicle transport and missense mutations in TFG cause several neurodegenerative diseases including hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P). The high coincidence ratio between HMSN-P and diabetes mellitus suggests TFG to have an important role(s) in glucose homeostasis. To examine this possibility, β-cell specific TFG knockout mice (βTFG KO) were generated. Interestingly, βTFG KO displayed marked glucose intolerance with reduced insulin secretion. Immunohistochemical analysis revealed smaller β-cell masses in βTFG KO than in controls, likely attributable to diminished β-cell proliferation. Consistently, β-cell expansion in response to a high-fat, high-sucrose (HFHS) diet was significantly impaired in βTFG KO. Furthermore, glucose-induced insulin secretion was also markedly impaired in islets isolated from βTFG KO. Electron microscopic observation revealed endoplasmic reticulum (ER) dilatation, suggestive of ER stress, and smaller insulin crystal diameters in β-cells of βTFG KO. Microarray gene expression analysis indicated downregulation of NF-E2 related factor 2 (Nrf2) and its downstream genes in TFG depleted islets. Collectively, TFG in pancreatic β-cells plays a vital role in maintaining both the mass and function of β-cells, and its dysfunction increases the tendency to develop glucose intolerance.This study was partly supported by a Grant-in-Aid for Research Activity Start-up (JSPS KAKENHI Grant Number JP15H06427) (to T.Y.) from the Ministry of Education, Science, Sports and Culture, Japan, and grants from Mitsubishi Tanabe Pharma (to T.Y.), Novartis Pharma (to T.Y.), Takeda Science Foundation (to Y.N.), Asahi Life Foundation (to Y.N.) and The Uehara Memorial Foundation (to Y.N.)

Association between statistical significance and time to publication among systematic reviews: a study protocol for a meta-epidemiological investigation

INTRODUCTION: Many studies have indicated the impact of bias in dissemination and publication in medical research. Existence of such bias among clinical trials has been repeatedly pointed out, but it has not been well studied in the field of systematic reviews (SRs). We therefore aim to investigate whether or not time lag bias and publication bias in SRs based on statistical significance in results exist. In addition, we will examine at what stage of paper publication process such bias, if any, creeps in. METHOD AND ANALYSIS: The present study is a meta-epidemiological study. We will include all SRs of interventions registered in the international prospective register of SRs (PROSPERO) before December 2014 if the SR has completed its analysis irrespective of its publication status. All contact authors of eligible SRs will be asked to participate in a survey administered through the Internet. Our primary outcome is time from protocol registration to full publication of SR as a journal article, defined as time from the registration date to the acceptance date among all the relevant SRs. We will examine the impact of statistically significant findings on the primary outcomes through time to event analyses. ETHICS AND DISSEMINATION: Ethics approval will be obtained from the Ethical Committee of the Kyoto University Graduate School of Medicine. This protocol has been registered in the University Hospital Medical Information Network Clinical Trials Registry. We will publish our findings in a peer-reviewed journal and also may present them at conferences. TRIAL REGISTRATION NUMBER: UMIN000028325