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This study aimed to evaluate the accuracy of the lacrimal syringing test (syringing) in relation to dacryocystography (DCG) and dacryoendoscopy (DE) in lacrimal pathway (LP) obstruction. We retrospectively reviewed 101 patients (188 LPs) who underwent syringing, cone-beam computed tomography (CBCT)-DCG, and DE to diagnose the degree and site of LP obstruction. The degree of obstruction was classified into patent, partial obstruction, and complete obstruction. The degree of LP obstruction was determined by combining the findings of DE and CBCT-DCG and was designated as DCG+DE. When differentiating complete or partial obstruction on DE was uncertain, complete or partial obstruction was assigned if the DCG showed evidence of contrast media obstruction or passage, respectively. The consistency between syringing and DCG+DE was evaluated by calculating the weighted kappa coefficient. The sensitivity and specificity of syringing were 94% and 89%, respectively. The weighted Cohen's kappa value of agreement between syringing and DCG+DE was κ = 0.73 ( = 0.04, 95% confidence interval [CI]: 0.66-0.80,  < 0.01). When divided into presaccal and postsaccal obstruction categories, the kappa values were κ = 0.40 (  = 0.11, 95% CI: 0.19-0.62,  < 0.01) and 0.55 (  = 0.09, 95% CI: 0.37-0.73,  < 0.01), respectively. Furthermore, when limited to common canaliculus obstruction (stenoses), which accounted for 78% (46 LPs) of the total presaccal obstructions, the kappa value was κ = 0.29 (  = 0.12, 95% CI: 0.05-0.54,  = 0.021), which demonstrated the lowest consistency between syringing and DCG+DE. Syringing was \"substantially\" in agreement with DCG+DE in detecting the degree of LP obstruction. Moreover, syringing was a sufficiently sensitive and specific test when performed by an experienced clinician. However, distinguishing between complete and partial obstructions by syringing was sometimes difficult, particularly in the common canaliculus obstruction (stenosis).

Previous studies have shown inconsistent prognostic accuracy for mortality with both quick sequential organ failure assessment (qSOFA) and the systemic inflammatory response syndrome (SIRS) criteria. We aimed to validate the accuracy of qSOFA and the SIRS criteria for predicting in-hospital mortality in patients with suspected infection in the emergency department. A prospective study was conducted including participants with suspected infection who were hospitalised or died in 34 emergency departments in Japan. Prognostic accuracy of qSOFA and SIRS criteria for in-hospital mortality was assessed by the area under the receiver operating characteristic (AUROC) curve. Of the 1060 participants, 402 (37.9%) and 915 (86.3%) had qSOFA ≥ 2 and SIRS criteria ≥ 2 (given thresholds), respectively, and there were 157 (14.8%) in-hospital deaths. Greater accuracy for in-hospital mortality was shown with qSOFA than with the SIRS criteria (AUROC: 0.64 versus 0.52, difference + 0.13, 95% CI [+ 0.07, + 0.18]). Sensitivity and specificity for predicting in-hospital mortality at the given thresholds were 0.55 and 0.65 based on qSOFA and 0.88 and 0.14 based on SIRS criteria, respectively. To predict in-hospital mortality in patients visiting to the emergency department with suspected infection, qSOFA was demonstrated to be modestly more accurate than the SIRS criteria albeit insufficiently sensitive. Clinical Trial Registration: The study was pre-registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000027258).

Purpose This study investigated the safety and efficacy of orthokeratology in myopic children in Japan. Study design Prospective clinical trial. Methods This study enrolled myopic children aged 6–16 years with a spherical equivalent of −1.00 D to −4.00 D and astigmatism of −1.5 D or lower, whose parents could manage contact lens use and could provide written informed consent. The children were treated with orthokeratology lenses (BREATH-O CORRECT R, Universal View Co., Ltd.) for 3 years. Slit-lamp findings, visual acuity, intraocular pressure, subjective refraction, corneal topography, corneal endothelial cell density, corneal thickness, and axial length were regularly assessed. Results This study included 96 eyes of 48 patients (average age, 10.7 ± 2.08 years). The average baseline spherical equivalent was −2.46 ± 0.97 D. The average baseline uncorrected visual acuity was 0.74 ± 0.32 logMAR, with significant improvement to −0.08 ± 0.18 logMAR at 4 weeks and 0.02 ± 0.21 logMAR at 3 years (both p  < 0.001, Dunnett’s test). The average baseline corneal endothelial cell density was 3053 ± 181 cells/mm 2 and 3028 ± 213 cells/mm 2 at postoperative 3 years ( p  = 0.9933, Dunnett’s test). The average axial length was 24.70 ± 0.78 mm at baseline, 24.77 ± 0.80 mm at 12 weeks, and 25.32 ± 0.85 mm at 36 months. Although mild corneal epithelial disorders occurred in 18% of eyes, they were successfully treated with eye drops, enabling resumption of lens usage. No serious adverse events were observed. Conclusion Orthokeratology lens (BREATH-O CORRECT R) use in children demonstrated good efficacy and safety during 3 years of follow-up.

Purpose Cytomegalovirus (CMV) corneal endotheliitis often causes severe visual impairment owing to irreversible corneal endothelial dysfunction. Given the side effects of systemic antiviral therapy, development of an approved topical antiviral agent for CMV corneal endotheliitis is desirable. This study evaluated the efficacy and safety of topical 0.15% GCV gel, ROH-101, in the treatment of CMV corneal endotheliitis in Japanese patients. Study design Open-label, multicenter, uncontrolled, phase 3 study (jRCT2051210064). Methods The study was conducted from August 2021 to December 2022, with a 2-week run-in period with 0.1% fluorometholone eye drops alone, a 12-week treatment period with additional ROH-101, and a 24-week post-treatment observation period after discontinuation of ROH-101. The primary endpoint was the proportion of patients achieving a CMV DNA copy number in the aqueous humor of less than 10 3 copies/mL at week 12. The clinical findings and safety were assessed over the treatment and post-treatment observation periods. Results Twelve eyes of 12 patients with PCR-proven CMV corneal endotheliitis were enrolled. Treatment was discontinued in 1 eye owing to an adverse event. The other 11 eyes completed 12 weeks of treatment with 63.6% achieving the primary endpoint. The clinical findings, such as corneal edema, coin-shaped lesions, and anterior chamber inflammation, improved in all 11 eyes and did not worsen in 8 eyes that completed the post-treatment observation period. Endothelial cell density was well maintained, and none of the 11 eyes showed corneal endothelial dysfunction. Mild adverse drug reactions were reported in 3 eyes (8.3%). Conclusion ROH-101 was a safe and efficacious treatment in Japanese patients diagnosed with CMV corneal endotheliitis.

BackgroundAlthough continuous regional arterial infusion (CRAI) of protease inhibitors and broad antibiotics has been suggested as one of the therapeutic option for patients with acute necrotic pancreatitis (ANP), the effectiveness has not been well-corroborated in clinical studies.MethodsWe conducted a retrospective cohort study using a Japanese national administrative database. Severe acute pancreatitis patients with a poorly enhanced pancreas region (i.e., definitive or clinically suspected ANP) were identified and dichotomized according to whether CRAI was performed. We compared the outcomes of in-hospital mortality, surgical interventions, hospital-free days, and healthcare costs between groups adjusted by the well-validated case-mix adjustment model using a multivariate mixed-effect regression analysis and a propensity score matching analysis.ResultsOf 243,312 acute pancreatitis patients, 702 eligible patients were identified, of these 339 patients underwent CRAI. The case-mix adjustment model established had good predictability for in-hospital mortality with an area under the receiver operating characteristics curve of 0.87. CRAI was significantly associated with reduced in-hospital mortality [14.5% in the CRAI group vs. 18.2% in the non-CRAI group, adjusted odds ratio (95% confidence interval; CI) = 0.60 (0.36–0.97)]. Significant associations were not observed for the frequency of surgical interventions and mean hospital-free days; however, significantly higher healthcare costs were observed in the CRAI group. Results of the propensity score matching analysis did not alter these results.ConclusionsAnalysis of a nationwide large-scale database suggested that CRAI was significantly associated with reduced in-hospital mortality for patients with ANP. Further randomized controlled trials are warranted.

Aim To compare in‐hospital mortality of severely injured trauma patients who underwent resuscitative endovascular balloon occlusion of the aorta (REBOA) or aortic cross‐clamping (ACC). Methods In this multicenter, retrospective cohort study using data from a nationwide trauma registry of tertiary emergency medical centers in Japan (n = 280), trauma patients who underwent aortic occlusion at the emergency department from 2004 to 2019 were divided into two groups according to the treatment they received: patients treated with ACC and patients who underwent placement of a REBOA catheter. Multiple imputations were used to handle the missing data. In‐hospital mortality of the patients who underwent REBOA or ACC was compared using a mixed‐effect logistic regression analysis and a propensity score‐matching analysis, in which the confounders, including baseline patient demographics and severity, were adjusted. Results Of 1,670 patients (1,137 with REBOA and 533 with ACC), 66% were male. The median age was 56 years, and the mortality rate was 55.2% in the REBOA group and 81.6% in the ACC group. The mixed‐effect model regression analysis showed a significantly lower odds ratio for in‐hospital mortality rate in the REBOA group (odds ratio 0.17; 95% confidence interval, 0.12–0.26). A similar odds ratio was observed in the propensity score matching analysis (odds ratio 0.27; 95% confidence interval, 0.18–0.40). Conclusion Compared with ACC, REBOA use was associated with decreased mortality in severely injured trauma patients. The purpose of this study was to examine the treatment methods and prognosis of patients with severe multiple trauma registered in the Japan Trauma Data Bank, and to examine the relevance of resuscitative endovascular balloon occlusion of the aorta (REBOA). The mixed‐effect model regression analysis showed a significantly lower odds ratio for in‐hospital mortality rate in the REBOA group. REBOA use was associated with decreased mortality compared to aortic cross‐clamping in severely injured trauma patients.

Background The benefits of a high plasma-to-red blood cell (RBC) ratio on the survival of injured patients who receive massive transfusions remain unclear, especially in older patients. We aimed to investigate the interaction of age with the plasma-to-RBC ratio and clinical outcomes of trauma patients. Methods In this retrospective study conducted from 2013 to 2016, trauma patients who received massive transfusions were included. Using a generalized additive model (GAM),we assessed how the plasma-to-RBC ratio and age affected the in-hospital mortality rates. The association of the plasma-to-RBC ratio [low (< 0.5), medium (0.5–1.0), and high (≥ 1.0)] with in-hospital mortality and the incidence of adverse events were assessed for the overall cohort and for patients stratified into non-geriatric (16–64 years) and geriatric (≥ 65 years) groups using logistic regression analyses. Results In total, 13,894 patients were included. The GAM plot of the plasma-to-RBC ratio for in-hospital mortality demonstrated a downward convex unimodal curve for the entire cohort. The low-transfusion ratio group was associated with increased odds of in-hospital mortality in the non-geriatric cohort [odds ratio 1.38, 95% confidence interval (CI) 1.22–1.56]; no association was observed in the geriatric group (odds ratio 0.84, 95% CI 0.62–1.12). An increase in the transfusion ratio was associated with a higher incidence of adverse events in the non-geriatric and geriatric groups. Conclusion The association of the non-geriatric age category and plasma-to-RBC ratio for in-hospital mortality was clearly demonstrated. However, the relationship between the plasma-to-RBC ratio with mortality among geriatric patients remains inconclusive.

This retrospective observational study compared the outcomes of transcatheter arterial embolization (TAE) versus open surgery in patients with blunt abdominal solid organ injury (liver, spleen, or kidney; abdominal Abbreviated Injury Scale [AIS] ≥ 3) with traumatic brain injury (TBI) (head AIS ≥ 3), using data from the Japan Trauma Data Bank (2004–2019). Patient characteristics were adjusted using propensity score matching. The primary endpoint was in-hospital mortality; secondary endpoints included 48-h mortality, transfusion requirements, and complications. After matching, 135 patients per group were analyzed. In-hospital mortality was significantly lower in the TAE group (25/135 [18.5%] vs. 42/135 [31.1%], adjusted odds ratio [AOR] 0.247, 95% confidence interval 0.101–0.605, p  = 0.002). TAE also showed lower 48-h mortality (10/135 [7.4%] vs. 22/135 [16.3%], AOR 0.306, p  = 0.008) and transfusion rates. Complication rates were similar. Subgroup analysis showed that TAE was associated with lower mortality in non-shock (AOR 0.392, p  = 0.032), elderly (AOR 0.293, p  = 0.044), and focal TBI patients (AOR 0.301, p  = 0.004) but not in patients with diffuse TBI. TAE may be a feasible treatment option for selected patients with blunt abdominal solid organ injury complicated by TBI, particularly in hemodynamically stable, elderly, and focal TBI patients. These findings require prospective validation.

The antitumor activity of activated CD8+ T cells in the tumor microenvironment seems to be limited due to their being metabolically unfit. This metabolic unfitness is closely associated with T‐cell exhaustion and impairment of memory formation, which are barriers to successful antitumor adoptive immunotherapy. We therefore assessed the role of glutamine metabolism in the antitumor activity of CD8+ T cells using a tumor‐inoculated mouse model. The adoptive transfer of tumor‐specific CD8+ T cells cultured under glutamine‐restricted (dGln) conditions or CD8+ T cells treated with specific inhibitors of glutamine metabolism efficiently eliminated tumors and led to better survival of tumor‐inoculated mice than with cells cultured under control (Ctrl) conditions. The decreased expression of PD‐1 and increased Ki67 positivity among tumor‐infiltrating CD8+ T cells cultured under dGln conditions suggested that the inhibition of glutamine metabolism prevents CD8+ T‐cell exhaustion in vivo. Furthermore, the transferred CD8+ T cells cultured under dGln conditions expanded more efficiently against secondary OVA stimulation than did CD8+ T cells under Ctrl conditions. We found that the expression of a pro‐survival factor and memory T cell‐related transcription factors was significantly higher in CD8+ T cells cultured under dGln conditions than in those cultured under Ctrl conditions. Given these findings, our study uncovered an important role of glutamine metabolism in the antitumor activity of CD8+ T cells. The novel adoptive transfer of tumor‐specific CD8+ T cells cultured in glutamine‐restricted conditions may be a promising approach to improve the efficacy of cell‐based adoptive immunotherapy. This manuscript uncovered an important role of glutamine metabolism in regulating antitumor activity of CD8+ T cells. Adoptive transfer of tumor‐specific CD8+ T cells cultured in glutamine‐restricted conditions improved the efficacy of CD8+ T cell‐based cancer adoptive immunotherapy.

The effectiveness and safety of transcatheter splenic artery embolization (SAE) compared to those of open surgery in patients with blunt splenic injury (BSI) remain unclear. This retrospective cohort-matched study utilized data from the Japan Trauma Data Bank recorded between 2004 and 2019. Patients with BSI who underwent SAE or open surgery were selected. A propensity score matching analysis was used to balance the baseline covariates and compare outcomes, including all-cause in-hospital mortality and spleen salvage. From 361,706 patients recorded in the data source, this study included 2,192 patients with BSI who underwent SAE or open surgery. A propensity score matching analysis was used to extract 377 matched pairs of patients. The in-hospital mortality rates (SAE, 11.6% vs. open surgery, 11.2%, adjusted relative risk (aRR): 0.64; 95% confidence interval [CI]: 0.38–1.09, p  = 0.10) were similar in both the groups. However, spleen salvage was significantly less achieved in the open surgery group than in the SAE group (SAE, 87.1% vs. open surgery, 32.1%; aRR: 2.84, 95%CI: 2.29–3.51, p  < 0.001). Survival rates did not significantly differ between BSI patients undergoing SAE and those undergoing open surgery. Nonetheless, SAE was notably associated with a higher likelihood of successful spleen salvage.