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Katsuhiko Shimizu,1 Masao Nakata,1 Shinsuke Saisho,1 Masayuki Inubushi,2 Norihito Okumura,3 Tomohiro Murakawa,4 Motohiro Yamashita,5 Hiroshige Nakamura,6 Yoshifumi Sano,7 Kazuhiko Kataoka,8 Shinichi Toyooka9 1Department of General Thoracic Surgery, Kawasaki Medical School, Kurashiki, Japan; 2Division of Nuclear Medicine, Department of Radiology, Kawasaki Medical School, Kurashiki, Japan; 3Department of Thoracic Surgery, Kurashiki Central Hospital, Kurashiki, Japan; 4Department of Thoracic Surgery, Kansai Medical University, Osaka, Japan; 5Department of Thoracic Surgery, Shikoku Cancer Center, Matsuyama, Japan; 6Division of General Thoracic Surgery, Tottori University Hospital, Yonago, Japan; 7Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine, Toon, Japan; 8Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center, Iwakuni, Japan; 9Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, JapanCorrespondence: Katsuhiko Shimizu, Department of General Thoracic Surgery, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan, Tel +81-86-462-1124, Fax +81-86-464-1124, Email kshimizu@med.kawasaki-m.ac.jpBackground: Induction therapy followed by surgery is recommended as an alternative treatment strategy for locally advanced non-small cell lung cancer (NSCLC). Patients who achieve pathologic response after induction therapy have better outcomes than non-responders; therefore, therapeutic response must be evaluated. Recently, new approaches for monitoring therapeutic responses, which are based on 18F‐Fluorodeoxyglucose positron emission tomography (FDG‐PET), have been developed. In this study, we evaluated the predictive value of Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST), which uses standardized uptake values corrected for lean body mass (SUL) and total lesion glycolysis (TLG).Methods: A total of 130 patients in the Setouchi Lung Cancer Group who underwent FDG-PET imaging before and after induction therapy prior to a planned surgical resection for NSCLC between 2007 and 2016 were studied retrospectively. The pathologic responses of the primary lung tumors and metastatic lymph nodes were compared with their responses based on evaluation using PERCIST.Results: Postoperative pathologic studies revealed pathologic complete response (pCR) in 42 (32.3%) patients. PERCIST was significantly correlated with pathologic response (p < 0.001). The sensitivity, specificity, and accuracy of PERCIST for predicting pCR were 16.7% (7/42), 88.6% (78/88), and 65.4% (85/130), respectively. Patients with pCR had significantly higher reduction rates in SULpeak for both primary lung tumors and metastatic lymph nodes and TLG for primary tumors than non-responders. In a multivariate Cox regression analysis, tumor site in upper lobes, reduction rate of TLG in primary tumor, and pathologic N0 were independent predictors of favorable recurrence-free survival (RFS).Conclusion: Our study suggested that PERCIST, especially the rate of TLG reduction rate, are useful to predict the pathological response and prognosis after induction therapy. Although improvement is necessary, PERCIST can be a promising method of the post-induction status in lung cancer. Further research is needed to confirm our findings.Keywords: non-small cell lung cancer, FDG PET, PERCIST, SUL, TLG

The spread of antimicrobial resistant organisms (AROs) poses a major threat to animal and human health. In Japan, the estimated disability-adjusted life years (DALYs) due to ARO infections is 137.9 per 100,000 persons, with methicillin-resistant Staphylococcus aureus (MRSA) being the main contributor. Factors that can contribute to DALYs in Japan include younger age and a higher number of deaths in patients with MRSA bacteremia. Moreover, longer hospital stays may contribute to the higher rates of MRSA bacteremia in Japan than in western countries. We reviewed the diagnostic procedure combination data collected from January 1, 2016 to December 31, 2020, in an acute care hospital in Tokyo, Japan. We found that the median time from admission to MRSA bacteremia onset was 26 days, which is longer than that observed in western countries however similar to that in South Korea. Furthermore, our cohort was older than those in the United States and South Korea, potentially contributing to the higher number of years of life lost in Japan. These results underscore the need to develop strategies to reduce hospitalization rates in Japan. Larger multicenter studies are needed to comprehensively evaluate the economic and health burdens of MRSA bacteremia in Japan.

We evaluated the diagnostic performance of Rapiim SARS-CoV-2-H (Rapiim-H)-a point-of-care qualitative antigen test-using nasopharyngeal swabs (NPS) and saliva samples and compared its results with those from antigen quantification and nucleic acid amplification tests. NPS and saliva were collected from patients with confirmed and suspected coronavirus disease (COVID-19). In total, 142 NPS and saliva samples were collected. In symptomatic cases, in which the first NPS sample was collected within 10 days of disease onset, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for COVID-19 diagnosis were 91.7 %, 88.6 %, 93.2 %, and 86.1 %, respectively. A similar analysis was performed on saliva samples, and the sensitivity, specificity, PPV, and NPV were 50.8 %, 91.4 %, 91.2 %, and 51.6 %, respectively. The Rapiim-H test using NPS demonstrated approximately 90 % sensitivity and specificity, particularly within the first 10 days after disease onset., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kei Yamamoto reports financial support was provided by Canon Medical Systems Corporation. Hideaki Kato reports a relationship with Shionogi and Co Ltd that includes: funding grants. Hideaki Kato reports a relationship with Asahi Kasei Pharma Corporation that includes: funding grants. Kei Yamamoto reports a relationship with FUJIREBIO Inc that includes: funding grants. Kei Yamamoto reports a relationship with Mizuho Medy Co Ltd that includes: funding grants. Kei Yamamoto reports a relationship with VisGene Co. Ltd. that includes: funding grants. Kei Yamamoto reports a relationship with Sanyo Chemical Industries Ltd that includes: funding grants. Kei Yamamoto reports a relationship with CarbGeM Inc. that includes: funding grants. Kei Yamamoto reports a relationship with Sysmex Corp that includes: funding grants. Kei Yamamoto reports a relationship with Toyobo Co Ltd that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the effect of studying abroad on catch-up vaccination coverage for measles, rubella, mumps, varicella, and tetanus during the pretravel consultation among young adult travelers., Methods: This retrospective cohort study analyzed data from the Japan Pretravel Consultation Registry (J-PRECOR) on individuals aged 18-21 years with childhood vaccination records. Propensity score weighting was used to estimate the average treatment effect on the proportion of participants receiving catch-up vaccination., Results: Among 1091 eligible participants, the catch-up vaccination need was highest for mumps (65.7 %) and varicella (49.0 %) and lowest for measles (9.9 %) and rubella (14.0 %). In the unadjusted analysis, the catch-up vaccination rate was 70.6 % for tetanus, 50.9 % for measles, 47.7 % for rubella, 40.0 % for mumps, and 23.9 % for varicella. In the weighted analysis, the study-abroad group had significantly higher catch-up vaccination rates for measles (54.6 % vs. 29.8 %, P = 0.039), rubella (53.0 % vs. 22.1 %, P < 0.001), and varicella (26.8 % vs. 10.9 %, P = 0.002), whereas the non-study-abroad group had a higher catch-up vaccination rate for tetanus (62.4 % vs. 78.4 %, P = 0.024)., Conclusion: Compared with other travelers, the catch-up vaccination rate among travelers studying abroad was higher for measles, rubella, and varicella, but lower for tetanus. In clients planning to study abroad, vaccinations required for travel should be recommended in addition to those required by the host institution, and vaccination against highly infectious diseases with potential for complications, such as measles, rubella, mumps, and varicella, should be recommended to clients traveling for reasons other than studying abroad., Competing Interests: Competing interests T.Matono has received speaker honoraria from MSD, Pfizer, Gilead, and GSK., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Left upper trisegmentectomy is expected to be as curative as lobectomy for lung cancer because the left upper lobe is anatomically the same as the combined upper and middle lobes of the right lung and the procedure can provide a sufficient surgical margin. In the present multicenter study, we compared the results of trisegmentectomy and lobectomy in patients with clinical stage T1c-2aN0M0 left upper lung cancer. We retrospectively analyzed the outcomes of patients with clinical stage T1c-2aN0M0 lung cancer in the left upper segment who underwent lobectomy or trisegmentectomy between January 2006 and June 2022. The trisegmentectomy group (S group) and lobectomy group (L group) comprised 33 and 132 patients, respectively. Comparisons of postoperative survival revealed no significant differences in overall survival (p = 0.761) or disease-free survival (p = 0.508) between the two groups. There were also no significant differences in survival after adjustment for clinical factors by Cox proportional hazards models and propensity score matching. Local recurrence was significantly more predominant in the S group than in the L group (p = 0.006). The S group had a worse postoperative survival than the L group when the tumor was located in anterior segment. Trisegmentectomy can provide an equivalent postoperative survive to lobectomy in patients with clinical stage T1c-2aN0M0 left upper segment lung cancer except in patients with tumor in anterior segment., (© 2024. Italian Society of Surgery (SIC).)

Purpose: To determine whether the clinical and paraclinical course of Fuchs endothelial corneal dystrophy (FECD) over 1 year is related to the extent of triplet repetition in the transcription factor 4 (TCF4) gene., Methods: A prospective study with a 1-year follow-up was conducted. A total of 104 patients (160 eyes) with FECD and an equivalent number of age- and sex-matched control subjects without FECD were included. At inclusion, the corneas were graded using the modified Krachmer grade (KG) and patients were genotyped for the number of trinucleotide repeats (TNRs) in the TCF4 gene by the short tandem repeat assay. Visual acuity, Scheimpflug tomographic features, and the Visual Function and Corneal Health Status using a visual disability instrument were measured on 2 visits at 1-year intervals., Results: KGs ranged from 1 to 6, and 46% of eyes had grades 1 to 4. 71% of the patients harbored TNR expansion (>40) versus 13% in control subjects ( P < 0.001). Severity at inclusion was higher in the presence of TNR expansion when considering eyes independently (mean grade ±SD, 4.08 ± 1.42) without TNR expansion and 4.66 ± 1.27 with TNR expansion ( P = 0.024). In 1 year, the ETDRS score significantly decreased by -2.97 (95% confidence interval -4.69 to -1.26, P = 0.001) and the ETDRS score with glare by -4.25 (95% confidence interval -6.22 to -2.27, P < 10 -5 ). There was no relationship between the rate of decline and TNR expansion or KG. Central corneal thickness and Visual Function and Corneal Health Status scores did not significantly vary., Conclusions: It is possible to measure a subtle progression of FECD over a period as short as 1 year. We did not find a relationship between the presence of TNR expansion and the speed of deterioration over 1 year. This work should facilitate the design of future clinical trials on FECD., Competing Interests: Conflicts of interest statement: P. Gain, N. Koizumi, N. Okumura, and G. Thuret were shown using the ICMJE disclosures form. The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Dietary supplementation with melinjo (Gnetum gnemon L.) seed extract (MSE) has been an integral part of an anti-obesity therapeutic regimen. To examine the relationship between anti-obesity and sleep, we explored the effect of MSE on sleep structure in high-fat diet (HFD)-induced obese mice. Although HFD did not alter the total amount of daily sleep, it significantly reduced the average duration of non-rapid eye movement (NREM) sleep and wakefulness episodes and significantly increased the number of these episodes. These findings indicate fragmented NREM sleep due to repeated brief awakenings in the HFD-fed mice. When 1% (w/v) MSE was given to HFD-fed mice, their weight or sleep structure were comparable to those of ND-fed mice, proving that dietary MSE completely hindered HFD-induced weight gain and sleep/wake fragmentation. Our data provide compelling evidence that MSE is a novel and promising dietary supplement that restores obesity-induced sleep architecture changes in mice.

There is a paucity of data on the clinical course and treatment of Staphylococcus argenteus . Herein, we describe a successfully treated case of S. argenteus bacteremia. A 76-year-old man with lung adenocarcinoma developed bacteremia caused by penicillin-resistant, oxacillin-susceptible S. argenteus , which was identified through mass spectrometry and nuc gene sequencing. He was diagnosed with a peripheral line-associated bloodstream infection and successfully treated with a 2-week course of cefepime, followed by cefazolin, concurrent with intravenous catheter removal. The isolate was positive for blaZ and negative for mecA . It was assigned to sequence type 2198 using multilocus sequence typing. Formerly classified as Staphylococcus aureus clonal complex 75, S. argenteus became a distinct species in 2015. Its identification has increased owing to widespread mass spectrometer use. Most East and Southeast Asian S. argenteus isolates reported to date are methicillin-susceptible, consistent with the susceptibility pattern of the isolate in our study. Given the potential equivalence in virulence between S. argenteus and S. aureus , we recommend treating S. argenteus with the same rigor as S. aureus until further clinical data becomes available., Competing Interests: The authors have no competing interests to declare., (© 2024 The Author(s).)

Vaccines against coronavirus disease 2019 (COVID-19) have been distributed in most countries for the prevention of onset and aggravation of COVID-19. Recently, there have been increasing numbers of reports on new-onset autoimmune and autoinflammatory diseases following COVID-19 vaccination, however, only little information is available on the long-term safety of these vaccines. Here, we experienced three cases of new-onset rheumatic diseases following COVID-19 vaccination, one case each of rheumatoid arthritis (RA), anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and systemic lupus erythematosus (SLE). The symptom onset ranged from one day to a few days following vaccination. The patients of AAV and SLE were treated successfully with glucocorticoid therapy, and the patient of RA died due to COVID-19. In the literature review of new-onset rheumatic diseases following COVID-19 vaccination, which including seven cases of RA, 37 cases of AAV and 18 cases of SLE, the mean time from vaccination to onset was approximately 11 to 12 days. Most cases improved with glucocorticoid, immunosuppressive drugs and biologic agents. Although such adverse effects are rare, and vaccines are useful in prevent onset and severity of infections, continued accumulation of similar cases is important in terms of examining the long-term safety and understanding pathogenic mechanism of rheumatic diseases.

Purpose: To evaluate the pharmacokinetics of ganciclovir eye drops by comparing solutions prepared from ganciclovir for intravenous infusion and ganciclovir gel and to assess the impact of systemic administration on drug levels in ocular tissues and serum., Study Design: Experimental study design., Methods: Ganciclovir solutions (0.5% and 1.0%) prepared by diluting DENOSINE ® IV Infusion in saline and 0.15% ganciclovir gel (Virgan ® ) were topically administered in rabbit eyes, with and without concomitant systemic administration of ganciclovir. The concentrations of ganciclovir in the corneal epithelium, stroma, and endothelium, aqueous humor; and blood plasma were analyzed by high-performance liquid chromatography (HPLC)., Results: The ganciclovir solutions (0.5% and 1.0%) maintained therapeutic ganciclovir levels in the corneal endothelium above the effective dose required for 50% inhibition (ED50) up to 6 h, albeit with a swift decline thereafter. The 0.15% ganciclovir gel maintained higher therapeutic concentrations in the corneal endothelium for up to 12 h, exceeding the ED50. Serum concentrations of ganciclovir were significantly elevated in the groups receiving combined systemic administration., Conclusion: Topical application of 0.15% ganciclovir gel maintained high endothelial concentrations, well above the therapeutic threshold, with or without systemic administration. Furthermore, the observed increase in ganciclovir levels within the plasma and aqueous humor following systemic administration posits it as a viable strategy for severe cases of cytomegalovirus corneal endotheliitis or those inadequately managed by local treatments alone., (© 2024. Japanese Ophthalmological Society.)

This study explores the impact of royal jelly (RJ) on small intestinal epigenomic changes. RJ, produced by honeybees, is known for its effects on metabolic diseases. The hypothesis is that RJ induces epigenomic modifications in small intestinal epithelial cells, affecting gene expression and contributing to metabolic health. Male db/m and db/db mice were used to examine RJ's effects through mRNA sequencing and CUT&Tag methods. This study focused on histone modifications and gene expression changes, with statistical significance set at p < 0.05. RJ administration improved insulin sensitivity and lipid metabolism without affecting body weight. GO and KEGG pathway analyses showed significant enrichment in metabolic processes, cellular components, and molecular functions. RJ altered histone modifications, increasing H3K27me3 and decreasing H3K23Ac in genes associated with the G2M checkpoint. These genes, including Smc2, Mcm3, Ccnd1, Rasal2, Mcm6, and Mad2l1, are linked to cancer progression and metabolic regulation. RJ induces beneficial epigenomic changes in small intestinal epithelial cells, improving metabolic health and reducing cancer-associated gene expression. These findings highlight RJ's potential as a therapeutic agent for metabolic disorders. Further research is needed to fully understand the mechanisms behind these effects and their implications for human health.

Aim: Several studies have shown the efficacy and safety of low-molecular-weight heparin use in coronavirus disease 2019 (COVID-19), but that of unfractionated heparin (UFH) has not been investigated. We investigated the prevalence of bleeding complications during UFH administration, its impact on mortality, and the risk factors of bleeding outcomes associated with UFH., Methods: This retrospective cohort study was conducted at a single-center tertiary care hospital, including hospitalized patients with COVID-19. The primary outcomes were measured as the prevalence of bleeding complications during hospitalization, and the secondary outcomes were thromboembolic events and 60-day mortality rates. Logistic regression analysis and propensity score matching were used to assess risk factors for bleeding complications and their impact on mortality., Results: Among 1035 included patients, 516 patients were treated with UFH. Twelve (2.3%) patients in the UFH group experienced major bleeding. The prevalence of major bleeding in patients treated with therapeutic-dose UFH was 9.2%. Logistic regression analysis showed that age ≥ 60 years (adjusted odds ratio [aOR], 3.89; 95% confidence interval [CI], 1.01-15.0; P＜.05) and COVID-19 severity (aOR, 35.9; 95% CI, 4.57-282; P＜.05) were associated with major bleeding complications. After propensity score matching, 11 major and 11 non-major bleeding cases (including minor bleeding) were matched. The 60-day cumulative mortality rate between the two groups did not differ significantly (P=.13, log-rank test)., Conclusions: The incidence of major bleeding in COVID-19 patients using therapeutic-dose UFH was relatively high. Critical COVID-19 and older age were risk factors for bleeding complications.

Objectives: This study aimed to evaluate the safety and feasibility of early chest tube removal after anatomic pulmonary resection, regardless of the drainage volume., Methods: We conducted a multicenter, randomized, controlled, noninferiority trial. Patients with greater than 300 mL drainage volume during postoperative day 1 were randomly assigned to group A (tube removed on postoperative day 2) and group B (tube retained until drainage volume ≤300 mL/24 hours). The primary end point was the frequency of respiratory-related adverse events (grade 2 or higher based on the Clavien-Dindo classification) within 30 days postoperatively., Results: Between April 2019 and October 2021, 175 patients were assigned to group A (N = 88) or group B (N = 87). One patient in group B who experienced chylothorax was excluded from the study. Respiratory-related adverse events were observed in 10 patients (11.4%) in group A and 12 patients (14.0%) in group B (P = .008). The frequencies of thoracentesis or chest tube reinsertion were not significantly different (8.0% and 9.3% in groups A and B, respectively, P = .752). Additionally, the duration of chest tube placement was significantly shorter in group A than in group B (median, 2 vs 3 days; P < .001). No significant difference between groups A and B was found in postoperative hospital stay (median, 6 vs 7 days, P = .231)., Conclusions: Early chest tube removal, regardless of drainage volume, was safe and feasible in patients who underwent anatomic pulmonary resection., Competing Interests: Conflict of Interest Statement K.T.: honoraria from AstraZeneca, Chugai, Ono, Nippon Kayaku, Johnson & Johnson, and Covidien. T.H.: payment or honoraria from Intuitive Surgical and Johnson and Johnson. M.T.: payment or honoraria Johnson & Johnson Japan, AstraZeneca KK, Eli Lilly Japan, Chugai Pharmaceutical Co, Ltd, Taiho Pharma, Medtronic Japan, Ono Pharmaceutical Co, Ltd, MSD, Bristol-Myers Squibb KK, and Novartis. N.O.: payment or honoraria from Johnson & Johnson. N.I.: payment or honoraria from Taiho Pharma, Bristol Myers, Chugai Pharma, Fuji Film Nihon Mediphysics, MSD, Daiichi-Sankyo, Boehringer Ingelheim, Shionogi, Medtronic, Johnson & Johnson, Olympus, Roche, and Ono Pharma. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Food-borne toxocariasis caused by the consumption of raw meat or liver has occasionally been reported from East Asia. We treated a 38-year-old Japanese man who was infected with Toxocara in China and underwent a four-week treatment with albendazole. The liver and lung lesions disappeared after the treatment, suggesting that the treatment was successful. One month after the end of the treatment, the patient relapsed, and albendazole was administered again for eight weeks. The patient has remained relapse-free for one year. Although toxocariasis can heal spontaneously, in some cases, such as the present case, the disease relapses even after long-term treatment. In conclusion, different durations of treatment are recommended by various guidelines, and the duration of treatment needs to be modified with each case, considering the response to the treatment., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)