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Introduction: Immune checkpoint inhibitors (ICIs) plus chemotherapy is now a standard treatment for non-small cell lung cancer (NSCLC). Whether ICI plus chemotherapy (ICI-chemo) or ipilimumab plus nivolumab (I-N)-based therapy is superior for patients with NSCLC with a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) of 1-49 % has not been evaluated., Methods: This multicenter retrospective study included NSCLC patients with a TPS score of 1-49 %, who began first-line chemotherapy. Propensity score matching analysis was used to adjust for various confounders and evaluate treatment efficacy., Results: A total of 401 patients were enrolled, of whom 308 received ICI-chemo and 93 received I-N-based therapy. The median OS was 21.0 months in the ICI-chemo group and 20.0 months in the I-N-based therapy group. After propensity score matching, there was no difference in OS or PFS between the ICI-chemo group and the I-N-based therapy group (OS: hazard ratios (HR), 0.83; 95 % confidence interval [CI], 0.54-1.26, PFS: HR, 0.72; 95 % CI, 0.52-1.00). Among PD-L1 TPS 25-49 %, there was a tendency for OS to be favorable for the ICI-chemo group (OS: HR, 0.30; 95 % CI, 0.09-0.85). Treatment discontinuation occurred for 26.2 % of the patients in the ICI-chemo group and 41.9 % in the I-N-based therapy group., Conclusions: Among PD-L1 TPS 1-49 %, there was no significant difference in survival outcomes between the ICI-chemo group and the I-N-based therapy group. Based on the results of a subgroup analysis, ICI-chemo may be superior for treating NSCLC with a TPS of 25-49 %., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Tanaka reported receiving lecture fees from AstraZeneca K.K, Chugai Pharmaceutical Co., Boehringer-Ingelheim Japan Inc., Ono Pharmaceutical Co., Pfizer Japan Inc., and Bristol-Meyers Squibb. Dr. Makiguchi reported receiving honoraria from Asahi KASEI, Boehringer-Ingelheim Japan, Inc., AstraZeneca K.K, Eli Lilly, GlaxoSmithKline, Ono Pharmaceutical Co., Teijin Pharma, Taiho Pharmaceutical, Chugai Pharmaceutical Co., and LTD. Dr. Tozuka reported receiving honoraria from AstraZeneca and Chugai Pharmaceutical Co. Dr. Kawashima reported receiving honoraria from AstraZeneca K.K, Chugai Pharmaceutical Co, Taiho Pharmaceutical, Eli Lilly, Kyowa Hakko-Kirin, and Life Technologies Japan Ltd. Dr. Koyama reported receiving honoraria from AstraZeneca K.K. and Chugai Pharmaceutical Co. Dr. Tambo reported receiving honoraria from Chugai Pharmaceutical Co, Taiho Pharmaceutical, MSD K.K, and the Daiichi Sankyo Company. Dr. Ogusu reported receiving speakers’ bureau from MSD K.K, Bristol-Meyers Squibb, and Chugai Pharmaceutical Co. Dr. Hasegawa reported receiving honoraria from AstraZeneca K.K, Chugai Pharmaceutical Co., Eli Lilly, and Merck. Dr. Miyauchi reported receiving honoraria from AstraZeneca, Eli Lilly, Chugai Pharmaceutical Co, Boehringer-Ingelheim Japan, Inc., Taiho Pharmaceutical, Kyowa Hakko-Kirin, Daiichi-Sankyo, MSD, Bristol Myers Squibb, Merck, Amgen, Ono Pharmaceutical Co., Thermo Fisher Scientific, Nippon Kayaku, Takeda Pharmaceutical Co., and Sysmex. He received advisory roles from Boehringer-Ingelheim Japan Inc., Ono Pharmaceutical Co, Daiichi-Sankyo, and Merck outside of the submitted work. Dr. Sakatani reported receiving speakers’ bureau from AstraZeneca, Eli Lilly, MSD K.K, Boehringer-Ingelheim Japan, Inc., Takeda Pharmaceutical Co., Taiho Pharmaceutical, and Bristol Myers Squibb. Dr. Tsuchiya-Kawano reported receiving speakers’ bureau from Bristol Myers Squibb, AstraZeneca, Taiho Pharmaceutical, Chugai Pharmaceutical Co., MSD K.K, Ono Pharmaceutical Co., and Kyowa Hakko-Kirin. Dr. Nishio reported receiving honoraria from Pfizer Japan Inc, Bristol Myers Squibb, Ono Pharmaceutical Co., Chugai Pharmaceutical Co., Taiho Pharmaceutical, AstraZeneca, Boehringer-Ingelheim Japan, Inc., MSD K.K, Novartis, Eli Lilly, Nippon Kayaku, Takeda Pharmaceutical Co., Merck, Janssen, Amgen, Eisai, and Daiichi-Sankyo. He received research funding from Pfizer Japan Inc, Bristol Myers Squibb, Taiho Pharmaceutical, AstraZeneca, MSD K.K, Takeda Pharmaceutical Co, Merck, Janssen, and Amgen, outside of the submitted work. All remaining authors have declared no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background/aim: The efficacy of cytotoxic chemo-therapy has been reported to improve after immune checkpoint inhibitor (ICI) administration. We previously conducted a multicenter prospective clinical study to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-PTX) after ICI treatment. In that study, some patients showed a long-term response to nab-PTX, which is not usually observed with single-agent chemotherapy. The present study aimed to evaluate the clinical characteristics of these patients., Patients and Methods: We retrospectively analyzed updated data from 29 patients enrolled in our clinical study who received nab-PTX monotherapy after ICI treatment. We defined a "long-term responder" as a patient who achieved a 1-year progression-free survival (PFS)., Results: Among the 29 patients, 10 (34.5%) were long-term responders, two of whom achieved a 5-year PFS. A key difference between long-term and non-long-term responders was that the long-term responders had a significantly higher number of patients with Eastern Cooperative Oncology Group-performance status of 0 (70.0% versus 10.5%; p=0.002). Furthermore, median cycles of previous ICIs and median treatment cycles were significantly higher in long-term responders than in non-long-term responders (8 cycles versus 3 cycles; p=0.03) (5.9 months versus 2.0 months; p=0.02). In the 10 long-term responders, six patients required at least a one-stage dose reduction owing to adverse events, and four patients required a two-stage dose reduction., Conclusion: Nab-PTX administration after ICI treatment may elicit a long-term response. A long-term response can be achieved even with a dose reduction due to adverse events., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Malnutrition and inflammation are common problems of adverse outcomes in various diseases as atherosclerosis. Recently, the concept of malnutrition-inflammation-atherosclerosis (MIA) syndrome is known to a crucial prognostic factor in patients with end-stage renal disease. We investigated the prognostic impact of the co-presence of MIA factors in patients with lower-extremity artery disease (LEAD) after endovascular therapy (EVT). This retrospective study included 284 patients with LEAD who underwent EVT. MIA factors were defined in patients with: low geriatric nutritional risk index (< 92) as "malnourished"; greater high-sensitivity C-reactive protein levels (≥ 0.1 mg/dL) as "inflamed"; a history of coronary artery revascularization, lacunar or atherothrombotic brain infarction as "atherosclerotic". We examined the relationship between baseline characteristics and major adverse cardiovascular and cerebrovascular events (MACCE) including all-cause mortality. Sixty-two patients (22%) died and 72 patients (25%) had MACCE, including all-cause death. Forty-four (16%) patients had every 3 of MIA (3-MIA) factors. The mean follow-up period was 737 days. Multivariate Cox proportional hazards regression analysis models revealed that 3-MIA factors correlated significantly with all-cause death [hazard ratio (HR) 3.46, 95% confidence interval (CI) 1.89-6.34; p < 0.001] and MACCE (HR 2.91, 95% CI 1.62-5.22; p < 0.001), after adjusting for relevant factors. Kaplan-Meier analysis revealed that the rates of all-cause death (p < 0.001) and MACCE (p < 0.001) were significantly higher when the MIA factors overlapped and are observed in patients with chronic limb-threatening ischemia. Among patients with LEAD after EVT, the co-presence of MIA factors was an independent risk factor for all-cause death and MACCE., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no competing financial interests or personal relationships that may have influenced the work reported in this study., (© 2024. The Author(s).)

A 62-year-old man had bilateral eyelid swelling for 4 months. Two months before admission, he developed fatigue and lost 5 kg of bodyweight. Further examination revealed elevated serum C-reactive protein, normal angiotensin-converting enzyme, elevated proteinase-3 antineutrophil cytoplasmic antibody (PR3-ANCA), and normal IgG4 concentration. Chest X-ray and computed tomography showed no enlarged hilar lymph nodes, but positron emission tomography-computed tomography showed fluorodeoxyglucose accumulation in both lacrimal glands, in lung nodules, and in the pancreas. Tissue biopsies of the lacrimal glands and pulmonary nodules showed granuloma with giant cells, but no IgG4-positive cells or fibrosis. Pancreatic tissue showed no findings of autoimmune pancreatitis. In the 2022 ACR/EULAR classification criteria for granulomatosis with polyangiitis, the total score was 10 points. Final comprehensive diagnosis was granulomatosis with polyangiitis, based on the negative results of differential diseases, such as IgG4-related diseases and sarcoidosis. Prednisolone 60 mg/day was started on day 8, and rituximab 500 mg/body/week on day 12. After beginning treatment, general malaise and lacrimal gland enlargement were resolved, PR3-ANCA and C-reactive protein became negative, and the nodular shadow in the lungs disappeared. This is the first report of granulomatosis with polyangiitis presenting both lacrimal gland and pancreatic lesions., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

The sentinel lymph node (SN) concept has a significant impact on cancer surgery. We aimed to examine which morphology of dendritic cells (DCs) and macrophages corresponds to "preconditioning" of the SN against cancer. Although macrophages are generally able to tolerate cancer metastasis, the CD169-positive subtype is believed to be a limited exception. Immunohistochemical and morphometric analyses were performed to examine DC-SIGN-, CD68-, and CD169-positive cells in SNs and non-SNs of 23 patients with gastric cancer with or without nodal metastasis. All patients survived for >5 years without recurrence. DCs were present in the subcapsular, paracortical, and medullary sinuses, the endothelia of which expressed DC-SIGN and smooth muscle actin (SMA). In the non-SNs of patients without metastasis, subcapsular DCs occupied a larger area than SNs, and this difference was statistically significant. Conversely, subcapsular DCs were likely to have migrated to the paracortical area of the SNs. DC clusters often overlapped with macrophage clusters; however, histiocytosis-like clusters of CD169-negative macrophages showed a smaller overlap. We found a significantly larger overlap between DC-SIGN and CD169-positive clusters in SNs than in non-SNs; the larger overlap seemed to correspond to a higher cross-presentation of cancer antigens between these cell populations. DC-SIGN-CD169-double positive cells might exist within this overlap. SNs in gastric cancers are usually preconditioned as a frontier of cancer immunity, but they may sometimes be suppressed earlier than non-SNs. DC-SIGN- and CD169-positive cells appeared to decrease owing to a long lag time from the primary lesion occurrence and a short distance from the metastasis., (© 2024 The Author(s). Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

Background: Open Hartmann's procedure has traditionally been the procedure of choice to treat complicated diverticulitis. We analyzed the ACS-NSQIP database to compare outcomes in patients who underwent emergent laparoscopic Hartmann's procedure (LHP) to those who had an open Hartmann's procedure (OHP)., Study Design: Data analyzed from 2015 to 2019 using ICD-10 codes. Patients were matched on several important covariates using a propensity score matching method (PSM). Patients were matched in a 4:1 ratio of controls to cases based on the propensity score., Results: We identified 5026, of which 456 had LHP and 4570 had OHP. PSM analysis yielded 369 LHP and 1476 OHP patients. LHP had lower rates of superficial surgical site infection (SSSI) compared to OHP (2.44% vs. 5.89%, p = 0.007). LHP had similar post-operative outcomes compared to OHP, including 30-day mortality (5.15% vs. 2.98%, p = 0.060), organ space surgical site infection (OSSSI) (14.36% vs. 12.60%, p = 0.161), wound disruption (1.36% vs. 2.44%, p = 0.349), median LOS (8 vs. 9 days, p = 0.252), readmission within 30 days (11.92% vs. 8.67%, p = 0.176), rate of reoperation (6.0 vs. 6.5%, p = 0.897), and discharge to home (76% vs. 77%, p = 0.992). LHP had longer operative times compared to OHP (median 129 vs. 118 min, p < 0.0001)., Conclusion: The LHP is associated with lower rates of SSSI. However, it is not associated with lower rates of mortality, OSSSI, readmissions and reoperations within 30 days. Surgical times are longer in LHP. More studies are needed to determine whether LHP offers advantages in the long-term, particularly in rates of incisional hernia and colostomy closure., Competing Interests: Declarations. Informed consent: This study does not need for an informed consent. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Acute respiratory failure (ARF) due to lateral medullary infarction (LMI) can be a fatal condition, although its details remain unclarified. To clarify clinical aspects of ARF due to LMI, we reviewed eight applicable cases treated in a tertiary hospital. Of them, we focused on the detailed clinical course of one case. We clarified that even patients with a serious clinical course may have no apparent magnetic resonance imaging abnormalities in respiratory control centers at the initial examination. We should be mindful that respiratory monitoring is necessary even without infarction of regions responsible for respiratory control at the initial presentation.

Background: Primary percutaneous coronary intervention (PCI) for ST-segment-elevation myocardial infarction (STEMI) complicated by cardiogenic shock (CS) may reduce the risk of subsequent cardiovascular events but remains challenging. The study aim was to evaluate the clinical characteristics and long-term outcomes of patients undergoing primary PCI for STEMI with CS., Methods: We conducted an observational cohort study of patients with STEMI who underwent primary PCI between April 2004 and December 2017 at Juntendo University Shizuoka Hospital. The primary outcome was cardiovascular death (CVD) during the median 3-year follow-up. We performed a landmark analysis for the incidence of CVD from 0 day to 1 year and from 1 to 10 years., Results: Among the 1758 STEMI patients in the cohort, 212 (12.1 %) patients with CS showed significantly higher 30-day CVD rate on admission than those without (26.4 % vs 2.9 %). Landmark Kaplan-Meier analysis showed that CVD from day 0 to year 1 was significantly higher in the patients with CS (log-rank p < 0.0001). Multivariate Cox regression analysis showed that CS was significantly associated with higher cardiovascular mortality (adjusted hazard ratio, 11.8; 95%confidence intervals, 7.78-18.1; p < 0.0001), but the mortality rates from 1 to 10 years were comparable (log-rank p = 0.68)., Conclusion: The cardiovascular 1-year mortality rate for patients with STEMI was higher for those with CS on admission than without, but the mortality rates of >1 year were comparable. Surviving the early phase is essential for patients with STEMI and CS to improve long-term outcomes., Competing Interests: Disclosures None. Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Competing Interests: There are no conflicts of interest.

Introduction: Recent studies have suggested enhanced therapeutic effects of subsequent chemotherapy after immune checkpoint inhibitor (ICI) treatment, highlighting the importance of subsequent treatment selection. Nanoparticle albumin-bound paclitaxel (nab-PTX) is commonly used in subsequent chemotherapies; however, its efficacy as a subsequent treatment after ICI treatment has not been reported., Methods: We retrospectively evaluated the efficacy and safety of nab-PTX using two prospective studies that we previously reported. The first study evaluated the efficacy and safety of nab-PTX as a second-line treatment after the failure of the first-line cytotoxic chemotherapy, excluding ICI (study 1; n = 32), and the other as a subsequent treatment after failure of ICI treatment, regardless of treatment line (study 2; n = 29)., Results: The objective response rate was significantly higher in study 2 {55.2% (95% confidence interval [CI]: 28.1-79.6)} than in study 1 (28.1% [95% CI: 13.7-46.7]) (p = 0.04). Although the disease control rate was slightly higher in study 2 (86.2% [95% CI: 65.9-97.0]) than in study 1 (71.9% [95% CI: 53.3-86.3]), there was no significant difference (p = 0.2). The median progression-free survival was significantly longer in study 2 than in study 1 (3.9 months [95% CI: 2.0-5.5] in study 1 vs. 5.6 months [95% CI: 3.0-12.8] in study 2; hazard ratio [HR]: 0.46 [95% CI: 0.27-0.81], p = 0.006). The median overall survival was slightly longer in study 2 despite the greater number of patients who received nab-PTX in late treatment line, but there was no significant difference between study 1 and study 2 (10.9 months [95% CI: 5.1-16.8] in study 1 vs. 11.9 months [95% CI: 7.6-24.8] in study 2; HR: 0.77 [95% CI: 0.46-1.31], p = 0.34). Safety profiles did not differ between the patients in studies 1 and 2., Conclusion: Nab-PTX monotherapy may be an effective subsequent treatment option after ICI treatment., (© 2024 S. Karger AG, Basel.)

Background: Living alone as a proxy for social isolation has been considered to increase the risk of cardiovascular disease. We thus investigated the impact of living alone on mortality in acute myocardial infarction (AMI) patients., Methods: Subjects comprised 277 AMI patients who underwent percutaneous coronary intervention (PCI). Associations between all-cause and cardiac deaths after PCI and baseline characteristics including living alone and Global Registry of Acute Coronary Events (GRACE) risk score were assessed., Results: Eighty-three patients (30%) were living alone. Thirty patients died after PCI, including 20 cardiac deaths. Patients living alone showed higher incidences of both all-cause and cardiac deaths compared with patients not living alone (18% vs. 8%, P  = 0.019 and 14% vs. 4%, P  = 0.004). Multivariate Cox proportional hazards regression analysis models showed living alone [hazard ratio (HR), 2.60; 95% confidence interval (CI), 1.20-5.62; P  = 0.016 and HR, 4.17; 95% CI, 1.60-10.84; P  = 0.003] and GRACE risk score (HR, 1.02; 95% CI, 1.01-1.03; P  = 0.003 and HR, 1.03; 95% CI, 1.01-1.04; P  < 0.001) correlated significantly with all-cause and cardiac deaths. Cox proportional hazards modeling revealed that patients living alone with GRACE risk score ≥162 derived from the receiver-operating characteristic curve showed a significantly greater risk of all-cause death than patients not living alone with GRACE risk score <162 (HR 16.57; 95% CI 6.67-41.21; P  < 0.001)., Conclusion: Among AMI patients, living alone represents an independent risk factor for all-cause and cardiac deaths after PCI, separate from GRACE risk score. Furthermore, AMI patients living alone with high GRACE risk scores may experience an additively increased risk of mortality after PCI., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Melanopsin signaling within intrinsically photosensitive retinal ganglion cell (ipRGC) subtypes impacts a broad range of behaviors from circadian photoentrainment to conscious visual perception. Yet, how melanopsin phototransduction within M1-M6 ipRGC subtypes impacts cellular signaling to drive diverse behaviors is still largely unresolved. The identity of the phototransduction channels in each subtype is key to understanding this central question but has remained controversial. In this study, we resolve two opposing models of M4 phototransduction, demonstrating that hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are dispensable for this process and providing support for a pathway involving melanopsin-dependent potassium channel closure and canonical transient receptor potential (TRPC) channel opening. Surprisingly, we find that HCN channels are likewise dispensable for M2 phototransduction, contradicting the current model. We instead show that M2 phototransduction requires TRPC channels in conjunction with T-type voltage-gated calcium channels, identifying a novel melanopsin phototransduction target. Collectively, this work resolves key discrepancies in our understanding of ipRGC phototransduction pathways in multiple subtypes and adds to mounting evidence that ipRGC subtypes employ diverse phototransduction cascades to fine-tune cellular responses for downstream behaviors., Competing Interests: EC, JB, TS, LB, TS No competing interests declared

Background: Evidence for use of second-line immunosuppressants for immune-related adverse events (irAEs) is inadequate. Therefore, a multicenter analysis should assess the efficacy of second-line immunosuppressants for severe irAEs associated with different malignant diseases., Methods: This descriptive study aims to investigate the effects of second-line immunosuppressants on corticosteroid-refractory irAEs in patients with lung cancer. We analyzed the effects of second-line immunosuppressants on underlying lung cancer and associated adverse effects., Results: Our study included 4589 patients who had received immune checkpoint inhibitor treatment, with 73 patients (1.6%) developing irAEs requiring second-line immunosuppressants. The most commonly observed irAE was pneumonitis (26 patients), followed by hepatobiliary disorders (15 patients) and enteritis (14 patients). We found a confirmed response rate of 42.3% for pneumonitis, which was lower than the response rates of 86.7% for hepatobiliary disorders and 92.9% for enteritis. The time from the start of corticosteroid therapy to the addition of a second-line immunosuppressant correlated significantly with the resolution of irAE to Grade 1 (correlation coefficients of r = 0.701, p < 0.005). The median progression-free survival and duration of response of underlying lung cancer from second-line immunosuppressant administration were 2.1 and 3.0 months, respectively. Of the patients with irAE, 27.4% developed infections and 5.5% might die due to infection., Conclusion: Second-line immunosuppressant response was confirmed in 72.2% of irAEs in patients with lung cancer, with lower response rates observed in irAE pneumonitis compared to other irAEs., (© 2023. The Author(s).)

Background: A pulmonary artery catheter is often used in cardiac surgery despite its uncertain effectiveness. The aim of this pilot study was to investigate the associations between the use of a pulmonary artery catheter and clinical outcomes in off-pump coronary artery bypass grafting., Methods: Patients over 20 years of age who had undergone off-pump coronary artery bypass grafting between December 2018 and November 2021 were enrolled in this single-center retrospective pilot study. The propensity score of pulmonary artery catheterization was calculated. Multivariate analysis including the propensity score as a covariate was performed to assess clinical outcomes. The primary outcome was the composite outcome of in-hospital death, unplanned intraoperative conversion to cardiopulmonary bypass, resuscitated cardiac arrest, mechanical circulatory support, myocardial infarction, stroke, new initiation of renal replacement therapy, inhaled nitric oxide, re-intubation and tracheostomy., Results: Among the 315 patients who were enrolled, 298 were included in the final analysis. A pulmonary artery catheter was inserted in 131 patients. There were 50 patients with the composite outcome including two in-hospital deaths. Multivariate logistic regression analysis showed that pulmonary artery catheterization was not significantly related to the composite outcome. Clinical outcomes worsened significantly as the number of anastomoses increased (odds ratio: 1.450, 95% confidence interval: 1.040-2.040, P=0.029)., Conclusions: Pulmonary artery catheterization did not improve the clinical outcomes in off-pump coronary artery bypass grafting in this pilot study.

Elevation of the ST segment after percutaneous coronary intervention (PCI) using rotational atherectomy (RA) for severely calcified lesions often persists after disappearance of the slow-flow phenomenon on angiography. We investigated clinical factors relevant to prolonged ST-segment elevation following RA among 152 patients with stable angina undergoing elective PCI. PCI procedures were divided into two strategies, RA without (primary RA strategy) or with (secondary RA strategy) balloon dilatation before RA. Incidence of prolonged ST-segment elevation after disappearance of slow-flow phenomenon was higher in the 56 patients with primary RA strategy (13%) than in the 96 patients with secondary RA strategy (3%, p = 0.039). Univariate logistic regression analysis showed levels of low-density lipoprotein cholesterol (LDL-C) (odds ratio [OR] 0.95, 95% confidence interval [CI] 0.93-0.99; p = 0.013), levels of triglycerides (OR 0.97, 95%CI 0.94-0.99; p = 0.040), and secondary RA strategy (OR 0.23, 95% CI 0.05-0.85; p = 0.028) were inversely associated with occurrence of prolonged ST-segment elevation following ablation. However, hemodialysis, diabetes mellitus, left-ventricular ejection fraction, lesion length ≥ 20 mm, and burr size did not show significant associations. Multivariate logistic regression analysis modeling revealed that secondary RA strategy was significantly associated with the occurrence of prolonged ST-segment elevation (Model 1: OR 0.24, 95% CI 0.05-0.95, p = 0.042; Model 2: OR 0.17, 95% CI 0.03-0.68, p = 0.018; Model 3: OR 0.21, 95% CI 0.03-0.87, p = 0.041) even after adjusting for levels of LDL-C and triglycerides. Secondary RA strategy may be useful to reduce the occurrence of prolonged ST-segment elevation following RA., (© 2023. The Author(s).)

In Abashiri, Hokkaido, northern Japan, composted sewage sludge (CSS) containing a large amount of zinc (Zn) and copper (Cu) is used as fertilizer in agriculture. The local environmental risks of Cu and Zn from such organic fertilizers were studied. The study area, especially the brackish lakes located near the farmlands, is important for inland fisheries. The risks posed by heavy metals to the brackish-water bivalve, Corbicula japonica, was therefore investigated as an example. First, the long-term effect of CSS application in agricultural fields was monitored. Second, using pot cultivation, factors influencing Cu and Zn availability in the presence of organic fertilizers were evaluated under different scenarios of SOM content. In addition, the mobility and availability of Cu and Zn in organic fertilizers were evaluated in a field experiment. In the pot cultivation, both organic and chemical fertilizers increased the availability of Cu and Zn with a decrease in pH, possibly caused by nitrification. However, this decrease in pH was inhibited by higher SOM content, i.e. SOM mitigated the heavy metal risk from organic fertilizer. In the field experiment, potato (Solanum tuberosum L.) was cultivated using CSS and pig manure (PM). As observed in the pot cultivation, the applied chemical and organic fertilizers increased the soil-soluble and 0.1 N HCl-extractable Zn with increased nitrate. Considering the habitat and the LC 50 values of C. japonica that were lower than the concentration of Cu and Zn in the soil solution phase, there is no significant risk from heavy metals in the organic fertilizers. However, the K d values for Zn were significantly lower for CSS or the PM-applied plot in the field experiment soil, indicating a higher Zn desorption rate from organically fertilized soil particles. The potential risk of heavy metals from agricultural lands under changing climate conditions must therefore be monitored carefully., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yasuo Mitsui Nakamaru reports financial support was provided by Tokyo University of Agriculture. Yasuo Mitsui Nakamaru reports a relationship with Tokyo University of Agriculture that includes: employment and funding grants. Yasuo Mitusi Nakamaru has patent pending to Yasuo Mitusi Nakamaru. Co-author Retsushi Matsuda previously studied at Tokyo University of Agriculture as a postgraduate student under the supervision of co-author Takeshi Sonoda., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: We performed pull-through hand-sewn coloanal anastomosis immediately after sphincter-preserving ultralow anterior resection (ULAR) [pull-through ultra (PTU)] to avoid permanent stoma and reduce postoperative complications of lower rectal tumors. This study aimed to compare the clinical outcomes of PTU versus non-PTU (stapled or hand-sewn coloanal anastomosis with diverting stoma) after sphincter-preserving ULAR for lower rectal tumors., Methods: This retrospective cohort study analyzed prospectively maintained data from 100 consecutive patients who underwent PTU (n = 29) or non-PTU (n = 71) after sphincter-preserving ULAR for rectal tumors between January 2011 and March 2023. In PTU, hand-sewn coloanal anastomosis was immediately performed using 16 stitches of 4-0 monofilament suture during primary surgery. The clinical outcomes were assessed. The primary outcomes were rates of permanent stomas and overall postoperative complications., Results: The PTU group was significantly less likely to require a permanent stoma than the non-PTU group (P < 0.01). None of the patients in the PTU group required permanent stoma and the rate of overall complications was significantly lower in the PTU group (P = 0.01). The median operative time was comparable between the two groups (P = 0.33) but the median operative time during the second stage was significantly shorter in the PTU group (P < 0.01). The rates of anastomotic leakage and complications of Clavien-Dindo grade III were comparable between the two groups. Diverting ileostomy was performed in two patients with an anastomotic leak in the PTU group. The PTU group was significantly less likely to require a diverting ileostomy than those in the non-PTU group (P < 0.01). The composite length of hospital stay was significantly shorter in the PTU group (P < 0.01)., Conclusions: PTU via immediate coloanal anastomosis for lower rectal tumors is a safe alternative to the current sphincter-preserving ULAR with diverting ileostomy for patients who wish to avoid a stoma., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Nutritional status is an important factor affecting prognosis of cardiovascular diseases. We compared major cardiovascular and cerebrovascular events (MACCE) between the malnutrition (geriatric nutritional risk index <92) and non-malnutrition (geriatric nutritional risk index ≥92) groups in 500 stable coronary artery disease patients undergoing percutaneous coronary intervention and evaluated coronary calcification by intravascular ultrasound. Incidences of all-cause death and MACCE differed between the malnutrition and non-malnutrition groups (22% vs 5%, P < 0.001 and 24% vs 6%, P < 0.001). In multivariate Cox proportional hazards regression, malnutrition significantly correlated with all-cause death (P = 0.006) and MACCE (P = 0.010). The proportion of moderate/severe calcification differed between the malnutrition (64%) and non-malnutrition groups (33%, P < 0.001). Multivariate logistic analysis identified age (P < 0.001), malnutrition (P = 0.048), and hemodialysis (P < 0.001) as significantly related to moderate/severe calcification. Malnutrition was an independent risk factor for all-cause death and MACCE in coronary artery disease patients after percutaneous coronary intervention and was associated with moderately/severely calcified lesions., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Recent clinical trials have shown that percutaneous coronary intervention (PCI) for non-culprit lesions (NCLs) reduces the risk of adverse events in patients with ST-segment elevation myocardial infarction (STEMI), but the effect on long-term outcomes remains unclear in acute coronary syndrome (ACS) patients and a real-world clinical setting., Methods: A retrospective observational cohort study of ACS patients who underwent primary PCI between April 2004 and December 2017 at Juntendo University Shizuoka Hospital, Japan, was performed. The primary endpoint was the composite of cardiovascular disease death (CVD death) and non-fatal myocardial infarction (MI) during the mean follow-up period of 2.7 years, and a landmark analysis for the incidence of the primary endpoint from 31 days to 5 years between the multivessel PCI group and the culprit only PCI group was performed. Multivessel PCI was defined as PCI including non-infarct-related coronary arteries within 30 days after the onset of ACS., Results: Of the 1109 ACS patients with multivessel coronary artery disease of the current cohort, multivessel PCI was performed in 364 (33.2 %) patients. The incidence of the primary endpoint from 31 days to 5 years was significantly lower in the multivessel PCI group (4.0 % vs. 9.6 %, log-rank p = 0.0008). Multivariate Cox regression analysis showed that multivessel PCI was significantly associated with fewer cardiovascular events (HR 0.37, 95 % CI 0.19-0.67, p = 0.0008)., Conclusion: In ACS patients with multivessel coronary artery disease, multivessel PCI may reduce the risk of CVD death and non-fatal MI compared to culprit-lesion-only PCI., Competing Interests: Declaration of competing interest The authors 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 © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: In this pilot study, we have evaluated the specific metabolic and immune-related benefits of the AFO-202 strain and N-163 strain of black yeast Aureobasidium pullulans-produced beta 1,3-1,6 glucan in healthy human subjects., Methods: Sixteen healthy Japanese male volunteers (aged 40 to 60 years) took part in this clinical trial. They were divided into four groups (n = 4 each): Group I consumed AFO-202 beta-glucan (2 sachets of 1 g each per day), IA for 35 days and IB for 21 days; Group II consumed a combination of AFO-202 beta-glucan (2 sachets of 1 g each) and N-163 beta-glucan (1 sachet of 15 g gel each per day), IIA for 35 days and IIB for 21 days., Results: Decrease in HbA1C and glycated albumin (GA), significant increase of eosinophils and monocytes and marginal decrease in D-dimer levels, decrease in neutrophil-to-lymphocyte ratio (NLR), with an increase in the lymphocyte-to-CRP ratio (LCR) and leukocyte-to-CRP ratio (LeCR) was observed in Group I between pre- and post-treatment. Decrease in total and LDL cholesterol, a decrease of CD11b, serum ferritin, galectin-3 and fibrinogen were profound in Group II between pre- and post-treatment. However, there was no statistically significant difference between day 21 and day 35 among the groups., Conclusion: This outcome warrants larger clinical trials to explore the potentials of these safe food supplements in the prevention and prophylaxis of diseases due to dysregulated metabolism, such as fatty liver disease, and infections such as COVID-19 in which balanced immunomodulation are of utmost importance, besides their administration as an adjunct to existing therapeutic approaches of both communicable and non-communicable diseases., (© The Author(s) 2023.)

Purpose: For patients with locally advanced non-small-cell lung cancer (LA-NSCLC) that progressed after definitive chemoradiotherapy (CRT) and durvalumab consolidation therapy, no subsequent standard treatment exists. The type of treatment selected for each timing of disease progression and its efficacy have not been investigated., Methods: We retrospectively enrolled patients with LA-NSCLC or inoperable NSCLC that progressed after definitive CRT and durvalumab consolidation therapy at 15 Japanese institutions. Patients were classified into the following: Early Discontinuation group (disease progression within 6 months after durvalumab initiation), Late Discontinuation group (disease progression from 7 to 12 months after durvalumab initiation), and Accomplishment group (disease progression from 12 months after durvalumab initiation)., Results: Altogether, 127 patients were analyzed, including 50 (39.4%), 42 (33.1%) and 35 (27.5%) patients from the Early Discontinuation, Late Discontinuation, and Accomplishment groups, respectively. Subsequent treatments were Platinum plus immune checkpoint inhibitors (ICI) in 18 (14.2%), ICI in 7 (5.5%), Platinum in 59 (46.4%), Non-Platinum in 35 (27.6%), and tyrosine kinase inhibitor in 8 (6.3%) patients. In the Early Discontinuation, Late Discontinuation, and Accomplishment groups, 4 (8.0%), 7 (16.7%), and 7 (20.0%) patients were receiving Platinum plus ICI; 21 (42.0%), 22 (52.4%), and 16 (45.7%) were receiving Platinum, and 20 (40.0%), 8 (19.0%), and 7 (20.0%) were receiving Non-Platinum, respectively. No significant difference in progression-free survival was observed in the timing of disease progression., Conclusion: In patients with LA-NSCLC hat progressed after definitive CRT and durvalumab consolidation therapy, subsequent treatment may change depending on the timing of disease progression., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Although transbronchial diagnostic procedures are sometimes difficult to perform because of the patient's respiratory or general conditions, endoscopic ultrasound with bronchoscope-guided fine-needle aspiration (EUS-B-FNA), a known transesophageal diagnostic procedure, might be useful for such cases. We conducted this prospective three-center observational study to evaluate the safety and efficacy of EUS-B-FNA in suspected lung cancer patients with poor respiratory or general conditions., Methods: Patients with suspected lung cancer with respiratory failure, Eastern Cooperative Oncology Group performance status of 2 or higher, or severe respiratory symptoms, were enrolled. The primary endpoints were the diagnostic yield of lung cancer and its safety, and the secondary endpoints were the success rate of molecular and programmed death ligand 1 (PD-L1) analyses, and the 6-month survival rate in patients with lung cancer., Results: We enrolled 30 patients, of which 29 were included in the analysis. Among them, 26 were eventually diagnosed with lung cancer. The diagnostic yield for lung cancer was 100% (26/26). There were no adverse events associated with EUS-B-FNA requiring procedure discontinuation. The success rates of molecular analysis for EGFR, ALK, ROS-1, and BRAF were 100% (14/14), 100% (11/11), 100% (9/9), and 75% (6/8), respectively. The success rate of the PD-L1 analysis was 100% (15/15). The 6-month survival rate in patients with lung cancer was 53.8% (95% confidence interval [CI]: 33.4-76.4), and the median overall survival (OS) was 196 days (95% CI: 142-446)., Conclusions: EUS-B-FNA is a safe and effective diagnostic method, even in patients with suspected lung cancer with poor respiratory or general conditions., Trial Registration: This clinical trial was registered at https://www.umin.ac.jp/ctr/index.htm (UMIN000041235, approved on 28/07/2020)., (© 2023. The Author(s).)

Background: Whether immunotherapy improves the efficacy or worsens adverse events of subsequent chemotherapy remains unclear. We performed a Phase 2 study to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as a treatment for advanced non-small cell lung cancer (NSCLC) after treatment with programmed cell death 1 or programmed death ligand 1 [PD-(L)1] inhibitor failure., Methods: Nab-paclitaxel (100 mg/m 2 ) was administered on Days 1, 8, and 15 of a 28-day cycle to patients with advanced NSCLC within 12 weeks after the failure of PD-(L)1 inhibitor treatment. The primary endpoint was objective response rate (ORR) in all patients; the secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety., Results: Thirty cases were registered, and 29 cases were included in the analysis. The ORR was 55.2% (95% confidence interval [CI]: 28.1%-79.6%) and the DCR was 86.2% (95% CI: 65.9%-97.0%). The median PFS was 5.6 months (95% CI: 4.4-6.7 months), and PFS rates at 1- and 2-year timepoints were 34.5% and 13.3%, respectively. The median OS was 11.9 months (95% CI: 0.8-23.0 months). Good performance status and responder of previous PD-(L)1 inhibitor therapy were independent predictors of PFS. Grade 3 or higher toxicities included leukopenia (27.6%), neutropenia (31.0%), peripheral sensory neuropathy (6.9%), increased alanine aminotransferase and aspartate aminotransferase levels (3.4%), and interstitial lung disease (3.4%)., Conclusions: Nab-paclitaxel therapy improved ORR after PD-(L)1 inhibitor treatment failure with a durable response of 13% and acceptable toxicities in patients with advanced NSCLC., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: The Wound, Ischemia, and foot Infection (WIfI) clinical stage has been thought to have a prognostic value in Chronic limb-threatening ischemia (CLTI) patients, and frailty and nutritional status appear to represent pivotal factor affecting prognosis among CLTI patients. The purpose of this study was to examine clinical factors (including frailty and nutritional status) relevant to WIfI clinical stage., Methods: This retrospective study investigated 200 consecutive CLTI patients. We individually assessed WIfI clinical stage, frailty according to the Clinical Frailty Scale (CFS) score, and malnutrition according to Geriatric Nutritional Risk Index (GNRI). We then compared mortality after endovascular intervention between a WIfI stage 1, 2 group and a stage 3, 4 group, and investigated associations between baseline characteristics (including CFS and GNRI) and WIfI clinical stage., Results: Among 200 patients, 123 patients (62%) showed WIfI stage 1 or 2, and the remaining 77 patients (38%) had WIfI stage 3 or 4. CFS score was significantly higher in the WIfI stage 3, 4 group [median 6.0, interquartile range (IQR) 5.5-7.0] compared with the WIfI stage 1, 2 group (median 5.0, IQR 4.0-6.0, p < 0.001), and GNRI was significantly lower in the WIfI stage 3, 4 group (median 88, IQR 80-97) than in the WIfI stage 1, 2 (median 103, IQR 94-111, p < 0.001). Forty patients (20%) died after endovascular intervention. Incidences of all-cause and cardiac deaths were higher in the WIfI stage 3, 4 group than in the WIfI stage 1, 2 group (27% vs. 15%, p = 0.047 and 12% vs. 3%, p = 0.040, respectively). Kaplan-Meier analysis showed a significantly lower survival rate in the WIfI stage 3, 4 group than in the WIfI stage 1, 2 group ( p = 0.002 by log-rank test). Multivariate logistic regression analysis using relevant factors from univariate analysis showed CFS score [odds ratio (OR) 2.06, 95% confidence interval (CI) 1.41-3.13, p < 0.001), diabetes mellitus (OR 3.17, 95%CI 1.17-8.61, p = 0.023) and GNRI (OR 0.93, 95%CI 0.89-0.97, p = 0.002) significantly associated with WIfI stage 3 or 4. In addition, multivariate ordinal logistic regression analysis for WIfI clinical stage showed CFS score (OR 1.43, 95%CI 1.09-1.89, p = 0.011), diabetes mellitus (OR 1.77, 95%CI 1.26-2.54, p < 0.001), and high-sensitivity C-reactive protein (OR 1.14, 95%CI 1.02-1.28, p = 0.041) were positively associated with WIfI clinical stage, and GNRI correlated negatively with WIfI clinical stage (OR 0.95, 95%CI 0.91-0.97, p < 0.001)., Conclusions: These results indicate that CLTI patients with high WIfI clinical stage may be more frail and malnourished, and be associated with poor prognosis after endovascular intervention.

The immune checkpoint inhibitor (ICI), nivolumab, has revolutionised the treatment of recurrent and metastatic oral cancer. However, the response rate to ICIs remains low, and identifying predictors of nivolumab response is critical. Although the neutrophil-to-lymphocyte ratio (NLR) has been suggested as a predictive marker of nivolumab response in patients with various types of cancer, its utility in oral squamous cell carcinoma (OSCC) has not been elucidated. In this retrospective multicentre cohort study, we evaluated the association between NLR and outcome of nivolumab treatment in 64 patients with OSCC treated between 2017 and 2020. The objective response and disease control rates were 25.1% and 32.9%, respectively. The rates for complete and partial responses were 15.7% (10/64) and 9.4% (6/64), respectively; stable and progressive disease rates were 7.8% (5/64) and 67.1% (43/64), respectively. Complete and partial responses were classified as responders, and stable and progressive diseases were classified as non-responders. The median (range) pre-treatment NLR among responders was 4.3 (2.8-8.0), which decreased to 4.0 (2.6-6.3) after nivolumab treatment, and the median (range) pre-treatment NLR among non-responders was 5.1 (2.7-7.9), which increased to 6.4 (4.0-14.0) with tumour growth. Moreover, overall survival was significantly worse in the group with a higher post-treatment NLR (≥5) than in the group with a lower NLR (<5). Patients with a post-treatment NLR of ≥6 had worse outcomes for salvage chemotherapy following nivolumab treatment. Thus, post-treatment NLR could be a useful marker for predicting the response to nivolumab treatment or salvage chemotherapy in patients with OSCC., (Copyright © 2023 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Weakly coordinating anions (WCAs) facilitate the stabilization and isolation of highly reactive and almost "naked" cations. Alkoxyaluminate-based WCAs such as [Al(OC(CF 3 ) 3 ) 4 ] - ([ pf ] - ) are widely used due to their synthetic accessibility and their high stability. However, small cations are still able to coordinate the oxygen atoms of the [ pf ] - anion or even to abstract an alkoxy ligand. The novel WCA [Al(OC 10 F 15 ) 4 ] - ([ pfAd ] - ; OC 10 F 15 = perfluoro-1-adamantoxy) is characterized by a very rigid core framework, thus indicating a higher stability towards fluoride-ion abstraction (DFT calculations) and providing hope to generate less disordered crystal structures. The [ pfAd ] - anion was generated by the reaction of the highly acidic alcohol perfluoro-1-adamantanol C 10 F 15 OH with LiAlH 4 in o -DFB. Li[ pfAd ] could not be synthesized free of impurities (and still contains unreacted alcohol). Yet, starting from contaminated Li[ pfAd ], the very useful pure salts Ag[ pfAd ], [Ph 3 C][ pfAd ] and [H(OEt 2 ) 2 ][ pfAd ] could be synthesized. The salts were characterized by NMR spectroscopy, single-crystal X-ray diffraction and IR spectroscopy. Additionally, [NO][ pfAd ] could be synthesized containing alcohol impurities but nonetheless enabled the synthesis of the salt P 9 + [ pfAd ] - . The synthesis of Tl[ pfAd ] in a mixture of H 2 O/acetone/ o -DFB demonstrated the water stability of the [ pfAd ] - anion.

Identification of structurally novel inhibitors of lysine methyltransferase G9a has been a subject of intense research in cancer epigenetics. Starting with the high-throughput screening (HTS) hit rac - 10a obtained from the chemical library of the University of Tokyo Drug Discovery Initiative, the structure-activity relationship of the unique substrate-competitive inhibitors was established with the help of X-ray crystallography and fragment molecular orbital (FMO) calculations for the ligand-protein interaction. Further optimization of the in vitro characteristics and drug metabolism and pharmacokinetics (DMPK) properties led to the identification of 26j (RK-701), which is a structurally distinct potent inhibitor of G9a/GLP (IC 50 = 27/53 nM). Compound 26j exhibited remarkable selectivity against other related methyltransferases, dose-dependent attenuation of cellular H3K9me2 levels, and tumor growth inhibition in MOLT-4 cells in vitro . Moreover, compound 26j showed inhibition of tumor initiation and growth in a carcinogen-induced hepatocellular carcinoma (HCC) in vivo mouse model without overt acute toxicity.

Sickle cell disease (SCD) is a heritable disorder caused by β-globin gene mutations. Induction of fetal γ-globin is an established therapeutic strategy. Recently, epigenetic modulators, including G9a inhibitors, have been proposed as therapeutic agents. However, the molecular mechanisms whereby these small molecules reactivate γ-globin remain unclear. Here we report the development of a highly selective and non-genotoxic G9a inhibitor, RK-701. RK-701 treatment induces fetal globin expression both in human erythroid cells and in mice. Using RK-701, we find that BGLT3 long non-coding RNA plays an essential role in γ-globin induction. RK-701 selectively upregulates BGLT3 by inhibiting the recruitment of two major γ-globin repressors in complex with G9a onto the BGLT3 gene locus through CHD4, a component of the NuRD complex. Remarkably, BGLT3 is indispensable for γ-globin induction by not only RK-701 but also hydroxyurea and other inducers. The universal role of BGLT3 in γ-globin induction suggests its importance in SCD treatment., (© 2023. The Author(s).)

Background: Aureobasidium pullulans (black yeast) AFO-202 strain-produced beta glucan, Nichi Glucan, has been shown to improve the behavior and sleep pattern along with an increase in α-synuclein and melatonin in children with autism spectrum disorder (ASD)., Objective: In this randomized pilot clinical study, we have evaluated the gut microbiota of subjects with ASD after consumption of Nichi Glucan., Methods: Eighteen subjects with ASD were randomly allocated: six subjects in the control group (Group 1): conventional treatment comprising remedial behavioral therapies and L-carnosine 500 mg per day, and 12 subjects (Group 2) underwent supplementation with Nichi Glucan 0.5 g twice daily along with the conventional treatment for 90 days., Results: Whole genome metagenome (WGM) sequencing of the stool samples at baseline and after intervention showed that among genera of relevance, the abundance of Enterobacteriaceae was decreased almost to zero in Group 2 after intervention, whereas it increased from 0.36% to 0.85% in Group 1. The abundance of Bacteroides increased in Group 1, whereas it decreased in Group 2. The abundance of Prevotella increased while the abundance of Lactobacillus decreased in both Group 1 and Group 2. Among species, a decrease was seen in Escherichia coli, Akkermansia muciniphila CAG:154, Blautia spp., Coprobacillus sp., and Clostridium bolteae CAG:59, with an increase of Faecalibacterium prausnitzii and Prevotella copri, which are both beneficial., Conclusion: AFO-202 beta 1,3-1,6 glucan, in addition to balancing the gut microbiome in children with ASD and its role in effective control of curli-producing Enterobacteriaceae that leads to α-synuclein misfolding and accumulation, may have a prophylactic role in Parkinson's and Alzheimer's diseases as well.

The patient was a 69-year-old man who called an ambulance due to dyspnea. When emergency medical technicians found him, he had collapsed into deep coma in front of his house. On arrival, he remained in a deep coma with severe hypoxia. He underwent tracheal intubation. An electrocardiogram showed ST elevation. Chest roentgen showed bilateral butterfly shadow. Cardiac ultrasound revealed diffuse hypokinesis. Head computed tomography (CT) showed early cerebral ischemic signs that had been initially overlooked. Urgent transcutaneous coronary angiography showed obstruction of the right coronary artery that was treated successfully. However, the next day, he was still in coma and demonstrated anisocoria. Repeated head CT showed diffuse cerebral infarction. He died on the 5 th day. We herein report a rare case of cardio-cerebral infarction with a fatal outcome. Patients with acute myocardial infarction and a coma state should be evaluated for cerebral perfusion or occlusion of major cerebral vessels by enhanced CT or an aortogram if percutaneous coronary intervention is performed., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Emergencies, Trauma, and Shock.)

Esophageal neuroendocrine neoplasms are extremely rare, and their prognosis is poor. Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are even more rare and are defined as tumors consisting of neuroendocrine carcinoma and either adenocarcinoma or squamous cell carcinoma. We report a rare case featuring endoscopic submucosal dissection (ESD) for an esophageal MiNEN, arising from the ectopic gastric mucosa in the lower thoracic esophagus. A 92-year-old male patient was referred to this hospital for investigation of an esophageal tumor. An endoscopic examination revealed a 10 mm elevated lesion, with 8 mm flat areas on the anal side, within the ectopic gastric mucosa located in the lower thoracic esophagus. ESD was carried out, and a histopathological examination revealed a tubular adenocarcinoma composed of differentiated neuroendocrine cells. Immunohistochemical staining was positive for synaptophysin and negative for chromogranin A. The labeling index of Ki-67 was more than 80%. Based on these results, we diagnosed the lesion as an esophageal MiNEN, arising in the ectopic gastric mucosa of the esophagus. The patient remains alive, without recurrence of cancer, 24 months after ESD., Competing Interests: The authors have no conflicts of interest to declare., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Background/aim: Combination chemotherapy with gemcitabine, nab-paclitaxel, oxaliplatin, and itraconazole (GnPO-ITC) was administered as first-line chemotherapy in patients with metastatic pancreatic cancer (mPC). The efficacy and toxicity of these treatments were retrospectively investigated., Patients and Methods: A total of 81 patients (mean age=64 years) with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 were enrolled in the study, and administered nab-paclitaxel (125 mg/m 2 ), gemcitabine (1,000 mg/m 2 ), and oxaliplatin (85 mg/m 2 ) on day 1 and itraconazole (400 mg) on days -2 to +2, repeated every 2 weeks., Results: Metastatic sites observed in patients included the liver (n=55, 68%), peritoneum (n=23, 28%), distant lymph nodes (n=24, 30%), and lungs (n=18, 22%). Within 28 days after initiation of chemotherapy, 15 patients (19%) experienced common ≥3 grade hematological adverse events. The major reason for discontinuation of treatment among the responders was peripheral sensory neuropathy in 36 patients (44%). The overall response rate to treatment was 64% [95% confidence interval (CI)=54-75%]. The median progression-free survival and median overall survival were 8.3 months (95% CI=6.8-9.8 months) and 14.4 months (95% CI=11.4-17.3 months), respectively. Among the 52 responders, 24 (46%) underwent conversion surgery, which did not improve survival (p=0.279). Second-line treatment with irinotecan was required in 71 (88%) patients. Hepatic arterial chemotherapy and radiotherapy were administered to 33 (41%) and 27 (33%) patients, respectively., Conclusion: The GnPO-ITC regimen showed promising efficacy with manageable toxicities for controlling disease progression and improving overall survival., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Antithrombin deficiency is a high-risk factor for venous thromboembolism during pregnancy, whereas cerebral venous thrombosis is rare. Cerebral venous thrombosis related to coronavirus disease 2019 (COVID-19) vaccines has been reported; however, there are a few reports of cerebral venous thrombosis after a messenger RNA (mRNA) vaccination. A 25-year-old female in her sixth week of pregnancy presented with headache 24 days after BNT162b2 mRNA COVID-19 vaccination. The following day, she presented with altered sensorium and was diagnosed with severe cerebral venous thrombosis. She demonstrated heparin resistance and was found to have an inherited antithrombin deficiency. A heterozygous missense variant in SERPINC1 (c.379T>C, p.Cys127Arg, 'AT Morioka') was detected by DNA analysis. Despite intensive care with unfractionated heparin, antithrombin concentrate, and repeated endovascular treatments, she died on the sixth day of hospitalization. Cerebral venous thrombosis in pregnant women with an antithrombin deficiency can follow a rapid and fatal course. Treatment with unfractionated heparin and antithrombin concentrate may be ineffective in severe cerebral venous thrombosis cases with antithrombin deficiency. Early recognition of antithrombin deficiency and an immediate switch to other anticoagulants may be required. Although the association between cerebral venous thrombosis and the vaccine is uncertain, COVID-19 vaccinations may require careful evaluation for patients with prothrombic factors.