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Objectives: Autoimmune pancreatitis (AIP) is a pancreatic manifestation of IgG4-related disease which is complicated by extra-pancreatic lesions such as IgG4-related sclerosing cholangitis. The appropriate biliary drainage method and period for type 1 AIP remain unclear. Therefore, we aimed to clarify the usefulness and safety of endoscopic nasobiliary drainage (ENBD) for type 1 AIP in patients with jaundice., Methods: This study enrolled 83 patients with type 1 AIP who underwent steroid therapy who underwent evaluation of contrast material outflow to the jejunum using cholangiography. The ENBD was removed when the contrast material outflowed into the duodenum; an endoscopic biliary stenting (EBS) was performed if it did not outflow., Results: Cholangiography and pancreatography were achieved in 83 (100%) and 77 (93%) patients, respectively. Liver function parameters were significantly decreased after ENBD. Bile juice cytology using ENBD revealed no evidence of malignancy. Two (2%) patients developed mild pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP). Endoscopic ultrasound-guided fine-needle aspiration biopsy was performed in 56 (67%) patients. ENBD was removed in 75 (90%) patients; EBS was performed in 8 (10%). Multivariate regression analysis showed pancreatic focal enlargement (OR=12.06, 95% CI: 1.28-113.62, P=0.03) as an independent risk factor for EBS., Conclusions: Although ENBD causes discomfort and the risk of self-removal, it differentiates AIP from malignant tumors, evaluates steroid effects using real-time cholangiography, and reduces the number of required ERCP procedures. ENBD could be one of the drainage options for type 1 AIP, depending on patients' background., Competing Interests: Conflict of interest: Takashi Ito, Tsukasa Ikeura, Masataka Masuda, Koh Nakamaru, Masaaki Shimatani, Kazushige Uchida, Makoto Takaoka, Kazuichi Okazaki, Makoto Naganuma have no conflict of interest or financial ties to disclose. Conflicts of Interest: The authors declare that they have no conflict of interest., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The fibrosis-4 (FIB4) index, a simple, noninvasive marker used for hepatic diseases, represents adverse outcomes. The aim of the present study was to evaluate whether the FIB4 index can predict adverse outcomes in patients with ST-elevation myocardial infarction (STEMI)., Methods: We investigated patients with STEMI who underwent primary percutaneous coronary intervention (PCI) and were alive at discharge. The cut-off FIB4 index at discharge was investigated using the survival classification and regression tree (CART) model to predict adverse outcomes. The primary outcome was all-cause mortality., Results: Between January 2006 and December 2018, 1354 patients with STEMI (median age, 68 years; men, 76.1%) were investigated. The median value of the FIB4 index was 1.21 (0.84-1.78). The CART model divided the study population into low (FIB4 index <0.945; n  = 435), intermediate (0.945 ≤ FIB4 index < 2.185; n  = 692), and high (FIB4 index ≥2.185; n  = 227) groups based on the significant predictive values for all-cause death. During a median follow-up period of 4.3 years, all-cause death occurred in 208 patients (15.4%). The Kaplan-Meier analysis showed a significant increase in mortality with higher FIB4 index values (log-rank, P  < 0.001). The multivariate Cox regression model revealed that the FIB4 index was an independent risk predictor for all-cause death in patients with STEMI [low group as reference vs. intermediate group, hazard ratio: 1.975; 95% confidence interval (CI): 1.166-3.346; P  = 0.011 and vs. high group, hazard ratio: 4.633; 95% CI: 2.549-8.418; P  < 0.001]., Conclusions: The FIB4 index was associated with the risk of all-cause mortality in patients with STEMI who underwent primary PCI., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Pathological fractures of benign bone tumors can be difficult to treat, and the underlying pathogenesis remains unclear. Herein, we aimed to determine preventive measures for pathological fractures in patients with benign bone tumors based on fracture outcomes. Between April 2015 and July 2023, we enrolled 18 consecutive patients with oncological pathological fractures treated at our department. Age, sex, histopathological diagnosis, site of origin, whether incisional or pathological fracture, treatment, operative time, blood loss, recurrence, and characteristics of impending and pathological fractures were examined. The median patient age was 22 years, comprising 9 males and 9 females. The pathology included bone cysts (n = 6), enchondromas (n = 5), fibrous dysplasia (n = 4), giant cell tumors (n = 2), and aneurysm bone cysts (n = 1). Six cases involved the humerus, 5 the femur, 3 the phalanges, 2 the toes, 1 the ribs, and 1 the tibia. Five and 13 cases were impending and pathological fractures, respectively. Thirteen patients underwent surgery, whereas 5 were treated conservatively. Surgical methods included curettage and artificial bone graft (n = 6); curettage and artificial bone graft plus compression hip screw fixation (n = 3); and curettage and artificial bone graft plus plate fixation, intramedullary nail, artificial head replacement, and plate fixation (n = 1 case each). The mean operative time and blood loss were 76 ± 56 minutes and 10 ± 80.1 mL, respectively. Recurrence occurred in 1 case. All impending fractures had onset in the lower extremity bones. Pathological fractures due to benign bone tumors of the lower extremities should not be overlooked as symptoms of pain., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: In patients with metastatic pancreatic neuroendocrine tumors (PanNETs), the Ki-67 index is objectively assessed by pathologists; however, liver tumor burden (LTB) depends on the subjective judgment of physicians. This study aimed to elucidate the usefulness of the semi-automated 3D volumetric assessment of LTB in patients with PanNET., Materials and Methods: We retrospectively reviewed 29 patients (40 computed tomographies [CTs]) with metastatic PanNETs. LTB was measured using a semiautomated 3D volumetric software program (volumetric assessment) or evaluated independently by 6 clinicians using CT imaging (visual assessment). The treatment map was classified into 3 groups based on LTB and Ki-67 index., Results: Visual and volumetric assessments of the LTB were well correlated. The LTB was significantly higher on visual assessment than volumetric assessment (P < 0.01). Categorization on the map was consistent between the visual and volumetric evaluations in 23 patients (equal group). The remaining 6 patients were overestimated by visual assessment (overestimated group). Progression-free survival was significantly longer in patients in the 'equal group' than the 'overestimated group' (981 vs 366 days, P < 0.01)., Conclusions: This pilot study revealed a good correlation between visual and volumetric assessments, and visual assessment overestimated LTB, compared to volumetric assessment., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Pancreatic stump closure in minimally invasive distal pancreatectomy (DP) commonly utilizes staplers due to its simplicity; however, postoperative pancreatic fistula (POPF) remains the most frequent complication. We have developed a novel stump closure technique using a transpancreatic mattress suture with a polyglycolic acid sheet (TP method) under robotic DP. This study aims to evaluate the efficacy of the TP method., Materials and Methods: This study included 145 cases of pure minimally invasive DP performed between February 2011 and July 2024: 34 robotic (R) and 97 laparoscopic (Lap). Surgical outcomes were compared across 3 groups based on the stump closure method: 18 cases using the TP method (TP group; R: 18), 22 with hand-sewn closure in a fish-mouth manner (FM group; Lap: 22), and 91 with a reinforced stapler (S group; R: 16, Lap: 75). Logistic regression analysis was employed to identify risk factors for POPF., Results: POPF occurred in 20 of 131 cases (grade B: 19, C: 1, 15.3%). The TP group exhibited the lowest POPF rate (TP vs FM vs S: 5.6% vs 27.3% vs 14.3%). Multivariate analysis identified pancreatic thickness ≥12 mm as an independent risk factor. For thickness <12 mm, no significant differences in POPF rates were observed (TP vs FM vs S: 0% vs 25.0% vs 5.6%). However, for thickness ≥12 mm, the TP group had a significantly lower POPF rate compared with the S group (TP vs FM vs S: 7.7% vs 28.6% vs 47.4%)., Conclusion: The TP method is superior to stapler closure in preventing POPF, especially in cases with pancreatic thickness of ≥12 mm., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: The Immunosuppressive Drugs Scientific Committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology established the second consensus report to guide therapeutic drug monitoring (TDM) of everolimus (EVR) and its optimal use in clinical practice 7 years after the first version was published in 2016. This version provides information focused on new developments that have arisen in the last 7 years. For the general aspects of the pharmacology and TDM of EVR that have retained their relevance, readers can refer to the 2016 document. This edition includes new evidence from the literature, focusing on the topics updated during the last 7 years, including indirect pharmacological effects of EVR on the mammalian target of rapamycin complex 2 with the major mechanism of direct inhibition of the mammalian target of rapamycin complex 1. In addition, various concepts and technical options to monitor EVR concentrations, improve analytical performance, and increase the number of options available for immunochemical analytical methods have been included. Only limited new pharmacogenetic information regarding EVR has emerged; however, pharmacometrics and model-informed precision dosing have been constructed using physiological parameters as covariates, including pharmacogenetic information. In clinical settings, EVR is combined with a decreased dose of calcineurin inhibitors, such as tacrolimus and cyclosporine, instead of mycophenolic acid. The literature and recommendations for specific organ transplantations, such as that of the kidneys, liver, heart, and lungs, as well as for oncology and pediatrics have been updated. EVR TDM for pancreatic and islet transplantation has been added to this edition. The pharmacodynamic monitoring of EVR in organ transplantation has also been updated. These updates and additions, along with the previous version of this consensus document, will be helpful to clinicians and researchers treating patients receiving EVR., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The optimal surgical indication for intraductal papillary mucinous neoplasms (IPMN) remains highly contentious. We aimed to determine the preoperative predictive factors of malignancy and independent prognostic factors in patients with IPMN who underwent curative-intent resection. In this study, 104 patients with a pathological diagnosis of IPMN who underwent curative-intent resection were included. Multivariate regression and Cox proportional-hazards analyses were performed to identify the predictive factors for invasive intraductal papillary mucinous carcinoma (IPMC) and prognostic factors for overall survival (OS) after surgery. Among the 104 patients, 24 (23.1%) were pathologically diagnosed with invasive IPMC, and the remaining 80 had low-grade dysplasia or high-grade dysplasia. The presence of high-risk stigmata was an independent predictive risk factor for invasive IPMC. The age-adjusted Charlson comorbidity index (ACCI) (≥4/<4) and geriatric nutritional risk index (GNRI) (<99/≥99) were independent poor prognostic factors for OS (hazard ratio [HR]: 9.39; 95% confidence interval [CI]: 1.90-46.54; P = .006 and HR: 4.37; 95% CI: 1.07-17.86, P = .040, respectively). Forty patients with ACCI ≥ 4 (38.5%) had a significantly lower 5-year OS rate than those with ACCI < 4 (74.3 vs 98.2%, P < .001). Similarly, 29 patients with GNRI < 99 (27.9%) had a significantly lower 5-year OS rate than those with GNRI ≥ 99 (76.0 vs 95.1%, P < .001). These 2 factors were associated with significantly worse disease-specific survival after surgery. The ACCI and GNRI emerged as independent prognostic factors after surgery in patients with IPMN. These findings highlight the importance of patient-conditional factors as valuable indicators for predicting favorable long-term survival outcomes after surgery and for facilitating a more precise assessment of surgical eligibility in patients with IPMN., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The indication of living donor liver retransplantation (re-LDLT) for retransplant candidates with chronic allograft failure (CAF) is increasing because of the high mortality rate of patients on the waiting list. However, evidence supporting re-LDLT for CAF remains scarce because of technical difficulties. We aimed to examine the feasibility based on our significant case experience., Methods: A total of 95 retransplant cases (adult: 53, pediatric: 42) between 2000 and 2020 were retrospectively reviewed. Graft survival after re-LDLT and deceased donor liver retransplantation (re-DDLT) was compared among recipients with CAF and acute allograft failure (AAF)., Results: Re-LDLTs for CAF were performed in 58 (61.1%) cases, re-DDLTs for CAF in 16 (16.8%) cases, re-LDLTs for AAF in 13 (13.7%) cases, and re-DDLTs for AAF in 8 (8.4%) cases. Re-DDLTs have become increasingly prevalent over time. Retransplantation for AAF results in lower graft survival than that for CAF in both adult and pediatric cases. All adult recipients who underwent re-LDLT for AAF died within 1 y after retransplantation. The 5-y graft survival between re-LDLT and re-DDLT for CAF was not significantly different (73.8% versus 75.0%, P  = 0.84). Operation time and blood loss were not significantly different., Conclusions: The survival rate of re-LDLT for recipients with CAF is permissible. Re-LDLT may be another treatment option for recipients with CAF., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Backgrounds: Establishment of quantitative, objective evaluation tool for facial palsy has been a big issue for clinicians and researchers, and in an era of artificial intelligence, AI-driven video analysis can be considered a reasonable solution for this long-discussed issue. We introduced facial keypoint detection, which detects facial landmarks with 68 points, but existing models had been organized almost solely with images of healthy individuals and low accuracy was presumed in the prediction of asymmetric faces of facial palsy patients.The accuracy of existing model was assessed through applying it to the movies of 30 facial palsy patients. Qualitative review clearly showed its insufficiency; prone to detect patients' faces as symmetric, and unable to detect closure of the eyes. Thus, we decided to enhance the model through machine learning process of annotation (fine-tuning)., Methods: 1181 images extracted from the movies of 196 patients were enrolled in the training, and these images underwent manual correction of 68 keypoints. The annotated data was integrated into the previous model with a stack of two Hourglass networks combined with Channel Aggregation Block., Results: The post-annotation model showed improvement in normalized mean error from 0.026 to 0.018, and also qualitatively keypoint detection on each facial unit revealed improvements., Conclusion: Our strict control of the inter- and intra-annotator variability successfully fine-tuned the presenting model, and we consider our new model as one of promising solutions for objective assessment of facial palsy., (Copyright © 2024 by the American Society of Plastic Surgeons.)

Objectives: To examine the significance of tumor budding as a prognostic factor of resected pancreatic ductal adenocarcinoma (PDAC) specimens after preoperative chemoradiotherapy (CRT)., Methods: Among 162 PDAC patients who underwent pancreatectomy after gemcitabine and S1-based CRT from 2012 to 2019, 131 were evaluated for tumor budding. Tumor buds were counted at the invasive front, where the degree of budding was the greatest (hematoxylin and eosin staining, ×20 magnification). Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were compared between the patients without tumor budding (non-TB group) and those with tumor buddings (TB group). Multivariate Cox proportional hazards analysis was conducted to examine the significance of tumor budding as a prognostic factor., Results: OS, DSS, and RFS (median survival time) of the non-TB group were significantly longer than those of the TB group (OS: 50.7 vs. 27.5 months, P = 0.014. DSS: 63.3 vs. 33.0 months, P = 0.014. RFS: 20.3 vs. 11.3 months, P = 0.028). Multivariate analysis identified adjuvant chemotherapy (P = 0.003) as a favorable prognostic factor of OS and tumor budding (P = 0.023) as an adverse prognostic factor of DSS., Conclusions: This study revealed that the presence of tumor budding was an independent adverse prognostic factor in PDAC patients resected after gemcitabine and S1-based CRT., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This study estimated an individual's genetic liability to cardiometabolic risk factors by polygenic risk score (PRS) construction and examined whether high cardiorespiratory fitness (CRF) modifies the association between PRS and cardiometabolic risk factors., Methods: This cross-sectional study enrolled 1296 Japanese adults aged ≥40 yr. The PRS for each cardiometabolic trait (blood lipids, glucose, hypertension, and obesity) was calculated using the LDpred2 and clumping and thresholding methods. Participants were divided into low-, intermediate-, and high-PRS groups according to PRS tertiles for each trait. CRF was quantified as peak oxygen uptake (V̇O 2peak ) per kilogram body weight. Participants were divided into low-, intermediate-, and high-CRF groups according to the tertile V̇O 2peak value., Results: Linear regression analysis revealed a significant interaction between PRS for triglyceride (PRS TG ) and CRF groups on serum TG levels regardless of the PRS calculation method, and the association between PRS TG and TG levels was attenuated in the high-CRF group. Logistic regression analysis revealed a significant sub-additive interaction between LDpred2 PRS TG and CRF on the prevalence of high TG, indicating that high CRF attenuated the genetic predisposition to high TG. Furthermore, a significant sub-additive interaction between PRS for body mass index and CRF on obesity was detected regardless of the PRS calculation method. These significant interaction effects on high TG and obesity were diminished in the sensitivity analysis using V̇O 2peak per kilogram fat-free mass as the CRF index. Effects of PRSs for other cardiometabolic traits were not significantly attenuated in the high-CRF group regardless of PRS calculation methods., Conclusions: The findings of the present study suggest that individuals with high CRF overcome the genetic predisposition to high TG levels and obesity., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

Background: Brexpiprazole is a second-generation antipsychotic approved in Japan in 2018; however, information on placental passage and breast milk transfer remains limited. In this report, the patient, a 30-year-old pregnant woman with schizophrenia, was medicated with brexpiprazole, risperidone, and quetiapine., Methods: The study used high-performance liquid chromatography-tandem mass spectrometry to determine the concentrations of brexpiprazole, quetiapine, risperidone, and its active metabolite (paliperidone) in maternal and neonatal plasma, cord venous plasma, and breast milk. Maternal plasma samples were obtained approximately 2 and 8 hours after the last administration of antipsychotics on the day of delivery and at the estimated drugs' trough time on days 1, 3, and 5 after delivery., Results: The maternal plasma concentrations of brexpiprazole, quetiapine, and paliperidone increased by approximately 3.5-fold on the fifth day compared with those on the day of delivery, whereas the risperidone concentration remained almost constant. Moreover, the neonatal plasma concentrations of the 4 drugs immediately after birth were indistinguishable from the umbilical cord concentrations and gradually decreased, except for risperidone. Relative infant doses of these compounds were below 1.1%., Conclusions: Pregnancy status notably alters the pharmacokinetic properties of antipsychotics. Therefore, close and careful monitoring of clinical symptoms should be considered during pregnancy and after delivery. Although brexpiprazole is transferred to neonates through the placenta, breastfeeding is still possible because the relative infant dose value of this drug was much less than 10%., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This prospective study investigated the relationship between inflammation, damage-associated molecular patterns (DAMPs), and thrombus formation on dialyzer membranes in critically ill patients undergoing renal replacement therapy (RRT) from July 2020 to August 2022, identifying mechanisms and interventions to prevent clotting. The patients were divided into two groups: inflammatory (n = 56, serum C-reactive protein >10 mg/dl) and noninflammatory control (n = 45, serum C-reactive protein <5 mg/dl). Cell-free deoxyribonucleic acid (DNA) levels, high mobility group box 1 protein (HMGB1), histone H3, and myeloperoxidase (MPO) in the lumen of the hollow fiber membrane of the dialyzer were quantified. Immunostaining assessed leukocytes, fibrin fibers, and platelet thrombi on the luminal surface of the hollow fiber membrane. The inflammatory group, compared to controls, exhibited elevated cell-free DNA, HMGB1, and MPO levels, although histone H3 remained unchanged. Damage-associated molecular patterns increased with disseminated intravascular coagulation (DIC) severity. Immunostaining in the inflammatory group revealed leukocytes, amorphous nuclei, neutrophil extracellular trap-like structures, fibrin fibers, and platelet thrombi on the hollow fiber membrane's luminal surface. Elevated DAMP levels in severely inflamed patients' dialyzer membranes, correlating with DIC severity, indicate a link between inflammation, coagulation activation, and dialyzer clotting. Research into thrombus prevention in RRT for DIC-affected critically ill patients is warranted., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the ASAIO.)

Background: Minimally invasive spleen-preserving distal pancreatectomy with Warshaw procedure (MI-WP), has gained widespread recognition for the treatment of benign and low-grade malignant tumors of the pancreatic body and tail. However, the comparative advantages of the robotic Warshaw procedure (R-WP) over the laparoscopic Warshaw procedure (L-WP) remain uncertain. This study aimed to compare the surgical outcomes between R-WP and L-WP., Materials and Methods: Among the 146 cases of MI-DP conducted between October 2020 and December 2023 (L-DP:115, R-DP:31), 33 cases of MI-WP were subjected to analysis, comprising the R-WP group (n=10) and the L-WP group (n=23)., Results: R-WP successfully completed all procedures under a purely laparoscopic approach, whereas L-WP necessitated conversion to open surgery in 2 cases (8.7%). Despite the significantly prolonged operative time in R-WP compared with L-WP (R-WP vs. L-WP: 421vs. 300 min), there was no significant difference in estimated blood loss between the 2 groups (R-WP vs. L-WP: 19 vs. 20 mL). Although the rate of major complications did not significantly differ between the 2 groups, 2 cases (8.7%) of L-WP required reoperation, including splenectomy in 1 instance. Furthermore, the incidence of postoperative splenic infarction was significantly higher in L-WP than in R-WP (R- vs. L-WP:0 vs. 43.5%, P =0.015). The length of hospital stay after surgery did not exhibit a significant difference between the 2 groups (R-WP vs. L-WP: 11 vs. 12 d)., Discussion: R-WP demonstrated superiority to L-WP for reducing the incidence of postoperative splenic infarction, potentially contributing to enhancing the spleen preservation rate., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Patients with type 2 diabetes mellitus are frequently hospitalized for heart failure. The ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/e'), measured by echocardiography, is a simple and convenient indicator of diastolic dysfunction. Various large clinical trials have reported that sodium glucose transporter-2 inhibitor therapy reduced cardiovascular events and hospitalizations in heart failure patients. We examined the effect of tofogliflozin on various physiological and cardiac function. A retrospective analysis was performed on elderly patients aged 65 years or older with type 2 diabetes mellitus attending Himi Municipal Hospital who were taking oral tofogliflozin 20 mg/day. Measurement of physiological and hormonal variables, blood sampling, and echocardiographic evaluations at 0, 1, 3, and 6 months were performed on those with ejection fraction (EF) of 40% or greater at the time of treatment. Statistical analysis was performed using t-tests and mixed-effects models, with brain natriuretic peptide less than or not less than 100 pg/mL, estimated glomerular filtration rate (eGFR) less than or not less than 50 mL/min/1.73 m2, and diuretics administered or not. Hypoglycemic effects were observed at 0, 1, 3, and 6 months. At each time point, EF was retained and E/e' was significantly reduced. On the other hand, most physiological parameters and laboratory results showed no clinical abnormalities. Mixed-effects models showed time-dependent reduction of E/e' in high/low brain natriuretic peptide, high/low eGFR, with or without diuretics between baseline and at 6 months. The interaction with time was significant in high/low eGFR. Tofogliflozin was shown to improve E/e', a measure of diastolic function, while maintaining EF, with hypoglycemic effects and no clinical side effects., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Solitary fibrous tumors can manifest at various anatomical sites, predominantly occurring at extrapleural sites with a peak incidence between 40 and 70 years. SFT necessitates long-term follow-up owing to its tumor characteristics. However, comprehensive reports covering the period from initial diagnosis to the patient's demise are lacking. Herein, we present a case of a malignant SFT of the buttocks that was treated at our hospital from the time of initial diagnosis to the end of life, with a literature review., Methods: A 54-year-old woman had a T1 low-to-isobaric and T2 isobaric-to-hyperintense mass in the psoas muscle on magnetic resonance imaging, diagnosed as an SFT. Wide excision was performed, followed by postoperative radiotherapy and chemotherapy. Multiple lung metastases were treated, while bone metastases appeared in the left femur. Multiple spinal metastases developed, causing respiratory distress due to pleural effusion. Best support care was initiated; however, a thrombus appeared in the inferior vena cava. Despite anticoagulant therapy, the patient died 11 years and 6 months after the initial surgery. Herein, marginal resection resulted in a relatively short operative time and average blood loss. The radiotherapy dose was 66 Gy; no complications occurred, and local recurrence was prevented. Tumor arthroplasty was performed to stabilize the affected limbs, and the patient required careful follow-up., Results: Despite the poor prognosis, the patient survived >11 years after surgery and had a favorable outcome., Conclusion: Long-term monitoring for potential complications remains necessary., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

In kidney transplant recipients (KTRs), viral infection can lead to antibody and/or T-cell mediated rejection, resulting in kidney transplant dysfunction. Therefore, it is critical to prevent infections. However, KTRs exhibit suboptimal responses to SARS-CoV-2 and/or influenza vaccines, partly due to immunosuppressant therapy. Inter- and intra-individual differences in the biological responses to vaccines may also affect patients' antibody production ability. This study included KTRs who received an messenger RNA SARS-CoV-2 vaccine (3 doses), and an inactivated quadrivalent influenza vaccine (1 or 2 doses). We measured the patients' total antibody titers against SARS-CoV-2 spike antigen, and hemagglutination inhibition (HI) titers against influenza A/H1N1, A/H3N2, B/Yamagata, and B/Victoria. Five patients were eligible for this study. Of these 5 KTRs, two produced anti-SARS-CoV-2 spike antibody titers to a seroprotective level, and also produced HI titers against A/H1N1 to a seroprotective level. Another 2 KTRs did not produce seroprotective anti-SARS-CoV-2 antibody titers, but produced seroprotective HI titers against A/H1N1. The remaining KTR produced a seroprotective anti-SARS-CoV-2 antibody titer, but did not produce a seroprotective HI titer against A/H1N1. The 2 KTRs who did not produce seroprotective anti-SARS-CoV-2 antibody titers following vaccination, later developed COVID-19, and this infection increased their titers over the seroprotective level. This study demonstrated that inter- and intra-individual differences in biological responses to vaccines should be considered in pediatric KTRs, in addition to immunosuppressant effects. Personalized regimens, such as augmented or booster doses of vaccines, could potentially improve the vaccination efficacy against SARS-CoV-2 and influenza., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: The study aimed to determine the relationship between knee extension torque induced by repetitive peripheral magnetic stimulation and the characteristics of the participants., Design: This was a basic study with noninvasive intervention. Knee extension torque induced by repetitive peripheral magnetic stimulation (repetitive peripheral magnetic stimulation-induced torque) and maximum voluntary contraction were measured. Stepwise method of multiple regression was performed to determine the factors affecting repetitive peripheral magnetic stimulation-induced torque at 100% intensity and repetitive peripheral magnetic stimulation-induced torque divided by maximum voluntary contraction (percent maximum voluntary contraction). Subcutaneous fat thickness, vastus lateralis muscle thickness measured by ultrasound, maximum voluntary contraction, and mean power frequency of electromyography during maximum voluntary contraction were selected as independent variables., Results: Repetitive peripheral magnetic stimulation was applied to the right vastus lateralis of 30 young healthy adults (average age, 21.1 ± 0.3 yrs). In the multiple regression analysis, repetitive peripheral magnetic stimulation-induced torque ( P < 0.001) was shown to be independently and significantly associated with maximum voluntary contraction (β = 0.510), subcutaneous fat thickness (β = -0.358), and vastus lateralis muscle thickness (β = 0.208), while percent maximum voluntary contraction value ( P < 0.05) was independently and significantly associated with vastus lateralis muscle thickness (β = 1.059)., Conclusions: Repetitive peripheral magnetic stimulation-induced torque decreases with thicker subcutaneous fat and increases with stronger maximum voluntary contraction or with thicker muscle., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Whole-intestine engineering can provide a therapeutic alternative to bowel transplantation. Intestinal components including the mucosa, muscular layer, enteric nervous system, and vasculature must be reestablished as a tubular organ to generate an artificial small intestine. This study proposes a novel approach to produce a transplantable, well-organized tubular small intestine using a decellularized scaffold., Methods: Male Lewis rat intestines were used to generate decellularized scaffolds. Patch or tubular grafts were prepared from the decellularized intestine and transplanted into the rat intestine orthotopically. Histological analysis of the decellularized intestine was performed up to 12 wk after transplantation., Results: Histological examination revealed abundant vascularization into the decellularized patch graft 1 wk after transplantation. Muscular and nervous components, as well as cryptogenesis, were observed in the decellularized patch graft 2 wk after transplantation. Sixteen of the 18 rats survived with normal intake of food and water after the decellularized tubular graft transplantation. Compared with silicone tube grafts, the decellularized tubular grafts significantly promoted the infiltration and growth of intestinal components including the mucosa, muscular layer, and nerve plexus from the recipients. Circular and longitudinal muscle with a well-developed myenteric plexus was regenerated, and intestinal motility was confirmed in the decellularized tubular graft 12 wk after transplantation., Conclusions: Orthotopic transplantation of decellularized intestine enhanced the reconstruction of the well-organized tubular small intestine with an enteric nervous system in vivo. Our method using a decellularized scaffold represents a promising approach toward whole-intestine engineering and provides a therapeutic alternative for the irreversible intestinal failure., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To compare the findings of magnetic resonance imaging (MRI) with advanced protocols in patients with various types of acute sensorineural hearing loss (ASNHL)., Study Design: Retrospective case review., Setting: Tertiary referral center., Patients: Two hundred eighty-seven patients with ASNHL., Interventions: All patients underwent MRI scanning, including heavily T2-weighted three-dimensional fluid-attenuated inversion recovery before and 4 hours after the intravenous administration of gadolinium contrast medium (delayed 3D-FLAIR). A hybrid of the reversed image of the positive endolymph signal and the native image of the perilymph signal image was constructed to visualize the endolymphatic space., Results: The detection rates of abnormal MRI findings vary significantly among different types of ASNHL. A hyperintense signal on delayed 3D-FLAIR was observed in all patients with intralabyrinthine schwannoma or vestibular schwannoma and 20.5% of patients with idiopathic sudden sensorineural hearing loss (ISSNHL) but was rarely observed in definite Ménière's disease (MD, 2.6%). In contrast, endolymphatic hydrops (EH) was frequently observed in patients with definite MD (79.5%) but was observed much less frequently in patients with ISSNHL (11.0%). In patients with cochlear MD and ALHL, detection rates of cochlear EH were similar to those with definite MD, whereas detection rates of vestibular EH were significantly lower than in patients with definite MD., Conclusions: The significantly different detection rates of abnormal MRI findings among various types of ASNHL shed light on the distinct pathophysiology of each disorder. A diagnosis based on MRI findings with advanced protocols may help select treatment strategies and provide prognostic information for patients., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2023, Otology & Neurotology, Inc.)

Abstract: Introduction: Acute respiratory distress syndrome (ARDS) is a severe hypoxemic respiratory failure with a high in-hospital mortality. However, the molecular mechanisms underlying ARDS remain unclear. Recent findings have indicated that the onset of severe inflammatory diseases, such as sepsis, is regulated by epigenetic changes. We investigated the role of epigenetic changes in ARDS pathogenesis using mouse models and human samples. Methods: Acute respiratory distress syndrome was induced in a mouse model (C57BL/6 mice, myeloid cell or vascular endothelial cell [VEC]-specific SET domain bifurcated 2 [Setdb2]-deficient mice [Setdb2 ff Lyz2 Cre+ or Setdb2 ff Tie2 Cre+ ], and Cre - littermates) by intratracheal administration of lipopolysaccharide (LPS). Analyses were performed at 6 and 72 h after LPS administration. Sera and lung autopsy specimens from ARDS patients were examined. Results: In the murine ARDS model, we observed high expression of the histone modification enzyme SET domain bifurcated 2 ( Setdb2 ) in the lungs. In situ hybridization examination of the lungs revealed Setdb2 expression in macrophages and VECs. The histological score and albumin level of bronchoalveolar lavage fluid were significantly increased in Setdb2 ff Tie2 Cre+ mice following LPS administration compared with Setdb2 ff Tie2 Cre- mice, whereas there was no significant difference between the control and Setdb2 ff Lyz2 Cre+ mice. Apoptosis of VECs was enhanced in Setdb2 ff Tie2 Cre+ mice. Among the 84 apoptosis-related genes, the expression of TNF receptor superfamily member 10b ( Tnfrsf10b ) was significantly higher in Setdb2 ff Tie2 Cre+ mice than in control mice. Acute respiratory distress syndrome patients' serum showed higher SETDB2 levels than those of healthy volunteers. SETDB2 levels were negatively correlated with the partial pressure of oxygen in arterial blood/fraction of inspiratory oxygen concentration ratio. Conclusion: Acute respiratory distress syndrome elevates Setdb2 , apoptosis of VECs, and vascular permeability. Elevation of histone methyltransferase Setdb2 suggests the possibility to histone change and epigenetic modification. Thus, Setdb2 may be a novel therapeutic target for controlling the pathogenesis of ARDS., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

The involvement of New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and melanoma-associated antigen A4 (MAGE-A4) in soft-tissue sarcoma pathogenesis has recently been reported; however, their involvement in desmoid tumors (DTs) remains unknown. This study aimed to determine the involvement of NY-ESO-1 and MAGE-A4 in DTs. Immunostaining for β-catenin, NY-ESO-1, and MAGE-A4 was performed on DT biopsy specimens harvested at our institution. The positivity rate for each immune component was calculated. In addition, the correlations between the positivity rates for the immune molecules were investigated. The correlation between the positivity rate and age or longest diameter of each immune molecule was also investigated. β-catenin showed staining mainly in the tumor cell nuclei of DTs. Both NY-ESO-1 and MAGE-A4 showed staining in the nucleus, cytoplasm, and infiltrating lymphocytes of DT cells. The mean positive cell rates for β-catenin, NY-ESO-1, and MAGE-A4 were 43.9 ± 21.7, 30 ± 21.6, and 68.9 ± 20.8, respectively. A strong negative correlation was observed between β-catenin and MAGE-A4 positivity rates (r = -0.64). The positivity rates for NY-ESO-1 and MAGE-A4 showed a moderate positive correlation (r = -0.42). A very strong negative correlation was observed between age and the NY-ESO-1 positivity rate (r = -0.72). A weak negative correlation was observed between age and the MAGE-A4 positivity rate (r = -0.28). A medium negative correlation was observed between the longest tumor diameter and NY-ESO-1 positivity (r = -0.37). NY-ESO-1 and MAGE-A4 may be involved in the DT microenvironment. Thus, NY-ESO-1 and MAGE-A4 may be useful in the diagnosis of DT., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

The coronavirus disease 2019 (COVID-19) pandemic has restricted many medical practices. We aimed to investigate the impact of the COVID-19 pandemic on the number of bronchoscopies, outpatients, and hospital admissions. We retrospectively analyzed the number of outpatients, admissions, and bronchoscopies performed between March 2020 and May 2022. We defined "Peak month of the pandemic," "Wave of the pandemic," "Month in the wave," and "Period of a state of emergency" for each analysis. In the first year of the COVID-19 pandemic, analysis of variance (ANOVA) in linear mixed models indicated significant effects of "month in each wave" on the number of bronchoscopies (P = .003), outpatients (P = .041), and admissions (P = .017). The number of outpatients, admissions, and bronchoscopies was significantly influenced by the first wave of the COVID-19 pandemic. In contrast, in the second year of the COVID-19 pandemic, a mixed-ANOVA indicated significant effects of "month in each wave" only on the number of outpatients (P = .020) but no significant effects on the number of bronchoscopies (P = .407) and admissions (P = .219). During the second year of the pandemic, the number of bronchoscopies and admissions was not significantly affected by the waves of the pandemic. There were no significant differences in the number of admissions and bronchoscopies between the fourth and sixth waves. Although the number of bronchoscopies was found to be significantly affected in the early stages of the COVID-19 pandemic, the impact of the pandemic was much more limited thereafter., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Although anti-tumor necrosis factor-α monoclonal antibody biological preparations (BP) agents are widely used as an established treatment tool for refractory ulcerative colitis (UC), whether leukocytapheresis/granulocytapheresis (L/G-CAP) has similar beneficial impact on the disease activity remains undetermined. Furthermore, the costs defrayed for the treatment with these 2 modalities have not been compared. We retrospectively evaluated whether L/G-CAP offered sustained beneficial effects over 2-year period. The patients who had moderately to severely active UC (Rachmilewitz clinical activity index (CAI) ≧ 5) and were treated with a series (10 sessions) of L/G-CAP (n = 19) or BP (n = 7) as an add-on therapy to conventional medications were followed. Furthermore, the cost-effectiveness pertaining to the treatment with L/G-CAP and BP was assessed over 12 months. At baseline, L/G-CAP and BP groups manifested similar disease activity (CAI, L/G-CAP; 7.0 [6.0-10.0], BP; 10.0 [6.0-10.0], P = .207). The L/G-CAP and BP treatment suppressed the activity, with CAI 1 or less attained on day 180. When the L/G-CAP group was dichotomized into L/G-CAP-high and L/G-CAP-low group based on CAI values (≥3 or < 3) on day 365, CAI was gradually elevated in L/G-CAP-high group but remained suppressed in L/G-CAP-low group without additional apheresis for 2 years. Anemia was corrected more rapidly and hemoglobin levels were higher in BP group. The cost of the treatment with L/G-CAP over 12 months was curtailed to 76% of that with BP (1.79 [1.73-1.92] vs 2.35 [2.29-3.19] million yen, P = .028). L/G-CAP is as effective as BP in a substantial number of patients over 2 years. The cost for the treatment of UC favors L/G-CAP although the correction of anemia may prefer BP. Thus, L/G-CAP can effectively manage the disease activity with no additional implementation for 2 years although further therapeutic modalities might be required in a certain population with high CAI observed on day 365., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Laparoscopic distal pancreatectomy (L-DP) is the standard procedure for treating left-sided pancreatic tumors. Stapler closure of the pancreas is the preferred method for L-DP; however, postoperative pancreatic fistula (POPF) remains a challenging problem. The present study aimed to compare the surgical outcomes of staple closure using a reinforcing stapler (RS) and transection using an ultrasonic dissector followed by hand-sewn (HS) closure in a fish-mouth manner in pure L-DP and to determine independent perioperative risk factors for clinically relevant postoperative pancreatic fistula (CR-POPF)., Patients and Methods: Among the 85 patients who underwent pure L-DP between February 2011 and August 2021, 80 of whom the pancreatic stump was closed with RS (n = 59) or HS (n = 21) were retrospectively investigated. Associations between potential risk factors and POPF were assessed using univariate analysis. The factors, of which the P value was determined to be <0.1 by univariate analysis, were entered into a multivariate regression analysis to ascertain independent predictive factors., Results: The surgery time and estimated blood loss were not significantly different between the two groups. Overall, 13 patients (16.3%) developed CR-POPF ( B = 12 and C = 1). The rate of CR-POPF was lower in RS than in HS; however, the difference was not statistically significant (RS vs HS: 11.9% vs 28.9%, P = 0.092). Consistent with the results for CR-POPF, the rate of Clavien-Dindo IIIa or more postoperative complications and the length of hospital stay were also not significantly different between the two groups (RS vs HS: 10.2, 12% vs 14.3%, 14 d). In the univariate analysis of risk factors for CR-POPF, the pancreatic thickness at the transection site, procedure for stump closure, and estimated blood loss were associated with a significantly higher rate of CR-POPF. The multivariate analysis revealed that the pancreatic thickness at the transection site (cutoff: 12 mm) was the only independent risk factor for CR-POPF (odds ratio: 6.5l, 95% CI: 1.4-30.4, P = 0.018). The rate of CR-POPF was much lower in RS than in HS for pancreatic thickness <12 mm (RS vs HS: 4.1% vs 28.6%), whereas that was rather higher in RS than in HS for pancreatic thickness ≥12 mm (RS vs HS: 50% vs 28.6%)., Conclusions: RS closure was superior to HS closure for pancreatic thickness <12 mm and for prevention of CR-POPF after pure L-DP. It is necessary to seek more reliable procedures for pancreatic stump closure in patients with a pancreatic thickness of ≥12 mm., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Rationale: Recently, the incidence of polyoncosis has been increasing due to advancements in treatment, such as antitumor therapy, which led to a prolonged survival. However, few patients with metastatic pancreatic ductal adenocarcinoma (PDAC) develop second tumors, which render a poor prognosis. We report a rare case of PDAC, which is metachronous with a fatal malignant lymphoma (ML)., Patient Concerns: A 68-year-old woman who had been monitored due to liver cirrhosis secondary to hepatitis C virus infection presented with a 10-mm pancreatic head cancer with lung metastasis and had started an anticancer therapy with gemcitabine. Approximately 18 months after diagnosis, lymphadenopathies around the pancreas were noted, which eventually spread to the entire body over time., Diagnosis: Diffuse large B-cell lymphoma was diagnosed using biopsies from cervical lymph nodes., Interventions and Outcomes: The patient started a gemcitabine + rituximab regimen; however, the patient died from cachexia-associated lymphoma progression, not PDAC., Lessons: ML should be considered when intra-abdominal lymphadenopathies are detected in patients with pancreatic cancer, and ML should be differentiated from lymph node metastasis of pancreatic cancer., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

To introduce wrapping vancomycin-containing cement around a mega-prosthesis (MP) as a novel method to prevent prosthetic joint infection after reconstruction surgery for malignant bone and soft tissue tumors. Five patients with malignant bone and soft tissue tumors treated at our hospital from April 2009 to December 2019 were included. The average age was 71.4 years. Four males and one female were included. Three patients had a bone tumor, and two had a soft tissue tumor. Three right thighs and two left femurs were affected. These tumors were identified histologically as undifferentiated pleomorphic sarcoma, spindle cell sarcoma, diffuse large cell B-cell lymphoma, metastasis of renal cancer, and metastasis of lung cancer. All patients underwent tumor resection and reconstruction with a MP. In all cases, vancomycin-containing cement (2 g/40 g) was wrapped around the implant at the extension. The average follow-up period was 30.4 months. We surveyed whether infection occurred after surgical treatment. We also investigated the Musculoskeletal Tumor Society score and clinical outcome. We observed no postoperative infection. One case of local recurrence was observed, and a hip dissection was performed. The Musculoskeletal Tumor Society score was 79.26 ± 1.26 (mean ± standard deviation) (range: 76-80.3). Three patients remained disease-free, one survived but with disease, and one died of disease. Wrapping vancomycin-containing cement around the MP may be a useful method of preventing postoperative joint infections., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Laparoscopic proximal gastrectomy (LPG) is an attractive option for the treatment of early gastric cancer in the upper third of the stomach. No optimal method of reconstruction after LPG has been established because of problems associated with postoperative reflux. Gastric tube reconstruction, a type of esophagogastrostomy, is a simple procedure, but it is associated with a high frequency of reflux esophagitis (RE). We investigated the relationship between RE and gastric emptying, along with nutritional parameters., Subjects and Methods: We compared gastric emptying in patients who had undergone curative LPG with gastric tube reconstruction for gastric cancer with that of patients after total gastrectomy (TG), distal gastrectomy (DG) and of healthy volunteers and patients after DG. The LPG group was divided into an RE LPG-RE (+) group and a non-reflux esophagitis (non-RE) an LPG-RE (-) group, and we compared gastric emptying and indices of nutrition, such as body weight and laboratory findings, between those among LPG-RE (+), LPG-RE (-), and TG groups., Results: The time lag between ingestion and peak 13 CO 2 expiration (T lag) in the healthy volunteer group was significantly shorter in the LPG group longer than those in the healthy volunteer LPG group and TG group. The T lag was significantly shorter in the RE LPG-RE (+) group than in the non-RE LPG-RE (-) group. The percentage change in body weight percentage in the non-RE LPG-RE (-) group was significantly larger than that in the RE LPG-RE (+) group at 12 months after surgery. Both the serum albumin and hemoglobin levels in the non-RE LPG-RE (-) tended to be preserved compared with those in the RE LPG-RE (+) group and TG group., Conclusions: Gastric emptying was accelerated after LPG, and was associated with RE. Our data suggest that RE could be associated with body weight loss after LPG., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Hospitalized elderly patients are often at risk of life-threatening infectious diseases such as pneumonia and urinary tract infection, thus diagnostic tools for bacterial infections are demanded. We developed a new predictive tool consolidating modified CURB-65, procalcitonin (PCT) and albumin (Alb)., Method: This is a retrospective study. Modified CURB-65 (mCURB-65) score, PCT, Alb, and various cardiovascular/respiratory/renal functions were measured. Survival analyses were conducted to assess 30-days mortality of elderly patients using mCURB-65 score, PCT and Alb. The consolidated scores were compared with the number of patients died., Results: There were 445 elderly patients included. Kaplan-Meier survival curves showed significant differences between the high and low groups of mCURB-65, PCT and Alb (log-rank test, P < .001). Cox proportional regression showed that the hazard ratios (95% confidence intervals) for high mCURB-65, high Alb, and high PCT were all significant, 1.95 (1.24-3.05), 0.50 (0.32-0.77), and 2.09 (1.32-3.31), respectively. The consolidated scores showed tendency of increase with proportion of the number of patients died., Conclusions: The consolidated score consisted of mCURB-65, PCT and Alb can be a useful tool to predict short-term mortality of the hospitalized elderly patients with infectious disease., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Bacillus Calmette-Guérin (BCG) instillation is the gold standard for the treatment of patients with pT1 bladder cancer but causes severe adverse effects. Few predictive factors have been established for intravesical recurrence and/or stage progression in bladder cancer. We analysed 138 patients who underwent transurethral resection of bladder tumour and were pathologically confirmed to have stage pT1 bladder cancer. Of these, 72 patients (52.2%) received intravesical BCG instillation, 12 patients (8.7%) demonstrated stage progression, and five patients (3.6%) died of the disease. The number of patients who received BCG instillation was more in the group with multifocal tumours than that in the group with unifocal tumours (p=0.0034). Among 53 patients (38.4%) who demonstrated cytokeratin 5/6 (CK5/6) expression, 15 patients (28.3%) showed CK5/6 expression in more than 10% of tumour cells and 38 patients (71.7%) showed CK5/6 expression in 1-10% of tumour cells. CK5/6 expression was observed in both invasive and non-invasive components in 15 patients (28.3%), only in invasive components in 30 patients (56.6%), and only in non-invasive components in eight patients (15.1%). Furthermore, CK5/6 expression was observed in tumour cells only in front of the invasive component and stroma in 24 patients. The proportion of CK5/6-expressing tumour cells in the invasive component was significantly higher than that in the non-invasive component (p<0.001). The follow-up period for patients who received BCG tended to be shorter than that in the non-BCG patients. The CK5/6-positive group displayed significantly shorter recurrence-free survival (RFS) than the CK5/6-negative group (p=0.0412). Importantly, CK5/6 expression was a significant predictive factor of inferior RFS in the BCG instillation group (p=0.0197). In contrast, CK5/6 expression was not significantly associated with RFS in the non-BCG instillation group (p=0.841). Thus, CK5/6 expression can be a predictive marker for RFS in patients with pT1 bladder cancer and can provide critical information for patient care., (Copyright © 2022 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

The prognosis for soft tissue sarcomas (STSs) is poor, especially for highly aggressive STSs, and the details of prognostic factors are unknown. This study aimed to investigate the prognostic factors for STSs in hematologic inflammatory markers. We included 22 patients with STSs treated at our institution. The STSs were histologically classified as follows: undifferentiated pleomorphic sarcoma, 7 cases; myxofibrosarcoma, 6 cases; and malignant peripheral nerve sheath tumor, 2 cases. The average patient age was 72.06 years. The numbers of patients who underwent each procedure were as follows: wide resection, 7; wide resection and flap, 2; marginal resection, 2; wide resection and radiation, 1; additional wide resection with flap, 1; wide resection and skin graft, 1; and radiotherapy only, 1. The median follow-up period was 26 months (3-92 months). The outcomes were as follows: continuous disease free, 6 cases; no evidence of disease, 6 cases; alive with disease, 1 case; and died of disease, 2 cases. Pretreatment blood examinations for C-reactive protein (CRP) and albumin levels; neutrophil, lymphocyte, and white blood cell (WBC) counts; and neutrophil/lymphocyte (N/L) ratio were investigated and correlated with tumor size, tissue grade, and maximum standardized uptake value (SUVmax). CRP level and neutrophil and WBC counts were positively correlated with tissue grade and SUVmax. N/L ratio was positively correlated with tumor size and SUVmax. CRP level, WBC and neutrophil counts, and N/L ratio may be poor prognostic factors for highly aggressive STSs., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Few large-scale investigations have been conducted on treatment of House-Brackmann grade VI (HB grade VI) Ramsay Hunt syndrome (RHS) patients. We compared recovery rates among patients receiving a normal-dose corticosteroid (prednisolone [PSL] 60 mg/d) or high-dose corticosteroid (PSL 200 mg/d), both with or without an antiviral agents. Recovery rates were also examined based on the order of presentation of herpetic vesicles versus facial palsy., Study Design: Retrospective case review., Setting: Tertiary referral center., Patients: A total of 128 patients with HB grade VI RHS were treated in our department between 1995 and 2017. These patients were divided into four treatment groups based on corticosteroid dosage and use of an antiviral agent., Methods: We assessed treatment outcomes for HB grade VI patients together with logistic regression analysis to investigate factors that can impact treatment outcomes, that is, sex, age, days to start of treatment, PSL dosage, and antiviral agent administration., Results: Recovery rates were best in the high-dose corticosteroid group with an antiviral agent (71.1%) in comparison with the normal-dose corticosteroid group with an antiviral agent (60.0%) or high-dose corticosteroid alone (57.1%). Significant factors for treatment outcomes were high-dose corticosteroid administration and early initiation of treatment. A better recovery rate was also found when the herpetic vesicles appeared before facial palsy., Conclusion: We showed that a combination of a high-dose corticosteroid and antiviral agent produced the best outcomes for patients with HB grade VI RHS. However, our results were not statistically significant because of small sample size., Competing Interests: The authors have no other funding, financial relationships, or conflicts of interest to disclose., (Copyright © 2022, Otology & Neurotology, Inc.)

Rationale: The genomic alteration of cutaneous angiosarcoma (cAS) is complex. Treatment efficacy of immunotherapy for cAS remains controversial and prognosis remains poor. Herein, we report a case of cAS with programmed cell death 1, programmed cell death ligand-1, New York esophageal squamous cell carcinoma-1, and melanoma-associated antigen 4., Patient Concerns: A 69-year-old man presented with a chief complaint of left thumb pain, with a soft tissue mass in the palmar side of the thumb. He had no past medical history. Three months prior, the man experienced the pain while scuba diving. He visited a nearby clinic, and magnetic resonance imaging revealed a soft tissue tumor on the palmar side of the thumb. He was referred to our hospital and a marginal excisional biopsy was performed., Diagnosis: Pathological findings revealed an angiosarcoma with high-flow serpentine vessels., Interventions: An excision was performed from the base of the thumb to achieve a wide margin., Outcomes: One year after the treatment, the patient has not experienced recurrence, metastasis, or complications., Lessons: Histopathology of the excised specimen was positive for programmed cell death 1, programmed cell death ligand-1, New York esophageal squamous cell carcinoma-1, and melanoma-associated antigen 4; their expression may be a therapeutic target for cAS. Combining immunotherapy with surgical treatment may be effective for cAS., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To determine the associations of pancreatobiliary maljunction (PBM) in the West., Background: PBM (anomalous union of common bile duct and pancreatic duct) is mostly regarded as an Asian-only disorder, with 200X risk of gallbladder cancer (GBc), attributed to reflux of pancreatic enzymes. Methods: Radiologic images of 840 patients in the US who underwent pancreatobiliary resections were reviewed for PBM and contrasted with 171 GBC cases from Japan., Results: Eight % of the US GBCs (24/300) had PBM (similar to Japan; 15/ 171, 8.8%), in addition to 1/42 bile duct carcinomas and 5/33 choledochal cysts. None of the 30 PBM cases from the US had been diagnosed as PBM in the original work-up. PBM was not found in other pancreatobiliary disorders. Clinicopathologic features of the 39 PBM-associated GBCs (US:24, Japan:15) were similar; however, comparison with non-PBM GBCs revealed that they occurred predominantly in females (F/M = 3); at younger (<50-year-old) age (21% vs 6.5% in non-PBM GBCs; P = 0.01); were uncommonly associated with gallstones (14% vs 58%; P < 0.001); had higher rate of tumor-infiltrating lymphocytes (69% vs 44%; P = 0.04); arose more often through adenoma-carcinoma sequence (31% vs 12%; P = 0.02); and had a higher proportion of nonconventional carcinomas (21% vs 7%; P = 0.03). Conclusions: PBM accounts for 8% of GBCs also in the West but is typically undiagnosed. PBM-GBCs tend to manifest in younger age and often through adenoma-carcinoma sequence, leading to unusual carcinoma types. If PBM is encountered, cholecystectomy and surveillance of bile ducts is warranted. PBM-associated GBCs offer an invaluable model for variant anatomy-induced chemical (reflux-related) carcinogenesis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Delta C-peptide derived by the glucagon stimulation test is a reliable value for the evaluation of the pancreatic endocrine function after pancreas transplantation. We examined the associations between delta C-peptide as pancreatic graft endocrine function and donor background factors., Methods: Sixty-five cases of pancreatic transplantation from brain-dead donors, which were performed in our facility, were enrolled in this study. Enrolled recipients underwent a glucagon stimulation test within 1 to 3 months after transplantation to evaluate the pancreatic graft endocrine function with delta C-peptide to compare donor background factors., Results: The following factors were associated with significant deterioration of the delta C-peptide: age of 50 years or greater, death from cerebrovascular accident, hemoglobin A1c level of 5.6% or greater, creatinine level of 1.0 mg/dL or greater, C-reactive protein level of 25 mg/dL or greater, and sodium level of 150 mmol/L or greater. In addition, increased numbers of these donor factors indicated significantly greater deterioration of the posttransplant pancreatic endocrine function ( P &lt; 0.001)., Conclusions: To secure insulin independence after pancreas transplantation, which means maintaining a delta C-peptide level of 1.0 ng/mL or greater on a glucagon stimulation test, the utilization of donors, who possesses more than equal to 3 of the donor factors identified in this study, should be carefully considered., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We reported on transcanal endoscopic myringoplasty in 25 cases preliminarily in 2014. Now our number of transcanal endoscopic myringoplasty reached to 209 ears and allowed us to adequately investigate the visibility, necessity of canalplasty, treatment results, and multivariate analysis., Study Design: A prospective case series., Setting: Tertiary referral center., Patients: Transcanal endoscopic myringoplasty was performed on 209 ears in 201 patients between 2011 and 2019 and followed up over 1 year., Methods: Preoperative endoscopic and microscopic views for the same patient were compared. We examined success rates at 1 year after surgery according to operation type, perforation size, operation side, gender, cause of perforation, and age, and also examined hearing results. Logistic regression analysis was performed to investigate the basic demographic and clinical characteristics of the patients associated with perforation closure., Results: The anterior edge of the preoperative perforation was not visible under microscopy in 14.4% of patients. In contrast, endoscopic views revealed the entire tympanic membrane in one field. However, canalplasty was required in 2.4% of tympanic procedures due to difficulty of manipulation. The overall closure rate for perforations was 90.4%. Logistic regression analysis revealed that age > 11 was the only significant factor associated with perforation closure. The average reduction in air-bone gap was 12.1 dB., Conclusion: The endoscopic myringoplasty produced better visualization, the same or better closure rates, and the same or lower complication rates as compared with traditional microscopic techniques., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2022, Otology & Neurotology, Inc.)

Introduction: A giant cell tumor of soft tissue (GCST) is a benign soft tissue tumor that often occurs subcutaneously in the extremities. Rare cases of malignant GCST have been reported, but its pathogenesis remains unclear., Patients Concerns: We report a case of a 68-year-old man who noticed a painless mass on his second toe one and a half years ago. He visited the Department of Dermatology at our hospital. Magnetic resonance imaging revealed a soft tissue tumor, surrounding the distal aspect of the second toe., Diagnosis: A biopsy of the tumor was performed by a dermatologist, and it revealed a malignant giant cell tumor of the toe., Interventions: He was referred to our department and underwent lay amputation for wide-margin resection., Outcomes: No recurrence or metastasis was observed 5 years after treatment., Conclusion: : Malignant GCST should be treated with wide-margin resection immediately after its diagnosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: The effect of renal dysfunction on clinical outcomes following fractional flow reserve (FFR)-guided deferral of revascularization remains unelucidated.We retrospectively analyzed 224 patients with atherosclerotic coronary lesions who underwent deferred revascularization based on an FFR of >0.80. The median follow-up interval was 28.1 months. Patients were divided into 2 groups: the hemodialysis (HD) and the non-HD group. The non-HD group was further classified into 2 subgroups according to their estimated glomerular filtration rate (eGFR) level: eGFR <45, equivalent to chronic kidney disease stage 3b-5 and eGFR ≥45. We evaluated major adverse cardiac events (MACE), defined as a composite of cardiac death, myocardial infarction, and any revascularization.MACE occurred in 36 patients (16.1%). The rate of HD was significantly higher in the MACE group (19% vs 6%, P < .01). In non-HD patients, the eGFR was significantly lower in the MACE group (51.2 vs 63.2 mL/min/1.73 m2, P < .01). Overall, univariate Cox regression analysis revealed a significant relationship between HD and MACE (HR 2.91, P = .01), as did the multivariate model (HR 2.90, P = .01). Of the MACE, more deaths occurred in HD patients (15.8% vs 2.9%, P = .03). Among non-HD patients, eGFR <45 (HR 2.70, P = .02), FFR (per 0.01, HR 0.87, P < .01), and low-density lipoprotein cholesterol (per 10 mg/dL, HR 1.17, P = .02) were independent predictors of MACE. Any revascularization was more common in patients with eGFR<45 than in those with eGFR ≥45 (21.4% vs 7.3%, P = .02). Kaplan-Meier estimates revealed that the HD group showed a significantly lower MACE-free survival rate than the nonHD group (log-rank P < .01). In non-HD patients, the eGFR<45 group showed a lower MACE-free survival rate than the eGFR ≥45 group (log-rank P = .01).HD and reduced eGFR in non-HD patients were associated with adverse cardiac events after FFR-guided deferral of revascularization., Competing Interests: The authors have no funding and conflicts of interests to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: To the best of our knowledge, the prognostic impact of distal pancreatectomy (DP) for pancreatic body and/or tail cancer involving portal vein (PV) has not been analyzed., Methods: A total of 155 patients with pancreatic body and/or tail cancer who were eligible candidates for resection between 2002 and 2017 were analyzed., Results: Twenty-seven patients had PV contact ≤180°. Fifteen patients underwent preoperative treatment; finally, 132 patients underwent DP, and 21 underwent DP with celiac axis resection. The overall survival (OS) of the PV contact group (n = 27, median survival time [MST], 25.6 months) was worse than the non-PV contact group (n = 128; MST, 58.4 months; P = 0.002); however, it was better than the unresectable group (MST, 14.2 months; P = 0.011). The OS of the PV contact with preoperative chemotherapy group (MST, not available) was comparable to the non-PV contact group and better than the PV contact without preoperative chemotherapy group (MST, 13.4 months; P = 0.017). The multivariate analysis identified PV contact ( P = 0.046) as one of the independent prognostic factors of OS., Conclusions: Pancreatic body and/or tail cancer contact with PV ≤180° should be considered borderline resectable because of poor survival., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Extraneural recurrence of a medulloblastoma is rare with dismal prognosis. A 9-year-old girl with medulloblastoma was treated with gross total resection followed by a combination of chemotherapy and radiotherapy. Fourteen months after treatment completion, she developed multifocal bone metastases. Despite chemotherapy combined with irradiation, she died 18 months after recurrence due to progressive disease. Fluorescence in situ hybridization on formalin-fixed paraffin-embedded tissue sections revealed MYCN amplification and TP53 loss, consistent with the genetic alterations of a rapidly progressive subgroup of recurrent medulloblastomas. In clinical practice, dismal biologic features can be determined using fluorescence in situ hybridization in defective materials., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

We investigated the relationship between paravertebral muscles and perimuscular connective tissues of the thoracolumbar fascia region and the four types of pain in patients suffering from chronic low back pain. A total of 17 patients with chronic low back pain participated in this study. Ultrasound imaging method was used to measure the thickness and echogenicity of the paravertebral muscles and perimuscular connective tissues. The measurement site considered in this study was located lateral to the midpoint between L2-3 and L4-5 spines. In addition, age, gender, BMI, numerical rating scale and the short-form McGill pain questionnaire 2 (includes questions with respect to continuous pain, intermittent pain, neuropathic pain and affective descriptors) were used for assessment. Statistical analysis was performed using correlation analysis and multiple regression analysis. A significant association was observed between paravertebral muscle echogenicity at L2-3 and the numerical rating scale (r = 0.499), between paravertebral muscle echogenicity at L4-5 with numerical rating scale (r = 0.538) and intermittent pain (r = 0.594), and between perimuscular connective tissue thickness at L2-3 and numerical rating scale (r = 0.762). We observed that the factor influencing perimuscular connective tissue thickness at L2-3 and L4-5 was intermittent pain (β = 0.513, β = 0.597, respectively). It was also observed that some of the imaging findings were associated with age and BMI. In conclusion, we observed that paravertebral muscle echogenicity and perimuscular connective tissue thickness in patients with chronic low back pain were associated with pain, especially intermittent pain., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Rationale: Vacuolated podocytes are the most common form of renal damage in Fabry disease, but other types of renal damage have been reported, such as membranous nephropathy (MN) or IgM nephropathy. Enzyme replacement therapy (ERT) is effective at preventing renal damage, but the nephropathies require appropriate treatment to prevent renal damage., Patient Concerns: A 22-year-old male with Fabry disease presented with proteinuria during ERT with agalsidase-β and carbamazepine. He had received the treatment for 10 years and maintained normal plasma globotryaosylceramide levels., Diagnosis: Renal biopsy revealed MN without vacuolated podocytes. Immunofluorescent staining of the IgG subclass revealed granular patterns of IgG1, G2, G4, and C3 deposition in the glomerular basement membrane., Interventions: The carbamazepine dose was reduced from 600 mg/day to 200 mg/day (serum concentration 10.0-11.0-4.0-5.0 μg/mL)., Outcomes: After reducing the carbamazepine dose, proteinuria was negative, and the patient has had a normal urinalysis for 17 months. Plasma globotryaosylceramide levels have also remained normal., Lessons: This report is a reminder of the co-existence of MN without vacuolated podocytes in Fabry disease during ERT with agalsidase-β and carbamazepine.Physicians should be aware of this form of renal damage in Fabry disease, even during treatment., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To demonstrate the clinical significance of 4-hour delayed gadolinium-enhanced three-dimensional fluid-attenuated inversion recovery (delayed 3D-FLAIR) in patients with intralabyrinthine schwannoma (ILS)., Patients: Three patients who were clinically diagnosed with ILS., Interventions: All patients underwent audiological examinations and magnetic resonance imaging (MRI) scans. The MR-protocol included axial MR cisternography, immediate gadolinium-enhanced T1-weighted sequence, and heavily T2-weighted 3D-FLAIR prior to and 4 hours after the intravenous administration of gadolinium contrast medium., Main Outcome Measures: All MR images were visually inspected., Results: In all three patients with ILS, delayed 3D-FLAIR MRI demonstrated a strong signal of cochlear fluid surrounding the tumor, which highlighted a tumor region that lacked signals., Conclusions: Delayed 3D-FLAIR MRI may serve as a novel diagnostic tool for the early detection of intralabyrinthine micro-schwannoma. The findings also shed light on the pathophysiology of ILS., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2021, Otology & Neurotology, Inc.)

Competing Interests: The authors declare no conflict of interest.

Objectives: Quantitative single-photon emission computed tomography (SPECT) with computed tomography (SPECT/CT) is known to improve diagnostic performance. Although SPECT-alone systems are used widely, accurate quantitative SPECT using these systems is challenging. This study aimed to improve the accuracy of quantitative bone SPECT of the lumbar spine with the SPECT-alone system., Methods: The cross-calibration factor (CCF) was measured using three kinds of phantoms and the optimal values were determined. The recovery coefficient with and without attenuation and scatter correction (ACSC) were compared. Bone SPECT/CT was performed on 93 consecutive patients with prostate cancer, and the standardized uptake values (SUVs) were compared using the respective CCFs. The first 60 patients were classified according to body weight, and the correlation coefficient between SUVs with and without ACSC were calculated; the slopes were defined as body weight-based coefficients (BWCs). In the remaining 33 patients, the SUV was adjusted according to BWC, and the accuracy of the adjustment was verified., Results: The quantitative SPECT values obtained from the CCF using SIM2 bone phantom showed nearly accurate radioactivity concentrations, even without ACSC. The recovery coefficients with and without ACSC were similar. Unadjusted SUVs with and without ACSC were strongly correlated; however, SUVs without ACSC were significantly higher than those with ACSC (P < 0.0001). The mean difference between the SUVs with and without ACSC disappeared when the SUVs without ACSC were adjusted by BWC (P = 0.9814)., Conclusions: Our cross-calibration method for quantitative bone SPECT enables interpretation with a harmonized SUV even in SPECT-alone systems., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The diagnosis and treatment of patients with psychogenic vertigo (PSY) is difficult because of the lack of reliable objective findings for this condition. We examined the characteristics of foam posturography in patients with peripheral vestibular disorders (PVD) and those with PSY. In particular, we focused on the objective findings of foam posturography in PSY., Methods: Between January 2010 and December 2011, 2-legged stance tasks were conducted in patients with vertigo/dizziness under 4 conditions: eyes opened with/without foam rubber and eyes closed with/without foam rubber. In terms of the velocity of movement of the center of pressure, we examined Romberg ratios, that is, the ratios of changes in visual conditions under the fixed foam rubber conditions, and foam rubber ratios, that is, the ratios of changes in foam rubber conditions under fixed visual conditions. These ratios were compared among 3 groups: healthy controls (CONT) (n=195), PVD (n=178), and PSY (n=32)., Results: Romberg ratios using foam rubber in the PVD group were significantly higher than those in the CONT group. Those in the PSY group were significantly lower. Likewise, the foam rubber ratios in the PVD group were significantly higher than those in the CONT group when the eyes were closed. Those in the PSY group were significantly lower., Conclusion: Judging from scores in Romberg ratios using foam rubber and foam rubber ratios when eyes were closed, foam posturography might have the potential to differentiate PSY from PVD., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Adrenocorticotropic hormone (ACTH) and cortisol reportedly play a role in glycemic control in patients with type 2 diabetes mellitus (T2DM); however, the underlying mechanism remains controversial. We retrospectively investigated the effect of tofogliflozin on serum ACTH and cortisol levels in elderly patients with T2DM.Patients received 20 mg tofogliflozin daily for 3 months. Serum ACTH and cortisol levels were measured at baseline, as well as after 1 month and 3 months of tofogliflozin therapy.Serum ACTH levels were significantly reduced 3 months after tofogliflozin treatment (P < .01). Additionally, serum cortisol levels were reduced 3 months after tofogliflozin treatment, demonstrating borderline significance (P = .05). The higher body mass index (BMI; ≥25 kg/m2) group showed higher ACTH and cortisol levels than the lower BMI (<25 kg/m2) group, with borderline significance (P = .05). Renin levels were significantly increased 1 month after treatment (P < .05), maintaining serum aldosterone levels in parallel with the extracellular fluid.Our findings suggested that tofogliflozin decreased both serum ACTH and cortisol levels, with higher levels observed in the high BMI group. Tofogliflozin increased serum renin levels while maintaining serum aldosterone and extracellular fluid levels. Collectively, tofogliflozin could affect the hypothalamic-pituitary-adrenal pathway in patients with T2DM, especially in the low BMI group., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: A major discrepancy between clinical and most experimental settings of liver ischemia-reperfusion injury (IRI) is the allogenicity., Methods: In the current study, we first established a murine model of allogeneic orthotopic liver transplantation with extended cold ischemia time (18 h). Roles of CD4 T cells in the pathogenesis of IRI in liver allografts were determined using a depleting anti-CD4 antibody. The clinical relevance of CD4 as a marker of liver IRI was analyzed retrospectively in 55 liver transplant patients., Results: CD4 depletion in both donors and recipients resulted in the most effective protection of liver allografts from IRI, as measured by serum transaminase levels and liver histology. CD4 depletion inhibited IR-induced intragraft neutrophil/macrophage infiltration and proinflammatory gene expressions. Quantitative reverse-transcriptase polymerase chain reaction analysis of human liver biopsies (2 h postreperfusion) revealed that posttransplant, rather than pretransplant, CD4 transcript levels correlated positively with proinflammatory gene expression profile. When we divided patients into subgroups according to intragraft CD4 levels, the high CD4 cohort developed a more severe hepatocellular damage than that with low CD4 levels., Conclusions: CD4 T cells play a key pathogenic role in IRI of allogeneic liver transplants, and intragraft CD4 levels in the early postreperfusion phase may serve as a potential biomarker and therapeutic target to ameliorate liver IRI and improve orthotopic liver transplantation outcomes., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Real-world clinical cases of molecularly targeted agent (MTA) administration to patients with advanced hepatocellular carcinoma (HCC) with ≥50% liver occupation have been reported, but treatment outcomes have rarely been described. We have encountered several cases in which albumin-bilirubin (ALBI) scores deteriorated markedly and C-reactive protein (CRP) levels elevated in the early post-dose period. The present study therefore investigated early clinical changes in ALBI score and CRP levels after initiating MTA in advanced HCC patients with ≥50% liver occupation, focusing on antitumor response at 6 weeks.This retrospective study included 46 HCC patients with liver occupation ≥50% and 191 patients with <50%, Child-Pugh score ≤7, and Eastern Cooperative Oncology Group Performance Status scores of 0 or 1, who were treated with sorafenib or lenvatinib as first-line systemic therapy at our hospital between June 2011 and January 2020. We analyzed their medical records up to March 2020 and investigated the outcomes and changes in CRP and ALBI scores classified according to antitumor response at 6 weeks.Overall survival was significantly longer in patients with partial response (PR) + stable disease (SD) (13.7 months) than in patients with progressive disease (PD) (1.7 months, P < .001) in the ≥50% group. Patients with antitumor response of PR + SD at 6 weeks in the ≥50% group showed more marked deterioration of ALBI score at 2 weeks than those in the <50% group. These significant differences between groups had again disappeared at 4 and 6 weeks. Focusing on patients with PD at 6 weeks, ALBI score deteriorated over time in both groups. Regarding CRP, on 6-week PR + SD patients, a significant increase in CRP levels at 1 and 2 weeks was evident in the >50% group compared to the <50% group. These significant differences between groups had again disappeared at 4 and 6 weeks. In PD patients, no difference between groups in CRP elevation occurred at 1 and 2 weeks.In MTA treatment for patients with ≥50% liver occupation, to obtain an antitumor response of PR + SD, adequate management might be important considering transient deteriorated ALBI scores and elevated CRP levels., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)