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Background: Characteristics, practice patterns, and clinical outcomes of secondary spontaneous pneumothorax (SSP) with heritable connective tissue disorders (Marfan, Ehlers-Danlos, and Birt-Hogg-Dubé syndromes) are unclear., Methods: A nationwide Japanese inpatient database that included data of 524 patients with SSP (884 hospitalizations) and 137,821 with primary spontaneous pneumothorax between July 2010 and March 2020 was used in this study. Hospitalization for SSP (n = 884) was categorized into surgical (n = 459) and nonsurgical (n = 425) groups, and the patient characteristics, treatment, and outcomes were compared between the groups. Multivariable analyses were performed to evaluate risk factors for pneumothorax recurrence. We also compared the characteristics of patients with different underlying heritable connective tissue disorders., Results: Compared with the nonsurgical group, the surgical group had less frequent readmission for pneumothorax (26% vs 44%; hazard ratio, 0.47; 95% CI, 0.38-0.58). Young patients (2.46; 1.83-3.32) or those with Birt-Hogg-Dubé syndrome (2.53; 1.77-3.63) had a high risk of recurrence. Pneumothorax occurred frequently in teenagers with Marfan syndrome, in those aged 20 to 39 years with Ehlers-Danlos syndrome, and in those aged ≥40 years with Birt-Hogg-Dubé syndrome., Conclusions: Detailed information on the characteristics and clinical course of SSP in heritable connective tissue disorders will aid in the clinical decision-making process., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This article has been retracted at the request of the authors due to an error in the study discovered after the paper was published. In this study, the cost-effectiveness of the recombinant zoster vaccine (RZV) (Shingrix®) for people living with HIV (PLWHIV) aged ≥50 years was analyzed, comparing a 2-dose RZV strategy to no RZV strategy. The initial model indicated that the no RZV strategy was more cost-effective than the 2-dose RZV strategy (Erratum to Table 2). However, an error occurred in the model, where the cost parameter for the 2-dose RZV strategy was mistakenly applied as if PLWHIV individuals received the 2-dose vaccine in every cycle, significantly inflating the cost of this strategy. Upon correcting the model to reflect that the 2-dose RZV is administered only at cycle 0, the revised results indicate that the 2-dose RZV strategy is dominant over the no RZV strategy (Erratum to Table 2). Given that this error leads to a completely reversed conclusion, this paper has been retracted., (Copyright © 2024 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: It is unclear whether the sequential administration of programmed death (PD)-1/programmed death-ligand 1 (PD-L1) inhibitors and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is associated with the development of severe interstitial pneumonitis (IP)., Patients and Methods: We identified 69,107 eligible patients with non-small cell lung cancer (NSCLC) from a Japanese national inpatient database, who initiated EGFR-TKI therapy. The study population was divided into the PD-1/PD-L1 inhibitor and non-prior PD-1/PD-L1 groups based on PD-1/PD-L1 administration before EGFR-TKI therapy. We conducted 1:4 matched-pair cohort analyses (n = 9,725) to compare the incidence of IP and in-hospital mortality within 90 days of administration of EGFR-TKI between the two groups after adjusting for the clinical background. Furthermore, we performed subgroup analyses categorized according to the duration of prior PD-1/PD-L1 inhibitor use., Results: IP occurred in 4.4% of patients in the matched-pair cohort. PD-1/PD-L1 inhibitor-use before EGFR-TKI therapy was significantly associated with IP (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.34-2.38) and in-hospital mortality (OR, 2.10; 95% CI, 1.72-2.55). Prior PD-1/PD-L1 inhibitor use in an interval of <6 months before EGFR-TKI administration was associated with a higher risk of IP than EGFR-TKI administration without prior PD-1/PD-L1 inhibitor. In-hospital mortality was higher in patients with prior PD-1/PD-L1 inhibitor use than that in those without prior PD-1/PD-L1 inhibitor use, irrespective of the treatment duration., Conclusion: Sequential use of PD-1/PD-L1 inhibitors and EGFR-TKIs in patients with non-small cell lung cancer was significantly associated with IP compared to EGFR-TKIs without prior PD-1/PD-L1 inhibitor administration., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The success rate of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is lower and the risk for complications higher compared with other non-CTO PCI. Although interventionalists focus on intimal plaque characteristics, the coronary media is an important (especially for techniques involving antegrade dissection and re-entry) but poorly understood structure in CTO PCI., Objectives: The aim of the present study was to investigate coronary medial wall thinning in CTO lesions and determine how this thinning might affect CTO PCI., Methods: A total of 2,586 sections were investigated, from arteries with evidence of CTO from 54 subjects (1,383 sections) and arteries without evidence of CTO from 54 subjects with non-coronary-related deaths (1,203 sections) after matching for age, gender, body weight, and body height., Results: The medial thickness in subjects with CTO was lower than that in those with non-coronary-related death (P < 0.001). In subjects with CTO, CTO lesions had thinner medial walls compared with those with lower luminal narrowing (P < 0.001). At the CTO distal segments, the 6- to 12-mm distal segment from the distal end of the CTO had significantly less luminal narrowing (P < 0.001), and similar medial thickness, compared with the distal end of the CTO. Immunohistochemical analysis revealed that short-duration CTO had more cleaved caspase-3-positive cells in media and had significantly more CD3 + , CD4 + , CD8 + , and CD4 + CD28 null T cells compared with long-duration CTO., Conclusions: CTO lesions demonstrated coronary medial thinning compared with non-CTO lesions. Further investigation of the cause-and-effect relationship among inflammation, apoptosis, and coronary medial wall thinning is warranted in future mechanistic studies., Competing Interests: Funding Support and Author Disclosures This study was supported by the CVPath Institute. Drs Virmani and Finn have received institutional research support from the National Institutes of Health (grant HL141425), a Leducq Foundation grant, 480 Biomedical, 4C Medical, 4Tech, Abbott, AccuMedical, Amgen, Biosensors, Boston Scientific, Cagent Vascular, Cardiac Implants, CeloNova BioSciences, Claret Medical, Concept Medical, Cook, Cardiovascular Systems, DuNing, Edwards Lifesciences, Emboline, Endotronix, Envision Scientific, Lutonix Bard, Gateway, LifeTech, LimFlow, MedAlliance, Medtronic, Mercator, Merill, MicroPort Medical, MicroVention, Mitralign, Mitra Assist, North American Science Associates, Nanova, Neovasc, Nipro, Novogate, Occlutech, OrbusNeich Medical, Phenox, Profusa, Protembis, Qool, Recor, Senseonics, Shockwave Medical, SINOMED, Spectranetics, Surmodics, Symic, Vesper, W.L. Gore, and Xeltis. Dr Finn has received honoraria from Abbott Vascular, Biosensors, Boston Scientific, CeloNova BioSciences, Cook Medical, Cardiovascular Systems, Lutonix Bard, Sinomed, and Terumo; and is a consultant to Amgen, Abbott Vascular, Boston Scientific, CeloNova BioSciences, Cook Medical, Lutonix Bard, and Sinomed. Dr Virmani has received honoraria from Abbott Vascular, Biosensors, Boston Scientific, CeloNova BioSciences, Cook Medical, Cordis, Cardiovascular Systems, Lutonix Bard, Medtronic, OrbusNeich Medical, SINOMED, Recor, Terumo, W.L. Gore, and Spectranetics; and is a consultant for Abbott Vascular, Boston Scientific, CeloNova BioSciences, Cook Medical, Cordis, Cardiovascular Systems, Edwards Lifesciences, Lutonix Bard, Medtronic, OrbusNeich Medical, Recor, SINOMED, Spectranetics, Surmodics, Terumo, W. L. Gore, and Xeltis. Dr Konishi has received a research grant from the Ito Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Accurate cup placement in total hip arthroplasty (THA) for patients with dysplasia is challenging due to the distinctive bone deformities. This study aimed to compare the accuracy of cup placement position and orientation across robotic arm-assisted systems (R-THA), computed tomography-based navigation (N-THA), and manual procedure (M-THA) in THA for osteoarthritis secondary to dysplasia., Methods: A total of 167 patients (197 hips), including 88 R-THAs, 45 N-THAs, and 46 M-THAs, were analyzed. Propensity score matching was performed to align the patient backgrounds. Horizontal and vertical centers of rotation were measured for cup position, whereas radiographic inclination and anteversion were measured for cup orientation. The proportion of cases with cup placement within 3 mm and 5° from the target was compared., Results: R-THA had a significantly higher percentage of cup placement within 3 mm of the target compared to N-THA (78% vs 49%; P  = .0041) and M-THA (78% vs 53%; P  = .013). Similarly, R-THA was significantly more successful in placing the cup within 5° of the target compared to N-THA (84% vs 58%; P  = .0049) and M-THA (91% vs 20%; P < .0001). Moreover, N-THA was significantly better at placing the cup within 5° of the target compared to M-THA (62% vs 14%; P < .0001), whereas there was no significant difference in the percentage of cup placement within 3 mm of the target (51% vs 51%; P  = 1.0)., Conclusions: Robotic arm-assisted system and computed tomography-based navigation improved accuracy in cup orientation compared to the manual procedure. Additionally, the robotic arm-assisted system further improved cup position accuracy., (© 2024 The Authors.)

We herein report a case of sporadic intra-abdominal desmoid-type fibromatosis in which contrast-enhanced ultrasonography (US) combined with superb microvascular imaging (SMI) was useful for preoperative diagnosis. 18-Fluorodeoxyglucose positron emission tomography performed for systematic screening for lung cancer revealed an abnormal accumulation in the abdominal cavity. Transabdominal US showed a tumor with a mixture of hypoechoic and hyperechoic areas. Contrast-enhanced US combined with SMI revealed dendritic blood flow signals and no abnormal vascular network within the tumor. Macroscopic examination of the resected specimen revealed a white tumor with relatively clear boundaries. Microscopic examination revealed spindle cells with poor atypia proliferating in bundles with collagenous stromal cells. Immunohistochemistry showed nuclear localization of beta-catenin within the tumor cells. From these findings, we finally diagnosed intra-abdominal desmoid-type fibromatosis. Contrast-enhanced US combined with SMI is useful for diagnosing intra-abdominal desmoid-type fibromatosis., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Background: Dropped head syndrome (DHS) is difficult to diagnose only by clinical examination. Although characteristic images on X-rays of DHS have been studied, changes in soft tissue of the disease have remained largely unknown. Magnetic resonance imaging (MRI) is useful for evaluating soft tissue, and we therefore performed this study with the purpose of investigating the characteristic signal changes of DHS on MRI by a comparison with those of cervical spondylosis., Methods: The study involved 35 patients diagnosed with DHS within 6 months after the onset and 32 patients with cervical spondylosis as control. The signal changes in cervical extensor muscles, interspinous tissue, anterior longitudinal ligament (ALL) and Modic change on MRI were analyzed., Results: Signal changes of cervical extensor muscles were 51.4% in DHS and 6.3% in the control group, those of interspinous tissue were 85.7% and 18.8%, and those of ALL were 80.0% and 21.9%, respectively, suggesting that the frequency of signal changes of cervical extensor muscles, interspinous tissue and ALL was significantly higher in the DHS group (p < 0.05). The presence of Modic change of acute phase (Modic type I) was also significantly higher in the DHS group than in the control group (p < 0.001)., Conclusion: MRI findings of DHS within 6 months after the onset presented the characteristic signal changes in cervical extensor muscles, interspinous tissue, ALL and Modic change. Evaluation of MRI signal changes is useful for an objective evaluation of DHS., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

We aimed to evaluate the practice and the associated outcomes of surgical treatment for young-onset colorectal cancer (YOCRC) patients presenting with synchronous liver metastases. The study cohort was divided into two groups according to surgery date: 131 patients in the early era (EE, 1998-2011) and 179 in the contemporary era (CE, 2012-2020). The CE had a higher rate of node-positive primary tumors, higher carcinoembryonic antigen level, and lower rate of RAS/BRAF mutations. The CE had higher rates of reverse or combined resection, multi-drug prehepatectomy chemotherapy, and two-stage hepatectomy. The median survival was 8.4 years in the CE and 4.3 years in the EE (p = 0.011). On multivariate analysis, hepatectomy in the CE was independently associated with improved overall survival (HR 0.48, p = 0.001). With a combination of perioperative systemic therapy, careful selection of treatment approach, and coordinated resections, durable cure can be achieved in YOCRC patients., (© 2024 Published by Elsevier Ltd.)

The importance of temporary mechanical circulatory support for treating acute heart failure with cardiogenic shock is increasingly recognized, and Impella (Abiomed, Danvers, MA, USA) has received particular attention in this regard. Impella is an axial flow left ventricular assist device (LVAD) built into the tip of a catheter. It is inserted via a peripheral artery and implanted into the left ventricle. Although the morphology of Impella is different from a typical LVAD, it has similar actions and effects as an LVAD in terms of left ventricular drainage and aortic blood delivery. Impella increases mean arterial pressure (MAP) and systemic blood flow, thereby improving peripheral organ perfusion and promoting recovery from multiple organ failure. In addition, left ventricular unloading with increased MAP increases coronary perfusion and decreases myocardial oxygen demand, thereby promoting myocardial recovery. Impella is also useful as a mechanical vent of the left ventricle in patients supported with veno-arterial extracorporeal membrane oxygenation. Indications for Impella include emergency use for cardiogenic shock and non-emergent use during high-risk percutaneous coronary intervention and ventricular tachycardia ablation. Its intended uses for cardiogenic shock include bridge to recovery, durable device, heart transplantation, and heart surgery. Prophylactic use of Impella in high-risk patients undergoing open heart surgery to prevent postcardiotomy cardiogenic shock is also gaining attention. While there have been many case reports and retrospective studies on the benefits of Impella, there is little evidence based on sufficiently large randomized controlled trials (RCTs). Currently, several RCTs are now ongoing, which are critical to determine when, for whom, and how these devices should be used. In this review, we summarize the principles, physiology, indications, and complications of the Impella support and discuss current issues and future expectations for the device., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Although neonatal disseminated intravascular coagulation (DIC) is associated with high mortality and severe complications, few studies have reported its clinical course. We aimed to describe the characteristics, treatments, and outcomes of neonatal DIC by using a national inpatient database., Methods: Using the Japanese Diagnosis Procedure Combination database, we identified 5533 patients with neonatal DIC who were admitted to neonatal intensive care units between July 2010 and March 2020. We categorized the patients into those with asphyxia (n = 2911) and those without asphyxia (n = 2622). We investigated the patient characteristics, treatments, and outcomes. We further categorized neonates with asphyxia according to its severity., Results: The gestational age of neonates with asphyxia was significantly lower than that of neonates without asphyxia (P < 0.001). Antithrombin was most commonly used for DIC (40%). Neonates with asphyxia were more likely to receive antithrombin (43% vs. 38%; P < 0.001), recombinant human soluble thrombomodulin (28% vs. 20%; P < 0.001), and fresh frozen plasma transfusion (68% vs. 51%; P < 0.001) than those without asphyxia. Neonates with asphyxia had higher in-hospital mortality (17% vs. 10%; P < 0.001), severe bleeding (11% vs. 6.8%; P < 0.001), and hospitalization costs than those without asphyxia. Additionally, neonates with severe asphyxia were more likely to receive several DIC therapies (such as recombinant human soluble thrombomodulin [30% vs. 24%]) and had higher in-hospital mortality (19% vs. 11%) and hospitalization costs than those with mild asphyxia., Conclusions: In this large retrospective study of neonatal DIC, patients with asphyxia received several treatments and demonstrated unfavorable outcomes when compared to those without asphyxia., Competing Interests: Declaration of competing interest Dr. Konishi received grants from Pfizer Co. Ltd., Kanzawa Medical Research Foundation, and Japan Kampo Medicines Manufacturers Association outside the submitted work. There are no other conflicts of interest to disclose., (Copyright © 2023 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

In a world increasingly confronted by cardiovascular diseases (CVDs) and an aging population, accurate risk assessment prior to cardiac surgery is critical. Although effective, traditional risk calculators such as the Japan SCORE, Society of Thoracic Surgeons score, and EuroSCORE II may not completely capture contemporary risks, particularly due to emerging factors such as frailty and sarcopenia. These calculators often focus on regional and ethnic specificity and rely heavily on evaluations based on age and underlying diseases. Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine that has been identified as a potential biomarker for sarcopenia and a tool for future cardiac risk assessment. Preoperative plasma GDF-15 levels have been associated with preoperative, intraoperative, and postoperative factors and short- and long-term mortality rates in patients undergoing cardiac surgery. Increased plasma GDF-15 levels have prognostic significance, having been correlated with the use of cardiopulmonary bypass during surgery, amount of bleeding, postoperative acute kidney injury, and intensive care unit stay duration. Notably, the inclusion of preoperative levels of GDF-15 in risk stratification models enhances their predictive value, especially when compared with those of the N-terminal prohormone of brain natriuretic peptide, which does not lead to reclassification. Thus, this review examines traditional risk assessments for cardiac surgery and the role of the novel biomarker GDF-15. This study acknowledges that the relationship between patient outcomes and elevated GDF-15 levels is not limited to CVDs or cardiac surgery but can be associated with variable diseases, including diabetes and cancer. Moreover, the normal range of GDF-15 is not well defined. Given its promise for improving patient care and outcomes in cardiovascular surgery, future research should explore the potential of GDF-15 as a biomarker for postoperative outcomes and target therapeutic intervention., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Immunotherapy using bispecific antibodies including bispecific T-cell engager (BiTE) has the potential to enhance the efficacy of treatment for relapsed/refractory multiple myeloma. However, myeloma may still recur after treatment because of downregulation of a target antigen and/or myeloma cell heterogeneity. To strengthen immunotherapy for myeloma while overcoming its characteristics, we have newly developed a BiTE-based modality, referred to as bridging-BiTE (B-BiTE). B-BiTE was able to bind to both a human immunoglobulin G-Fc domain and the CD3 molecule. Clinically available monoclonal antibodies (mAbs) were bound with B-BiTE before administration, and the mAb/B-BiTE complex induced antitumor T-cell responses successfully while preserving and supporting natural killer cell reactivity, resulting in enhanced antimyeloma effects via dual-lymphoid activation. In contrast, any unwanted off-target immune-cell reactivity mediated by mAb/B-BiTE complexes or B-BiTE itself appeared not to be observed in vitro and in vivo. Importantly, sequential immunotherapy using 2 different mAb/B-BiTE complexes appeared to circumvent myeloma cell antigen escape, and further augmented immune responses to myeloma relative to those induced by mAb/B-BiTE monotherapy or sequential therapy with 2 mAbs in the absence of B-BiTE. Therefore, this modality facilitates easy and prompt generation of a broad panel of bispecific antibodies that can induce deep and durable antitumor responses in the presence of clinically available mAbs, supporting further advancement of reinforced immunotherapy for multiple myeloma and other refractory hematologic malignancies., (© 2023 by The American Society of Hematology.)

Background: Although the loading dose (LD) of vancomycin (VCM) contributes to its efficacy, it may not be conducted adequately. Herein, the objective was to evaluate the effect of LD on patient prognosis using therapeutic drug monitoring by pharmacists and elucidate the impact of an antimicrobial stewardship program (ASP)-driven educational intervention on the LD implementation rate and patient prognosis., Materials and Methods: First, a retrospective cohort study was conducted involving 121 adult patients administered with VCM and compared with 28-day mortality in LD and non-LD groups. To avoid confounding, the propensity score method was employed. Second, post-training with ASP-driven lectures, a questionnaire survey was conducted for healthcare workers, including physicians, nurses, and pharmacists. The rates of VCM LD implementation and 28-day mortality were compared during a period of one year and 9 months between the pre-ASP (n = 38) and post-ASP (n = 33) groups., Results: After propensity score matching, the 28-day mortality in the LD group was significantly improved, suggesting that the early increase in blood levels of VCM due to an LD is an important factor influencing patient prognosis. After the lecture, a questionnaire survey revealed that the understanding rates of "well" and "slightly well" for educational lectures exceeded 80% of all healthcare workers. The rate of LD implementation significantly increased to 63.6% (21/33) in the post-ASP group compared with 31.6% (12/38) in the pre-ASP group (p = 0.007), and the 28-day mortality declined from 23.7% (9/38) to 6.1% (2/33) (p = 0.041)., Conclusion: This method of ASP-driven educational intervention would facilitate LD implementation, improving patient prognosis., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Although intravascular lithotripsy (IVL) has been an emerging novel option to treat vascular calcification, the specific effects on histology have not been systematically examined., Objectives: The authors examined the histologic effects of IVL on coronary calcified lesions from human autopsy hearts and evaluated the diagnostic ability of optical coherence tomography (OCT) and micro-computed tomography (CT) to detect calcium fracture as identified by the gold standard histology., Methods: Eight coronary lesions were treated with IVL, and 7 lesions were treated with 10 atm inflation using an IVL catheter balloon without lithotripsy pulses (plain old balloon angioplasty [POBA]). OCT and micro-CT imaging were performed before and after treatment, and the presence of calcium fracture was assessed. The frequency and size of fractures were measured and compared with the corresponding histology., Results: All 15 treated lesions were diagnosed as sheet calcium by histology. Histological evidence of calcium fracture was significantly greater in the IVL group compared with the POBA group (62.5% vs 0.0%; P = 0.01). Calcified lesions with fracture had a larger maximum arc degree of calcification (median 145.6 [IQR: 134.4-300.4] degrees vs 107.0 [IQR: 88.9-129.1] degrees; P = 0.01). Micro-CT and histology showed an excellent correlation for fracture depth (R 2  = 0.83; P < 0.0001), whereas OCT showed less correlation (R 2  = 0.37; P = 0.11). The depth of fractures measured by OCT were significantly shorter than with those measured by histology (0.49 [IQR: 0.29-0.77] mm vs 0.88 [IQR: 0.64-1.07] mm; P = 0.008)., Conclusions: IVL demonstrated a histologically superior fracturing effect on coronary calcified lesions compared with POBA. OCT failed to identify the presence of some calcium fractures and underestimated the depth of fracture when compared with micro-CT., Competing Interests: Funding Support and Author Disclosures This study was funded by Shockwave Medical through a grant to CVPath Institute, Inc. Drs Kawai, Sato, Kawakami, Konishi, and Ghosh are employees of CVPath Institute. Dr Hokama is an employee of Shockwave Medical. Dr Virmani is an employee of CVPath Institute; and is a consultant for Abbott Vascular, Boston Scientific, Celonova, OrbusNeich Medical, Terumo Corporation, W. C. Gore, Edwards Lifesciences, Cook Medical, CSI, Recor Medical, SinoMedical Sciences Technology, Surmodics, and Bard BD. Dr Finn is an employee of CVPath Institute; and has received consultant fees/honoraria from Abbott Vascular, Amgen, Biosensors, Boston Scientific, Celonova, Cook Medical, CSI, Lutonix Bard, Sinomed, and Terumo Corporation., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Post-myocardial infarction ventricular septal rupture (PIVSR) is becoming increasingly rare in the percutaneous coronary intervention era; however, the mortality rates remain high. Surgical repair is the gold standard treatment for PIVSR but is associated with surgical difficulty and high mortality. Therefore, the timing of surgery is controversial (i.e. either undertake emergency surgery or wait for resolution of organ failure and scarring of the infarcted area). Although long-term medical management is usually ineffective, several mechanical circulatory support (MCS) devices have been used to postpone surgery to an optimal timing. Recently, in addition to venous arterial extracorporeal membrane oxygenation (VA-ECMO), new MCS devices, such as Impella (Abiomed Inc., Boston, MA, USA), have been developed. Impella is a pump catheter that pumps blood directly from the left ventricle, in a progressive fashion, into the ascending aorta. VA-ECMO is a temporary MCS system that provides complete and rapid cardiopulmonary support, with concurrent hemodynamic support and gas exchange. When left and right heart failure and/or respiratory failure occur in cardiogenic shock or PIVSR after acute myocardial infarction, ECpella (Impella and VA-ECMO) is often introduced, as it can provide circulatory and respiratory assistance in a shorter period. This review outlines the basic concepts of MCS in PIVSR treatment strategies and its role as a bridge device, and discusses the efficacy and complications of ECpella therapy and the timing of surgery., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Brown algae contain a polysaccharide-rich cell wall, mainly composed of alginate and fucoidan which have been extensively studied for their individual structure and bioactivities. Particularly, the cell wall of Cladosiphon okamuranus is rich in fucoidan rather than alginate. However, little is known about its arrangement or interlinking with other polysaccharides such as cellulose in the cell wall. To determine its structure in detail, the cell wall was sequentially fractionated into five fractions: hot water (HW), ammonium oxalate, hemicellulose-I (HC-I), HC-II, and cellulose. Almost 80% of the total cell wall recovered from alcohol insoluble residue in C. okamuranus consisted of HW and HC-I, which mainly contained fucoidan composed of fucose, glucuronic acid, and sulfate in molar ratios of 1.0:0.3:0.9 and 1.0:0.2:0.3, respectively. Methylation analysis revealed that fucoidan in HW and HC-I structurally differed in terms of content of sulfate, and sugar residue which was 1,4-linked xylose and 1,4-linked fucose. Small angle X-ray scattering measurements also showed distinct conformational differences between HW and HC-I. These structural heterogeneities of fucoidan may be related to their localization, and fucoidan in HC-I may be involved in reinforcing cell wall structure by cross-linking to cellulose., 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 © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Half of the local regional recurrences from rectal cancer are nowadays located in the lateral compartments, most likely due to lateral lymph node (LLN) metastases. There is evidence that a lateral lymph node dissection (LLND) can lower the lateral local recurrence rate. An LLND without neoadjuvant (chemo)radiotherapy in patients with or without suspected LLN metastases has been the standard of care in the East, while Western surgeons believed LLN metastases to be cured by neoadjuvant treatment and total mesorectal excision (TME) only. An LLND in patients without enlarged LLNs might result in overtreatment with low rates of pathological LLNs, but in patients with enlarged LLNs who are treated with (C)RT and TME only, the risk of a lateral local recurrence significantly increases to 20%. Certain Eastern and Western centers are increasingly performing a selective LLND after neoadjuvant treatment in the presence of suspicious LLNs due to new scientific insights, but (inter)national consensus on the indication and surgical approach of LLND is lacking. An LLND is an anatomically challenging procedure with intraoperative risks such as bleeding and postoperative morbidity. It is therefore essential to carefully select the patients who will benefit from this procedure and where possible to perform the LLND in a minimally invasive manner to limit these risks. This review gives an overview of the current evidence of the assessment of LLNs, the indications for LLND, the surgical technique, pitfalls in performing this procedure and the future studies are discussed, aiming to contribute to more (inter)national consensus., 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 © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The frequency and oncologic outcomes of lateral lymph node (LLN) metastasis at the most distal lateral compartment (DLC) among clinical stage II-III low rectal cancer patients treated with neoadjuvant (chemo)radiotherapy (nCRT) are poorly understood. The aim was to investigate the oncologic impact of LLN metastasis in the DLC versus the proximal lateral compartment (PLC)., Materials and Methods: Consecutive patients with low rectal cancer treated with nCRT followed by total mesorectal excision and selective LLN dissection including the DLC were analyzed retrospectively. DLC was defined as the area distal to the infra-piriformis foramen on axial MRI images. Size and location of LLN metastasis on MRI, and survival were retrospectively assessed., Results: Of the 718 patients, 72 (10.0%) had pathological LLN metastasis. Thirty-two (44.4%) had metastasis in the DLC (DLC group), while 40 (55.6%) had metastasis in the PLC without metastasis in the DLC (PLC group). The proportion of ypN2 category tended to be lower in the DLC group (15.6% vs 35.0%, P = 0.105). The median number of metastatic LLN was similar (1 vs. 1, P = 0.691). The median short-axis size of metastatic LLN was smaller in the DLC group than in the PLC group on pre-treatment (P < 0.001) and re-staging (P = 0.004) MRI. By multivariable analysis, LLN metastasis in the DLC was predictive of better disease-free survival (HR, 0.412; 95% CI, 0.159-0.958, P = 0.039)., Conclusion: LLN metastasis in the DLC is frequent and has favorable oncologic outcomes after surgical dissection with nCRT., 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 © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Diagnosing heart failure with preserved ejection fraction (HFpEF) is challenging. Although the H 2 FPEF score and HFA-PEFF algorithm have been proposed for diagnosing HFpEF, previous validation studies were conducted in stable chronic heart failure (HF). Moreover, information on their applicability in the Asian population is limited. We sought to investigate these scores' diagnostic performance for HFpEF in Japanese patients recently hospitalized due to acute decompensated HF., Methods: We examined patients with HFpEF recently hospitalized with acute decompensated HF from a nationwide HFpEF-specific multicenter registry (HFpEF group) and control patients who underwent echocardiography to investigate the cause of dyspnea in our hospital (Non-HFpEF group)., Results: The studied population included 372 patients (194 HFpEF group and 178 Non-HFpEF group; HFpEF prevalence, 52%). A high H 2 FPEF score (6-9 points) could diagnose HFpEF with a high specificity of 97% and a positive predictive value (PPV) of 94%, and a low H 2 FPEF score (0-1 point) could rule out HFpEF with a high sensitivity of 97% and a negative predictive value (NPV) of 93%. HFpEF could be diagnosed with a high HFA-PEFF score (5-6 points) (specificity, 84%; PPV, 82%) or ruled out with a low HFA-PEFF score (0-1 point) (sensitivity, 99%; NPV, 89%). The H 2 FPEF score was significantly superior to the HFA-PEFF score in diagnostic accuracy (area under the curve: 0.89 vs. 0.82, respectively, p = 0.004)., Conclusions: The H 2 FPEF and the HFA-PEFF scores had acceptable diagnostic accuracy in diagnosing HFpEF in Japanese patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Some clinicians administer antibiotics in adhesive SBO treatment to prevent bacterial translocation without evidence confirming reduced sepsis and mortality. We aimed to evaluate the effectiveness of preventive antibiotic administration in nonoperative treatment of adhesive small bowel obstruction (SBO) in a retrospective study., Methods: Using a Japanese national inpatient database, we identified 114,786 eligible patients with adhesive SBO and divided patients into a group who did not receive intravenous antibiotics in the initial 2 consecutive days after admission (control group, n = 71,666) and a group who received intravenous antibiotics ≥2 days after admission (antibiotic group, n = 43,120). To compare the in-hospital mortality, occurrence of sepsis, septic shock, Clostridioides difficile colitis, length of stay, and total costs between the two groups, we performed instrumental variable analyses to adjust for measured and unmeasured confounding factors., Results: Overall, in-hospital mortality was 2.2%, and the occurrence of sepsis was 0.8%. In the instrumental variable analyses, no significant differences were found for in-hospital mortality, occurrence of sepsis, septic shock, Clostridioides difficile colitis, or total hospitalization costs. The antibiotic group showed a longer length of stay than the control group (coefficient, 1.9 days; 95% confidence interval, 0.6-3.2)., Conclusions: In this large nationwide cohort of patients with adhesive SBO, we found no benefit regarding preventive antibiotic administration in nonoperative treatment; however, antibiotic administration was associated with a longer hospital stay. These results did not support routine administration of antibiotics at admission to prevent bacterial translocation., Competing Interests: Declaration of competing interest The authors declare no conflicts of interests., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: The number of pregnant women with dilated cardiomyopathy (DCM) is relatively small, and therefore their prognosis after pregnancy is unknown. This study aims to elucidate pregnancy outcomes among women with DCM, as well as the long-term prognosis after pregnancy., Methods: Thirty-five pregnancies and deliveries in 30 women, diagnosed with DCM before pregnancy, were retrospectively analyzed., Results: All women had a left ventricular ejection fraction (LVEF) over 30% and belonged to the New York Heart Association (NYHA) class I or II before pregnancy. The mean gestational age at delivery was 36 weeks with 15 (43%) preterm deliveries. Eight pregnancies (23%) were complicated by peripartum cardiac events including 1 ventricular arrhythmia, 6 heart failures, and 1 significant deterioration in LVEF requiring termination of pregnancy. NYHA class II, pre-pregnancy use of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker/diuretics, elevated brain natriuretic peptide (BNP), and advanced diastolic dysfunction assessed by Doppler echocardiography were defined as risk factors for cardiac events. Although the more severe cases took beta-blockers during pregnancy, the rates of cardiac events and decreasing LVEF did not differ significantly between those taking beta-blockers and those who were not. Values of LVEF decreased by almost 10% after the average 4-year post-delivery follow-up period. The long-term event-free survival was considerably worse among women with peripartum cardiac events than in those without (p<0.0001)., Conclusions: DCM women with pre-pregnancy LVEF over 30% tolerated pregnancy, but the rate of preterm delivery was high. Peripartum cardiovascular events occurred more often in women with NYHA class II, as well as those who received medications before and during pregnancy and showed more elevated BNP and advanced diastolic dysfunction before pregnancy. Beta-blockers likely allowed similar outcomes for DCM patients with lower initial LVEFs. Close monitoring later in life is required, particularly among the women with peripartum cardiac events., (Copyright © 2020. Published by Elsevier Ltd.)

Objective: To determine whether preoperative presence of degenerative lumbar spondylolisthesis (DS) worsens the minimum 10-year outcome of patients undergoing microendoscopic decompression (MED) for lumbar spinal stenosis (SS)., Methods: Eighty patients undergoing MED were classified into 2 groups: DS group (34 SS with DS patients) and SS group (46 SS without DS patients). The degrees of improvement (DOIs) by the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) and intensities of improvement (IOIs) by Visual Analog Scale (VAS) at 120-159 (mean, 138.4) months after MED of the DS and SS groups were statistically compared. Patients with DS were classified into 2 groups based on the effectiveness by VAS or JOABPEQ: effective group (E group: IOI or DOI ≥20) and ineffective group (I group). All preoperative radiologic measurements were statistically compared between the E and I groups., Results: Significant decreases in low back pain, leg pain, and numbness, as measured by VAS, were noted at follow-up in the DS and SS groups. The effectiveness rates of pain-related disorders, lumbar spine dysfunction, and gait disturbance by JOABPEQ were almost equally high in the DS and SS groups. Statistical comparisons of the DOIs in all 5 functional scores and IOIs in low back pain, leg pain, and numbness showed no significant differences between the DS and SS groups. No significant differences were confirmed between the E and I groups concerning preoperative spondylolisthesis and instability., Conclusions: Our study indicated that preoperative DS did not worsen the outcome of patients with SS undergoing MED., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Cholinergic neural activation from the medial septal nucleus to hippocampus plays a crucial role in episodic memory as a regulating system for glutamatergic neural activation in the hippocampus. As a candidate regulating factor for acetylcholine synthesis in the medial septal nucleus, hippocampal cholinergic neurostimulating peptide (HCNP) was purified from the soluble fraction of young adult rat hippocampus. HCNP is released from its precursor protein (HCNP-pp), also referred to as phosphatidylethanolamine-binding protein 1. We recently reported that HCNP-pp conditional knockout (KO) mice, in which the HCNP-pp gene was knocked out at 3 months of age by tamoxifen injection, display no significant behavioral abnormalities, whereas HCNP-pp KO mice have a diminished cholinergic projection to CA1 and a decreased of theta activity in CA1. In this study, to address whether HCNP-pp reduction in early life is associated with behavioral changes, we evaluated the behavior of HCNP-pp KO mice in which HCNP-pp was downregulated from an early phase (postnatal days 14-28). As unexpected, HCNP-pp KO mice had no behavioral deficits. However, a significant positive correlation between HCNP-pp and gamma-aminobutyric acid A (GABA A ) receptor α3 subunit mRNA expression was found in individuals. This finding suggests involvement of HCNP-pp in regulating GABA A receptor α3 gene expression., Competing Interests: Declaration of competing interest We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the submitted work., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The histopathological diagnosis of cardiac sarcoidosis (CS) is challenging because of sampling error in endomyocardial biopsy (EMB) and the determinants of positive EMB are unclear. Reduced left ventricular ejection fraction (LVEF) is a simple parameter of the extent of myocardial damage, and higher serum angiotensin-converting enzyme (ACE) activity would indicate the spread of disease activity in CS patients. Thus, we sought to examine whether these parameters are related to the histopathological diagnosis of CS by EMB., Methods: A total of 94 consecutive clinically diagnosed CS patients between August 1986 and March 2019 who were admitted to two academic hospitals were examined. We determined EMB as positive if non-caseating epithelioid granulomas were confirmed in the myocardial tissue. Patients were divided into two groups according to positive (n = 37) and negative (n = 57) EMB. We assessed the relationship between LVEF, serum ACE activity and positive EMB., Results: Multivariable analysis revealed that both LVEF and serum ACE were independently associated with positive EMB (OR 0.83, 95% CI 0.70-0.99; OR 1.39, 95% CI 1.02-1.90, respectively). Moreover, patients with both lower LVEF (<37%, median) and higher ACE activity (≥13.5 IU/L, median) had the highest frequency of positive EMB (p = .003). The combination of lower LVEF and higher serum ACE showed better specificity (91.2%) and positive predictive value (73.7%) than either LVEF or serum ACE alone for positive EMB., Conclusions: Lower LVEF and higher serum ACE activity were associated with positive EMB, suggesting that these parameters might be useful for predicting positive EMB in CS patients., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Recent studies have shown better postoperative outcomes in mildly obese patients, a phenomenon called the obesity paradox. In the field of breast cancer surgery, however, previous studies have only shown an association between obesity and worse postoperative outcomes using multivariable analysis; the obesity paradox has not been investigated in patients undergoing breast cancer surgery., Patients and Methods: We identified patients who underwent mastectomy for stage 0 to III breast cancer from July 2010 to March 2017 using a Japanese nationwide inpatient database. We used restricted cubic spline analyses to investigate potential nonlinear associations between body mass index (BMI) and outcomes (postoperative complications, 30-day readmission, duration of anesthesia, length of hospital stay, and hospitalization costs). We also performed multivariable regression analyses for the outcomes., Results: Among 239,108 eligible patients, 25.6% had a BMI of > 25.0 kg/m 2 . BMI showed U-shaped associations with postoperative complications, length of stay, and hospitalization costs, and a linear association with duration of anesthesia. The proportion of postoperative complications was lowest at a BMI of around 22.0 kg/m 2 , while the length of stay was shortest and total costs were lowest at a BMI of around 20.0 kg/m 2 . Compared to a BMI of 22.0 kg/m 2 , a BMI of > 30.0 kg/m 2 was significantly associated with greater postoperative complications, 30-day readmission, duration of anesthesia, length of stay, and hospitalization costs., Conclusion: Restricted cubic spline analyses displayed U-shaped associations between BMI and in-hospital complications, length of stay, and hospitalization costs, but none of the associations showed the obesity paradox., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to describe the clinical features of nocardiosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT), focusing on new Nocardia species., Methods: We retrospectively reviewed data from patients with nocardiosis after allo-HSCT treated at our hospital and documented cases in the medical literature., Results: Fifty-seven cases were identified from our institution and the literature review. Although 51 patients (89.5%) responded to initial treatment, 28 (49.1%) patients were switched over to other treatment regimens due to the recurrence of nocardiosis or adverse events of antimicrobials. Nocardiosis-attributed mortality occurred in ten patients (17.5%). Antimicrobial susceptibilities varied among intra- and inter-species except linezolid (LZD). In the present study, five species were newly discovered after 2000, including N. cyriacigeorgica, N. veterana, N. abscessus, N. aobensis, and N. mexicana. All isolates of N. cyriacigeorgica, N. veterana, N. abscessus, and N. aobensis were sensitive to trimethoprim/sulfamethoxazole, amikacin (AMK), imipenem (IPM), and LZD; however, N. mexicana was resistant to AMK and IPM., Conclusion: Newly identified Nocardia species have various antimicrobial susceptibility patterns. Long-term maintenance therapy could be challenging due to the adverse events of antimicrobials, especially in the allo-HSCT setting. Prudent evaluation is crucial for selecting a second-line or further treatment options., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Sagittal spinal alignment has mainly analyzed in the standing position. According to previous studies, there are significant differences in lumbopelvic alignment between the standing and sitting positions and cervical alignment is affected by lumbopelvic alignment. In this study, therefore, we hypothesized that cervical sagittal alignments are different between the standing and sitting positions., Methods: A total of 108 patients with spinal degenerative diseases underwent whole spine radiography. Cervical lordosis (CL), C2-7 SVA, T1S, C7-S1 SVA, TK, LL, SS, PT, and PI were measured in the standing and sitting positions. Patients were classified into 3 groups according to the changes in CL (ΔCL, CL in the sitting position - CL in the standing position); ΔCL < -3° (Decreased group: DG; 28.7%), -3° ≤ ΔCL ≤ 3° (Unchanged group: UG; 41.7%), and ΔCL > 3° (Increased group: IG; 29.6%)., Results: The parameters of the UG in the standing position were closer to the ideal alignment (SRS-Schwab classification). In the DG, CL, T1S, and C7-S1 SVA in the standing position were significantly higher than in the UG. In the IG, PI-LL in the standing position was significantly higher than in the UG. In the sitting position, pelvis was rotated posteriorly (decrease in SS and increase in PT) and lumbar lordosis was flattened (decrease in LL) in all groups, and C2-7 SVA was significantly higher in the DG than in the UG., Conclusions: CL was different between the standing and sitting positions in 58.3% of individuals. However, patients with good spinal sagittal alignment appeared to not undergo any changes in cervical alignment. Our results suggest the possibility that patients who had a positive imbalance and large PI-LL mismatch in the standing position had decreased CL and increased CL, respectively, when in the sitting position., (Copyright © 2019 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

The volume-regulated anion channel is composed of leucine-rich repeat-containing protein A (LRRC8A) and is activated by hypotonic conditions to implement the process of regulatory volume decrease. The role of LRRC8A in regulating genes related to progression of esophageal squamous cell carcinoma (ESCC) was investigated, as well as the prognostic significance of LRRC8A expression in this tumor. Knockdown experiments were conducted using ESCC cell lines and LRRC8A siRNA to assess the influence of this protein on tumor function. In addition, the gene expression profile of ESCC was determined by microarray analysis. Immunohistochemistry was performed on 64 primary tumor samples from ESCC patients receiving radical esophagectomy. It was found that depletion of LRRC8A decreased cell proliferation and migration and also promoted apoptosis. Microarray data demonstrated G 1 /S checkpoint regulation and up-regulation or down-regulation of phosphatidylinositol 3-kinase/AKT signaling, matrix metalloproteinase, and integrin signaling-related genes (including p21, p27, MMP1, and ITGAV) in LRRC8A-depleted cells. Immunohistochemistry showed that LRRC8A expression was related to the pathologic N and T stage categories, and strong LRRC8A expression was correlated with a worse prognosis of ESCC. These findings indicate that LRRC8A modulates tumor progression by influencing cell cycle, apoptosis, and migration, providing new insights into its function as an effector or biomarker of ESCC., (Copyright © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Substitution of inorganic ions into β-tricalcium phosphate (β-TCP) is a well-known approach for facilitating biological functions of bioceramics. However, the dissolution mechanism of those β-TCPs is still under intensive debates. In the present study, the effect of copper substitution into β-TCP crystal structure on the local chemical structure and dissolution property of the copper-doped β-TCP (CuTCP) was investigated to clarify the dissolution mechanism of β-TCP. A copper-dependent decrease in the dissolution rate of CuTCP with time was observed. The 1 H →  31 P nuclear magnetic resonance (NMR) spectra of 10 mol% copper-doped β-TCP after the dissolution test demonstrated an amorphous hydrated layer on the surface of β-TCP core particles, which contained hydroxyapatite and dicalcium phosphate dihydrate and anhydrate. As such, all the dissolution curves could be curve-fitted by a heterogeneous dissolution model composing of fast and slow dissolution components. Overall, dissolution mechanism could be proposed as follows: the CuTCP particles initially dissolved by hydrolysis based on the fast dissolution component. Subsequently, the amorphous hydrated layers were formed on their surface, and caused the diffusion-controlled dissolution. As the result, the slow dissolution component would be dominant, and led to the decreased dissolution rate. STATEMENT OF SIGNIFICANCE: Understanding the dissolution mechanism of copper doped β-tricalcium phosphate (CuTCP) is crucial for designing an angiogenetic controlled copper release CuTCP for therapeutic biomaterials. However, dissolution mechanism of β-TCP or CuTCP is still under intensive debates. This study demonstrated for the first time, that amorphous hydrated layers were formed on the CuTCP particle surface during its dissolution process, which caused a diffusion-controlled dissolution, and decreased the dissolution rate of CuTCP. This work not only provided a novel dissolution mechanism of β-TCP or CuTCP, but also a new finding for designing an angiogenetic controlled copper release CuTCP for therapeutic biomaterials., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Disseminated adenovirus (ADV) infection is a fatal complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), however, it is rare following autologous peripheral blood stem cell transplantation (auto-PBSCT) or chemotherapy alone., Case: A 66-year-old Japanese female with relapsed and refractory multiple myeloma (RRMM) received auto-PBSCT, achieving partial response. To obtain a greater response, pomalidomide/dexamethasone was started on day 28 after auto-PBSCT, but was stopped on day 41 due to thrombocytopenia, fever, and gross hematuria. Additionally, she complained of abdominal pain on day 46. Blood tests revealed elevation of transaminases and alkaline phosphatase. There was no evidence of bacterial or fungal infections or progression of MM. ADV titer in urine and serum were 3.41 × 10 5 copies/mL and 6.76 × 10 3 copies/mL, respectively. CT scans revealed cystitis, urethritis, and peritonitis. Since more than two organs were infected with ADV, she was diagnosed with disseminated ADV disease. After 5 weeks of supportive care, all symptoms resolved. ADV titer decreased to 5.90 × 10 2 copies/mL in urine and became negative in serum on day 80. However, she succumbed to the MM a little more than a month later., Conclusion: Disseminated ADV infection can occur even in non-allogeneic transplant settings, such as in severely immunocompromised patients with MM who receive auto-PBSCT and repeated salvage therapies. Although it is a rare event, the mortality rate of this disease is very high, and hence, early diagnosis and interventions are needed in suspected cases., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Aims: In comparison with a low linear energy transfer (LET) radiation, a high-LET radiation induces more complex DNA damage. This study wonders whether radiation-induced bystander effect (RIBE) is dependent of LET., Materials and Methods: Chinese hamster ovary CHO-9 cells and its subline EM-C11 cells (SSB repair deficient) and XR-C1 cells (DSB repair deficient) were irradiated by γ-rays, α-particles, or carbon ions with different LETs of 13, 30 and 70 keV/μm. Cell proliferation, cell death, DNA damage, cell cycle distribution and some protein expressions were measured with the cell counting kit-8 (CCK-8), colony formation, micronuclei (MN), flow cytometry and western blot, respectively., Key Findings: A series of cell responses were induced by these radiations in a LET-dependent manner, including proliferation inhibition, cell death, MN induction, G 2 /M phase arrest and the expression of γH2AX protein. These cell injuries were also depended on DNA repair capacity, and XR-C1 cells were the most sensitive to each radiation. Furthermore, when the cells were treated with the conditioned medium (CM) collected from irradiated CHO-9 cells, the MN induction and cell death response in the bystander cells of EM-C11 or XR-C1 increased along with LET of irradiation, and the bystander damage was easier to be induced in EM-C11 and XR-C1 cells than that in CHO-9 cells., Significance: Both cellular DNA repair capacity and the LET value of radiation could deeply influence damage extents of not only the irradiated cells but also the bystander cells., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Aims: Precise endoscopic assessment of complete response to neoadjuvant chemoradiotherapy before surgery is important for optimizing surgical and non-surgical treatment. We prospectively evaluated the accuracy of the newly proposed endoscopic criteria to identify complete response, using magnifying chromoendoscopy., Methods: New endoscopic criteria were created to define endoscopic complete response, near complete response and incomplete response, using magnifying chromoendoscopy. The criteria contained notable endoscopic findings, including shape of the scar, state of the ulcer, finding of white moss, presence of residual protruded nodules, regenerated pits of the scar, presence of neoplastic pit patterns, and extension of rectal wall. Seventy-nine patients with rectal cancer who received neoadjuvant chemoradiotherapy were prospectively evaluated 1-3 days before resection. Diagnostic accuracy to identify pathological complete response and interobserver agreement among a supervising colonoscopist and two trainees were investigated., Results: Pathological complete response was obtained in 17 patients (21.5%). The diagnostic accuracy of endoscopic complete response was 85%, with a sensitivity of 47%, specificity of 97%, positive predictive value of 80% and negative predictive value of 77%. The kappa-value for interobserver agreement across 3 doctors was 0.57 (standard error, 0.74; 95% confidence interval, 0.39-0.76)., Conclusion: The newly proposed endoscopic criteria using magnifying chromoendoscopy achieved excellent diagnostic accuracy to determine good responders to neoadjuvant chemoradiotherapy in rectal cancer, with fair interobserver agreement. The criteria could be clinically useful to select patients for non-surgical management., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Understanding the mechanisms underlying the radiation-induced bystander effect (RIBE) and bi-directional signaling between irradiated carcinoma cells and their surrounding non-irradiated normal cells is relevant to cancer radiotherapy. The present study investigated propagation of RIBE signals between human lung carcinoma A549 cells and normal lung fibroblast WI38 cells in bystander cells, either directly or indirectly contacting irradiated A549 cells. We prepared A549-GFP/WI38 co-cultures and A549-GFP/A549 co-cultures, in which A549-GFP cells stably expressing H2BGFP were co-cultured with either A549 cells or WI38 cells, respectively. Using the SPICE-NIRS microbeam, only the A549-GFP cells were irradiated with 500 protons per cell. The level of γ-H2AX, a marker for DNA double-strand breaks (DSB), was subsequently measured for up to 24h post-irradiation in three categories of cells: (1) "targeted"/irradiated A549-GFP cells; (2) "neighboring"/non-irradiated cells directly contacting the "targeted" cells; and (3) "distant"/non-irradiated cells, which were not in direct contact with the "targeted" cells. We found that DSB repair in targeted A549-GFP cells was enhanced by co-cultured WI38 cells. The bystander response in A549-GFP/A549 cell co-cultures, as marked by γ-H2AX levels at 8h post-irradiation, showed a decrease to non-irradiated control level when approaching 24h, while the neighboring/distant bystander WI38 cells in A549-GFP/WI38 co-cultures was maintained at a similar level until 24h post-irradiation. Surprisingly, distant A549-GFP cells in A549-GFP/WI38 co-cultures showed time dependency similar to bystander WI38 cells, but not to distant cells in A549-GFP/A549 co-cultures. These observations indicate that γ-H2AX was induced in WI38 cells as a result of RIBE. WI38 cells were not only involved in rescue of targeted A549, but also in the modification of RIBE against distant A549-GFP cells. The present results demonstrate that radiation-induced bi-directional signaling had extended a profound influence on cellular sensitivity to radiation as well as the sensitivity to RIBE., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background/objective: The significance of extended lymphadenectomy for colorectal cancer with extraregional lymph node metastasis, such as para-aortic lymph node metastasis, has not been established. The purpose of this study was to evaluate the significance of extended lymphadenectomy for colorectal cancer with synchronous isolated extraregional lymph node metastasis., Methods: Between July 2004 and December 2013, 16 patients with synchronous extraregional lymph node metastasis without other organ metastases underwent curative resection and extended lymphadenectomy (R0 group). The clinical characteristics and survival outcomes of the R0 group were compared with those of 12 patients with extraregional lymph node metastasis who underwent palliative surgery (control group)., Results: In the R0 group, the 5-year cancer-specific survival (CSS) rate was 70.3% and the 5-year relapse-free survival (RFS) rate was 60.5%. The 5-year CSS differed significantly between the R0 and control groups (70.3% vs. 12.5%; p = 0.0003). Univariate analyses revealed that the total numbers of metastatic lymph nodes and metastatic regional lymph nodes present were significantly associated with RFS (p = 0.019 for both)., Conclusion: Findings from our study suggest that extended lymphadenectomy for colorectal cancer with synchronous isolated extraregional lymph node metastasis might be effective in carefully selected patients., (Copyright © 2015. Published by Elsevier Taiwan.)

A 76-year-old man who had undergone tricuspid annuloplasty 13 years earlier was admitted to our hospital because of a high fever. Although he was treated with antibiotics for pneumonia, a mild fever persisted. Computed tomography and gallium scintigraphy revealed a mediastinal abscess with an expanded polytetrafluoroethylene (ePTFE) membrane. There were no positive cultures or sternal changes indicating poststernotomy mediastinitis. The membrane was removed by a left parasternal approach without resternotomy, and its total removal was essential for the patient's recovery. This is the first reported case of sterile mediastinal abscess caused by an ePTFE membrane after a cardiac operation., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The antioxidative response mediated by transcription factor NRF2 is thought to be a pivotal cellular defense system against various extrinsic stresses. It has been reported that activation of the NRF2 pathway confers cells with resistance to ionizing radiation-induced damage. However, the underlying mechanism remains largely unknown. In the current research, it was found that α-particle radiation has the ability to stimulate NRF2 expression in human osteosarcoma U-2 OS cells. Knockdown of cellular NRF2 level by shRNA-mediated gene silencing decreased the survival rate, increased the micronucleus formation rate and apoptosis rate in irradiated cells. Consistently, knockdown of NRF2 resulted in decreased expression of p65 and Bcl-2, and increased expression of p53 and Bax. Besides, it was observed that increased expression of NRF2 was partially dependent on radiation induced phosphorylation of ERK 1/2. Further results showed that radiation promoted autophagy flux which leads to the enhanced phosphorylation of ERK 1/2, as evidenced by the resultls that knockdown of ATG5 (Autophagy protein 5) gene by shRNA suppressed both radiation induced ERK 1/2 phosphorylation and NRF2 upregulation. Based on these results, it is proposed that attenuation of NRF2 antioxidative pathway can sensitize U-2 OS cells to radiation, where NRF2 antioxidative response is regulated by autophagy mediated activation of ERK 1/2 kinases., (Copyright © 2016 Elsevier B.V. All rights reserved.)