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We describe the case of a 70-year-old Japanese man with familial amyotrophic lateral sclerosis (fALS) associated with a p.Gly93Ser mutation in the copper/zinc superoxide dismutase (SOD1) gene. This mutation is one of the relatively rare SOD1 mutations, with only one previous autopsy report, and is known for its longer disease duration. As previously reported, the patient had weakness in the lower limbs at age 33, followed by dysphagia, dysesthesia in the lower limbs, and autonomic dysfunction. He required mechanical ventilation at age 44 and died of acute pancreatitis at age 70. Neuropathologically, multisystem degeneration was observed beyond lesions typical of familial ALS with posterior column involvement. In addition, there was no SOD1-positive inclusion in the remaining motor neurons. The absence of SOD1-positive inclusion is a rare feature observed predominantly in long survival cases with SOD1 gene mutations. We hypothesize that the considerably lower amount of abnormal SOD1 protein in the motor neuron cells might explain our patient's extraordinarily long clinical course., (© 2024 Japanese Society of Neuropathology.)

Objective: To investigate the impact of different ventilatory support options on opioid use among patients with amyotrophic lateral sclerosis (ALS)., Methods: We retrospectively reviewed 889 consecutive patients with ALS and enrolled 399 eligible patients. All patients were followed until death or tracheostomy. Clinical characteristics of patients and the timing of initial opioid administration were evaluated. Patients were categorized into four subgroups: (1) 160 patients who never used a ventilator, (2) 120 patients who used only noninvasive ventilation (NIV), (3) 61 patients who transitioned from NIV to tracheostomy and invasive ventilation (TIV), and (4) 58 patients who underwent TIV without prior NIV. We compared the prevalence of opioid use across these groups and assessed its relationship with ventilatory support options using multivariate logistic analysis., Results: A total of 130 patients (32.6%) used opioids. The number of patients who used opioids in each group was as follows: 55 (34.4%) in Group 1, 69 (57.5%) in Group 2, 5 (8.2%) in Group 3, and 1 (1.7%) in Group 4 ( p  < 0.0001). Multivariate logistic analysis revealed that, compared to Group 1, the use of NIV only was positively associated with opioid use ( p  = 0.002). In contrast, transitioning from NIV to TIV (Group 3) and using TIV only (Group 4) were negatively associated with opioid use ( p  = 0.0001 and 0.001, respectively)., Conclusions: The choice of ventilatory support significantly influences opioid use in patients with ALS. Patients who opted against TIV required opioids to relieve distress more commonly than those who chose TIV.

Treatment with an inhibitor of glucose use via glucose transporters (GLUT) has been shown to attenuate experimental abdominal aortic aneurysm (AAA) development in mice. Vascular smooth muscle cell (VSMC) signaling seems to be essential for angiotensin II (Ang II)-induced AAA in mice. Accordingly, we have tested a hypothesis that VSMC silencing of the major GLUT, GLUT1, prevents AAA development and rupture in mice treated with Ang II plus β-aminopropionitrile. A mouse model of inducible VSMC GLUT1 deletion was created and aortic GLUT1 silencing was confirmed. Without Ang II plus β-aminopropionitrile treatment, no difference was observed regarding the external aortic diameter (control 1.06 ± 0.18 mm vs deletion 0.97 ± 0.26 mm) or systolic blood pressure (control 102 ± 9 mm Hg vs deletion 107 ± 11 mm Hg) between control or GLUT1-silenced mice. With treatment, control mice as well as VSMC GLUT1-silenced mice equally developed AAA (control 2.37 ± 0.75 mm vs deletion 2.41 ± 0.93 mm), whereas a tendency toward lower blood pressure was observed in GLUT1 silenced mice (control 150 ± 9 mm Hg vs deletion 135 ± 22 mm Hg). No significant difference was observed regarding the rate of rupture-dependent mortality. We concluded that VSMC GLUT1 is dispensable for AAA development induced by Ang II in mice., Competing Interests: None., (© 2024 The Author(s).)

The KEAP1-NRF2 system induces the expression of antioxidant genes in response to various types of oxidative stress. Some cancer cells activate this system, which increases their malignancy through genetic mutations. We performed a retrospective cohort study using the C-CAT database, which contains the gene-panel sequence data from 60,056 cases of diagnosed solid tumors. We analyzed somatic mutations in NRF2 and KEAP1 genes and their associations with clinical outcomes. Variants in the NRF2 gene were clustered in exon 2, which encodes the DLG and ETGE motifs essential for KEAP1 interaction. The NRF2 variants were frequently observed in esophageal and lung squamous cell carcinoma with frequencies of 35.9% and 19.6%, respectively. Among these mutations, the NRF2 variants in the ETGE motif were indicators of a worse prognosis. KEAP1 variants were found in 2.5% of all cases. The variants were frequent in lung cancer and showed a worse prognosis in lung and other types of adenocarcinomas. We then conducted gene expression analysis using TCGA data. While cancers with DLG and ETGE variants were similar in terms of gene expression profiles, there were significant differences between cancers with KEAP1 and NRF2 variants. Our results indicate that genetic alteration of the KEAP1-NRF2 pathway is a major factor in patient prognosis for each cancer type and its genetic variant. Variants in NRF2 and KEAP1 genes can characterize the biological basis of each cancer type and are involved in carcinogenesis, resistance to therapy, and other biological differences., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

One of the dense granule proteins named GRA15 in Toxoplasma gondii (T. gondii), is known to support an innate immune response in host through activation of NF-κB. However, little is known about advantages of GRA15 for parasites. By examining the role of GRA15 in the host-parasite interactions, it was clarified that GRA15 in T. gondii suppressed acquired immune responses in host. Wild-type parasite infection to C57BL/6 mice resulted in lower titers of T. gondii antibody and lower plasma cell counts compared to Δgra15 T. gondii. To identify host cells in which GRA15 acts to suppress antibody production, we generated conditional knock-in mice that express GRA15 in specific cell lineages. Anti-T. gondii antibodies were not reduced in macrophages of conditional knock-in mice after infection with Δgra15 T. gondii, while the production of T. gondii antibody was suppressed in dendritic cells of the conditional knock-in mice (CD11c-Cre/GRA15cKI). In the CD11c-Cre/GRA15cKI immunized with ovalbumin (OVA), the titers of anti-OVA antibody were reduced compared to control mice. Furthermore, the number of OVA antigen-specific T cells was also decreased in CD11c-Cre/GRA15cKI. These data showed that GRA15 in dendritic cells suppressed T cell-mediated humoral immunity. These findings might implicate the pathological significance of GRA15 and facilitate Toxoplasma vaccines production., Competing Interests: Declaration of competing interest The authors have no conflicting financial interests to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Two-dimensional organic-inorganic perovskites have been attracted as candidates for multiferroic materials that exhibit two or more ferroic orders such as ferromagnetism, ferroelectricity, ferroelasticity, and ferrotoroidicity. Here, we introduce the structure, ferroelastic domains and magnetic properties of the two-dimensional organic-inorganic perovskite [C 6 H 9 (CH 2 ) 2 NH 3 ] 2 FeCl 4 (CHEA-Fe) composed of 2-(1-cyclohexenyl)ethylammonium and FeCl 4 2- . CHEA-Fe underwent two ferroelastic phase transitions from tetragonal to orthorhombic at 332 K and to monoclinic at 232 K with decreasing temperature and exhibited ferroelastic domains under polarized light as a consequence of these ferroelastic phase transitions. Magnetization measurements exhibited two magnetization jumps at the transition temperature, which agrees with ferroelastic phase transitions. Furthermore, CHEA-Fe acted as canted antiferromagnetism below T N = 85.7 K. The isothermal magnetization revealed a magnetic hysteresis when the magnetic field was applied along the stacking axis of the layers., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Aim: Reactivation of hepatitis B virus (HBV) after liver transplantation (LT) remains a problem; thus, development of more effective HBV reactivation prophylaxis is desirable. We evaluated the efficacy of a combination of a long-term nucleotide analog (NA), such as entecavir (ETV) or tenofovir alafenamide (TAF), and short-term hepatitis B immunoglobulin (HBIG) in preventing HBV reactivation and compared it with conventional HBV prophylaxis., Methods: Between February 1999 and August 2023, 135 patients underwent living-donor liver transplantation for liver cirrhosis or acute liver failure caused by HBV infection or received an LT from a hepatitis B core antibody-positive donor. Recipients who had undergone LT were classified as being in the first or second era (namely until September 2017 and from October 2017), respectively, and outcomes of prophylaxis against HBV reactivation were compared between the two eras., Results: In the second era, recipients with HBV-related disease or who had received hepatitis B core antibody-positive liver received combination therapy with short-term HBIG and an NA such as TAF and ETV long-term. The duration of HBIG treatment was markedly shorter than in the first era in both categories of patients and HBIG could be discontinued in all cases. Surprisingly, we observed HBV reactivation in the first era, but not in the second era, in both groups., Conclusions: We have established a protocol for prophylaxis against HBV reactivation using a combination of short-term HBIG and long-term NA. This protocol was found to be sufficient to prevent HBV reactivation after LT., (© 2024 Japan Society of Hepatology.)

Aim: Sarcopenia is reportedly associated with a poor prognosis in patients who undergo living-donor liver transplantation (LDLT), most of whom are not able to tolerate muscle strengthening exercise training. Myostatin is one of the myokines and a negative regulator of skeletal muscle growth. The clinical feasibility of an electrical muscle stimulation (EMS) system, which exercises muscle automatically by direct electrical stimulation, has been reported. In this study, we aimed to determine the effect of perioperative application of SIXPAD, which is a type of EMS system, with reference to the serum myostatin and sarcopenia in LDLT patients., Method: Thirty patients scheduled for LDLT were divided into a SIXPAD group (n = 16) and a control group (n = 14). In the SIXPAD group, EMS was applied to the thighs twice daily. The serum myostatin was measured in samples obtained before use of SIXPAD and immediately before LDLT. The psoas muscle index (PMI) at the level of the third lumbar vertebra and the quadriceps muscle area were compared on computed tomography images before use of SIXPAD and 1 month after LDLT., Results: The preoperative serum myostatin was found to be higher in LDLT patients than in healthy volunteers and EMS significantly reduced the serum myostatin. Electrical muscle stimulation prevented a postoperative reduction not only in the area of the quadriceps muscles but also in the PMI despite direct stimulation of the thigh muscles., Conclusion: Stimulation of muscles by EMS decreases the serum myostatin and helps to maintain skeletal muscle in patients who have undergone LDLT., (© 2024 Japan Society of Hepatology.)

Purpose: Infectious complications, particularly post-transplant sepsis, have a critical impact on postoperative outcomes. This study examined the effects of perioperative synbiotic treatment on postoperative outcomes in patients receiving early enteral nutrition., Methods: We reviewed 210 living-donor liver transplantation procedures and retrospectively analyzed the postoperative outcomes with and without perioperative synbiotic treatment (live lactic acid bacteria, bifidobacteria, and oligosaccharides) 5 days before and after living-donor liver transplantation., Results: The synbiotic group (n = 34) had significantly fewer male donors (38.2% vs. 61.9%, p = 0.011) and a higher proportion of ABO-incompatible grafts (52.9% vs. 25.6%, p = 0.021) than the non-synbiotic group (n = 176). The incidence of sepsis was significantly lower in the synbiotic group than in the non-synbiotic group (0% vs. 7.4%, p = 0.029), with a lower incidence rate of sepsis due to bacteremia with intestinal bacteria (0% vs. 4.6%, p = 0.089). There were no significant differences in the proportions of acute rejection, small-for-size graft syndrome, or postoperative liver function between the two groups. Furthermore, there was no significant difference in the graft survival rates after LDLT between two groups. (p = 0.24)., Conclusion: Perioperative synbiotic treatment prevents post-transplant sepsis, even with early enteral nutrition., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Purpose: Treatment outcomes are predicted by analyzing peripheral blood markers such as serum lactate dehydrogenase (LDH). We conducted this study to investigate whether serum LDH levels can predict the prognosis of patients treated with atezolizumab plus bevacizumab (ATZ/BEV) therapy for hepatocellular carcinoma (HCC) and whether LDH levels correlate with metabolic changes., Methods: We enrolled 66 HCC patients treated with ATZ/BEV. Based on the change in serum LDH levels before and after treatment, the patients were divided into two groups, and the prognosis of each group was examined. Moreover, the association of LDH levels with tumor metabolism was analyzed by fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT)., Results: There were 32 patients categorized as the LDH-decrease group. Kaplan-Meier survival analysis indicated worse progression-free survival (PFS) in the LDH-increase group than in the LDH-decrease group (p = 0.0029). Multivariate analysis showed that an increase in the LDH level was an independent risk factor for worse PFS (p = 0.0045). The baseline LDH level correlated significantly with a high maximum standardized uptake value of 18 F-FDG, according to the PET/CT findings. Transcriptomic analyses of specimens resected after ATZ/BEV therapy showed downregulated mitochondria-related pathways., Conclusion: Serum LDH levels are a potential prognostic marker and an indicator of tumor metabolism., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

We developed a reliable high-performance liquid chromatographic analysis method using a relative molar sensitivity (RMS) technique that does not require an authentic, identical reference analyte material to quantify blood serum carbamazepine, phenytoin, voriconazole, lamotrigine, meropenem, mycophenolic acid, linezolid, vancomycin, and caffeine levels for routine blood concentration measurements. Carbamazepine and caffeine were also used as non-analyte reference materials to calculate the RMS of each analyte. The RMS was calculated from the ratio of the slope of the calibration equation (analyte/non-analyte reference material), then used to quantify analytes in control serum samples spiked with carbamazepine, phenytoin, voriconazole, meropenem, mycophenolic acid, linezolid or vancomycin. In addition, the concentrations of these six drugs in control serum samples determined by the proposed RMS method agreed well with that obtained using a conventional method. The proposed RMS method is a promising tool for the clinical determination of nine drugs, given the accuracy, precision, and efficiency of quantifying these analytes., (© 2024. The Author(s).)

Purpose: Although the incidence of recipients and donors with overweight and obesity is increasing worldwide, few reports have focused on outcomes of preoperative weight reduction (WR) in living-donor liver transplantation (LDLT). Therefore, we examined the outcomes and the impact of WR on the postoperative course., Methods: We analyzed 217 consecutive LDLT procedures performed from 2017 to 2022. We divided the recipients and donors into a WR group and non-WR group., Results: Twenty-two recipients (10.1%) achieved WR (preoperative recipient WR [RWR] group), reducing their weight by 6.8% ± 6.0% within 2.2 ± 1.4 months with a significant decrease in body mass index (BMI) (P < .0001). The RWR group showed no significant differences in short-term postoperative outcomes (operative factors, postoperative liver function tests, amount of ascites, and morbidity) or in the graft survival rate as a long-term outcome (P = .24) compared with the non-RWR group. Forty-one donors (18.9%) achieved WR (preoperative donor WR [DWR] group), reducing their weight by 9.7% ± 6.3% within 3.2 ± 5.8 months with a significant decrease in BMI (P < .0001). Compared with the non-DWR group, the DWR group showed no significant differences in short-term postoperative outcomes between themselves and recipients or in the graft survival rate (P = .49). Furthermore, WR resulted in an increase to 32 donor-eligible and 6 recipient-eligible patients., Conclusion: WR in LDLT recipients and donors had no harmful effect on postoperative outcomes and should lead to increase recipients' chance of undergoing LDLT and to expand the donor pool., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

The clinical course of residual ventricular septal defects after congenital heart disease repair is not completely elucidated in the medical literature. This study assessed the incidence, size, and clinical course of residual defects.This single-center retrospective study included 132 patients who survived after ventricular septal defect patch closure (n = 107) and intracardiac repair of double-outlet right ventricle (n = 16) and tetralogy of Fallot (n = 9). Residual defect was evaluated on transthoracic echocardiogram upon hospital discharge and at outpatient clinic visits.The median age at surgery was 1.2 (0.3-13.9) years. In total, 45 (34.1%) patients presented with residual defects upon hospital discharge. The residual defects were within 2 mm (n = 27), 2-3 mm (n = 15), and > 3 mm (n = 3), and the median size was 1.5 (0.5-3.8) mm. There was no late mortality during a median follow-up of 5.4 years. Among 42 residual defects measuring < 3 mm upon hospital discharge, 37 (82.2%) spontaneously closed. Further, five defects decreased in size (1.8 ± 0.6 mm upon hospital discharge vs1.2 ± 0.8 mm at the latest visits, p = 0.15). However, the size of three residual defects measuring > 3 mm upon hospital discharge increased, and two patients required re-surgery for residual defect.Significant residual defect requiring reoperation was rare. In most cases, residual defects measuring < 3 mm upon hospital discharge spontaneously closed within 5 years, and the size of the other defects decreased., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Telenursing e-learning courses have been shown to enhance nurses' skills and knowledge; however, the subjective learning experience is unclear. In this study, we identified meta-inferences to quantitatively and qualitatively understand this experience, as well as the types of knowledge gained through an e-learning course and how they are linked to each other, in order to enhance nurses' confidence in their understanding of telenursing., Methods: We employed a single-arm intervention with a mixed-methods convergent parallel design. We converged participants' self-reported pre- and post-course confidence scores with their reflections on the learning experience, which were reported qualitatively as improved or unimproved. A total of 143 Japanese nurses with a mean of 20 years of nursing experience participated in this study., Results: Among the participants, 72.7% demonstrated improved confidence in their understanding of telenursing after completing the e-learning course. The baseline confidence score was originally higher in the group that reported unimproved confidence (p < .001). Although there was no statistical difference in the usability and practicality scores between the two groups, the qualitative learning experience in these aspects differed in terms of the depth of knowledge of telenursing obtained., Conclusions: Nurses' quantitative confidence in their understanding of telenursing after course completion was incongruent with their qualitative perspectives of the learning experience. Nursing educators, healthcare policymakers, and other stakeholders should consider that learners' overconfidence in their understanding of telenursing and comprehension of e-learning materials may result in their failure to develop key telenursing competencies, skills, and knowledge., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Ischemia-reperfusion (I/R) leads to tissue damage in transplanted kidneys, resulting in acute kidney injury (AKI) and chronic graft dysfunction, which critically compromises transplant outcomes, such as graft loss. Linaclotide, a guanylate cyclase C agonist clinically approved as a laxative, has recently been identified to exhibit renoprotective effects in a chronic kidney disease (CKD) model. This study evaluates the therapeutic effects of linaclotide on AKI triggered by I/R in a rat model with an initial comparison with other laxatives. Here, we show that linaclotide administration resulted in substantial reduction in serum creatinine levels, reflective of enhanced renal function. Histological examination revealed diminished tubular damage, and Sirius Red staining confirmed less collagen deposition, collectively indicating preserved structural integrity and mitigation of fibrosis. Further analysis demonstrated lowered expression of TGF-β and associated fibrotic markers, α-SMA, MMP2, and TIMP1, implicating the downregulation of the fibrogenic TGF-β pathway by linaclotide. Furthermore, one day after I/R insult, linaclotide profoundly diminished macrophage infiltration and suppressed critical pro-inflammatory cytokines such as TNF, IL-1β, and IL-6, signifying its potential to disrupt initial inflammatory mechanisms integral to AKI pathology. These findings suggest that linaclotide, with its established safety profile, could extend its benefits beyond gastrointestinal issues and potentially serve as a therapeutic intervention for organ transplantation. Additionally, it could provide immediate and practical insights into selecting laxatives for managing patients with AKI or CKD, regardless of the cause, and for those receiving dialysis or transplant therapy., Competing Interests: Declaration of competing interest From 2011 to 2016, MA was affiliated with the Innovation Center for Immunoregulation and Therapeutics, Graduate School of Medicine, Kyoto University, which was funded in part by Astellas Pharma Inc. The other authors declare that they have no apparent conflicting financial interests or personal relationships that could be perceived as influencing the results presented in this manuscript., (Copyright © 2024. Published by Elsevier Inc.)

A 35-year-old woman was admitted for the examination of lower leg edema and proteinuria. A kidney biopsy showed membranous nephropathy (MN) with fine granular deposits of IgG along the glomerular capillary and poor spike formation, differing from primary MN in the presence of positive IgG3 and C1q. Lupus nephritis was excluded because serum complement and anti-dsDNA antibody, anti-Smith antibody, and anti-cardiolipin antibody tests were negative. The serological test for syphilis was positive, as was the Treponema pallidum hemagglutination test. The patient was diagnosed with syphilis, and the proteinuria disappeared with antibiotic treatment. In MN with positive IgG3 and C1q, syphilis nephropathy may be a differential diagnosis.

Hypertension is a major cause of cardiovascular diseases such as myocardial infarction and stroke. Cardiovascular fibrosis occurs with hypertension and contributes to vascular resistance, aortic stiffness, and cardiac hypertrophy. However, the molecular mechanisms leading to fibroblast activation in hypertension remain largely unknown. There are two types of fibrosis: replacement fibrosis and reactive fibrosis. Replacement fibrosis occurs in response to the loss of viable tissue to form a scar. Reactive fibrosis occurs in response to an increase in mechanical and neurohormonal stress. Although both types of fibrosis are considered adaptive processes, they become maladaptive when the tissue loss is too large, or the stress persists. Myofibroblasts represent a subpopulation of activated fibroblasts that have gained contractile function to promote wound healing. Therefore, myofibroblasts are a critical cell type that promotes replacement fibrosis. Although myofibroblasts were recognized as the fibroblasts participating in reactive fibrosis, recent experimental evidence indicated there are distinct fibroblast populations in cardiovascular reactive fibrosis. Accordingly, we will discuss the updated definition of fibroblast subpopulations, the regulatory mechanisms, and their potential roles in cardiovascular pathophysiology utilizing new knowledge from various lineage tracing and single-cell RNA sequencing studies. Among the fibroblast subpopulations, we will highlight the novel roles of matrifibrocytes and immune fibrocytes in cardiovascular fibrosis including experimental models of hypertension, pressure overload, myocardial infarction, atherosclerosis, aortic aneurysm, and nephrosclerosis. Exploration into the molecular mechanisms involved in the differentiation and activation of those fibroblast subpopulations may lead to novel treatments for end-organ damage associated with hypertension and other cardiovascular diseases., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Mitochondrial dysfunction has been implicated in various types of cardiovascular disease including hypertension. Mitochondrial fission fusion balance is critical to mitochondrial quality control, whereas enhanced fission has been reported in several models of cardiovascular disease. However, limited information is available regarding the contribution of mitochondrial fission in hypertension. Here, we have tested the hypothesis that inhibition of mitochondrial fission attenuates the development of hypertension and associated vascular remodeling. In C57BL6 mice infused with angiotensin II for 2 weeks, co-treatment of mitochondrial fission inhibitor, mdivi1, significantly inhibited angiotensin II-induced development of hypertension assessed by radiotelemetry. Histological assessment of hearts and aortas showed that mdivi1 inhibited vessel fibrosis and hypertrophy induced by angiotensin II. This was associated with attenuation of angiotensin II-induced decline in mitochondrial aspect ratio seen in both the endothelial and medial layers of aortas. Mdivi1 also mitigated angiotensin II-induced cardiac hypertrophy assessed by heart weight-to-body weight ratio as well as by echocardiography. In ex vivo experiments, mdivi1 inhibited vasoconstriction and abolished the enhanced vascular reactivity by angiotensin II in small mesenteric arteries. Proteomic analysis on endothelial cell culture media with angiotensin II and/or mdivi1 treatment revealed that mdivi1 inhibited endothelial cell hypersecretory phenotype induced by angiotensin II. In addition, mdivi1 attenuated angiotensin II-induced protein induction of periostin, a myofibroblast marker in cultured vascular fibroblasts. In conclusion, these data suggest that mdivi1 prevented angiotensin II-induced hypertension and cardiovascular remodeling via multicellular mechanisms in the vasculature., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Amyotrophic lateral sclerosis (ALS) is an adult-onset intractable motor neuron disease characterized by selective degeneration of cortical neurons in the frontotemporal lobe and motor neurons in the brainstem and spinal cord. Impairment of these neural networks causes progressive muscle atrophy and weakness that spreads throughout the body, resulting in life-threatening bulbar palsy and respiratory muscle paralysis. However, no therapeutic strategy has yet been established to halt ALS progression. Although evidence for clinical practice in ALS remains insufficient, novel research findings have steadily accumulated in recent years. To provide updated evidence-based or expert consensus recommendations for the diagnosis and management of ALS, the ALS Clinical Practice Guideline Development Committee, approved by the Japanese Society of Neurology, revised and published the Japanese clinical practice guidelines for the management of ALS in 2023. In this guideline, disease-modifying therapies that have accumulated evidence from randomized controlled trials were defined as "Clinical Questions," in which the level of evidence was determined by systematic reviews. In contrast, "Questions and Answers" were defined as issues of clinically important but insufficient evidence, according to reports of a small number of cases, observational studies, and expert opinions. Based on a literature search performed in February 2022, recommendations were reached by consensus, determined by an independent panel, reviewed by external reviewers, and submitted for public comments by Japanese Society of Neurology members before publication. In this article, we summarize the revised Japanese guidelines for ALS, highlighting the regional and cultural diversity of care processes and decision-making. The guidelines cover a broad range of essential topics such as etiology, diagnostic criteria, disease monitoring and treatments, management of symptoms, respiration, rehabilitation, nutrition, metabolism, patient instructions, and various types of care support. We believe that this summary will help improve the daily clinical practice for individuals living with ALS and their caregivers.

Pesticides are widely used to improve crop productivity by eliminating weeds and pests. Conventional pesticide development involves synthesizing compounds, testing their activities, and studying their effects on the ecosystem. However, as pesticide discovery has an extremely low success rate, many compounds must be synthesized and tested. To overcome the high human, financial, and time costs of this process, machine learning is attracting increasing attention. In this study, we used machine learning for the molecular design of novel seed compounds for herbicides and insecticides. Classification models were constructed by using compounds that had been tested as herbicides and insecticides, and an inverse analysis of the constructed models was conducted. In the molecular design of herbicides, we proposed 186 new samples as herbicides using ensemble learning and a method for expressing explanatory variables that consider the relationships among eight weed species. For the molecular design of insecticides, we used undersampling and ensemble learning for the analysis of unbalanced data. Based on approximately 340,000 compounds, 12 potential insecticides were proposed, of which 2 exhibited actual activity when tested. These results demonstrate the potential of the developed machine-learning method for rapidly identifying novel herbicides and insecticides., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

A 58-year-old woman with rheumatoid arthritis was diagnosed with methotrexate-associated Hodgkin lymphoma. After receiving several chemotherapy regimens, she started nivolumab treatment. Two weeks later, she was hospitalized with worsening finger, wrist, and elbow joint pain. A synovial biopsy of the wrist joint showed villous synovial proliferation and linear infiltration of CD68-/CD3-positive T cells (with more CD8 than CD4 T cells) but no CD20-positive B cells or CD138-positive macrophages. These findings corresponded to synovitis associated with immune-related adverse events, which are induced mainly by T cells and are different from typical rheumatoid arthritis (RA), in which B cells play a central role.

We conducted a retrospective case-control study to assess the efficacy of personalized health guidance interventions on individuals with type 2 diabetes mellitus and obesity. A selection was made of individuals in regular visits to the Takagi Hospital for medical checkups between January 2017, and October 2021. Totally, 108 subjects (cases) with health guidance were divided into 2 groups: one group without pharmacotherapy for diabetes mellitus in medical institutions ( n  = 92) and another group with pharmacotherapy ( n  = 116). Cases were provided with personalized health guidance interventions by public health nurses for 30 min, in accordance with the Japanese clinical guidelines for the prevention of lifestyle-related diseases. Sex- and age-matched controls were chosen from individuals with diabetes mellitus without health guidance. The intervention without pharmacotherapy resulted in improvements in health indicators, including body weight, waist circumference, diastolic blood pressure, triglyceride levels, and γ-glutamyl trans-peptidase. These positive effects were not observed in the control group without health guidance. The therapeutic effects of health guidance were observed in cases where pharmacotherapy was administered. In conclusion, the implementation of individual health guidance interventions may prove to be effective for individuals with type 2 diabetes mellitus and obesity who regularly attend medical checkups., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2024 JCBN.)

Introduction: While opioids have been found to be useful in relieving suffering in amyotrophic lateral sclerosis (ALS), there is a lack of evidence concerning how and how much to use them in practice. This study was conducted to clarify how opioids were used for patients with ALS., Methods: We performed a retrospective case-based analysis at a single tertiary neurology center in Tokyo from 2010 to 2018. We enrolled patients with ALS who had died before the end of 2018. We examined the opioid dosage equivalent of morphine hydrochloride and patients' clinical backgrounds, focusing on ventilatory support., Results: Morphine was administered in 110 patients with ALS, and 84 were followed up until their death. Of these 84 patients, 57 (69.9%) did not use mechanical ventilation until death (no-MV group), and 21 (22.9%) utilized only non-invasive ventilation (NIV group). Final morphine dosage in the NIV group was significantly higher (mean 65.7 mg [SD 54.6], range 10-200 mg) than in the no-MV group (mean 31.7 mg [SD 26.9], range 0-120 mg; p = 0.015, Welch's t-test). The NIV group needed psychotropic drugs more frequently than the no-MV group (62% [n = 13] vs. 35% [n = 20])., Conclusion: Patients in the NIV group used opioids for a statistically significantly longer time and at a higher dose than those in the no-MV group. Symptom control with opioids alone may be difficult, and the development of multifaceted evaluation and care is desirable., (© 2023. The Author(s) under exclusive licence to Belgian Neurological Society.)

Background: Liver transplantation is the definitive therapy for patients with decompensated cirrhosis. Marfan syndrome is a systemic inheritable connective tissue disease associated with fibrillin-1 gene mutations, which cause abnormalities in connective tissue. Vascular changes due to Marfan syndrome occur mostly in the main vessels due to the high amount of connective tissue within the vessel wall and the high pressure and blood flow to which they are exposed. The incidence of changes in visceral arteries is about 0.42% and usually presents with cystic medial necrosis. This report is the first deceased-donor liver transplantation with a donor with Marfan syndrome with a history of abdominal surgery., Case Presentation: A patient in his 50s underwent liver transplantation for decompensated alcoholic cirrhosis. The donor, a 50s male with Marfan syndrome, was diagnosed with brain-death due to a cerebral hemorrhage caused by a cerebral aneurysm. The donor's clinical presentation as Marfan syndrome was aortic dissection, with multiple surgical procedures performed from the aortic root to the abdominal aorta. An intraoperative biopsy of the hepatic artery showed no abnormality, so this organ was considered appropriate. The surgery was completed without any problems of the arterial anastomosis. The patient's postoperative course was uneventful, and he was transferred to a hospital for recuperation on the 18th postoperative day. One year after the surgery, the patient is still alive without any complications from the transplantation or arterial problems., Conclusions: Even if the patient had a history of surgery for vascular anomalies extending to the abdominal aorta due to Marfan syndrome, the patient can be a donor for liver transplantation under appropriate judgment, including intraoperative biopsy., (© 2024. The Author(s).)

Selective removal of excess or damaged mitochondria is an evolutionarily conserved process that contributes to mitochondrial quality and quantity control. This catabolic event relies on autophagy, a membrane trafficking system that sequesters cytoplasmic constituents into double membrane-bound autophagosomes and delivers them to lysosomes (vacuoles in yeast) for hydrolytic degradation and is thus termed mitophagy. Dysregulation of mitophagy is associated with various diseases, highlighting its physiological relevance. In budding yeast, the pro-mitophagic single-pass membrane protein Atg32 is upregulated under prolonged respiration or nutrient starvation, anchored on the surface of mitochondria, and activated to recruit the autophagy machinery for the formation of autophagosomes surrounding mitochondria. In this chapter, we provide protocols to assess Atg32-mediated mitophagy using fluorescence microscopy and immunoblotting., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aim: Many recent studies have shown a relationship between various systemic diseases and the gut microbiota (GM), with the gut-liver axis receiving particular attention. In contrast, no report has comprehensively shown the effects of GM on the pathophysiology of patients undergoing living donor liver transplantation (LDLT)., Method: We enrolled 16 recipients who underwent LDLT for liver cirrhosis, and 17 donors constituted the reference group. We examined the differences in GM between recipients and donors. We also examined the relationships between GM, short-chain fatty acids, and portal vein pressure (PVP) in recipients., Results: There was no significant difference in alpha-diversity between the recipients and donors, but there was variation in beta-diversity among the recipients. The abundance of the phylum Bacteroidetes was significantly higher in recipients than in donors ( P  = 0.016), and it was positively correlated with PVP ( r  = 0.511, P  = 0.043). Propionic acid, which is a component of short-chain fatty acids, was positively correlated with PVP ( r  = 0.544, P  = 0.0295), the phylum Bacteroidetes ( r  = 0.677, P  = 0.004), and total bilirubin concentration ( r  = 0.501, P  = 0.048). Propionic acid was negatively correlated with serum albumin concentration ( r  = -0.482, P  = 0.043)., Conclusion: Our findings suggest relationships between fecal Bacteroidetes levels, propionic acid concentrations, and PVP in patients with liver cirrhosis undergoing LDLT., (© 2023 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Objective: To investigate somatosensory pathway function in patients with amyotrophic lateral sclerosis (ALS) dependent on invasive ventilation and in a completely locked-in state (CLIS)., Methods: We examined median nerve somatosensory evoked potentials (SEPs) in 17 ALS patients in a CLIS, including 11 patients with sporadic ALS, one with familial ALS with genes not examined, four with a Cu/Zn superoxide-dismutase-1 (SOD1) gene variant (Val118Leu, Gly93Ser, Cys146Arg), and one with a fused-in-sarcoma gene variant (P525L). We evaluated N9, N13, N20 and P25, and central conduction time (CCT); the data were compared with those of 73 healthy controls., Results: N20 and N13 were abolished in 12 and 10 patients, and their latencies was prolonged in four and three patients, respectively. The CCT was prolonged in five patients with measurable N13 and N20. Two patients with SOD1 gene mutations had absent or slightly visible N9. Compared to the CCT and latencies and amplitudes of N13 and N20 in the controls, those in the patient cohort were significantly abnormal., Conclusions: The central somatosensory pathway is severely involved in patients with ALS in a CLIS., Significance: Our findings suggest that median nerve SEP cannot be utilized for communication in patients with ALS in a CLIS., Competing Interests: Declarations of Competing Interest None., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

This is a case of a 2.7-year-old girl with trisomy 21 and double outlet right ventricle who underwent epicardial pacemaker system placement for a surgical atrioventricular block and achieved atrioventricular conduction recovery immediately after residual ventricular septal defect closure. Although ventricular pacing ratio was 100% before re-operation, it declined to approximately 25% on the 6 th post-operative day and was <1% 3 years after re-operation.

Objectives: The number of patients receiving antiplatelet therapy (APT) who have undergone laparoscopic radical nephrectomy is increasing. However, it is unclear whether APT affects the outcomes of patients undergoing radical nephrectomy. We investigated the perioperative outcomes of radical nephrectomy in patients with and without APT., Methods: We retrospectively collected data from 89 Japanese patients who underwent laparoscopic radical nephrectomy for clinically diagnosed renal cell carcinoma (RCC) at Kokura Memorial Hospital between March 2013 and March 2022. We analyzed information related to APT. We divided the patients into two groups: the APT group (patients receiving APT) and the N-APT group (patients not receiving APT). Moreover, the APT group was further divided into the C-APT group (patients with continuous APT) and the I-APT group (patients with interrupted APT). We compared the surgical outcomes of these groups., Results: Among 89 patients eligible for the study, 25 received APT and 10 continued APT. Even though the patients who received APT had a high American Society of Anesthesiologists physical status and many complications, including smoking, diabetes, hypertension, and chronic heart failure, no significant difference in the intra- or postoperative outcomes, including bleeding complications, was observed regardless of whether the patients received APT or continued APT., Conclusions: We concluded that in laparoscopic radical nephrectomy, continuation of APT is an acceptable strategy for patients with thromboembolic risk caused by interruption of APT., (© 2023 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Disaster preparation is an important issue for patients with amyotrophic lateral sclerosis (ALS). However, to the best of our knowledge, no studies have investigated disaster preparedness among patients with ALS. In this study, we aimed to investigate disaster preparation in patients with ALS and their caregivers, including their families, in Japan. We conducted a nationwide webinar in September 2022 titled "ALS Café" and distributed a self-report questionnaire to participants with questions about awareness of disaster preparedness, social countermeasures, stockpiles, and electricity demand. Forty-eight patients with ALS (27 male; average age 60.0 ± 9.3 years) and 23 caregivers (8 male; 55.7 ± 9.9 years) responded. The median revised ALS Functional Rating Scale score was 30.5, and 25% of the patients with ALS were on a ventilator. More than 70% of the respondents answered that they were not prepared for disasters, increasing to 89% in patients not using ventilators. In the event of their phones being down, 86% of the respondents had no plans for alternative means of communication. <30% of the respondents, including ventilator users, had secured human resources for transportation. Twenty-five percent of the respondents did not stockpile food and beverages, and 12% of the ventilator users had no government-recommended ventilator preparation equipment. Thus, although patients with ALS and their families with ventilators have a high awareness of disaster preparedness, their awareness remains insufficient. Furthermore, patients with ALS and their families without ventilators have a low awareness of disaster preparedness. Therefore, better education regarding disaster preparedness is necessary for these groups., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Cortical responses in somatosensory evoked potentials (SEP) are enhanced in patients with amyotrophic lateral sclerosis (ALS). This study investigated whether sensory gating is involved in the pathophysiology of sensory cortical hyperactivity in ALS patients. The median nerve SEP was recorded at rest and during voluntary finger movements in 14 ALS patients and 13 healthy control subjects. The parietal N20, P25, and frontal N30 were analyzed, and sensory gating was assessed by measuring the amplitude of each component during finger movement. The amplitudes of the N20 onset-peak, N20 peak-P25 peak, and N30 onset-peak were higher in ALS patients than in controls. Nonetheless, there were no significant differences in the amplitude reduction ratio of SEPs between patients and controls. There was a significant correlation between the baseline amplitudes of the N20 onset-peak or N20 peak-P25 peak and their gating ratios in patients with ALS. Our findings indicate that the excitability of the primary sensory cortex and secondary motor cortex is enhanced in ALS, while sensory gating is preserved in the early stages of ALS. This result suggests that enhanced SEP is caused by the hyperexcitability of the primary sensory and secondary motor cortices but not by the dysfunction of inhibitory mechanisms during voluntary movements.

As greenhouse gases such as CO 2 continue to promote global warming, the reduction of CO 2 emissions is attracting increasing attention. In this study, we design a process for producing dimethyl ether (DME), which is a promising means of using CO 2 as a resource. Design variables such as temperature and pressure need to be optimized to reduce CO 2 emissions while maintaining high product purity and DME production. Conventional process designs determine these design variables from the chemical background and through trial-and-error simulations, which are very time-consuming. The proposed method optimizes the design variables efficiently by repeating the process simulations and selecting promising candidates for the design variables using machine learning. For an adaptive design of experiments, Bayesian optimization is used to achieve the objectives of the DME process while efficiently optimizing the design variables. In addition, we also optimize the design variables considering variations in the temperature and pressure data, meaning robust Bayesian optimization. The proposed method successfully identifies design variables that satisfy all experimental targets in an average of 54 simulations while achieving 100% of the targets with product purity 0.95-1.00, amount of DME in the product 350-845 kmol/h, and CO 2 emissions 0-835 kmol/h, confirming the effectiveness of the proposed robust Bayesian optimization method., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: The hemoglobin-albumin-lymphocyte-platelet (HALP) score is a combination index that assesses nutritional status and systemic inflammatory response and is reported to predict prognosis in several cancer types. However, researches about the usefulness of the HALP score in intrahepatic cholangiocarcinoma (ICC) are limited., Methods: This was a single-center, retrospective study of 95 patients who underwent surgical resection for ICC between 1998 and 2018. We divided patients into two groups by calculating the cutoff value of the HALP score and examined clinicopathological characteristics, prognosis, and sarcopenia. Tumor-infiltrating lymphocytes (TILs), CD8 + TILs, and FOXP3 + TILs were evaluated by immunohistochemical staining of resected tumors., Results: Of 95 patients, 22 were HALP-low. The HALP-low group had significantly lower hemoglobin (p = 0.0007), lower albumin (p = 0.0013), higher platelet counts (p < 0.0001), fewer lymphocytes (p < 0.0001), higher CA19-9 levels (p = 0.0431), and more lymph node metastasis (p = 0.0013). Multivariate analysis revealed that the independent prognostic factors for disease-free survival were maximum tumor size (≥ 5.0 cm) (p = 0.0033), microvascular invasion (p = 0.0108), and HALP score (≤ 25.2) (p = 0.0349), and that factors for overall survival were lymph node metastasis (p = 0.0020) and HALP score (≤ 25.2) (p = 0.0014). The HALP-low group contained significantly more patients with sarcopenia (p = 0.0015). Immunohistochemistry showed that counts of CD8 + TILs were significantly lower in the HALP-low group (p = 0.0075)., Conclusions: We demonstrated that low HALP score is an independent prognostic factor for ICC patients undergoing curative hepatic resection and is associated with sarcopenia and the immune microenvironment., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Aim: We aimed to evaluate the association between the intraoperative indocyanine green (ICG) fluorescence imaging (FI) pattern, preoperative magnetic resonance imaging (MRI) findings using gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA), preoperative diffusion-weighted imaging (DWI) of MRI, and histological differentiation of hepatocellular carcinoma (HCC)., Methods: We retrospectively reviewed the data for 80 tumors of 64 patients. Intraoperative ICG FI patterns were classified into cancerous or rim-positive type. We evaluated the signal intensity ratio of the tumor and the surrounding liver tissue in the portal phase (SIRPP) and intensity in the hepatobiliary phase (HBP) of Gd-EOB-DTPA-enhanced MRI, the apparent diffusion coefficient (ADC) in the DWI of MRI, and clinicopathologic factors., Results: In the rim-positive group, the rate of poorly differentiated HCC and hypointensity type in HBP were significantly higher, and SIRPP and ADC were significantly lower than the rim-negative group. In the cancerous group, the rate of well or moderately differentiated HCC and hyperintensity type in HBP, SIRPP, and ADC were significantly higher than the noncancerous group. Multivariate analysis identified low SIRPP, low ADC, and hypointensity type in HBP as the significant predictive factors for rim-positive HCC and high SIRPP, high ADC, and hyperintensity type in HBP as the significant predictive factors for cancerous HCC. The positive rate of programmed cell death 1-ligand 1 and vessels that encapsulate tumor clusters status of the rim-positive HCC and HCC with low SIRPP were significantly higher than the control group., Conclusions: The intraoperative ICG FI pattern of HCC closely correlated with histological differentiation, preoperative SIRPP and intensity type in the Gd-EOB-DTPA MRI, and preoperative ADC in the DWI of MRI., (© 2023 Japan Society of Hepatology.)

A 16-year-old Japanese girl developed a fever, thrombocytopenia, and renal dysfunction. Treatment was started with steroids, but cervical lymphadenopathy and ascites developed. A lymph node biopsy indicated TAFRO syndrome. The patient's renal function deteriorated, and dialysis was started. Refractory hypertension and subsequent encephalopathy developed. Treatment was started with an anti-IL-6 receptor antibody and an anti-CD20 monoclonal antibody. A kidney biopsy showed malignant nephrosclerosis-like microangiopathy and glomerular collapse due to narrowing of the small arteries. The majority of TAFRO syndrome cases are adult-onset, with glomerular microangiopathy. To our knowledge, this is the first report of adolescent-onset TAFRO syndrome presenting with malignant nephrosclerosis-like lesions associated with hypertension.

Many countries are facing the advent of super-aging societies, where sarcopenia and frailty will become pertinent problems. The prevalence of comorbidities is a major problem in countries with aged populations as elderly people suffer from various diseases, such as diabetes, heart failure, chronic kidney disease and dementia. All of these diseases are associated with sarcopenia and frailty, and they frequently cause falls, fractures, and a decline in activities of daily living. Fractures in the elderly people are associated with bone fragility, which is influenced by diabetes and chronic kidney disease. Nutritional support for chronic disease patients and sarcopenic individuals with adequate energy and protein intake, vitamin D supplementation, blood glucose level management for individuals with diabetes, obesity prevention, nutritional education for healthy individuals, and the enlightenment of society could be crucial to solve the health-related problems in super-aging societies., Competing Interests: The authors declare no conflict of interest.

Aim: The hemoglobin, albumin, lymphocyte, and platelet (HALP) score reflects the immune system and the nutritional status of patients, and prognosis in various cancers. However, the HALP score in hepatocellular carcinoma has not been reported., Methods: Data were analyzed retrospectively from Child-Pugh A patients undergoing hepatic resection for single hepatocellular carcinoma ≤5 cm. For cross-validation, patients were divided into the training (332 patients) and validation cohort (210 patients). In the training cohort, we divided patients into two groups by appropriate cut-off value of the HALP score, and univariable and multivariable analyses were conducted for disease-free and overall survival (OS) between two groups. In the validation cohort, we examined OS by Kaplan-Meier analysis in the same cut-off value of the HALP score in the training cohort., Results: The HALP-low group was significantly older (p = 0.0003), had fewer hepatitis B surface antigen-positive patients (p = 0.0369), higher prothrombin time (p = 0.0141), lower fibrosis-4 index (p = 0.0206), bigger maximum tumor size (p = 0.0196), and less histological liver fibrosis (p = 0.0077). Multivariate analysis showed that the independent prognostic factors for disease-free survival were fibrosis-4 index ≥2.67 (p = 0.0008), simple nodular type with extranodular growth or confluent multinodular type (p = 0.0221), and intrahepatic metastasis (p = 0.0233), and that for OS were fibrosis-4 index ≥2.67 (p = 0.0020), HALP ≤45.6 (p = 0.0228), and poor differentiation (p = 0.0305). In the validation cohort, Kaplan-Meier analysis revealed the trend toward significantly impaired OS (p = 0.0220) in the HALP-low group., Conclusion: We showed that a low HALP score is the independent prognostic factor for Child-Pugh A patients undergoing curative hepatic resection for single and small hepatocellular carcinoma., (© 2023 Japan Society of Hepatology.)

Background: Macroglossia is one of the clinical signs that emerges in patients with amyotrophic lateral sclerosis (ALS) who are undergoing invasive ventilation., Objective: We aimed to investigate the relationship between the progression of macroglossia and the clinical characteristics during the advanced stages of ALS., Methods: Forty-one patients with ALS using invasive ventilation with tracheostomy were prospectively followed over a 3-year period. We evaluated the prevalence of macroglossia, motor disabilities including oral function, communication ability (communication stage I to V) as a marker of disease progression, and nutritional factors. We analyzed the potential factors affecting the progression of macroglossia using a multivariate logistic analysis., Results: The number of patients with macroglossia was increased during the follow-up (from 24.4 to 53.7%), while the communication stage progressed from 2.6 in average (SD 1.7) to 3.5 (1.4). During the study, body weight increased, while energy intake decreased, suggesting progressive hypometabolism. Eight patients had newly developed macroglossia during the study and showed greater progression of communication impairment than those without macroglossia. Multivariate logistic regression analysis showed that communication impairment was a factor associated with macroglossia., Conclusion: Macroglossia in advanced ALS with invasive ventilation is associated with disease progression., (© 2023. Fondazione Società Italiana di Neurologia.)

Objectives: To assess long-term survival and reoperation-free survival after the arterial switch operation (ASO) and analyze the outcomes of reoperations after hospital discharge., Methods: This was a single-institution retrospective study of 476 hospital survivors of ASO since August 1982. Preoperative diagnoses included 286 transpositions of the great arteries with intact septum, 143 transpositions with ventricular septal defect, and 47 double outlet right ventricles. There were 236 neonatal ASOs, 30 aortic arch repairs, 22 concomitant left ventricular outflow tract obstruction reliefs, 16 preoperative mild pulmonary regurgitations, and 13 intramural coronary arteries., Results: During a median follow-up of 21.1 years (range, 0.1-39.2 years), 25 late deaths (5.3%) and 91 reoperations in 69 patients (14.5%) were noted. The reoperations included 44 left-sided reoperations in 34 patients (7.1%), 35 right-sided reoperations in 30 patients (6.3%), and 12 other reoperations in 12 patients (2.5%). Among the 69 patients who underwent reoperation, those with left-sided reoperations had lower survival at 15 years after reoperation compared to those with non-left-sided reoperations (91.2% vs 100%; P  = .015; log-rank, 5.9). Multivariable analysis identified non-neonatal ASO, preoperative pulmonary regurgitation, intramural coronary artery, aortic arch repair, and concomitant left ventricular outflow tract obstruction relief as risk factors for left-sided reoperations. Reoperation-free survival was significantly higher in neonatal ASO compared with non-neonatal ASO (89.2% vs 75.2% at 20 years; P  < .001; log-rank, 13.4)., Conclusions: Hospital survivors of neonatal ASO had favorable long-term outcomes., (© 2023 The Author(s).)

We herein report a case of enterocutaneous fistula in a patient with autosomal dominant polycystic kidney disease (ADPKD). A 37-year-old Japanese man was admitted to our hospital. Three months prior to transfer to our hospital, he developed intense flank pain with gross hematuria. His serum creatinine had decreased to 7.8 mg/dL and hemodialysis was started, but gross hematuria persisted and he developed hypotension. Upon admission, plain chest radiography did not reveal any free air, but computed tomography (CT) showed generalized ventral subcutaneous air from the head to the lower extremities and enlarged kidneys. Enterography showed leakage of contrast medium from the descending colon into the subcutaneous area. C-reactive protein was 23.1 mg/dL. A colostomy was placed in the transverse colon proximal to the perforation, and systemic subcutaneous drainage was performed. The fever subsequently resolved, and the C-reactive protein test became negative. Three months later, renal artery embolization was performed, and 12 months thereafter, CT showed a marked decrease in kidney size. We assume that a markedly enlarged kidney leaded to intestinal perforation, which developed into an enterocutaneous fistula. Consequently, intestinal fluid leaked into the subcutaneous cavity of the abdominal wall and spread systemically, resulting in extensive subcutaneous abscesses., (© 2022. The Author(s).)

We evaluated kidney histology in a 43-year-old woman with autosomal dominant tubulointerstitial kidney disease subtype hepatocyte nuclear factor 1β. Magnetic resonance imaging showed multiple cysts in the renal medullary area, and computed tomography showed hypoplasia of the pancreatic body and tail. A kidney biopsy showed thinning of the cortex, size reduction of glomerular tuft area, proximal tubule clustering, fibrosis around the tubules, loss of peritubular capillaries, and multilayered epithelial cells of cortical collecting ducts; this last finding was consistent with so-called medullary dysplasia specific to congenital disease, in which the renal pelvic epithelial cells enter the collecting duct.

An 11 year-old boy underwent pulmonary vegetectomy and right ventricle-to-pulmonary artery conduit replacement for septic pulmonary embolism secondary to prosthetic conduit fungal endocarditis. He had previous surgical history of Senning/Rastelli procedure for corrected transposition of the great arteries at 5 years old. He was diagnosed with prosthetic fungal endocarditis caused by Candida parapsilosis, and suffered from growing vegetation and progressive septic pulmonary embolism despite fungal treatment. At emergent operation, pulmonary vegetectomy was performed under intermittent moderate hypothermic circulatory arrest, and infected conduit with vegetation was replaced. Approximately 2 years after the operation, he is well under anti-fungal medication., (© 2022. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

The recipient muscle status is closely associated with postoperative poor survival in recipients of living donor liver transplantation (LDLT). However, it is uncertain whether LDLT donor muscle quality and quantity affect graft quality. Hence, we analyzed the correlation between donor muscle status and graft function. We measured the skeletal muscle mass index (SMI) and intramuscular adipose tissue content (IMAC) of 380 LDLT donors. We examined the correlation between donor SMI or IMAC and graft mortality, the occurrence rates of small-for-size graft (SFSG) syndrome, and 6-month graft survival rates. The donor SMI had no effect on the occurrence of SFSG syndrome and graft survival, while a high IMAC in both male and female donors was significantly correlated with the rate of SFSG syndrome [high vs low: (male donors) 15.8% vs. 2.5%, p = 0.0003; (female donors) 12.8% vs. 3.1%, p = 0.0234] and 6-month graft survival rates [(male donors) 87.7% vs 95.9%, p = 0.02; (female donors) 83.0% vs. 99.0%, p < 0.0001]. Multivariate analysis revealed that a high donor IMAC (HR; 5.42, CI; 2.13-13.8, p = 0.0004) was an independent risk factor for 6-month graft survival, and the donor IMAC is useful for donor selection for high-risk recipients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tomiyama, Harada, Toshima, Nakayama, Toshida, Morinaga, Kosai-Fujimoto, Tomino, Kurihara, Takeishi, Nagao, Morita, Itoh and Yoshizumi.)

Although there have been a few liver transplantations (LTs) between identical twins, to our knowledge hepatic damage after LT in an immunosuppressant-free patient has not been reported. Autoimmune liver disease recurrence after LT is also a postoperative problem. In this follow-up to our previous report, we present the case of a 57-year-old man with acute liver failure who underwent living donor liver transplantation (LDLT) from an identical twin. Six months after LDLT, the patient was free from immunosuppressive medication and showed good liver function. However, 1 year after LDLT, he developed liver damage and was diagnosed with autoimmune hepatitis by liver biopsy. His liver function was improved with steroid pulse therapy and the resumption of immunosuppressive medications. Even after LDLT from an identical twin, careful management is required for patients to remain free of immunosuppressive medications, considering the background liver disease., (Copyright © 2022. Published by Elsevier Inc.)

Ototoxicity is a dose-limiting adverse event for concurrent chemoradiotherapy (CCRT) with high-dose cisplatin for locally advanced head and neck squamous cell carcinoma (HNSCC). Both irradiation to the Eustachian tube (ET) and weight loss are risk factors for patulous ET. The aim of this prospective, observational study was to elucidate the incidences of patulous ET conditions before and after CCRT in HNSCC patients by means of ET function tests. This prospective, observational study was conducted in 27 HNSCC patients who received CCRT with high-dose cisplatin, and ET function tests (sonotubometry and tubo-tympano-aerodynamic graphy) were performed before and 3 months after CCRT. Factors potentially affecting the incidence of patulous ET conditions after CCRT were evaluated. Of the 54 ears from 27 patients investigated, patulous ET conditions were observed in 12 ears (22.2%) from 9 patients (33.3%) before CCRT and 15 ears (27.8%) from 11 patients (40.7%) at 3 months after CCRT. Only patulous ET conditions before CCRT in each ear were significantly associated with patulous ET conditions after CCRT ( p  = 0.010). This is the first report to describe the incidences of patulous ET conditions before and after CCRT in HNSCC patients. HNSCC patients are potentially at higher risk of patulous ET., Competing Interests: Conflict of interestThe authors declare that they have no conflicts of interest., (© Association of Otolaryngologists of India 2022.)

Objective High-dose melphalan and autologous stem cell transplantation (ASCT) therapy for AL amyloidosis are now associated with reduced mortality based on the application of strict criteria. However, there is no long-term evidence concerning the performance of induction therapy with newer agents, such as bortezomib or daratumumab. Concerns regarding long-term relapse despite treatment with ASCT exist, and missing the opportunity to perform ASCT might occur if induction proves to not be efficacious and cardiac amyloidosis progression deprives the patients of a chance to receive ASCT. We herein report good amyloid control by vincristine, doxorubicin, and dexamethasone (VAD) induction therapy and argue the importance of induction therapy before ASCT. Methods We compared patients who underwent VAD induction and ASCT (VAD+ASCT) with patients who underwent frontline ASCT in our hospital. Patients A total of 26 patients with histologically proven AL amyloidosis were included (18 in the VAD+ASCT group and 8 in the frontline ASCT). Results In the VAD+ASCT group, the 10-year overall survival and renal response rates were 82% and 43%, respectively. The renal response rate at two years in the VAD+ASCT group was significantly better than that in the frontline ASCT group. Although there was no significant difference in the survival rates between the two groups, the time to next treatment or death was significantly better in the VAD+ASCT group than in the the frontline ASCT group. Acute kidney injury was the most frequent reason for failure to receive two courses of VAD, and early mortality was mainly due to gastrointestinal complications. Conclusion Considering that only those who underwent 2 courses of VAD experienced a 10-year renal response, induction therapy was deemed to be directly related to the long-term control of AL amyloidosis.

Purpose: We hypothesized that elderly patients with greater skeletal muscle mass have better activities of daily living (ADLs) than those with less skeletal muscle mass. The aim of this study was to evaluate the relationship between ADL improvement and changes in skeletal muscle mass among older patients ≥ 80 years of age who were undergoing rehabilitation for vertebral compression fracture (VCF)., Methods: This case-control study was conducted at a rehabilitation hospital. The participants were 149 patients aged ≥ 80 years undergoing VCF rehabilitation. Patients were divided into two groups based on changes in their skeletal muscle mass index (SMI) during the hospitalization period: one group with increased SMI and the other without increased SMI. Between-group and multivariate analyses were performed to evaluate the factors associated with SMI increase., Results: The functional independence measure (FIM) gain was significantly higher in the group with SMI increase (36.0 [27.0-52.5], p = 0.016) than in the group without SMI increase (29.0 [19.0-41.0]). SMI gain was significantly associated with motor FIM gain (coefficient, 4.857; 95% confidence interval, 1.311-8.403; p = 0.008). Motor FIM and MMSE on admission, the necessity of assistance in ADL before the injury, and Charlson Comorbidity Index, were also significantly associated with motor FIM gain., Conclusions: This study indicated that rehabilitation to gain skeletal muscle was effective in improving ADLs in elderly patients with VCF. We might encourage older patients with VCFs to undertake rehabilitation for the purpose of building skeletal muscle and improving their ADLs, and to not refrain from such rehabilitation due to old age and fractures., (© 2022. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

Abstract: Nasopharyngeal foreign bodies (FBs), which are generally caused by a strong, external force, are seldomly encountered. Removing these FBs is challenging for otorhinolaryngological surgeons because of the vital structures surrounding the nasopharynx, such as the skull base, cranial nerves, and internal carotid artery. Here, the authors report the case of a 69-year-old man referred to our hospital after accidentally cutting his face while using a grinder. Grinder fragments were deeply embedded in the face, thus becoming nasopharyngeal FBs. The authors evaluated three-dimensional volume rendering images and immediately removed these FBs using an endoscopic endonasal transseptal approach under general anesthesia. The postoperative course was uneventful. Using the endoscopic endonasal transseptal approach after evaluating preoperative three-dimensional volume rendering images may help eliminate nasopharyngeal FBs safely., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by Mutaz B. Habal, MD.)