Anorectal Transplantation: The First Long-term Success in a Canine Model.

OBJECTIVE: Anorectal transplantation is a challenging procedure but a promising option for patients with weakened or completely absent anorectal function. SUMMARY BACKGROUND DATA: We constructed a canine model of anorectal transplantation, evaluated the long-term outcomes, and controlled rejection and infection in allotransplantation. METHODS: In the pudendal nerve function study, 6 dogs were randomly divided into 2 groups, transection and anastomosis, and were compared with a control using anorectal manometry, electromyography, and histological examination. In the anorectal transplantation model, 4 dogs were assigned to 4 groups: autotransplant, allotransplant with immunosuppression, allotransplant without immunosuppression, and normal control. Long-term function was evaluated by defecography, videography, and histological examination. RESULTS: In the pudendal nerve function study, anorectal manometry indicated that the anastomosis group recovered partial function 6 months postoperatively. Microscopically, the pudendal nerve and the sphincter muscle regenerated in the anastomosis group. Anorectal transplantation was technically successful with a 3-stage operation: colostomy preparation, anorectal transplantation, and stoma closure. The dog who underwent allotransplantation and immunosuppression had 2 episodes of mild rejection, which were reversed with methylprednisolone and tacrolimus. The dog who underwent allotransplantation without immunosuppression had a severe acute rejection that resulted in graft necrosis. Successful dogs had full defecation control at the end of the study. CONCLUSIONS: We describe the critical role of the pudendal nerve in anorectal function and the first long-term success with anorectal transplantation in a canine model. This report is a proof-of-concept study for anorectal transplantation as a treatment for patients with an ostomy because of anorectal dysfunction.

Continuous cyclosporine a infusion in patients with severe Kawasaki disease.

BACKGROUND: The efficacy and safety of continuous intravenous infusion of cyclosporine A (CICsA) in patients with intravenous immunoglobulin-resistant Kawasaki disease are unclear. METHODS: Between 2010 and 2020, 83 patients with Kawasaki disease that was not responsive to intravenous immunoglobulin (total dose ≥ 4 g/kg) were enrolled. All patients were started on CICsA (3 mg/kg/day) and switched to oral cyclosporine A (CsA) (4-6 mg/kg/day). Treatment efficacy, occurrence of coronary artery lesions (CALs), and laboratory parameters were evaluated. Patients were divided into two groups according to CICsA response: the responder group (afebrile ≤24 h after CICsA without additional treatment) and the weak responder group (afebrile >24 h after CICsA requiring additional treatment). RESULTS: Fifty-five patients became afebrile within 24 and 74 h became afebrile in less than 72 h. Adverse events included hypertension in four and hyperkalemia in two patients. Thirty-nine patients were defined as responders and 44 patients as weak responders. There were no significant differences in CAL between the two groups. In weak responders, white blood cells, neutrophils, and C-reactive protein levels were higher, and albumin, immunoglobulin G, and CsA concentration were lower than in responders, indicating that weak responders had more severe inflammatory findings. However, there were no significant differences in CAL. Logistic regression analysis revealed that the response to treatment for CICsA was associated with immunoglobulin G levels at baseline and CsA concentrations the day after CICsA. CONCLUSION: Although CICsA required additional treatments in about half of the cases, a favorable clinical course was observed by using this strategy, especially for reducing CAL.

An Adolescent Patient with Sick Sinus Syndrome Complicated by Hypothyroidism Carrying an SCN5A Variant.

Previous studies have reported that hypothyroidism can lead to sick sinus syndrome (SSS) or other rhythm disturbances. Variants in the alpha subunit of the cardiac sodium channel (SCN5A) are known to be among the genetic causes of SSS. We encountered an adolescent patient with SSS and hypothyroidism who also harbored an SCN5A variant. The patient was a 13-year-old girl who was referred to our hospital because of bradycardia identified during a school electrocardiography screening. Clinical examination revealed severe hypothyroidism due to Hashimoto thyroiditis and SSS. After levothyroxine supplementation, her symptoms of hypothyroidism improved; however, the SSS did not. Genetic testing revealed a heterozygous variant (c.1066 G>A, p.Asp356Asn) in SCN5A. This is the first report of the coexistence of SSS due to an SCN5A variant and severe hypothyroidism in an adolescent patient. While patients with SCN5A variants exhibit phenotypic heterogeneity due to the presence of various modifiers, the presence of severe hypothyroidism may affect the development of SSS. This case highlights the importance of genetic analysis, including testing for SCN5A variants, in patients with hypothyroidism complicated by SSS or cardiac conduction disorders.

A Case of Infantile Mitochondrial Cardiomyopathy Treated with a Combination of Low-Dose Propranolol and Cibenzoline for Left Ventricular Outflow Tract Stenosis.

Hypertrophic cardiomyopathy is a common cardiac complication in mitochondrial disorders, and the morbidity rate in neonatal cases is up to 40%. The mortality rate within 3 months for neonatal-onset mitochondrial cardiomyopathy is known to be high because there is currently no established treatment.We report the case of a male infant with neonatal-onset mitochondrial disorder presenting lactic acidosis and hypertrophic cardiomyopathy. Genetic analysis of the patient revealed recurrent m.13513G>A, p.Asp393Asn in mitochondrially encoded NADH dehydrogenase 5 gene (MT-ND5). Low-dose propranolol was initially administered for cardiomyopathy; however, he developed hypertrophic obstructive cardiomyopathy (HOCM) at 3 months of age. To reduce the risk of hypoglycemia associated with high-dose propranolol, cibenzoline, a class Ia antiarrhythmic drug, was added at a dose of 2.5 mg/kg/day and increased weekly to 7.5 mg/kg/day with monitoring of the blood concentration of cibenzoline. Left ventricular outflow tract stenosis (LVOTS) dramatically improved from 5.4 to 1.3 m/second in LVOTS peak velocity after 6 weeks, without notable adverse effects. The plasma N-terminal pro-brain natriuretic peptide level decreased from 65,854 to 10,044 pg/mL. Furthermore, myocardial hypertrophy also improved, as the left ventricular mass index decreased from 173.1 to 108.9 g/m2 after 3 months of the treatment.The administration of cibenzoline, in conjunction with low-dose propranolol, may serve an effective treatment for HOCM in infantile patients with mitochondrial disorders.

[A Case of Pancreatic Cancer That Was Radically Resected after Chemotherapy and Radiation Therapy, but Recurred Early and Followed a Rapid Course].

A 71-year-old man presented to our hospital with abdominal pain. He was diagnosed with acute pancreatitis and pancreatic cancer. Peritoneal washing cytology(CY)was positive, and laparotomy findings revealed severe inflammatory changes of pancreatitis, suggesting a high likelihood of the need for combined resection of other organs. Therefore, following the exploratory laparotomy, mFOLFIRINOX was initiated as chemotherapy. After 24 courses of mFOLFIRINOX, he developed drug-induced pneumonia. Therefore, chemotherapy was interrupted, and a steroid was started. Radiotherapy was administered during steroid tapering. There was no evidence of local progression or distant metastasis. A radical resection that included pancreaticoduodenectomy and right hemicolectomy was performed 23 months after the exploratory laparotomy. CY was negative and R0 resection was achieved. However, 5 months after the operation, he developed liver abscesses and cholangitis and was suspected to have liver metastasis. He underwent PTAD and PTCD, but died due to liver failure 8 months postoperatively. The early recurrence of this case might have been caused by the lack of postoperative chemotherapy due to his frailty. Surgical indications should be carefully judged if there is a high risk of recurrence after NAC and a high possibility that ACT cannot be performed after radical surgery.

Role of respiratory uncoupling in drug-induced mitochondrial permeability transition.

Mitochondrial injury contributes to severe drug-induced liver injury. Particularly, mitochondrial permeability transition (MPT) is thought to be relevant to cytolytic hepatitis. However, the mechanism of drug-induced MPT is unclear and prediction of MPT is not adequately evaluated in the preclinical stage. In a previous study, we found that troglitazone, a drug withdrawn due to liver injury, induced MPT via mild depolarization probably resulting from uncoupling. Herein, we investigated whether other drugs that induce MPT share similar properties as troglitazone, using isolated mitochondria from rat liver. Of the 22 test drugs examined, six drugs, including troglitazone, induced MPT and showed an uncoupling effect. Additionally, receiver operating characteristic analysis was conducted to predict the MPT potential from the respiratory control ratio, an indicator of uncoupling intensity. Results showed that 2.5 was the best threshold that exhibited high sensitivity (1.00) and high specificity (0.81), indicating that uncoupling was correlated with MPT potential. Activation of calcium-independent phospholipase A2 appeared to be involved in uncoupling-induced MPT. Furthermore, a strong relationship between MPT intensity and the uncoupling effect among similar compounds was confirmed. These results may help in predicting MPT potential using cultured cells and modifying the chemical structures of the drugs to reduce MPT risk.

[Ischemic Colitis after Closure of Temporary Ileostomy for Low Anterior Resection of Rectal Cancer in a Dialysis Patient-A Case Report].

Dialysis patients are at increased risk of ischemic colitis and are likely to develop irreversible ischemic colitis. We report a rare case of ischemic colitis after the closure of a temporary ileostomy for low anterior resection(LAR)of rectal cancer in a dialysis patient. A 77-year-old man undergoing maintenance dialysis was diagnosed as having colorectal cancer with a type 2 tumor at the anastomosis site of high anterior resection performed for sigmoid colon cancer 14 years ago. After undergoing excision which included the anastomosis site of the previous operation, LAR with anastomosis in the transverse colon and rectum and temporary ileostomy were performed. Seven months later, closure of the temporary ileostomy was performed, which resulted in ileus and septic shock. Computed tomography(CT)revealed inflammation in the colon on the oral side of the anastomosis, which was diagnosed as ischemic colitis. Ischemic colitis did not improve with conservative treatment, and fever reoccurred at each maintenance dialysis session. Therefore, ileostomy was performed again, but multiple organ failure due to disseminated intravascular coagulopathy(DIC)progressed and he died. It is considered that Hartmann's operation should be selected for dialysis patients with serious underlying diseases, and if ischemic colitis is observed after closure of the stoma temporary colostomy in such patients, the lesion site of ischemic colitis should be excised promptly and colostomy should be performed again.

Simultaneous Volumetric and Functional Assessment of the Right Ventricle in Hypoplastic Left Heart Syndrome After Fontan Palliation, Utilizing 3-Dimensional Speckle-Tracking Echocardiography.

BACKGROUND: Right ventricular (RV) volumetric and functional assessments are both crucial for the management of patients with hypoplastic left heart syndrome (HLHS). 3-dimensional echocardiography (3DE) for volume measurements and 2D speckle-tracking echocardiography (2D-STE) for strain analysis are performed separately. 3D-STE is capable of evaluating those parameters simultaneously and providing principal strain (PS), unifying the concepts of myofiber orientation and contraction into a single, maximal contractile direction. However, the application of 3D-STE to HLHS has not been studied and so became the aim of our study.Methods and Results:64 HLHS patients after Fontan palliation underwent 3D-STE analysis measuring RV end-diastolic volume index (EDVi), ejection fraction (EF), global PS (GPS), global circumferential strain (GCS), and global longitudinal strain (GLS). Volume measurements were compared between 3D-STE and 3DE, and strains were compared between 3D- and 2D-STE. EDVi and EF showed strong correlations between 3D-STE and 3DE (r=0.93 and 0.87, respectively). GCS and GLS showed moderate correlations between 3D- and 2D-STE (r=0.65 and 0.61, respectively). GPS showed highest magnitude and excellent correlation with EF (r=-0.95). CONCLUSIONS: Simultaneous volumetric and functional assessment by 3D-STE was a useful method in this HLHS cohort. PS is a promising parameter for evaluating the RV function of HLHS, which could be useful during longitudinal follow-up.

Percutaneous Atrial Septal Defect Closure in Adult Ebstein's Anomaly with Exertional Hypoxemia.

In Ebstein's anomaly, percutaneous atrial septal defect (ASD) closure for the treatment of hypoxemia due to a right-to-left interatrial shunt remains controversial. We report the case of a 40-year-old woman with Ebstein's anomaly who developed cyanosis and shortness of breath on exercise. Her symptoms improved after percutaneous ASD closure and her clinical course has been good during follow-up. The balloon ASD occlusion test, combined with dobutamine stimulation before the procedure, is useful to confirm treatment indication. A prior electrophysiological evaluation is also important because Ebstein's anomaly is often complicated by atrioventricular recurrent tachycardia.

Effect of scheduled intravenous acetaminophen on postoperative nausea and vomiting in patients undergoing laparoscopic gynecologic surgery.

PURPOSE: The aim of this study was to assess the effect of scheduled intravenous acetaminophen (SIVA) on the incidence of postoperative nausea and vomiting (PONV) in patients undergoing laparoscopic gynecologic surgery (LGS). METHODS: This retrospective observational study identified consecutive patients who underwent LGS at our institution from January to November of 2017 and were managed with either our hospital's old protocol (Group H) or a new protocol using SIVA (Group S). Primary outcomes included the incidences of PONV and the amount of additional antiemetic required in the postoperative period. The secondary outcomes included the pain score on postoperative day 1, the requirement for additional analgesic medications, and the length of hospitalization (LOH). RESULTS: Patients in Group S had significantly lower incidences of PONV from postoperative days 0 to 1 and required significantly less antiemetics or tramadol than those in Group H (P = 0.0085). Patients at a low risk for PONV in Group S had significantly lower incidences of PONV than those in Group H (P = 0.0129). Further, the amount of additional tramadol required was lower in Group S than in Group H (P = 0.0021). CONCLUSION: Introduction of SIVA into the postoperative pain management protocol of LGS may reduce the incidence of PONV and the amount of adjunctive antiemetic medication required from postoperative days 0 to 1. In patients undergoing LGS, PONV prophylaxis using antiemetics should be prescribed depending on PONV risk profile; however, SIVA prophylaxis can be used in all patients regardless of PONV risk profile.

Zweigelt and Niagara skin extracts suppress cyclobutane pyrimidine dimer formation due to UV irradiation in NHEK cells: first attempt.

The grape skins after pressing the juice are a major problem for winery. However, because it contains a large amount of polyphenols, development of effective usages are expected to construct sustainable waste use. In this study, we examined whether grape skin extract is effective for recovery of DNA damage caused by UV irradiation. Extract from Zweigelt and Niagara skin was prepared by methanol, and UV irradiation was performed at 10 mJ/cm2 (250 nm) and 15 mJ/cm2 (290 nm) using human normal skin cells. As results, the decreased cell viability due to UV irradiation was improved by adding Niagara or Zweigelt skin extract. On the other hand, cyclobutane pyrimidine dimer production due to UV irradiation decreased significantly by Niagara or Zweigelt extract. In addition, the effects of grape skin extracts on the expression of sirtuin gene were also examined.

The impact of epidural catheter insertion level on pain control after esophagectomy for esophageal cancer.

BACKGROUND: Although the effectiveness of epidural anesthesia on pain control after esophagectomy has been reported, the appropriate insertion level of the epidural catheter remains unclear for adequate postoperative pain control. We investigated the relationship between the epidural catheter insertion level and postoperative pain control after esophagectomy for esophageal cancer. METHODS: We analyzed retrospectively 63 patients who underwent McKeown esophagectomy for esophageal cancer between October 2014 and November 2018. The epidural catheter was inserted at the T4-T10 level before general anesthesia induction, and epidural anesthesia was started during the operation. In the analysis, the epidural catheter insertion level was divided into three groups (over T6/T7, T7/T8, and under T8/T9) and determined. Postoperative pain was evaluated a numeric rating scale (NRS) for at least 7 postoperative days, and the first NRS after extubation was used to evaluate the impact of the epidural catheter insertion level on pain control. RESULTS: Ten patients (15.9%) failed pain control. The χ2 test and a forward stepwise logistic regression analysis revealed that only the epidural catheter insertion level affected pain control (P < 0.05). The T7/T8 insertion level significantly decreased postoperative pain after esophagectomy. In the subgroup analysis, epidural catheter insertion under T8/T9 significantly increased postoperative pain after esophagectomy when thoracoscopy/laparoscopy was assisted. No significant differences were observed in the incidence of postoperative complications among the epidural catheter insertion levels. CONCLUSIONS: The T7/T8 epidural catheter insertion level contributed to postoperative pain relief and could lead to enhanced recovery after esophagectomy for esophageal cancer.

Estimated glomerular filtration rate after nephrectomy for Wilms tumor.

BACKGROUND: The aim of this study was to assess long-term residual kidney function after unilateral nephrectomy for non-syndromic Wilms tumor (NSWT). METHODS: Of the patients who underwent one-sided NSWT at Tohoku University Hospital between 1977 and 2003, nine were followed up until age ≥18 years. For these nine patients, we retrospectively evaluated estimated glomerular filtration rate (eGFR) in childhood (3-10 years old), adolescence (11-17 years old) and adulthood (≥18 years). RESULTS: Mean age at the last follow up was 23.0 years. Tumor classification was as follows: stage I tumor, n = 6; stage II tumor, n = 3; mixed-type nephroblastoma, n = 8; and congenital mesoblastic nephroma, n = 1. Mean eGFR was 101.3 ± 21.2 mL/min/1.73 m2 in childhood, 106.0 ± 32.1 mL/min/1.73 m2 in adolescence and 100.5 ± 20.7 mL/min/1.73 m2 in adulthood. Therefore, no significant change in eGFR was observed over the three life stages evaluated. Further, none of the patients met the diagnostic criteria for chronic kidney disease by early adulthood. CONCLUSIONS: eGFR after unilateral nephrectomy in patients with NSWT remained ≥60 mL/min/1.73 m2 during the transition from childhood to early adulthood, with no development of chronic kidney disease or end-stage kidney failure.

Xq26.1-26.3 duplication including MOSPD1 and GPC3 identified in boy with short stature and double outlet right ventricle.

Xq25q26 duplication syndrome has been reported in individuals with clinical features such as short stature, intellectual disability, syndromic facial appearance, small hands and feet, and genital abnormalities. The symptoms are related to critical chromosome regions including Xq26.1-26.3. In this particular syndrome, no patient with congenital heart disease was previously reported. Here, we report a 6-year-old boy with typical symptoms of Xq25q26 duplication syndrome and double outlet right ventricle (DORV) with pulmonary atresia (PA). He had the common duplicated region of Xq25q26 duplication syndrome extending to the distal region including the MOSPD1 locus. MOSPD1 regulates transforming growth factor beta (TGFß) 2,3 and may be responsible for cardiac development including DORV. In the patient's lymphocytes, mRNA expression of TGFß2 was lower than control, and might cause DORV as it does in TGFß2-deficient mice. Therefore, MOSPD1 is a possible candidate gene for DORV, probably in combination with GPC3. Further studies of the combined functions of MOSPD1 and GPC3 are needed, and identification of additional patients with MOSPD1 and GPC3 duplication should be pursued.

[Tetralogy of Fallow with Total Anomalous Pulmonary Vein Return and Atrial Septal Defect;Successful Two-staged Surgical Management;Report of a Case].

A combination of tetralogy of Fallot( TOF) and total anomalous pulmonary venous return(TAPVR) is rare and results in chronic volume and pressure load of the right side of the heart and underfilling of the left heart. We report a successful 2-staged surgical correction of TOF associated with TAPVR and atrial septal defect. The patient was unsuitable for total primary intracardiac correction because the volume of the left ventricle was considered to be small. First, repair of anomalous pulmonary venous return and palliative right ventricle outflow tract reconstruction were simultaneously performed in 2 months of birth. One year after 1st operation, cardiac catheterization revealed that normalization of left ventricle volume, so 2nd operation was planned. Total correction of ventricular septal defect and right ventricle outflow reconstruction was performed and the patient was discharged on the 21st postoperative day with good hemodynamic status.

Dominant ectosymbiotic bacteria of cellulolytic protists in the termite gut also have the potential to digest lignocellulose.

Wood-feeding lower termites harbour symbiotic gut protists that support the termite nutritionally by degrading recalcitrant lignocellulose. These protists themselves host specific endo- and ectosymbiotic bacteria, functions of which remain largely unknown. Here, we present draft genomes of a dominant, uncultured ectosymbiont belonging to the order Bacteroidales, 'Candidatus Symbiothrix dinenymphae', which colonizes the cell surface of the cellulolytic gut protists Dinenympha spp. We analysed four single-cell genomes of Ca. S. dinenymphae, the highest genome completeness was estimated to be 81.6-82.3% with a predicted genome size of 4.28-4.31 Mb. The genome retains genes encoding large parts of the amino acid, cofactor and nucleotide biosynthetic pathways. In addition, the genome contains genes encoding various glycoside hydrolases such as endoglucanases and hemicellulases. The genome indicates that Ca. S. dinenymphae ferments lignocellulose-derived monosaccharides to acetate, a major carbon and energy source of the host termite. We suggest that the ectosymbiont digests lignocellulose and provides nutrients to the host termites, and hypothesize that the hydrolytic activity might also function as a pretreatment for the host protist to effectively decompose the crystalline cellulose components.

Femoral nerve block-sciatic nerve block vs. femoral nerve block-local infiltration analgesia for total knee arthroplasty: a randomized controlled trial.

BACKGROUND: The use of femoral nerve block (FNB) combined with sciatic nerve block (SNB) after total knee arthroplasty (TKA) has recently become controversial. Local infiltration analgesia (LIA) has been reported to be effective for postoperative TKA pain control. We aimed to assess whether LIA with continuous FNB is as effective as SNB combined with continuous FNB. METHODS: This was a prospective, randomized, single-center, observer-blinded, parallel group comparison trial of 34 American Society of Anesthesiologists (ASA) physical status 1-3 patients who underwent TKA and fulfilled the inclusion and exclusion criteria. Patients were randomized into two groups: a periarticular LIA and FNB group (group L, n = 17), and an SNB and FNB group (group S, n = 17). In both groups, participants received FNB with 20 mL of 0.375% ropivacaine, and 5 mL h(-1) of 0.2% ropivacaine after surgery. In group L, participants received 100-ml injections of 0.2% ropivacaine and 0.5 mg epinephrine to the surgical region. In group S, participants received SNB with 20 ml of 0.375% ropivacaine. After TKA, Numeric Rating Scale (NRS) scores for the first 24 h post-operation were compared via repeated-measures analysis of variance (ANOVA) as the primary outcome. Other outcome measures included NRS score changes within groups, area under the curve for the NRS scores, total analgesic dose, change in knee flexion and extension, pain control satisfaction, nausea and vomiting, and hospital stay duration. RESULTS: NRS score changes were greater in group L than in group S (P < 0.01, ANOVA) and greater in group L than in group S at three postoperative time points: 3 h (P < 0.01), 6 h (P < 0.01), and 12 h (P = 0.013; Mann-Whitney U test). Changes in the mean NRS score were observed in each group (P < 0.01, Friedman test). No significant differences were detected in the other outcome measures (Mann-Whitney U, Wilcoxon signed-rank, and chi-squared tests). CONCLUSIONS: Sciatic nerve block with femoral nerve block is superior to local anesthetic infiltration with femoral nerve block for postoperative pain control within 3-12 h of total knee arthroplasty. TRIAL REGISTRATION: UMIN-CTR ID: 000013364 R: 000015591.

[Perioperative Management of Emergency Gastrointestinal Surgery in a Patient with Left Ventricular Non-compaction].

Left ventricular non-compaction (LVNC) is a rare congenital cardiomyopathy characterized by heart failure, arrhythmia, and embolic events. A 65-year-old man, previously diagnosed as LVNC, was admitted to the emergency department with severe abdominal pain. He was diagnosed as appendicitis and treated conservatively with antibiotics. The echocardiogram examination showed left ventricular ejection fraction of less than 25%, and his B-type natriuretic peptide assay was > 5,000 pg x ml(-1) on admission. Ten days after admission, he underwent emergency surgery for suspected perforation of vermiform appendix. Transesophageal echocardiography (TEE) was used for real-time evaluation of cardiac function and restrictive fluid management during surgery. He was transferred to intensive care unit (ICU) for postoperative care, and extubated 16 hours after surgery. On the third postoperative day, he was discharged from ICU without any complications. We consider that perioperative hemodynamic management with TEE may be useful for gastrointestinal tract surgeries in patients with severe cardiac disease, such as LVNC.

Comparison of local infiltration of analgesia and sciatic nerve block in addition to femoral nerve block for total knee arthroplasty.

We conducted a prospective randomized controlled trial to test the null hypothesis that there is no difference between sciatic nerve block (SNB) and local infiltration of analgesia (LIA) regarding postoperative analgesia after total knee arthroplasty (TKA), when administrated in addition to femoral nerve block (FNB). Forty-six patients scheduled for TKA were randomized into two groups: concomitant administration of FNB and SNB or FNB and LIA. Average pain scores during the first 21days after surgery were similar in the two groups and remained at low level. There was no significant difference in the need for adjuvant analgesics, patient satisfaction level, the time to achieve rehabilitation goals, and length of hospital stay. The LIA offers a potentially safer alternative to SNB as an adjunct to FNB.

Time-restricted feeding has a limited effect on hepatic lipid accumulation, inflammation and fibrosis in a choline-deficient high-fat diet-induced murine NASH model.

Nonalcoholic steatohepatitis (NASH) occurs worldwide and is characterized by lipid accumulation in hepatocytes, hepatic inflammation, fibrosis, and an increased risk of cirrhosis. Although a major proportion of NASH patients exhibit obesity and insulin resistance, 20% lack a high body mass and are categorized as "non-obese NASH". Time-restricted feeding (TRF), limiting daily food intake within certain hours, improves obesity, lipid metabolism, and liver inflammation. Here, we determined whether TRF affects NASH pathology induced by a choline-deficient high-fat diet (CDAHFD), which does not involve obesity. TRF ameliorated the increase in epididymal white adipose tissue and plasma alanine transaminase and aspartate transaminase levels after 8 weeks of a CDAHFD. Although gene expression of TNF alpha in the liver was suppressed by TRF, it did not exhibit a suppressive effect on hepatic lipid accumulation, gene expression of cytokines and macrophage markers (Mcp1, IL1b, F4/80), or fibrosis, as evaluated by Sirius red staining and western blot analysis of alpha-smooth muscle actin. A CDAHFD-induced increase in gene expression related to fibrogenesis (Collagen 1a1 and TGFß) was neither suppressed by TRF nor that of alpha-smooth muscle actin but was increased by TRF. Our results indicated that TRF has a limited suppressive effect on CDAHFD-induced NASH pathology.