Clinical Efficacy and Body Composition Changes with Sodium Glucose Cotransporter 2 Inhibitor/Glucagon-like Peptide-1 Antagonist Combination Therapy in Patients with Type 2 Diabetes Mellitus-associated Nonalcoholic Fatty Liver Disease.

Objective Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) treatment guidelines recommend sodium glucose cotransporter 2 inhibitor (SGLT2I) and glucagon-like peptide-1 agonist (GLP-1A) therapy in patients with type 2 diabetes mellitus (T2DM). SGLT2I improves the pathological condition of NAFLD/NASH in T2DM patients. However, cases of rebound during long-term SGLT2I treatment have been reported. This study investigated the efficacy of SGLT2I and GLP-1A combination therapy in diabetic patients with NAFLD by examining changes in computed tomography (CT)-based body composition and clinical outcomes. Methods Fifteen patients (5 men/10 women) with T2DM-associated NAFLD who had not responded to SGLT2I treatment and were being treated with GLP-1A combination therapy were included. Changes in the liver function, visceral adipose tissue index (VATI), and subcutaneous adipose tissue index (SATI) were compared using CT to evaluate the body composition. Results SGLT2I significantly improved alanine aminotransferase (28.0 to 13.0 IU/L), alkaline phosphatase (250.0 to 77.0 IU/L), and gamma glutamyl transpeptidase (23.0 to 12.0 IU/L) levels. The body mass index (BMI) decreased from 25.7 to 25.2 kg/m2. A CT-based analysis showed a significant improvement in SATI (80.9 to 66.1, p=0.002), with no significant change in VATI (53.2 to 51.5). GLP-1A addition improved the BMI (25.2 to 23.5 kg/m2) and hemoglobin A1c (6.5% to 6.2%, p=0.001). A further analysis revealed additional improvement in SATI (66.1 to 56.6, p=0.007) and a significant decrease in VATI (51.5 to 48.3, p=0.001). Conclusion SGLT2I and GLP-1A combination therapy improved the liver function, body composition, and glycemic control in diabetic patients with NAFLD/NASH, as well as SATI and VATI. The optimal timing of combination therapy remains to be determined.

Hepatic steatosis and skeletal muscle alterations during the COVID-19 lockdown in a cohort of patients with chronic liver disease in Japan.

AIM: Following the coronavirus disease outbreak, a state of public emergency was declared worldwide, which enforced lifestyle changes. This study therefore aimed to investigate the changes in lifestyle, body composition, hepatic steatosis, and fibrosis in patients with chronic liver disease (CLD) under lockdown. METHODS: During the lockdown period, 1344 patients with CLD answered a lifestyle questionnaire. In 298 patients, body composition and liver stiffness measure (LSM)/controlled attenuation parameter (CAP) were analyzed by InBody and FibroScan, respectively, and serial data were obtained in 137 patients. RESULTS: More than half of the CLD patients answered decreases in physical activity and frequency of outings during lockdown, while diet was less affected. Overall, 58% of patients showed elevations in CAP values, which were not different statistically over time. Women, but not men, were more likely to increase CAP values during lockdown. Neither LSM nor serum fibrosis markers were elevated chronologically during lockdown. In men, body mass index (BMI), body fat percentage, and visceral fat area (VFA) were significantly increased, whereas in women, lower-limb muscle mass was significantly decreased. Patients with decreased SMI showed elevations in CAP and VFA values, and patients who exercised less showed increases in BMI. CONCLUSION: In response to lockdown, men tended to increase body fat but the degree of hepatic steatosis was less affected, while women were more likely to exacerbate hepatic steatosis with skeletal muscle loss among CLD patients. Gender-specific approaches need to be established for management of CLD patients to avoid exacerbation or comorbidity of steatotic liver disease.

Efficacy of Adding Locoregional Therapy in Non-Complete Remission Hepatocellular Carcinoma Treated With Atezolizumab Plus Bevacizumab: A Preliminary Study.

BACKGROUND/AIM: Atezolizumab plus bevacizumab (Atez/Bev) therapy is extremely effective and has a high response rate in hepatocellular carcinoma (HCC) treatment. This study investigated the efficacy of adding locoregional therapy with Atez/Bev for non-complete response (CR) HCC cases. PATIENTS AND METHODS: Twenty-eight HCC patients without CR during Atez/Bev therapy received locoregional therapy, and treatment efficacy was evaluated based on the modified RECIST criteria. RESULTS: The study included 23 male and five female participants with a mean age of 73.5 years. In the Atez/Bev and locoregional combination therapy effective group, both transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) were combined in all patients. A significant reduction in neutrophil-to-lymphocyte ratio (NLR) was observed after adding locoregional therapy (p=0.039). Moreover, a combination of TACE and RFA was performed in all patients of the CR group. When assessing the add-on effect of the combination of TACE and RFA in the progressive disease (PD) group, seven patients were found to achieve non-PD. For patients who did not achieve PD, a significant NLR reduction was noted after the addition of locoregional therapy. CONCLUSION: Adding locoregional therapy such as TACE/RFA was found to exert an effect even in non-CR patients who had received Atez/Bev therapy. A reduction in NLR after locoregional therapy was noted. Even when a response is not obtained during Atez/Bev therapy, it is important to avail the option to add locoregional therapy, as it may contribute to improved prognosis via immune modulation with tolerable adverse reactions.

Risk factors for difficult endoscopic hemostasis for colonic diverticular bleeding and efficacy and safety of transcatheter arterial embolization.

This study aimed to investigate the risk factors for difficult endoscopic hemostasis in patients with colonic diverticular bleeding and to evaluate the efficacy and safety of transcatheter arterial embolization (TAE) for colonic diverticular bleeding. This study included 208 patients with colorectal diverticular hemorrhage. The non-interventional radiotherapy group consisted of patients who underwent successful spontaneous hemostasis (n = 131) or endoscopic hemostasis (n = 56), whereas the interventional radiotherapy group consisted of patients who underwent TAE (n = 21). Patient clinical characteristics were compared to identify independent risk factors for the interventional radiotherapy group. Furthermore, the hemostasis success rate, rebleeding rate, complications, and recurrence-free survival were compared between patients who underwent endoscopic hemostasis and those who underwent TAE. Bleeding from the right colon (odds ratio [OR]: 7.86; 95% confidence interval [CI]: 1.6-38.8; P = .0113) and systolic blood pressure <80 mm Hg (OR: 0.108; 95% CI: 0.0189-0.62; P = .0126) were identified as independent risk factors for the interventional radiology group. The hemostasis success rate (P = 1.00), early rebleeding rate (within 30 days) (P = .736), late rebleeding rate (P = 1.00), and recurrence-free survival rate (P = .717) were not significantly different between the patients who underwent TAE and those who underwent endoscopic hemostasis. Patients in the TAE group experienced more complications than those in the endoscopic hemostasis group (P < .001). Complications included mild intestinal ischemia (19.0%) and perforation requiring surgery (4.8%). Patients who required interventional radiotherapy were more likely to bleed from the right colon and presented with a systolic blood pressure of <80 mm Hg. TAE is an effective treatment for patients with colonic diverticular hemorrhage that is refractory to endoscopic hemostasis. However, complications must be monitored carefully.

Benefit of an action camera in endoscopy education for medical students under COVID-19.

BACKGROUND: Endoscopy is an important form of clinical gastroenterology education because it gives students the opportunity to learn about diagnosis procedures and even treatment. During the COVID-19 pandemic, medical students were observed from outside the endoscopy room due to the risk of airborne infection. In this study, we investigated the efficacy of combining endoscopy education with doctor's-eye-view videos of the procedure obtained using live-action cameras (GoPro®). METHODS: From February to May 2021, endoscopists wore GoPro Hero8 cameras on their heads to display a doctor's-eye view video outside the room. The efficacy of the GoPro videos in combination with endoscopic monitoring was evaluated by 15 participating medical students. The participants rated the efficacy on a 5-point scale and commented on the positive and negative points. RESULTS: A total of 78.6% of participants evaluated the GoPro as good; 57.2% answered that it increased their understanding, with 71.4% stating that it increased their understanding of procedures in particular. A total of 85.7% of the students answered that their interest in endoscopy had increased, and 85.7% evaluated the benefit of the GoPro videos as good. In addition, 64.3% answered that the method was effective in preventing COVID-19 infection. Education using GoPro videos enabled students to feel as if they were conducting the endoscopy themselves and enabled them to concentrate on learning. CONCLUSIONS: Practical endoscopic education using a GoPro is an effective educational tool that not only increases understanding of endoscopic practice but also stimulates students' interest and awareness of their future as doctors.

Effects of body composition and liver function after long-term pemafibrate treatment on dyslipidemia-associated non-alcoholic fatty liver disease.

Aim of the study: Owing to the association between non-alcoholic fatty liver disease (NAFLD) and dyslipidemia, there is a need for new treatment strategies to manage both conditions concomitantly. Our aim in this study was to evaluate the effectiveness of pemafibrate in alleviating dyslipidemia-associated NAFLD, including the evaluation of its effects on liver function and body composition. Material and methods: The study sample included 67 patients with dyslipidemia-associated NAFLD (29 males, mean age 65.7 years [range, 58.4-73.7]) who were administered pemafibrate continuously for a period of at least 12 months, between June 2019 and January 2022. Outcomes were the change in body composition indices (visceral adipose tissue index - VATI, subcutaneous adipose tissue index - SATI, and skeletal muscle index - SMI), lipid biochemistry, and liver function, reserve, and fibrosis score, from baseline to the 12-month time point of pemafibrate treatment. Results: Pemafibrate treatment improved liver function (alanine aminotransferase, aspartate aminotransferase, g-glutamyl transpeptidase, and alkaline phosphatase), and lipid biochemistry (triglycerides and total cholesterol). Improvements in ferritin and hepatic reserve (Mac-2 binding protein, albumin-to-bilirubin score, and NAFLD fibrosis score) were also observed, as well as a decrease in SATI. Conclusions: Pemafibrate improved dyslipidemia, liver function, and hepatic reserve. The positive effects of pemafibrate on body composition likely contributed to the improvements in liver function. Longer-term treatment may be necessary to influence VATI and thus to further evaluate the relationship between improved body composition and NAFLD with pemafibrate treatment.

Prognostic Value of TACE With Irinotecan-loaded Drug-eluting Beads (DEBIRI) in Patients With Liver Metastases from Unresectable Colorectal Cancer.

BACKGROUND/AIM: The standard of care for patients with colorectal cancer and liver metastases, who fail to respond to systemic chemotherapy has not yet been established. Therefore, we investigated the prognostic value of transarterial chemoembolization (TACE) using irinotecan-loaded drug-eluting beads (DEBIRI) in treating liver metastases due to colorectal cancer. PATIENTS AND METHODS: Forty-six patients with colorectal cancer and unresectable liver metastases, who received systemic chemotherapy beyond the third line at our hospital between July 2014 and April 2020 were analyzed. They were divided into two groups: 1) Seventeen patients who received TACE with DEBIRI, and 2) twenty-nine patients who did not receive TACE. RESULTS: The median age was 68 years (range=37-85 years), and the male-to-female ratio was 29:17. The primary sites were the cecum in six cases, ascending colon in seven cases, transverse colon in two cases, descending colon in three cases, sigmoid colon in 14 cases, and rectum in 14 cases. All patients had received at least two prior systemic chemotherapy regimens including oxaliplatin-based and irinotecan-based regimens, and trifluridine tipiracil hydrochloride (38 patients) or regorafenib (12 patients) as the third line or beyond (overlap). Median survival was 272 days overall, 416 days in the TACE group, and 229 days in the non-TACE group, with significantly better survival in the TACE group (p=0.0126). CONCLUSION: TACE with DEBIRI may improve the prognosis of patients with liver metastases from unresectable colorectal cancer. We suggest that TACE with DEBIRI should be highly considered, especially in patients in whom liver metastasis may be a prognostic factor.

Comparison of Ablation Volume Between Emprint® and Mimapro® Systems for Hepatocellular Carcinoma -A Preliminary Study.

Background: Microwave ablation (MWA) is a standard percutaneous local therapy for hepatocellular carcinoma (HCC). Next-generation MWA is reported to create a more spherical ablation zone than radiofrequency ablation (RFA). We compared the ablation zone and aspect ratio of two 2.45 GHz MWA ablation probes; Emprint® (13G) and Mimapro® (17G). We compared the ablation zone to the applied energy after MWA in patients with hepatocellular carcinoma (HCC). Furthermore, we investigated local recurrence. Materials and Methods: We included 20 patients with HCC, with an average tumour diameter of 33.2 ± 12.2 mm, who underwent MWA using Emprint®, and 9 patients who underwent MWA using Mimapro® with an average tumour diameter of 31.1 ± 10.5 mm. Both groups underwent the same ablation protocol using the same power settings. The images obtained after MWA showed the treatment ablation zone and aspect ratio, which were measured and compared using three-dimensional image analysis software. Results: The aspect ratios in the Emprint® and Mimapro® groups were 0.786 ± 0.105 and 0.808 ± 0.122, respectively, with no significant difference (p = 0.604). The ablation time was significantly shorter in the Mimapro® group than in the Emprint® group, and there was no significant difference in the frequency of popping or the ablation volume. There were no significant differences in local recurrence between the two groups. Conclusion: There was no significant difference in the aspect ratios of the ablation diameter, and the ablation zone was almost spherical in both cases. Mimapro® at 17G was less invasive than Emprint® at 13G.

The plasma degradome reflects later development of NASH fibrosis after liver transplant.

Although liver transplantation (LT) is an effective therapy for cirrhosis, the risk of post-LT NASH is alarmingly high and is associated with accelerated progression to fibrosis/cirrhosis, cardiovascular disease and decreased survival. Lack of risk stratification strategies hampers early intervention against development of post-LT NASH fibrosis. The liver undergoes significant remodeling during inflammatory injury. During such remodeling, degraded peptide fragments (i.e., 'degradome') of the ECM and other proteins increase in plasma, making it a useful diagnostic/prognostic tool in chronic liver disease. To investigate whether liver injury caused by post-LT NASH would yield a unique degradome profile that is predictive of severe post-LT NASH fibrosis, a retrospective analysis of 22 biobanked samples from the Starzl Transplantation Institute (12 with post-LT NASH after 5 years and 10 without) was performed. Total plasma peptides were isolated and analyzed by 1D-LC-MS/MS analysis using a Proxeon EASY-nLC 1000 UHPLC and nanoelectrospray ionization into an Orbitrap Elite mass spectrometer. Qualitative and quantitative peptide features data were developed from MSn datasets using PEAKS Studio X (v10). LC-MS/MS yielded ~ 2700 identifiable peptide features based on the results from Peaks Studio analysis. Several peptides were significantly altered in patients that later developed fibrosis and heatmap analysis of the top 25 most significantly changed peptides, most of which were ECM-derived, clustered the 2 patient groups well. Supervised modeling of the dataset indicated that a fraction of the total peptide signal (~ 15%) could explain the differences between the groups, indicating a strong potential for representative biomarker selection. A similar degradome profile was observed when the plasma degradome patterns were compared being obesity sensitive (C57Bl6/J) and insensitive (AJ) mouse strains. The plasma degradome profile of post-LT patients yielded stark difference based on later development of post-LT NASH fibrosis. This approach could yield new "fingerprints" that can serve as minimally-invasive biomarkers of negative outcomes post-LT.

Ex Vivo Experimental Study of the Ablation Area of Bovine Liver Using STARmed Radiofrequency Ablation.

BACKGROUND/AIM: Ablating a spherical area during hepatocellular carcinoma ablation therapy is a very important issue. We aimed to determine the ablation area of bovine liver using various radiofrequency ablation (RFA) protocols. MATERIALS AND METHODS: Bovine liver (1-2 kg) was placed in an aluminum tray, which was punctured with STARmed VIVA 2.0 17-gauge (G) and 15-G electrodes using a current-carrying tip. Under the step-up or linear method, with an ablation time up to one break and RFA output stop, the size of the color change area (representing the thermally coagulated area) of the bovine liver was measured along the vertical and horizontal axes, and the ablated volume and total heat generated were calculated. RESULTS: 5-W per minute increases protocol resulted in greater horizontal and vertical diameters of the ablated area than 10-W per minute increases protocol under the step-up method. For 5-W and 10-W per minute increases under the step-up method, the aspect ratio was 0.81 and 0.67 with a 17-G electrode, and 0.73 and 0.69 with a 15-G electrode, respectively. For 5-W and 10-W increases under the linear method, the aspect ratio was 0.89 and 0.82, respectively. Sufficient ablation was obtained, with vertical and horizontal diameters of 50 mm and 43.50 mm, respectively. Although the ablation time was long, the watt output value at the break and average watt value were low. CONCLUSION: Gradual increase in output (5 W) using the step-up method yielded a more spherical ablation area, and longer ablation time in the linear method with a 15-G electrode could result in a more spherical ablation area in real clinical practice in humans. Future studies should examine concerns regarding long ablation times.

The Wait Time for Surgery Following Injury Affects Functional Outcomes and Complications After an Ankle Fracture: A Propensity Score-Matched Multicenter Study, the TRON Study.

BACKGROUND: The present study aimed to evaluate the hypothesis that a 1-week extension of the waiting period to perform surgery for ankle fracture might affect postoperative results and complications. METHODS: We used our multicenter database named TRON (Trauma Research Group of Nagoya). In all, 779 patients who underwent surgery for ankle fracture, who had no comorbidities were eligible. After exclusion, we analyzed 596 patients. We divided the patients into 2 groups according to whether they were operated on within 7 days after the injury with propensity score matching. RESULTS: The operative time of the delayed operation group (DO group) was significantly longer than that of the early operation group (EO group) (115.87 ± 56.59 vs 85.93 ± 34.58 minutes; P < .001). The rate of infection in the DO group was significantly higher than that of the EO group (16 patients [6.5%] vs 4 patients [1.6%]; P = .016). CONCLUSION: Waiting for more than a week to perform ankle surgery may lead to longer operative times and increased infection rates. LEVELS OF EVIDENCE: III.

Endoscopic treatment of Bouveret syndrome with a combination of electrohydraulic lithotripsy and balloon expansion: A case report.

Bouveret syndrome is a rare type of ileus caused by the impaction of gallstones passing through a cholecystoenteric fistula in the duodenum. Endoscopic treatment with minimally invasive procedures is preferable for patients with this syndrome, typically for elderly individuals with a high surgical risk. Conventional endoscopic techniques often fail to remove impacted stones that are generally large and occasionally solid. We report the case of an 88-year-old bedridden woman with severe dementia who presented with difficulty in breathing. The patient was diagnosed with aspiration pneumonia. In addition, computed tomography showed a cholecystoduodenal fistula and a gallstone 37 mm in diameter that impacted the duodenal bulb. Bouveret syndrome was diagnosed on the basis of the computed tomography findings. The impacted stone was too large and hard to split with standard endoscopic lithotripsy using grasping forceps, mechanical lithotripter, polypectomy snare, basket catheter, and electrohydraulic lithotripsy (EHL). However, EHL with a dual-channel therapeutic endoscope was achieved to drill a narrow hole approximately 20 mm deep into the stone, in four sessions. The stone was subsequently split by inflating the balloon, which was inserted into the hole, to 10 mm in diameter at 3 atm. All the split stones were spontaneously excreted during defecation after a few days. If the gallstone is too hard to fragment by endoscopic EHL alone, a combination of EHL and balloon expansion might be a useful alternative.

An Investigation of Popping During Radiofrequency Ablation After Lenvatinib Administration for Hepatocellular Carcinoma.

BACKGROUND/AIM: Lenvatinib is available as a molecular target agent for hepatocellular carcinoma (HCC). In this study, we investigated the popping phenomena in patients with HCC who underwent radiofrequency ablation (RFA) after taking lenvatinib. PATIENTS AND METHODS: Fifty-nine patients with HCC between 21-30 mm in diameter and no history of systemic treatment were enrolled in the study. The patients underwent RFA using a VIVA RFA SYSTEM with an ablation tip of 30 mm in length. For the initial lenvatinib administration, 16 patients had an adequate course of treatment and were treated with RFA as add-on therapy (combination group). The other 43 patients were treated by RFA monotherapy (monotherapy group). The popping frequency during RFA was recorded and compared. RESULTS: Popping frequency in the combination group (RFA combined with lenvatinib) was significantly higher than that in the monotherapy group. There was no significant difference between the combination group and the monotherapy group in ablation time, maximum output level, tumour temperature after ablation, or initial resistance value. CONCLUSION: Popping frequency was significantly higher in the combination group. It is possible that the intra-tumour temperature increased rapidly during RFA in the combination group due to the inhibitory effect of lenvatinib on tumour angiogenesis, leading to the occurrence of popping. Further studies are needed to investigate popping after RFA, and precise protocols need to be developed.

The plasma degradome reflects later development of NASH fibrosis after liver transplant.

Although liver transplantation (LT) is an effective therapy for cirrhosis, the risk of post-LT NASH is alarmingly high and is associated with accelerated progression to fibrosis/cirrhosis, cardiovascular disease, and decreased survival. Lack of risk stratification strategies hamper liver undergoes significant remodeling during inflammatory injury. During such remodeling, degraded peptide fragments (i.e., 'degradome') of the ECM and other proteins increase in plasma, making it a useful diagnostic/prognostic tool in chronic liver disease. To investigate whether inflammatory liver injury caused by post-LT NASH would yield a unique degradome profile, predictive of severe post-LT NASH fibrosis, we performed a retrospective analysis of 22 biobanked samples from the Starzl Transplantation Institute (12 with post-LT NASH after 5 years and 10 without). Total plasma peptides were isolated and analyzed by 1D-LC-MS/MS analysis using a Proxeon EASY-nLC 1000 UHPLC and nanoelectrospray ionization into an Orbitrap Elite mass spectrometer. Qualitative and quantitative peptide features data were developed from MSn datasets using PEAKS Studio X (v10). LC-MS/MS yielded ∼2700 identifiable peptide features based on the results from Peaks Studio analysis. Several peptides were significantly altered in patients that later developed fibrosis and heatmap analysis of the top 25 most significantly-changed peptides, most of which were ECM-derived, clustered the 2 patient groups well. Supervised modeling of the dataset indicated that a fraction of the total peptide signal (∼15%) could explain the differences between the groups, indicating a strong potential for representative biomarker selection. A similar degradome profile was observed when the plasma degradome patterns were compared being obesity sensitive (C57Bl6/J) and insensitive (AJ) mouse strains. Both The plasma degradome profile of post-LT patients yields stark difference based on later development of post-LT NASH fibrosis. This approach could yield new "fingerprints" that can serve as minimally-invasive biomarkers of negative outcomes post-LT.

Fibrosis resolution in the mouse liver: Role of Mmp12 and potential role of calpain 1/2.

Although most work has focused on resolution of collagen ECM, fibrosis resolution involves changes to several ECM proteins. The purpose of the current study was twofold: 1) to examine the role of MMP12 and elastin; and 2) to investigate the changes in degraded proteins in plasma (i.e., the "degradome") in a preclinical model of fibrosis resolution. Fibrosis was induced by 4 weeks carbon tetrachloride (CCl4) exposure, and recovery was monitored for an additional 4 weeks. Some mice were treated with daily MMP12 inhibitor (MMP408) during the resolution phase. Liver injury and fibrosis was monitored by clinical chemistry, histology and gene expression. The release of degraded ECM peptides in the plasma was analyzed using by 1D-LC-MS/MS, coupled with PEAKS Studio (v10) peptide identification. Hepatic fibrosis and liver injury rapidly resolved in this mouse model. However, some collagen fibrils were still present 28d after cessation of CCl4. Despite this persistent collagen presence, expression of canonical markers of fibrosis were also normalized. The inhibition of MMP12 dramatically delayed fibrosis resolution under these conditions. LC-MS/MS analysis identified that several proteins were being degraded even at late stages of fibrosis resolution. Calpains 1/2 were identified as potential new proteases involved in fibrosis resolution. CONCLUSION. The results of this study indicate that remodeling of the liver during recovery from fibrosis is a complex and highly coordinated process that extends well beyond the degradation of the collagenous scar. These results also indicate that analysis of the plasma degradome may yield new insight into the mechanisms of fibrosis recovery, and by extension, new "theragnostic" targets. Lastly, a novel potential role for calpain activation in the degradation and turnover of proteins was identified.

Early weight bearing and mobilization decrease perioperative complications in patients after ankle fracture; the retrospective multicenter (TRON group) study.

BACKGROUND: Open reduction and internal fixation (ORIF) for unstable ankle fractures (AF) are relatively predictable with excellent outcomes. Rehabilitation strategies are still being debated after surgical intervention for AF: non-weight bearing and cast immobilization for six weeks after the surgical repair of unstable AF or early functional treatment with partial weight bearing. This study aimed to compare early weight bearing and functional outcomes and complications. METHODS: Between April 2014 and March 2019, 1421 patients with AF underwent ORIF at 11 institutions (TRON group). The patients were divided into two groups: Group E started weight bearing within six weeks after surgery, and group L started weightbearing for more than six weeks after. To adjust for baseline difference between groups, a propensity score-matched algorithm was used to match Group E with Group L in a 1:1 ratio of 294 cases each. We compared the American Orthopedic Foot and Ankle Society (AOFAS) score as the functional outcome, the rate of wound dehiscence, superficial and deep infections, blistering, nonunion, neurapraxia, and reoperation at 3, 6, and 12 months after surgery. RESULTS: The mean period of non-weight bearing was significantly shorter in group E (3.68 ± 1.02 vs. 6.67 ± 1.43; P < 0.001). The mean period of cast immobilization term were shorter in group E (1.84 ± 1.35 vs. 2.65 ± 1.51; P < 0.001). There were no differences in the AOFAS score at any period. The rates of deep infection and reoperation in Group E were significantly lower than those in Group L (1.7% vs. 6.1%; P = 0.009, 2.0% vs. 7.8%; P = 0.002, respectively). There were no significant differences in superficial infection (9 vs. 15; P = 0.297), nonunion (9 vs. 15 P = 0.30), blistering (4 vs. 3; P = 1.00), neurapraxia (2 vs. 1; P = 1.00), and wound dehiscence (15 vs. 18; P = 0.72). CONCLUSIONS: Although functional outcome was similar depending on whether early weight bearing was allowed, the rates of deep infection and reoperation decreased in patients with early weight bearing. We recommend early postoperative weight bearing in patients with a surgically treated AF.

A plasma peptidomic signature reveals extracellular matrix remodeling and predicts prognosis in alcohol-related hepatitis.

Alcohol-related hepatitis (AH) is plagued with high mortality and difficulty in identifying at-risk patients. The extracellular matrix undergoes significant remodeling during inflammatory liver injury that can be detected in biological fluids and potentially used for mortality prediction. EDTA plasma samples were collected from AH patients (n= 62); Model for End-Stage Liver Disease (MELD) score defined AH severity as moderate (12-20; n=28) and severe (>20; n=34). The peptidome data was collected by high resolution, high mass accuracy UPLC-MS. Univariate and multivariate analyses identified differentially abundant peptides, which were used for Gene Ontology, parent protein matrisomal composition and protease involvement. Machine learning methods were used on patient-specific peptidome and clinical data to develop mortality predictors. Analysis of plasma peptides from AH patients and healthy controls identified over 1,600 significant peptide features corresponding to 130 proteins. These were enriched for ECM fragments in AH samples, likely related to turnover of hepatic-derived proteins. Analysis of moderate versus severe AH peptidomes showed a shift in abundance of peptides from collagen 1A1 and fibrinogen A proteins. The dominant proteases for the AH peptidome spectrum appear to be CAPN1 and MMP12. Increase in hepatic expression of these proteases was orthogonally-validated in RNA-seq data of livers from AH patients. Causal graphical modeling identified four peptides directly linked to 90-day mortality in >90% of the learned graphs. These peptides improved the accuracy of mortality prediction over MELD score and were used to create a clinically applicable mortality prediction assay. A signature based on plasma peptidome is a novel, non-invasive method for prognosis stratification in AH patients. Our results could also lead to new mechanistic and/or surrogate biomarkers to identify new AH mechanisms. Lay summary: We used degraded proteins found the blood of alcohol-related hepatitis patients to identify new potential mechanisms of injury and to predict 90 day mortality.

Mirizzi Syndrome Type IV Successfully Treated with Peroral Single-operator Cholangioscopy-guided Electrohydraulic Lithotripsy: A Case Report with Literature Review.

A 76-year-old man presented with liver dysfunction and intrahepatic bile duct dilatation. Imaging studies showed two large stones that had become impacted in the common hepatic duct, which was fused with the gallbladder. The patient was diagnosed with Mirizzi syndrome type IV. Hepaticojejunostomy and stone removal failed due to dense gallbladder adhesions involving the right hepatic artery. The bile flow was temporarily restored; however, the patient experienced cholangitis 16 months later. The stones were extracted via peroral single-operator cholangioscopy (SOC)-guided electrohydraulic lithotripsy. This is the first case in which stones were completely removed by SOC-guided treatment in a patient with Mirizzi syndrome type IV.

Adverse Local Tissue Reaction and Late-Onset Eosinophilic Gastroenteritis After Primary Total Hip Arthroplasty: A Case Report.

CASE: A 67-year-old woman suffered from chronic diarrhea at 10 years after right total hip arthroplasty. She also had a pseudotumor caused by an adverse local tissue reaction (ALTR) in her right pelvis. We performed revision arthroplasty, in part because we suspected the diarrhea may have been associated with the intrapelvic pseudotumor. She was later diagnosed with eosinophilic gastroenteritis (EGE). CONCLUSION: Although these two diseases were thought be be related through a similar immune reaction, our patient's clinical course suggests that the ALTR and EGE were independent events.

WNT7B Regulates Cholangiocyte Proliferation and Function During Murine Cholestasis.

We previously identified an up-regulation of specific Wnt proteins in the cholangiocyte compartment during cholestatic liver injury and found that mice lacking Wnt secretion from hepatocytes and cholangiocytes showed fewer proliferating cholangiocytes and high mortality in response to a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet, a murine model of primary sclerosing cholangitis. In vitro studies demonstrated that Wnt7b, one of the Wnts up-regulated during cholestasis, induces proliferation of cholangiocytes in an autocrine manner and increases secretion of proinflammatory cytokines. We hypothesized that loss of Wnt7b may exacerbate some of the complications of cholangiopathies by decreasing the ability of bile ducts to induce repair. Wnt7b-flox mice were bred with Krt19-cre mice to deplete Wnt7b expression in only cholangiocytes (CC) or with albumin-Cre mice to delete Wnt7b expression in both hepatocytes and cholangiocytes (HC + CC). These mice were placed on a DDC diet for 1 month then killed for evaluation. Contrary to our expectations, we found that mice lacking Wnt7b from CC and HC + CC compartments had improved biliary injury, decreased cellular senescence, and lesser bile acid accumulation after DDC exposure compared to controls, along with decreased expression of inflammatory cytokines. Although Wnt7b knockout (KO) resulted in fewer proliferating cholangiocytes, CC and HC + CC KO mice on a DDC diet also had more hepatocytes expressing cholangiocyte markers compared to wild-type mice on a DDC diet, indicating that Wnt7b suppression promotes hepatocyte reprogramming. Conclusion: Wnt7b induces a proproliferative proinflammatory program in cholangiocytes, and its loss is compensated for by conversion of hepatocytes to a biliary phenotype during cholestatic injury.