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Background Several studies have shown that there are no significant differences in anastomotic leakage associated with Transanal total mesorectal excision (taTME) versus laparoscopic TME (lapTME) for rectal cancer; however, little is known about late anastomotic leakage, such as that primarily found in the chronic presacral sinus. We aimed to compare the occurrence of anastomotic leakage and chronic presacral sinus in rectal cancer for taTME and lapTME. Methods In this retrospective cohort study, data were collected for patients with rectal cancer who underwent surgery between January 2009 and September 2019. Of the 220 patients included in this study, 182 were in the lapTME group and 38 in the taTME group. We compared factors associated with anastomotic leakage and chronic presacral sinus formation between the two groups. A binary-logistic model was used to determine the risk factors for chronic presacral sinus. Results Anastomotic leakage occurred in six patients (15.8%) in the taTME group and 36 patients (19.7%) in the lapTME group. Chronic presacral sinus occurred in three patients (7.9%) in the taTME group and 15 patients (8.2%) in the lapTME group. There was no significant difference in anastomotic leakage or chronic presacral sinus between groups (P = 0.569 and P = 1.000, respectively). Pathologic stage III or higher was significantly associated with chronic presacral sinus formation (P = 0.006). Conclusion There were no significant differences between taTME and lapTME regarding the incidence of anastomotic leakage or chronic presacral sinus. Almost one-third of anastomotic leakages developed into chronic presacral sinus.

INTRODUCTION The necessity of antiviral therapy (AVT) for hepatitis B virus (HBV)-infected compensated cirrhosis with low-level viremia (LLV) is controversial. Herein, we evaluated its natural history. METHODS From 3 tertiary hospitals, we enrolled untreated patients with compensated cirrhosis with persistent serum HBV-DNA levels

Whether entecavir (ETV) or tenofovir alafenamide (TAF) is better at preventing hepatocellular carcinoma (HCC) development among patients with chronic hepatitis B (CHB) remains unclear. The present study was conducted to explore the ability of these two antivirals to prevent HCC. From 2012 to 2019, treatment-naive CHB patients undergoing ETV or TAF therapy were recruited at three academic teaching hospitals. The TAF group comprised patients starting TAF as first-line antiviral and those switching antivirals from tenofovir disoproxil fumarate to TAF. Patients with decompensated cirrhosis or HCC at enrollment were excluded from the analysis. Cumulative probabilities of HCC were assessed using the Kaplan–Meier method. In total, 1810 patients (1525 and 285 in ETV and TAF groups, respectively) were recruited. The annual HCC incidence was statistically not different between the ETV and TAF groups (1.67 vs. 1.19 per 100 person-years, respectively) with an adjusted hazard ratio (HR) of 0.681 (p = 0.255), as determined by multivariate analysis. Male, hypertension, liver cirrhosis, FIB-4 index, and albumin were independent prognostic factors for HCC development. Propensity score-matched and inverse probability of treatment weighting analyses yielded similar results, with non-statistically different HCC incidence between the ETV and TAF groups (1.07 vs. 1.19 per 100 person-years (HR = 0.973; p = 0.953) and 1.67 vs. 1.89 per 100 person-years, respectively (HR = 0.949; p = 0.743). These findings suggest that ETV- and TAF-treated CHB patients have similar risk of developing HCC. Further studies with the larger sample size and longer follow-up are needed to validate these results.

Hye Won Lee,1– 3,* Hyun Woong Lee,4,* Jae Seung Lee,1– 3 Yun Ho Roh,5 Hyein Lee,3 Seung Up Kim,1– 3 Jun Yong Park,1– 3 Do Young Kim,1– 3 Sang Hoon Ahn,1– 3 Beom Kyung Kim1– 3 1Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; 2Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea; 3Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea; 4Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; 5Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea*These authors contributed equally to this workCorrespondence: Beom Kyung KimDepartment of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun–Gu, Seoul, 03722, Republic of KoreaTel +82-2-2228-1930Fax +82-2-393-6884Email beomkkim@yuhs.acBackground: Dynamic changes in fibrosis markers occur under long-term antiviral treatment (AVT) for chronic hepatitis B. We evaluated prognostic values of on-treatment liver stiffness (LS) compared to ultrasonography findings and determined its optimal cutoff.Methods: The cumulative probability of hepatocellular carcinoma (HCC) was assessed among 880 patients receiving entecavir or tenofovir for ≥ 2 years. LS was measured using transient elastography.Results: After ≥ 2 years’ AVT, the proportion of patients with cirrhosis on ultrasonography decreased from 54.7% to 44.9% and the mean LS decreased from 13.6 to 8.2 kPa (both p< 0.001). However, unlike cirrhosis on ultrasonography before AVT (p< 0.001), that after ≥ 2 years’ AVT did not discriminate HCC risk (p=0.792). Using the Contal and O’Quigley’s method, pre-AVT and on-treatment LS of 12.0 and 6.4 kPa, respectively, were chosen as optimal cutoffs to successfully discriminate HCC risk (both p< 0.001). However, through stratification using both pre-AVT and on-treatment LS, the prognosis was finally determined according to on-treatment LS of 6.4 kPa, regardless of pre-AVT LS of 12.0 kPa. Using on-treatment LS of 12 kPa suggested by Caucasians with CHB receiving long-term AVT, patients with higher LS were more likely to develop HCC than those with lower LS (p=0.017); however, there was no significant difference between those with on-treatment LS of 6.4– 11.9 and ≥ 12.0 kPa (p=0.920).Conclusion: For HCC risk stratification in patients receiving long-term AVT, on-treatment LS cutoff should be lowered to 6.4 kPa, which is more predictive than 12 kPa or cirrhosis on ultrasonography. Further studies are required for validation.Keywords: antiviral treatment, hepatitis B, liver stiffness, hepatocellular carcinoma

We compared the clinical efficacies of hepatic arterial infusion chemotherapy (HAIC) vs. sorafenib as sequential maintenance therapy following liver-directed concurrent chemoradiotherapy (LD-CCRT) for locally advanced-stage hepatocellular carcinoma (HCC). Patients undergoing HAIC with 5-fluorouracil and cisplatin (HAIC-maintain group, n = 151) or sorafenib (Sorafenib-maintain group, n = 37) after LD-CCRT were consecutively enrolled. The study endpoints were overall survival (OS), progression-free survival (PFS), and treatment response rates. The median OS among HAIC-maintain and Sorafenib-maintain groups were 15.9 and 24.3 months (p = 0.287), whereas the median PFS were 8.1 and 9.1 months (p = 0.651), respectively. During the planned treatments, the radiological objective response rate (54.3% vs. 64.9%; p = 0.246), and conversion rate to surgical resection or liver transplantation after successful down-staging (15.9% vs. 18.9%; p = 0.657) were comparable between the HAIC-maintain and Sorafenib-maintain groups. Similar results were found after the inverse probability of treatment weighting and propensity score-matching analyses. Regarding treatment-related adverse events, the HAIC-maintain group showed worse profiles in terms of leukopenia (all grades [p = 0.001] and grades 3 or 4 [p = 0.041]) and hypoalbuminemia (p = 0.001) than the Sorafenib-maintain group. The overall clinical efficacies between the sequential treatment of HAIC vs. sorafenib after LD-CCRT were comparable for locally advanced HCC.

This work presents the formic acid oxidation (FAO) behavior on three model Pt deposit catalysts on Au. The investigated model Pt catalysts were single-layered Pt deposits, plateau-type Pt deposits and tall conical Pt deposits, produced via irreversible adsorption of Pt ions according to the protocols of conventional route, CO route and iodine route, respectively. The shapes and populations of the model Pt deposits were controlled by the deposition protocols and number of deposition cycles. The most effective Pt deposit catalyst in FAO was verified to be single-layered one with a population of ∼50% which inhibited dehydration (poison formation) and promoted dehydrogenation. As the population of Pt deposits became higher than 50%, the dehydration process activated to decrease the FAO catalytic efficiency. Furthermore, multiple layered Pt deposits such as conical ones were not so efficient due to activation of dehydration even at a population below 50%. More detailed analysis of the observed voltammograms in the negative-going scan suggested that dehydrogenation took place at two different potentials depending on the shapes and populations of Pt deposits. One was low potential dehydrogenation occurring on separated single-layered Pt deposits at 0.14 V; the other was high potential dehydrogenation taking place on continuous Pt surface at 0.34 V. This particular suggestion was successfully applicable to explaining the FAO voltammograms of Pt electrodes of disk and nanoparticle.

It is unclear whether tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF) is more effective for preventing hepatocellular carcinoma (HCC) development in patients with chronic hepatitis B (CHB). In this study, we compared the effectiveness of these two antiviral agents for preventing HCC. We included treatment-naive CHB patients undergoing antiviral therapy with TDF only (TDF group) or a TAF-based regimen (TAF group) at three academic teaching hospitals from 2012 to 2019. The TAF group included patients receiving TAF as first-line treatment and patients switching from TDF to TAF. Patients with decompensated cirrhosis or HCC at enrollment were excluded. Cumulative probabilities of HCC were assessed using Kaplan-Meier methodology. In total, 2,117 patients were included: 1,832 in the TDF group and 285 in the TAF group. The annual HCC incidence was not significantly different between TDF and TAF groups: 1.66 vs. 1.19 per 100 person-years [PY], respectively (multivariate analysis: adjusted hazard ratio [HR] 0.774 [reference: TDF group]; p = .438). Male, liver cirrhosis, hepatitis B e antigen negativity, Fibrosis-4 index>3.25 and low albumin were independently associated with a higher risk of HCC. Propensity score-matched and inverse probability of treatment weighting analyses yielded similar results: 1.56 vs. 1.19 per 100 PY, respectively (HR 1.175; p = .708) and 1.66 vs. 1.29 per 100 PY, respectively (HR 0.888; p = .446). The risk of HCC development was not significantly different between TDF and TAF groups of CHB patients. Further studies with a larger sample size and longer follow-up are required to validate our results.

Neuromyelitis optica (NMO) is an autoimmune disease that primarily targets astrocytes. Autoantibodies (NMO-IgG) against the water channel protein, aquaporin 4 (AQP4), are a serologic marker in NMO patients, and they are known to be responsible for the pathophysiology of the disease. In the brain, AQP4 is mainly expressed in astrocytes, especially at the end-feet, where they form the blood-brain barrier. Following the interaction between NMO-IgG and AQP4 in astrocytes, rapid AQP4 endocytosis initiates pathogenesis. However, the cellular and molecular mechanisms of astrocyte destruction by autoantibodies remain largely elusive. We established an in vitro human astrocyte model system using induced pluripotent stem cells (iPSCs) technology in combination with NMO patient-derived serum and IgG to elucidate the cellular and functional changes caused by NMO-IgG. Herein, we observed that NMO-IgG induces structural alterations in mitochondria and their association with the endoplasmic reticulum (ER) and lysosomes at the ultrastructural level, which potentially leads to impaired mitochondrial functions and dynamics. Indeed, human astrocytes display impaired mitochondrial bioenergetics and autophagy activity in the presence of NMO-IgG. We further demonstrated NMO-IgG-driven ER membrane deformation into a multilamellar structure in human astrocytes. Together, we show that NMO-IgG rearranges cellular organelles and alter their functions and that our in vitro system using human iPSCs offers previously unavailable experimental opportunities to study the pathophysiological mechanisms of NMO in human astrocytes or conduct large-scale screening for potential therapeutic compounds targeting astrocytic abnormalities in patients with NMO.

Summary The ε4 allele of APOE-encoding apolipoprotein (ApoE) is one of the strongest genetic risk factors for Alzheimer’s disease (AD). One of the overarching questions is whether and how this astrocyte-enriched risk factor initiates AD-associated pathology in neurons such as amyloid-β (Aβ) accumulation. Here, we generate neurons and astrocytes from isogenic human induced pluripotent stem cells (hiPSCs) carrying either APOE ε3 or APOE ε4 allele and investigate the effect of astrocytic ApoE4 on neuronal Aβ production. Secretory factors in conditioned media from ApoE4 astrocytes significantly increased amyloid precursor protein (APP) levels and Aβ secretion in neurons. We further found that increased cholesterol secretion from ApoE4 astrocytes was necessary and sufficient to induce the formation of lipid rafts that potentially provide a physical platform for APP localization and facilitate its processing. Our study reveals the contribution of ApoE4 astrocytes to amyloidosis in neurons by expanding lipid rafts and facilitating Aβ production through an oversupply of cholesterol., Graphical abstract, Highlights • ApoE4 ACM induces neuronal lipid raft expansion and Aβ42 overproduction • Co-localization of lipid rafts and APP increases in neurons by ApoE4 ACM • Increasing cholesterol in media recapitulates the effects of ApoE4 ACM on neurons • Cholesterol depletion in ApoE4 ACM abolishes its effects on neurons, In this report, Seo and colleagues use human iPSCs to generate isogenic neurons and astrocytes carrying either APOE ε3 or APOE ε4 allele and demonstrate that ApoE4 astrocytes secrete more cholesterol to the extracellular space, which is sufficient and necessary to induce lipid raft expansion and Aβ42 overproduction in neurons.

CAGE-B and SAGE-B scores, consisting of age and fibrotic burden as cirrhosis and/or liver stiffness, were recently proposed to predict hepatocellular carcinoma (HCC) risk among Caucasian chronic hepatitis B (CHB) patients undergoing long-term antiviral therapy. We externally validated their predictive performances among an independent cohort from Asia, compared to other conventional prediction models. We consecutively recruited CHB patients with well-controlled viremia (serum HBV DNA

With the increasing use of ultrasound for assuring safe and accurate caudal or epidural block for postoperative analgesia in children, hidden spinal dysraphism may be found incidentally. Children with congenital anomalies such as VATER or VACTERL frequently present with accompanying occult spinal dysraphisms (OSD), which is characterized with skin-covered lesions such as tethered spinal cord (TSC), meningocele, or lipomyelomeningocele. OSDs are usually found incidentally during the evaluation for other diseases or after neurological symptoms manifest. However, in children with a simple urogenital anomaly, OSD may not be found until the symptoms of OSD manifest because ultrasound screening is not routinely performed in neonates. We report a case of TSC that was discovered during routine ultrasound for caudal block in an asymptomatic child undergoing urological surgery. A 12-month-old, 9.8 kg, otherwise healthy female infant was scheduled to receive a pyeloureterostomy for hydronephrosis. When the patient was placed in lateral decubitus position for caudal block after general anesthesia, an intergluteal simple dimple (1.2 cm in length) was noted. Upon ultrasound (LOGIQe™; GE Healthcare, Wauwatosa, WI, USA) for the spinal structure, we found a thickened filum terminale (FT) 2.2 mm in diameter with low-lying conus medullaris (CM) (L3 level) (Fig. 1A and 1B). We did not perform a caudal block and recommended magnetic resonance imaging (MRI) study for further evaluation. In the postoperative MRI, TSC with FT lipoma was confirmed (Fig. 1C) and detethering surgery was performed after one month. Fig. 1 Ultrasound (A, B) and MRI (C) findings. CM: conus medullaris, FT: filum terminale. In (C), the solid arrow and dotted arrow indicate the low-lying CM and thickened FT. The prognosis of TSC depends mostly on early diagnosis and treatment. While the exact incidence of TSC is not known, greater clinical awareness and MRI diagnostics have lead to a higher rate of incidental detection. Although several studies have reported that children with lumbosacral lipoma have other congenital malformations combined with urogenital anomalies, the association between TSC with a single urogenital anomaly has not been clearly established [1,2]. There have been arguments that minor skin markers are not a stigmata of OSD. One study found OSD to be present in children with minor skin markers and in children without skin markers [3]. Compared to normal infants, in which the CM terminates above L1/2 and the thickness of the FT is < 2 mm at the L5/S1 level, the CM in this patient was located at the L3 level and the FT thickness was 2.2 mm upon ultrasound. Therefore, a pediatric patient presenting with a single urogenital anomaly together with a minor skin marker may require greater attention with further investigation into a possible underlying OSD. Ultrasound is a simple and effective screening method for detecting spinal abnormalities. In clinical practice, if the ultrasound is available for a caudal block, lumbosacral spinal structures should be evaluated thoroughly even in children with a single urogenital anomaly.