Since its publication in 2007, the Tokyo Guidelines for the management of acute cholangitis and cholecystitis (TG07) have been widely adopted. The validation of TG07 conducted in terms of clinical ...practice has shown that the diagnostic criteria for acute cholecystitis are highly reliable but that the definition of definite diagnosis is ambiguous. Discussion by the Tokyo Guidelines Revision Committee concluded that acute cholecystitis should be suspected when Murphy’s sign, local inflammatory findings in the gallbladder such as right upper quadrant abdominal pain and tenderness, and fever and systemic inflammatory reaction findings detected by blood tests are present but that definite diagnosis of acute cholecystitis can be made only on the basis of the imaging of ultrasonography, computed tomography or scintigraphy (HIDA scan). These proposed diagnostic criteria provided better specificity and accuracy rates than the TG07 diagnostic criteria. As for the severity assessment criteria in TG07, there is evidence that TG07 resulted in clarification of the concept of severe acute cholecystitis. Furthermore, there is evidence that severity assessment in TG07 has led to a reduction in the mean duration of hospital stay. As for the factors used to establish a moderate grade of acute cholecystitis, such as leukocytosis, ALP, old age, diabetes, being male, and delay in admission, no new strong evidence has been detected indicating that a change in the criteria used in TG07 is needed. Therefore, it was judged that the severity assessment criteria of TG07 could be applied in the updated Tokyo Guidelines (TG13) with minor changes. TG13 presents new standards for the diagnosis, severity grading and management of acute cholecystitis.
Free full-text articles and a mobile application of TG13 are available via
http://www.jshbps.jp/en/guideline/tg13.html
.
Glutathione (GSH) plays diverse roles in the physiological processes, stress defense, growth, and development of plants. This study investigated the effects of exogenous GSH on the biochemical ...responses of reactive oxygen species and antioxidant levels in rice (
Oryza sativa
L. cv. Dasan) seedlings under arsenic (As) stress. As treatment inhibited growth; increased the level of superoxide, hydrogen peroxide, and malondialdehyde; and enhanced the uptake of As by the roots and shoots in hydroponically grown 14-day-old seedlings. Furthermore, it reduced GSH content and GSH redox ratios, which have been correlated with the decrease in ascorbate (AsA) redox state. Whereas the exogenous application of GSH in As-treated seedlings reduced As-induced oxidative stress, improved antioxidant defense systems by maintaining antioxidant and/or redox enzyme homeostasis, and increased the AsA and GSH contents, the GSH application also increased the As translocation from the roots to the shoots. These results indicated that the increase in GSH redox state can be linked to an increase in the AsA redox ratio
via
the induction of the AsA–GSH cycle. Therefore, the results suggest that exogenous GSH application should be a promising approach to enhance As stress resistance in rice plants.
The NLRP3 inflammasome plays a key role in responding to pathogens, and endogenous damage and mitochondria are intensively involved in inflammasome activation. The NLRP3 inflammasome forms ...multiprotein complexes and its sequential assembly is important for its activation. Here, we show that NLRP3 is ubiquitinated by the mitochondria-associated E3 ligase, MARCH5. Myeloid cell-specific March5 conditional knockout (March5 cKO) mice failed to secrete IL-1β and IL-18 and exhibited an attenuated mortality rate upon LPS or Pseudomonas aeruginosa challenge. Macrophages derived from March5 cKO mice also did not produce IL-1β and IL-18 after microbial infection. Mechanistically, MARCH5 interacts with the NACHT domain of NLRP3 and promotes K27-linked polyubiquitination on K324 and K430 residues of NLRP3. Ubiquitination-defective NLRP3 mutants on K324 and K430 residues are not able to bind to NEK7, nor form NLRP3 oligomers leading to abortive ASC speck formation and diminished IL-1β production. Thus, MARCH5-dependent NLRP3 ubiquitination on the mitochondria is required for NLRP3-NEK7 complex formation and NLRP3 oligomerization. We propose that the E3 ligase MARCH5 is a regulator of NLRP3 inflammasome activation on the mitochondria.
To gain deeper insights into transcriptomes and epigenomes of organoids, liver organoids from two states (expandable and more differentiated) were subjected to single-cell RNA-seq (scRNA-seq) and ...single-cell ATAC-seq (scATAC-seq) analyses. Mitochondrial gene expression was higher in differentiated than in non-differentiated hepatocytes, with ATAC-seq peaks increasing near the mitochondrial control region. Differentiation of liver organoids resulted in the expression of transcription factors that act as enhancers and repressors. In addition, epigenetic mechanisms regulating the expression of alpha-fetoprotein (AFP) and albumin (ALB) differed in liver organoids and adult liver. Knockdown of PDX1, an essential transcription factor for pancreas development, led to the hepatic maturation of liver organoids through regulation of AFP and ALB expression. This integrative analysis of the transcriptomes and epigenomes of liver organoids at the single-cell level may contribute to a better understanding of the regulatory networks during liver development and the further development of mature in vitro human liver models.
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•Liver organoids exhibited cell compositions similar to human liver tissue•Mitochondrial gene expression increased in the mature hepatocytes of liver organoid•Differences between liver organoid and tissue were revealed by single-cell data•Knockdown of PDX1 led to the hepatic maturation of liver organoids
Molecular mechanism of gene regulation; Integrative aspects of cell biology; Experimental models in systems biology; Transcriptomics
Background:
Although endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) with transmural stenting has increased for biliary decompression in patients with an inaccessible papilla, the optimal ...biliary access point and the learning curve of EUS-HGS have not been studied. We evaluated the optimal biliary access point and learning curve for technically successful EUS-HGS.
Methods:
129 consecutive patients (male n = 81, 62.3%; malignant n = 113, 87.6%) who underwent EUS-HGS due to an inaccessible papilla were enrolled. EUS finding and procedure times according to each needle puncture attempt in EUS-HGS were prospectively measured. Learning curves of EUS-HGS were calculated for two main outcome measurements (procedure time and adverse events) by using the moving average method and cumulative sum (CUSUM) analysis, respectively.
Results:
A total of 174 EUS-HGS attempts were performed in 129 patients. The mean number of needle punctures was 1.35 ± 0.57. Using the logistic regression model, bile duct diameter of the puncture site ⩽ 5 mm odds ratio (OR) 3.7, 95% confidence interval (CI): 1.71–8.1, p < 0.01 and hepatic portion length linear distance from the mural wall to the punctured bile duct wall on EUS; mean hepatic portion length was 27 mm (range 10–47 mm) > 3 cm (OR 5.7, 95% CI: 2.7–12, p < 0.01) were associated with low technical success. Procedure time and adverse events were shorter after 24 cases, and stabilized at 33 cases of EUS-HGS, respectively.
Conclusions:
Our data suggest that a bile duct diameter > 5 mm and hepatic portion length 1 cm to ⩽ 3 cm on EUS may be suitable for successful EUS-HGS. In our learning curve analysis, over 33 cases might be required to achieve the plateau phase for successful EUS-HGS.
Background and Aim
While recent evidences support endoscopic resection as curative in ampullary tumors with high‐grade intraepithelial neoplasia, only small case series have reported endoscopic ...management of early‐stage ampullary cancer; thus, radical surgery remains the only accepted treatment modality. We evaluated the long‐term outcomes of early ampullary adenocarcinoma administered endoscopic management.
Methods
We retrospectively reviewed electronic medical records of 715 patients undergoing endoscopic papillectomy (EP) in a single tertiary medical center in Korea in 2004–2016. We included patients incidentally diagnosed with early‐stage adenocarcinoma (Tis and T1a, American Joint Committee on Cancer 8th edition) after EP and with >2 years of follow‐up data and analyzed their demographics, histopathologic data, and clinical outcomes.
Results
Among 70 total patients in the EP‐alone (n = 42) and subsequent surgery (n = 28) groups, we observed no significant differences in demographics or tumor size (2.0 ± 0.6 vs 1.9 ± 0.5 cm, P = 0.532), histologic grade (P = 0.077), tumor extent (P = 1.000), lymphovascular invasion (2.4% vs 10.7%, P = 0.344), or complete resection rates (57.1% vs 57.1%, P = 1.000) between groups. Adenocarcinoma lesions were larger in the subsequent surgery group (0.7 ± 0.5 vs 1.1 ± 0.7 cm, P = 0.002). The EP‐alone group received more additional ablative treatment (42.9% vs 14.3%, P = 0.024). The 5‐year disease‐free and cancer‐free survival rates were 79.1% vs 87.4% (P = 0.111) and 93.5% versus 87.4% (P = 0.726), respectively, and did not differ significantly between groups.
Conclusions
Endoscopic papillectomy followed by endoscopic surveillance showed long‐term outcomes comparable with surgical resection for early ampullary cancer and maybe curable alternative to surgery for incidentally found early‐stage ampullary cancer, especially in patients unfit for or refusing radical surgery.
Zn(II)–porphyrin sensitizers, coded as SGT‐020 and SGT‐021, are designed and synthesized through donor structural engineering. The photovoltaic (PV) performances of SGT sensitizer‐based ...dye‐sensitized solar cells (DSSCs) are systematically evaluated in a thorough SM315 as a reference sensitizer. The effect of the donor ability and the donor bulkiness on photovoltaic performances is investigated for establishing the structure–performance relationship in the platform of porphyrin‐triple bond‐benzothiadiazole‐acceptor sensitizers. By introducing a more bulky fluorene unit to the amine group in the SM315, the power conversion efficiency (PCE) is enhanced with the increased short‐circuit current (Jsc) and open‐circuit voltage (Voc), due to the improved light‐harvesting ability and the efficient prevention of charge recombination, respectively. As a consequence, a maximum PCE of 12.11% is obtained for SGT‐021, whose PCE is much higher than the 11.70% PCE for SM315. To further improve their maximum efficiency, the first parallel tandem DSSCs employing cobalt electrolyte in the top and bottom cells are demonstrated and an extremely high efficiency of 14% is achieved, which is currently the highest reported value for tandem DSSCs. The series tandem DSSCs give a remarkably high Voc value of >1.83 V. From this DSSC tandem configuration, 7.4% applied bias photon‐to‐current efficiency is achieved for solar water splitting.
The effect of the donor ability and bulkiness on DSSC photovoltaic performances is investigated to exceed a world champion porphyrin. The first parallel tandem DSSCs employing cobalt electrolyte are demonstrated with an extremely high efficiency of 14%. The series tandem DSSCs give a remarkably high Voc value of >1.83 V, achieving 7.4% applied bias photon‐to‐current efficiency for solar water splitting.
An artificial intelligence (AI) model using chest radiography (CXR) may provide good performance in making prognoses for COVID-19.
We aimed to develop and validate a prediction model using CXR based ...on an AI model and clinical variables to predict clinical outcomes in patients with COVID-19.
This retrospective longitudinal study included patients hospitalized for COVID-19 at multiple COVID-19 medical centers between February 2020 and October 2020. Patients at Boramae Medical Center were randomly classified into training, validation, and internal testing sets (at a ratio of 8:1:1, respectively). An AI model using initial CXR images as input, a logistic regression model using clinical information, and a combined model using the output of the AI model (as CXR score) and clinical information were developed and trained to predict hospital length of stay (LOS) ≤2 weeks, need for oxygen supplementation, and acute respiratory distress syndrome (ARDS). The models were externally validated in the Korean Imaging Cohort of COVID-19 data set for discrimination and calibration.
The AI model using CXR and the logistic regression model using clinical variables were suboptimal to predict hospital LOS ≤2 weeks or the need for oxygen supplementation but performed acceptably in the prediction of ARDS (AI model area under the curve AUC 0.782, 95% CI 0.720-0.845; logistic regression model AUC 0.878, 95% CI 0.838-0.919). The combined model performed better in predicting the need for oxygen supplementation (AUC 0.704, 95% CI 0.646-0.762) and ARDS (AUC 0.890, 95% CI 0.853-0.928) compared to the CXR score alone. Both the AI and combined models showed good calibration for predicting ARDS (P=.079 and P=.859).
The combined prediction model, comprising the CXR score and clinical information, was externally validated as having acceptable performance in predicting severe illness and excellent performance in predicting ARDS in patients with COVID-19.
Background and Aims
EUS‐guided biliary drainage (EUS‐BD) has been proposed as an alternative for patients after failed ERCP. To date, the evaluation of dedicated device for one‐step EUS‐BD has been ...limited. To determine feasibility and safety of a newly designed 7F stent introducer with tapered metal tip as a push‐type dilator for one‐step metal stent placement without additional fistula dilation in EUS‐BD.
Methods
Thirty‐two patients with malignant biliary obstruction and failed ERCP were randomly assigned to a dedicated stent introducer with a modified hybrid metal stent (DH group, n = 16) or a conventional 8.5F biliary metal stent introducer with a fully covered metal stent (FC group, n = 16). The technical success, procedural times, clinical success rate, and adverse event rates were evaluated.
Results
One‐step technical success without additional fistula dilation in the DH was 88% (14/16). Multi‐step process in a stent placement was performed in all patients of the FC group. The procedural time in the DH was significantly shorter than the FC (10 vs. 15 min, P = 0.007). No difference in overall technical or clinical success was seen between the groups. The rate of an early adverse event was common in the FC compared with the DH (31.3% 5/16 in the FC vs. 6.3% 1/16 in the DH, P = 0.172), although not statistically significant.
Conclusions
A dedicated device for one‐step EUS‐BD may be technically feasible, safe, and shorten the procedural times with less chance of an additional fistula dilation process, resulting in a potential reduction of the early adverse events.
Background
Type 1 autoimmune pancreatitis (AIP), as a pancreatic manifestation of IgG4-related disease, shows a favorable prognosis in the short term. However, disease relapse is common in long-term ...follow-up, despite a successful initial treatment response. This study aimed to identify the predictors of relapse and long-term outcomes in patients with type 1 AIP.
Methods
Patients with more than 2 years of follow-up who met the International Consensus Diagnostic Criteria for type 1 AIP were included. Patients who had undergone pancreatic operations associated with AIP or who lacked sufficient clinical data were excluded.
Results
All 138 patients achieved clinical remission with initial steroid therapy, and 66 (47.8%) experienced relapse during a median 60 (range 24–197) months follow-up. Among the relapsed patients, about 74% (49/66) relapsed within 3 years. About 60% (82/138) had other organ involvement (OOI), most commonly in the proximal bile duct (26.8%). At first diagnosis, OOI, and especially OOI of the proximal bile duct, was a significant independent predictor of relapse (hazard ratio 2.65; 95% confidence interval 1.44–4.89;
p
= 0.002), according to multivariate analysis. During the follow-up period, 16 (11.6%) patients experienced endocrine/exocrine dysfunction and 32 (23.2%) patients developed de novo pancreatic calcifications/stones. No pancreatic cancer occurred in any patients.
Conclusions
Type 1 AIP has common relapses, and patients with OOI, especially OOI of the proximal bile duct, appear to be at increased risk for relapse. Long-term sequelae, including pancreatic insufficiency and pancreatic calcifications/stones, are common in patients with relapse. To reduce the relapse, longer maintenance treatment may be needed especially for patients at high risk for relapse.
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