Timing of Direct Oral Anticoagulants Resumption Following Colorectal Endoscopic Submucosal Dissection: A Nationwide Study in Japan.

INTRODUCTION: With the increasing use of direct oral anticoagulants (DOACs), managing these agents around endoscopic submucosal dissection (ESD) is crucial. However, due to the need for a large number of cases, studies examining the timing of resumption are lacking, resulting in varied recommendations across international guidelines. We aimed to perform a comparative study about the resumption timing of DOACs after colorectal ESD using a nationwide database in Japan. METHODS: We conducted a retrospective cohort study on colorectal ESD using the Diagnosis Procedure Combination database from 2012 to 2023. Patients using anticoagulants other than DOACs were excluded, and only those who resumed DOACs within 3 days were included. From eligible patients, we divided them into early (the day after ESD) and delayed (2-3 days after ESD) resumption groups. We used inverse probability of treatment weighting to assess the delayed bleeding and thromboembolic events within 30 days. Delayed bleeding was defined as bleeding requiring endoscopic hemostasis or blood transfusion after ESD. RESULTS: Of 176,139 colorectal ESDs, 3,550 involved DOAC users, with 2,698 (76%) categorized as early resumption and 852 (24%) categorized as delayed resumption groups. After inverse probability of treatment weighting adjustment, the early resumption group did not significantly increase delayed bleeding compared with the delayed resumption group (odds ratio 1.05; 95% confidence interval 0.78-1.42; P = 0.73). However, it significantly reduced the risk of thromboembolic events (odds ratio 0.45; 95% confidence interval 0.25-0.82; P < 0.01). DISCUSSION: Resuming DOACs the day after colorectal ESD was associated with reduced thromboembolic events without significant increase in risk of delayed bleeding.

Optimal cutoff values of drain amylase for predicting pancreatic fistula are different between open and laparoscopic distal pancreatectomy.

BACKGROUND: Drainage fluid amylase (DFA) is useful for predicting clinically relevant postoperative pancreatic fistula (CR-POPF) after distal pancreatectomy (DP). However, difference in optimal cutoff value of DFA for predicting CR-POPF between open DP (ODP) and laparoscopic DP (LDP) has not been investigated. This study aimed to identify the optimal cutoff values of DFA for predicting CR-POPF after ODP and LDP. METHODS: Data for 294 patients (ODP, n = 127; LDP, n = 167) undergoing DP at Kobe University Hospital between 2010 and 2021 were reviewed. Propensity score matching was performed to minimize treatment selection bias. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff values of DFA for predicting CR-POPF for ODP and LDP. Logistic regression analysis for CR-POPF was performed to investigate the diagnostic value of DFA on postoperative day (POD) three with identified cutoff value. RESULTS: In the matched cohort, CR-POPF rates were 24.7% and 7.9% after ODP and LDP, respectively. DFA on POD one was significantly lower after ODP than after LDP (2263 U/L vs 4243 U/L, p < 0.001), while the difference was not significant on POD three (543 U/L vs 1221 U/L, p = 0.171). ROC analysis revealed that the optimal cutoff value of DFA on POD one and three for predicting CR-POPF were different between ODP and LDP (ODP, 3697 U/L on POD one, 1114 U/L on POD three; LDP, 10564 U/L on POD one, 6020 U/L on POD three). Multivariate analysis showed that DFA on POD three with identified cutoff value was the independent predictor for CR-POPF both for ODP and LDP. CONCLUSIONS: DFA on POD three is an independent predictor for CR-POPF after both ODP and LDP. However, the optimal cutoff value for it is significantly higher after LDP than after ODP. Optimal threshold of DFA for drain removal may be different between ODP and LDP.

Association of serum magnesium levels with renal prognosis in patients with chronic kidney disease.

BACKGROUND: Magnesium deficiency is associated with various health conditions, but its impact on the progression of chronic kidney disease (CKD) remains unclear. This study aimed to investigate the association between serum magnesium levels and prognosis of renal function in CKD patients. METHODS: This is an analysis of the Japan Chronic Kidney Disease Database Ex　(J-CKD-DB-Ex), which is a multicenter prospective cohort including CKD patients enrolled from January 1, 2014 to December 31, 2020. We included adult outpatients with CKD stage G3 and G4 at the time of initial magnesium measurement. Patients were classified by magnesium levels as low (<1.7 mg/dl), normal (1.7-2.6 mg/dl), or high (>2.6 mg/dl). The primary outcomes were the composite of an eGFR < 15 ml/min/1.73 m2 or a ≥30% reduction in eGFR from the initial measurement, which was defined as CKD progression. We applied the Kaplan-Meier analysis and Cox regression hazard model to examine the association between magnesium levels and CKD progression. RESULTS: The analysis included 9868 outpatients during the follow-up period. The low magnesium group was significantly more likely to reach CKD progression. Cox regression, adjusting for covariates and using the normal magnesium group as the reference, showed that the hazard ratio for the low magnesium group was 1.20 (1.08-1.34). High magnesium was not significantly associated with poor renal outcomes compared with normal magnesium. CONCLUSION: Based on large real-world data, this study demonstrated that low magnesium levels are associated with poorer renal outcomes.

Prognostic value of initial serum sodium level in predicting disease severity in patients with COVID-19: A multicenter retrospective study.

INTRODUCTION: Early prediction of coronavirus disease (COVID-19) severity is crucial. Hyponatremia has been linked to poor outcomes in hospitalized COVID-19 patients, but its association with mild cases is unclear. This study aimed to investigate whether initial serum sodium level is a risk factor for COVID-19 severity in patients with mild-to-moderate disease. METHODS: A multicenter retrospective cohort study was conducted in 10 hospitals in Fukui City, Japan, from July 1, 2020, to October 31, 2021. The study included 1055 adult patients with asymptomatic, mild, or moderate COVID-19 confirmed by a positive RT-PCR test. The primary outcome was the need for oxygen therapy after hospitalization, and the secondary outcome was the composite of in-hospital death and critical care interventions. The association between initial serum sodium level (at the emergency department or on admission) and outcomes was examined, adjusting for age, sex, hypertension, and pneumonia presence. RESULTS: Of the 1267 patients diagnosed with COVID-19 during the study period, 1055 were eligible (median age: 45 years; 54 % male). Hyponatremia was observed in 5.2 % of patients upon admission. A lower initial serum sodium level was associated with an increased risk of the need for oxygen therapy after hospitalization (adjusted odds ratio [OR] per 1 mmol/L lower, 1.12 [95 % confidence interval {CI}, 1.05-1.19]) and the composite of critical care and in-hospital death (adjusted OR per 1 mmol/L lower, 1.09 [95 % CI, 0.99-1.20]). CONCLUSIONS: Among patients with mild COVID-19, lower initial serum sodium level was a risk factor for COVID-19 progression.

Development and validation of a scoring system for in-hospital mortality following band ligation in esophageal variceal bleeding.

OBJECTIVES: We aimed to develop and validate a simple scoring system to predict in-hospital mortality after endoscopic variceal ligation (EVL) for esophageal variceal bleeding. METHODS: Data from a 13-year study involving 46 Japanese institutions were split into development (initial 7 years) and validation (last 6 years) cohorts. The study subjects were patients hospitalized for esophageal variceal bleeding and treated with EVL. Variable selection was performed using least absolute shrinkage and selection operator regression, targeting in-hospital all-cause mortality as the outcome. We developed the Hospital Outcome Prediction following Endoscopic Variceal Ligation (HOPE-EVL) score from ß coefficients of multivariate logistic regression and assessed its discrimination and calibration. RESULTS: The study included 980 patients: 536 in the development cohort and 444 in the validation cohort. In-hospital mortality was 13.6% and 10.1% for the respective cohorts. The scoring system used five variables: systolic blood pressure (<80 mmHg: 2 points), Glasgow Coma Scale (≤12: 1 point), total bilirubin (≥5 mg/dL: 1 point), creatinine (≥1.5 mg/dL: 1 point), and albumin (<2.8 g/dL: 1 point). The risk groups (low: 0-1, middle: 2-3, high: ≥4) in the validation cohort corresponded to observed and predicted mortality probabilities of 2.0% and 2.5%, 19.0% and 22.9%, and 57.6% and 71.9%, respectively. In this cohort, the HOPE-EVL score demonstrated excellent discrimination ability (area under the curve [AUC] 0.890; 95% confidence interval [CI] 0.850-0.930) compared with the Model for End-stage Liver Disease score (AUC 0.853; 95% CI 0.794-0.912) and the Child-Pugh score (AUC 0.798; 95% CI 0.727-0.869). CONCLUSIONS: The HOPE-EVL score practically and effectively predicts in-hospital mortality. This score could facilitate the appropriate allocation of resources and effective communication with patients and their families.

National trends in hospitalizations for gastrointestinal bleeding in Japan.

Gastrointestinal bleeding (GIB) is a significant public health concern, predominantly associated with high morbidity. However, there have been no reports investigating the trends of GIB in Japan using nationwide data. This study aims to identify current trends and issues in the management of GIB by assessing Japan's national data. We analyzed National Database sampling data from 2012 to 2019, evaluating annual hospitalization rates for major six types of GIB including hemorrhagic gastric ulcers, duodenal ulcers, esophageal variceal bleeding, colonic diverticular bleeding, ischemic colitis, and rectal ulcers. In this study, hospitalization rates per 100,000 indicated a marked decline in hemorrhagic gastric ulcers, approximately two-thirds from 41.5 to 27.9, whereas rates for colonic diverticular bleeding more than doubled, escalating from 15.1 to 34.0. Ischemic colitis rates increased 1.6 times, from 20.8 to 34.9. In 2017, the hospitalization rate per 100,000 for colonic diverticular bleeding and ischemic colitis surpassed those for hemorrhagic gastric ulcers (31.1, 31.3, and 31.0, respectively). No significant changes were observed for duodenal ulcers, esophageal variceal bleeding, or rectal ulcers. The findings of this study underscore a pivotal shift in hospitalization frequencies from upper GIB to lower GIB in 2017, indicating a potential shift in clinical focus and resource allocation.

Reappraisal of Malignant Risk Assessment for Small (≤20 mm) Non-functioning Pancreatic Neuroendocrine Tumors.

BACKGROUND: Optimal management of non-functioning pancreatic neuroendocrine tumors (PanNETs) ≤20 mm is controversial. The biological heterogeneity of these tumors poses challenges when deciding between resection and observation. METHODS: In this multicenter, retrospective cohort study, we analyzed all patients (n = 78) who underwent resection of non-functioning PanNETs ≤20 mm at three tertiary medical centers from 2004 to 2020 to assess the utility of preoperatively available radiological features and serological biomarkers of non-functioning PanNETs in choosing an optimal surgical indication. The radiological features included non-hyper-attenuation pattern on enhancement computed tomography (CT; hetero/hypo-attenuation) and main pancreatic duct (MPD) involvement, and serological biomarkers included elevation of serum elastase 1 and plasma chromogranin A (CgA) levels. RESULTS: Of all small non-functioning PanNETs, 5/78 (6%) had lymph node metastasis, 11/76 (14%) were WHO grade II, and 9/66 (14%) had microvascular invasion; 20/78 (26%) had at least one of these high-risk pathological factors. In the preoperative assessment, hetero/hypo-attenuation and MPD involvement were observed in 25/69 (36%) and 8/76 (11%), respectively. Elevated serum elastase 1 and plasma CgA levels were observed in 1/33 (3%) and 0/11 (0%) patients, respectively. On multivariate logistic regression analysis, hetero/hypo-attenuation (odds ratio [OR] 6.1, 95% confidence interval [CI] 1.7-22.2) and MPD involvement (OR 16.8, 95% CI 1.6-174.3) were significantly associated with the high-risk pathological factors. The combination of the two radiological worrisome features correctly predicted non-functioning PanNETs with high-risk pathological factors, with about 75% sensitivity, 79% specificity, and 78% accuracy. CONCLUSIONS: This combination of radiological worrisome features can accurately predict non-functioning PanNETs that may require resection.

Targeted therapy using polymyxin B hemadsorption in patients with sepsis: a post-hoc analysis of the JSEPTIC-DIC study and the EUPHRATES trial.

BACKGROUND: Polymyxin B hemadsorption (PMX-HA) reduces blood endotoxin levels, but characteristics of patients with sepsis likely to benefit from PMX-HA are not well known. We sought to identify patient subgroups likely to benefit from PMX-HA. METHODS: We retrospectively identified 1911 patients with sepsis from a retrospective observational study in Japan (the JSEPTIC-DIC study) and 286 patients with endotoxemic septic shock from a randomized controlled trial in North America that restricted patients to those with high endotoxin activity (the EUPHRATES trial). We applied the machine learning-based causal forest model to the JSEPTIC-DIC cohort to investigate heterogeneity in treatment effects of PMX-HA on 28-day survival after adjusting for potential confounders and ascertain the best criteria for PMX-HA use. The derived criteria for targeted therapy by PMX-HA were validated using the EUPHRATES trial cohort. RESULTS: The causal forest model revealed heterogeneity in treatment effects of PMX-HA. Since patients having higher treatment effects were more likely to have severe coagulopathy and hyperlactatemia, we identified the potential treatment targets of PMX-HA as patients with PT-INR > 1.4 or lactate > 3 mmol/L. In the EUPHRATES trial cohort, PMX-HA use on the targeted subpopulation (75% of all patients) was significantly associated with higher 28-day survival (PMX-HA vs. control, 68% vs. 52%; treatment effect of PMX-HA, + 16% [95% CI + 2.2% to + 30%], p = 0.02). CONCLUSIONS: Abnormal coagulation and hyperlactatemia in septic patients with high endotoxin activity appear to be helpful to identify patients who may benefit most from PMX-HA. Our findings will inform enrollment criteria for future interventional trials targeting patients with coagulopathy and hyperlactatemia.

Development and Validation of a Novel Method for Converting the Japan Coma Scale to Glasgow Coma Scale.

BACKGROUND: The Japan Coma Scale (JCS) is the most frequently adopted method for evaluating level of consciousness in Japan. However, no validated method for converting the JCS to the Glasgow Coma Scale (GCS) exists. The aims of the present study were to develop and validate a method to convert the JCS to GCS. METHODS: This is a multicenter retrospective analysis involving three emergency departments (EDs) in Japan. We included all adult patients who visited the ED between 2017 and 2020. The participating facilities were divided into two cohorts-one cohort to develop a table to convert the JCS to GCS (development cohort), and the other cohort to validate the conversion table (validation cohort). The conversion table of the JCS to GCS was developed based on the median values of the GCS. The outcome was the concordance rate between the JCS and GCS. RESULTS: We identified 8,194 eligible patients. The development cohort included 7,373 patients and the validation cohort included 821 patients. In the validation cohort, the absolute and relative concordance rates were 80.3% (95% confidence interval, 77.4-82.9%) and 93.2% (95% confidence interval, 91.2-94.8%), respectively. CONCLUSION: This study developed and validated a novel method for converting the JCS to GCS. Assuming the offset by a single category between the JCS and GCS is acceptable, the concordance rate was over 90% in the general adult patient population visiting the ED. The conversion method may assist researchers to convert JCS scores into GCS scores, which are more commonly recognized among global audiences.

Risk Factors for Recurrence of Cholangitis After Pancreaticoduodenectomy and Comparison of Stents in Hepaticojejunostomy.

BACKGROUND: Postoperative cholangitis is a common complication of pancreaticoduodenectomy. Frequent cholangitis impairs patients' quality of life after pancreaticoduodenectomy. However, the risk factors for recurrence of cholangitis remain unclear. Hence, this retrospective study aimed to identify risk factors for recurrence of cholangitis after pancreaticoduodenectomy. METHODS: The medical records of patients who underwent pancreaticoduodenectomy between 2015 and 2019 in our institution were retrospectively reviewed. At least two episodes of cholangitis a year after pancreaticoduodenectomy were defined as 'recurrence of cholangitis' in the present study. Univariate and multivariate analyses were performed. RESULTS: The recurrence of cholangitis occurred in 40 of 207 patients (19.3%). Multivariate analysis revealed that internal stent (external, RR: 2.16, P = 0.026; none, RR: 4.76, P = 0.011), firm pancreas (RR: 2.61, P = 0.021), constipation (RR: 3.49, P = 0.008), and postoperative total bilirubin>1.7 mg/dL (RR: 2.94, P = 0.006) were risk factors of recurrence of cholangitis. Among patients with internal stents (n = 54), those with remnant stents beyond 5 months had more frequent recurrence of cholangitis (≥5 months, 75%; <5 months, 30%). CONCLUSIONS: Internal stents, firm pancreas, constipation, and postoperative high bilirubin levels are risk factors for cholangitis recurrence after pancreaticoduodenectomy. In addition, the long-term implantation of internal stents may trigger cholangitis recurrence.

Explorative Clustering of the Nitrogen Balance Trajectory in Critically Ill Patients: A Preliminary post hoc Analysis of a Single-Center Prospective Observational Study.

BACKGROUND: The nitrogen balance estimates a protein net difference. However, since it has a number of limitations, it is important to consider the trajectory of the nitrogen balance in the clinical course of critically ill patients. OBJECTIVES: We herein exploratively classified the nitrogen balance trajectory using a machine learning method. METHOD: This is a post hoc analysis of a single-center prospective study for the patients admitted to our Emergency and Critical Center ICU. The nitrogen balance was evaluated with 24-h urine collection from ICU days 1-10 with 9 points. K-means clustering was performed to classify the nitrogen balance trajectory. We also evaluated factors associated with uncovered clusters. RESULTS: Seventy-six eligible patients were included in the present study. After clustering, the nitrogen balance trajectory was classified into 4 classes. Class 1 was trajected as a negative balance over 10 days (24 patients). Class 2 had a positive conversion on day 3 or 4 (8 patients). Class 3 had a positive conversion on day 8 or 9 (28 patients). Class 4 initially had a positive balance and then converted to a negative balance (16 patients). Sepsis complication and steroid use were associated with negative nitrogen balance trajectory. Class 2 was associated with lower length of hospital stay and femoral muscle volume loss, however, frequently had frailty and sarcopenia on admission. Active nutrition therapy intention was not correlated with positive trajectory. CONCLUSIONS: The nitrogen balance trajectory in critically ill patients may be classified into 4 classes for clinical practice. Among patients emergently admitted to the ICU, the positive conversion of the nitrogen balance might be delayed over 10 days.

Trauma mechanisms and patterns of blunt cervical vascular injury: A descriptive study using a nationwide trauma registry.

OBJECTIVE: Blunt cervical vascular injury (BCVI) is a non-penetrating trauma to the carotid and/or vertebral vessels following a direct injury to the neck or by the shearing of the cervical vessels. Despite its potentially life-threatening nature, important clinical features of BCVI such as typical patterns of co-occurring injuries for each trauma mechanism are not well known. To address this knowledge gap, we described the characteristics of patients with BCVI to identify the pattern of co-occurring injuries by common trauma mechanisms. METHODS: This is a descriptive study using a Japanese nationwide trauma registry from 2004 through 2019. We included patients aged ≥13 years presenting to the emergency department (ED) with BCVI, defined as a blunt trauma to any of the following vessels: common/internal carotid artery, external carotid artery, vertebral artery, external jugular vein, and internal jugular vein. We delineated characteristics of each BCVI classified according to three damaged vessels (common/internal carotid artery, vertebral artery, and others). In addition, we applied network analysis to unravel patterns of co-occurring injuries among patients with BCVI by four common trauma mechanisms (car accident, motorcycle/bicycle accident, simple fall, and fall from a height). RESULTS: Among 311,692 patients who visited the ED for blunt trauma, 454 (0.1%) patients had BCVI. Patients with common/internal carotid artery injuries presented to the ED with severe symptoms (e.g., the median Glasgow Coma Scale was 7) and had high in-hospital mortality (45%), while patients with vertebral artery injuries presented with relatively stable vital signs. Network analysis showed that head-vertebral-cervical spine injuries were common across four trauma mechanisms (car accident, motorcycle/bicycle accident, simple fall, and fall from a height), with co-occurring injuries of the cervical spine and vertebral artery being the most common injuries due to falls. In addition, common/internal carotid artery injuries were associated with thoracic and abdominal injuries in patients with car accidents. CONCLUSIONS: Based on analyses of a nationwide trauma registry, we found that patients with BCVI had distinct patterns of co-occurring injuries by four trauma mechanisms. Our observations provide an important basis for the initial assessment of blunt trauma and could support the management of BCVI.

Dose reduction of olaparib in older patients: Insights from an analysis of a National Database in Japan.

AIM: Although the advent of a poly polymerase inhibitors has greatly advanced the tailoring of cancer treatment, there is a dearth of real-world evidence on the actual use of olaparib in aging populations, especially those using national-level data. METHODS: We extracted and analyzed all prescriptions of olaparib in female outpatients from the National Database Open Data Japan (NDB Open Data) from April 2019 to March 2021. The recommended standard dose of olaparib is four tablets of the 150 mg formulation per day, while the 100 mg formulation of olaparib can be considered as an alternative dose in the occurrence of hematologic toxicity. We calculated the proportion of 100 mg compared to the 150 mg prescriptions across age groups. A Cochrane-Armitage trend test was used to examine the association of age groups with the proportion of 100 mg prescriptions. RESULTS: The total number of prescriptions of the 100 mg formulation and the 150 mg formulation were 1449 222, and 4233 625, respectively. Overall, 45.1% (2567 513/5682 847 prescriptions) of olaparib were prescribed for patients 65 years of age or older in females. Stratified by age group, the proportion of 100 mg compared to the 150 mg prescriptions significantly increased with age (p < 0.0001). CONCLUSIONS: Given that the 100 mg formulation of olaparib can be considered as an alternative dose in Japan in the occurrence of hematologic toxicity, our observations indicate the dose reduction of olaparib in older patients in Japan. Further investigations are necessary to assess its efficacy and safety at a reduced dose.

Use of a short cartridge stapler is beneficial in pancreatic transection at the neck during laparoscopic distal pancreatectomy.

Stapling is the standard method for pancreatic transection during laparoscopic distal pancreatectomy. Although most surgeons use a 60 mm cartridge stapler, space limitations created by laparoscopic surgery make the instrument difficult to handle, especially during pancreatic transection at the neck. Therefore, we currently use a 45 mm cartridge stapler for laparoscopic pancreatic transection at the neck. Between October 2019 and December 2020, we performed pancreatic transection using a 45 mm cartridge stapler in 27 patients. Fifteen patients experienced biochemical leakage, but no patients developed clinically relevant pancreatic fistula. The compactness of the 45 mm cartridge has several benefits: (1) less space is required for flexing, opening, and closing the device; (2) it enables easy insertion of the lower jaw behind the pancreas, even if the dissected space behind the pancreas is narrow; (3) less obstruction of the surgeons' view prevents accidental injury to the surrounding tissues and vessels. These benefits may enable safe pancreatic transection.

Transarterial chemoembolization for liver metastases of a pancreatic neuroendocrine neoplasm: a single-center experience.

Transarterial chemoembolization (TACE) is performed for pancreatic neuroendocrine tumor (PanNEN) liver metastases; however, the safety and efficacy of TACE procedures, especially for patients who have undergone previous pancreatic surgery, have not been established. We reviewed 48 TACE procedures (1-6 procedures/patient) performed on 11 patients with PanNEN liver metastases, including 16 TACE procedures (4-6 procedures/patient) for 3 patients with a history of biliary-enteric anastomosis. The overall tumor objective response rate was 94%. The incidence of Clavien‒Dindo grade ≥ 2 complications was 1/16 (6%) and 1/32 (3%), and the median time to untreatable progression was 31 (14-41) and 27 (2-60) months among patients with and without a history of biliary-enteric anastomosis, respectively. Although validation is needed in future studies, our experiences have shown that TACE treatment is a viable treatment option for PanNEN liver metastases, even after biliary-enteric anastomosis with experienced teams and careful patient follow-up.

Web-based application for predicting the potential target phenotype for recombinant human thrombomodulin therapy in patients with sepsis: analysis of three multicentre registries.

A recent randomised controlled trial failed to demonstrate a beneficial effect of recombinant human thrombomodulin (rhTM) on sepsis. However, there is still controversy in the effects of rhTM for sepsis due to the heterogeneity of the study population. We previously identified patients with a distinct phenotype that could be a potential target of rhTM therapy (rhTM target phenotype). However, for application in the clinical setting, a simple tool for determining this target is necessary. Thus, using three multicentre sepsis registries, we aimed to develop and validate a machine learning model for predicting presence of the target phenotype that we previously identified for targeted rhTM therapy. The predictors were platelet count, PT-INR, fibrinogen, fibrinogen/fibrin degradation products, and D-dimer. We also implemented the model as a web-based application. Two of the three registries were used for model development (n = 3694), and the remaining registry was used for validation (n = 1184). Approximately 8-9% of patients had the rhTM target phenotype in each cohort. In the validation, the C statistic of the developed model for predicting the rhTM target phenotype was 0.996 (95% CI 0.993-0.998), with a sensitivity of 0.991 and a specificity of 0.967. Among patients who were predicted to have the potential target phenotype (predicted target patients) in the validation cohort (n = 142), rhTM use was associated with a lower in-hospital mortality (adjusted risk difference, - 31.3% [- 53.5 to - 9.1%]). The developed model was able to accurately predict the rhTM target phenotype. The model, which is available as a web-based application, could profoundly benefit clinicians and researchers investigating the heterogeneity in the treatment effects of rhTM and its mechanisms.

Standardization of laparoscopic anatomic liver resection of segment 2 by the Glissonean approach.

BACKGROUND: Anatomic liver resection (ALR) has been established to eliminate the tumor-bearing hepatic region with preservation of the remnant liver volume for liver malignancies. Recently, laparoscopic ALR has been widely applied; however, there are few reports on laparoscopic segmentectomy 2. This study aimed to present the standardization of laparoscopic segmentectomy 2 with surgical outcomes. METHODS: This study included seven patients who underwent pure laparoscopic segmentectomy 2 by the Glissonean approach from January 2020 to December 2021. Four of them had hepatocellular carcinoma, two had colorectal liver metastasis, and one had hepatic angiomyolipoma, which was preoperatively diagnosed with hepatocellular carcinoma. In all patients, preoperative three-dimensional (3D) simulation images from dynamic CT were reconstructed using a 3D workstation. The layer between the hepatic parenchyma and the Glissonean pedicle of segment 2 (G2) was dissected to encircle the root of G2. After clamping or ligation of the G2, 2.5 mg of indocyanine green was injected intravenously to identify the boundaries between segments 2 and 3 with a negative staining method under near-infrared light. Parenchymal transection was performed from the caudal side to the cranial side according to the demarcation on the liver surface, and the left hepatic vein was exposed on the cut surface if possible. RESULTS: The mean operative time for all patients was 281 min. The mean blood loss was 37 mL, and no transfusion was necessary. Estimated liver resection volumes significantly correlated with actual liver resection volumes (r = 0.61, P = 0.035). After the operation, one patient presented with asymptomatic deep venous and pulmonary thrombosis, which was treated with anticoagulant therapy. The mean length of hospital stay was 8.9 days. CONCLUSION: Laparoscopic segmentectomy 2 by the Glissonean approach is a feasible and safe procedure with the preservation of the nontumor-bearing segment 3 for liver tumors in segment 2.

Prognostic Impact of Inflammation-Based Scores for Extrahepatic Cholangiocarcinoma.

INTRODUCTION: Although the relationship between systemic inflammatory responses and prognosis has been known in various cancers, it remains unclear which scores are most valuable for determining the prognosis of extrahepatic cholangiocarcinoma. We aimed to verify the usefulness of various inflammation-based scores as prognostic factors in patients with resected extrahepatic cholangiocarcinoma. METHODS: We analyzed consecutive patients undergoing surgical resection for extrahepatic cholangiocarcinoma at our institution between January 2000 and December 2019. The usefulness of the following inflammation-based scores as prognostic factor was investigated: glasgow prognostic score (GPS), modified GPS, neutrophil-to-lymphocyte ratio, platelet to lymphocyte ratio, lymphocyte-to-monocyte ratio, prognostic nutrition index, C-reactive protein to albumin ratio (CAR), controlling nutritional status (CONUT), and prognostic index. RESULTS: A total of 169 patients were enrolled in this study. Of the nine scores, CAR and CONUT indicated prognostic value. Furthermore, multivariate analysis for overall survival revealed that high CAR (>0.23) was an independent prognostic factor (hazard ratio: 1.816, 95% confidence interval: 1.135-2.906, p = 0.0129), along with lymph node metastasis and curability. There was no difference in tumor staging and short-term outcomes between the low CAR (≤0.23) and high CAR groups. CONCLUSIONS: CAR was the most valuable prognostic score in patients with resected extrahepatic cholangiocarcinoma.

External validation of the POP score for predicting obstetric and gynecological diseases in the emergency department.

BACKGROUND: The POP score was developed as an easy screening tool for predicting obstetrics and gynecological (OBGYN) diseases in the emergency department (ED), and consists of three predictors, each representing one point: past history of OBGYN diseases, no fever or digestive symptoms, and peritoneal irritation signs). However, its external validity has not yet been evaluated. We aimed to perform the external validation of the POP score. METHODS: This is a multi-center, retrospective cohort study using ED data of three tertiary care hospitals in Japan between Jan 2017 and October 2020. Young adult women aged 16-49 years with abdominal pain were included in the analysis. The probability of OBGYN diseases was calculated using a logistic regression model of the POP score. Predictions were compared with observations to evaluate the calibration of the model. Further, the diagnostic ability (sensitivity, specificity, and likelihood ratio) of the POP score was evaluated. RESULTS: Of 66,599 ED visits, 1026 young adult women (median age [interquartile range]: 31 [23-41] years) were included for the analysis. The c-statistic was 0.645 [95% confidence interval (CI): 0.603-0.687]. The predicted probabilities of OBGYN diseases was generally well-calibrated to the observations. When the cut-off was set between 2 and 3 points for the ruling in of OBGYN diseases, the positive likelihood ratio was 9.72 [95% CI: 3.33-28.4]. When the cut-off was set between 0 and 1 points for ruling out of OBGYN diseases, negative likelihood ratio was 0.181 [95% CI: 0.059-0.558]. CONCLUSIONS: Using ED data of three tertiary care hospitals, we externally validated the POP score for prediction of OBGYN diseases in the ED. The POP score likely has clinical value for screening OBGYN diseases in young adult women with abdominal pain in the ED.

Machine learning in gastrointestinal surgery.

Machine learning (ML) is a collection of algorithms allowing computers to learn directly from data without predetermined equations. It is used widely to analyze "big data". In gastrointestinal surgery, surgeons deal with various data such as clinical parameters, surgical videos, and pathological images, to stratify surgical risk, perform safe surgery and predict patient prognosis. In the current "big data" era, the accelerating accumulation of a large amount of data drives studies using ML algorithms. Three subfields of ML are supervised learning, unsupervised learning, and reinforcement learning. In this review, we summarize applications of ML to surgical practice in the preoperative, intraoperative, and postoperative phases of care. Prediction and stratification using ML is promising; however, the current overarching concern is the availability of ML models. Information systems that can manage "big data" and integrate ML models into electronic health records are essential to incorporate ML into daily practice. ML is fundamental technology to meaningfully process data that exceeds the capacity of the human mind to comprehend. The accelerating accumulation of a large amount of data is changing the nature of surgical practice fundamentally. Artificial intelligence (AI), represented by ML, is being incorporated into daily surgical practice.