CHST4 Gene as a Potential Predictor of Clinical Outcome in Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) develops primarily from asbestos exposures and has a poor prognosis. In this study, The Cancer Genome Atlas was used to perform a comprehensive survival analysis, which identified the CHST4 gene as a potential predictor of favorable overall survival for patients with MPM. An enrichment analysis of favorable prognostic genes, including CHST4, showed immune-related ontological terms, whereas an analysis of unfavorable prognostic genes indicated cell-cycle-related terms. CHST4 mRNA expression in MPM was significantly correlated with Bindea immune-gene signatures. To validate the relationship between CHST4 expression and prognosis, we performed an immunohistochemical analysis of CHST4 protein expression in 23 surgical specimens from surgically treated patients with MPM who achieved macroscopic complete resection. The score calculated from the proportion and intensity staining was used to compare the intensity of CHST4 gene expression, which showed that CHST4 expression was stronger in patients with a better postoperative prognosis. The median overall postoperative survival was 107.8 months in the high-expression-score group and 38.0 months in the low-score group (p = 0.044, log-rank test). Survival after recurrence was also significantly improved by CHST4 expression. These results suggest that CHST4 is useful as a prognostic biomarker in MPM.

Prediction of the neurological outcomes post-cardiac arrest: A prospective validation of the CAST and rCAST.

INTRODUCTION: The neurologic prognosis of out-of-hospital cardiac arrest (OHCA) patients in whom return of spontaneous circulation (ROSC) is achieved remains poor. The aim of this study was to externally and prospectively validate two scoring systems developed by us: the CAST score, a scoring system to predict the neurological prognosis of OHCA patients undergoing targeted temperature management (TTM), and a simplified version of the same score developed for improved ease of use in clinical settings, the revised CAST (rCAST) score. METHODS: This study was a prospective, multicenter, observational study conducted using the SOS KANTO 2017 registry, an OHCA registry involving hospitals in the Kanto region (including Tokyo) of Japan. The primary outcome was favorable neurological outcome (defined as Cerebral Performance Category score of 1 or 2) at 30 days and the secondary outcomes were favorable neurological outcome at 90 days and survival at 30 and 90 days. The predictive accuracies of the original CAST (oCAST) and rCAST scores were evaluated by using area under the receiver operating characteristic curve (AUC). RESULTS: Of 9909 OHCA patients, 565 showed ROSC and received TTM. Of these, we analyzed the data of 259 patients in this study. The areas under the receiver operating characteristic curve (AUCs) of the oCAST and rCAST scores for predicting a favorable neurological outcome at 30 days were 0.86 and 0.87, respectively, and those for predicting a favorable neurological outcome at 90 days were 0.87 and 0.88, respectively. The rCAST showed a higher predictive accuracy for the neurological outcome as compared with the NULL-PLEASE score. The patients with a favorable neurological outcome who had been classified into the high severity group based on the rCAST tended to have hypothermia at hospital arrival and to not show any signs of loss of gray-white matter differentiation on brain CT. Neurological function at 90 days was correlated with the rCAST (r = 0.63, p < 0.001). CONCLUSIONS: rCAST showed high predictive accuracy for the neurological prognosis of OHCA patients managed by TTM, comparable to that of the oCAST score. The scores on the rCAST were strongly correlated with the neurological functions at 90 days, implying that the rCAST is a useful scale for assessing the severity of brain injury after cardiac arrest.

Prognostic impact of highly solid component in early-stage solid lung adenocarcinoma.

Background: Based on computed tomography (CT) findings of lung cancer, solid nodules have a much worse prognosis than subsolid nodules, even if the nodules are subcentimeter in size. There is, however, no systematic method for determining the prognosis of solid tumors on CT. This study aimed to discover the prognostic factor of early-stage solid lung adenocarcinoma using three-dimensional CT volumetry. Methods: Patients with pathological stage I solid lung adenocarcinoma who underwent complete resection between 2007 and 2012 were selected in this retrospective study. Clinicopathological data and preoperative multidetector CT findings, such as tumor size on the two-dimensional axial image, three-dimensional tumor volume between -600 and 199 HU, and three-dimensional solid volume between 0 and 199 HU, which corresponded to highly solid components, were compared between recurrence and non-recurrence. Furthermore, these radiological values were compared to pathological invasive volume (PIV). Results: During this time, 709 patients had their lung cancer completely removed. From this cohort, 90 patients with pathological stage I solid lung adenocarcinoma were selected. In addition, recurrence was found in 26 patients (28.9%). Although two-dimensional axial image, serum carcinoembryonic antigen (CEA) level, and SUVmax on 18F fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) did not differ statistically between recurrent and non-recurrent patients, three-dimensional tumor and solid tumor volume did. Multivariate analysis indicated that three-dimensional solid tumor volume [hazard ratio: 2.440; 95% confidence interval (CI): 1.110-5.361, P=0.026] and epidermal growth factor receptor (EGFR) mutation (hazard ratio: 4.307; 95% CI: 1.328-13.977, P=0.015) were significantly associated with disease-free survival (DFS). When three-dimensional tumor and solid tumor volume were compared to PIV, three-dimensional solid tumor volume (3,091 mm3 on average) showed a highly similar value with PIV (2,930 mm3 on average), whereas three-dimensional tumor volume (6,175 mm3 on average) was significantly larger than PIV (P<0.001). Conclusions: In patients with early-stage solid lung adenocarcinoma, the measurement of three-dimensional solid tumor volume, which is correlated with PIV, accurately predicted the postoperative outcome.

Systematic Review and Meta-Analysis of the Use of Serum Leucine-Rich Alpha-2 Glycoprotein to Assess Crohn's Disease Activity.

BACKGROUND: Although fecal calprotectin is the most widely used biomarker for assessing Crohn's disease activity, serum leucine-rich alpha-2 glycoprotein has recently attracted attention, especially in Japan. Here we performed a systematic review and meta-analysis of serum leucine-rich alpha-2 glycoprotein to obtain evidence for its accuracy in assessing Crohn's disease activity. METHODS: On February 1, 2023, we performed searches of PubMed, Web of Science, and CENTRAL. The Prospero number is CRD42023396034. The primary outcomes were the sensitivity and specificity of serum leucine-rich alpha-2 glycoprotein for assessing Crohn's disease activity. We used a bivariate generalized linear mixed model, assuming a binomial distribution at the test level and a bivariate normal distribution at the between-test level. RESULTS: We selected 9 studies involving 797 individuals in our systematic review. Regarding the primary outcomes, the synthesized sensitivity and specificity of serum leucine-rich alpha-2 glycoprotein were 77.0% (95% confidence interval, 67.8% to 84.2%) and 81.1% (95% confidence interval, 72.6% to 87.4%), respectively. The area under the curve was 0.86, and the partial area under the curve was 0.78. Regarding between-study heterogeneity, both the I2 value by Zhou and Dendukuri approach and the I2 value by Holling sample size-adjusted approaches were 0%. CONCLUSIONS: Our systematic review and meta-analysis of serum leucine-rich alpha-2 glycoprotein demonstrated its accuracy in assessing Crohn's disease activity. Further studies are needed to demonstrate its clinical utility and clinical validity.

We conducted the first systematic review and meta-analysis of the ability of serum leucine-rich alpha-2 glycoprotein (LRG) to assess Crohn's disease activity and found that the synthesized sensitivity and specificity were 77.0% and 81.1%, respectively.

Evaluating glucose variability through OGTT in early pregnancy and its association with hypertensive disorders of pregnancy in non-diabetic pregnancies: a large-scale multi-center retrospective study.

BACKGROUND: Recent evidence suggests increased glucose variability (GV) causes endothelial dysfunction, a central pathology of hypertensive disorders of pregnancy (HDP). We aimed to investigate the association between GV in early pregnancy and subsequent HDP development among non-diabetes mellitus (DM) pregnancies. METHODS: This multicenter retrospective study used data from singleton pregnancies between 2009 and 2019. Among individuals who had 75 g-OGTT before 20 weeks of gestation, we evaluated GV by 75 g-OGTT parameters and examined its relationship with HDP development, defining an initial-increase from fasting-plasma glucose (PG) to 1-h-PG and subsequent-decrease from 1-h-PG to 2-h-PG. RESULTS: Approximately 3.0% pregnancies (802/26,995) had 75 g-OGTT before 20 weeks of gestation, and they had a higher prevalence of HDP (14.3% vs. 7.5%). The initial-increase was significantly associated with overall HDP (aOR 1.20, 95% CI 1.02-1.42), and the subsequent-decrease was associated with decreased and increased development of early-onset (EoHDP: aOR 0.56, 95% CI 0.38-0.82) and late-onset HDP (LoHDP: aOR 1.38, 95% CI 1.11-1.73), respectively. CONCLUSIONS: A pattern of marked initial-increase and minor subsequent-decrease (i.e., sustained hyperglycemia) was associated with EoHDP. Contrarily, the pattern of marked initial-increase and subsequent-decrease (i.e., increased GV) was associated with LoHDP. This provides a new perspective for future study strategies.

The prognostic impact of limited-staging surgery in patients with stage IA epithelial ovarian cancer: a multi-center study with a propensity score-adjusted analysis.

OBJECTIVE: Complete-staging surgery is recommended for stage IA ovarian cancer, but may be omitted for various reasons, including the preservation of fertility and an advanced age. We herein investigated the prognostic impact of limited-staging surgery in patients with stage IA epithelial ovarian cancer. METHODS: We retrospectively collected data on 4730 patients with malignant ovarian tumors from the databases of multiple institutions and ultimately included 293 with stage IA epithelial ovarian cancer. Limited-staging surgery was defined as one that did not involve hysterectomy, systematic retroperitoneal lymphadenectomy or the collection of ascites cytology. We used an inverse probability of treatment weighting analysis with propensity scores and estimated the hazard ratios of recurrence and death with limited-staging surgery. RESULTS: In total, 176 out of 293 patients (39.9%) were assigned to the limited-staging surgery group. After propensity score adjustments, no significant differences were observed in recurrence-free survival or overall survival between the limited- and complete-staging surgery groups. Even in the subgroup analysis with age stratification, recurrence-free survival and overall survival were similar in the limited- and complete-staging surgery groups. CONCLUSIONS: The present results indicate the limited prognostic impact of limited-staging surgery for stage IA epithelial ovarian cancer.

Factors associated with adverse drug reactions or death in very elderly hospitalized patients with pulmonary tuberculosis.

The aging of patients with tuberculosis and better therapeutic management for them are recent concerns. This study aimed to identify risk factors for adverse drug reactions (ADRs) or death in very elderly patients with pulmonary tuberculosis and to assess the association between the dosage of antituberculosis drugs and outcomes. We conducted a multicenter retrospective study at two hospitals. Hospitalized patients (≥ 80 years old) with pulmonary tuberculosis who were treated with antituberculosis drugs were enrolled. Multivariate analysis was performed to assess factors associated with ADRs or death within 60 days after treatment initiation. In total, 632 patients were included. The primary endpoint occurred in 268 patients (190 ADRs and 78 deaths). A serum albumin level < 2.5 g/dL, respiratory failure, and dependent activities of daily living were independent risk factors for ADRs or death. However, a low dosage (< 8 mg/kg/day) of rifampicin was associated with a lower risk of the primary outcomes. Delayed time to negative sputum culture conversion was not observed in the lower dosage of rifampicin group. Very elderly hospitalized tuberculosis patients with the aforementioned risk factors should be carefully monitored to receive safer treatment. Rifampicin dosage reduction may be considered for very elderly tuberculosis patients to prevent ADRs/death.

Efficacy of Endoscopic Ultrasound-guided Celiac Plexus Neurolysis for Abdominal Pain in Patients With Unresectable Pancreatic Cancer: Network Meta-analysis of Randomized Controlled Trials.

GOALS: We conducted a systematic review and network meta-analysis to investigate the effect of endoscopic ultrasound-guided celiac plexus neurolysis added to medical management (EUS-CPN+MM) compared with MM, percutaneous CPN (P-CPN)+MM, or intraoperative CPN (I-CPN)+MM for abdominal pain associated with unresectable pancreatic cancer. BACKGROUND: Many approaches to CPN have been proposed since 1919. EUS-CPN, which is less invasive and safer than traditional procedures, has been preferred recently, but the superiority of EUS-CPN+MM has not been fully investigated. STUDY: We performed searches of PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) on March 16, 2021. We conducted the network meta-analysis using a frequentist weighted least-squares approach. We used a random-effects model to synthesize the primary outcome, defined as the mean difference between treatment groups in standardized pain intensity scores at 4 and 12 weeks. RESULTS: We selected 10 RCTs involving 662 individuals. At 4 weeks, the estimated mean difference between the EUS-CPN+MM and MM groups was -1.30 (95% CI: -2.19 to -0.41) in favor of EUS-CPN+MM, and that between the EUS-CPN+MM and P-CPN+MM groups was -0.88 (95% CI: -1.82 to 0.06). At 12 weeks, the estimated mean difference between the EUS-CPN+MM and MM groups was -2.58 (95% CI: -3.68 to -1.48), and that between the EUS-CPN+MM and P-CPN+MM groups was -2.44 (95% CI: -4.03 to -0.84), both in favor of EUS-CPN+MM. CONCLUSIONS: The combination of EUS-CPN+MM was effective at 4 and 12 weeks, although the risk of bias in synthesized studies was generally high, necessitating careful interpretation.

Effect of omega-3 fatty acids on cardiovascular events in high-risk patients with hypertriglyceridemia in Japan: a 3-year post-marketing surveillance study (OCEAN3 survey).

BACKGROUND: Studies on the efficacy of prescription omega-3 polyunsaturated fatty acids to reduce cardiovascular events have produced conflicting results. RESEARCH DESIGN AND METHODS: This 3-year prospective post-marketing surveillance study evaluated the effect of omega-3-acid ethyl esters (O3AEE; usual dosage 2 g/day) on cardiovascular events in high-risk statin-treated Japanese patients with hypertriglyceridemia. Statin-treated patients not receiving O3AEE were included as a reference cohort. The composite primary endpoint was cardiovascular death, myocardial infarction, stroke, angina requiring coronary revascularization, or peripheral arterial disease requiring surgery or peripheral arterial intervention. RESULTS: At 3 years, Kaplan-Meier estimated cumulative incidence of the primary endpoint was 2.5% (95% confidence interval, 2.1%-2.9%) in O3AEE-treated patients (N = 6,580) and 2.7% (2.4%-3.1%) in non-O3AEE-treated patients (N = 7,784; hazard ratio, 0.99; 95% confidence interval, 0.79-1.23). Incidence of heart failure requiring hospitalization was 0.4% with O3AEE versus 0.8% in non-O3AEE-treated patients (hazard ratio, 0.47; 95% confidence interval, 0.28-0.78; P < 0.05). CONCLUSIONS: Among patients receiving statins, cardiovascular event incidence did not differ significantly between O3AEE-treated patients and non-O3AEE-treated patients. Further studies are required before definitive conclusions can be drawn on the effect of O3AEE on cardiovascular event incidence in high-risk patients with hypertriglyceridemia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02285166.

The finger-to-nose test improved diagnosis of cerebrovascular events in patients presenting with isolated dizziness in the emergency department.

It is difficult to identify patients with isolated dizziness caused by cerebrovascular events. The estimated risk of cerebrovascular events in isolated dizziness patients is not completely understood. We aimed to evaluate the association of the finger-to-nose test (FNT) in diagnosing cerebrovascular events in isolated dizziness patients in emergency departments (EDs). We combined 2 datasets from a single center for consecutive isolated dizziness patients, with the same inclusion and exclusion criteria. Those who met any of the following criteria were excluded: no FNT data, age < 16 years, and psychological trauma. The primary outcome was cerebrovascular event, which was defined as cerebral stroke due to cerebral infarction, cerebral hemorrhage, vertebral artery dissection, or transient ischemic attack. In the combined dataset, there were 357 patients complaining of isolated dizziness and 31 cerebrovascular events. After adjusted by 5 previously reported risk factors for cerebrovascular event, (age, hypertension, hyperlipidemia, diabetes mellitus, nystagmus), a multivariable logistic model analysis showed that the existence of FNT abnormalities was significantly associated with cerebrovascular events (odds ratio, 25.3; 95% confidence interval, 7.3-88.2; p < 0.001). There was a significant increase in predictive accuracy, with an AUC increase of 0.116 in the in a ROC analysis (p = 0.023). The existence of FNT abnormalities is considered as a strong risk factor that could be useful for predicting cerebrovascular events in isolated dizziness patients. We recommend the FNT for screening isolated dizziness patients in EDs to judge whether they need to undergo further diagnostic evaluation.

Extended-spectrum antibiotics for community-acquired pneumonia with a low risk for drug-resistant pathogens.

OBJECTIVES: The potential hazards of extended-spectrum antibiotic therapy for patients with community-acquired pneumonia (CAP) with low risk for drug-resistant pathogens (DRPs) remain unclear; however, risk assessment for DRPs is essential to determine the initial antibiotics to be administered. The study objective was to assess the effect of unnecessary extended-spectrum therapy on the mortality of such patients. METHODS: A post hoc analysis was conducted after a prospective multicenter observational study for CAP. Multivariable logistic regression analysis was performed to assess the effect of extended-spectrum therapy on 30-day mortality. Three sensitivity analyses, including propensity score analysis to confirm the robustness of findings, were also performed. RESULTS: Among 750 patients with CAP, 416 with CAP with a low risk for DRPs were analyzed; of these, 257 underwent standard therapy and 159 underwent extended-spectrum therapy. The 30-day mortality was 3.9% and 13.8% in the standard and extended-spectrum therapy groups, respectively. Primary analysis revealed that extended-spectrum therapy was associated with increased 30-day mortality compared with standard therapy (adjusted odds ratio 2.82; 95% confidence interval 1.20-6.66). The results of the sensitivity analyses were consistent with those of the primary analysis. CONCLUSION: Physicians should assess the risk for DRPs when determining the empirical antibiotic therapy and should refrain from administering unnecessary extended-spectrum antibiotics for patients with CAP with a low risk for DRPs.

Bias correction based on weighted likelihood for conditional estimation of subgroup effects in randomized clinical trials.

Currently, many confirmatory randomized clinical trials (RCTs) with predictive markers have taken the all-comers approach because of the difficulty in developing predictive markers that are biologically compelling enough to apply the enrichment approach to restrict the patient population to a marker-defined subgroup. However, such a RCT with weak marker credentials can conclude that the new treatment is efficacious only in the subgroup, especially when the primary analysis demonstrates some treatment efficacy in the subgroup, but the overall treatment efficacy is not significant under a control of study-wise alpha rate. In this article, we consider conditional estimation of subgroup treatment effects, given the negative result in testing the overall treatment efficacy in the trial. To address the problem of unstable estimation due to the truncation in the distribution of the test statistic on overall treatment efficacy, we propose a new approach based on a weighted likelihood for the truncated distribution. The weighted likelihood can be derived by invoking a randomized test with a smooth critical function for the overall test. Our approach allows for point and interval estimations of the conditional effects consistently based on the standard maximum likelihood inference. Numerical evaluations, including simulations and application to real clinical trials, and guidelines for implementing our methods with R-codes, are provided.

Blinded sample size re-estimation for comparing over-dispersed count data incorporating follow-up lengths.

Blinded sample size re-estimation (BSSR) is an adaptive design to prevent the power reduction caused by misspecifications of the nuisance parameters in the sample size calculation of comparative clinical trials. However, conventional BSSR methods used for overdispersed count data may not recover the power as expected under the misspecification of the working variance function introduced by the specified analysis model. In this article, we propose a BSSR method that is robust to the misspecification of the working variance function. A weighted estimator of the dispersion parameter for the BSSR is derived, where the weights are introduced to incorporate the difference in the distribution of follow-up length between the interim analysis with BSSR and the final analysis. Simulation studies demonstrated the power of the proposed BSSR method was relatively stable under misspecifications of the working variance function. An application to a hypothetical randomized clinical trial of a treatment to reduce exacerbation rate in patients with chronic obstructive pulmonary disease is provided.

Effects of lymphocyte and neutrophil counts and their time courses on mortality in patients with postoperative pneumonia.

The prognostic significance of absolute lymphocyte count (ALC) and absolute neutrophil count (ANC) remains unclear in patients with postoperative pneumonia (POP). The study objectives were to investigate the prognostic effects of ALC and ANC in POP patients, and to evaluate the time courses of ALC and ANC during hospitalization. This post-hoc analysis of a single-center prospective observational study evaluated consecutive POP patients, and comparatively analyzed community-acquired pneumonia (CAP) patients to highlight features of POP. In total, 228 POP patients and 1027 CAP patients were assessed. Severe lymphopenia (ALC < 500 cells/µL) at diagnosis was associated with worse 90-day survival in both types of pneumonia. In POP patients, neutrophilia (ANC > 7500 cells/µL) was associated with better survival, whereas CAP patients with neutrophilia tended to have a lower survival rate. Prolonged lymphopenia and delayed increase in neutrophils were characteristic time-course changes of non-survivors in POP. The time courses of ALC and ANC between survivors and non-survivors in POP trended differently from those in CAP. Our study showed that ALC and ANC at pneumonia diagnosis can serve as prognostic factors in POP patients. Differences in time-course changes of ALC and ANC between survivors and non-survivors may provide important information for future immunological research in pneumonia.

Obesity contributes to the stealth peritoneal dissemination of ovarian cancer: a multi-institutional retrospective cohort study.

OBJECTIVE: The clinical significance of a higher BMI on the prognosis of ovarian cancer remains controversial; therefore, a more detailed analysis is demanded. This study investigated the impact of BMI on peritoneum-specific recurrence to clarify the involvement of adipose tissue in the proliferation of cancer cells at sites of peritoneal dissemination. METHODS: Among 4,730 patients with malignant ovarian tumors, 280 diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IIIC epithelial ovarian cancer and who underwent complete resection in the primary surgery were included in the present study. RESULTS: There were 42, 201, and 37 women in the low, normal, and high BMI groups, respectively. Peritoneum-specific recurrence-free survival and overall survival were both significantly shorter in patients with a high BMI than in those with a normal BMI (p = 0.028 and 0.018, respectively). No significant differences were observed in the distribution of sites of recurrence between these two groups. A multivariate analysis identified obesity as an independent prognostic factor in addition to pT3 tumor staging and positive ascites cytology. CONCLUSIONS: Patients with a high BMI had a significantly worse prognosis than those with a normal BMI, and peritoneal adipose tissue may have contributed to this difference.

Who are the long-term survivors of recurrent ovarian carcinoma?: a retrospective analysis of a multicenter study.

BACKGROUND: The aim of the present study was to investigate the incidence and hallmarks of long-term survivors of recurrent ovarian carcinoma (LTSROC) in a large-scale retrospective cohort of patients from a multicenter study group. METHODS: We performed a regional multicenter retrospective study between January 1986 and September 2021 using clinical data collected under the central pathological review system. Patients who underwent surgery for primary OC at diagnosis and developed recurrent tumors after the initial treatment were included. We defined LTSROC as patients who survived for 5 years or longer after initial tumor recurrence and examined factors affecting the long-term survival of ROC and outcomes of LTSROC. RESULTS: We collected information on patients with malignant ovarian tumors and finally 657 of them that developed ROC were included in the study population. Sixty-eight (10.4%) patients were LTSROC while 399 (60.7%) were short-term survivors of recurrent ovarian carcinoma. In a multivariate logistic regression analysis, negative ascites cytology [odds ratio (OR) 1.865; 95% CI 1.026-3.393; p = 0.041] and a recurrence-free interval (RFI) of 1 year or longer (OR 2.896; 95% CI 1.546-5.425; p < 0.001) were identified as independent factors associated with LTSROC. Approximately 80% of LTSROC presented with solitary recurrent tumors. Furthermore, more than 50% of LTSROC underwent tumor debulking surgery for the first recurrent tumor with or without chemotherapy. CONCLUSION: RFI of 1 year or longer and negative ascites cytology in the initial surgery were identified as independent predictive factors for LTSROC.

Systematic review and meta-analysis of celiac plexus neurolysis for abdominal pain associated with unresectable pancreatic cancer.

INTRODUCTION: Celiac plexus neurolysis (CPN) has been developed as adjunctive therapy to medical management (MM) of abdominal pain associated with unresectable pancreatic cancer. We aimed to conduct a systematic review and meta-analysis to obtain updated and more accurate evidence on the efficacy of additional types of CPN, including endoscopic ultrasound-guided CPN (EUS-CPN). METHODS: On March 16, 2021, we performed searches of PubMed, Web of Science, and CENTRAL for original randomized controlled trials (RCTs). We defined the primary outcome as a standardized pain intensity score with a range of 0-10, and evaluated the mean difference between the CPN + MM and MM groups at 4, 8, and 12 weeks after the initiation of treatment. We used a random-effects model to synthesize the mean differences across RCTs. RESULTS: We selected 10 RCTs involving 646 individuals. The synthesized mean difference in the pain intensity score between the CPN + MM and MM groups was -0.58 (95% confidence interval [CI]: -1.09 to -0.07) (p = 0.034) in favor of CPN + MM at 4 weeks, -0.46 (95%CI: -1.00 to 0.08) (p = 0.081) at 8 weeks, and - 1.35 (95%CI: -3.61 to 0.92) (p = 0.17) at 12 weeks. CONCLUSIONS: This updated meta-analysis of CPN demonstrates its efficacy for managing abdominal pain at 4 weeks. Although there are various limitations, when abdominal pain in patients with unresectable pancreatic cancer is poorly controlled with MM alone, CPN should be an option even if the duration of effect is short-lived, taking into account the absence of serious adverse events.

Prediction of Prehospital Change of the Cardiac Rhythm From Nonshockable to Shockable in Out-of-Hospital Patients With Cardiac Arrest: A Post Hoc Analysis of a Nationwide, Multicenter, Prospective Registry.

Background Predicting a spontaneous rhythm change from nonshockable to shockable before hospital arrival in patients with out-of-hospital cardiac arrest can help emergency medical services develop better strategies for prehospital treatment. The aim of this study was to identify predictors of spontaneous rhythm change before hospital arrival in patients with out-of-hospital cardiac arrest and develop a predictive scoring system. Methods and Results We retrospectively reviewed data of eligible patients with out-of-hospital cardiac arrest with an initial nonshockable rhythm registered in a nationwide registry between June 2014 and December 2017. We performed a multivariable analysis using a Cox proportional hazards model to identify predictors of a spontaneous rhythm change, and a ridge regression model for predicting it. The data of 25 804 patients were analyzed (derivation cohort, n=17 743; validation cohort, n=8061). The rhythm change event rate was 4.1% (724/17 743) in the derivation cohort, and 4.0% (326/8061) in the validation cohorts. Age, sex, presence of a witness, initial rhythm, chest compression by a bystander, shock with an automated external defibrillator by a bystander, and cause of the cardiac arrest were all found to be independently associated with spontaneous rhythm change before hospital arrival. Based on this finding, we developed and validated the Rhythm Change Before Hospital Arrival for Nonshockable score. The Harrell's concordance index values of the score were 0.71 and 0.67 in the internal and external validations, respectively. Conclusions Seven factors were identified as predictors of a spontaneous rhythm change from nonshockable to shockable before hospital arrival. We developed and validated a score to predict rhythm change before hospital arrival.

Epicardial adipose tissue volume is associated with abdominal aortic aneurysm expansion.

BACKGROUND: The epicardial adipose tissue volume (EATV) is associated with cardiovascular diseases such as coronary artery disease. However, no information is available regarding the relationship between the EATV and abdominal aortic aneurysm (AAA) expansion. In the present study, we evaluated the association between the EATV and AAA growth and sought to identify the predictors of AAA expansion. METHODS: Between June 2009 and December 2019, 906 patients had undergone endovascular or open repair of AAAs at our institution. Patients with previous cardiac surgery, previous ascending thoracic aortic surgery, a ruptured AAA, an infected AAA, an inflammatory AAA, a saccular aneurysm, a solitary iliac aneurysm, or reintervention after treatment of the AAA were excluded. A total of 237 patients with at least two preoperative computed tomography (CT) scans performed >180 days apart were included in the present study. The EATV within the pericardium was retrospectively quantified from the preoperative non-contrast-enhanced CT images using a three-dimensional workstation. The EATV index was defined as the EATV divided by the body surface area. The AAA expansion rate was defined as an increase in the AAA diameter annually, and the patients were divided into the slow-expansion group (expansion rate, <5 mm/y) and the fast-expansion group (expansion rate, ≥5 mm/y). The correlation between the expansion rate and the EATV index was analyzed, and the cutoff value for the EATV index was determined using a receiver operating characteristics curve. Multivariate analysis was used to assess the predictors of the AAA expansion rate. RESULTS: The expansion rate of AAA correlated positively with the EATV index (R = 0.237; P < .001). The initial aneurysm diameter (P < .001) and EATV index (P = .009) differed significantly between the two groups. The cutoff for the EATV index was 60.3 cm3/m2 (area under the curve, 0.658; 95% confidence interval [CI], 0.568-0.749; sensitivity, 1.000; specificity, 0.309). Multivariate analysis revealed that the initial aneurysm diameter and an EATV index of >60.3 cm3/m2 were significantly associated with the AAA expansion rate. CONCLUSIONS: The results of the present study have demonstrated that the EATV index is associated with AAA expansion.

Dynamic Risk Prediction via a Joint Frailty-Copula Model and IPD Meta-Analysis: Building Web Applications.

Clinical risk prediction formulas for cancer patients can be improved by dynamically updating the formulas by intermediate events, such as tumor progression. The increased accessibility of individual patient data (IPD) from multiple studies has motivated the development of dynamic prediction formulas accounting for between-study heterogeneity. A joint frailty-copula model for overall survival and time to tumor progression has the potential to develop a dynamic prediction formula of death from heterogenous studies. However, the process of developing, validating, and publishing the prediction formula is complex, which has not been sufficiently described in the literature. In this article, we provide a tutorial in order to build a web-based application for dynamic risk prediction for cancer patients on the basis of the R packages joint.Cox and Shiny. We demonstrate the proposed methods using a dataset of breast cancer patients from multiple clinical studies. Following this tutorial, we demonstrate how one can publish web applications available online, which can be manipulated by any user through a smartphone or personal computer. After learning this tutorial, developers acquire the ability to build an online web application using their own datasets.