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Background Programmed cell death-ligand 1 (PD-L1) may be a useful molecule for targeted immunotherapy. Therefore, this meta-analysis aimed to investigate PD-L1 expression in breast cancer and its associations with clinicopathological factors and outcomes, which may help determine whether PD-L1 expression is a useful prognostic marker. Methods The Medline Ovid, Cochrane, PubMed, Google Scholar, and Web of Knowledge databases were searched for studies that evaluated the prognostic or clinicopathological significance of PD-L1 expression in patients with breast cancer, and reported at least one survival-related outcome. Results Six studies that included 7877 cases were selected for the analysis. Higher PD-L1 expression in all cells was related to higher histological grade and lymph node metastasis. Higher PD-L1 expression in tumor cell was related to larger tumor size, estrogen receptor negativity, progesterone receptor negativity, human epidermal growth factor type-2 positivity, and triple-negative breast cancer. PD-L1 positivity in all cells was associated with poorer disease-free survival, although it was not significantly associated with overall survival. Conclusion The present meta-analysis revealed that cases of breast cancer with PD-L1 positivity in all cells exhibited higher histological grades, lymph node metastasis, and poorer disease-free survival. Therefore, positive expression of PD-L1 may be a useful prognostic marker in breast cancer.

Adjuvant chemotherapy after surgery improves survival of patients with stage II–III, resectable gastric cancer. However, the overall survival benefit observed after adjuvant chemotherapy is moderate, suggesting that not all patients with resectable gastric cancer treated with adjuvant chemotherapy benefit from it. We aimed to develop and validate a predictive test for adjuvant chemotherapy response in patients with resectable, stage II–III gastric cancer. In this multi-cohort, retrospective study, we developed through a multi-step strategy a predictive test consisting of two rule-based classifier algorithms with predictive value for adjuvant chemotherapy response and prognosis. Exploratory bioinformatics analyses identified biologically relevant candidate genes in gastric cancer transcriptome datasets. In the discovery analysis, a four-gene, real-time RT-PCR assay was developed and analytically validated in formalin-fixed, paraffin-embedded (FFPE) tumour tissues from an internal cohort of 307 patients with stage II–III gastric cancer treated at the Yonsei Cancer Center with D2 gastrectomy plus adjuvant fluorouracil-based chemotherapy (n=193) or surgery alone (n=114). The same internal cohort was used to evaluate the prognostic and chemotherapy response predictive value of the single patient classifier genes using associations with 5-year overall survival. The results were validated with a subset (n=625) of FFPE tumour samples from an independent cohort of patients treated in the CLASSIC trial (NCT00411229), who received D2 gastrectomy plus capecitabine and oxaliplatin chemotherapy (n=323) or surgery alone (n=302). The primary endpoint was 5-year overall survival. We identified four classifier genes related to relevant gastric cancer features (GZMB, WARS, SFRP4, and CDX1) that formed the single patient classifier assay. In the validation cohort, the prognostic single patient classifier (based on the expression of GZMB, WARS, and SFRP4) identified 79 (13%) of 625 patients as low risk, 296 (47%) as intermediate risk, and 250 (40%) as high risk, and 5-year overall survival for these groups was 83·2% (95% CI 75·2–92·0), 74·8% (69·9–80·1), and 66·0% (60·1–72·4), respectively (p=0·012). The predictive single patient classifier (based on the expression of GZMB, WARS, and CDX1) assigned 281 (45%) of 625 patients in the validation cohort to the chemotherapy-benefit group and 344 (55%) to the no-benefit group. In the predicted chemotherapy-benefit group, 5-year overall survival was significantly improved in those patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only (80% [95% CI 73·5–87·1] vs 64·5% [56·8–73·3]; univariate hazard ratio 0·47 [95% CI 0·30–0·75], p=0·0015), whereas no such improvement in 5-year overall survival was observed in the no-benefit group (72·9% [66·5–79·9] in patients who received chemotherapy plus surgery vs 72·5% [65·8–79·9] in patients who only had surgery; 0·93 [0·62–1·38], p=0·71). The predictive single patient classifier groups (chemotherapy benefit vs no-benefit) could predict adjuvant chemotherapy benefit in terms of 5-year overall survival in the validation cohort (pinteraction=0·036 in univariate analysis). Similar results were obtained in the internal evaluation cohort. The single patient classifiers validated in this study provide clinically important prognostic information independent of standard risk-stratification methods and predicted chemotherapy response after surgery in two independent cohorts of patients with resectable, stage II–III gastric cancer. The single patient classifiers could complement TNM staging to optimise decision making in patients with resectable gastric cancer who are eligible for adjuvant chemotherapy after surgery. Further validation of these results in prospective studies is warranted. Ministry of ICT and Future Planning; Ministry of Trade, Industry, and Energy; and Ministry of Health and Welfare.

The use of capnography monitoring devices has been shown to lower the rates of hypoxemia via early detection of respiratory depression, and facilitate more accurate titration of sedatives during procedures. The aim of the current meta-analysis was to compare the incidence of hypoxemia associated with standard monitoring alone during gastrointestinal endoscopy to that associated with standard monitoring with the addition of capnography. The MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials scientific databases were searched to identify relevant studies. We performed a meta-analysis of randomized controlled trials undertaken up to January 2018 that met our predefined inclusion criteria. The study outcome measures were incidence of hypoxemia, severe hypoxemia, apnea, the use of assisted ventilation, the use of supplemental oxygen, and change in vital signs. We included nine trials assessing a total of 3,088 patients who underwent gastrointestinal procedural sedation. Meta-analysis of study outcome revealed that capnography significantly reduced the incidence of hypoxemia (odds ratio 0.61, 95% CI 0.49-0.77) and severe hypoxemia (odds ratio 0.53, 95% CI 0.35-0.81). However, there were no significant differences in other outcomes including incidence of apnea, assisted ventilation, supplemental oxygen, and changes in vital signs. Early procedure termination and patient satisfaction-related outcomes did not differ significantly in the capnography group and the standard monitoring group. This study indicates that capnography monitoring is an important addition with regard to the detection of hypoxemia during gastrointestinal procedural sedation, and should be considered in routine monitoring during gastrointestinal endoscopy.

The solder joint is a key component in land grid array (LGA) sockets. A simplified solder joint has been widely used in finite element model (FEM) computations because the J-lead interconnection solder joint is relatively complex. Therefore, there are discrepancies between the physical phenomenon and FEM simulations. In this study, an alternative method to simulate the J-lead interconnection solder joint through an interface program using surface evolver software is presented. Simulations of the J-lead interconnection solder joint were improved to reduce the mismatch between the actual physical shape and the simplified finite element models that are typically used to predict component reliability. To perform these simulations, an interface program capable of simulating solder interconnections for twelve different pad–solder combinations was developed. Predictions of J-lead interconnection solder joints were carried out using the interface program. Geometric comparisons between experimental data and predictions showed good agreement, with the exception of wetting height. To evaluate the prediction accuracy of the simulated J-lead solder joints, FEM analysis was performed for the static load and the thermal cycle.

We investigated the potential application of preoperative serum metabolomes in predicting recurrence in patients with resected pancreatic cancer. From November 2012 to June 2014, patients who underwent potentially curative pancreatectomy for pancreatic ductal adenocarcinoma were examined. Among 57 patients, 32 were men; 42 had pancreatic head cancers. The 57 patients could be clearly categorized into two main clusters using 178 preoperative serum metabolomes. Patients within cluster 2 showed earlier tumor recurrence, compared with those within cluster 1 (p = 0.034). A nomogram was developed for predicting the probability of early disease-free survival in patients with resected pancreatic cancer. Preoperative cancer antigen (CA) 19–9 levels and serum metabolomes PC.aa.C38_4, PC.ae.C42_5, and PC.ae.C38_6 were the most powerful preoperative clinical variables with which to predict 6-month and 1-year cancer recurrence-free survival after radical pancreatectomy, with a Harrell’s concordance index of 0.823 (95% CI: 0.750–0.891) and integrated area under the curve of 0.816 (95% CI: 0.736–0.893). Patients with resected pancreatic cancer could be categorized according to their different metabolomes to predict early cancer recurrence. Preoperative detectable parameters, serum CA 19–9, PC.aa.C38_4, PC.ae.C42_5, and PC.ae.C38_6 were the most powerful predictors of early recurrence of pancreatic cancer.

The delta neutrophil index (DNI), which reflects the ratio of circulating immature neutrophils, has been reported to be highly predictive of mortality in systemic inflammation. We investigated the prognostic significance of DNI value for early mortality and neurologic outcomes after pediatric cardiac arrest (CA). We retrospectively analyzed the data of eligible patients (<19 years in age). Among 85 patients, 55 subjects (64.7%) survived and 36 (42.4%) showed good outcomes at 30 days after CA. Cox regression analysis revealed that the DNI values immediately after the return of spontaneous circulation, at 24 hours and 48 hours after CA, were related to an increased risk for death within 30 days after CA ( P < 0.001). A DNI value of higher than 3.3% at 24 hours could significantly predict both 30-day mortality (hazard ratio: 11.8; P < 0.001) and neurologic outcomes (odds ratio: 8.04; P  = 0.003). The C statistic for multivariable prediction models for 30-day mortality (incorporating DNI at 24 hours, compression time, and serum sodium level) was 0.799, and the area under the receiver operating characteristic curve of DNI at 24 hours for poor neurologic outcome was 0.871. Higher DNI was independently associated with 30-day mortality and poor neurologic outcomes after pediatric CA.

We investigated the association of perioperative antiplatelet therapy (APT) and outcomes in patients with drug-eluting stent (DES) placement for noncardiac surgery (NCS). In consecutive 23,358 patients who underwent percutaneous coronary interventions between 2005 and 2016, total of 2,179 patients that required 2,179 elective NCS after DES placement were retrospectively analyzed. A net adverse clinical event (NACE), composite of death, myocardial infarction, stent thrombosis, and major bleeding, was assessed at 30 days. Of 2,179 patients, 937 patients (43%) underwent NCS with discontinuation of APT. For overall, NACE occurred in 10 patients who discontinued APT (1.1%) and 22 patients who continued APT (1.8%) without significant differences (hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.28 to 1.27, p = 0.182). Also, adjusted NACE event rates were not different between groups for overall NCSs (adjusted HR 0.76, 95% CI 0.38 to 1.52, p = 0.440), for NCSs >1, ≤12 months after DES, and for NCSs >12 months after DES. Our findings persisted (adjusted HR 1.26, 95% CI 0.51 to 3.10, p = 0.618) when those who continued dual-APT were excluded from the continuation of APT group due to a higher tendency of NACE compared with those who continued single-APT (adjusted HR 2.26, 95% CI 0.98 to 5.21, p = 0.055). However, the patients who discontinued APT for >7 days had a significantly higher NACE than those who discontinued for ≤7 days (adjusted HR 6.93, 95% CI 2.16 to 22.24, p = 0.001). In conclusion, discontinuation of APT may not be associated with higher NACEs 30 days postsurgery compared with continuation of APT, when APT was discontinued for ≤7 days in patients undergoing elective NCS after DES implantation.

Nucleos(t)ide analogues (NUCs) are not routinely recommended for patients with hepatitis B e antigen-positive chronic hepatitis B virus (HBV) infection who have persistently elevated serum HBV DNA level (>20,000 IU/mL) but normal alanine aminotransferase (<40 IU/L) level. Here, we evaluated the cumulative risks of hepatocellular carcinoma (HCC) in such patients (the untreated persistently elevated serum HBV DNA [pEDNA] group) compared with inactive carriers (the IC group). Patients with untreated pEDNA (n = 126) and IC (n = 621) were enrolled between 2006 and 2012. Patients with cirrhosis or HCC at enrollment or a history of NUC treatment were excluded. The cumulative HCC risks at 5 and 9 years in the untreated pEDNA group were 1.1% and 1.9%, which were comparable with those of the IC group (P = 0.549). Inverse probability of treatment weighting and propensity score matching also showed similar HCC risks. In the untreated pEDNA group, there were no cases of HCC in the subgroup with serum HBV DNA level >1,000,000 IU/mL (immune-tolerant phase), which was significantly (P = 0.002) different compared with those with an intermediate serum HBV DNA level (20,000-1,000,000 IU/mL). The cumulative HCC risk in the untreated pEDNA group was minimal and comparable with that of the IC group. Further studies are required to determine whether early NUC treatment, indeed, reduces the HCC risk in patients with an intermediate serum HBV DNA level.

The risk of osteoporosis in patients with chronic inflammatory neuropathy (CIN) has not been evaluated in detail. We conducted a population-based case-control study nested in a retrospective cohort to analyze osteoporosis risk among patients with CIN using a nationwide database. Patients with CIN based on the Korean Classification of Disease diagnostic code were included and were matched to controls. A Cox proportional hazards regression model was used to evaluate the effect of CIN on osteoporosis. After propensity score matching, 585 CIN patients and 585 controls were selected. Patients with CIN had an increased osteoporosis risk (hazard ratio [HR] = 2.293, 95% confidence interval [CI] 1.460–3.601) compared with controls. The osteoporosis risk was higher among male patients with CIN than among male controls (HR = 5.404, 95% CI 2.252–12.969), while there were no significant differences among women. Among the CIN patients, the average daily dose of corticosteroids was higher in those who developed osteoporosis (19.6 mg [10.8–49.3]) than those who did not (16.2 mg [7.2–29.1], p = 0.001). The osteoporosis risk among CIN patients is higher than among controls. High risk of osteoporosis in male patients may indicate that osteoporosis in CIN patients results from the disease itself or related treatments.

Aims: To evaluate the differences and changes of testicular volume and elasticity in normal (NL) testes and undescended testes (UDTs) of children using shear wave elastography (SWE).Materials and methods: Testicular ultrasound images from children younger than 60 months old were retrospectively reviewed. Testicular volumes and elasticities were compared between the UDT group and NL group. In patients with unilateral UDT (uUDT), we also compared the values between uUDT and contralateral grossly normal (CGN) testis groups.Results: There were 25 UDTs including 4 bilateral in the UDT groupand 54 normal testes in the NL group. While testicular volume was significantly smaller in UDT (vs. NL) and uUDT (vs. CGN) groups, the elasticity was not different. Testicular volume was positively correlated with age in both NL (r=0.474) and CGN (r=0.729) groups (p<0.001), while there was no correlation in the UDT group. Testicular stiffness showed negative correlation with age in the NL group (r=-0.390, p=0.004) and positive correlation in the UDT group (r=0.426, p=0.034).Conclusions: Instead of increasing volume and decreasing stiffness of normal testes during development of the early 60 months, UDTsexhibited smaller volume and increasing stiffness. The CGN testes of uUDT patients showed increasing volume without stiffness change.