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Background: Prostate cancer (PCa) is the third leading cause of death from cancer in the United States. We aimed to disclose the prognostic values of examined (dissected) lymph node (ELN), negative lymph node (NLN), and positive (metastatic) lymph node (PLN) counts and lymph node (LNs) ratio in PCa patients. Methods: We extracted data of PCa patients diagnosed between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) program. We included patients with a histologically confirmed diagnosis having at least one ELN and with the PCa as the primary tumor only. Results: We have included 96,064 patients. Multivariable Cox proportional hazards regression modelsdisclosed that patients having more ELNs were associated with better survival. However, we demonstrated that patients having more PLNs were associated with worse survival. Additionally, older age, unmarried patients, with Gleason's score of 8–10, T4 and M1 stages and those who received chemotherapy and/or radiation but did not receive surgery were significantly associated with worse PCa survival. Conclusions: We have disclosed several independent predictors affecting PCa patients including age, marital status, Gleason's score, T and N stages, having received therapy, surgery, and ELN and PLN counts. Moreover, we demonstrated that patients with lower ELN and higher PLN counts were a high-risk group. We strongly recommend adding the ELN and/or PLN counts into consideration during patient staging/treatment. [ABSTRACT FROM AUTHOR]

Background: Dengue is one of the most common infectious diseases. The aim of this study was to systematically review acute disseminated encephalomyelitis (ADEM) and to represent a new case. Methodology/Principal findings: We searched for articles in nine databases for case reports, series or previous reviews reporting ADEM cases in human. We used Fisher’s exact and Mann-Whitney U tests. Classification trees were used to find the predictors of the disease outcomes. We combined findings using fixed- and random-effects models. A 13-year-old girl was admitted to the hospital due to fever. She has a urinary retention. The neurological examinations revealed that she became lethargic and quadriplegic. She had upper limbs weakness and lower limbs complete paraplegia. Her status gradually improved after the treatment. She was nearly intact with the proximal part of her legs had a mild weakness in discharge. The prevalence of ADEM among dengue patients was 0.4% [95% confidence intervals (95% CI) 0.1–2.5%], all neurological disorders among dengue was 2.6% [95% CI 1.8–3.8%], and ADEM among neurological disorders was 6.8% [95% CI 3.4–13%]. The most frequent manifestation of ADEM was altered sensorium/consciousness (58%), seizures and urination problems (35%), vision problems (31%), slurred speech (23%), walk problems (15%) then ataxia (12%). There was a significant difference between cases having complete recovery or bad outcomes in the onset day of neurological manifestations being earlier and in temperature being higher in cases having bad outcomes (p-value < 0.05). This was confirmed by classification trees which included these two variables. Conclusions/Significance: The prevalence of ADEM among dengue and other dengue-related neurological disorders is not too rare. The high fever of ADEM cases at admission and earlier onset day of neurological manifestations are associated with the bad outcomes. [ABSTRACT FROM AUTHOR]

Liver injury with marked elevation of aspartate aminotransferase enzyme (AST) is commonly observed in dengue infection. To understand the pathogenesis of this liver damage, we compared the plasma levels of hepatic specific, centrilobular predominant enzymes (glutamate dehydrogenase, GLDH; glutathione S transferase-α, αGST), periportal enriched 4-hydroxyphenylpyruvate dioxygenase (HPPD), periportal predominant arginase-1 (ARG-1), and other non-specific biomarkers (paraoxonase-1, PON-1) in patients with different outcomes of dengue infection. This hospital-based study enrolled 87 adult dengue patients, stratified into three groups based on plasma AST levels (< 80, 80–400, > 400 U/L) in a 1:1:1 ratio (n = 40, n = 40, n = 40, respectively. The new liver enzymes in the blood samples from the 4th to 6th days of their illness were measured by commercial enzyme-linked immunosorbent assay (ELISA) or colorimetric kits. Based on the diagnosis at discharge days, our patients were classified as 40 (46%) dengue without warning signs (D), 35 (40.2%) dengue with warning signs (DWS), and 11 (12.6%) severe dengue (SD) with either shock (two patients) or AST level over 1000 U/L (nine patients), using the 2009 WHO classification. The group of high AST (> 400 U/L) also had higher ALT, GLDH, ARG-1, and HPPD than the other groups, while the high (> 400 U/L) and moderate (80–400 U/L) AST groups had higher ALT, αGST, ARG-1, and HPPD than the low AST group (< 80 U/L). There was a good correlation between AST, alanine aminotransferase enzyme (ALT), and the new liver biomarkers such as GLDH, αGST, ARG-1, and HPPD. Our findings suggest that dengue-induced liver damage initiates predominantly in the centrilobular area toward the portal area during the dengue progression. Moreover, these new biomarkers should be investigated further to explain the pathogenesis of dengue and to validate their prognostic utility. Key messages: Arginase-1, α-glutathione S transferase, and 4-hydroxyphenylpyruvate dioxygenase levels were significantly associated with dengue severity and can serve as good prognostic predictors for liver injury. Our findings suggest that dengue-induced liver damage initiates predominantly in the centrilobular area toward the portal area during the dengue progression. [ABSTRACT FROM AUTHOR]

Macrolides are bacteriostatic antibiotics with a broad spectrum of activity against Gram-positive bacteria. The aim of this study was to systematically review and meta-analyze the association between infantile hypertrophic pyloric stenosis (IHPS) and macrolides. Nine databases were searched systematically for studies with information on the association between macrolides and IHPS. We combined findings using random effects models. Our study revealed 18 articles investigating the association between macrolides and IHPS. There was a significant association between the development of IHPS and erythromycin (2.38, 1.06-5.39). The association was strong when erythromycin was used during the first 2 weeks of life (8.14, 4.29-15.45). During breastfeeding, use of macrolides showed no significant association with IHPS in infants (0.96, 0.61-1.53). IHPS was not associated with erythromycin (1.11, 0.9-1.36) or macrolides use during pregnancy (1.15, 0.98-1.36).Conclusions: There is an association between erythromycin use during infancy and developing IHPS in infants. However, no significant association was found between macrolides use during pregnancy or breastfeeding. Additional large studies are needed to further evaluate potential association with macrolide use. What is known? • Erythromycin intake in the first 2 weeks of life is associated with an increased risk of pyloric stenosis. What is New? • There is currently no evidence of significant association between macrolides use during pregnancy or breastfeeding and pyloric stenosis. [ABSTRACT FROM AUTHOR]

Background Our study aimed to compare three different percutaneous coronary intervention (PCI) approaches: culprit-only (COR) and complete (CR) revascularization – categorizing into immediate (ICR) or staged (SCR). Methods We searched 13 databases for randomized controlled trials. Articles were included if they compared at least two strategies. To have more studies in each analysis, an adjusted analysis was performed using person-years to incorporate follow-up durations and obtain pooled rate ratios (RR), with their corresponding 95% confidence interval. Results Thirteen trials were included with a population of 2830 patients. COR significantly increased major adverse cardiac event (MACE) (adjusted RR 1.67, 95% CI: 1.27–2.19) and repeat revascularization (2.12, 1.67–2.69), which was driven by repeat PCI, without any difference in all-cause mortality and myocardial infarction (MI) compared to CR. When categorizing CR into SCR and ICR, the trend repeated with COR increased MACE (1.99, 1.53–2.6 for ICR), cardiovascular mortality (2.06, 1.07–3.96 for ICR), MI for ICR (1.72, 1.04–2.86), repeat revascularization and repeat PCI for both ICR and SCR. Non-cardiovascular mortality, stroke, nephropathy, re-hospitalization, stent thrombosis and bleeding were similar among all approaches. Conclusions In MVD-STEMI patients, CR is better than COR in terms of MACE, cardiovascular mortality, repeat revascularization with no difference in safety outcomes. There was a trend towards to a reduction of cardiovascular mortality and MI in ICR compared to SCR when each matched with COR; even though there is no statistically significant difference between ICR and SCR when compared together. [ABSTRACT FROM AUTHOR]

Background: Herbal medicine has been a rich source of new drugs exemplified by quinine and artemisinin. In this study, a variety of Japanese traditional herbal medicine ('Kampo') were examined for their potential anti-malarial activities. Methods: A comprehensive screening methods were designed to identify novel anti-malarial drugs from a library of Kampo herbal extracts (n = 120) and related compounds (n = 96). The anti-malarial activity was initially evaluated in vitro against chloroquine/mefloquine-sensitive (3D7) and-resistant (Dd2) strains of Plasmodium falciparum. The cytotoxicity was also evaluated using primary adult mouse brain cells. After being selected through the first in vitro assay, positive extracts and compounds were examined for possible in vivo anti-malarial activity. Results: Out of 120 herbal extracts, Coptis rhizome showed the highest anti-malarial activity (IC50 1.9 µg/mL of 3D7 and 4.85 µg/mL of Dd2) with a high selectivity index (SI) > 263 (3D7) and > 103 (Dd2). Three major chlorinated compounds (coptisine, berberine, and palmatine) related to Coptis rhizome also showed anti-malarial activities with IC50 1.1, 2.6, and 6.0 µM (against 3D7) and 3.1, 6.3, and 11.8 µM (against Dd2), respectively. Among them, coptisine chloride exhibited the highest anti-malarial activity (IC50 1.1 µM against 3D7 and 3.1 µM against Dd2) with SI of 37.8 and 13.2, respectively. Finally, the herbal extract of Coptis rhizome and its major active compound coptisine chloride exhibited significant anti-malarial activity in mice infected with Plasmodium yoelii 17X strain with respect to its activity on parasite suppression consistently from day 3 to day 7 post-challenge. The effect ranged from 50.38 to 72.13% (P < 0.05) for Coptis rhizome and from 81 to 89% (P < 0.01) for coptisine chloride. Conclusion: Coptis rhizome and its major active compound coptisine chloride showed promising anti-malarial activity against chloroquine-sensitive (3D7) and -resistant (Dd2) strains in vitro as well as in vivo mouse malaria model. Thus, Kampo herbal medicine is a potential natural resource for novel anti-malarial agents. [ABSTRACT FROM AUTHOR]

Background: The National Program for Chagas disease was implemented in Bolivia in 2006, and it greatly decreased the number of infections through vector control. Subsequently, a treatment regimen of benznidazole (BNZ) was started in seropositive school-age children living in certified vector control areas. Methods and findings: We conducted a 12-month follow-up study and seven blood samples were taken during and after the treatment. Serology, conventional diagnostic PCR (cPCR) and quantitative Real-time PCR (qPCR) were performed. Plasma Th1/Th2/Th17 cytokines levels were also determined. Approximately 73 of 103 seropositive children complied with BNZ, with three interruptions due to side effects. To evaluate each individual’s treatment efficacy, the cPCR and qPCR values during the final 6 months of the follow-up period were observed. Among 57 children who completed follow-up, 6 individuals (11%) showed both cPCR(+) and qPCR(+) (non reactive), 24 (42%) cPCR(-) but qPCR(+) (ambiguous) and 27 (47%) cPCR(-) and qPCR(-) (reactive). Within 14 Th1/Th2/Th17 cytokines, IL-17A showed significantly higher levels in seropositive children before the treatment compared to age-matched seronegative children and significantly decreased to the normal level one-year after. Moreover, throughout the follow-up study, IL-17A levels were positively co-related to parasite counts detected by qPCR. At the 12 months’ time point, IL-17A levels of non-reactive subjects were significantly higher than either those of reactive or ambiguous subjects suggesting that IL-17A might be useful to determine the reactivity to BNZ treatment. Conclusions: Plasma levels of IL-17A might be a bio-marker for detecting persistent infection of T. cruzi and its chronic inflammation. [ABSTRACT FROM AUTHOR]

Objective: After MRI studies suggested the efficacy of ethyl-EPA in reducing the progressive brain atrophy in Huntington disease (HD), trials were conducted to test its efficacy as a treatment for HD. Trials that continued for 6 months did not find any significant improvement, urging discontinuation of the drug. However, trials that continued for 12 months indicated improvement of motor functions in these patients. Methods: We searched 12 electronic databases to find randomised clinical trials relevant to our inclusion criteria. After screening, only five papers were included. Continuous and binary variables were analysed to compute the pooled mean difference (MD) and risk ratio (RR), respectively. Quality effect model meta-analysis was used as a post hoc analysis for studies at 12 months. Findings: Meta-analysis indicated that ethyl-eicosapentaenoic acid (EPA) has no significant effect on any scale of HD at 6 months. At 12 months, two studies suggested significant improvements of the Total Motor Score and Total Motor Score–4 in both fixed and quality effect models [MD = −2.720, 95% CI (−4.76, –.68), p = 0.009; MD = −2.225, 95% CI (−3.842, −0.607), p = 0.007], respectively. Maximal chorea score showed significant results [MD = −1.013, 95% CI (−1.793, −0.233), p = 0.011] in only fixed-effect model, while no improvement was detected for Stroop colour naming test or symbol digit modality. Conclusion: Meta-analysis indicated a significant improvement of motor scores only after 12 months. These results should be interpreted cautiously because only two studies had assessed the efficacy of ethyl-EPA after 12 months with one of them having a 6-month open-label phase. [ABSTRACT FROM AUTHOR]

Background: Patients undergoing non-cardiac surgery are at risk for peri-operative major cardiac events (PMCEs). The most common risk assessment tool is Revised Cardiac Risk Index (RCRI). N-terminal pro-brain natriuretic peptide (NT-proBNP) measured peri-operatively has prognostic information but the implication is uncertain. This study aimed to determine the accuracy of combining NT-proBNP and RCRI in predicting the PMCE in major non-cardiac surgery.Methods: We performed a prospective cohort study to include non-cardiac surgical patients with moderate or high risk. PMCE included myocardial infarction, pulmonary edema, severe cardiac arrhythmias, and cardiac death occurring within 30 days post-operatively. Logistic regression models and the receiver operating characteristic (ROC) curves were used to determine the discriminative ability of NT-proBNP alone or incorporation with RCRI or its components in predicting PMCE.Results: A total of 366 patients was included in the study with 48 PMCEs. When predicting PMCE, the area under the ROC curve (AUC) (95%-CI) of NT-proBNP alone and NT-proBNP incorporated with RCRI were 0.875 (0.819-0.932) and 0.882 (0.827-0.937), respectively. When incorporating NT-proBNP with the RCRI's components, the best four chosen models had the AUCs between 0.879 and 0.891. All these AUCs were not significantly different with the AUC of NT-proBNP alone.Conclusions: Higher preoperative NT-proBNP level leads to the increased risk of PMCE in patients undergoing non-cardiac surgery. Compared to NT-proBNP alone, the combination of NT-proBNP with the RCRI and other factors does not improve the accuracy in predicting PMCE. Future large studies are required to build a more accurate risk score. [ABSTRACT FROM AUTHOR]

There is no definitive predictor of dengue severity, and this has led to a very large number of unnecessary hospitalizations worldwide. Although mast cell mediators are believed to a play role in dengue severity, the lack of precise kinetic data demands further research on early predictors. We enrolled 111 patients with confirmed dengue and 85 with “other febrile illness” (OFI) in a hospital-based prospective study in Vietnam. Dengue patients were classified as level 1, 2, or 3 based on the clinical intervention received. Blood samples were collected from each patient every day (pre- and post-defervescence) and after discharge. Plasma chymase, total IgE, and dengue-specific IgE were measured. Dengue-specific IgE levels showed an increasing trend during the course of illness and remained high even at post-discharge, although no significant difference was observed among severity levels. Total IgE showed no such trend. The specific IgE/total IgE ratio (S/T ratio) remained constantly higher in level 3 patients compared to other levels, with a significant difference at some time points. The S/T ratio of acute phase samples (before defervescence) tended to increase with increasing severity (level 1 < 2 < 3), and was significantly higher in level 3 patients than in level 1 and OFI patients. As an early predictor of severity allowing level 3 patients to be distinguished from other dengue patients, the S/T ratio achieved a sensitivity of 75% and specificity of 68%. We describe the kinetic profiles of IgEs, their ratio, and chymase levels at different severity levels. The S/T ratio was found to be associated with dengue severity, suggesting that it could potentially be used as an early predictor of severity. [ABSTRACT FROM AUTHOR]

Abstract: As diagnostic and therapeutic modalities for Hodgkin's Lymphoma (HL) continue to improve, patient‐related factors affecting survival become more difficult to identify. Very little is known about the relationship between the primary site of lymph node (LN) involvement and survival of HL patients. We retrospectively analyzed the United States Surveillance, Epidemiology and End Results (SEER) database for 12,658 HL patients reported between 1973 and 2010 using survival analysis and time‐interval multiple logistic regression (MLR) to disclose that relationship. The effect of all primary LN sites on the survival of HL patients was supported. The intra‐abdominal (IAB) primary LN site was significantly associated with the worst survival. The pelvic (P) LN sites were significantly and independently associated with nearly 2 times and 2.5 times the probability of having 1‐year overall mortality (OM) and 1‐year cancer‐specific mortality (CSM), respectively. Head, face and neck (HFN) primary LN sites were significant and independent predictors of better overall and HL‐specific survival. A worse survival with the intra‐abdominal primary LN site was probably related to their association with higher age, or advanced stages of HL. The biological basis behind the aggressiveness of intra‐abdominal and pelvic LN sites is yet to be investigated. [ABSTRACT FROM AUTHOR]