Association of HMGB1, S100A12 and IL-17A Expression with Immunoglobulin-Resistant in Kawasaki Disease and the Comparisons Between Different Adjunctive Therapeutic Approaches

Objective: The DAMPs such as HMGB1, S100A12 and IL-17A have been reported to predict poor response to IVIG. The aim of this study was to analyze the role of HMGB1,S100A12 and IL-17A in the detection of inflammation in KD patients with IVIG-resistant, and to investigate the value of different adjunctive therapy.Method: This study enrolled 126 patients diagnosed with KD, as well as age-matched 16 febrile control subjects. The demographic or clinical data, laboratory parameter and blood sample were collected. Various laboratory parameters as predictive factors for IVIG-resistant were calculated. And the serum levels of IL-17A and mRNA expression levels of HMGB1 and S100A12 were tested in all patients. For patients with acute KD in IVIG-resistant, we studied the levels of laboratory variables when using of IVIG retreatment, methylprednisolone, infliximab for children patients. Result: The variance of laboratory parameters between the febrile control group and KD group were analyzed. Regarding laboratory parameters, KD individuals were found to have lower levels of L%, PA, CD4+, CD8+ and higher levels of WBC, N%, CRP, ESR, NT-proBNP, ALT, CD4+/CD8+ (P<0.05 or P<0.01). For KD group, the 53 IVIG-resistant patients had significantly higher levels of blood S100A12, HMGB1, serum IL-17A levels And N%, CRP, NT-pro BNP, TBIL, ALT, AST and lower levels of L%, PLT (P<0.05 or P<0.01) in comparison to the IVIG-responsive patients. For patients with acute KD in IVIG-resistant, after initial IVIG-treatment, the adjunctive therapy of IVIG, methyl prednisolone or infliximab were used, the inflammatory symptoms and laboratory inflammatory markers were improved when treated with those drugs. Conclusion: IVIG-resistant was associated with higher levels of HMGB1, S100A12, IL-17A, CRP, NT-pro BNP, TBIL, ALT, AST and lower levels of L%, PLT before IVIG, especially when combined, were useful predictors for IVIG-resistant in KD. In addition, the adjunctive therapy of methylprednisolone and infliximab showed more effective in relief clinical symptoms than IVIG retreatment.

American visceral leishmaniasis in a state of northeastern Brazil: clinical, epidemiological and laboratory aspects

In Brazil, American visceral leishmaniasis (AVL) has become a public health concern due to its high incidence and lethality. This study aimed to analyze the clinical, epidemiological, and laboratory aspects of AVL in a state of Brazil. This descriptive, cross-sectional, retrospective, and quantitative study of notified cases of AVL was carried out in Alagoas between 2008 and 2017 from data obtained from DATASUS/SINAN. Sociodemographic, clinical, and laboratory variables were analyzed. A descriptive analysis was performed using absolute values and valid percentages, using tables and/or graphs. Data processing was performed using Stata 12.0®. Results with P <0.05 were considered statistically significant. During the study period, 352 cases of AVL were reported, of which 6.82% died and 38.92% had met a cure criterion. Male patients were predominant (66.76%). Of the total infected patients, 16.76% had attended only the 1st to the 4th grades, with those most affected aged 1 to 4 years (28.69%). Laboratory diagnostic criteria were most commonly used to confirm the notified cases (76.42%), whereas 51.70% and 8.52% of the cases had positive parasitological and immunofluorescence diagnoses, respectively. Finally, the study showed a higher prevalence of the disease in children, men and in rural residents. Although with low lethality, the expressive frequency of AVL in the State of Alagoas was still verified, since there was an increase in the number of cases during the years of the study.

Predicting treatment outcomes using 18F-FDG PET biomarkers in patients with non-small-cell lung cancer receiving chemoimmunotherapy

Background: Predictive markers for treatment response and survival outcome have not been identified in patients with advanced non-small-cell lung cancer (NSCLC) receiving chemoimmunotherapy. We aimed to evaluate whether imaging biomarkers of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) and routinely assessed clinico-laboratory values were associated with clinical outcomes in patients with advanced NSCLC receiving pembrolizumab plus platinum-doublet chemotherapy as a first-line treatment. Methods: We retrospectively enrolled 52 patients with advanced NSCLC who underwent baseline 18F-FDG PET/CT before treatment initiation. PET/CT parameters and clinico-laboratory variables, constituting the prognostic immunotherapy scoring system, were collected. Optimal cut-off values for PET/CT parameters were determined using the maximized log-rank test for progression-free survival (PFS). A multivariate prediction model was developed based on Cox models for PFS, and a scoring system was established based on hazard ratios of the predictive factors. Results: During the median follow-up period of 16.7 months (95% confidence interval: 15.7–17.7 months), 43 (82.7%) and 31 (59.6%) patients experienced disease progression and death, respectively. Objective response was observed in 23 (44.2%) patients. In the multivariate analysis, maximum standardized uptake value, metabolic tumour volume2.5, total lesion glycolysis2.5, and bone marrow-to-liver uptake ratio from the PET/CT variables and neutrophil-to-lymphocyte ratio (NLR) from the clinico-laboratory variables were independently associated with PFS. The scoring system based on these independent predictive variables significantly predicted the treatment response, PFS, and overall survival. Conclusion: PET/CT variables and NLR were useful biomarkers for predicting outcomes of patients with NSCLC receiving pembrolizumab and chemotherapy as a first-line treatment, suggesting their potential as effective markers for combined PD-1 blockade and chemotherapy.

Additional resource for diabetes diagnostics in animals and humans

Veterinary doctors often observe cases of unexplained elevated glucose and ketones in urine of domestic animals without any other signs of diabetes. We studies these effects from the standpoint of the phenomenon of interdependent conditions in animals and humans, described by T.V.Novosadyuk in 2000. She was the first to provide a theoretical and practical foundation for clinical cases of simultaneously developing similar diseases in domestic animals and their owners. During the last 5 years we studied health of humans in families where domestic animals are affected by the laboratory abnormalities described above. In vast majority of cases it has been found out that animal owners have diabetes mellitus of variable severity. At the same time there were no disorders of carbohydrate metabolism in animal owners in 11 cases. We recommended members of these families to undergo a specialized examination. In all of these cases latent diabetes mellitus was found in humans who had especially close relationships with animals. These findings led to initiation of treatment in humans. At the same time animals were treated with a collar with a linen sack attached containing Peganum Harmala 30 globules. Repeated laboratory tests were performed after one month of such treatment. Normalization of laboratory variables was observed in all of the cases. Based on the study results we developed an algorhythm of activities that helps to diagnose early and latent forms of diabetes mellitus in domestic animals and their owners. This algorhythm includes: - test for glucose and/or ketones in animal urine after correction of feeding and care defects. - blood and urine glucose tests in family members of animal owners. In cases of deviations from normal values we recommended them to consult appropriate specialists and begin treatment immediately. - animals are given collars with Peganum Harmala 30 globules in a linen sack attached. - granules are removed when laboratory values normalize in animals. Control urinalysis is performed every three months durign a year. This approach is especially useful in latent early forms of diabetes mellitus when abnormal findings in animals or their owners enable us to suspect a similar disease in another. In such a way, the suggested algorithm is effective for organization of preclinical diagnostics in both domestic animals and their owners. In the future it is possible to enrich not only veterinary but also medical practice with new options for effective patient aid by practical development of the use of animal and human interdependent conditions.

Gender-Specific Differences in Self-Care, Treatment-Related Symptoms, and Quality of Life in Hemodialysis Patients

Gender and sex differences affect women with kidney failure (KF) negatively at all stages of the disease. This study assessed gender differences in self-care, hemodialysis symptoms, and quality of life in a sample of 102 adult KF patients treated with hemodialysis, from two clinical centers in Mexico. Self-care agency, quality of life, and the symptoms related to hemodialysis were evaluated through questionnaires, and sociodemographic and laboratory variables were obtained from the clinical records. Compared to male patients, female patients reported similar self-care, lower quality of life subscales (symptoms, physical functioning, pain, and overall health), and higher prevalence and intensity of hemodialysis symptoms. There were gender differences regarding the correlation between self-care and quality of life, symptoms intensity, and symptoms prevalence. In conclusion, women with KF treated with hemodialysis perceived a higher impact of hemodialysis and reported a lower quality of life than men. Despite having a similar self-care agency, the self-care correlations with quality of life and hemodialysis symptoms appeared different between men and women treated with chronic hemodialysis. Such differences may be important in future nursing interventions to improve self-care and quality of life among KF patients.

Development and Validation of a Nomogram to Predict the Overall Survival of Patients with Stage I Non-Small Cell Lung Cancer After Surgery

Background: This study aimed to establish an effective prognostic nomogram for stage I non-small cell lung cancer (NSCLC) patients receiving surgery.Methods: Stage I NSCLC patients at Taizhou Hospital of Zhejiang Province from October 2010 to June 2014 were included. Clinical, pathological and laboratory variables ascertained before surgery were selected through least absolute shrinkage and selection operator and Cox regression analysis, and a nomogram model was established. The nomogram model was validated using stage I NSCLC patients from the same institution between July 2014 and December 2015. Results: Training cohort included 274 patients. From 46 potential predictors, the independent risk factors for Overall survival (OS) of patients with stage I NSCLC were age, CA125, and tumor diameter. The C index of the nomogram model was 0.759(95% confidence interval (CI)，0.666–0.852). The area under the ROC curve of the nomogram was 0.776. The patients in the low-risk subgroup had significantly better survival than those in the high-risk subgroup (logrank, p < 0.001). The AUC in the validation cohort was 0.809, and the C index was 0.707(95% CI, 0.572-0.842).Conclusion: We developed a nomogram model that includes clinical, pathological and laboratory variables to predict the OS of stage I NSCLC patients.

Assessment of Serum Spexin Levels In Obese Adolescents with Metabolic Syndrome Antecedents: Preliminary Results

Objective: Spexin (SPX) is a novel peptide implicated in food intake and satiety. Spexin levels are reduced in obese patients. Aim: To compare serum SPX levels in obese adolescents versus healthy controls and to assess the associations of metabolic syndrome (metS) antecedents with serum SPX levels. Methods: Eighty consecutive obese adolescents aged 10-18 years and 80 healthy peers were enrolled. Anthropometric measurements, pubertal examinations and clinical blood pressure measurements were performed. Fasting blood samples were drawn for glucose, insulin, lipids, uric acid, alanine aminotransferase (ALT) and SPX. Metabolic syndrome (metS) was diagnosed using International Diabetes Federation criteria. Associations of serum SPX with clinical and laboratory variables were assessed. Results: Obese adolescents had lower serum SPX levels than healthy peers (50 pg/mL [25%-75% IQR: 25-98 pg/mL] and 67.0 pg/mL [25%-75% IQR:32.5-126.0 pg/mL; respectively], p =0.035). Twenty (25 %) obese adolescents were diagnosed as having metS. Obese adolescents with metS had lower SPX than those without metS (24.5 pg/mL [25%-75% IQR: 15.3-49.5 pg/mL] and 69.0 pg/mL [25%-75% IQR: 42.0-142.0 pg/mL]; respectively p<0.0001). The frequencies of hyperuricemia, IR and elevated ALT were similar in obese adolescents with metS and those without metS (p > 0.05 for all). Serum uric acid levels were correlated significantly with serum SPX after correcting for BMI and HOMA-IR (r =-0.41, p<0.05). A serum SPX level at a cut -off level of 49.5 pg/mL predicted the presence of metS in obese adolecents with 75 % sensitivity and 71 % specifity. Conclusions: Obese adolescents have reduced SPX levels, and this reduction is more pronounced in those with metS. Further research is needed to verify the utility of SPX as a biomarker in the diagnosis of metS in obese adolescents.

Factors predictive of complicated appendicitis in children

Background: Clinical features of acute appendicitis are often overlapping with other abdominal pathology in children. This increases the risk of complicated appendicitis (CA). It is still difficult to identify CA preoperatively. The study aims to identify pre operative risk factors in children for CA.Methods: A prospective study was conducted in pediatric surgery unit of department of general surgery of a university hospital of Kathmandu, Nepal. All children up to 16 years diagnosed and operated for appendicitis were included in the study. Based on intraoperative findings and histopathological examination (HPE), patients were grouped in simple appendicitis (SA) and CA. Pre-operative clinical and laboratory variables of between simple and CA were compared. P£0.05 was considered as significant.Results: A total of 73 children were included out of which 61 (83.6%) had SA and 12 (16.4%) had CA. Mean age of participants was 12.8±2.9 years. More than half (64.4%) of the participants were male. The median duration of symptoms was 2 days. In bivariate analysis, gender, serum Na, duration of symptoms and rebound tenderness were significantly associated with severity of appendicitis. In multivariate analysis, rebound tenderness (OR-15.36) and duration of symptoms (OR-9.96) were found to be associated with CA.Conclusions: Male patients, rebound tenderness, longer duration of symptoms and hyponatremia can be used to predict CA. Duration of symptoms and rebound tenderness are independent risk factors for CA.

Elevated Serum Neuropeptide FF Levels Are Associated with Cognitive Decline in Patients with Spinal Cord Injury

Background. Spinal cord injury (SCI) has high incidence globally and is frequently accompanied by subsequent cognitive decline. Accurate early risk-categorization of SCI patients for cognitive decline using biomarkers can enable the timely application of appropriate neuroprotective measures and the development of new agents for the management of SCI-associated cognitive decline. Neuropeptide FF is an endogenous neuropeptide with a multitude of functions and is associated with neuroinflammatory processes. This prospective study investigated the predictive value of serum neuropeptide FF levels measured after acute SCI for subsequent cognitive decline. Methods. 88 patients presenting with acute SCI without preexisting neurological injury, brain trauma, or severe systemic illness and 60 healthy controls were recruited. Serum neuropeptide FF levels, clinical, and routine laboratory variables including low-density lipoprotein, high-density lipoprotein, fasting blood glucose, total triiodothyronine (TT3), total thyroxine (TT4), and thyroid-stimulating hormone (TSH) levels collected from all subjects were assessed. Montreal cognitive assessment (MoCA) was performed 3 months after enrollment. SCI patients were grouped according to quartile of serum neuropeptide FF level and MoCA scores were compared using ANOVA. Additionally, multivariate linear regression with clinical and laboratory variables was performed to predict MoCA scores. Results. SCI patients displayed significantly higher baseline serum neuropeptide FF levels than healthy controls ( 38.5 ± 4.1 versus 23.4 ± 2.0 pg / ml , p < 0.001 ∗ ∗ ). SCI patients in higher quartiles of baseline serum neuropeptide FF displayed significantly lower MoCA scores at 3 months. Linear regression analysis indicated serum neuropeptide FF levels as a significant independent predictor of worse MoCA scores after SCI ( r = 0.331 , p = 0.034 ∗ ). Conclusion. Early serum neuropeptide FF levels significantly and independently predicted cognitive decline after acute SCI among patients without preexisting neurological disorders.

Biomarker Association with Hypertension in Mild Versus Severe Sickle Cell Disease Genotypes of a Single Center Cohort, in Comparison with African Americans from the Nhanes Study

Introduction: Previous studies have reported that patients with sickle cell disease (SCD) have lower systemic blood pressures when compared with age-, sex-, and race-matched controls. We compared systolic and diastolic blood pressure (SBP and DBP) measurements in an SCD patient cohort followed at our clinical center with values obtained from background population using African Americans from the National Health and Nutrition Examination Survey (NHANES) study. Furthermore, we evaluated the association of SBP and DBP with clinical and laboratory variables in our patient cohort in comparison to NHANES. Methods: We cross-sectionally analyzed 442 adult SCD patients receiving medical care at the University of Illinois at Chicago (UIC) between 2009-2018, categorized as severe (HbSS/Sβ 0-thalassemia; n=342) or mild (HbSC/Sβ +-thalassemia; n=100) genotypes. 884 African American from the NHANES were age-, sex-, and race- matched as control in a 2:1 ratio. We evaluated associations between systolic and diastolic BP and 32 clinical and laboratory variables. Evaluation of medians, interquartile range (IQR), Wilcoxon rank sum and the χ2 test, were performed on covariates. Clinical associations between biomarkers and primary outcomes of SBP, DBP, were determined by first applying single marker regression with covariates. Significant biomarkers were then analyzed by multi-marker regression and model selection to predict the relative strength of outcome association for these biomarkers. All variables included were normally distributed or transformed to normal distribution. Results: The median age of participants ranged from 31-38 years for both SCD cohorts and NHANES control. 16%, 21% and 8% of the mild genotype patients, severe genotype patients and NHANES controls, respectively were on at least one antihypertensive medication for either hypertension or proteinuria. The median (IQR) for systolic and diastolic BP for the patients with mild genotype were 122 mm Hg (112-130) and 78mmHg (70-84); severe genotype 119 mmHg (110-128) and 70 mmHg (64-75); NHANES 118(110-128) and 70 mmHg (62-78). Systolic blood pressures did not differ among the SCD groups versus NHANES, but diastolic blood pressures were higher in the mild SCD genotype patients than severe SCD patients (P&lt;0.0001) or NHANES (P&lt;0.0001), regardless of antihypertensive therapy. After controlling for covariates, in the severe genotype patients SBP associated significantly with gender and prior diagnosis of hypertension, but SBP associated only with hemoglobin level in the mild genotype patients. In contrast diastolic BP associated with gender and hemoglobin in the mild genotype but had no significant association in the severe genotype patients. In the NHANES controls, we observed that SBP was significantly associated with age, gender, BMI, prior hypertension, LDH, total bilirubin, urine albumin-creatinine ratio; and DBP associated with age, BMI, WBC count (Table 1). Discussion: Our SCD patient cohorts demonstrate a much higher median SBP, and for the mild genotype patients, higher DBP than was described for their age group in the cooperative study of sickle cell disease (Pegelow et al 1997). When compared with a contemporary NHANES cohort, we failed to observe a lower SBP or DBP as was expected. Higher systolic blood pressure has been reported as risk factor for the development of silent cerebral infarct in HbSS children (DeBaun et al 2014). Our study also shows that BP changes in SCD may be less influenced by traditional anthropometric measures and clinical markers. Figure 1 Figure 1. Disclosures Saraf: Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding. Gordeuk: Modus Therapeutics: Consultancy; Novartis: Research Funding; Incyte: Research Funding; Emmaus: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; CSL Behring: Consultancy.