Predictive Significance of the Prognostic Nutritional Index (PNI) in Patients with Severe COVID-19.

BACKGROUND: The prognostic nutritional index (PNI) has been reported to significantly correlate with poor survival and postoperative complications in patients with various diseases, but its relationship with mortality in COVID-19 patients has not been addressed. METHOD: A multicenter retrospective study involving patients with severe COVID-19 was conducted to investigate whether malnutrition and other clinical characteristics could be used to stratify the patients based on risk. RESULTS: A total of 395 patients were included in our study, with 236 patients in the training cohort, 59 patients in the internal validation cohort, and 100 patients in the external validation cohort. During hospitalization, 63/236 (26.69%) and 14/59 (23.73%) patients died in the training and validation cohorts, respectively. PNI had the strongest relationships with the neutrophil-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) level but was less strongly correlated with the CURB65, APACHE II, and SOFA scores. The baseline PNI score, platelet (PLT) count, LDH level, and PaO2/FiO2 (P/F) ratio were independent predictors of mortality in COVID-19 patients. A nomogram incorporating these four predictors showed good calibration and discrimination in the derivation and validation cohorts. A PNI score less than 33.405 was associated with a higher risk of mortality in severe COVID-19 patients in the Cox regression analysis. CONCLUSION: These findings have implications for predicting the risk of mortality in COVID-19 patients at the time of admission and provide the first direct evidence that a lower PNI is related to a worse prognosis in severe COVID-19 patients.

The effect of vitamin D supplementation on the muscle damage after eccentric exercise in young men: a randomized, control trial.

BACKGROUND: Vitamin D contributes to the optimal functioning of muscles. This study was designed to determine the modulating effect of vitamin D supplementation on the degree of muscle cell damage caused by eccentric exercise in young men. METHODS: 60 male volunteers (20-24 years old) taking part in this study were divided in two groups - with suboptimal (S) and optimal (O;) 25(OH)D plasma levels. These groups were randomly subdivided into groups with vitamin D supplementation (experimental: SE and OE) and controls (SC and OC). Before the supplementation (Test I) and after 3 months (Test II), participants were subjected to two rounds of eccentric exercise tests on a declined treadmill (running speed corresponded 60% VO2peak determined in each subject in incremental exercise test). During each test, blood samples used for determination of 25(OH)D, Il-1ß, myoglobin (Mb) levels and CK, LDH activity were taken at three timepoints: before the test, 1 h and 24 h after it ended. After distribution normality testing (Saphiro-Wilk test), statistical analyses were performed. Non-parametric: Kruskal-Wallis test and the Wilcoxon test were applied, and the Dunn-Bonferroni test as a post-hoc test. RESULTS: In all groups, after 3 months, higher concentrations of 25(OH)D were indicated (SE p = 0.005; SC p = 0.018; OE p = 0.018; OC p = 0.028). SE and SC groups showed higher baseline concentrations of Il-1ß and significantly higher concentrations of this interleukin after 1 h compared to groups with an optimal 25(OH)D level. After supplementation, the SE group reacted with a similar jump in concentration of Il-1ß as the OC and OE groups. The change after 1 h after exercise in Test II was significantly different from that from Test I (p = 0.047) in SE group. Lower Mb concentrations indicated 1 h after exercise in Test II for SC and SE groups were indicated. CK activity did not differentiate the studied groups. Plasma calcium and phosphate disorders were also not indicated. CONCLUSIONS: The study has shown that vitamin D doses determined from the plasma concentration of 25(OH)D of individuals to match their specific needs can significantly reduce muscle cell damage induced by eccentric exercise.

Laboratory Findings Associated With Severe Illness and Mortality Among Hospitalized Individuals With Coronavirus Disease 2019 in Eastern Massachusetts.

Importance: The coronavirus disease 2019 (COVID-19) pandemic has placed unprecedented stress on health systems across the world, and reliable estimates of risk for adverse hospital outcomes are needed. Objective: To quantify admission laboratory and comorbidity features associated with critical illness and mortality risk across 6 Eastern Massachusetts hospitals. Design, Setting, and Participants: Retrospective cohort study of all individuals admitted to the hospital who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by polymerase chain reaction across these 6 hospitals through June 5, 2020, using hospital course, prior diagnoses, and laboratory values in emergency department and inpatient settings from 2 academic medical centers and 4 community hospitals. The data were extracted on June 11, 2020, and the analysis was conducted from June to July 2020. Exposures: SARS-CoV-2. Main Outcomes and Measures: Severe illness defined by admission to intensive care unit, mechanical ventilation, or death. Results: Of 2511 hospitalized individuals who tested positive for SARS-CoV-2 (of whom 50.9% were male, 53.9% White, and 27.0% Hispanic, with a mean [SD ]age of 62.6 [19.0] years), 215 (8.6%) were admitted to the intensive care unit, 164 (6.5%) required mechanical ventilation, and 292 (11.6%) died. L1-regression models developed in 3 of these hospitals yielded an area under the receiver operating characteristic curve of 0.807 for severe illness and 0.847 for mortality in the 3 held-out hospitals. In total, 212 of 292 deaths (72.6%) occurred in the highest-risk mortality quintile. Conclusions and Relevance: In this cohort, specific admission laboratory studies in concert with sociodemographic features and prior diagnosis facilitated risk stratification among individuals hospitalized for COVID-19.

Blood Predictive Biomarkers for Patients With Non-small-cell Lung Cancer Associated With Clinical Response to Nivolumab.

BACKGROUND: Immunotherapy is a promising cancer treatment, but surrogate biomarkers of clinical efficacy have not been fully validated. The aim of this work was to evaluate several biomarkers as predictors of response to nivolumab monotherapy in patients with non-small-cell lung cancer. PATIENTS AND METHODS: Blood samples was collected at baseline, at 2 months after treatment start, and at disease progression. Lactate dehydrogenase level (LDH), neutrophils, and leukocyte values were obtained from medical record. Interleukin (IL)-8, IL-11, and kynurenine/tryptophan levels were determined by enzyme-linked immunosorbent assay. Total protein was extracted from circulating CD8+ T cells, and BCL-2 interacting mediator of cell death (BIM) protein expression tested by western blotting. RESULTS: Baseline LDH levels were significantly higher in non-responder patients than in those who responded (P = .045). The increase in indoleamine 2,3 dioxygenase activity was related to progression of disease, mainly in patients who did not respond to nivolumab treatment (P = .001). Increased levels of circulating IL-8 were observed in initially responding patients at time of progression, and it was related to lower overall survival (hazard ratio, 7.49; P = .025). A highest expression of BIM in circulating CD8+ T cells could be related to clinical benefit. The Student t test and Mann-Whitney U test were used to compare groups for continuous variables. Time to events was estimated using the Kaplan-Meier method, and compared by the log-rank test. CONCLUSIONS: Changes in plasma LDH and IL-8, indoleamine 2,3 dioxygenase activity, and BIM expression in CD8+ T cells could be used to monitor and predict clinical benefit from nivolumab treatment in these patients.

Development of a Novel Prognostic Risk Classification System for Malignant Pleural Mesothelioma.

INTRODUCTION: This study aimed to assess prognostic factors to better understand malignant pleural mesothelioma (MPM) and to develop a new classification protocol beyond the standard tumor node metastasis (TNM) staging system. MATERIALS AND METHODS: We retrospectively reviewed the data of 188 patients with MPM who had not undergone surgical resection. For each patient, we calculated the maximum standardized uptake value (SUVmax), metabolic tumor volume, and total lesion glycolysis (TLG) on pretreatment 18F-fluoro-2-deoxyglucose-positron emission tomography/computed tomography. Using the Cox proportional hazards model, we evaluated the relationships among potential MPM predictors, including age, gender, performance status, histologic type, stage, possible serum markers, and volume-based positron emission tomography parameters, as well as overall survival. RESULTS: The median survival was 461 days, and the 1- and 2-year overall survival rates were 60.70% and 31.10%, respectively. Univariate and multivariate analyses revealed that the significant independent predictors of poor survival outcomes were the non-epithelioid histologic type, elevated serum lactate dehydrogenase levels, a neutrophil-to-lymphocyte ratio of ≥ 5.0, and a TLG of ≥ 525 g. We then used these results to develop a prognostic risk classification system. From the resulting survival curve, we found a significant difference among the 3 risk groups of independent variables. Moreover, there were significant differences between all pairs of 2 separated risk groups. CONCLUSIONS: Pathologic subtypes, serum lactate dehydrogenase, neutrophil-to-lymphocyte ratio, and TLG in 18F-fluoro-2-deoxyglucose-positron emission tomography/computed tomography were independent and significant prognostic factors of MPM. Using this model, we created a new risk classification system that supplants the standard TNM staging protocol.

IL­37 expression is decreased in patients with hyperhomocysteinemia and protects cells from inflammatory injury by homocysteine.

As a novel anti­inflammatory cytokine of the interleukin (IL)­1 family, IL­37 protects the human body from diseases characterized by excessive inflammation. The pathologic process of hyperhomocysteinemia (hHcy) is accompanied by persistent inflammation. However, little is known regarding the role of IL­37 in hHcy. In the present study, the levels of cytokines including IL­37, IL­1ß, IL­6 and tumor necrosis factor­α in the supernatant were detected by ELISA. mRNA and protein expression were detected by Reverse transcription­quantitative PCR and western blotting, respectively. LDH level was determined by ELISA and the cell viability was detected through CCK­8 kit. In the present study, mean serum IL­37 levels of patients with hHcy were 32.3% lower than those of controls (P<0.01). In peripheral blood mononuclear cells (PBMCs) from patients with hHcy, mean IL­37 mRNA expression was 73.5% lower (P<0.01) and IL­37 protein expression was 77.7% lower compared with that of healthy controls (P<0.01). Furthermore, the results demonstrated that exogenous homocysteine (Hcy) stimulation markedly downregulated the mRNA and protein expression levels of IL­37 in PBMCs in vitro. In 293T cells, overexpression of IL­37 restored the cell viability impaired by Hcy, and reduced the release of lactate dehydrogenase and the proinflammatory cytokines IL­1ß, IL­6 and tumor necrosis factor­α. In conclusion, IL­37 was downregulated by Hcy in vivo and in vitro, and IL­37 exhibited a protective role against cell injury induced by Hcy.

Validation of the Marginal Zone Lymphoma International Prognostic Index.

The Marginal Zone Lymphoma International Prognostic Index (MALT-IPI) was recently developed for use in patients with mucosa-associated lymphoid tissue (MALT) lymphoma based on age, serum lactate dehydrogenase level, and Ann Arbor stage. In this study, we aimed to validate the MALT-IPI. A total of 455 MALT lymphoma patients were included in this study from between January 2005 and February 2017. Event-free survival (EFS), progression-free survival (PFS), cause-specific survival (CSS), and overall survival (OS) were the primary outcomes. Of the 455 patients, MALT-IPI low-, intermediate-, and high-risk groups included 309 (67.9%), 126 (27.7%), and 20 (4.4%) individuals, respectively. When comparing the low-risk group (L MALT-IPI) with the intermediate-high-risk group (I-H MALT-IPI), EFS, PFS, CSS, and OS were significantly different (p = 0.000, p = 0.000, p = 0.027, and p = 0.037). The International Prognostic Index and the Follicular Lymphoma International Prognostic Index failed to predict the prognosis of MALT lymphoma. Use of the MALT-IPI significantly differentiated L MALT-IPI from I-H MALT-IPI with respect to EFS, PFS, CSS, and OS. MALT-IPI is a valuable tool for the prediction of MALT lymphoma prognosis.

Effects of eculizumab treatment on quality of life in patients with paroxysmal nocturnal hemoglobinuria in Japan.

In paroxysmal nocturnal hemoglobinuria (PNH), various symptoms due to intravascular hemolysis exert a negative impact on patients' quality of life (QOL). To determine clinical factors related with improvements in QOL in PNH patients treated, we analyzed changes in QOL scales in PNH patients treated with eculizumab based on data collected from post-marketing surveillance in Japan. Summary statistics were obtained using figures from QOL scoring systems and laboratory values, and evaluated by t test. One-year administration of eculizumab improved the most QOL items in comparison with the baseline. In particular, significant improvement of EORTC QLQ-C30 was observed in fatigue, dyspnea, physical function, and global health status. Canonical correlation analysis revealed a high correlation between QOL and laboratory values. Changes in serum lactate dehydrogenase (LDH) and hemoglobin showed strong correlations with QOL improvement. Quality of life improvement was independent of patients' baseline characteristics of co-occurrence of bone marrow failure (BMF), or the degree of LDH. In this analysis, we found that the degree of QOL improvement was independent of the baseline LDH before eculizumab treatment and of co-occurrence of BMF. Paroxysmal nocturnal hemoglobinuria patients who have not received eculizumab treatment due to mild hemolysis may benefit from eculizumab treatment.

Time Course of Oxidative Stress, Inflammation, and Muscle Damage Markers for 5 Days After a Soccer Match: Effects of Sex and Playing Position.

Souglis, A, Bogdanis, GC, Chryssanthopoulos, C, Apostolidis, N, and Geladas, ND. Time course of oxidative stress, inflammation and muscle damage markers for 5 days after a soccer match: Effects of sex and playing position. J Strength Cond Res 32(7): 2045-2054, 2018-This study examined the influence of sex and playing position on the time course of selected oxidative stress, inflammation, and muscle damage markers after an official soccer match. Sixty professional soccer players (30 men and 30 women) were divided into 3 groups, according to their playing position: defenders, midfielders, and attackers. Each group consisted of 10 male and 10 female players. Sixty healthy volunteers (30 men and 30 women) served as control. Blood samples were taken before and after the match and daily for 5 days after the match. Analysis of variance revealed different responses over time between sex and playing positions, as shown by the 3-way interaction, for creatine kinase (CK), protein carbonyls (PCs), catalase, fibrinogen, uric acid (UA), lactate dehydrogenase, reduced glutathione, C-reactive protein, and interleukin 6 (p < 0.01). Male players had higher values compared with women of the same playing position, for all oxidative, inflammatory, and muscle damage indices (p < 0.01). Also, in both sexes, midfielders had higher peaks in all indices compared with defenders (p < 0.05). Five days after the game CK and UA concentrations had not returned to pregame levels in any exercise group, whereas PCs were still elevated in male midfielders and attackers (p < 0.05). These results show that sex and playing position influence the time course of selected oxidative stress, inflammation, and muscle damage markers after an official soccer game. This information should be taken into account by practitioners for the design of training programs after match play.

Aptamer-mediated Plasmodium-specific diagnosis of malaria.

There is a critical need for better malaria rapid diagnostic tests to discriminate Plasmodium falciparum and Plasmodium vivax infection given the recent observation of HRP2 deletions in P. falciparum parasites. We previously identified a DNA aptamer, 2008s, that targets P. falciparum lactate dehydrogenase (PfLDH) and developed a sensitive aptamer-tethered enzyme capture (APTEC) assay. Here, we characterise two different LDH-binding DNA aptamers in their species-specific activities, then integrate within biochemical diagnostic assays and test in clinical samples. An enzyme-linked oligonucleotide assay demonstrated that aptamer pL1 bound with high affinity to both PfLDH and P. vivax lactate dehydrogenase (PvLDH), whereas aptamer 2008s was specific to PfLDH. An aptamer-tethered enzyme capture (APTEC) assay confirmed the specificity of 2008s in binding and capturing the enzyme activity of PfLDH which could be observed colorimetrically. In malaria patient samples, the 2008s APTEC assay was specific for P. falciparum blood samples and could discriminate against P. vivax blood samples. An aptamer for specific detection of falciparum malaria holds promise as a new strategy for species-specific malaria diagnosis rather than the conventional HRP2 immuno-assay.

Correlation of C-Reactive Protein and Cardiac Enzymes with Angiographic Severity of Coronary Artery Disease in Pakistani Patients with Acute Coronary Syndrome.

OBJECTIVE: To determine the correlation of C-reactive protein (CRP) levels with the severity of coronary stenosis on angiography and the association of cardiac enzymes with the degree of stenosis in acute coronary syndrome (ACS) patients. Secondly, to compare association of angiographic severity of vascular stenosis with CRP in patients with ST segment elevation myocardial infarction (STEMI) and non-STEMI / Unstable angina (UA). STUDY DESIGN: Prospective, descriptive study. PLACE AND DURATION OF STUDY: Khan Research Laboratories (KRL) Hospital, from October 2014 to March 2015. METHODOLOGY: CRP was measured on diagnosis of ACS in 70 patients. Cardiac enzymes were measured 6 hours after the onset of chest pain. Angiographic scoring for degree of stenosis and number of culprit vessels was done. Two groups consisting of patients with STEMI (group 1) and with NSTEMI/UA (group 2) were made. RESULTS: No correlation was found between CRP levels and angiographic stenosis in patients with ACS (r=0.162, p>0.05). No association was found between eosinophil count and severity of stenosis (p=0.88). Rise of cardiac enzymes and degree of coronary stenosis showed a positive correlation (p <0.001). There was significant difference in the means of coronary artery stenosis scores between the two groups (Gensini score of groups 1 and 2: 35.9 ±4 and 14 ±8, respectively) p<0.001, but there was no significant difference in CRP levels. CONCLUSION: CRP is a marker of inflammation in ACS rather than a risk factor for determining the severity of vascular stenosis. Rise in cardiac enzymes still grade high in predicting severity of vascular stenosis than eosinophil count or CRP levels.

Identifying Malignant Pleural Effusion by A Cancer Ratio (Serum LDH: Pleural Fluid ADA Ratio).

AIM: We studied the diagnostic potential of serum lactate dehydrogenase (LDH) in malignant pleural effusion. METHODS: Retrospective analysis of patients hospitalized with exudative pleural effusion in 2013. RESULTS: Serum LDH and serum LDH: pleural fluid ADA ratio was significantly higher in cancer patients presenting with exudative pleural effusion. In multivariate logistic regression analysis, pleural fluid ADA was negatively correlated 0.62 (0.45-0.85, p = 0.003) with malignancy, whereas serum LDH 1.02 (1.0-1.03, p = 0.004) and serum LDH: pleural fluid ADA ratio 0.94 (0.99-1.0, p = 0.04) was correlated positively with malignant pleural effusion. For serum LDH: pleural fluid ADA ratio, a cut-off level of >20 showed sensitivity, specificity of 0.98 (95 % CI 0.92-0.99) and 0.94 (95 % CI 0.83-0.98), respectively. The positive likelihood ratio was 32.6 (95 % CI 10.7-99.6), while the negative likelihood ratio at this cut-off was 0.03 (95 % CI 0.01-0.15). CONCLUSION: Higher serum LDH and serum LDH: pleural fluid ADA ratio in patients presenting with exudative pleural effusion can distinguish between malignant and non-malignant effusion on the first day of hospitalization. The cut-off level for serum LDH: pleural fluid ADA ratio of >20 is highly predictive of malignancy in patients with exudative pleural effusion (whether lymphocytic or neutrophilic) with high sensitivity and specificity.

Hepatoprotective effects of sesamol loaded solid lipid nanoparticles in carbon tetrachloride induced sub-chronic hepatotoxicity in rats.

Sesamol is a phenolic component of sesame seed oil, which has been established as an antioxidant and also possesses potential for hepatoprotection. However, its protective role in carbon tetrachloride (CCl4 ) induced sub-chronic hepatotoxicity has not been studied. Limited oral bioavailability (BA) and rapid elimination (as conjugates) in rats is reported for sesamol. Considering its significant antioxidant potential and compromised BA, we packaged sesamol into solid lipid nanoparticles (S-SLNs) to enhance its hepatoprotective bioactivity. S-SLNs prepared by microemulsification method were nearly spherical in shape with an average particle size of 120.30 nm and their oral administration at 8 mg/kg body weight (BW) showed significantly (p < 0.001) better hepatoprotection than free sesamol (FS) and a well established hepatoprotective antioxidant silymarin [SILY (25 mg/kg BW); p < 0.05) in CCl4 induced sub-chronic liver injury in rats. Evaluations were done in terms of histological changes in the liver tissue, liver injury markers (serum alanine aminotransferase, serum aspartate aminotransferase, and serum lactate dehydrogenase); oxidative stress markers (lipid peroxidation, superoxide dismutase, and reduced glutathione) and proinflammatory response marker (tumor necrosis factor-alpha).

Intermedin protects against renal ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress.

BACKGROUND: Intermedin (IMD) is a novel member of the calcitonin/calcitonin gene-related peptide family. Endoplasmic reticulum stress (ERS) has been implicated in the pathology of renal ischemia/reperfusion (IRI). In the present study, we investigated whether IMD could reduce ERS damage after renal ischemia. METHODS: The kidneys of SD rats were subjected to 45 min of warm ischemia followed by 24 h of reperfusion. The hypoxia/reoxygenation(H/R) model in NRK-52E cells consisted of hypoxia for 1 h and reoxygenation for 2 h. IMD was over-expressed in vivo and in vitro using the vector pcDNA3.1-IMD. The serum creatinine concentration and lactate dehydrogenase (LDH) activity in the plasma were determined. Histologic examinations of renal tissues were performed with PAS staining. Real-time PCR and Western blotting were used to determine the mRNA and protein levels, respectively. Additionally, ER staining was used to detect the ERS response. RESULTS: In the rat renal IRI model, we found that IMD gene transfer markedly improved renal function and pathology and decreased LDH activity and cell apoptosis compared with the kidneys that were transfected with the control plasmid. IMD significantly attenuated the ERS stress parameters compared with IRI group. Indeed, IMD down-regulated glucose-regulated protein 78 (GRP78), C/EBP homologous protein(CHOP), and caspase 12 protein and mRNA levels. Moreover, in the NRK-52E cell H/R model, IMD overexpression prevented the apoptosis induced by H/R. Furthermore, IMD ameliorated the ER structural changes and concomitantly decreased the levels of GRP78, CHOP and caspase-12. CONCLUSION: This study revealed that IMD protects against renal IRI by suppressing ERS and ERS-related apoptosis.

Extracellular histone H3 levels are inversely correlated with antithrombin levels and platelet counts and are associated with mortality in sepsis patients.

OBJECTIVE: Sepsis is a leading cause of death worldwide. Extracellular histones are cytotoxic compounds mediating death in murine sepsis and circulating nucleosome levels predict mortality in human inflammation and sepsis. Whether or not circulating extracellular histone H3 correlates with other plasma parameters and/or ICU scoring systems has not been completely established, nor if levels of circulating extracellular histones can be used as predictive markers for clinical outcome in sepsis. METHODS: We measured plasma histone H3 (H3) levels in the plasma of 43 sepsis patients who were admitted to the Intensive Care Unit and determined their correlation with disease severity, organ failure, mortality and coagulation- and tissue homeostasis parameters including LDH levels, thrombin potential (ETP), prothrombin levels, antithrombin levels and platelet counts. RESULTS: Median H3 levels of sepsis patients at the ICU were significantly increased in non-survivors as compared to survivors with levels found being 3.15µg/ml versus 0.57µg/ml respectively, P=0.04. H3 levels are positively correlated with lactate dehydrogenase (LDH) activity (Spearman's rho=0.49, P<0.001), and negatively correlated with antithrombin levels (rho=-0.34, P=0.027) and platelet counts (rho=-0.33, P=0.031). CONCLUSIONS: We conclude that circulating H3 levels correlate with mortality in sepsis patients and inversely correlate with antithrombin levels and platelet counts.

Behavioral, histopathological and biochemical impairments observed in mice envenomed by the scorpion: Hottentota gentili (Pallary, 1924).

Hottentota gentili is a black scorpion which has been considered as dangerous specie by many authors. However there are no data regarding minimal lethal dose and effects of the scorpion venom till now. We therefore aimed, by the present investigation, to assess on the one hand, the LD50 of H. gentili venom by sublethal injection and the effects on some vital organs, by a histological and a biochemical tools. On the other hand, the possible neurobehavioral impairments, in Swiss mice, 3 h, 6 h and 12 h following envenomation. The LD50 of H. gentili scorpion venom was found to be 0.46 mg/kg by subcutaneous injection route. Venom produced focal fragmentation of myocardial fibers, while lungs showed rupture of the alveolar structure. Intestines showed selective histopathological changes. Concomitantly, there was a significant rise in the serum enzymes levels, as well as hyperkalemia and a high level of plasma albumine and creatine. Proteinuria was also observed. The observed behavioral effects were a hypoactivity in the both experiments 30 min and 3 h after injection. The envenomation produced an increased immobility time only 30 min and 3 h post injection in the tail suspension test (TST).

Placental growth factor concentration in maternal circulation decreases after fetal death: lessons from a case series study.

PURPOSE: Placental growth factor (PlGF) has been suggested as a possible biomarker for major placenta-related disorders such as preeclampsia and intrauterine growth restriction. However, experimental findings suggest that PlGF concentrations may be influenced by other factors besides the placenta. In the present study, we examined how acute fetal injury affects PlGF concentrations in maternal circulation. We therefore monitored PlGF concentrations in maternal circulation before and after feticide. METHODS: A prospective comparative study was performed. Blood samples were drawn prospectively between January and July 2012, before and after feticide at predetermined time points in relation to the procedure (0, 30, 60, and 120 min). The levels of lactate dehydrogenase (LDH) in the maternal circulation were measured to detect acute tissue damage. PlGF concentrations were measured by standard human ELISA. RESULTS: Following feticide (60 and 120 min), PlGF concentrations decreased significantly compared to the concentrations before feticide. LDH concentrations did not change before and after feticide. CONCLUSIONS: Our finding, along with the detailed review of the literature described in our work, supports a new concept in which primary fetal distress can affect PlGF concentration in maternal circulation. A large-scale study is required to strengthen our finding.

Laboratory parameters identify familial haemophagocytic lymphohistiocytosis from other forms of paediatric haemophagocytosis.

Haemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome of immune dysregulation and is classified as primary or secondary according to the underlying aetiology. The treatment strategies recommended for these two groups differ substantially; however, it is thought to be impossible to predict the underlying causes of HLH using conventional laboratory tests. Recent studies show that serum levels of soluble interleukin-2 receptor (sIL2R) and ferritin are useful for differentiating some forms of HLH. The present study reports that combinations of common laboratory parameters, such as the percentage of total lymphocytes within the peripheral blood leucocyte population, serum levels of lactate dehydrogenase and the sIL2R/ferritin ratio, are useful for identifying patients with familial haemophagocytic lymphohistiocytosis and for differentiating the underlying aetiology of paediatric HLH during the early course of the disease. These findings suggest that the pathogenesis of HLH differs greatly in terms of innate and adaptive immunity depending on the aetiology and may provide a new approach to unravelling the complex pathophysiology underlying this syndrome.

Preoperative serum liver enzyme markers for predicting early recurrence after curative resection of hepatocellular carcinoma.

BACKGROUND: Early recurrence of hepatocellular carcinoma (HCC) is associated with worse prognosis after liver resection. This study aimed to investigate the prognostic value of common liver enzyme markers in HCC early recurrence after curative hepatectomy and to establish a simple predictive model for HCC early recurrence. METHODS: A total of 200 patients who had undergone curative resection for HCC were retrospectively analyzed. The patients were divided into early recurrence (within 2 years) and non-early recurrence groups. Demographical characteristics, preoperative liver function parameters, surgical factors and tumor related factors of the patients were assessed by univariate analysis to identify potential significant predictors for early recurrence after resection of HCC. Parameters with statistical significance were entered into a Cox proportional hazard model to find independent risk factors. Receiver operating characteristic analysis was done to determine optimal cut-off values and the number of combined factors in multi-factor predictive model. RESULTS: Of 13 potential risk factors for early recurrence identified by univariate analysis, high lactate dehydrogenase (LDH>206 U/L, HR=1.711, P=0.006), high aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AST/ALT>0.96, HR=1.769, P=0.006), elevated alpha-fetoprotein (AFP<8.6 ng/mL, HR=2.079, P=0.007), small resection margin (≤1 cm, HR=2.354, P<0.001) and advanced TNM stage (TNM III-IV, HR=2.164, P<0.001) were independent risk factors for early recurrence of HCC shown by multivariate analysis. Patients with three or more concurrent independent risk factors had significantly higher risk for early recurrence than those with low risk factors. The sensitivity and specificity of this predictive model are 53.6% and 80.7%, respectively (area under curve=0.741, 95% CI 0.674-0.800, P<0.0001). CONCLUSIONS: Preoperative common liver enzyme markers, LDH and AST/ALT ratio, were independently associated with early recurrence of HCC. The combination of serum liver enzyme markers with AFP, resection margin and TNM stage better predicted early recurrence of HCC after curative resection in a simple multi-factor model.

Endothelial nitric oxide synthase gene intron 4 VNTR polymorphism in sickle cell disease: relation to vasculopathy and disease severity.

BACKGROUND: Impaired NO bioavailability represents the central feature of endothelial dysfunction, and is a common denominator in the pathogenesis of vasculopathy in sickle cell disease (SCD). Evidence indicates the contribution of 4a allele of endothelial NO synthase (eNOS) gene to cardiac and renal diseases. We studied the 27-base pair tandem repeat polymorphism in intron 4 of eNOS gene in 51 patients with SCD compared with 55 healthy controls and evaluated its role in disease severity and hemolysis-associated complications. PROCEDURE: Transfusion history, vaso-occlusive crisis, thrombotic events, urinary albumin excretion, and echocardiography were assessed. Analysis of eNOS intron 4 gene polymorphism was performed by polymerase chain reaction. RESULTS: The distribution of eNOS alleles and genotypes was similar between patients with SCD and controls. Compared with bb genotype, the frequency of eNOS4a allele (aa and ab genotypes) was significantly higher in patients with elevated tricuspid regurgitant velocity (TRV) (P = 0.009), nephropathy (P = 0.006), or history of cerebral stroke (P = 0.029). Logistic regression analysis revealed that eNOS4a allele was an independent risk factor for elevated TRV (P < 0.001). Patients with SCD and eNOS4a allele had higher lactate dehydrogenase, serum ferritin, D-Dimer, and von Willebrand factor antigen (P < 0.05). CONCLUSIONS: We suggest that eNOS intron 4 gene polymorphism is related to endothelial dysfunction and vasculopathy in SCD and could provide utility for prediction of increased susceptibility to vascular complications.