Lactate Deshydrogenase Research Articles

Antifibrotic effects of vitamin D3 on human lung fibroblasts derived from patients with idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease. Up to now, no treatment can stop the progression of IPF. Vitamin D3 (VD) reduces experimental lung fibrosis in murine models and depletion of vitamin D3 might be associated with the reduced survival of patients with IPF. In this context, we determined if VD can prevent the pro-fibrotic functions of human lung fibroblasts (HLFs) isolated from patients with IPF. IPF and control HLFs were derived from surgical lung biopsies collected from patients with IPF or with primary lung cancer, respectively. VD (3-100 nM) markedly reduced the basal and PDGF-induced proliferation of HLFs. VD also altered cell cycle by increasing the percentage of IPF HLFs arrested in the G0/G1 phase, and by downregulating the expression of various cell cycle regulatory proteins. In addition, VD barely prevented the TGF-β1-induced differentiation in HLFs. At 100 nM, VD slightly reduced the expression of the pro-fibrotic marker α-smooth muscle actin, and had no effect on fibronectin and collagen-1 expression. In contrast, 100 nM VD strongly inhibited the aerobic glycolytic metabolism induced by TGF- β1. Finally, VD reduced both the secretion of lactate, the levels of lactate deshydrogenase mRNA and the activity of intracellular LDH in IPF HLFs. In conclusion, our study shows that VD reduced pro-fibrotic functions of HLFs. These findings suggest that it might be interesting to assess the potential clinical benefits of vitamin D supplementation in patients with IPF, especially on lung function decline.

Prognostic value of von Willebrand factor levels in patients with metastatic melanoma treated by immune checkpoint inhibitors

BackgroundAn increased incidence of thrombotic complications associated with an increased mortality rate has been observed under immune checkpoint inhibition (ICI). Recent investigations on the coagulation pathways have highlighted the direct...

Recurrent Mutations of the Active Adenylation Domain of UBA1 in Atypical Form of VEXAS Syndrome.

Recurrent Mutations of the Active Adenylation Domain of UBA1 in Atypical Form of VEXAS Syndrome.

Hemolysis interference on clinical chemistry tests analyzed on DxC 700 AU (Beckman Coulter®) and kaliemia rendering algorithm

The influence of hemolysis was evaluated for 26 clinical chemistry parameters on DxC 700AU (Beckman Coulter®). Ten sample pools were prepared and separated into six aliquots. These aliquots were overloaded with hemolysis in increasing amounts to reach levels equivalent to the maximum hemolysis thresholds H1 (+), H2 (++), H3 (+++) and H4 (++++). Each aliquot is compared to its reference aliquot (not hemolyzed) and a ratio is calculated for each parameter. We proposed that there was a significant difference if, for a given analyte and threshold, more than 20% of the ratios are above the total acceptable limit variability. A significant difference was found for TGP, TGO, cholesterol, creatine kinase (CPK), lactate deshydrogenase (LDH), phosphorus and potassium at H1 (+), chlorine, iron, γ-glutamyltransferase (GGT), and magnesium at H2 (++), amylase and alkaline phosphatase (PAL) at H3 (++++), and prealbumin at H4 (++++). No interference was found until H4 included for uric acid, calcium, creatinine, lipase, glucose, HDL-cholesterol, triglycerides, urea, sodium and immunoglobulins A, G and M. The overestimation of kalemia was calculated as a function of hemolysis, ranging from 0.28 mM +/–0.047 (upper H1 threshold) to 1.37 mM +/–0.126 (upper H4 threshold). Its estimation makes it possible to propose a result rendering algorithm of kalemia according to the hemolysis index. Evaluation of the automates hemolysis indexes is highly recommended for each laboratory. It can allow for some critical parameters the establishment of a decision tree facilitating the result rendering, after clinicobiological consultation.

Association between lung immune prognostic index, microbiome, and immunotherapy outcomes in non–small cell lung cancer.

9050 Background: Host-related inflammatory biomarkers and gut microbiome are two major prognostic factors for non-small cell lung cancer (NSCLC) patients (pts) treated with immune checkpoint inhibitors (ICI). In this study, we aimed to assess an association between the Lung Immune Prognostic Index (LIPI) and the microbiome composition on ICI outcomes in two independent cohorts of NSCLC pts. Methods: We included 205 patients with advanced NSCLC treated with ICI (monotherapy or in combination with chemotherapy) from two independent cohorts. Metagenomics microbiome profiling was performed on the Canadian discovery cohort of 72 pts while 16S rRNA microbiome sequencing was used in the Japanese validation cohort of 133 pts. The LIPI score was calculated using the dNLR (neutrophils/[leucocytes-neutrophils]) and lactate deshydrogenase (LDH). Pts were classified as Good (G: 0 high factor), Intermediate (I: 1 high factor) and Poor (P: 2 high factors). Median overall survival (OS) was estimated using the Kaplan-Meier method. Microbiome diversity indexes and bacterial relative abundances were compared according to LIPI groups. Results: Among the 72 pts included in the discovery cohort, the median follow-up of 20.6 months (mos). The LIPI was distributed as follows: G (n = 31, 43.1%), I (31, 43.1%), P (10, 13.8%) and baseline characteristics were well balanced between the 3 groups. When segregating pts according to LIPI, the OS was 25.6 mo, 19.8 mo, and 5.7 mo in the G, I (HR: 1.71, 95%CI: 0.80-3.65) and P (HR: 3.97, 95%CI: 1.60-9.82) groups, respectively (p = 0.003). The microbiome alpha diversity was lower in the P group compared with the G group (p = 0.03), and there was a trend towards different microbiome composition in beta diversity (p = 0.055) between both groups. Pts in the G group had a favorable microbiome (enriched in Ruminococcus and Anaerostipes), while pts from the P group had an unfavorable microbiome (enriched in Enterobacteriaceae and Clostridium symbiosum and lavalense). Next, in the validation cohort of 133 pts, LIPI was distributed as follows: G (n = 62, 46.6%), I (51, 38.3%), P (20, 15%). Pts with G LIPI had not reached their median OS compared to pts in the I [15.7 mo HR: 1.60 (0.88-2.94)] and P [8.8 mo groups, HR: 2.02 (0.98-4.19)], p = 0.03. Similar to the discovery cohort, at the genus level, G LIPI group had enrichment of Ruminococcus as well as Anaerostipes compared with pts in the P and I groups with an overrepresentation of Hungatella. Conclusions: Host-related inflammatory biomarkers, represented by the LIPI, seemed to be associated with microbiome and ICI outcomes in pts treated with NSCLC. This observation was validated in an external validation cohort. This link could be in relation to the presence of proinflammatory bacteria in pts with poor LIPI.

Hist-O-02 - High PD1 expression H score is associated with Sézary diagnosis: study of 91 patients with erythroderma

Erythroderma is a diagnostic challenge for dermatologists and pathologists. We aimed to identify clinical, histological and immunohistochemical markers that can be used to improve erythroderma diagnosis. This single-centre retrospective study included patients with erythroderma. To be included, erythroderma cases needed an accurate final diagnosis, at minimum one year of follow-up, available pictures and available skin biopsies to be reviewed. The demographic, clinical, biological (lactate deshydrogenase, eosinophilia, immunophenotype) and molecular features (T-cell clone in blood and skin) were recorded. All skin biopsies were reviewed for the following features: psoriasiform hyperplasia, parakeratosis, neutrophil microabscess, spongiosis, eosinophil infiltrate, lichenoid lesion, necrotic keratinocytes, epidermotropism, atypical lymphocytes, as well as routine immunostainings (CD3, CD4, CD8). Additional T follicular helper markers (PD1, ICOS and CXCL13), CD7 loss and Ki-67 proliferation index were also studied. For PD1 expression, percentage of positive lymphocytes as well as staining intensity (+ to +++) were recorded, all together combined in the semi-quantitative H score= [0 × (% cells 0) + 1 × (% cells 1+) + 2 × (% cells 2+) + 3 × (% cells 3+)]. Among 91 patients included with erythroderma, 21 were diagnosed as eczema, 17 as psoriasis, 20 as drug-induced erythroderma (DE), 13 as erythrodermic mycosis fungoides (E-MF) and 20 as Sézary syndrome (SS). Nail alterations, ear involvement and severe scaling were associated with psoriasis (p=0.044). Fever and hypereosinophilia were associated with DE diagnosis (p=0.044 and p=0.0003). Atypical lymphocytes in the skin were more frequent in E-MF and SS (p=0.044), as well as an abnormal blood immunophenotype and identical skin and blood T-cell clone. In SS, PD1 expression by T cells was significantly higher than in other aetiologies, as percentage of positive lymphocytes and intensity. PD1 H-score >50 was associated with SS (p<0.001, Se=75%; Sp=92%), with good reproducibility between observers, kappa coefficient of 0.66 (95% CI 0.33–1.00). CXCL13 expression was also associated with SS (p=0.044); CD7 loss was more frequent in E-MF and SS (p=0.022), and Ki-67 index was higher in SS and DE (p=0.041). In this large series erythroderma, we report the PD1 expression, and specifically the PD1 H-score combining percentage and intensity scoring, as a tool for differential diagnosis between SS and other aetiologies including E-MF. Interdisciplinary expertise combining clinical, pathological, and molecular data remain essential for erythroderma diagnosis. Erythroderma is a diagnostic challenge for dermatologists and pathologists. We aimed to identify clinical, histological and immunohistochemical markers that can be used to improve erythroderma diagnosis. This single-centre retrospective study included patients with erythroderma. To be included, erythroderma cases needed an accurate final diagnosis, at minimum one year of follow-up, available pictures and available skin biopsies to be reviewed. The demographic, clinical, biological (lactate deshydrogenase, eosinophilia, immunophenotype) and molecular features (T-cell clone in blood and skin) were recorded. All skin biopsies were reviewed for the following features: psoriasiform hyperplasia, parakeratosis, neutrophil microabscess, spongiosis, eosinophil infiltrate, lichenoid lesion, necrotic keratinocytes, epidermotropism, atypical lymphocytes, as well as routine immunostainings (CD3, CD4, CD8). Additional T follicular helper markers (PD1, ICOS and CXCL13), CD7 loss and Ki-67 proliferation index were also studied. For PD1 expression, percentage of positive lymphocytes as well as staining intensity (+ to +++) were recorded, all together combined in the semi-quantitative H score= [0 × (% cells 0) + 1 × (% cells 1+) + 2 × (% cells 2+) + 3 × (% cells 3+)]. Among 91 patients included with erythroderma, 21 were diagnosed as eczema, 17 as psoriasis, 20 as drug-induced erythroderma (DE), 13 as erythrodermic mycosis fungoides (E-MF) and 20 as Sézary syndrome (SS). Nail alterations, ear involvement and severe scaling were associated with psoriasis (p=0.044). Fever and hypereosinophilia were associated with DE diagnosis (p=0.044 and p=0.0003). Atypical lymphocytes in the skin were more frequent in E-MF and SS (p=0.044), as well as an abnormal blood immunophenotype and identical skin and blood T-cell clone. In SS, PD1 expression by T cells was significantly higher than in other aetiologies, as percentage of positive lymphocytes and intensity. PD1 H-score >50 was associated with SS (p<0.001, Se=75%; Sp=92%), with good reproducibility between observers, kappa coefficient of 0.66 (95% CI 0.33–1.00). CXCL13 expression was also associated with SS (p=0.044); CD7 loss was more frequent in E-MF and SS (p=0.022), and Ki-67 index was higher in SS and DE (p=0.041). In this large series erythroderma, we report the PD1 expression, and specifically the PD1 H-score combining percentage and intensity scoring, as a tool for differential diagnosis between SS and other aetiologies including E-MF. Interdisciplinary expertise combining clinical, pathological, and molecular data remain essential for erythroderma diagnosis.

Uses of Elaeis guineensis oil for Stress Management during the Transportation of Catfish Fingerlings: A Dose-Dependent Outcome

Cameroonian farmers used Elaeis guineensis oil (EGO) named usually palm oil to reduce stress and mortality during the transportation of catfish fingerlings. The present study is aimed to evaluate the uses of EGO for stress management during the transportation of catfish fingerlings. Antioxidant activities of EGO were assessed in vitro. 1500 fingerlings were transported from Douala (Littoral Region, Cameroon) to Yaoundé (Centre Region Cameroon). The transportation was for 7 h 55 min in black tins of 10 L which contain 8 L of water and 100 fingerlings each. The following treatment was administrated: commercial anti-stress, 2, 4, and 6 drops of EGO. Control received no treatment and all groups were triplicated. After 10 fingerlings were sacrificed by decapitation. Total protein, total bilirubin (TB), triglycerides level, and lactate deshydrogenase (LDH) activity were assessed in the liver as well as oxidant stress parameters. Brain and gills were fixed for histopathological analysis. Results showed that transportation of catfish fingerlings induced a significant increase of TB level and LDH activity in the liver. Indeed, it induced cerebellar and gills necrosis. Moreover, EGO exhibits antioxidant activities in vitro against DPPH, ABTS radicals, and possesses a ferric reducing antioxidant power of 6.31 mEAG/g. This observation was confirmed in vivo by the increase in a dose-dependent manner of GSH and nitrites levels in the liver compared to control. However, the administration of 6 drops of EGO increased significantly (p &lt; 0.05) the activity of LDH in the liver compared to control. Thus, high dose induced anaerobic respiration which was confirmed by alveolar necrosis in gills and neurodegeneration although low dose of EGO (2-4 drops) prevented those alterations compared to control. Hence, low doses of Elaeis guineensis oil can prevent liver, cerebellar and gills impairment during artisanal transportation to reduce the effects of stress.

Oleuropein Protects Against Cerebral Ischemia Injury in Rats: Molecular Docking, Biochemical and Histological Findings.

This study was designed to evaluate the underlying protective mechanisms of oleuropein involved in alleviating brain damage in a rat model of ischemic stroke. Male Wistar rats were divided into four groups; Control, stroke (MCAO), MCAO + clopidogrel (Clop) and MCAO + oleuropein (Ole). Results showed that the MCAO group evidenced significant brain edema (+ 9%) as well as increases of plasma cardiac markers such as lactate deshydrogenase (LDH), creatine kinase (CK-MB), fibrinogen and Trop-T by 11 %, 43%, 168 and 590%, respectively, as compared to the control group. Moreover, infarcted rats exhibited remarkable elevated levels of angiotensin converting enzyme (ACE), both in plasma and brain tissue, with astrocyte swelling and necrotic neurons in the infarct zone, hyponatremia, and increased rate of thiobarbituric acid-reactive substances (TBARS) by 89% associated with decreases in the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (Cat) by 51%, 44 and 42%, respectively, compared to normal control rats. However, MCAO rats treated with oleuropein underwent mitigation of cerebral edema, correction of hyponatremia, remarkable decrease of plasma fibrinogen and cardiac dysfunctional enzymes, inhibition of ACE activity and improvement of oxidative stress status in brain tissue. Furthermore, in silico analysis showed considerable inhibitions of ACE, protein disulfide isomerase (PDI) and TGF-β1, an indicative of potent anti-embolic properties. Overall, oleuropein offers a neuroprotective effect against ischemic stroke through its antioxidative and antithrombotic activities.

Nephroprotective effect of aqueous acetonic extract of Morus alba and its underlying mechanisms against glyphosate-induced toxicity - in vivo model

Glyphosate, the active substance in RoundupR, is the most widely used pesticide in the world and may be present as a residue in derived foods and drinking water. Previous reports have confirmed that extracts from leaves of Morus alba exert many pharmacological activities. However, renoprotective effects of M. alba extract and its underling molecular mechanism is still unknown. Wistar rats (180-200 g) were used in this study (n=5-6). A control group received 0.2 ml normal saline intraperitoneally (i.p) once daily for two weeks. Control animals received standard diet. Treated groups received either polyphenolic extract (100 mg/kg,i.p) or glyphosate (100 mg/kg, i.p), or co-administration (extract ?g ml?1 kg b.w. and glyphosate 100 mg kg?1 b.w, i.p), daily until the 15thday of treatment. Lactate deshydrogenase LDH, serum concentrations of blood urea, creatinine and nitric oxide were measured using standard coloromertic methods. Renal oxidative stress, evidenced by increased malondialdehyde (MDA) and protein carbonyl levels and decline in superoxide dismutase (SOD) activity, was significantly alleviated by mulberry leaves extract (MLE) administration. MLE also appears to be able to modulate altered biochemical parametres by maintaining free iron and Ca2 + homeostasis, and regulate the endogenous antioxidant enzymes system. It seems that concurrent use of the aqueous acetonic fraction of M. alba, rich in chlorogenic acid and its isomeres, can protect kidneys from glyphosate-induced nephrotoxicity. Overall, MLE may possess protective activity against glyphosate-induced toxicity, which may be attributed to chlorogenic acid and its isomers, the most abundant phenolic acids present in its extracts. Mulberry leaves are a source of phenolic compounds and can be a good start towards discovering a new chemical compound which may lead to a new drug. A mulberry extract supplement could serve as a candidate for developing a safe, and promising nutraceutical product for the management of nephrotoxicity.

Is Molecular Characterization Useful for Targeted Therapy Orientation in Patients with Relapsed or Refractory DLBCL Included in Early Phase Clinical Trials?

Is Molecular Characterization Useful for Targeted Therapy Orientation in Patients with Relapsed or Refractory DLBCL Included in Early Phase Clinical Trials?

SUN-166 THROMBOTIC MICROANGIOPATHY IN KIDNEY DISEASE: SEVERAL ETIOLOGIES

Thrombotic microangiopathy (TMA) in kidney disease is an histopathologic finding which is characterized by endothelial cell injury and microavascular thrombosis. It is a lesion associated with multiple etiologies. The presentation depends on the cause and typically includes the triad of hemolytic anemia, thrombocytopenia and acute kidney injury. In this paper, we propose to relate different etiologies of TMA noted on kidney biopsies and examine their clinical manifestations and laboratory data. We realized a retrospective descriptive monocentric study which took place at the internal medicine department in Charles Nicolle hospital in Tunisia. Over a period of 15 years (from January 2001 to January 2016). We collected the clinical and laboratory data in patients wich have had renal biopsies revealing histological TMA. We documented histological TMA in one hundred patients: 52 man and 48 women. The mean age of patients at the time of renal biopsy was 38,5+/-12,9 years (range 19-72). Seventy patients had high blood pressure. The diastolic blood pressure ranged from 50 to 130mmhg. Neurological examination was normal in 87 patients, 6 patients had systemized motor deficit and 7 patients had generalized seizures. Urine analysis showed: only 4 patients didn't have protenuria and 23 patients didn't have hematuria. Results of the laboratory investigations were as follows: hemoglobin was decreased in 75 patients. The mean hemoglobin concentration was 8,7+/-2,4g/dl (range15-4,2g/dl). The thrombocytes were decreased in only 30 patients. The mean thrombocyte concentration was 214.730+/-95.241/mm (range 19000-450000/mm). The level of serum lactate deshydrogenase was elevated in 38 patients. Coombs test was negative in 70 patients and red blood cell fragments were observed in 22 patients. Kidney injury was noted in 92 patients. Histological TMA was related to: malignant hypertension in 19 patients, an auto-immune disease in 20 cases, to oestroprogestatif medication in a patients, associated to a nephropathy in 47 case, post kidney transplantation in 9 cases, post stem cell transplantation in 1 cas, post partum in 2 cases and associated to multiple myelomain 1 case. In summary histological TMA can occur in a multiple range of diseases and the clinical manifestations can be extremely diverse. These findings leads to conclude to the necessity of a clear care pathway in thrombotic microangiopathies (TMA's) and the necessity to develop our knowledge about the mechanism and risk factor off all TMA'sincluding the role of the alternative complement pathway in secondaryTMA's.

Involvement of Toll-like Receptor 4 in Neutrophil-Mediated Inflammation, Oxidative Stress and Tissue Damage Induced by Scorpion Venom.

Systemic inflammatory response and generation of oxidative stress are known to contribute to scorpion venom-induced tissue damage. TLR receptors might represent a link between oxidative stress and inflammation; we therefore investigated whether or not TLR4 is involved in venom-induced immunopathology. The obtained results showed that pharmacological targeting of TLR4 with the selective inhibitor TAK-242 (Resatorvid) prevents the inflammatory response induced by subcutaneous administration of Androctonus australis hector (Aah) venom, as revealed by a significant decrease of neutrophil cell count in peripheral blood associated with significant decline of neutrophil degranulation and sequestration to the lung, liver, and kidney tissues. Moreover, TAK-242 administration inhibited nitrite levels increase in serum, malondialdehyde (MDA), and protein carbonyl tissue contents concomitantly with a significant increase of catalase activity and reduced glutathione (GSH) level in tissue homogenates. Furthermore, venom-induced increases in serum levels of organ dysfunction markers (lactate deshydrogenase, aminotransferase ALT and AST, creatinine and urea) were also significantly suppressed by pre-treatment with TLR4 inhibitor, concordantly with a remarkable improvement in the histological features in lung and liver tissues. The results of the present study indicate the potential role of TLR4 in venom-induced immunopathology and show the in vivo requirement of TLR4 signaling in mediating venom-induced tissue damage.

The role of lactate deshydrogenase levels on non-small cell lung cancer prognosis: a meta-analysis

The role of serum lactate dehydrogenase (LDH) on the clinical outcomes of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs) treatment remained to be elucidated. Therefore, we did this meta-analysis. We searched databases including PubMed, EMBASE, and Cochrane Library till to June, 2017. The relationships between the LDH levels and overall survival (OS) and progression free survival (PFS) were assessed by calculating hazard ratios (HRs) and 95% confidence intervals (CIs). The association between the LDH levels and disease control rate (DCR) was calculated by odds ratio (OR) and 95% CI. Seven studies were included in the meta-analysis. As for DCR, the result from this meta-analysis was not positive (OR=0.71; 95% CI 0.21 - 2.37; P=0.57). As for PFS, the result of the meta-analysis indicated that elevated LDH was significantly associated with shorter PFS (HR=1.88; 95%CI, 1.37-2.59). When studies were stratified by ethnicity, significant association was also observed in Asian group (HR=2.36; 95%CI, 1.57-3.55). As for OS, patients with high levels of LDH showed significantly shorter OS (HR=2.44; 95%CI, 1.84-3.23). In the subgroup by race, significant associations were found in Asian group (HR=2.62; 95%CI, 1.61-4.26) and Caucasian population (HR=2.36; 95%CI, 1.66-3.34). In conclusion, this meta-analysis suggested that elevated LDH level was associated with the poor PFS and OS of NSCLC patients receiving EGFR-TKIs treatment.

Predictive Factors for Survival in Sickle Cell Disease: A Cohort Study Using Etendard Data

IntroductionThe prospective ETENDARD study (NCT00434902) evaluated 398 outpatients with sickle cell disease (SCD) enrolled between February 2007 and March 2009 at referral centers in France. All patients were homozygous for hemoglobin S or had Sβ0 thalassemia. This study estimated the prevalence of pulmonary hypertension (PH) related to SCD to be 6%, based on the presence of a tricuspid regurgitation velocity (TRV) ≥2.5 m/s and a mean pulmonary arterial pressure (mPAP) measured by right-sided heart catheterization (RHC) ≥25 mmHg (Parent et al, New Engl J Med 2011). The long-term prognostic value of TRV≥2.5 m/s according to the level of mPAP measured by RHC has not been clearly established.MethodsUsing updated 10-year follow up data from the ETENDARD cohort study, we analyzed the overall survival of patients according to their TRV/mPAP status, as follows: patients with a TRV<2.5 m/s (group A), patients with a TRV≥2.5 m/s and a mPAP<25 mmHg (group B), and patients with a TRV≥2.5 m/s and a mPAP≥25 mmHg (group C). Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards modeling was used to compute hazard ratios (HR) along with their 95% confidence intervals (CI95).ResultsThe 398 enrolled patients were followed-up for a mean time of 106±26 months (median 112 months, interquartile range 106-119). TRV was≥2.5 m/s in 109 patients (27.4%). RHC was performed in 98 of them and confirmed PH diagnosis (mPAP≥25 mmHg) in 24 (6%). Overall survival was significantly decreased in patients with a TRV≥2.5 m/s (groups B/C vs. A; HR=2.5 [CI95 1.3-4.7], p=0.006, Figure 1A). However, after accounting for mPAP level, no statistically significant difference was found between patients with a TRV<2.5 m/s and those with TRV≥2.5 m/s and mPAP<25 mmHg (group A vs. B, log-rank p=0.54), while patients with a TRV≥2.5 m/s and a confirmed diagnosis of PH by RHC (mPAP≥25 mmHg) had a significantly decreased survival in comparison with the two other groups (groups A/B vs. C, p<0.0001, Figure 1B), yielding the following HRs in Cox analysis: HR=1.0 (group A), HR=1.3 (group B, CI95 0.5-3.0, p=0.59] and HR=6.0 (group C, CI95 2.7-13.3, p<0.0001). At time of inclusion, patients with confirmed diagnosis of PH by RHC (group C) were older and characterized by lower 6-min walk distance, higher rate of leg ulcers, lower PaO2 and forced vital capacity, and higher levels of alkaline phosphatase, lactate deshydrogenase and γ-glutamyl transferase (all p<0.05). Clearance of creatinine was significantly lower in both groups with TRV≥2.5 m/s. All these parameters and systemic arterial pressures at time of inclusion were associated with a higher risk of mortality in univariate analysis.ConclusionWhile an isolated VRT≥2.5 m/s on transthoracic echocardiography was found to be a moderate prognostic factor for overall survival, our findings reveal highly contrasted outcomes depending on the mPAP values measured by RHC. Only the combination of a VRT≥2.5 m/s and a mPAP≥25 mmHg is associated with a worse prognosis, confirming that a RHC is mandatory in case of PH suspicion on transthoracic echocardiography in SCD patients. DisclosuresBartolucci:Addmedica: Research Funding; GBT: Membership on an entity's Board of Directors or advisory committees; Fondation Fabre: Research Funding; Novartis US: Membership on an entity's Board of Directors or advisory committees.

Inhibitory Effect of fermented pectin on key metabolic enzymes associated with diabetes, obesity; and Liver-Kidney tissues toxicities

Consumption of a high fat and sugar diets induced serious disorders and diseases such as obesity, hyperlipidemia and type2 diabetes. Food fiber exerts various beneficial effects in health. The present study evaluate the effect of Soluble Fermentable Dietary Pectin (SFDP) in high-fat/fructose diet (HFFD) induced obesity, hyperlipidemia and hyperglycemia. The findings indicate that administration of SFDP to HFFD rats improved body weight by decreasing lipase activity in intestine and pancreas by 34% and 22% respectively as compared to untreated HFFD rats; consequently decrease in body weight by 19%; and also decrease in TC and LDL-c and TG rates by 15%, 14%, and 32% and increase in HDL-c by 32%. In addition, consumption of SFDP significantly suppressed α-amylase activity (key enzyme related to hyperglycemia) and this leads to decrease in blood glucose level by 24% than those in the diabetic rats. In addition, SFDP efficiently protected the hepatic and kidney functions observed by the considerable decrease of aspartate and alanine transaminases (AST and ALT) and lactate deshydrogenase (LDH), creatinine (Creat) and urea contents in the serum of diabetic rats. The beneficial effects of SFDP were also evidenced histological study of liver, kidney and heart tissues. Overall, the findings of the present study indicate that SFDP displays a number of promising properties and can used as therapeutic agents in for amelioration of obesity, hyperlipidemia and hyperglycemia.

Thromboembolic (TE) complications in germ cell tumor (GCT) patients: Should use of peripherally inserted central catheters (PICC-Line) be pursued?

571 Background: Patients with GCT receiving cisplatin-based chemotherapy are at high risk of TE events (TEE). Several risk factors have been reported previously, such as cisplatin, Lactate Deshydrogenase, body surf area (BSA)... Methods: we conducted a retrospective study of all patients (pts) with GCT, treated with platinum salts and followed at the university hospital and anticancer center of Bordeaux (June 2007 - January 2015). The following characteristics were recorded: age, performans status, BSA, histological type, site of primitive tumor, stage, prognosis (IGCCCG classification), size of retroperitoneal lymphnode, LDH, type of venous pathway (peripheral vein, implantable venous access port or PICC-Line), prophylaxis of anticoagulant or not, TEE and median time to onset. Results: 206 pts were selected. Thirty-six (17.4%) had one or more venous or arterial TEE during or within 3 months of the end of chemotherapy: 26 deep vein thromboses, 13 pulmonary embolisms and 4 arterial accidents (2 acute limb ischemia and 2 acute coronary syndromes). The median time between treatment initiation and occurrence of TEE was 38.5 days [7-248]. Among the 12 pts with PICC-line, 6 (50%) had a TEE, including 4 cases of pulmonary embolism. In addition to the presence of a PICC-line (OR 4.62 [1.28, 15.56]), factors associated with an increased TE risk in univariate analysis were the use of implantable venous access port (OR: 3.97 [1.81; 9.12]), size of retroperitoneal adenopathy ≥ 2 cm ([2-5 cm]: OR: 24.39 [4.50 - 454.39]; &gt; 5cm : OR : 26.25 [5,00 - 484.5]), stage II (OR : 10.19 [1,9 - 188.96]), stage III (OR :27.2 [5.34 - 479.9]), prognosis group (good : OR : 11.16 [2.16 - 205.04]) ; intermediate : OR : 31.50 [4.81 – 624.20] ; unfavorable : OR : 33.35 [5.7 – 637.34]), VIP (etoposide-ifosfamide-cisplatin) protocol (OR :6.35 [1.51 – 28.15]) and high LDH level (OR :3.88 [1.63 – 10.34]). Conclusions: These results suggest a significant association between PICC-line and the occurrence of TEE in univariate analysis. PICC-line is not risk-free and should be used sparingly in pts with GCT whose treatment objective remains primarily a cure at the cost of less toxicity.

The effect of Opuntia ficus-indica juice supplementation on oxidative stress, cardiovascular parameters, and biochemical markers following yo-yo Intermittent recovery test.

The aim of the study was to investigate the effect of a flavonoid‐rich fresh fruit juice on cardiovascular, oxidative stress, and biochemical parameters during the yo‐yo intermittent recovery test (YYIRT). Twenty‐two healthy males subjects participated in this study divided into two groups: An experimental group (EG: n = 11) who consumed the antioxidant supplement and a control group (CG: n = 11). All participants performed two test sessions at 07:00 hr before and after 2 weeks of supplementation with Opuntia ficus‐indica juice. Blood samples were taken before (P1) and immediately (P2) after the YYIRT. Our results showed that following the 2,2‐diphenyl‐1‐ picrylhydrazyl (DPPH ●) test, the Opuntia ficus‐indica juice has an antioxidant capacity for capturing free radicals (p < .05) and reducing oxidative stress related to exercise. Concerning biochemical and cardiovascular parameters, our results showed a significant increase on total cholesterol (TC) (p < .01), triglycerides (TG) (p < .05), high‐density lipoprotein (HDL) (p < .01), low‐density lipoprotein (LDL) (p < .01), creatine kinase (CK) (p < .01), lactate deshydrogenase (LDH) (p < .01), glucose (GLC) (p < .01), systolic (SBP), and diastolic blood pressure (DBP) (p < .01) immediately after exercise. However, TC (p < .05), TG (p < .05) and LDL (p < .05), the maximal heart rate (HRmax), the CK (p < .05), and LDH (p < .01) as well as the malondialdehyde (MDA) (p < .01) demonstrated a significant decrease after supplementation of Opuntia ficus‐indica juice before and immediately after YYIRT. However, no significant effect on HDL (p > .05), GLC (p > .05) levels nor the SBP and DBP (p > .05) was observed after supplementation with Opuntia ficus‐indica juice. The supplementation leads to an improvement on YYIRT performance (The total distance covered during the YYIRT,VO 2max, VMA) and the rating of perceived exertion (RPE). Opuntia ficus‐indica juice has a potent antioxidant activity that reduces total and LDL‐cholesterol with only a moderate lowering of HDL‐cholesterol and oxidative stress. Moreover, supplementation decreases muscle damage caused by the endurance exercise.

Retrospective Analysis of 56 Cases of Transformed Waldenström Macroglobulinemia. a Study on Behalf of the French Innovative Leukemia Organization (FILO)

Introduction : Histologic transformation (HT) to an aggressive non-Hodgkin lymphoma is a well-described event in the natural history of patients with indolent lymphomas, mainly follicular lymphomas and chronic lymphocytic leukemia/small lymphocytic lymphoma. HT has been reported also in lymphoplasmacytic lymphoma (LPL)/Waldenström macroglobulinemia (WM) but only case reports or small patients series are available.Material and methods : We retrospectively searched the databases of 14 French and Belgian centers for patients with sequential or simultaneous diagnosis of LPL/WM and diffuse large B-cell lymphoma (DLBCL). Fifty-six patients (39 men and 17 women) were analyzed of whom 8 had simultaneous diagnosis of LPL/WM and DLBCL. At the time of diagnosis of LPL/WM, the median age was 65 years (range, 33-85 years). Thirty-one percent of patients presented lymphadenopathy and 27% splenomegaly. The median level of serum monoclonal IgM was 17.7 g/L (range, 2.3-66.7 g/L). The IPSSWM was available for 32 patients : 12 (38%) were low, 13 (40%) were intermediate and 7 (22%) were high-risk. At time of HT, 3 patients were previously untreated for WM. The median number of therapies for WM was 2 (range, 0-5), including chlorambucil (60%) and fludarabine-based regimens (48%). Only half of the patients were exposed to rituximab. The median time from LPL/WM diagnosis to HT for patients with sequential diagnosis (n = 48) was 59 months (range, 4-300 months). At time of transformation, 32 patients (57%) presented altered ECOG performance status (≥ 2) and B symptoms were found in about half of the patients. Tumor mass higher than 5 cm and extranodal involvement were found in 54% and 95% of patients respectively. The median serum IgM level was 6.7 g/L (range, 0-40 g/L). Serum lactate deshydrogenase levels were elevated in 72% of cases. Histology was mainly represented by DLBCL, with only 2 cases described as B-cell lymphoma, intermediate between DLBCL and Burkitt lymphoma. In situ hybridization for EBER was negative in 17 of 18 informative cases. The median number of lines of therapy given for HT was 1 (range, 0-5). First-line treatment for HT consisted of CHOP-like regimen +/- rituximab in 47 patients (85%). Five patients (9%) received DHAP association and 3 (5%) GEMOX due to cerebral involvement and/or previous CHOP-exposure. Rituximab was part of the first-line treatment for HT in 49 patients (89%). Six patients underwent autologous stem cell transplantation (SCT) and 3 allogeneic SCT. The overall response rate after first-line treatment for HT was 55% (complete response, 45%) and the median progression-free survival and overall survival after HT were 18 and 25 months respectively. The majority of deaths were attributed to disease progression (75%) or infections (18%).Conclusion : HT appears to be a critical event in the clinical course of patients with LPL/WM, associated with poor outcome. Risk factors for developing DLBCL and molecular pathogenesis of transformation in patients with LPL/WM remain to be studied. DisclosuresDupuis:janssen: Honoraria; ABBVIE: Membership on an entity's Board of Directors or advisory committees. Leblond:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

The Use of Ferritin to Identify Critically Ill Patients With Secondary Hemophagocytic Lymphohistiocytosis.

Thrombocytopenia is a common, multifactorial, finding in ICU. Hemophagocytosis is one of the main explanatory mechanisms, possibly integrated into hemophagocytic lymphohistiocytosis syndrome, of infectious origin in the majority of cases in ICU. The hemophagocytic lymphohistiocytosis is probably underdiagnosed in the ICU, although it is associated with dramatic outcomes. The main objectives of this work were to identify the frequency of secondary hemophagocytic lymphohistiocytosis, and the main prognostic factors for mortality. We conducted a retrospective observational study in all adult patients admitted with suspected or diagnosed hemophagocytic lymphohistiocytosis, between January 1, 2000, and August 22, 2012. A total of 106 patients (42%) had significant hemophagocytosis on bone marrow examination, performed for exploration of thrombocytopenia, bicytopenia, or pancytopenia. The median age was 56 (45-68) and the median Simplified Acute Physiology Score 2 was 55 (38-68). The main reason for ICU admission was hemodynamic instability (58%), predominantly related to sepsis (45% cases). The main precipitating factor found was a bacterial infection in 81 of 106 patients (76%), including 32 (30%) with Escherichia coli infection. Forty six of 106 patients (43%) died in the ICU. They were significantly older, had higher Simplified Acute Physiology Score 2, plasma lactate deshydrogenase bilirubin, and serum ferritin. The fibrinogen and the percentage of megakaryocytes were significantly lower in nonsurvivors when compared with survivors. In multivariate analysis, only serum ferritin significantly predicted death related to hemophagocytosis. A serum ferritin greater than 2,000 μg/L predicted death with a sensitivity of 71% and a specificity of 76%. A decreased percentage of megakaryocytes also predicted patient death in the ICU. Hemophagocytosis is common in thrombocytopenic patients with sepsis, frequently included in a postinfectious hemophagocytic lymphohistiocytosis setting. Our study reveals that ferritin could be a reliable prognostic marker in these patients, and hold particular interest in discussing a specific treatment for hemophagocytic lymphohistiocytosis.

English

Para phenyl diamine (PPD) is an aromatic amine derivative of Aniline that is widely used as a cosmetic product, particularly in hair dye preparations. PPD acute poisoning leads to respiratory distress, rhabdomyolysis, muscle necrosis and renal failure. Cardiac complications are rarely reported in the literature. We will present a case of PPD poisoning presenting as myocarditis, associated to rhabdomyolysis with a fatal outcome. A 22-year-old man was hospitalized for ingestion of a hair dye. At admission it had a severe edema of the face and neck. Laboratory exams showed renal failure, increased serum lactate deshydrogenase, creatine phosphokinase and troponine T. Toxicological screening showed the presence of Paraphenyl Diamine in blood and stomach. The patient died in the tenth day due to a cardiogenic shock. A forensic autopsy was performed. The pericardium was spotted by multiple hemorrhagic petechiae. The myocardium and the epicardium had multiple hemorrhagic areas. Histological examinations revealed the presence of acute inflammation of the myocardium and epicardium associated with severe ulceration of the endocardium. Inflammatory infiltrate consisted mainly of neutrophils with frequent micro abscesses in the myocardium and epicardium. Death was attributed to Paraphenyl Diamine poisoning complicated with rhabdomyolysis and acute myocarditis. Keywords: para phenyd diamine, poisoning, hair dye, myocarditis. Language: en