Complement Factor H as a potential atherogenic marker in chronic Chagas’ disease

We aimed to investigate the association between plasma levels of complement Factor H (FH) with cardiac involvement, inflammatory and cardiometabolic parameters in patients with chronic Chagas’ disease (CD). FH plasmatic levels were determined in 80 chronic CD patients. Glycaemic index, lipidogram (high‐density lipoprotein cholesterol HDL‐C, low‐density lipoprotein cholesterol LDL‐C, triglycerides and total cholesterol) and Ultrasensitive C‐Reactive Protein (uCRP) values were obtained from medical records. Height, weight, body mass index (BMI) blood pressure and left ventricular ejection fraction (LVEF) were obtained from echocardiography examinations. Comparisons between chronic CD clinical forms were performed using Mann‐Whitney test and correlation Spearman’s test. FH levels were correlated positively with triglycerides (P = .001, r = .39), LDL‐C (P = .009, r = .3), cholesterol (P = .02, r = .28), uCRP (P = .029, r = .31) and BMI (P = .008, r = .34); and negatively with HDL‐C (P = .03, r = ?.25) levels. Dyslipidemic patients showed higher FH levels compared to normolipidemic, although no difference for FH levels was observed between chronic CD clinical forms. Alternative pathway of complement may be a link between immune response and metabolic disorders, with important immunoregulatory role in chronic CD.     

Triglyceride and high‐density lipoprotein levels as the markers of disease activity and their association with TNF‐α and TNF receptor system in systemic lupus erythematosus

Objective: There are some clues that measurement of triglyceride (TG) and high‐density lipoprotein (HDL) and their correlation with tumor necrosis factor alpha (TNF‐α), soluble TNF‐α receptor type 1 and type 2 (sTNFR1, sTNFR2) in serum could be valuable in the assessment of disease activity of systemic lupus erythematosus (SLE) patients. Methods: In this cross‐sectional study, fasting blood samples were obtained from 86 SLE patients referred to the Rheumatology Research Center of Tehran University in Shariati Hospital, Iran. Disease activity was determined by using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). TG and HDL obtained after overnight fasting were analysed by routine chemistry. Levels of circulating TNF‐α, sTNFR1, and sTNFR2 were determined by enzyme‐linked immunosorbent assay. Results: Triglyceride levels were associated with SLEDAI (r = 0.59, P < 0.001), TNF‐α (r = 0.27, P < 0.01), and with sTNFR1 (r = 0.54, P < 0.001); on the contrary, HDL levels were negatively associated with SLEDAI (r = –0.29, P < 0.007), TNF‐α (r = –0.27, P < 0.01), and sTNFR1 (r = –0.35, P < 0.001). The correlation of TG and HDL with sTNFR2 were (r = 0.13, P > 0.23) and (r = –0.17, P > 0.1), respectively. In multiple logistic regression models, the levels of TNF‐α and HDL were omitted. Conclusion: Dyslipoproteinemia with high TG/low HDL levels correlates with disease activity in SLE, and enhanced activity in the TNF‐α/sTNFR system. With results of this study and the same studies, serum levels of TG, HDL, TNF‐α, sTNFR1, sTNFR2 are valuable markers for estimation of disease activity in SLE.     

Pre‐transplant comorbidity burden and post‐transplant chronic graft‐versus‐host disease

The Haematopoietic Cell Transplantation‐Comorbidity Index (HCT‐CI) was designed as a predictor of non‐relapse mortality after HCT. Chronic graft‐versus‐host disease (GVHD) contributes to mortality after HCT. Here, we investigated whether the HCT‐CI could predict development of chronic GVHD or post‐chronic GVHD mortality. We retrospectively analysed data from 2909 patients treated with allogeneic HCT for malignant and non‐malignant haematological conditions at four institutions. In Cox regression models adjusted for potential confounders, increasing HCT‐CI was not statistically significantly associated with the development of chronic GVHD [hazard ratio (HR) = 1·02, P = 0·34]. Yet, the index was associated with an increased risk of non‐relapse mortality (HR = 1·29, P < 0·0001) as well as overall mortality (HR = 1·25, P < 0·001) following the development of chronic GVHD. The association between HCT‐CI and post‐chronic GVHD mortality was similar regardless of donor type or stem cell source. HCT‐CI scores could be incorporated in the design of clinical trials for treatment of chronic GVHD.     

From short‐term blood pressure variability to atherosclerosis: Relative roles of vascular stiffness and endothelial dysfunction

Both arterial blood pressure (BP) average levels and short‐term BP variability (BPV) relate to hypertension‐mediated organ damage, in particular increased carotid artery intima‐media thickness (IMT) and carotid‐femoral pulse wave velocity (PWV). Endothelial dysfunction possibly mediates such damage. The authors aimed at further investigating such role in hypertensive patients. In 189 recently diagnosed, untreated hypertensive patients the authors evaluated, in a cross‐sectional design, the relationships of BP average levels and short‐term systolic (S) BPV (standard deviation of awake SBP or of 24‐hour‐weighted SBP) with IMT and PWV, and how much these relationships are explained by endothelial function parameters—brachial artery flow‐mediated dilation (FMD) and digital reactive hyperemia index (RHI). Multivariable models assessed the strength of these relationships to derive a plausible pathogenetic sequence. Both average SBP values and our measures of SBPV were significantly related to IMT (24‐hour mean SBP: r = .156, P = .034; 24‐hour‐weighted SBPV: r = .157, P = .033) and to PWV (24‐hour mean SBP: r = .179, P = .015; 24‐hour‐weighted SBPV: r = .175; P = .018), but only poorly related to FMD or RHI (P > .05 for all). At univariable regression analysis, FMD and RHI were both related to IMT, (P < .001), but not to PWV. When FMD and RHI were added to average SBP and SBPV parameters in a multivariable model, both significantly (P < .005) contributed to predict IMT, but not PWV. Thus, endothelial dysfunction relates to IMT independently of BP parameters, but appears to play a minor role in the association between BP variability‐related variables and arterial stiffening.     

Dynamics of liver stiffness by transient elastography in patients with chronic hepatitis C virus infection receiving direct‐acting antiviral therapy—Results from the German Hepatitis C‐Registry

The impact of direct‐acting antiviral (DAA) therapies on fibrosis regression remains uncertain. In the current study, we prospectively evaluated dynamics of liver stiffness by transient elastography (TE) in patients with chronic HCV infection receiving DAA‐based treatment. Patients (260) were enrolled in the German Hepatitis C‐Registry (DHC‐R), a national multicentre real‐world cohort. Liver stiffness (LS) was assessed at baseline, end of treatment (EOT) and 24 weeks after EOT (FU24) by TE. Biochemical, virological and clinical data were obtained in parallel. In patients with SVR, there was a significant improvement of LS between baseline (median [range], 8.6 [1.7‐73.5] kPa) and FU24 (7.9 [1.7‐75 kPa]; P < .0001) as well as between EOT (8.4 [1.7‐73.5 kPa]) and FU24 [P < .0001]. Stratified by fibrosis stage, patients classified into F4 had higher magnitude of LS reduction between BL (median [range], 25.1 [13.5‐73.5] kPa) and FU24 (21.5 [3.1‐75] kPa; P = .002) compared to those with F2‐F3 (8.9 [7.1‐12.4] kPa and 8.8 [4.2‐29.1]; P = .060) or F0‐F1 (5.3 [1.7‐7] kPa and 5.2 [1.7‐7.7]; P = .064). In cirrhotic patients, low platelets were significantly associated with lack of liver stiffness improvement, both at EOT (P = .018) and at FU24 (P = .012). LS significantly correlated with ALT (r = .371), AST (r = .552), platelets (r = ?.499), GGT (r = .250), bilirubin (r = .230), APRI score (r = .512), FIB‐4 score (r = .517) and FORNS index (r = .562); P < .0001. Liver elastography improved significantly in our real‐world cohort after DAA‐based therapy. As LS correlates similarly with transaminase levels and serum fibrosis markers, it might reflect both reduction of necroinflammation and fibrosis regression.     

Persistent augmentation of central arterial stiffness following viral clearance by direct‐acting antivirals in chronic hepatitis C

Chronic hepatitis C virus (HCV) infection is associated with risk of cardiovascular diseases. Although direct‐acting antivirals (DAA) result in rapid eradication of HCV, their long‐term impact on arterial stiffness remains unclear. This study aimed to evaluate changes in parameters of central arterial stiffness from pretreatment, through sustained virological response, to one year after viral clearance. Patients with chronic HCV receiving DAA treatment were enrolled prospectively. Medical history and comorbidities of all patients were collected. Lipid profiles, liver stiffness by transient elastography and central blood pressures using pulse wave analysis of the brachial artery by cuff sphygmomanometry were measured before treatment, at viral clearance and at one year following viral clearance. Augmentation index (AIx), a parameter of aortic stiffness, was calculated as the ratio of augmentation pressure to central pulse pressure. After DAA treatment, all included patients with chronic HCV (n = 102) had achieved viral clearance. Cholesterol, low‐density lipoprotein (LDL) and triglyceride/high‐density lipoprotein (TG/HDL) increased significantly at viral clearance and persisted at one year (all P < .001). AIx was also elevated significantly at viral clearance and persisted one year later (P < .001). Changes in AIx remained significant only in patients with increased values from baseline in either LDL (P < .01) or TG/HDL (P < .001). Central arterial stiffness and lipid profiles in patients with chronic HCV worsen immediately after viral eradication by DAA treatment and persist at one year. Worsening of lipid profiles after DAA treatment contributes to central arterial stiffness in this patient population and persists long term.     

Fertility and sexual function in long‐term survivors of haematological malignancy: using patient‐reported outcome measures to assess a neglected area of need in the late effects clinic

Problems of sexual function and fertility in long‐term survivors (≥5 years) of haematological malignancy are often neglected in clinic. Our centre carried out a questionnaire study in this population addressing patient‐perceived fertility and sexual function. 718 patients responded (56% of those invited; 39% Hodgkin, 45% non‐Hodgkin lymphoma, 16% acute leukaemia). Respondent women were more likely to remain childless than a normal control population. Self‐reported infertility was more likely in men than women [odds ratio (OR) 1·77, P = 0·001]. Myeloablative therapy increased the likelihood of childlessness (OR 2·48, P = 0·004). Few attended fertility support services (12%). 24% of men banked sperm and 29% of these used the sample, of which 46% resulted in successful pregnancy. Fertility clinic attendance and sperm storage was more likely post‐1990 (OR 4·05, P < 0·001; OR 5·05, P < 0·001 respectively). Reporting a negative impact of cancer on sexual function was more common in women than men (OR 2·20, P < 0·001), and increased with current age and age at diagnosis (by 3–4% per year, P ≤ 0·001) but decreased with longer follow‐up (by 2%/year, P = 0·005). Patients on anti‐depressants and those reporting cancer‐related body change/appearance concerns more frequently reported a negative impact (P < 0·04 and P < 0·03 respectively). These self‐reported outcomes confirm literature findings, suggest improvement over time, but highlight a need for involvement of support services.     

Precore G1896A mutation is associated with reduced rates of HBsAg seroclearance in treated HIV hepatitis B virus co‐infected patients from Western Africa

The nucleotide substitution G1896A on the precore (pc) region has been implicated in virological and serological responses during treatment in hepatitis B virus (HBV)‐infected patients. Whether this mutation affects the therapeutic course of HIV‐HBV co‐infected patients, especially from Western Africa, is unknown. In this prospective cohort study, 86 antiretroviral (ARV)‐naïve HIV‐HBV co‐infected patients from Côte d'Ivoire, initiating ARV‐treatment containing lamivudine (n = 53) or tenofovir (n = 33), had available baseline pc sequences. Association of the pcG1896A mutation with time to undetectable HBV‐DNA, hepatitis B “e” antigen (HBeAg) seroclearance (in HBeAg‐positive patients), and hepatitis B surface antigen (HBsAg) seroclearance was evaluated using Cox proportional hazards regression. At ARV‐initiation, median HBV‐DNA was 6.04 log₁₀ copies/mL (IQR = 3.70‐7.93) with 97.7% harbouring HBV genotype E. Baseline pcG1896A mutation was identified in 51 (59.3%) patients, who were more commonly HBeAg‐negative (P < .001) and had basal core promotor A1762T/G1764A mutations (P < .001). Patients were followed for a median 36 months (IQR = 24‐36). Cumulative proportion of undetectable HBV‐DNA was significantly higher in patients with baseline mutation (pcG1896A = 86.6% vs no pcG1896A = 66.9%, P = .04), but not after adjusting for baseline HBV‐DNA levels and anti‐HBV agent (P = .2). No difference in cumulative proportion of HBeAg seroclearance was observed between mutation groups (pcG1896A = 57.1% vs no pcG1896A = 54.3%, P = .7). Significantly higher cumulative proportion of HBsAg seroclearance was observed in patients without this mutation (pcG1896A = 0% vs no pcG1896A = 36.9%, P < .001), even after adjusting for baseline HBsAg quantification and anti‐HBV agent (P < .001). In conclusion, lacking the pcG1896A mutation before ARV initiation appeared to increase HBsAg seroclearance rates during treatment. The therapeutic implications of this mutation need further exploration in this setting.     

A different perspective on sofosbuvir‐ledipasvir treatment of patients with HCV genotype 1b cirrhosis: The ital‐c network study

The effectiveness of a 12‐week course of sofosbuvir‐ledipasvir in treatment‐experienced HCV genotype 1b‐infected patients with cirrhosis is still under debate. Our primary endpoint was to compare the sustained virological response at post‐treatment week 12 (SVR12) of sofosbuvir‐ledipasvir in combination with ribavirin for 12 weeks, and sofosbuvir‐ledipasvir alone for 24 weeks. This was a prospective observational study that enrolled 424 (195 naive, 229 experienced; 164 treated for 12 weeks with Ribavirin and 260 with sofosbuvir‐ledipasvir alone for 24 weeks) consecutive HCV genotype 1b‐infected patients with cirrhosis. The SVR12 rates were 93.9% and 99.2% in patients treated for 12 and 24 weeks, respectively (P = .002). The baseline characteristics of patients treated for 12 weeks were significantly different from those treated for 24 weeks as regards their younger age (P = .002), prevalence of Child‐Pugh class A (P = .002), lower MELD scores (P = .001) and smaller number of nonresponders (P = .04). The shorter treatment was significantly associated with a lower SVR12 in univariate and multivariate analyses (P = .007 and P = .008, respectively). The SVR rate was unaffected by age, gender, BMI, Child‐Pugh class, MELD score or previous antiviral treatment. Patients receiving ribavirin experienced more episodes of ascites and headache but less recurrence of hepatocellular carcinoma (HCC), and were prescribed more diuretics and cardiopulmonary drugs. No patient discontinued treatment. The therapeutic regimen of sofosbuvir‐ledipasvir plus ribavirin administered for 12 weeks was less effective than sofosbuvir‐ledipasvir alone given for 24 weeks. At odds with European guidelines, the recommended 12‐week treatment with sofosbuvir‐ledipasvir alone might be suboptimal for this setting of patients.     

Improved outcome for children with non‐high risk acute lymphoblastic leukaemia after using an ALL IC‐BFM 2002‐based protocol in Shanghai,China

We report the outcome of 92 non‐high risk children with acute lymphoblastic leukaemia (ALL) following a Berlin‐Frankfürt‐Münster (BFM) Intercontinental ALL ‐based protocol. Compared with a matched historical control group, we found a lower incidence of treatment‐related early death (1·2% vs. 10·9%, P = 0·015), a higher 6‐year event‐free survival (75·4 ± 4·9% vs. 58·2 ± 6·7%, P = 0·02), reduced total in‐hospital costs per person (US $) (10267·0 vs. 18331·0, P < 0·001) and fewer total in‐hospital days (164 vs. 296, P < 0·001). This ALL‐BFM based protocol was quite tolerable in our institution and will be extended to high‐risk patients.     

Body checking and body avoidance in eating disorders: Systematic review and meta‐analysis

This review sought to systematically review and quantify the evidence related to body checking and body avoidance in eating disorders (EDs) to gauge the size of effects, as well as examine potential differences between clinical and nonclinical populations, and between different ED subtypes. PsycINFO, PsycARTICLES, PsycEXTRA, Cochrane Library, and MEDLINE databases were searched for academic literature published until October 2017. A grey literature search was also conducted. Fifty‐two studies were identified for the systematic review, of which 34 were eligible for meta‐analysis. Only female samples were included in the meta‐analysis. ED cases experienced significantly higher body checking (d = 1.26, p < .001) and body avoidance (d = 1.88, p < .001) overall relative to healthy controls, but neither behaviour varied by ED subtype. In nonclinical samples, body checking (r = .60) and body avoidance (r = .56) were significantly correlated with ED pathology (p < .001). These findings support transdiagnostic theoretical models and approaches to ED treatment and early intervention programmes.     

Mutational landscape of B‐cell post‐transplant lymphoproliferative disorders

It is currently unclear whether post‐transplant diffuse large B‐cell lymphomas (PT‐DLBCL) display a similar genomic landscape as DLBCL in immunocompetent patients (IC‐DLBCL). We investigated 50 post‐transplant lymphoproliferative disorders (PTLDs) including 37 PT‐DLBCL samples for somatic mutations frequently observed in IC‐DLBCL. Targeted Next Generation Sequencing (NGS) using the Ion Torrent platform and a customized panel of 68 genes was performed on genomic DNA. Non‐tumoural tissue was sequenced to exclude germline variants in cases where available. A control cohort of 76 IC‐DLBCL was available for comparative analyses. In comparison to IC‐DLBCLs, PT‐DLBCL showed more frequent mutations of TP53 (P = 0·004), and absence of ATM and B2M mutations (P = 0·004 and P = 0·016, respectively). In comparison to IC‐DLBCLs, Epstein–Barr virus (EBV)⁺ PT‐DLBCL had fewer mutated genes (P = 0·007) and particularly fewer mutations in nuclear factor‐κB pathway‐related genes (P = 0·044). TP53 mutations were more frequent in EBV^‐ PT‐DLBCL as compared to IC‐DLBCL (P = 0·001). Germinal centre B cell (GCB) subtype of PT‐DLBCL had fewer mutations and mutated genes than GCB‐IC‐DLBCLs (P = 0·048 and 0·04 respectively). Polymorphic PTLD displayed fewer mutations as compared to PT‐DLBCL (P = 0·001). PT‐DLBCL differs from IC‐DLBCL with respect to mutations in genes related to DNA damage control and immune‐surveillance, and EBV association is likely to have a bearing on the mutational pattern.     

Hospital and out‐of‐hospital mortality in 670 hypertensive emergencies and urgencies

Long‐term mortality in patients with acute severe hypertension is unclear. The authors aimed to compare short‐term (hospital) and long‐term (12 months) mortality in these patients. A total of 670 adults presenting for acute severe hypertension between January 1, 2015, and December 31, 2015, were included. A total of 57.5% were hypertensive emergencies and 66.1% were hospitalized: 98% and 23.2% of those with hypertensive emergencies and urgencies, respectively (P = .001). Hospital mortality was 7.9% and was significantly higher for hypertensive emergencies (12.5% vs 1.8%, P = .001). At 12 months, 106 patients died (29.4%), mainly from hypertensive emergencies (38.9% vs 8.9%, P = .001). Median survival was 14 days for neurovascular emergencies and 50 days for cardiovascular emergencies. Patients with hypertensive emergencies or urgencies had bad long‐term prognosis. Short‐term mortality is mainly caused by neurovascular emergencies, but cardiovascular emergencies are severe, with high mortality at 12 months. These results justify better follow‐up and treatment for these patients.     

Association between daily salt intake of 3‐year‐old children and that of their mothers: A cross‐sectional study

This study investigated the association between the daily salt intake of 3‐year‐old children and that of their mothers. A total of 641 children were studied. The daily salt intake of the children and their mothers was estimated by morning and spot urine methods, respectively. In the multivariable analysis, a 1 g higher maternal daily salt intake was associated with a 0.14 g (95% confidence interval [CI], 0.07‐0.22, P < .001) higher salt intake of her children. In the secondary analysis, the odds ratios for excess salt intake of children were 1.61 (95% CI, 1.01‐2.55, P = .045) and 1.81 (95% CI, 1.12‐2.91, P = .015) for 9.7‐11.5 g and 11.5 g or more of maternal daily salt intake, respectively. Our findings could help to convince mothers of the importance of appropriate salt intake, not only for themselves but also for their children.     

BAALC and WT1 expressions from diagnosis to hematopoietic stem cell transplantation: consecutive monitoring in adult patients with core‐binding‐factor‐positive AML

No consecutive analysis of BAALC and WT1 expressions associated with core‐binding factor AML (CBF‐AML) from diagnosis to hematopoietic stem cell transplantation (HSCT) has yet been reported. We investigated BAALC and WT1 expressions using a method of real‐time quantitative polymerase chain reaction (RQ‐PCR) at diagnosis, after induction chemotherapy, at pre‐HSCT, and at post‐HSCT period in 45 consecutive patients [t(8,21) (n = 28), inv(16) (n = 17)], who received HSCT as a post‐remission treatment. BAALC and WT1 RQ‐PCR decrement ratio (DR) was also calculated at post‐induction chemotherapy, at pre‐HSCT, and at post‐HSCT compared with the diagnostic level. Higher BAALC expression at diagnosis showed significantly inferior OS (P = 0.031), EFS (P = 0.011), and higher CIR (P = 0.002) rates. At post‐HSCT, both higher BAALC and WT1 expressions showed significantly inferior OS (P = 0.005, 0.016), EFS (P = 0.002, 0.006), and higher CIR (P = 0.001, 0.003) rates. A subgroup of t(8;21) showing higher BAALC and WT1 expressions at post‐HSCT were also associated with inferior OS (P = 0.018, 0.015) and higher CIR rates (P = 0.019, 0.011). While BAALC DR showed no significant results on outcomes, WT1 DR more than 2‐log at post‐HSCT showed significantly lower CIR rate (P = 0.028). This study showed that higher post‐HSCT BAALC and WT1 expressions in patients with CBF‐AML may be good markers of minimal residual disease for the prediction of survival and relapse after HSCT.     

Gender differences in C‐reactive protein,interleukin‐1 receptor antagonist and adiponectin levels in the metabolic syndrome: a population‐based study

Aims We explored gender differences in the association of high‐sensitivity C‐reactive protein (hs‐CRP), interleukin‐1 receptor antagonist (IL‐1Ra) and adiponectin with the metabolic syndrome (MetS) defined by the National Cholesterol Education Program (NCEP) and the International Diabetes Federation (IDF) criteria. Methods A population‐based study of 923 middle‐aged subjects in Pieksämäki, East Finland. Results The prevalence of the MetS according to the IDF and NCEP definitions was 38% and 34% in men (N = 405) and 34% and 27% in women (N = 497), respectively. hs‐CRP and IL‐1Ra levels were higher in subjects with the MetS compared with those without the MetS in both sexes (P < 0.001). The levels of hs‐CRP (P < 0.001) and IL‐1Ra (P = 0.0016 for NCEP criteria, P = 0.0028 for IDF criteria) were significantly higher in women with MetS than in men with MetS. In contrast, in subjects without MetS, no gender differences in the levels of hs‐CRP or IL‐1Ra were found. Conclusion Women with MetS, defined by the IDF or NCEP criteria, had higher levels of hs‐CRP and IL‐1Ra than did men with MetS. Thus, low‐grade inflammation may contribute to the high risk of cardiovascular disease in women with MetS.     

Selective T‐cell depletion targeting CD45RA reduces viremia and enhances early T‐cell recovery compared with CD3‐targeted T‐cell depletion

1 Background

T‐cell depletion (TCD) effectively reduces severe graft‐versus‐host disease in recipients of HLA‐mismatched allografts. However, TCD is associated with delayed immune recovery and increased infections. We hypothesized that specific depletion of CD45RA+ naive T cells, rather than broad depletion of CD3+ T cells, can preserve memory‐immunity in the allografts and confer protection against important viral infections in the early post‐transplant period.

2 Methods

Sixty‐seven patients who received TCD haploidentical donor transplantation for hematologic malignancy on 3 consecutive trials were analyzed.

3 Results

Patients receiving CD45RA‐depleted donor grafts had 2000‐fold more donor T cells infused, significantly higher T‐cell counts at Day +30 post transplant (550/μL vs 10/μL; P < .001), and higher T‐cell diversity by Vbeta spectratyping at Day +100 (P < .001). Importantly, these recipients experienced a significant reduction in both the incidence (P = .002) and duration (P = .02) of any viremia (cytomegalovirus, Epstein‐Barr virus, or adenovirus) in the first 6 months post transplant. Specifically, recipients of CD3‐depleted grafts were more likely to experience adenovirus viremia (27% vs 4%, P = .02).

4 Conclusion

CD45RA‐depletion provided a large number of donor memory T cells to the recipients and was associated with enhanced early T‐cell recovery and protection against viremia.     

Tumour Necrosis Factor‐alpha (TNF‐α) and its soluble receptor type 1 (sTNFR I) in human active and healed leishmaniases

The role of tumour necrosis factor‐alpha (TNF‐α) is not fully understood in human leishmaniasis. We analysed the alterations in the levels of TNF‐α, soluble TNF receptor type 1 (sTNFR I), IL‐17 and IL‐22 productions in active and healed leishmaniases. Blood samples were collected from volunteers with active cutaneous leishmaniasis (ACL), the same subjects after lesion healing (healed CL = HCL), volunteers with active visceral leishmaniasis (AVL), healed VL (HVL) and healthy controls. Levels of cytokines were titrated on Leishmania Ag‐stimulated PBMC culture. The mean level of TNF‐α production from stimulated cells was significantly higher in ACL than controls (P < 0·001) and significantly reduced after treatment in HCL volunteers (P < 0·05). The mean level of sTNFR I production was significantly higher in ACL than controls (P < 0·001) and significantly reduced after treatment in HCL volunteers (P < 0·05). The mean level of IL‐22 production in AVL was significantly higher than controls (P < 0·05) and was significantly lower in HVL compared with AVL (P < 0·001) and controls (P < 0·05). The levels of TNF‐α (P = 0·0025) and sTNFR I (P < 0·01) productions from PBMCs showed significant decreasing trend after treatment in each CL volunteer. Reduction in TNF‐α is associated with clinical response to treatment and healing of CL lesions due to L. major.     

Association of pulse wave velocity and intima‐media thickness with cardiovascular risk factors in young adults

Pulse wave velocity (PWV), a measure of arterial stiffness, and intima‐media thickening (IMT), a measure of early atherosclerosis, are intermediate markers of cardiovascular disease which are predictive of cardiovascular events. Traditionally, both were thought to result from accumulative exposure to traditional cardiovascular risk factors. However, their association with risk factors in young adults in low‐income settings is unknown. We sought to investigate the association between PWV and IMT with traditional cardiovascular risk factors in the Andhra Pradesh Children and Parents Study cohort from Southern India. Male and female adults (N = 1440) aged between 20 and 24 years underwent measures of PWV and IMT. Exposure variables included smoking, body mass index (BMI), mean arterial pressure (MAP), glucose, homeostatic model assessment of insulin resistance (HOMA‐IR), total cholesterol, high‐density lipoprotein cholesterol (HDL‐cholesterol), and triglycerides. Association between outcome and exposure variables was assessed using linear regression analysis. Average values for PWV and IMT were 5.9 ± 0.6 m/s and 0.5 ± 0.1 mm. In univariable analysis, PWV associated with MAP, BMI, smoking, total cholesterol, glucose, and HOMA‐IR and IMT associated with MAP, BMI, tobacco use, and HDL‐cholesterol. In multivariable analysis, PWV remained strongly positively associated with MAP increasing by 0.5 m/s (P < .001) for a 10 mm Hg increase in MAP (R² = .37). In contrast, IMT negatively associated with HDL‐cholesterol (β = ?.10; P = .012, R² = .02). There was weak evidence that PWV and IMT positively associated with BMI. In young adults from Southern India, PWV positively associated with blood pressure and IMT negatively associated with HDL‐cholesterol. This suggests separate etiologies for atherosclerosis and arterial stiffening in young adults.     

High PRDM16 expression identifies a prognostic subgroup of pediatric acute myeloid leukaemia correlated to FLT3‐ITD,KMT2A‐PTD,and NUP98‐NSD1: the results of the Japanese Paediatric Leukaemia/Lymphoma Study Group AML‐05 trial

Recent reports described the NUP98‐NSD1 fusion as an adverse prognostic marker for acute myeloid leukaemia (AML) and PRDM16 (also known as MEL1) as the representative overexpressed gene in patients harbouring NUP98‐NSD1 fusion. PRDM16 gene expression levels were measured via real‐time polymerase chain reaction in 369 paediatric patients with de novo AML, of whom 84 (23%) exhibited PRDM16 overexpression (PRDM16/ABL1 ratio ≥ 0·010). The frequencies of patients with high or low PRDM16 expression differed widely with respect to each genetic alteration, as follows: t(8;21), 4% vs. 96%, P < 0·001; inv(16), 0% vs. 100%, P < 0·001; KMT2A (also termed MLL)‐ partial tandem duplication, 100% vs. 0%, P < 0·001; NUP98‐NSD1, 100% vs. 0%, P < 0·001. The overall survival (OS) and event‐free survival (EFS) among PRDM16‐overexpressing patients were significantly worse than in patients with low PRDM16 expression (3‐year OS: 51% vs. 81%, P < 0·001, 3‐year EFS: 32% vs. 64%, P < 0·001) irrespective of other cytogenetic alterations except for NPM1. PRDM16 gene expression was particularly useful for stratifying FLT3‐internal tandem duplication‐positive AML patients (3‐year OS: high = 30% vs. low = 70%, P < 0·001). PRDM16 overexpression was highly recurrent in de novo paediatric AML patients with high/intermediate‐risk cytogenetic profiles and was independently associated with an adverse outcome.