Blood pressure variability and outcome in acute severe stroke: A post hoc analysis of CHASE—A randomized controlled trial

The influence of blood pressure variability (BPV) on outcomes in patients with severe stroke is still largely unsettled. Using the data of CHASE trial, the authors calculated the BPV during the acute phase and subacute phase of severe stroke, respectively. The primary outcome was to investigate the relationship between BPV and 90‐day modified Rankin scale (mRS) ≥ 3. The BPV was assessed by eight measurements including standard deviation (SD), mean, maximum, minimum, coefficient of variation (CV), successive variation (SV), functional successive variation (FSV), and average real variability (ARV). Then, the SD of SBP was divided into quintiles and compared the quintile using logistic regression in three models. The acute phase included 442 patients, and the subacute phase included 390 patients. After adjustment, six measurements of BPV during the subacute phase rather than acute phase were strongly correlated with outcomes including minimum (odds ratio [OR]: 0.83, 95% confidence interval [CI]: 0.69‐0.99, p = .037), SD (OR: 1.10, 95% CI: 1.03‐1.17, p = .007), CV (OR: 1.12, 95% CI: 1.03‐1.23, p = .012), ARV (OR: 1.13, 95% CI: 1.05‐1.20, p < .001), SV (OR: 1.09, 95% CI: 1.04‐1.15, p = .001), and FSV (OR: 1.12, 95% CI: 1.05‐1.19, p = .001). In the logistic regression, the highest fifth of SD of SBP predicted poor outcome in all three models. In conclusion, the increased BPV was strongly correlated with poor outcomes in the subacute phase of severe stroke, and the magnitude of association was progressively increased when the SD of BP was above 12.     

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.     

Fear of hypoglycemia and its determinants in insulin‐treated patients with type 2 diabetes mellitus

The aim of the present study was to investigate the prevalence of fear of hypoglycemia, in association with severe hypoglycemia and social factors, in insulin‐treated patients with type 2 diabetes mellitus. A questionnaire survey on hypoglycemia and patient–physician communication was carried out in 355 patients with insulin‐treated type 2 diabetes mellitus patients at 16 hospitals and clinics. A fear of hypoglycemia was reported by 27.7% of patients. A stepwise logistic regression analysis found that severe hypoglycemia during the past 1 year was a significant determinant of fear of hypoglycemia (odds ratio 2.16, 95% confidence interval 1.06–4.41; P = 0.034), and age (odds ratio 1.02, 95% confidence interval 1.00–1.05, P = 0.038) and living alone (odds ratio 1.93, 95% confidence interval 1.00–3.73, P < 0.05) were significantly higher in patients with fear of hypoglycemia than in those without it.     

Medication Routines and Adherence Among Hypertensive African Americans

Poor adherence to prescribed medication regimens remains an important challenge preventing successful treatment of cardiovascular diseases such as hypertension. While studies have documented differences in the time of day or weekday vs weekend on medication adherence, no study has examined whether having a medication‐taking routine contributes to increased medication adherence. The purpose of this study was to: (1) identify patients’ sociodemographic factors associated with consistent medication‐taking routine; (2) examine associations between medication‐taking consistency, medication adherence, and blood pressure (BP) control. The study included black patients with hypertension (n = 190; 22 men and 168 women; age, mean±standard deviation 54 ± 12.08 years) who completed a practice‐based randomized controlled trial. Findings showed that medication‐taking consistency was significantly associated with better medication adherence (F = 9.54, P = .002). Associations with the consistency index were not statistically significant for diastolic BP control (odds ratio, 1.319; 95% confidence interval, 0.410–4.246; P = .642) and systolic BP control (odds ratio, 0.621; 95% confidence interval, 0.195–1.974; P = .419).     

The association of circulating monocyte count with coronary collateral growth in patients with diabetes mellitus

The status of inflammation may affect the collateral development in patients with diabetes mellitus (DM). Monocytes were found to have an important role in collateral growth in animal studies. We aimed to investigate the possible association of circulating monocyte count with collateral development in patients with DM and severe coronary artery disease (CAD). We enrolled 134 consecutive patients with DM who had ≥95 stenosis in at least one major coronary artery and investigated the relationship between circulating monocyte count and collateral growth. When we analyzed the coronary angiograms of eligible patients, we found that 64 of them had good collateral growth and 70 had poor collateral growth according to the Cohen–Rentrop method. The monocyte count was significantly different between good and poor collateral growth groups (643 ± 184 vs. 479 ± 143 per mm³, P < 0.001). In the analysis comparing the Rentrop score with the Gensini score and circulating monocyte count, we found significant correlations (r = 0.293, P = 0.001 and r = 0.455, P < 0.001, respectively). The duration of ischemic symptoms tended to be longer in the good collateral group (1.9 ± 4.1 vs. 0.8 ± 1.3 years, P = 0.079). The Gensini score was also correlated with the duration of myocardial ischemic symptoms (r = 0.299, P = 0.004). Multivariate analysis revealed an increased monocyte count in the good collateral group [odds ratio (OR), 5.726; 95% confidence interval (CI), 1.817–18.040, P = 0.003, the cut-off value for monocyte was defined as 550 cell/mm³]. The increased circulating monocyte count in diabetic patients was evidently related to good coronary collateral growth. This finding may be potentially important in clinical and basic cardiovascular medicine.     

Magnetic resonance imaging pattern of bone marrow involvement as a new predictive parameter of disease progression in newly diagnosed patients with multiple myeloma eligible for autologous stem cell transplantation

We investigated the prognostic value of the magnetic resonance imaging (MRI) pattern of bone marrow involvement in patients with multiple myeloma (MM) eligible for autologous stem cell transplantation (ASCT). 126 patients with untreated MM indicated for ASCT underwent spine MRI and cytogenetic analysis at diagnosis. All patients received ASCT after induction therapy of VAD (vincristine, doxorubicin, dexamethasone; n = 55) or a thalidomide‐based regimen (TCD; n = 71). Thalidomide maintenance therapy was performed in 68 patients. The MRI pattern was normal in 27, focal in 47, and diffuse/variegated in 52 patients. Patients with the diffuse/variegated pattern showed significantly higher stage (P = 0·038), higher β‐2 microglobulin level (P = 0·001) and severe anaemia (P = 0·015). However, the cytogenetics were not different among the MRI patterns (P = 0·890). Progression‐free survival (PFS) was lower in the diffuse/variegated pattern (P = 0·002) than other patterns, but not overall survival (OS) (P = 0·058). Thalidomide maintenance therapy was correlated only with PFS (P = 0·001). High‐risk cytogenetics were associated with both poorer PFS (P < 0·001) and OS (P = 0·003). In a multivariate analysis, the diffuse/variegated MRI pattern was an independent predictor of disease progression (Hazard Ratio, 1·922; 95% confidence interval, 1·185–3·118; P = 0·008). The diffuse/variegated MRI pattern is a novel prognostic factor for disease progression in MM patients eligible for ASCT.     

Diagnostic yield of the cytomegalovirus (CMV) antigenemia assay and clinical features in solid organ transplant recipients and hematopoietic stem cell transplant recipients with CMV pneumonia

Data are limited on the value of non‐invasive diagnostic methods, such as the cytomegalovirus (CMV) antigenemia assay, and the clinical features of CMV pneumonia in patients who have undergone solid organ transplant (SOT) compared with those who have had hematopoietic stem cell transplant (HSCT). All adult patients with suspected CMV pneumonia, who had received SOT or HSCT in a tertiary hospital during a 5‐year period, were retrospectively enrolled. CMV pneumonia was defined as clinical and radiographic evidence of pneumonia in association with the isolation of CMV in viral cultures of bronchoalveolar lavage or lung tissue specimens, or with the identification of CMV in lung tissue. In total, 36 patients with CMV pneumonia were identified. Of these, 29 (80%) had received SOT and 7 (20%) had received HSCT. The incidence of CMV pneumonia in the patients with SOT (3.0 per 1000 person‐years [95% confidence interval {CI} 0.6–8.7]) was lower than in those with HSCT (17.0 per 1000 person‐years [95% CI 9.9–27.2], P = 0.003) and CMV‐related mortality showed a tendency to have lower mortality in patients with SOT (10% [3/29]) than with HSCT (43% [3/7], P = 0.07). The overall sensitivity of the CMV assay (≥ 1/200,000 leukocytes) in patients with CMV pneumonia was 69% (95% CI 52–84%). The CMV antigenemia test is of limited value in diagnosing CMV pneumonia, given the high cost of false‐negative diagnoses of CMV pneumonia.     

Novel cardiovascular biomarkers in unexplained syncopal attacks: the SYSTEMA cohort

Objectives

The aim of the study was to investigate the resting levels of novel cardiovascular biomarkers in common types of noncardiac syncope.

Design and setting

An observational study was conducted including 255 patients (mean age 60 years, range 15–93; 45% men) with unexplained syncopal attacks. Subjects underwent an expanded head‐up tilt test including carotid sinus massage, and nitroglycerin provocation if indicated. Using logistic regression, we explored the associations between specific diagnoses of syncope and resting levels of circulating biomarkers: C‐terminal pro‐arginine vasopressin (CT‐proAVP), C‐terminal endothelin‐1 precursor fragment (CT‐proET‐1), midregional fragments of pro‐atrial natriuretic peptide (MR‐proANP) and pro‐adrenomedullin (MR‐proADM).

Results

A total of 142 (56%) patients were diagnosed with vasovagal syncope (VVS), 85 (33%) with orthostatic hypotension (OH) and 47 (18%) with carotid sinus hypersensitivity (CSH); in addition, 74 (29%) patients had more than one diagnosis. Thirty‐five patients (14%) demonstrated a cardioinhibitory reflex. The probability of VVS was highest in the first quartile of MR‐proANP [Q1 vs. Q4: odds ratio (OR) 5.57, 95% confidence interval (CI) 1.86–16.74; P < 0.001] and CT‐proET‐1 (OR 7.17, 95% CI 2.43–21.13; P < 0.001). By contrast, the probability of OH was highest in the fourth quartile of CT‐proET‐1 (Q4 vs. Q1: OR 8.66, 95% CI 2.49–30.17; P < 0.001). Furthermore, CSH was most frequently observed in the first quartile of MR‐proANP (Q1 vs. Q4: OR 6.57, 95% CI 1.62–26.62; P = 0.008) among those over 60 years of age, whereas the cardioinhibitory reflex was strongly associated with low CT‐proET‐1 levels (Q1 vs. Q4: OR 69.7, 95% CI 6.97–696.6; P < 0.001). Moreover, in patients with VVS, a high concentration of CT‐proET‐1 was predictive of OH (OR per 1 SD 2.4, 95% CI 1.15–5.02; P = 0.02), whereas low CT‐proET‐1 suggested involvement of the cardioinhibitory reflex (OR per 1SD 0.42, 95% CI 0.25–0.70; P = 0.001).

Conclusions

The levels of MR‐proANP and CT‐proET‐1 are markedly changed in common forms of syncope, suggesting the involvement of novel neurohormonal mechanisms in syncopal attacks.     

24‐hour aortic blood pressure variability showed a stronger association with carotid damage than 24‐hour brachial blood pressure variability: The SAFAR study

We aim to compare 24‐hour aortic blood pressure variability (BPV) with brachial BPV in relation to carotid damage as estimated by carotid intima‐media thickness (CIMT) and cross‐sectional area (CCSA). Four hundred and forty five individuals received brachial and aortic 24‐hour ambulatory BP monitoring with a validated device (Mobil‐O‐Graph). Systolic BPV was estimated by average real variability (ARV) and time‐weighted standard deviation (wSD). In multiple logistic regression analysis, CIMT > 900 μm was significantly and independently associated with aortic ARV (OR = 1.38; 95% CI: 1.04‐1.84), aortic wSD (OR = 1.65; 95% CI: 1.19‐2.29) and brachial ARV (OR = 1.53; 95% CI: 1.07‐2.18), but not with brachial wSD. CCSA > 90th percentile was significantly and independently associated with aortic ARV (OR = 1.50; 95% CI: 1.07‐2.10) and wSD (OR = 1.70; 95% CI: 1.12‐2.56), but not with brachial BPVs. In receiver operator characteristics curve analysis, aortic wSD identified CCSA > 90th percentile better than brachial wSD (AUC: 0.73 vs 0.68, P < .01). In conclusion, aortic 24‐hour systolic BPV showed a slightly stronger association with carotid damage than brachial BPV.     

HLA‐DQ polymorphisms with HBV infection: different outcomes upon infection and prognosis to lamivudine therapy

Two recent genome‐wide studies showed that the single‐nucleotide polymorphisms in the HLA‐DQ region (rs2856718 and rs9275572) were associated with chronic hepatitis B virus infection and chronic hepatitis C virus‐associated hepatocellular carcinoma in Japanese patients. We tested the effects of the two single‐nucleotide polymorphisms for all major HBV outcomes and lamivudine treatment in Han Chinese. A total of 1649 samples were enrolled, and peripheral blood samples were collected in this study. The single‐nucleotide polymorphisms in the HLA‐DQ region were genotyped using matrix‐assisted laser desorption/ionization time of flight mass spectrometry. Our study demonstrated the clear relevance of HLA‐DQ rs2856718 and rs9275572 with HBV susceptibility, natural clearance and HBV‐associated HCC. HLA‐DQ rs2856718G and rs9275572A were strongly associated with decreased risk of chronic HBV infection (odds ratio = 0.641; P = 2.64 × 10⁻⁴; odds ratio = 0.627, P = 7.22 × 10⁻⁵) and HBV natural clearance (odds ratio = 0.610; P = 4.80 × 10⁻⁴; odds ratio = 0.714, P = 0.013). Moreover, rs9275572A was also associated with development of cirrhosis and hepatocellular carcinoma (odds ratio = 0.632, P = 0.008). In addition, we showed for the first time to our knowledge that rs9275572 was a predictor for lamivudine therapy (viral response: odds ratio = 2.599, P = 4.43 × 10⁻⁴; biochemical response: odds ratio = 2.279, P = 4.23 × 10⁻⁴). Our study suggested that HLA‐DQ loci were associated with both HBV clearance and HBV‐related diseases and outcomes of lamivudine treatment in Han Chinese.     

Haematopoietic stem cell transplantation for relapsed or refractory anaplastic large cell lymphoma: a study of children and adolescents in Japan

To evaluate haematopoietic stem cell transplantation (HSCT) in children and adolescents, we reviewed the records of 47 patients who were ≤18 years, had relapsed or refractory anaplastic large cell lymphoma, and received HSCT between 1990 and 2010. At HSCT, complete remission (CR) was less common in allogeneic HSCT recipients (n = 24) than in autologous HSCT recipients (n = 23) (P = 0·01). The autologous and allogeneic HSCT groups differed in terms of 5‐year event‐free survival (EFS) (38% vs. 50%, P = 0·63), cumulative incidence of progress or relapse (49% vs. 28%, P = 0·25), and treatment‐related mortality (12% vs. 25%, P = 0·40). However, these differences were not significant. Patients with non‐CR at autologous HSCT had a significantly lower EFS rate (14% vs. 48%, P = 0·03). Conversely, although those with non‐CR at allogeneic HSCT had a lower EFS rate, this was not significant (44% vs. 63%, P = 0·26). Reduced‐intensity conditioning regimens were used for three of the 16 allogeneic HSCTs received by patients with non‐CR. These three patients achieved CR, surviving 32–65 months after HSCT. These results demonstrated that allogeneic HSCT might be a treatment option for patients who do not achieve CR through conventional chemotherapy.     

The efficacy and safety of continued hydroxycarbamide therapy versus switching to ruxolitinib in patients with polycythaemia vera: a randomized,double‐blind,double‐dummy,symptom study (RELIEF)

The randomized, double‐blind, double‐dummy, phase 3b RELIEF trial evaluated polycythaemia vera (PV )‐related symptoms in patients who were well controlled with a stable dose of hydroxycarbamide (also termed hydroxyurea) but reported PV ‐related symptoms. Patients were randomized 1:1 to ruxolitinib 10 mg BID (n  = 54) or hydroxycarbamide (prerandomization dose/schedule; n  = 56); crossover to ruxolitinib was permitted after Week 16. The primary endpoint, ≥50% improvement from baseline in myeloproliferative neoplasm ‐symptom assessment form total symptom score cytokine symptom cluster (TSS ‐C; sum of tiredness, itching, muscle aches, night sweats, and sweats while awake) at Week 16, was achieved by 43·4% vs. 29·6% of ruxolitinib‐ and hydroxycarbamide‐treated patients, respectively (odds ratio, 1·82; 95% confidence interval, 0·82–4·04; P  =  0·139). The primary endpoint was achieved by 34% of a subgroup who maintained their hydroxycarbamide dose from baseline to Weeks 13–16. In a post hoc analysis, the primary endpoint was achieved by more patients with stable screening‐to‐baseline TSS ‐C scores (ratio ≤ 2) receiving ruxolitinib than hydroxycarbamide (47·4% vs. 25·0%; P  =  0·0346). Ruxolitinib treatment after unblinding was associated with continued symptom score improvements. Adverse events were primarily grades 1/2 with no unexpected safety signals. Ruxolitinib was associated with a nonsignificant trend towards improved PV ‐related symptoms versus hydroxycarbamide, although an unexpectedly large proportion of patients who maintained their hydroxycarbamide dose reported symptom improvement.     

Impact of chronic kidney disease on the severity of initially diagnosed coronary artery disease and the patient prognosis in the Japanese population

This study evaluated the relationship between the severity of coronary artery disease (CAD) and traditional coronary risk factors, metabolic syndrome, and chronic kidney disease (CKD). Three hundred and forty-three patients (35–90 years of age) with initial diagnosis of CAD were separated into two groups: 165 patients with single-vessel coronary artery disease (SVD group) and 178 patients with multivessel coronary artery disease (MVD group). We compared the risk factors for CAD between the two groups. An adjusted multivariate analysis showed that only CKD was associated with MVD (odds ratio, 2.85; 95% confidence interval [CI], 1.76–4.63; P = 0.00002). Next, the relationship between the severity of CAD, CKD, and the incidence of subsequent major adverse cardiac event (MACE) was investigated in 338 patients during the patient follow-up. The risk of MACE was approximately threefold higher in the group with MVD and CKD stage of 3 or greater than in the group with SVD but without CKD stage of 3 or greater (adjusted hazard ratio, 3.40; 95% CI, 1.26–9.17; P = 0.016). A statistical analysis also suggested that having MVD and advanced CKD was a more powerful risk factor for MACE. The comparison of risk factors between patients with SVD and patients with MVD revealed that CKD was the most important risk factor for MVD. In addition, having MVD and advanced CKD together was a crucial risk factor for subsequent MACE. To reduce the progression of CAD and to improve the prognosis of patients with MVD, the renal status should therefore be carefully assessed during treatment for CAD.     

Improved joint health in subjects with severe haemophilia A treated prophylactically with recombinant factor VIII Fc fusion protein

Introduction

Joint arthropathy is the long‐term consequence of joint bleeding in people with severe haemophilia.

Aim

This study assessed change in joint health over time in subjects receiving recombinant factor VIII Fc fusion protein (rFVIIIFc) prophylaxis.

Methods

ALONG is the phase 3 pivotal study in which the benefit of rFVIIIFc as a prophylactic treatment for bleeding control was shown in previously treated severe haemophilia patients ≥12 years of age (arm 1: 25‐65 IU/kg every 3‐5 days, arm 2: 65 IU/kg weekly and arm 3: episodic). After completing ALONG, subjects had the option to enrol into the extension study (ASPIRE). This interim, post hoc analysis assessed changes in joint health over ~2.8 years in these patients.

Results

Forty‐seven subjects had modified Haemophilia Joint Health Score (mHJHS) data at A‐LONG baseline, ASPIRE baseline and ASPIRE Year 1 and Year 2. Compared with A‐LONG baseline (23.4), mean improvement at ASPIRE Year 2 was ?4.1 (95% confidence interval [CI], ?6.5, ?1.8; P = .001). Regardless of prestudy treatment regimen, subjects showed continuous improvement in mHJHS from A‐LONG baseline through ASPIRE Year 2 (prestudy prophylaxis: ?2.4, P = .09; prestudy episodic treatment: ?7.2, P = .003). Benefits were seen in subjects with target joints (?5.6, P = .005) as well as those with severe arthropathy (?8.8, P = .02). The mHJHS components with the greatest improvement at ASPIRE Year 2 were swelling (?1.4, P = .008), range of motion (?1.1, P = .03) and strength (?0.8, P = .04).

Conclusions

Prophylaxis with rFVIIIFc may improve joint health over time regardless of prestudy prophylaxis or episodic treatment regimens.     

The interferon‐gamma (IFN‐γ) +874T allele reduces the risk of hepatitis B infection in an Asian population

Increasing evidence suggests that polymorphism of the interferon‐gamma (IFN‐γ) gene in the first intron at position +874 may be associated with chronic hepatitis B virus (HBV) infection and/or HBV clearance. However, the results of relevant studies have been inconsistent. To derive a more precise estimation of the association, we performed a meta‐analysis. In total, 10 independent studies including 1661 chronic HBV‐infected patients and 1142 controls were included in this meta‐analysis. In studies following Hardy–Weinberg equilibrium (HWE), a significantly decreased risk of chronic HBV infection was associated with the IFN‐γ + 874TT genotype in the overall population (TT vs AA: odds ratio (OR) = 0.714, 95% confidence interval (CI) = 0.526–0.969, P = 0.031) when compared with a spontaneously recovered population. Subgroup analysis by ethnicity revealed a similar association in Asian individuals (TT vs AA: OR = 0.706, 95% CI = 0.518–0.962, P = 0.028). Moreover, when compared with a healthy control group, the 874T allele was associated with a significant lower risk of chronic HBV infection in the overall populations (TA vs AA: OR = 0.439, 95% CI = 0.193–0.997, P = 0.049; TT + TA vs AA: OR = 0.475, 95% CI = 0.271–0.832, P = 0.009) and in Asian individuals (TA vs AA: OR = 0.862, 95% CI = 0.744–0.999, P = 0.048). In conclusion, the IFN‐γ + 874TT genotype and 874T allele reduce the risk of chronic HBV infection in Asian individuals.     

Prognostic value of paroxysmal nocturnal haemoglobinuria clone presence in aplastic anaemia patients treated with combined immunosuppression: results of two‐centre prospective study

Paroxysmal nocturnal haemoglobinuria (PNH) clones are frequently detected in patients with aplastic anaemia (AA). To evaluate the prognostic role of PNH clone presence we conducted a prospective study in 125 AA patients treated with combined immunosuppressive therapy (IST). Seventy‐four patients (59%) had a PNH clone (PNH+ patients) at diagnosis, with a median clone size of 0·60% in granulocytes and 0·15% in red blood cells. The response rate at 6 months was higher in PNH+ patients than that in PNH‐ patients, both after first‐ and second‐line IST: 68% vs. 45%, P = 0·0164 and 53% vs. 13%, P = 0·0502 respectively. Moreover, 42% of PNH+ patients achieved complete remission compared with only 16% of PNH‐ patients (P = 0·0029). In multivariate logistic regression analysis, PNH clone presence (odds ratio 2·56, P = 0·0180) and baseline absolute reticulocyte count (ARC) ≥30 × 10⁹/l (odds ratio 5·19, P = 0·0011) were independent predictors of response to treatment. Stratification according to PNH positivity and ARC ≥30 × 10⁹/l showed significant distinctions for cumulative incidence of response, overall and failure‐free survival. The results of this prospective study confirmed the favourable prognostic value of PNH clone presence in the setting of IST for AA.     

Controlled Epstein–Barr virus reactivation after allogeneic transplantation is associated with improved survival

Epstein–Barr virus reactivation (EBV‐R) frequently occurs in patients having allogeneic hematopoietic stem cell transplantation (HSCT). We evaluated the impact of controlled EBV‐R on survival of 190 patients (114M/76F, median age: 51 yr, range 18–69), having HSCT for hematological malignancies (105 acute leukemias and myelodysplasias, 71 lymphoproliferative disorders, 14 others). Overall survival (OS) and progression‐free survival (PFS) were compared between patients with and without EBV‐R. Of 138, patients had reduced‐intensity conditioning regimen. Various stem cell sources (141 PB, 33 umbilical cord blood and 16 bone marrow) were used. Patients with EBV‐R had longer PFS and OS than those without EBV‐R: PFS at 2 yr 69% vs. 51% and at 5 yr 47% vs. 38% (P < 0.04); OS at 2 yr 76% vs. 64% and at 5 yr 63% vs. 47%) (P < 0.001). The use of rituximab had no impact on OS and PFS, but it reduced the intensity of GVHD, despite the fact that TRM was not significantly different between the two groups of patients. So, rituximab may have an additional effect to other factors on PFS and OS. In multivariate analysis, antithymocyte globulin administration was not a significant factor for PFS (P = 0.68) and for OS (P = 0.81). Circulating NK cells were significantly increased by 22% (P = 0.03) in EBV‐R patients with no differences for other parameters. Controlled EBV‐R in the setting of HSCT is associated with better OS and PFS, with a significant increase in circulating NK cells.     

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.     

Acute in‐hospital blood pressure variability predicts early neurological deterioration in acute minor stroke or transient ischemic attack with steno‐occlusive arterial disease

It is generally known that acute minor stroke and transient ischemic attack (TIA) seem to be benign. However, their occurrence in patients with steno‐occlusive arterial disease may result in early neurological deterioration (END). We aimed to elucidate the effect of blood pressure variability (BPV) on the development of END. Consecutive acute minor stroke and TIA patients within 24 hours of onset were prospectively recruited from the Affiliated Hospital of Yangzhou University between Aug 2015 and Feb 2019. END was defined as an NIHSS score increased ≥1 during the first 72 hours compared with the initial NIHSS score. During this period, the mean, maximum (max), the difference between the maximum and minimum (max‐min), the SD, and coefficient of variation of BP (BP_CV) were calculated. Of the 160 total patients enrolled in the study (mean age, 68.01 ± 9.33 years; 50.6% female), 52 (32.5%) patients occurred END during the first 72h after admission. To express the BPV as a categorical variable, we classified the subjects into one of four groups, representing four quartiles of BPV. In the multivariable analyses, the lowest quartiles were considered as reference groups. The results showed that patients who fell in the fourth quartile (SBP_max‐min:OR = 3.289, 95% CI 1.147‐9.430; SBP_SD:OR = 3.313, 95% CI 1.041‐10.547; SBP_CV:OR = 3.425, 95% CI 1.164‐10.077; DBP_SD:OR = 3.124, 95% CI 1.065‐9.158) had a significantly higher risk of END after adjusting the variables (age, female, diabetes mellitus, atrial fibrillation, and CRP with P values <.1 in univariate analyses). Our study demonstrated that the acute in‐hospital BPV was associated with the development of END in acute minor stroke and TIA with steno‐occlusive arterial disease.     

Meta‐analysis of observational studies: hepatitis C and survival after renal transplant

Recent evidence has shown that anti‐HCV‐positive serologic status is significantly linked to lower patient and graft survival after renal transplant, but conflicting results have been given on this point. The aim of this study was to conduct a systematic review of the published medical literature concerning the impact of HCV infection on all‐cause mortality and graft loss after RT. The relative risk of all‐cause mortality and graft loss was regarded as the most reliable outcome end‐point. Study‐specific relative risks were weighted by the inverse of their variance to obtain fixed‐ and random‐effect pooled estimates for mortality and graft loss with HCV across the published studies. We identified eighteen observational studies involving 133 530 unique renal transplant recipients. The summary estimate for adjusted relative risk (aRR) of all‐cause mortality was 1.85 with a 95% confidence interval (CI) of 1.49; 2.31 (P < 0.0001); heterogeneity statistics, Ri = 0.87 (P‐value by Q‐test = 0.001). The overall estimate for adjusted RR of all‐cause graft loss was 1.76 (95% CI, 1.46; 2.11) (P < 0.0001), heterogeneity statistics, Ri = 0.65 (P‐value by Q‐test = 0.001). Stratified analysis did not change meaningfully these results. Meta‐regression showed that living donor rate had a favourable influence on patient (P = 0.031) and graft survival (P = 0.01), whilst diabetes mellitus having a detrimental role on patient survival (P = 0.001). This meta‐analysis of observational studies supports the notion that HCV‐positive patients after RT have an increased risk of mortality and graft loss. Further studies are in progress to understand better the mechanisms underlying the relationship between HCV and mortality or graft dysfunction after renal transplant.