MR findings in iatrogenic Gerbode defect

Congenital or acquired communication between left ventricle and right atrium is rare and can be easily overlooked as an eccentric tricuspid regurgitation jet. MRI is the ideal modality for accurate diagnosis, providing details for surgical planning about the location and size of the defect.     

Percutaneous Fetal Atrial Balloon Septoplasty for Simple Transposition of the Great Arteries With an Intact Atrial Septum

We report the first ultrasonographically guided percutaneous balloon atrial septoplasty (BAS), to our knowledge, in a fetus with transposition of the great arteries and an intact ventricular and atrial septum (37 + 2 weeks). After vaginal delivery at 38 weeks, the infant had an elective septostomy (day 1) and an arterial switch procedure (day 7), with an uneventful postoperative course. For centres with experience in fetal cardiac interventions, fetal BAS is a superior management option compared with the alternatives for this high-risk physiology.     

Enhancement of paclitaxel and carboplatin therapies by CCL2 blockade in ovarian cancers

Ovarian cancer is associated with a leukocyte infiltrate and high levels of chemokines such as CCL2. We tested the hypothesis that CCL2 inhibition can enhance chemotherapy with carboplatin and paclitaxel. Elevated CCL2 expression was found in three non‐MDR paclitaxel resistant ovarian cancer lines ES‐2/TP, MES‐OV/TP and OVCAR‐3/TP, compared to parental cells. Mice xenografted with these cells were treated with the anti‐human CCL2 antibody CNTO 888 and the anti‐mouse MCP‐1 antibody C1142, with and without paclitaxel or carboplatin. Our results show an additive effect of CCL2 blockade on the efficacy of paclitaxel and carboplatin. This therapeutic effect was largely due to inhibition of mouse stromal CCL2. We show that inhibition of CCL2 can enhance paclitaxel and carboplatin therapy of ovarian cancer.     

Management and outcomes for patients with TTP: analysis of 100 cases at a single institution

The advent of plasma exchange has led to a dramatic improvement in the survival of patients with thrombotic thrombocytopenic purpura (TTP), though approximately 10% of patients still die and a third suffer relapses. Clinical features that identify poor risk patients have not been clearly identified. We reviewed 100 patients who were treated for a first episode of TTP at the Cleveland Clinic between 2000 and 2012 to identify factors predictive of poor outcomes. On multivariate analysis, increasing age, especially age > 60 (RR: 7.08, 95% CI: 2.15–23.39, P = 0.002), severe neurological symptoms at presentation (RR: 18.37, 95% CI: I4.19–80.13, P < 0.001) and a persistently elevated LDH level after two plasma exchanges were predictive of mortality. Patients with ADAMTS13 activity above or below 5% did not differ in terms of clinical presentation or mortality and relapse rates, although ADAMTS13 activity > 5% was an independent predictor of adverse renal outcomes (need for dialysis and progression to chronic kidney disease). These variables may be useful for risk stratification and identification of patients who could potentially benefit from early institution of adjunctive therapy. Am. J. Hematol. 88:560–565, 2013. © 2013 Wiley Periodicals, Inc.     

Three-question set from Michigan Neuropathy Screening Instrument adds independent prognostic information on cardiovascular outcomes: analysis of ALTITUDE trial

Aims/hypothesis

The self-administered Michigan Neuropathy Screening Instrument (MNSI) is used to diagnose diabetic peripheral neuropathy. We examined whether the MNSI might also provide information on risk of death and cardiovascular outcomes.

Methods

In this post hoc analysis of the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE) trial, we divided 8463 participants with type 2 diabetes and chronic kidney disease (CKD) and/or cardiovascular disease (CVD) into independent training (n = 3252) and validation (n = 5211) sets. In the training set, we identified specific questions that were independently associated with a cardiovascular composite outcome (cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction/stroke, heart failure hospitalisation). We then evaluated the performance of these questions in the validation set.

Results

In the training set, three questions (‘Are your legs numb?’, ‘Have you ever had an open sore on your foot?’ and ‘Do your legs hurt when you walk?’) were significantly associated with the cardiovascular composite outcome. In the validation set, after multivariable adjustment for key covariates, one or more positive responses (n = 3079, 59.1%) was associated with a higher risk of the cardiovascular composite outcome (HR 1.54 [95% CI 1.28, 1.85], p < 0.001), heart failure hospitalisation (HR 1.74 [95% CI 1.29, 2.35], p < 0.001), myocardial infarction (HR 1.81 [95% CI 1.23, 2.69], p = 0.003), stroke (HR 1.75 [95% CI 1.20, 2.56], p = 0.003) and three-point major adverse cardiovascular events (MACE) (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke) (HR 1.49 [95% CI 1.20, 1.85], p < 0.001) relative to no positive responses to all questions. Associations were stronger if participants answered positively to all three questions (n = 552, 11%). The addition of the total number of affirmative responses to existing models significantly improved Harrell’s C statistic for the cardiovascular composite outcome (0.70 vs 0.71, p = 0.010), continuous net reclassification improvement (+22% [+10%, +31%], p = 0.027) and integrated discrimination improvement (+0.9% [+0.4%, +2.1%], p = 0.007).

Conclusions/interpretation

We identified three questions from the MNSI that provide additional prognostic information for individuals with type 2 diabetes and CKD and/or CVD. If externally validated, these questions may be integrated into the clinical history to augment prediction of CV events in high-risk individuals with type 2 diabetes.

     

Risk factors for cardiac autonomic neuropathy in type 1 diabetes mellitus

Aims/hypothesis Cardiac autonomic neuropathy (CAN) is associated with increased morbidity and mortality in type 1 diabetes. Apart from glycaemic control, risk factors for CAN have not been extensively studied.Methods As part of the EURODIAB Prospective Complications Study, CAN—defined as either a loss of heart rate variability or postural hypotension on standing—was assessed at baseline and follow-up (7.3±0.6 years from baseline) in patients with type 1 diabetes.Results Follow-up measurements were available for 956 participants without CAN at baseline (age at baseline 31.3±8.9 years, duration of diabetes 13.5±8.3 years). During follow-up, 163 (17%) subjects developed CAN, yielding an incidence of 23.4 per 1,000 person-years. Blood pressure, weight, the presence of cardiovascular disease, albuminuria, distal symmetrical polyneuropathy (DSP) and retinopathy at baseline were associated with the incidence of CAN after adjustment for sex, duration of diabetes and HbA₁c. In a multivariate regression model, baseline factors associated with an increased risk of developing CAN were age [odds ratio (OR)=1.3 per decade, 95% CI 1.1–1.7], HbA₁c (OR=1.2 per percentage point, 95% CI 1.1–1.4), systolic blood pressure (OR=1.1 per 10 mmHg, 95% CI 1.0–1.3), feeling faint on standing (OR=2.0, 95% CI 1.2–3.2), DSP (OR=1.9, 95% CI 1.2–3.0) and retinopathy (OR=1.7, 95% CI 1.1–2.6).Conclusion/interpretation This study confirms the importance of exposure to hyperglycaemia as a risk factor for CAN. A small set of variables, including HbA₁c, hypertension, DSP and retinopathy, predict the risk of CAN. Clinical trials are needed to address the impact of intensive antihypertensive treatment on CAN in type 1 diabetes.