Femoral hypoplasia-unusual CASE REPORTS Case 1A 30-year-old primigravida was referred to our unit at 21 weeks' gestation because of a suspicion of severe bilateral femoral hypoplasia in her male fetus. The family history was negative for congenital anomalies. The patient did not have insulin-dependent diabetes mellitus. Ultrasound examination showed fetal biometry consistent with a gestational age of 21 weeks, with the exception of the femora, which appeared severely hypoplastic. The left femur was completely absent whereas the right one measured only a few millimeters (Figure 1a and b). Ultrasound imaging of the fetal face revealed the presence of unilateral right cleft lip and palate (Figure 1d). Unilateral right renal agenesis was also observed. In the counseling session, the couple was informed of the putative diagnosis and outcome of femoral hypoplasia-unusual facies syndrome (FHUFS), and the possible management options.After counseling, the couple opted for termination of the pregnancy. The diagnosis of FHUFS was confirmed at autopsy. In particular, severe bilateral and asymmetric femoral hypoplasia (Figure 1c), unilateral cleft lip/palate ( Figure 1e) and unilateral renal agenesis were found. In addition, the face showed the typical features of FHUFS: a long philtrum, thin upper lip, moderate micrognathia and low-set ears (Figure 1e). Other features consistent with the diagnosis of FHUFS found at autopsy included a short neck and a pelvis with vertically orientated iliac blades. Case 2A 28-year-old obese woman (gravida 2, para 1) with insulin-dependent diabetes mellitus was referred to our unit at 21 weeks' gestation because of an abnormal second-trimester anomaly scan. The family history was unremarkable, with no consanguinity reported. On ultrasound examination, severe hypoplasia of the left femur was observed (Figure 2a), whereas the contralateral femoral shaft appeared unremarkable, with length in the normal range 1 . Examination of the fetal face revealed severe micrognathia (Figure 2c) and the ears appeared low set. No other abnormalities were observed. A diagnosis of FHUFS was made. After counseling, the couple opted for termination of the pregnancy. At autopsy, severe unilateral hypoplasia of the left femur, severe micrognathia and low-set ears were confirmed (Figure 2b and d). Also noted were a short nose with a broad tip, a thin upper lip and a cleft palate (Figure 2d, inset), confirming the diagnosis of FHUFS. Case 3A 24-year-old primigravida was referred to our unit at 13 weeks' gestation after the detection of abnormal lower limbs at the nuchal translucency scan. There was no

BackgroundThe independent prognostic impact of diabetes mellitus (DM) and prediabetes mellitus (pre‐DM) on survival outcomes in patients with chronic heart failure has been investigated in observational registries and randomized, clinical trials, but the results have been often inconclusive or conflicting. We examined the independent prognostic impact of DM and pre‐DM on survival outcomes in the GISSI‐HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca‐Heart Failure) trial.Methods and ResultsWe assessed the risk of all‐cause death and the composite of all‐cause death or cardiovascular hospitalization over a median follow‐up period of 3.9 years among the 6935 chronic heart failure participants of the GISSI‐HF trial, who were stratified by presence of DM (n=2852), pre‐DM (n=2013), and non‐DM (n=2070) at baseline. Compared with non‐DM patients, those with DM had remarkably higher incidence rates of all‐cause death (34.5% versus 24.6%) and the composite end point (63.6% versus 54.7%). Conversely, both event rates were similar between non‐DM patients and those with pre‐DM. Cox regression analysis showed that DM, but not pre‐DM, was associated with an increased risk of all‐cause death (adjusted hazard ratio, 1.43; 95% CI, 1.28–1.60) and of the composite end point (adjusted hazard ratio, 1.23; 95% CI, 1.13–1.32), independently of established risk factors. In the DM subgroup, higher hemoglobin A1c was also independently associated with increased risk of both study outcomes (all‐cause death: adjusted hazard ratio, 1.21; 95% CI, 1.02–1.43; and composite end point: adjusted hazard ratio, 1.14; 95% CI, 1.01–1.29, respectively).ConclusionsPresence of DM was independently associated with poor long‐term survival outcomes in patients with chronic heart failure.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00336336.

Cardiovascular (CV) disease is the leading cause of death in chronic kidney disease (CKD) and end-stage renal disease (ESRD). A key driver in this pathology is increased aortic stiffness, which is a strong, independent predictor of CV mortality in this population. Aortic stiffening is a potentially modifiable biomarker of CV dysfunction and in risk stratification for patients with CKD and ESRD. Previous work has suggested that therapeutic modification of aortic stiffness may ameliorate CV mortality. Nevertheless, future clinical implementation relies on the ability to accurately and reliably quantify stiffness in renal disease. Pulse wave velocity (PWV) is an indirect measure of stiffness and is the accepted standard for non-invasive assessment of aortic stiffness. It has typically been measured using techniques such as applanation tonometry, which is easy to use but hindered by issues such as the inability to visualize the aorta. Advances in cardiac magnetic resonance imaging now allow direct measurement of stiffness, using aortic distensibility, in addition to PWV. These techniques allow measurement of aortic stiffness locally and are obtainable as part of a comprehensive, multiparametric CV assessment. The evidence cannot yet provide a definitive answer regarding which technique or parameter can be considered superior. This review discusses the advantages and limitations of non-invasive methods that have been used to assess aortic stiffness, the key studies that have assessed aortic stiffness in patients with renal disease and why these tools should be standardized for use in clinical trial work.

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Background: Autoantibodies can be identified in approximately 60% of UK children with JDM. With the development of quantitative techniques such as ELISA to detect these autoantibodies there is a growing interest in the clinical utility of autoantibodies in predicting disease activity and the risk of associated complications. To date, the titre of anti-MDA5 has been shown to be useful in predicting response to treatment in Japanese children with JDM and in adults small studies have also shown a relationship between the titres of anti-Jo-1, anti-MDA5, anti-HMGCR and anti-SRP with disease activity measures. Methods: Serum samples and matched clinical data were obtained from 285 patients with JDM recruited to the UK Juvenile Dermatomyositis Cohort and Biomarker Study. After initial screening for the presence of autoantibodies by immunoprecipitation, the antibody titre of those with anti-TIF1g, anti-NXP2 and anti-MDA5 was assessed by ELISA using recombinant antigen. First and last available samples were analysed for each autoantibody subgroup (32 patients with anti-TIF1g, 30 with anti-NXP2 and 15 with anti-MDA5) along with multiple serial samples in those where an initial sample was available within 6 months of diagnosis (12 patients with anti-TIF1g, 8 with anti-NXP2 and with 4 anti-MDA5). Between three and eight samples were available per patient. Results: Autoantibody titre was seen to change over the follow-up period and reduced in the majority of patients in all autoantibody subgroups. In the last available sample (taken 1-19 years post diagnosis) autoantibody titre had reduced below the ELISA positive threshold in eight (25%) patients with anti-TIF1g, seven (23%) with anti-NXP2 and eight (53%) with anti-MDA5. Analysis of serial samples showed a relationship between autoantibody titre and change in disease activity as measured by the physician global assessment score (PGAS). While numbers were too small to demonstrate statistical significance within individual patients, trends were striking and a strong positive correlation was confirmed. Conclusion: Autoantibody titre in JDM changes over time and reduces in the majority of patients. Within individual patients autoantibody titre correlates with disease activity as measured by the Physician Global Assessment Score. A corresponding rise in autoantibody titre to mirror Physician Global Assessment Score in those patients who relapsed, suggests that this does not simply represent regression to the mean. Limitations of this study include few patients with serial samples available, variably timed blood sampling and non-standardized treatment. Further work is needed to confirm these results and to assess whether alterations in autoantibody titre pre-date changes in disease activity; if so, and given the clinical sub-phenotypes associated with these antibodies, the routine testing of autoantibodies early in diagnostic workup is to be recommended. Disclosure statement: S.L.T. has received research support in the form of a BMA Doris Hillier Grant 2012. All other authors have...