Clinical characteristics, sex hormones, and long-term follow-up in Swiss postmenopausal women presenting with Takotsubo cardiomyopathy

Background:

The overwhelming majority of patients with stress cardiomyopathy (SC) are postmenopausal women, suggesting an important pathophysiologic role of the female sex hormones. Preliminary data suggest that myocardial stunning might be provoked by estrogen deficiency.

Hypothesis:

We hypothesized that, compared with age‐ and gender‐matched patients with myocardial infarction (MI) or patients with normal coronary arteries, patients with SC would exhibit altered levels of sex hormones. Furthermore, we aimed to describe the clinical course and the pattern of sex hormones of the SC patients during long‐term follow‐up.

Methods:

Blood samples obtained on hospital admission were analyzed for estradiol (E2), progesterone (P), luteinizing hormone (LH), and follicle‐stimulating hormone (FSH) in women with SC (n = 17), age‐matched women with acute MI (n = 16), and women with normal coronary arteries (n = 15). Six years after the initial event, SC patients underwent a clinical and echocardiographic follow‐up and reassessment of sex hormones.

Results:

Estrogen concentrations at hospital admission were significantly higher in the SC group compared with the MI and the control groups, with no difference in P, FSH, and LH concentrations. Follow‐up E2 after 6 years in SC patients was lower than during the acute SC episode. Follow‐up P in these patients was lower than P in the MI and control groups during the acute event, with a similar trend for E2. After a median follow‐up of 6.4 years, 1 sudden cardiac death occurred and 2 patients suffered from SC recurrence.

Conclusions:

During the acute event, E2 concentrations are elevated in postmenopausal SC patients compared with women with acute MI or with normal coronary arteries. The higher E2 concentrations might have exerted atheroprotective effects and thus diverted the stress response to SC rather than MI. Recurrence and/or sudden cardiac death remains a potential risk of SC. Clin. Cardiol. 2012 DOI: 10.1002/clc.21986 Roman Brenner, MD, and Daniel Weilenmann, MD, contributed equally to this work and should be considered first authors. The authors have no funding, financial relationships, or conflicts of interest to disclose.     

EGFR mutation testing on cytological and histological samples in non-small cell lung cancer: a Polish,single institution study and systematic review of European incidence

The targeted treatment of advanced non-small-cell lung cancer (NSCLC) depends on confirmation of activating somatic EGFR mutation. The aim of the study was to evaluate the incidence of EGFR mutations in NSCLC detected in cytological and histological material and present literature review on European EGFR mutation incidence. 273 patients with confirmed NSCLC were entered into the study: 189 histological, paraffin-embedded materials, 12 fresh and 72 fixed cytological specimens. DNA was extracted from both types of material and the EGFR mutation in exons 18-21 was analyzed by direct sequencing. In addition the EGFR gene copy number in cases with sufficient histological material (110 patients) was evaluated by fluorescent in situ hybridization (FISH) technique. The percentage of EGFR somatic mutations was 10.62%. FISH positive results (amplification or high polysomy of EGFR gene) were identified in 33 patients (30.0%). The strongest clinicopathological correlation with the EGFR mutation was found for histological type (adenocarcinoma; p < 0.01), gender (females; p < 0.01) and FISH positive result (p < 0.05). This is the first, single institution study that estimates the EGFR mutation incidence in the Polish population. Cytological material recovered from fixed preparations and stained with hematoxylin and eosin showed DNA quality comparable to fresh tumor cells and histological samples.     

Resistant hypertension in visceral obesity

BackgroundVisceral obesity increases the risk of arterial hypertension (78% of cases of hypertension in men and 65% of cases in women). The aim of the study is to assess the role of visceral obesity in causing resistant hypertension (RH).MethodsThe survey was performed on 5065 hypertensive patients with visceral obesity. BP control was analyzed on the basis of office and home BP measurements. Patients reporting non-compliance were excluded from the study.ResultsThe percentage of RH after excluding undertreated patients (receiving less than 3 drugs or on at least 3-drug regimen without diuretic and without reaching target BP goal) was 13.9%. RH was more frequent only in obese with BMI ≥ 35 and < 40 kg/m² (16.2%) and in morbidly obese individuals (26.5%). Patients with BMI ≥ 35 and < 40 kg/m² and with morbid obesity were receiving three-drug therapy more frequently than patients with visceral obesity and BMI < 30 kg/m². A multiple regression analysis revealed that obesity was associated with RH independent from longer than 5-year period of antihypertensive therapy, diabetes, smoking cigarettes, cardiovascular disease and heart failure. The analysis of home BP measurement revealed that in 11.1% of patients RH was in fact “white coat” hypertension.ConclusionsUndertreatment, underuse of diuretics in multidrug regimens, and the “white-coat” effect are the most common reasons for over-diagnosing resistant hypertension in patients with visceral obesity. Obesity is an independent risk factor for the occurrence of RH.     

Genetic influence on bone phenotypes and body composition: a Swedish twin study

Bone mineral density (BMD), bone size and bone turnover are independent determinants of fractures in elderly. Earlier twin studies of these phenotypes have revealed high heritability for BMD and bone area, and more moderate heritability for bone turnover markers. No previous Scandinavian study has evaluated the genetic and environmental contribution to the variance of these phenotypes, despite the fact that Scandinavian countries have the highest incidence of osteoporotic fractures worldwide. Participants were selected from the Swedish Twin Registry. All intact like-sexed twin pairs born in 1965 or earlier and living in the county of Uppsala were invited to participate. A total of 102 twin pairs (45 monozygotic and 57 dizygotic) accepted the invitation to participate. All twins underwent measurement of BMD and bone area using dual-energy X-ray absorptiometry. Hip geometry was also calculated. Markers for bone formation (osteocalcin) and bone resorption (CrossLaps) were measured in serum. We observed a substantial heritability for BMD at the lumbar spine (0.85; 95 % CI 0.54–0.90), the femoral neck (0.75; 95 % CI 0.62–0.83), and the proximal femur (0.84; 95 % CI 0.74–0.90). The values for bone area were approximately similar to those for BMD. Bone turnover markers had a slightly lower genetic influence with a value of 0.69 (0.53–0.80) for osteocalcin and 0.58 (95 % CI 0.33–0.75) for CrossLaps. As a comparison, the heritabilities of body height and weight were 0.95 and 0.82, respectively. The high heritability on bone phenotypes among Swedish middle-aged and older men and women should encourage further work on the identification of specific genetic pathways. Continuing research in this area could reveal the mechanisms behind the strong genetic susceptibility of bone-related phenotypes.     

Impact of Early Parenteral Nutrition on Metabolism and Kidney Injury

A poor nutritional state and a caloric deficit associate with increased morbidity and mortality, but a recent multicenter, randomized controlled trial found that early parenteral nutrition to supplement insufficient enteral nutrition increases morbidity in the intensive care unit, including prolonging the duration of renal replacement therapy, compared with withholding parenteral nutrition for 1 week. Whether early versus late parenteral nutrition impacts the incidence and recovery of AKI is unknown. Here, we report a prespecified analysis from this trial, the Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients (EPaNIC) study. The timing of parenteral nutrition did not affect the incidence of AKI, but early initiation seemed to slow renal recovery in patients with stage 2 AKI. Early parenteral nutrition did not affect the time course of creatinine and creatinine clearance but did increase plasma urea, urea/creatinine ratio, and nitrogen excretion beginning on the first day of amino acid infusion. In the group that received late parenteral nutrition, infusing amino acids after the first week also increased ureagenesis. During the first 2 weeks, ureagenesis resulted in net waste of 63% of the extra nitrogen intake from early parenteral nutrition. In conclusion, early parenteral nutrition does not seem to impact AKI incidence, although it may delay recovery in patients with stage 2 AKI. Substantial catabolism of the extra amino acids, which leads to higher levels of plasma urea, might explain the prolonged duration of renal replacement therapy observed with early parenteral nutrition.The development of AKI is a frequent and devastating condition in patients admitted to the intensive care unit (ICU). Short-term mortality is high and increases with worsening AKI stages.¹ In AKI survivors, renal recovery is often incomplete, progression to ESRD may be accelerated, and longer-term mortality rates are increased compared with non-AKI patients.^2,3 Patient management consists of maximal prevention of additional renal damage by hemodynamic stabilization and prevention of (iatrogenic) nephrotoxicity. A curative strategy for established AKI is currently unavailable.⁴Observational studies, finding associations between a poor nutritional state and increased morbidity and mortality of AKI patients⁵ and between accumulation of a caloric deficit and poor renal and survival outcome of ICU patients,^6,7 have led to the hypothesis that feeding could ameliorate kidney injury and improve survival of ICU patients. However, nutrition, especially parenteral nutrition (PN), also has potential complications.^8–11 Because of the lack of adequately designed studies, nutritional guidelines are largely based on expert opinion.^12–14 These opinions invariably recommend the early initiation of enteral feeding but substantially differ in their recommendation on when to start supplemental PN.The Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients (EPaNIC) study was the first large, multicenter, randomized controlled trial (RCT) addressing this important question. The study showed that early initiation of PN increased dependency on intensive care compared with withholding supplemental PN for 1 week (hereafter labeled early PN and late PN, respectively).¹⁵ Indeed, early PN prolonged the ICU and hospital length of stay (LOS), increased the incidence of new infections, and prolonged the need for mechanical ventilation. Renal harm was suggested by a clear prolongation of the duration of renal replacement therapy (RRT) in ICU and a trend for more AKI (defined as a doubling or more of ICU admission plasma creatinine). However, the number of patients requiring RRT was unaltered, and recovery to premorbid kidney function was not investigated.It was preplanned to study the detailed impact of early versus late PN on the incidence and recovery of AKI and the time course of blood/urine markers of renal function during ICU stay.¹⁶ A priori, we hypothesized that early PN would attenuate kidney injury. However, the original study findings suggested that AKI incidence and renal recovery could be aggravated by increased macronutrient provision in the acute phase of critical illness.     

Accessory extensor pollicis longus

Phylogenetically the accessory extensor pollicis longus in man seems to find its origin in the deep extensor layer, and this has largely been described in primates. I describe a case and present a comprehensive review of other publications on the subject.