Elevated third-trimester haemoglobin A 1c predicts preterm delivery in type 1 diabetes

The prevalence of preterm delivery is considerably elevated in women with type 1 diabetes. The aim of the study was to evaluate haemoglobin A(1c) (HbA(1c)) as a predictor of preterm delivery. Two hundred thirteen consecutive pregnant women with type 1 diabetes and normal urinary albumin excretion were included prospectively. HbA(1c) was analyzed at 10, 20 and 28 weeks of gestation. Seventy-one women (33%) delivered pre term and 142 at term. At 10 weeks of gestation, HbA(1c) was 7.3% (S.D. 1.0) vs. 6.9% (S.D. 0.9) (P<.01), at 20 weeks of gestation 6.6% (S.D. 0.7) vs. 6.1% (S.D. 0.7) (P<.001) and at 28 weeks of gestation 6.7% (S.D. 0.8) vs. 6.1% (S.D. 0.7) (P<.001). When comparing HbA(1c) at 10, 20 and 28 weeks of gestation, HbA(1c) at 28 weeks of gestation (P<.001) was the best predictor of preterm delivery. The adjusted odds ratio per 1% increment in HbA(1c) at 28 weeks of gestation was 2.8 (95% CI 1.7-4.4). HbA(1c) at 28 weeks of gestation was a clinical significant predictor of preterm delivery in type 1 diabetes.     

Colonization of Extended-Spectrum-β-Lactamase- and NDM-1-Producing Enterobacteriaceae among Pregnant Women in the Community in a Low-Income Country: a Potential Reservoir for Transmission of Multiresistant Enterobacteriaceae to Neonates

The spread of extended-spectrum-β-lactamase-producing Enterobacteriaceae (ESBL-PE) in low-income countries, where the burden of neonatal sepsis is high, may have a serious impact on neonatal mortality rates. Given the potential for mother-to-child transmission of multiresistant bacteria, this study investigated the ESBL-PE rectal colonization among pregnant women at delivery in the community in Madagascar and estimated a prevalence of 18.5% (95% confidence interval, 14.5% to 22.6%). One strain of Klebsiella pneumoniae isolated was also a New Delhi metallo-β-lactamase-1 (NDM-1) producer.     

Moderne Schilddrüsenchirurgie – das endokrin-chirurgische Verständnis des Operateurs und seine Verantwortung für Resektionsausmaß und Komplikationsrate

Wiener Medizinische Wochenschrift - Die hohe Qualität der Schilddrüsenchirurgie impliziert ein endokrin-chirurgisches Verständnis des Operateurs mit dem Ziel einer bestmöglichen...     

How to diagnose heart failure with preserved ejection fraction: the HFA–PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)

Making a firm diagnosis of chronic heart failure with preserved ejection fraction (HFpEF) remains a challenge. We recommend a new stepwise diagnostic process, the ‘HFA–PEFF diagnostic algorithm’. Step 1 (P=Pre‐test assessment) is typically performed in the ambulatory setting and includes assessment for heart failure symptoms and signs, typical clinical demographics (obesity, hypertension, diabetes mellitus, elderly, atrial fibrillation), and diagnostic laboratory tests, electrocardiogram, and echocardiography. In the absence of overt non‐cardiac causes of breathlessness, HFpEF can be suspected if there is a normal left ventricular (LV) ejection fraction, no significant heart valve disease or cardiac ischaemia, and at least one typical risk factor. Elevated natriuretic peptides support, but normal levels do not exclude a diagnosis of HFpEF. The second step (E: Echocardiography and Natriuretic Peptide Score) requires comprehensive echocardiography and is typically performed by a cardiologist. Measures include mitral annular early diastolic velocity (e′), LV filling pressure estimated using E/e′, left atrial volume index, LV mass index, LV relative wall thickness, tricuspid regurgitation velocity, LV global longitudinal systolic strain, and serum natriuretic peptide levels. Major (2 points) and Minor (1 point) criteria were defined from these measures. A score ≥5 points implies definite HFpEF; ≤1 point makes HFpEF unlikely. An intermediate score (2–4 points) implies diagnostic uncertainty, in which case Step 3 (F₁: Functional testing) is recommended with echocardiographic or invasive haemodynamic exercise stress tests. Step 4 (F₂: Final aetiology) is recommended to establish a possible specific cause of HFpEF or alternative explanations. Further research is needed for a better classification of HFpEF.     

Thrombospondin-1 Deficiency Causes a Shift from Fibroproliferative to Inflammatory Kidney Disease and Delays Onset of Renal Failure

Thrombospondin-1 (TSP1) is a multifunctional matricellular protein known to promote progression of chronic kidney disease. To gain insight into the underlying mechanisms through which TSP1 accelerates chronic kidney disease, we compared disease progression in Col4a3 knockout (KO) mice, which develop spontaneous kidney failure, with that of Col4a3;Tsp1 double-knockout (DKO) mice. Decline of excretory renal function was significantly delayed in the absence of TSP1. Although Col4a3;Tsp1 DKO mice did progress toward end-stage renal failure, their kidneys exhibited distinct histopathological lesions, compared with creatinine level–matched Col4a3 KO mice. Although kidneys of both Col4a3 KO and Col4a3;Tsp1 DKO mice exhibited a widened tubulointerstitium, predominant lesions in Col4a3 KO kidneys were collagen deposition and fibroblast accumulation, whereas in Col4a3;Tsp1 DKO kidney inflammation was predominant, with less collagen deposition. Altered disease progression correlated with impaired activation of transforming growth factor-β1 (TGF-β1) in vivo and in vitro in the absence of TSP1. In summary, our findings suggest that TSP1 contributes to progression of chronic kidney disease by catalyzing activation of latent TGF-β1, resulting in promotion of a fibroproliferative response over an inflammatory response. Furthermore, the findings suggest that fibroproliferative and inflammatory lesions are independent entities, both of which contribute to decline of renal function.Progression of chronic kidney disease (CKD) toward end-stage renal failure (ESRF) is a prominent problem in clinical nephrology.¹ The incidence of CKD is rising, but effective therapies to halt progression of disease remain elusive.² Progression of CKD results from a complex interplay of pathologies that involve all constituents of the kidney, which makes it difficult to single out targets for effective therapeutic strategies.³The extent of so-called tubulointerstitial fibrosis is often considered to be the rate-limiting step in progression of CKD.¹ This idea is founded on histopathological analysis of large cohorts of kidney biopsies, which demonstrated that only tubulointerstitial fibrosis (which at the time was determined as the relative volume of the interstitium within a kidney biopsy section) correlates with and also predicts progression of CKD toward ESRF, irrespective of the underlying primary disease.^{4, 5, 6, 7} Widening of the tubulointerstitium, which is referred to as tubulointerstitial fibrosis, is caused by a composite of extracellular matrix (ECM) accumulation, sterile inflammation, accumulation of activated fibroblasts, and rarefaction of microvessels.¹ Although the relevance of each of these events to progression of fibrosis and CKD is hotly debated, this knowledge led to the concept that tubulointerstitial fibrosis is a common pathway of all chronic progressive kidney diseases and that effective antifibrotic therapies could potentially halt progression of CKD irrespective of the underlying disease. However, such therapies are not yet available.¹Our aim was to gain insight into mechanisms that underlie the contribution of thrombospondin-1 (TSP1) to progression of CKD. TSP1 is the most-studied member of the thrombospondin family of matricellular proteins.⁸ Previous studies have demonstrated that pharmacological suppression or genetic depletion of TSP1 attenuates disease progression in animal models of CKD.^{9, 10, 11, 12, 13} TSP1 is a 450-kDa trimeric ECM protein, which does not fulfill primarily structural roles in the matrix, but instead functions as an extracellular modulator of cell function.^{8, 14} Most prominently, TSP1 is known to inhibit angiogenesis, inhibit inflammation, activate MMP-dependent ECM turnover, and facilitate fibroblast migration and activation, all of which are considered important contributors to progression of CKD.^{8, 10} To delineate through which of its known biological activities TSP1 impacts progression of CKD, we compared progression of kidney disease of Col4a3 knockout (KO) mice (deficient in type IV collagen α3 chain) with that of Col4a3;Tsp1 double-knockout (DKO) mutant mice.¹⁵Here, we demonstrate that decrease of excretory renal function is delayed if TSP1 is absent. Furthermore, tissue analysis of plasma creatinine level–matched kidneys of Col4a3 KO and of Col4a3;Tsp1 DKO revealed that in Col4a3 KO mice disease progression is predominantly associated with fibrosis, whereas inflammation is the predominant interstitial pathology in Col4a3;Tsp1 DKO mice. We provide evidence that this altered disease progression is due to impaired activation of latent transforming growth factor-β1 (TGF-β1) in the absence of TSP1. Our findings provide evidence that both fibroproliferative injury and inflammation can independently cause expansion of the interstitium, leading to decline of excretory renal function.