Determinants of circulating calcitriol in cardiovascular disease.

Circulating calcitriol may contribute to the risk of cardiovascular disease (CVD), but its regulation in patients with CVD is poorly characterized. We therefore aimed to assess determinants of circulating calcitriol in these patients. We analyzed 2183 independent samples from a large cohort of patients scheduled for coronary angiography and 1727 independent samples from different other cohorts from patients with a wide range of CVDs, including heart transplant candidates, to quantify the association of different parameters with circulating calcitriol. We performed univariable and multivariable linear regression analyses using the mathematical function that fitted best with circulating calcitriol. In the multivariable analysis of the large single cohort, nine parameters remained significant, explaining 30.0 % (32.4 % after exclusion of 22 potential outliers) of the variation in circulating calcitriol (r=0.548). Log-transformed 25-hydroxyvitamin D [25(OH)D] and log-transformed glomerular filtration rate were the strongest predictors, explaining 17.6 % and 6.6 %, respectively, of the variation in calcitriol. In the analysis of the combined other cohorts, including heart transplant candidates, the multivariable model explained a total of 42.6 % (46.1 % after exclusion of 21 potential outliers) of the variation in calcitriol (r=0.653) with log-transformed fibroblast growth factor-23 and log-transformed 25(OH)D explaining 29.0 % and 6.2 %, respectively. Circulating 25(OH)D was positively and FGF-23 inversely associated with circulating calcitriol. Although significant, PTH was only a weak predictor of calcitriol in both analyses (<2.5 %). In patients with CVD, FGF-23 and 25(OH)D are important independent determinants of circulating calcitriol. The relative importance of these two parameters may vary according to CVD severity. Future studies should focus on the clinical importance of regulating circulating calcitriol by different parameters.

Effect of frugivory on the germination of cumbaru (Dipteryx alata) seeds ingested by tapirs (Tapirus terrestris) in the area of Cerrado, Brazil.

Endozoochory refers to the ingestion of fruits by animals and their release through faeces as it plays an important role in maintaining ecosystems. This study aimed to evaluate the effect of cumbaru fruit ingestion by tapirs on cumbaru seed germination. In latrines, fruits ingested and excreted by the animals were collected among tapir faeces. The collected material was taken to the laboratory and placed in a germination chamber and greenhouse. Fruit ingestion and its subsequent defection propitiated a higher germination rate and germination vigor compared to non-ingested fruit grown in a germination chamber and greenhouse. The results in the greenhouse showed that the latrines (decomposing organic matter) have different thermal conditions (higher temperature), in relation to the external environment, which probably accelerated the germination processes. Evaluation of seedlings grown in a greenhouse and germination chamber indicated that growth in the greenhouse was better due to humic and fulvic acids, which are common stimulants of seed germination and seedling growth. Therefore, tapirs can be considered good fruit dispersers and inducers of cumbaru seeds germination.

Liogenys Guerin-Méneville, 1831 (Coleoptera: Scarabaeidae: Melolonthinae: Diplotaxini) of northern South America and Central America: taxonomic overview with four new species.

The biodiversity of northern South American and Central American Liogenys Guérin-Méneville, 1831 (Coleoptera: Scarabaeidae: Melolonthinae: Diplotaxini) is reviewed. Four new species are described: L. clipeosetosa Cherman, new species; L. genieri Smith Cherman, new species; L. granadina Cherman, new species; and L. schneiderae Cherman, new species. The male of L. quadridens (Fabricius, 1798) and the female of L. quadridentata Blanchard, 1851 are described for the first time. Liogenys gebieni Moser, 1921 is a new junior subjective synonym of L. macropelma Bates, 1887. The northernmost record of Liogenys is emended to Trinidad and Tobago for L. granadina Cherman, new species and L. schneiderae new species. Diplotaxis puberea cuprascens (Bates, 1887) new combination, Diplotaxis puberea puberea (Bates, 1887) new combination, and Diplotaxis pubisternis (Bates, 1887) new combination are all transferred from Liogenys to Diplotaxis Kirby, 1837. Lectotypes are designated for Liogenys gebieni Moser, 1921; Melolontha quadridens Fabricius, 1798; and Liogenys quadridentatus Blanchard, 1851. An identification key to northern South American Liogenys is presented.

Liogenys Guérin-Méneville, 1831 (Coleoptera: Scarabaeidae: Melolonthinae) from the southern South American Transition Zone and boundaries: taxonomic overview with four new species.

The biodiversity of Liogenys Guérin-Méneville, 1831 (Coleoptera: Scarabaeidae: Melolonthinae: Diplotaxini) from the southern South American Transition Zone and boundaries is presented. Four new species are described: L. brachyclypeata Cherman, new species; L. lucialmeidae Cherman, new species; L. martinezi Cherman, new species; and L. maxillaricuspis Cherman, new species. The synonymy of L. flaveola Moser, 1924 (= L. kadleci Frey, 1970) is proposed. Lectotypes are designated for L. flavida Moser, 1918; L. pallidicornis Blanchard, 1851 (currently L. xanthocera Harold, 1869); and L. rufoflava Moser, 1918. Redescriptions are provided for all the species mentioned above plus L. calcarata Frey, 1970 and L. kunzteni Moser, 1921, as well as an identification key and updated geographical distributions to all species in the region. All species are present in the Monte province, except of L. kuntzeni (Andean provinces of Chile). Liogenys flavida and L. rufoflava have the broadest distribution, the latter here expanded to Paraguay and Chile.

Cercyon Leach, 1817 (Coleoptera: Hydrophilidae: Sphaeridiinae) from Brazil: new species and records

Abstract The study of ca. 280 specimens of Cercyon Leach, 1817 (Hydrophilidae: Sphaeridiinae: Megasternini) deposited in the Coleção Entomológica Pe. J.S. Moure, Universidade Federal do Paraná, Brazil, revealed a new species from Atlantic Rain Forest biome in Paraná State (Southern Brazil) and new records. Cercyon (Cercyon) curi sp. nov. is herein described and illustrated, belonging to the Neotropical C. variegatus species group. Cercyon (Cercyon) nigriceps (Marsham, 1802) is recorded for the first time in Paraná State, and Cercyon (Cercyon) inquinatus Wollaston, 1854 from Amazonas State (Northern Region); these records extend the distributional range of both species in Brazil. Cercyon (Cercyon) praetextatus (Say, 1825) is recorded for the first time from Brazil based on specimens collected in Paraná. Those three species were previously recorded as introduced in South America.

Synthesis and Characterizations of a Collagen-Rich Biomembrane with Potential for Tissue-Guided Regeneration.

OBJECTIVES: In this study, a collagen-rich biomembrane obtained from porcine -intestinal submucosa for application in guided bone regeneration was developed and characterized. Then, its biological and mechanical properties were compared with that of commercial products (GenDerm [Baumer], Lumina-Coat [Critéria], Surgitime PTFE [Bionnovation], and Surgidry Dental F [Technodry]). MATERIALS AND METHODS: The biomembrane was extracted from porcine intestinal submucosa. Scanning electron microscopy, spectroscopic dispersive energy, glycosaminoglycan quantification, and confocal microscopy by intrinsic fluorescence were used to evaluate the collagen structural patterns of the biomembrane. Mechanical tensile and deformation tests were also performed. STATISTICAL ANALYSIS: The results of the methods used for experimental membrane characterizations were compared with that obtained by the commercial membranes and statistically analyzed (significance of 5%). RESULTS: The collagen-rich biomembrane developed also exhibited a more organized, less porous collagen fibril network, with the presence of glycosaminoglycans. The experimental biomembrane exhibited mechanical properties, tensile strength, and deformation behavior with improved average stress/strain when compared with other commercial membranes tested. Benefits also include a structured, flexible, and -bioresorbable characteristics scaffold. CONCLUSIONS: The experimental collagen-rich membrane developed presents physical-chemical, molecular, and mechanical characteristics similar to or better than that of the commercial products tested, possibly allowing it to actively participating in the process of bone neoformation.

Structural study of the cremaster muscle in patients with retractile testis.

OBJECTIVE: To analyze the structure of the cremaster in patients with retractile testis (RT), comparing the distribution of nerves, elastic system and muscles with patients having cryptorchidism and inguinal hernia (IH). PATIENTS AND METHODS: We studied 31 patients, 17 with RT (mean age=5.17years); 9 with IH (mean age=2.6) and 5 with cryptorchidism (mean age=3). A cremaster biopsy was performed and submitted to routine histological processing and studied using histochemistry and immunohistochemistry. The samples were photographed under an Olympus BX51 microscope. The images were processed with the Image J software and the cremaster muscle structures were quantified. Means were compared statistically using ANOVA and the unpaired t-test (p<0.05). RESULTS: There were no differences (p=0.08) in diameter of muscle fiber between the groups. The muscle fiber density differed between patients with RT and IH (p=0.02): RT (mean=17.71%, SD=16.67), IH (mean=38.06%, SD=14) and cryptorchidism (mean=21.47%, SD=16.18). There was no difference (p=0.07) in the density of elastic fibers in the three groups. We observed a lower concentration of cremaster nerves of patients with RT compared with IH (p=0.0362): RT (mean=1.72%, SD=0.58), IH (mean=3.28% SD=0.94) and cryptorchidism (mean=2.52%, SD=0.53). CONCLUSIONS: Retractile testis is not a normal variant, and presented a similar cremaster muscle structure as in patients with cryptorchidism. LEVEL OF EVIDENCE: II; prospective comparative study.

[Congenital disorders of lipoprotein metabolism]. / Angeborene Störungen im Lipoproteinstoffwechsel.

Congenital disorders of lipid metabolism are caused by a wide range of variants of the genes for receptors, apolipoproteins, enzymes, transfer factors, and cellular cholesterol transporters. Clinically most relevant are autosomal dominant familial hypercholesterolemia (FH) and familial combined hyperlipoproteinemia (FCHL). FH has a prevalence of 1:250. It is due to mutations of the low density lipoprotein (LDL) receptor, less often to mutations of the apolipoprotein B (APOB), the proprotein convertase subtilisin/kexin type 9 (PCSK9), or the signal transducing adapter family member 1 (STAP1). FH often leads to early atherosclerosis. Its diagnosis can definitely be made only by molecular genetic testing. The detection of mutations of the LDLR, APOB, or PCSK9 is an indicator for extremely high cardiovascular risk, independently of the concentration of LDL cholesterol. FCHL is also common (1:100) and is seen in about 10% of patients with early myocardial infarction. It is produced by combinations of frequent genetic variants affecting triglycerides and LDL cholesterol. Other monogenic hyperlipoproteinemias (HLP) affect the catabolism of chylomicrons (familial chylomicronemia) or of remnants of triglyceride-rich lipoproteins (type III hyperlipoproteinemia). Multiple hereditary disorders in HDL metabolism - with a broad spectrum of clinical significance - are known. Currently, second generation sequencing methods are used to simultaneously analyze multiple disease-causing genes. This approach cost-neutrally provides additional information such as the genetic risk of atherosclerosis and predisposition to statin intolerance.

Independent associations of vitamin D metabolites with anemia in patients referred to coronary angiography: the LURIC study.

PURPOSE: Anemia and vitamin D deficiency are both frequent in adult patients. Whether low vitamin D metabolite levels are an independent risk factor for different subtypes of anemia remains to be studied in detail. METHODS: In 3299 patients referred for coronary angiography, we investigated the association of 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D [1,25(OH)2D] with anemia [hemoglobin (Hb) <12.5 g/dl] of specific subtypes. RESULTS: Compared with patients with 25OHD levels in the adequate range (50-125 nmol/l), patients with deficient 25OHD concentrations (<30 nmol/l; 33.6 % of patients) had 0.6 g/dl lower Hb levels. Hb values were 1.3 g/dl lower in patients with 1,25(OH)2D levels <40 pmol/l (5.4 % of patients), compared with patients in the highest 1,25(OH)2D category (>70 pmol/l). Of the participants, 16.7 % met the criteria for anemia. In multivariate-adjusted regression analyses, the odds ratios for anemia in the lowest 25OHD and 1,25(OH)2D categories were 1.52 (95 % CI 1.15-2.02) and 3.59 (95 % CI 2.33-5.52), compared with patients with 25OHD levels in the adequate range and patients with 1,25(OH)2D levels >70 pmol/l. The probability of anemia was highest in patients with combined 25OHD and 1,25(OH)2D deficiency [multivariable-adjusted odds ratio 5.11 (95 % CI 2.66-9.81)]. Patients with anemia of chronic kidney disease had the highest prevalence of 25OHD deficiency and 1,25(OH)2D concentrations of <40 pmol/l. CONCLUSIONS: Low 25OHD and 1,25(OH)2D concentrations are independently associated with anemia. Patients with poor kidney function are most affected. Interventional trials are warranted to prove whether administration of plain or activated vitamin D can prevent anemia.

[Clinical importance of HDL cholesterol]. / Klinische Bedeutung des HDL-Cholesterins.

BACKROUND: Each year 16-17 million determinations of high-density lipoprotein cholesterol (HDL-C) are conducted and interpreted in Germany. Recently acquired data have led to a fundamental reassessment of the clinical significance of HDL-C. METHOD: This review article is based on a selective literature search. RESULTS: Low HDL­C levels usually indicate an increased cardiovascular risk, particularly in primary prevention but the epidemiological relationship between HDL­C and the risk is complex. The HDL plays a role in the back transport and excretion of cholesterol; however, the biological functions of HDL are dependent on the protein and lipid composition, which is not reflected by the HDL­C concentration. If the composition of HDL is pathologically altered it can also exert negative vascular effects. CONCLUSION: Compared with low-density lipoprotein cholesterol (LDL-C), HDL­C is of secondary importance for cardiovascular risk stratification and the calculation of the LDL-C:HDL­C ratio is not useful for all patients. Low HDL­C levels should prompt a search for additional metabolic and inflammatory pathologies. An increase in HDL­C through lifestyle changes (e.g. smoking cessation and physical exercise) has positive effects and is recommended; however, HDL­C is currently not a valid target for drug therapy.

Do retractile testes have anatomical anomalies?

OBJECTIVES: To assess the incidence of anatomical anomalies in patients with retractile testis. MATERIALS AND METHODS: We studied prospectively 20 patients (28 testes) with truly retractile testis and compared them with 25 human fetuses (50 testes) with testis in scrotal position. We analyzed the relations among the testis, epididymis and patency of the processus vaginalis (PV). To analyze the relations between the testis and epididymis, we used a previous classification according to epididymis attachment to the testis and the presence of epididymis atresia. To analyze the structure of the PV, we considered two situations: obliteration of the PV and patency of the PV. We used the Chi-square test for contingency analysis of the populations under study (p<0.05). RESULTS: The fetuses ranged in age from 26 to 35 weeks post-conception (WPC) and the 20 patients with retractile testis ranged in ages from 1 to 12 years (average of 5.8). Of the 50 fetal testes, we observed complete patency of the PV in 2 cases (4%) and epididymal anomalies (EAs) in 1 testis (2%). Of the 28 retractile testes, we observed patency of the PV in 6 cases (21.4%) and EA in 4 (14.28%). When we compared the incidence of EAs and PV patency we observed a significantly higher prevalence of these anomalies in retractile testes (p=0.0116). CONCLUSIONS: Retractile testis is not a normal variant with a significant risk of patent processos vaginalis and epididymal anomalies.

Do retractile testes have anatomical anomalies?

ABSTRACT Objectives: To assess the incidence of anatomical anomalies in patients with retractile testis. Materials and Methods: We studied prospectively 20 patients (28 testes) with truly retractile testis and compared them with 25 human fetuses (50 testes) with testis in scrotal position. We analyzed the relations among the testis, epididymis and patency of the processus vaginalis (PV). To analyze the relations between the testis and epididymis, we used a previous classification according to epididymis attachment to the testis and the presence of epididymis atresia. To analyze the structure of the PV, we considered two situations: obliteration of the PV and patency of the PV. We used the Chi-square test for contingency analysis of the populations under study (p <0.05). Results: The fetuses ranged in age from 26 to 35 weeks post-conception (WPC) and the 20 patients with retractile testis ranged in ages from 1 to 12 years (average of 5.8). Of the 50 fetal testes, we observed complete patency of the PV in 2 cases (4%) and epididymal anomalies (EAs) in 1 testis (2%). Of the 28 retractile testes, we observed patency of the PV in 6 cases (21.4%) and EA in 4 (14.28%). When we compared the incidence of EAs and PV patency we observed a significantly higher prevalence of these anomalies in retractile testes (p=0.0116). Conclusions: Retractile testis is not a normal variant with a significant risk of patent processus vaginalis and epididymal anomalies.

Saturated fatty acids are not off the hook.

A recent meta-analysis by Chowdhury et al. (2014) has disclaimed the association between coronary artery diseases and either circulating blood levels or the intake of total saturated fatty acids (SFA). Scrutiny revealed that two of the eight studies included in the meta-analysis focused on the proportion of pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0) and their impact on cardiovascular disease (CVD) risk. These odd-chain fatty acids are markers for milk or ruminant fat intake. Both studies indicated inverse associations between milk-fat intake and first-ever myocardial infarction. Neither of the two studies described the association between total circulating blood SFA on coronary outcomes. In contrast to the cardioprotective effects of dairy consumption, we expected that an elevated intake of palmitic acid (C16:0) and stearic acid (C18:0) de novo may raise CVD risk. Thus, it is of particular importance to differentiate the effects of individual circulating SFA on cardiovascular outcomes. Excluding the studies that evaluated the association of fatty acids from milk fat and cardiovascular outcomes revealed a positive association of total SFA blood levels and coronary outcome (RR 1.21, CI 1.04-1.40). Therefore, results obtained from studies of C15:0 and C17:0 cannot be mixed with results from studies of other SFA because of the opposite physiological effects of regular consumption of foods rich in C16:0 and C18:0 compared to high intake of milk or ruminant fat. In our opinion, it is vital to analyze the impact of individual SFA on CVD incidence in order to draw prudent conclusions.

Severe forms of concealed penis without hypospadias: Surgical strategies.

INTRODUCTION: Concealed penis (CP) may vary in severity and includes megaprepuce (MP) as a variant. Many different surgical strategies have been described in order to maximize penile exposure and to deal with skin deficiency. We describe the strategies that we use to overcome technical problems in severe cases of CP. MATERIALS AND METHODS: Six consecutive cases of severe CP (including 3 with MP) were treated in a 2-year period between January 2011 and April 2013. These patients were treated using extensive degloving, removal of dysplastic dartos, Alexander's preputial flap, scrotal flaps and skin grafts. Three patients had been previously circumcised. Cases associated with hypospadias, obesity, disorders of sexual differentiation and micropenises were excluded. RESULTS: All six patients attained good results, with good exposure of the penis, ability to void standing with a well-directed flow and reasonable esthetic results. A technical algorithm for the treatment of primary or recurring cases of CP is proposed. CONCLUSION: Alexander' s distally based ventral preputial flap is a useful technical resource to treat MP cases. Free skin grafts and/or laterally based scrotal flaps may be used to cover the penis after release in severe cases of CP.

Forensic use of a subtropical blowfly: the first case indicating minimum postmortem interval (mPMI) in southern Brazil and first record of Sarconesia chlorogaster from a human corpse.

Southern Brazil is unique due to its subtropical climate. Here, we report on the first forensic entomology case and the first record of Sarconesia chlorogaster (Wiedemann) in a human corpse in this region. Flies' samples were collected from a body indoors at 20°C. Four species were found, but only Chrysomya albiceps (Wiedemann) and S. chlorogaster were used to estimate the minimum postmortem interval (mPMI). The mPMI was calculated using accumulated degree hour (ADH) and developmental time. The S. chlorogaster puparium collected was light in color, so we used an experiment to establish a more accurate estimate for time since initiation of pupation where we found full tanning after 3 h. Development of C. albiceps at 20°C to the end of the third instar is 7.4 days. The mPMI based on S. chlorogaster (developmental time until the third instar with no more than 3 h of pupae development) was 7.6 days.

Alterations in the coagulation system of active smokers from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study.

Smoking is an important and preventable risk factor of cardiovascular diseases with effects on blood coagulation. Our aim was to analyze the influence of smoking on coagulation parameters. Concentrations or activities of blood coagulation factors were compared in 777 active smokers and 1,178 lifetime non-smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. The association with mortality was examined using Cox regression. The findings show that AS had a tendency toward thrombosis. They displayed significantly higher values for fibrinogen, soluble fibrinogen, factor XIII, and tissue factor pathway inhibitor; whereas FVII, FVIII, FXII, von Willebrand factor (vWF), and thrombomodulin were decreased. The Cox regression analysis showed fibrinogen, FVIII, vWF, thrombomodulin, and tissue factor pathway inhibitor to be independent risk factors for mortality in active smokers with hazard ratios of 1.16 (95% CI: 1.02-1.31), 1.40 (1.22-1.59), 1.37 (1.22-1.56), 1.19 (1.07-1.31), and 1.22 (1.06-1.40) per increase of one standard deviation. We conclude that active smokers have an increased thrombogenic potential associated with significant changes in the coagulation system. Individual parameters of the coagulation system are independent predictors of mortality. Therefore, parameters of the coagulation system, apart from other risk factors for cardiovascular disease (e.g., lipids or life-style) should be determined for risk prediction in active smokers.

C-reactive protein and lipoprotein-associated phospholipase A2 in smokers and nonsmokers of the Ludwigshafen Risk and Cardiovascular Health study.

Measurement of high sensitivity CRP (hsCRP) and lipoprotein-associated phospholipase A2 (LpPLA2) provides information on systemic inflammation and stability of atherosclerotic plaques. Data analyzing the effect of smoking on these parameters are sparse. The aim of our study was the analysis of these parameters in active smokers and never-smokers. The study included 777 smokers and 1,178 never-smokers, of whom 221 and 302 died during a follow-up, respectively. The values of LpPLA2 and hsCRP were significantly higher in smokers than in never-smokers. Mortality was highest in smokers and never-smokers with elevation of both biomarkers. Multivariate adjusted hazard ratios for patients in the highest tertile of both hsCRP and LpPLA2 compared with patients in the lowest tertile of both markers were 1.85 (1.04-3.28) in never-smokers and 1.94 (1.10-3.45) in smokers. Our data confirmed the predictive value of hsCRP and LpPLA2. However, there were a relevant number of patients with an increase of only one of these parameters. Therefore, beside other risk factors for cardiovascular disease, both parameters should be determined at least in high risk patients.

Evolving biomarkers improve prediction of long-term mortality in patients with stable coronary artery disease: the BIO-VILCAD score.

OBJECTIVE: Algorithms to predict the future long-term risk of patients with stable coronary artery disease (CAD) are rare. The VIenna and Ludwigshafen CAD (VILCAD) risk score was one of the first scores specifically tailored for this clinically important patient population. The aim of this study was to refine risk prediction in stable CAD creating a new prediction model encompassing various pathophysiological pathways. Therefore, we assessed the predictive power of 135 novel biomarkers for long-term mortality in patients with stable CAD. DESIGN, SETTING AND SUBJECTS: We included 1275 patients with stable CAD from the LUdwigshafen RIsk and Cardiovascular health study with a median follow-up of 9.8 years to investigate whether the predictive power of the VILCAD score could be improved by the addition of novel biomarkers. Additional biomarkers were selected in a bootstrapping procedure based on Cox regression to determine the most informative predictors of mortality. RESULTS: The final multivariable model encompassed nine clinical and biochemical markers: age, sex, left ventricular ejection fraction (LVEF), heart rate, N-terminal pro-brain natriuretic peptide, cystatin C, renin, 25OH-vitamin D3 and haemoglobin A1c. The extended VILCAD biomarker score achieved a significantly improved C-statistic (0.78 vs. 0.73; P = 0.035) and net reclassification index (14.9%; P < 0.001) compared to the original VILCAD score. Omitting LVEF, which might not be readily measureable in clinical practice, slightly reduced the accuracy of the new BIO-VILCAD score but still significantly improved risk classification (net reclassification improvement 12.5%; P < 0.001). CONCLUSION: The VILCAD biomarker score based on routine parameters complemented by novel biomarkers outperforms previous risk algorithms and allows more accurate classification of patients with stable CAD, enabling physicians to choose more personalized treatment regimens for their patients.

Penile hair tourniquet resulting in hypospadias failure.

Penile hair tourniquet (PHT) is a painless form of penile ischemia, typically seen in toddlers with long-haired mothers, caused by entanglement of hair on the balano-prepucial sulcus, normally associated with circumcision. Its association with hypospadias has been reported only once. A school-aged boy admitted for surgery to treat hypospadias failure was incidentally detected to have PHT and severe hourglass deformity of the penis. Urethral anastomosis and glanuloplasty were done after removal of the constricting ring, without complications. Normal erections were reported during follow up. Treatment may involve urethral reconstruction and penile reimplantation in extreme cases.

C-reactive protein predicts mortality in patients referred for coronary angiography and symptoms of heart failure with preserved ejection fraction.

AIMS: Heart failure with preserved ejection fraction (HFpEF) has a different pathophysiological background compared to heart failure with reduced ejection fraction (HFrEF). Tailored risk prediction in this separate heart failure group with a high mortality rate is of major importance. Inflammation may play an important role in the pathogenesis of HFpEF because of its significant contribution to myocardial fibrosis. We therefore aimed to assess the predictive value of C-reactive protein (CRP) in patients with HFpEF. METHODS AND RESULTS: Plasma levels of CRP were determined in 459 patients with HFpEF in the LUdwigshafen Risk and Cardiovascular Health (LURIC) study using a high-sensitivity assay. During a median follow-up of 9.7 years 40% of these patients died. CRP predicted all-cause mortality with an adjusted hazard ratio (HR) of 1.20 [95% confidence interval (CI) 1.02-1.40, P = 0.018] and cardiovascular mortality with a HR of 1.32 (95% CI 1.08-1.62, P = 0.005) per increase of one standard deviation. CRP was a significantly stronger mortality predictor in HFpEF patients than in a control group of 522 HFrEF patients (for interaction, P = 0.015). Furthermore, CRP added prognostic value to N-terminal pro B-type natriuretic peptide (Nt-proBNP): the lowest 5-year mortality rate of 6.8% was observed for patients in the lowest tertile of Nt-proBNP as well as CRP. The mortality risk peaked in the group combining the highest values of Nt-proBNP and CRP with a 5-year rate of 36.5%. CONCLUSION: It was found that CRP was an independent and strong predictor of mortality in HFpEF. This observation may reflect immunological processes with an adverse impact on the course of HFpEF.