A polymorphism at IGF1 locus is associated with anemia

In vitro and in vivo studies suggest that IGF-1 has a role in erythropoiesis. There is evidence that the rs35767 C/T polymorphism near IGF1 is associated with plasma IGF-1 levels. We investigated the effect of this polymorphism on hemoglobin (Hb) concentration and anemia. The study group comprised 3286 adult Whites. The rs35767 polymorphism was screened using a TaqMan allelic discrimination assay. The rs35767 polymorphism was not associated with age, gender, BMI, waist circumference, smoking, blood pressure, plasma glucose, HbA1c, type 2 diabetes, HOMA-IR, hsCRP, eGFR, and lipid profile. Erythrocyte sedimentation rate (ESR), fibrinogen, and fasting insulin levels were significantly lower in TT genotype carriers compared with C allele carriers. Hb concentration was significantly higher in carriers of the TT genotype compared with C allele carriers, and a lower proportion of TT carriers had anemia. As compared with TT genotype carriers, those bearing the CC genotype had a 2.4-fold higher risk of anemia (OR 2.40, 95%CI 1.19-4.82), and those with the CT genotype had a 2.0-fold higher risk of anemia (OR 2.06, 95%CI 1.04-4.11). The association remained significant when fasting insulin, eGFR, smoking, diabetes, ACE inhibitors, sartans or diuretics treatments, use of metformin and pioglitazone were added to the model, but its independence was not retained after inclusion of fibrinogen and ESR values into the model. In conclusion, rs35767 TT allele carriers exhibited significantly higher concentrations of Hb, and lower risk of anemia compared with C allele carriers supporting the idea that IGF-1 plays a role in erythropoiesis homeostasis

Elevated hemoglobin glycation index identify non-diabetic individuals at increased risk of kidney dysfunction

Hemoglobin glycation index (HGI), calculated as the difference between the observed value of HbA1 and the predicted HbA1c based on plasma glucose concentration, is a measure of the individual tendency toward non-enzymatic hemoglobin glycation which has been found to be positively associated with nephropathy in subjects with diabetes. In this cross-sectional study we aimed to evaluate whether higher HGI levels are associated with impaired kidney function also among nondiabetic individuals. The study group comprised 1505 White nondiabetic individuals stratified in quartiles according to HGI levels. Estimated glomerular filtration rate (eGFR) was calculated by using the MDRD equation. Individuals in the intermediate and high HGI groups exhibited a worse metabolic phenotype with increased levels of visceral obesity, total cholesterol, triglycerides, inflammatory biomarkers such as hsCRP and white blood cells count and lower values of HDL and insulin sensitivity assessed by Matsuda index in comparison to the lowest quartile of HGI. Subjects in the intermediate and high HGI groups displayed a graded decrease of eGFR levels in comparison with the lowest quartile of HGI. In a logistic regression analysis individuals in the highest quartile of HGI exhibited a significantly 3.6-fold increased risk of having chronic kidney disease (95% CI: 1.13-11.24, P = 0.03) and a significantly 1.6-fold increased risk of having a mildly reduced kidney function (95% CI: 1.19-2.28, P = 0.003) in comparison to individuals in the lowest HGI group. In conclusion HGI may be a useful tool to identify nondiabetic individuals with an increased risk of having kidney dysfunction

Sample size calculations for randomized controlled trials and for prediction models

The two study protocols are published in this issue Colorectal Disease: FALCON, a multicentre randomised controlled trial of strategies to reduce surgical site infection, and AFAR, a predictive model of atrial fibrillation after colonic resection. Both are exemplars of excellent research design that surgeon researchers should seek to emulate. Trial statisticians were involved at an early stage and the protocols have been through several rounds of peer review by trial methodologists, prior to being funded by the National Institute for Health Research (NIHR). In this article we address the important question of sample size calculations and how they should be approached for these very different forms of study

Is survival really better after repeated lung metastasectomy?

Several groups have observed that average survival time after a second lung metastasectomy is longer than after a first metastasectomy. The randomised controlled trial Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) found no survival benefit from lung metastasectomy. In fact, median survival was longer, and four-year overall survival was higher, in the control group than in those randomly assigned to metastasectomy, although not significantly so. The illusion of benefit is because survival without metastasectomy has been assumed to be near zero, as stated in Society of Thoracic Surgeons’ Expert Consensus Document on Pulmonary Metastasectomy 2019. It has been repeatedly found that survival is influenced by the selection of patients who have characteristics associated with better prognosis. The passage of time while monitoring and assessing patients, and observing their rate of progression, provides for immortal time bias. Reselection of the most favourable patients for repeated metastasectomy is the likely reason for any differences in survival between first and repeated metastasectomy operations

Association between noninvasive fibrosis markers and cardio-vascular organ damage among adults with hepatic steatosis

Evidence suggests that advanced fibrosis, as determined by the noninvasive NAFLD fibrosis score (NFS), is a predictor of cardiovascular mortality in individuals with ultrasonography-diagnosed NAFLD. Whether the severity of histology (i.e., fibrosis stage) is associated with more pronounced cardiovascular organ damage is unsettled. In this study, we analyzed the clinical utility of NFS in assessing increased carotid intima-media thickness (cIMT), and left ventricular mass index (LVMI). In this cross-sectional study NFS, cIMT and LVMI were assessed in 400 individuals with ultrasonography-diagnosed steatosis. As compared with individuals at low probability of liver fibrosis, individuals both at high and at intermediate probability of fibrosis showed an unfavorable cardio-metabolic risk profile having significantly higher values of waist circumference, insulin resistance, high sensitivity C-reactive protein (hsCRP), fibrinogen, cIMT, and LVMI, and lower insulin-like growth factor-1 (IGF-1) levels. The differences in cIMT and LVMI remained significant after adjustment for smoking and metabolic syndrome. In a logistic regression model adjusted for age, gender, smoking, and diagnosis of metabolic syndrome, individuals at high probability of fibrosis had a 3.9-fold increased risk of vascular atherosclerosis, defined as cIMT.0.9 mm, (OR 3.95, 95% CI 1.12–13.87) as compared with individuals at low probability of fibrosis. Individuals at high probability of fibrosis had a 3.5-fold increased risk of left ventricular hypertrophy (LVH) (OR 3.55, 95% CI 1.22–10.34) as compared with individuals at low probability of fibrosis. In conclusion, advanced fibrosis, determined by noninvasive fibrosis markers, is associated with cardiovascular organ damage independent of other known factors

Blue Straggler masses from pulsation properties. I. The case of NGC6541

We used high-spatial resolution images acquired with the WFC3 on board HST to probe the population of variable blue straggler stars in the central region of the poorly studied Galactic globular cluster NGC 6541. The time sampling of the acquired multi wavelength (F390W, F555W and F814W) data allowed us to discover three WUma stars and nine SX Phoenicis. Periods, mean magnitudes and pulsation modes have been derived for the nine SX Phoenicis and their masses have been estimated by using pulsation equations obtained from linear non adiabatic models. We found masses in the range 1.0-1.1Mo, with an average value of 1.06+-0.09 Mo (sigma = 0.04), significantly in excess of the cluster Main Sequence Turn Off mass (~ 0.75Mo). A mild trend between mass and luminosity seems also to be present. The computed pulsation masses turn out to be in very good agreement with the predictions of evolutionary tracks for single stars, indicating values in the range ~ 1.0-1.2 Mo for most of the BSS population, in agreement with what discussed in a number of previous studies.Comment: 8 pages, 9 figures, ApJ, accepte

Constraining the true nature of an exotic binary in the core of NGC 6624

We report on the identification of the optical counterpart to Star1, the exotic object serendipitously discovered by Deutsch et al. in the core of the Galactic globular cluster NGC 6624. Star1 has been classified by Deutsch et al. as either a quiescent Cataclysmic Variable or a low-mass X-ray binary. Deutsch et al. proposed StarA as possible optical counterpart to this object. We used high-resolution images obtained with the Hubble Space Telescope to perform a variability analysis of the stars close to the nominal position of Star1. While no variability was detected for StarA, we found another star, here named COM_Star1, showing a clear sinusoidal light modulation with amplitude \Delta m_F435W~0.7 mag and orbital period of P_orb~98 min. The shape of the light curve is likely caused by strong irradiation by the primary heating one hemisphere of the companion, thus suggesting a quite hot primary.Comment: Accepted for publication by ApJ Letters; 6 pages, 5 figure

A narrative review of individualized treatments of genitourinary tumors: Is the future brighter with molecular evaluations?

Few molecular prognostic and predictive biomarkers have been identified so far in genitourinary tumors. We started from a literature search to explore the status of the art of molecular pathology tests as diagnostic, prognostic, predictive biomarkers in genitourinary cancers. Next generation sequencing approaches now provide mind-changing information in the fields of kidney cancer diagnosis, predictive oncology of urothelial cancer, understanding the causes of testicular and penile cancer, and the comprehension of the drivers of prostate cancer progression beyond androgen regulation. The classification of kidney cancer will be based soon on molecular changes. The causes of non-HPV related penile cancer are largely unknown. The emerging high incidence of testicular cancer could be explained only on the basis of molecular changes. The response to novel therapeutic agents in prostatic and urothelial cancer will require thorough molecular tumor characterization. The hereditary risk of patients with early onset prostate cancer and their potential treatment with targeted therapy requires germline and somatic genetic assays. The implementation of effective biomarkers for the response to immune check-point inhibitors in genitourinary cancer is based on the assessment of inflammatory expression profiles and the tumor mutational burden. This review deals with the current tests and provides a tentative foresee of the future molecular biomarkers of genitourinary cancer

Serum IgG2 levels are specifically associated with whole-body insulin-mediated glucose disposal in non-diabetic offspring of type 2 diabetic individuals. a cross-sectional study

.Preclinical studies suggested that IgG2c isotype may specifically impair skeletal muscle insulin sensitivity in mice. In this study we investigated the association between serum levels of the four IgG subclasses and insulin sensitivity in non-diabetic individuals. Total IgG, IgG1, IgG2, IgG3 and IgG4 levels were measured in 262 subjects. Whole-body insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp. IgG2 levels were positively correlated with BMI, waist circumference, 2-h postload glucose levels and complement C3. Serum IgG2, but not IgG1, IgG3 and IgG4 levels were negatively correlated with whole-body insulin sensitivity (r = −0.17; P = 0.003) and muscle insulin sensitivity index (r = −0.16; P = 0.03) after adjustment for age and gender. No significant correlation was found between IgG2 levels and hepatic insulin resistance assessed by HOMA-IR and liver IR index. In a multivariable regression analysis including variables known to affect insulin sensitivity such as age, gender, BMI, smoking, lipids, inflammatory markers, fasting and 2-h post-load glucose levels, IgG2 levels were independently associated with insulin-stimulated glucose disposal (β = −0.115, 95% CI: −0.541 to −0.024; P = 0.03). These data demonstrate the independent association between higher levels of IgG2 and decreased whole-body insulin sensitivity, thus confirming in humans the animal-based evidence indicating the pathogenic role of IgG2 in insulin resistance

The increasing temperature as driving force for spatial distribution patterns of Parapenaeus longirostris (Lucas 1846) in the Strait of Sicily (Central Mediterranean Sea)

The deep-water rose shrimp Parapenaeus longirostris (DPS), a demersal decapod representing the most important component of crustacean landings in the Mediterranean Sea, has been suggested as a species that may exhibit temperature-driven changes in the spatio-temporal dynamics. Considering that Mediterranean waters are warming up faster than oceans, understanding the relationships of DPS populations with temperature variations and the related changes in spatial patterns is absolutely key for its management. Using a long-term dataset covering 13-years from scientific surveys (International Bottom Trawl-Surveys in the Mediterranean, MEDITS; Italian national trawl surveys, GRUND) in the Strait of Sicily (central Mediterranean Sea), the annual DPS spatial patches and the depth distribution were investigated using geostatistical and quotient analyses. The patches dimension and depth range occupation were then related to sea temperature by using linear regression analysis. Results showed that both the dimension of DPS spatial patches and the depth distribution range occupied increased concurrently with temperature. Our findings corroborate that the ongoing sea warming widen areas suitable for this species and in which it can expand its spatial distribution