Severe adrenal insufficiency in six neonates with normal newborn screening for CAH.

BACKGROUND: Newborn screening (NBS) reduces the risk of mortality in congenital adrenal hyperplasia (CAH), mainly due to the salt-wasting form of 21-hydroxylase deficiency. There is limited knowledge regarding the results of NBS in non-CAH primary adrenal insufficiency (non-CAH PAI). PATIENTS AND METHODS: Clinical and NBS for CAH data of neonates who were diagnosed with non-CAH PAI between January and December 2022 were examined. RESULTS: Patients (n = 6, 4 females) were presented with severe hyperpigmentation (n = 6), hypoglycemia (n = 4), hyponatremia (n = 3), hyperkalemia (n = 1), respiratory distress syndrome (n = 1) between 3rd hour to 2 months of life. All had normal NBS results. The median first-tier 17-hydroxyprogesterone (17OHP) concentration in NBS for CAH was 0.14 ng/mL (range; 0.05-0.85). Molecular studies revealed biallelic mutations in the MC2R (n = 4; 3 homozygous, 1 compound heterozygous), MRAP (n = 1) and STAR (n = 1) genes. Glucocorticoid with or without mineralocorticoid replacement was initiated once the diagnosis of non-CAH PAI was established. CONCLUSION: Neonates with non-CAH PAI have always normal NBS due to persistently low 17OHP, even when these newborn infants are severely symptomatic for adrenal insufficiency. Clinicians should be alert for signs of adrenal insufficiency in neonates, even if the patient has a 'normal' screening for CAH, so as not to delay diagnosis and treatment. This fact should be kept in mind particularly in countries where these conditions are more common than elsewhere.

Natural history of Wolcott-Rallison syndrome: A systematic review and follow-up study.

BACKGROUND AND AIMS: To systematically review the literature for reports on Wolcott-Rallison syndrome, focusing on the spectrum and natural history, genotype-phenotype correlations, patient and native liver survival, and long-term outcomes. METHODS: PubMed, Livio, Google Scholar, Scopus and Web of Science databases were searched. Data on genotype, phenotype, therapy, cause of death and follow-up were extracted. Survival and correlation analyses were performed. RESULTS: Sixty-two studies with 159 patients met the inclusion criteria and additional 30 WRS individuals were collected by personal contact. The median age of presentation was 2.5 months (IQR 2) and of death was 36 months (IQR 50.75). The most frequent clinical feature was neonatal diabetes in all patients, followed by liver impairment in 73%, impaired growth in 72%, skeletal abnormalities in 59.8%, the nervous system in 37.6%, the kidney in 35.4%, insufficient haematopoiesis in 34.4%, hypothyroidism in 14.8% and exocrine pancreas insufficiency in 10.6%. Episodes of acute liver failure were frequently reported. Liver transplantation was performed in six, combined liver-pancreas in one and combined liver-pancreas-kidney transplantation in two individuals. Patient survival was significantly better in the transplant cohort (p = .0057). One-, five- and ten-year patient survival rates were 89.4%, 65.5% and 53.1%, respectively. Liver failure was reported as the leading cause of death in 17.9% of cases. Overall survival was better in individuals with missense mutations (p = .013). CONCLUSION: Wolcott-Rallison syndrome has variable clinical courses. Overall survival is better in individuals with missense mutations. Liver- or multi-organ transplantation is a feasible treatment option to improve survival.

Adult thymus contains FoxN1(-) epithelial stem cells that are bipotent for medullary and cortical thymic epithelial lineages.

Within the thymus, two major thymic epithelial cell (TEC) subsets-cortical and medullary TECs-provide unique structural and functional niches for T cell development and establishment of central tolerance. Both lineages are believed to originate from a common progenitor cell, yet the cellular and molecular identity of these bipotent TEC progenitors/stem cells remains ill defined. Here we identify rare stromal cells in the murine adult thymus, which under low-attachment conditions formed spheres (termed "thymospheres"). These thymosphere-forming cells (TSFCs) displayed the stemness features of being slow cycling, self-renewing, and bipotent. TSFCs could be significantly enriched based on their distinct surface antigen phenotype. The FoxN1 transcription factor was dispensable for TSFCs maintenance in situ and for commitment to the medullary and cortical TEC lineages. In summary, this study presents the characterization of the adult thymic epithelial stem cells and demonstrates the dispensability of FoxN1 function for their stemness.

Prolonged Bleeding After Dental Extraction Due to Decreased Serum Level of Von Willebrand Factor Caused by Untreated Profound Hypothyroidism.

BACKGROUND: Delayed diagnosis of hypothyroidism may result in atypical presentations. Here, we report a case with decreased serum level and activity of von Willebrand factor due to untreated profound hypothyroidism. OBSERVATION: A 9-year-old girl, presented with prolonged gingival bleeding after dental extraction. Clinical findings of the case were consistent with hypothyroidism, and the laboratory workup results revealed decreased serum level and activity of von Willebrand factor associated with profound hypothyroidism. Restoration of euthyroidism normalized the coagulation parameters. CONCLUSION: Delayed diagnosis of hypothyroidism may lead to atypical presentations such as bleeding diathesis. Profound hypothyroidism should be considered in the differential diagnosis of acquired von Willebrand disease to avoid undue treatment.

The effects of stocking density on growth, morphological development, behavior, and welfare parameters in pheasants (Phasianus colchicus).

In pheasants, which are generally raised in large flocks, stocking density is important for their growth and development, normal behavior and welfare. But there is still a lack of information on the optimum stocking density for game birds. This research was conducted on a total of 200 pheasants to examine the effects of low (5 pheasant/m2) and high (10 pheasant/m2) stocking density rearing practices on body weight, morphological development, behavioral characteristics and welfare parameters such as foot-pad dermatitis and plumage quality. When we look at the study results, it was determined that the density of stocking did not make a difference in the first 13 weeks of age, but pheasants reared at low density at the ages of 14-16 weeks reached higher body weight. In terms of body weight at 14, 15, and 16 weeks, the low stocking density group had an average of approximately 41, 71, and 94 g higher than the high stocking density group, respectively (p<0.05). It had been found that low density provides better morphological development. The low group was found to be significantly higher than the high group in terms of ornithological size, wingspan, back length, tail length, head length and head width, 5.9 cm, 2 cm, 1.3 cm, 7.6 cm, 1.7 mm and 1 mm, respectively (p<0.05). Since the animals in the low group had more individual space, they had the opportunity to perch and therefore exhibit more passive behavior. On the other hand, pheasants in the low group exhibited higher levels of aggressive behavior (p<0.05). More foraging behavior was observed in the higher group and the low-density group consumed more feed in the 14th week (p<0.05). But no significant differences were detected between groups in terms of feed consumption in other weeks (p>0.05). A 1.12 point higher score was calculated in the low group compared to the high group, especially in terms of tail feather quality, and as a result, pheasants reared in low stocking density had better plumage quality (p<0.05). It had been determined that as the stocking density decreases in the rearing of pheasants, they exhibit easier flight and roosting behaviors and therefore they were less affected by feather pecking behavior and had better feather quality. In addition, it had been determined that pheasants grow and develop better in this group, which had more rest opportunities. In conclusion, rearing at low stocking density is recommended for better fattening performance and better welfare conditions.

The effect of umbilical cord blood spexin, free 25(OH) vitamin D3 and adipocytokine levels on intrauterine growth and anthropometric measurements in newborns.

Spexin is a newly described peptide and is known to reduce the uptake of long-chain fatty acids into adipocytes. The serum spexin levels of obese children between the ages of 12-18 are lower. The effect of serum spexin and free 25(OH) vitamin D3 levels on intrauterine development in newborns is unknown. Our aims is to evaluate the effects of spexin and adipocytokin levels in the cord blood of term newborn babies on the weight of the baby according to the gestation age (GA) and anthropometric measurement results. Babies who were born in our hospital and whose GA was ≥37 weeks were evaluated in three groups as appropriate for GA (AGA), small for GA (SGA) and large for GA (LGA). A total of 84 babies, including an equal number of infants in AGA, SGA and LGA groups, were included in the study. Spexin, leptin, active ghrelin, free 25(OH) vitamin D3, glucose, and insulin levels in the cord blood of infants were examined at birth. The results were compared according to GA and birth weight (BW). There was no statistically significant difference between groups in terms of mean spexin, active ghrelin, free 25(OH) vitamin D3, and insulin levels. The mean leptin level was significantly higher in LGA group than SGA and AGA groups (p 0.004). The mean spexin and leptin levels were higher in girls than in boys (respectively p value 0.029, 0.003). Although there is a significant positive correlation between BW, head circumference, height, umbilical circumference, umbilical circumference/height ratio and the mean leptin levels (p < 0.001), there was no significant correlation between mean spexin, active ghrelin, free 25 (OH) vitamin D3, insulin, and glucose levels. This study suggests that spexin may not have an effect on intrauterine development.

Miniaturisation of a peptide-based electrochemical protease activity sensor using platinum microelectrodes.

Proteases are ideal target biomarkers as they have been implicated in many disease states, including steps associated with cancer progression. Electrochemical peptide-based biosensors have attracted much interest in recent years. However, the significantly large size of the electrodes typically used in most of these platforms has led to performance limitations. These could be addressed by the enhancements offered by microelectrodes, such as rapid response times, improved mass transport, higher signal-to-noise and sensitivity, as well as more localised and less invasive measurements. We present the production and characterisation of a miniaturised electrochemical biosensor for the detection of trypsin, based on 25 µm diameter Pt microelectrodes (rather than the ubiquitous Au electrodes), benchmarked by establishing the equivalent Pt macroelectrode response in terms of quantitative response to the protease, the kinetics of cleavage and the effects of non-specific protein binding and temperature. Interestingly, although there was little difference between Au and Pt macroelectrode response, significant differences were observed between the responses of the Pt macroelectrode and microelectrode systems indicative of increased reproducibility in the microelectrode SAM structure and sensor performance between the electrodes, increased storage stability and a decrease in the cleavage rate at functionalised microelectrodes, which is mitigated by measurement at normal body temperature. Together, these results demonstrate the robustness and sensitivity of the miniaturised sensing platform and its ability to operate within the clinically-relevant concentration ranges of proteases in normal and disease states. These are critical features for its translation into implantable devices.

Evaluation of retinal neurovascular structures by optical coherence tomography and optical coherence tomography angiography in children and adolescents with type 1 diabetes mellitus without clinical sign of diabetic retinopathy.

BACKGROUND: The aim of the study was to investigate whether retinal neurovascular structural impairment in children and adolescents with type 1 diabetes mellitus (T1D) without clinical signs of diabetic retinopathy (DR) could be detected early via optical coherence tomography (OCT) and OCT angiography (OCTA). METHODS: In the current prospective, cross-sectional, observational clinical study children and adolescents with T1D without DR were evaluated between December 2018 and May 2019. Retinal neurovascular structures in the macular and optic disc regions were examined in detail and quantitatively assessed using OCT and OCTA. Data from subjects with T1D were compared with data from healthy controls. Whether retinal neurovascular structural changes were significantly associated with puberty stage, diabetes duration, and HbA1c level was also investigated. RESULTS: The T1D group included 110 eyes and the control group included 84 eyes. In the T1D group the mean inside disc vessel density (VD) was significantly lower than that of the control group (p < 0.001), as was the mean superior temporal disc VD (p < 0.043). Puberty stage was significantly associated with retinal thickness, parafoveal superficial capillary plexus VD, and peripapillary retinal nerve fiber layer thickness (p < 0.05). Diabetes duration and HbA1c level was significantly correlated with retinal layer thickness, foveal avascular zone diameter, and superficial and deep capillary plexus VDs. CONCLUSION: In children and adolescents with T1D without clinical signs of DR, the VD of the disc region is affected earlier than the macular region. In these patients, early neurovascular impairment can be detected non-invasively via OCT and OCTA.

Determination of insulin resistance and its relationship with hyperandrogenemia,anti-Müllerian hormone, inhibin A, inhibin B, and insulin-like peptide-3 levels in adolescent girls with polycystic ovary syndrome

Background/aim: This study aims to investigate the association between polycystic ovary syndrome (PCOS) and obesity and insulin resistance (IR) with respect to anti-Müllerian hormone (AMH), inhibin A (INH-A), inhibin B (INH-B), and insulin-like peptide 3 (INSL3) levels, all factors which may have an impact on IR. Materials and methods: In this cross sectional study, 52 adolescent girls diagnosed with PCOS[groups:nonobese (NO), n = 23; overweight/obese (OW/O), n = 29] were included. Blood samples were obtained to measure AMH, INH-B, INH-A, and INSL3 levels, together with hormonal and biochemical assessments. Oral glucose tolerance test (OGTT) was performed and the indexes of IR [homeostasis model assessment: insulin resistance (HOMA-IR) and Matsuda index] were calculated. Results: Insulin resistance was 56.5% with OGTT and 30.4% with HOMA-IR in nonobese-PCOS girls. There was a correlation between INH-A and HOMA-IR even when controlled for body mass index (BMI). INH-B and FAI also had correlations with HOMA-IR which disappeared when controlled for BMI. In regression analyses, AMH (odds ratio = [0.903, P = 0.015) and FAI (odds ratio = 1.353, P = 0.023) are found to be contributors to IR. Their effect was BMI-independent. In ROC analysis, the cutoff value for FAI was 5.93 (sensitivity 71%) to define IR in PCOS girls. Conclusion: AMH and FAI may contribute to IR (defined by OGTT) in PCOS. FAI might be used as a supporting IR marker (defined by OGTT) in adolescent girls with PCOS.

Integrin-Rac signalling for mammary epithelial stem cell self-renewal.

BACKGROUND: Stem cells are precursors for all mammary epithelia, including ductal and alveolar epithelia, and myoepithelial cells. In vivo mammary epithelia reside in a tissue context and interact with their milieu via receptors such as integrins. Extracellular matrix receptors coordinate important cellular signalling platforms, of which integrins are the central architects. We have previously shown that integrins are required for mammary epithelial development and function, including survival, cell cycle, and polarity, as well as for the expression of mammary-specific genes. In the present study we looked at the role of integrins in mammary epithelial stem cell self-renewal. METHODS: We used an in vitro stem cell assay with primary mouse mammary epithelial cells isolated from genetically altered mice. This involved a 3D organoid assay, providing an opportunity to distinguish the stem cell- or luminal progenitor-driven organoids as structures with solid or hollow appearances, respectively. RESULTS: We demonstrate that integrins are essential for the maintenance and self-renewal of mammary epithelial stem cells. Moreover integrins activate the Rac1 signalling pathway in stem cells, which leads to the stimulation of a Wnt pathway, resulting in expression of ß-catenin target genes such as Axin2 and Lef1. CONCLUSIONS: Integrin/Rac signalling has a role in specifying the activation of a canonical Wnt pathway that is required for mammary epithelial stem cell self-renewal.

MRI-based evaluation of the factors leading to pituitary iron overload in patients with thalassemia major.

AIM: Given the lack of studies evaluating pituitary iron overload in patients with thalassemia major, we used magnetic resonance imaging (MRI) to evaluate these patients and the factors affecting the disease process. MATERIALS AND METHODS: The 84 patients with ß-thalassemia major who were included in this study were referred to our clinic for cardiac and hepatic T2(*) MRI. T2(*)-weighted images of the pituitary gland, heart, and liver were obtained using a 1.5-tesla MRI unit and a multi-echo gradient-echo sequence. Associations between pituitary T2(*), cardiac T2(*), hepatic T2(*), pituitary height, serum ferritin (SF) level, patient age, and other demographic findings were assessed. RESULTS: Pituitary T2(*) values correlated with hepatic T2(*) values, cardiac T2(*) values, SF level, and patient age (P≤0.001, 0.001, 0.001, 0.01, respectively) but not with pituitary height (P=0.76). Pituitary and cardiac T2(*) values were lower in the subset of patients who underwent splenectomy (P=0.046 and P=0.002, respectively). CONCLUSION: Pituitary iron overload rapidly increases during puberty and in this study correlated with cardiac and hepatic T2(*) values, patient age, SF level, and liver size, but not with the height of the pituitary. Pituitary iron overload also increases following splenectomy. Together, these findings indicate that numerous factors contribute to pituitary iron overload.

Recurrent pilonidal disease surgery: Is it second primary or reoperative surgery?

OBJECTIVE: Pilonidal sinus disease (PSD) effects mainly young men's social and work life with frequent recurrence rate. Reoperation for unimproved or recurrent disease is somehow troublesome. Surgeons may think that changing treatment strategy after recurrence may prevent further relapses of PSD. We analyzed patients with recurrent pilonidal sinus to determine their predisposing features for recurrence and the outcomes of the preferred surgical methods. MATERIAL AND METHODS: From 2007 to 2012, out of 95 recurrent pilonidal sinus disease (rPSD) patients, 62 operated cases were included and examined retrospectively. Their retrospective data were examined for demographics, 1(st) and 2(nd) operation types, patient satisfaction and pain scores. For cases with insufficient preoperative or postoperative data, phone call and interviews were done to obtain data. Some were kindly invited to the outpatient examination. Student's t test, Mann-Whitney U test, and Kaplan Meier test for disease free survival time were used where appropriate. P values less than 0.05 were accepted to be statistically significant. RESULTS: Total of 62 rPSD patients were examined. Male:female ratio was 2.9:1. The mean age after 1(st) and 2(nd) operations were 24.7 and 28.1 years, respectively. One and five-year recurrence rates were 33.9% and 66.1%, respectively. The mean interval between the 1(st) and 2(nd) operations was 45.6 months. Excision and midline closure was the most frequent type of operation followed by flap reconstructions and excision-lay open procedures. The 1(st) operation types of rPSD cases were different from that of 2(nd) operations. Pain perception and satisfaction scores were better in flap reconstruction groups. CONCLUSION: Reoperative surgery of rPSD is satisfactory with certain precautions. Relapses after flap reconstruction procedures with a well-being period should be referred as second primary disease. Changing surgical strategy is not always indicated as some patients with recurrence have relapsing or second primary disease that have distinct clinical course. Re-flap surgery after any kind of relapse is well appreciated.

Increased arterial stiffness in young normotensive patients with Turner syndrome: associations with vascular biomarkers.

OBJECTIVES: Factors contributing to arteriopathy in patients with Turner syndrome (TS) remain unclear. We assessed arterial stiffness in young, normotensive patients with TS and correlated arterial stiffness with vascular biomarkers, GH treatment and oestrogen exposure. Sixty-one patients with TS (mean age, 12·6 years; range 6·6-21·3 years) were matched for age and sex with 61 healthy peers. Associations between arterial stiffness and high-sensitivity C-reactive protein (hsCRP), B-type natriuretic peptide (BNP), atrial NP (ANP), plasma aldosterone/plasma renin activity (PRA), IGF1 and IGFBP3 were examined after adjusting for well-established confounders of vascular disease. RESULTS: Carotid intima media thickness standard deviation score (SDS), arterial stiffness index SDS and incremental modulus of elasticity SDS were higher, and distensibility coefficient SDS was lower in patients with TS. The duration of GH treatment and oestrogen exposure was not associated with indices of arterial stiffness. TS patients had higher hsCRP, BNP and ANP. Plasma aldosterone/PRA, IGF1 and IGFBP3 were similar in patients and controls. Multivariable regression analyses (R(2) = 0·200-0·668, P < 0·01) showed that BNP was associated with all indices of arterial stiffness. We found that hsCRP was associated with distensibility coefficient SDS (ß = -0·16, P < 0·01). TS was independently associated with increased arterial stiffness (ß = 0·420-3·424, P < 0·001 for all, R(2) = 0·06-0·31). CONCLUSIONS: Young, normotensive TS patients had increased arterial stiffness than that of healthy peers. BNP, and possibly hsCRP, was independently associated with arterial stiffness in TS. Further research will determine any causal inference of these relationships.

Gastric Remnant Cancer: Continuing Serious and Insidious Problem for Surgeons.

BACKGROUND/AIMS: Gastric remnant cancers (GRC) are usually detected at a later stage resulting in low rates of curative resection and a consequently poor prognosis. The incidence and etiology of GRC have been changing recently because of early detection and improved outcomes in patients with gastric cancers. This study was performed to evaluate the clinicopathological characteristics and prognosis of patients with GRC. METHODOLOGY: From January 2004 and July 2014, 27 patients with GRC who underwent surgery were analyzed retrospectively. The clinicopathological and follow-up data of 27 patients were evaluated including age, gende types of reconstruction, tumor location, histological types, TNM stages, surgical treatment and prognosis. RESULTS: Total 221 patients underwent gastrectomy for gastric cancer and ulcer disease and 27 (12.7%) consecutive GRC patients were included in this study. The median survival for all 27 patients was 20.0 ± 2.4 months. Previous malign disease, advanced TNM stage and non-curative resection were the negative prognostic factors for survival in patients with remnant stomach cancer (p < 0.05). CONCLUSIONS: Regular follow-up is one of the important factors affecting the early diagnosis and median survive time of patients with GRC. Curative resection is recommended operative treatment procedure to improve the survival when GRC patient diagnosed.

Totally Curative Surgical Resection of Retrorectal Tumors.

BACKGROUND/AIMS: Retrorectal (also known as presacral) tumor (RT) is a rare disease of retrorectal space. There is no large numbered case series in the literature. Well documented small numbered case series will help to establish meta-analysis and surgical decision making. METHODOLOGY: Between 2000 and 2014 medical records of patients with diagnosis of RT at two institutions were reviewed. Clinical features, diagnostic studies, type of surgery, surgical findings, surgical technique, and histopathology of the tumor, morbidity and survival are examined based on data registry. RESULTS: During 14 years period of time, total of 12 patients operated with diagnosis of RT were retrieved to this study. There were five men and seven women. The median age at the time of diagnosis was 43 (27-56) years. The most frequent findings were pain and palpable mass. There were five anterior, four posterior and three anteroposterior approaches for surgery. There is no recurrence or disease related mortality observed after median of 7 years (1-14). CONCLUSION: The primary and only satisfactory treatment is surgery for RTs. Prognosis is directly related primary local control with complete excision, which is often difficult to achieve for malignant lesions.

Characteristics of Emergency Gastrointestinal Stromal Tumor (GIST).

BACKGROUND/AIMS: Gastrointestinal Stromal Tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract (GIT). Importance of GISTs is increasing while surgeons are facing with more frequent either in emergency setting of elective cases. Delineating the presentation and management of emergency GIST is important. METHODOLOGY: From 2005 to 2014, emergency cases with final diagnosis of GIST were examined retrospectively. Total of 13 operated cases were evaluated by patients characteristics, clinical presentation, operational findings and postoperative prognosis. RESULTS: There were 9 male and 4 female with the mean age of 48.15 years. The most frequent presentations are ileus and GIT hemorrhage both covering the 84% of patients. Small bowel was the dominating site with ileus. Stomach was the second frequent site of the disease with the finding of hemorrhage. CONCLUSION: Emergency patients are more likely to come with small bowel GIST and obstruction symptoms. Hemorrhage is the most frequent symptom for emergency GIST of stomach and duodenum.

Vascular importance of the miR-212/132 cluster.

RATIONALE: Many processes in endothelial cells including angiogenic responses are regulated by microRNAs. However, there is limited information available about their complex cross-talk in regulating certain endothelial functions. AIM: The objective of this study is to identify endothelial functions of the pro-hypertrophic miR-212/132 cluster and its cross-talk with other microRNAs during development and disease. METHODS AND RESULTS: We here show that anti-angiogenic stimulation by transforming growth factor-beta activates the microRNA-212/132 cluster by derepression of their transcriptional co-activator cAMP response element-binding protein (CREB)-binding protein (CBP) which is a novel target of a previously identified pro-angiogenic miRNA miR-30a-3p in endothelial cells. Surprisingly, despite having the same seed-sequence, miR-212 and miR-132 exerted differential effects on endothelial transcriptome regulation and cellular functions with stronger endothelial inhibitory effects caused by miR-212. These differences could be attributed to additional auxiliary binding of miR-212 to its targets. In vivo, deletion of the miR-212/132 cluster increased endothelial vasodilatory function, improved angiogenic responses during postnatal development and in adult mice. CONCLUSION: Our results identify (i) a novel miRNA-cross-talk involving miR-30a-3p and miR-212, which led to suppression of important endothelial genes such as GAB1 and SIRT1 finally culminating in impaired endothelial function; and (ii) microRNAs may have different biological roles despite having the same seed sequence.

Pelvic ultrasound findings in prepubertal girls with precocious adrenarche born appropriate for gestational age.

BACKGROUND: Precocious adrenarche (PA) refers to the clinical onset of excess androgen in girls before the age of 8. It is associated with an increased risk of functional ovarian hyperandrogenism after puberty. PA may be associated with polycystic ovary syndrome (PCOS). We compared pelvic ultrasound (US) findings of girls with PA born appropriate for gestational age (AGA) to healthy body mass index (BMI)-matched peers to determine whether US findings in AGA-born PA girls are associated with PCOS antecedents. SUBJECTS AND METHODS: We conducted a cross-sectional study on 56 AGA-born girls with PA (6·9 ± 0·6 years) and 33 BMI-matched prepubertal AGA-born peers (7·1 ± 1·0 years). Hormonal data, homeostasis model assessment of insulin resistance (HOMA-IR), insulin sensitivity index (ISIcomp ) and pelvic US findings were compared. Associations of pelvic US findings with clinical and metabolic data were investigated. RESULTS: Precocious adrenarche girls had greater height and bone age-adjusted uterine length (UL; P = 0·01) and UL standard deviation score (SDS) (P = 0·02) than BMI-matched peers. Mean ovarian volume (MOV), MOV SDS, uterine volume, uterine cross-sectional area and ovarian morphology were similar between the groups (P > 0·05). MOV and MOV SDS correlated with ISIcomp (r = -0·683, P < 0·001; r = -0·760, P < 0·001; respectively). Correlations of pelvic US findings with other biochemical data did not reach significance (P > 0·05). Multivariate regression analysis revealed that in girls with PA, ISIcomp had the most significant effect on MOV SDS (R(2) = 0·731, ß = -4·784, P = 0·001). CONCLUSIONS: Appropriate for gestational age-born PA girls have greater UL measurements than AGA-born BMI-matched peers. In AGA-born girls with PA, decreasing insulin sensitivity is strongly and independently associated with an increase in MOV. Longitudinal follow-up of our cohort after menarche will allow us to establish how many AGA-born girls with PA will ultimately develop PCOS.

Doppler-derived strain imaging detects left ventricular systolic dysfunction in children with Turner syndrome.

OBJECTIVES: Children with Turner syndrome (TS) are at increased risk of cardiovascular disease (CVD), but associations with subclinical CVD are not well-characterized. The purpose of this study was to assess myocardial function using strain imaging (SI) by echocardiography in children with TS and without known CVD. METHODS: The study included 48 children with TS aged 4-16 years and 20 healthy control children. Children with TS were excluded if they had a cardiac malformation, a decreased left ventricular (LV) systolic function, or any chronic disease. Each child had an echocardiographic examination with conventional echocardiography and one-dimensional longitudinal strain (1DST) echocardiography. RESULTS: Septal and lateral systolic strain (S) and strain rate (SR) values, which are indicative of longitudinal myocardial function, were significantly decreased in TS patients. However, LV ejection fraction (LVEF) and LV fractional shortening (LVFS) was not significantly different between groups. LV mass index (LVMi), interventricular septum (IVS) thickness, LV posterior wall (LVPW) thickness, and left atrial (LA) diameter index were significantly higher in TS children compared to controls. Peak transmitral flow velocity in late diastole (peak A) was significantly higher, whereas peak transmitral flow velocity in early diastole (peak E), deceleration time (DT), and the ratio of early to late diastolic filling were significantly lower, in TS patients. CONCLUSION: Reduced LV systolic S and SR in children with TS may indicate early myocardial dysfunction before any detectable change in LVEF.

Evaluation of factors affecting mortality in Fournier's Gangrene: Retrospective clinical study of sixteen cases.

OBJECTIVE: Fournier's gangrene is a progressive, necrotizing fasciitis due to synergistic infection of the perineum and external genitalia that is associated with high mortality and morbidity. The purpose of this study is to review the diagnostic and treatment methods that effect mortality in Fournier's gangrene. MATERIAL AND METHODS: Sixteen patients who were diagnosed and treated at our clinic between 2011 and 2013 due to Fournier's gangrene were retrospectively analyzed. The surviving and non-surviving patient groups were compared in terms of age, sex, onset time of symptoms, isolated microorganisms, concomitant diseases, Fournier's gangrene severity index (FGSI), and length of hospital stay. RESULTS: Ten of our cases (62.5%) were male and six (37.5%) were female, with a mean age of 61.2±12.3 (42-73) years. The mortality rate was 18.8% (3 cases). The mean duration of symptoms before admission was 4.31±1.81 (2-8) days. This period was 6.67±1.52 days in patients who succumbed to death, and 3.77±1.42 days in patients who survived (p=0.007). Ten cases (62.5%) had concomitant diabetes mellitus. The most common organism isolated in wound cultures was Escherichia coli (68.7%), and Acinetobacter baumannii, Proteus mirabilis, methicillin-resistant Staphylococcus aureus and Enterococcus spp. in the remaining patients. The mean FGSI of surviving patients was 3.84±1.77, and 7.66±0.57 in fatal cases (p=0.003). The mean length of hospital stay was 25.5 days (2-57) and duration of hospitalization was significantly longer in survivors (p<0.05). CONCLUSION: The delay in diagnosis and higher FGSI may be responsible for worsening of prognosis and mortality in Fournier's gangrene. Early diagnosis and determination of the severity of the disease, aggressive surgical debridement and appropriate antimicrobial therapy may improve prognosis.