Phenotypic and mutational spectrum of ROR2-related Robinow syndrome.

Robinow syndrome is characterized by a triad of craniofacial dysmorphisms, disproportionate-limb short stature, and genital hypoplasia. A significant degree of phenotypic variability seems to correlate with different genes/loci. Disturbances of the noncanonical WNT-pathway have been identified as the main cause of the syndrome. Biallelic variants in ROR2 cause an autosomal recessive form of the syndrome with distinctive skeletal findings. Twenty-two patients with a clinical diagnosis of autosomal recessive Robinow syndrome were screened for variants in ROR2 using multiple molecular approaches. We identified 25 putatively pathogenic ROR2 variants, 16 novel, including single nucleotide variants and exonic deletions. Detailed phenotypic analyses revealed that all subjects presented with a prominent forehead, hypertelorism, short nose, abnormality of the nasal tip, brachydactyly, mesomelic limb shortening, short stature, and genital hypoplasia in male patients. A total of 19 clinical features were present in more than 75% of the subjects, thus pointing to an overall uniformity of the phenotype. Disease-causing variants in ROR2, contribute to a clinically recognizable autosomal recessive trait phenotype with multiple skeletal defects. A comprehensive quantitative clinical evaluation of this cohort delineated the phenotypic spectrum of ROR2-related Robinow syndrome. The identification of exonic deletion variant alleles further supports the contention of a loss-of-function mechanism in the etiology of the syndrome.

Graft and Patient Survival in Kidney Transplant Recipients Over the Age of Sixty-Five.

INTRODUCTION: Elderly patients have increased morbidity and mortality compared to younger patients due to existing comorbid diseases and chronic immunosuppression. Therefore, the option of kidney transplantation for renal replacement therapy in elderly patients is still being controversial. Our aim in this study was to evaluate graft function, graft and patient survival, and associated factors in kidney transplant recipients over 65 years of age, at 11 years of follow-up. METHODS: The study included 53 patients aged 65-76 years, out of a total of 1319 patients who underwent live kidney transplantation in the Organ Transplant Center of Acibadem International Hospital between October 2010 and July 2021. Demographic characteristics and creatinine values were recorded. Graft survival rates and patient survival rates at one, three, and five years were analyzed. RESULTS: Fifty-three patients, 14 female, 39 male, aged 65-76 years were included in the study. The follow-up period of the patients was 7-125 months. During the follow-up, 20 patients died. Graft loss occurred in two of 20 patients who died, and 18 patients died with working grafts. Graft loss developed in two of the 33 surviving patients. In the whole group, one-, three-, and five-year patient survival rates were 94%, 81%, and 76%, respectively. CONCLUSION: These results emphasize that kidney transplantation is a viable treatment option in elderly patients who have been well evaluated before kidney transplantation.

Long-Term Outcomes of Left versus Right Laparoscopic Living Donor Nephrectomy with Multiple Renal Arteries.

OBJECTIVES: The objective of this study was to compare the long-term graft outcomes of left-versus-right donor nephrectomy with multiple renal arteries (MRAs), and therefore creating a reference for the expansion of the potential living kidney donor pool. METHODS: Laparoscopic live donor nephrectomy cases between May 2010 and October 2020 were included in this retrospective cross-sectional study. The data relating to donor and recipient demographics, surgical and anatomical characteristics, recipient, and graft status were retrieved and compared using nonparametric statistical methods and multivariate regression. Analyses were fit for survival factors. RESULTS: A total of 1,009 recipients were included in this retrospective cross-sectional study with their donors. 16.7% of the donors had been discovered to have more than one renal artery supplying the donated kidney. The acute rejection rate was 12.8%. Death-censored graft survival at postoperative year 5 for single renal artery (SRA) transplants was 89.6%, 89.5% for left-sided MRAs, and 88.2% for right-sided ones. CONCLUSIONS: Both right donor nephrectomy and left donor nephrectomy are safe procedures with no significant negatively impacted rates for neither survival nor complications of the recipients in the long-term, compared to SRA ones.

Vitamin D and Nerve Conduction In Pediatric Type-1 Diabetes Mellitus.

INTRODUCTION: The aim of this study is to investigate a possible association between vitamin D deficiency and diabetic peripheral neuropathy in pediatric patients with type 1 diabetes mellitus. MATERIALS-METHODS: Twenty-nine patients with type 1 diabetes mellitus and 19 healthy controls were included to the study. All individuals were evaluated for diabetic peripheral neuropathy with nerve conduction studies. Complete blood cell count, biochemical investigations, serum vitamin D levels, hemoglobin A1c levels were recorded. RESULTS: No statistically significant differences between the diabetes and control groups in terms of gender, age, body weight, height, body mass index, systolic and diastolic blood pressures, laboratory investigations, serum vitamin D levels and nerve conduction studies was found. Patients with diabetes were grouped as patients with normal serum vitamin D levels and patients with vitamin D deficiency. Sensory nerve action potential of sural nerve and motor peroneal nerve velocity were statistically significantly lower in diabetic patients with vitamin D deficiency compared to diabetic patients with normal vitamin D levels (p 0.009 and 0.005 respectively). CONCLUSION: Our results suggested that hypovitaminosis D might lead to development of neuropathic changes particularly on the lower limb nerves even in the early stages of the disease. It should be kept in mind that patients with hypovitaminosis D should be elaborately examined and closely followed up for the development of diabetic neuropathic changes, even if glucose control is achieved.

The relationship between calcification inhibitor levels in chronic kidney disease and the development of atherosclerosis.

AIM: We aimed to investigate the factors affecting the development of atherosclerosis and the role of calcification inhibitors fetuin-A, matrix-Gla protein (MGP), osteoprotegerin (OPG) in atherosclerosis progress. MATERIAL AND METHODS: The study was planned to investigate the relationship of serum OPG, MGP and fetuin-A levels with the development of atherosclerosis in the stage 2-3-4-5 chronic kidney disease (CKD) patients who did not require dialysis treatment. RESULTS: 32 (17 female, 15 male) healthy individuals and 92 (49 females, 43 males) CKD patients were included. The mean carotid intima-media thickness (CIMT), C-reactive protein (CRP), fetuin-A, OPG and MGP of the two groups were compared statistically. In CKD patients, age, body mass index (BMI), CRP, triglyceride, urea, systolic blood pressure (SBP), fasting blood sugar have a positive linear relationship, fetuin-A, OPG, GFR have a negative linear relationship with CIMT. The mean CIMT, right CIMT, left CIMT, blood urea, CRP, urinary albumin excretion creatinine and age show a negative linear relationship with fetuin-A. CONCLUSION: Fetuin-A levels begin to decline from the early stages of CKD and are significantly lower in patients with atherosclerosis as expressed with CIMT. This suggests that fetuin-A may be used as an early marker in CKD for increased cardiovascular risk. Early recognition of these risk factors is important and large-scale studies on vascular calcification inhibitors are needed.

Assessment of clinical outcomes in renal transplant recipients with COVID-19.

The coronavirus disease 2019 (COVID-19) has affected more than a hundred million individuals and caused more than three million deaths worldwide. Specific risk groups were defined for increased risk of mortality and morbidity in COVID-19, and renal transplant recipients are at a significantly increased risk regarding outcomes due to their immunosuppressed conditions. This study evaluated the general characteristics of kidney transplant recipients with COVID-19 infection. Among 1257 transplant cases, 56 had COVID-19 infection, and 23 (41%) were hospitalized during the 9-month study period. Among all COVID-19 cases, 58% were male with a mean age of 45.5 (±13.2, 19-71) years, and the most frequent comorbidities were hypertension (70.9%) and diabetes (23.6%). Hospitalized patients were older (p = 0.03) and had higher rates of hypertension (p = 0.008), diabetes (p = 0.002), and ischemic heart disease (p = 0.03). Therapeutic management included antimetabolite withdrawal and prednisolone increase in 71%, calcineurin inhibitor withdrawal in 8% and decrease in 58%, hydroxychloroquine in 17%, tocilizumab in 3%, and antivirals in 67% of patients. Acute kidney injury and respiratory failure developed in 34% and 85%, respectively. The mortality rate was 23%. These results emphasized that the COVID-19 infection in renal transplant recipients significantly increases the risk of morbidity and mortality. Therefore, these patients should be intervened earlier and monitored closely to prevent poor outcomes.

Molecular Diagnosis of Monogenic Diabetes and Their Clinical/Laboratory Features in Turkish Children

Objective: Monogenic diabetes is a heterogeneous disease that causes functional problems in pancreatic beta cells and hyperglycemia. The aim of this study was to determine the clinical and laboratory features, the admission characteristics and distribution of monogenic form of diabetes in childhood in Turkey. Methods: Patients aged 0-18 years, who were molecularly diagnosed with monogenic diabetes, and consented to participate, were included in the study. Results: Seventy-seven (45.6%) female and 92 male cases with a mean age of 8.18±5.05 years at diagnosis were included. 52.7% of the cases were diagnosed with monogenic diabetes by random blood glucose measurement. The reason for genetic analysis in 95 (56.2%) of cases was having a family member diagnosed with diabetes under the age of 25. At the time of diagnosis, ketone was detected in urine in 16.6% of the cases. Mean hemoglobin A1c on admission, fasting blood glucose, fasting insulin, and c-peptide values were 7.3±2.1%, 184.9±128.9 mg/dL, 9.4±22.9 IU/L, 1.36±1.1 and ng/L respectively. GCK-MODY was found in 100 (59.2%), HNF1A-MODY in 31 (18.3%), and variants in ABCC8 in 6 (3.6%), KCNJ11 in 5 (3%), HNF4A in 2 (1.2%), and HNF1B in 2 (1.2%). Conclusion: Recent studies have indicated HNF1A-MODY is the most frequent of all the MODY-monogenic diabetes cases in the literature (50%), while GCK-MODY is the second most frequent (32%). In contrast to these reports, in our study, the most common form was GCK-MODY while less than 20% of cases were diagnosed with HNF1A-MODY.

Evaluation of children with type 1 diabetes mellitus in terms of overweight/obesity in tertiary care hospital.

OBJECTIVES: Obesity is a growing problem in type 1 diabetes mellitus (T1DM) today. The aim of our study is to determine the frequency of overweight/obesity at the time of diagnosis and during follow-up in children with T1DM as well as review the conditions that may accompany. METHODS: A total of 315 patients with T1DM were retrospectively analyzed. The patients were divided into two groups as normal weight and overweight/obese. The two groups were compared in terms of age at diagnosis, birth weight, anthropometric measurements, insulin dose used and blood pressure measurements, and insulin, c-peptide, hemoglobin A1c, triglyceride, and high-density lipoprotein levels at the time of diagnosis and follow-up. RESULTS: The height, weight and body mass index standard deviation (BMI SD) scores, and c-peptide levels at the time of diagnosis of the overweight/obese group were higher than those with normal weight (p<0.001 and p = 0.008, respectively). The frequency of dyslipidemia and hypertension was higher in the overweight/obese group than in the normal weight group [18.2 vs. 5% (p = 0.015) and 10 vs. 1.5% (p = 0.003), respectively]. CONCLUSIONS: In our study, the fact that the overweight/obese group had higher BMI and c-peptide and lower HDL values at the time of diagnosis can be evaluated as indicators that insulin resistance syndrome can accompany T1DM from the beginning (double diabetes). When determining the treatment and follow-up strategies of patients with T1DM, considering the risk of obesity and taking the necessary precautions is very important in terms of morbidity.

What is the relationship between obesity and new circadian rhythm parameters in Turkish children and adolescents? A case-control study.

BACKGROUND: Although the relationship between circadian rhythm parameters and obesity in children and adolescents is recognized, there are few studies on this topic. The concept of sleep-corrected social jetlag (SJLsc) has been formulated recently, but its relationship with childhood obesity has not yet been established. Therefore, we thought that SJL might play an important role in the etiology of obesity. Accordingly, we aimed to compare circadian rhythm parameters between obese and normal-weight children and adolescents. METHODS: Seventy-nine obese and eighty-two normal-weight children and adolescents aged between 8 and 17 years participated in this case-control study, which took place in the Mardin province of Turkey. Data were collected with a sociodemographic information form, the Childhood Chronotype Questionnaire, and anthropometric measurements. RESULTS: The average ages of the obese participants and controls were 12.3 ± 2.3 and 12.4 ± 2.2 years, respectively. Obese young people had greater evening preference, longer sleep debt duration, SJL duration and SJLsc duration, and higher Morningness-Eveningness Scale (MeScale) scores; and shorter mean sleep duration (p<0.005). In regression analyses, BMI z scores were significantly correlated with all circadian rhythm parameters, except SJLsc duration, while WC z scores were significantly correlated with all circadian rhythm parameters, except mean sleep duration. After adjustment, the high MeScale scores (OR: 1.142, p<0.05) and the presence of psychiatric disorder in the mother (OR: 15.075, p<0.05) were associated with obesity. CONCLUSIONS: Circadian rhythm parameters can play an important role in the etiology of obesity. Future studies with larger samples and fewer confounding factors are needed to clarify the etiological factors.

Relationship of Obesity and Related Disorders with Ocular Parameters in Children and Adolescent.

PURPOSE: To evaluate the effect of obesity and obesity-related high blood pressure (BP) on the retinal nerve fiber layer (RNFL) and macula in children and adolescents. MATERIALS AND METHODS: Thirty-two obese patients followed up in the pediatrics endocrinology clinic between 2018 and 2019 were evaluated in the ophthalmology clinic. The results were compared with 25 healthy subjects, matched for age and sex. Anthropometric measurements, and systolic and diastolic BP were measured. The study consisted of three groups: Group 1, patients with obesity; Group 2, those with obesity and associated hypertension (obesity-related HT); and Group 3, healthy controls. A complete ophthalmologic examination was performed. Macular and RNFL thicknesses were determined using spectral domain optical coherence tomography (SD-OCT). RESULTS: There were no statistically significant differences between the groups in terms of gender, age, and intraocular pressure (p > .05). The inferior RNFL thickness and central foveal thickness were statistically thinner in the obesity-related HT group (p < .001 and p = .040). The systolic and diastolic BP and fasting glucose values were significantly higher in the obesity-related HT group than the other groups (p < .001; p < .001; p = .026, respectively). In linear regression modeling in obese and obesity-related HT groups, a significant assocation was found between diastolic BP and temporal RNFL thickness (p = .027) as well as between the systolic BP and triglyceride values and the nasal RNFL thickness values (p = .016 and p = .025, respectively). CONCLUSIONS: Inferior RNFL thickness and central foveal thickness were significantly thinner in patients with obesity-related HT. The effects of obesity-related HT on the retina should be evaluated using SD OCT, since no signs were found in a routine ocular examination.

Comparison of Long-Term Outcomes of Standard and Transvaginal Kidney Extraction in Laparoscopic Living Donor Nephrectomy.

Background: A limited number of publications are available in the literature regarding laparoscopic living donor nephrectomy with vaginal extraction (LLDN-VE) for kidney transplantation. The aim of this study was to compare long-term recipient outcomes of standard laparoscopic living donor nephrectomy (S-LLDN) and LLDN-VE. Methods: A total of 652 patients [119 LLDN-VE (18.3%) and 533 S-LLDN (81.7%)] were included in this retrospective cross-sectional study. The data related to donor and recipient demographics, surgical and anatomical characteristics, and recipient and graft status were retrieved and compared using nonparametric statistical methods. Kaplan-Meier and Cox proportional hazards regression analyses were applied to compute survival according to the surgical technique. Results: The mean follow-up duration was 73.0 ± 25.4 months for S-LLDN and 69.8 ± 20.4 months for LLDN-VE recipients. The main determinants of long-term outcomes were the serum creatinine (SCr) levels, death-censored graft survival, and recipient survival at the end of the post-op 5th year. LLDN-VE recipients' discharge SCr was found to be statistically lower (P = .049) than S-LLDN patients. Graft survival rates censored for death were 93.8% for the S-LLDN and 93.3% for the LLDN-VE recipients. Cox regression analysis showed significance for younger donor age (P = .010) with the application of 17 parameters, indicating better graft survival outcomes for kidney recipients with younger donors. Conclusions: Compared with the standard method, the long-term results of LLDN-VE are in accordance with or could even be more advantageous than S-LLDN in certain aspects. LLDN-VE appears to be a feasible, safe, and cosmetically superior approach with no negative postoperative sexual or morbid effects on the donor.

Utility of estimated glucose disposal rate for predicting metabolic syndrome in children and adolescents with type-1 diabetes.

Objectives To determine the clinical utility of the estimated glucose disposal rate (eGDR) for predicting metabolic syndrome (MetS) in children and adolescents with type-1 diabetes (T1D). Methods Modified criteria of the International Diabetes Federation were used to determine MetS in children and adolescents between 10 and 18 years of age with T1D. The eGDR, a validated marker of insulin sensitivity, was calculated in two different ways using either the waist-to-hip ratio (WHR) or waist circumference (WC). Receiver operating characteristic (ROC) curve analysis was performed to ascertain cut-off levels of the eGDR to predict MetS. Results A total of 200 patients (52% male) with T1D were enrolled in the study. The prevalence of MetS was 10.5% (n: 21). Lower eGDR levels, indicating greater insulin resistance, were found in T1D patients with MetS when compared to those without (6.41 ± 1.86 vs. 9.50 ± 1.34 mg/kg/min) (p < 0.001). An eGDRWHR cut-off of 8.44 mg/kg/min showed 85.7% sensitivity and 82.6% specificity, while an eGDRWC cut-off of 8.16 mg/kg/min showed 76.1% sensitivity and 92.1% specificity for MetS diagnosis. The diagnostic odds ratio was 28.6 (7.3-131.0) for the eGDRWHR cut-off and 37.7 (10.8-140.8) for the eGDRWC cut-off. Conclusions The eGDR is a mathematical formula that can be used in clinical practice to detect the existence of MetS in children and adolescents with T1D using only the WC, existence of hypertension, and hemoglobin A1c levels. An eGDR calculated using the WC could be a preferred choice due to its higher diagnostic performance.

Revisiting Classical 3ß-hydroxysteroid Dehydrogenase 2 Deficiency: Lessons from 31 Pediatric Cases.

CONTEXT: The clinical effects of classical 3ß-hydroxysteroid dehydrogenase 2 (3ßHSD2) deficiency are insufficiently defined due to a limited number of published cases. OBJECTIVE: To evaluate an integrated steroid metabolome and the short- and long-term clinical features of 3ßHSD2 deficiency. DESIGN: Multicenter, cross-sectional study. SETTING: Nine tertiary pediatric endocrinology clinics across Turkey. PATIENTS: Children with clinical diagnosis of 3ßHSD2 deficiency. MAIN OUTCOME MEASURES: Clinical manifestations, genotype-phenotype-metabolomic relations. A structured questionnaire was used to evaluate the data of patients with clinical 3ßHSD2 deficiency. Genetic analysis of HSD3B2 was performed using Sanger sequencing. Novel HSD3B2 mutations were studied in vitro. Nineteen plasma adrenal steroids were measured using LC-MS/MS. RESULTS: Eleven homozygous HSD3B2 mutations (6 novel) were identified in 31 children (19 male/12 female; mean age: 6.6 ±â€…5.1 yrs). The patients with homozygous pathogenic HSD3B2 missense variants of > 5% of wild type 3ßHSD2 activity in vitro had a non-salt-losing clinical phenotype. Ambiguous genitalia was an invariable feature of all genetic males, whereas only 1 of 12 female patients presented with virilized genitalia. Premature pubarche was observed in 78% of patients. In adolescence, menstrual irregularities and polycystic ovaries in females and adrenal rest tumors and gonadal failure in males were observed. CONCLUSIONS: Genetically-documented 3ßHSD2 deficiency includes salt-losing and non-salt-losing clinical phenotypes. Spared mineralocorticoid function and unvirilized genitalia in females may lead to misdiagnosis and underestimation of the frequency of 3ßHSD2 deficiency. High baseline 17OHPreg to cortisol ratio and low 11-oxyandrogen concentrations by LC-MS/MS unequivocally identifies patients with 3ßHSD2 deficiency.

Prevalence of Obesity and Metabolic Syndrome in Children with Type 1 Diabetes: A Comparative Assessment Based on Criteria Established by the International Diabetes Federation, World Health Organisation and National Cholesterol Education Program

Objective: To determine the prevalence of obesity and metabolic syndrome (MetS) in children and adolescents with type 1 diabetes (T1D) and to compare the widely accepted and used diagnostic criteria for MetS established by the International Diabetes Federation (IDF), World Health Organisation (WHO) and National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII). Methods: We conducted a descriptive, cross sectional study including T1D patients between 8-18 years of age. The three sets of criteria were used to determine the prevalence of MetS and findings compared. Risk factors related to MetS were extracted from hospital records. Results: The study included 200 patients with T1D (52% boys). Of these, 18% (n=36) were overweight/obese (body mass index percentile ≥85%). MetS prevalence was 10.5%, 8.5% and 13.5% according to IDF, WHO and NCEP criteria, respectively. There were no statistically significant differences in age, gender, family history of T1D and T2D, pubertal stage, duration of diabetes, hemoglobin A1c levels and daily insulin doses between patients with or without MetS. In the overweight or obese T1D patients, the prevalence of MetS was 44.4%, 38.8% and 44.4% according to IDF, WHO and NCEP-ATPIII criteria, respectively. Conclusion: Obesity prevalence in the T1D cohort was similar to that of the healthy population of the same age. Prevalence of MetS was higher in children and adolescents with T1D compared to the obese population in Turkey. The WHO criteria include microvascular complications which are rare in childhood and the NCEP criteria do not include a primary criterion while diagnosing non-obese patients according to waist circumference as MetS because the existence of diabetes is considered as a direct criterion. Our study suggests that IDF criteria which allows the diagnosis of MetS with obesity and have accepted criteria for the childhood are more suitable for the diagnosis of MetS in children and adolescents with T1D.

Comparison of Treatment Regimens in Management of Severe Hypercalcemia Due to Vitamin D Intoxication in Children

Objective: No large study has been conducted to date to compare the effectiveness of prednisolone, alendronate and pamidronate as first-line treatment in children with hypercalcemia due to vitamin D intoxication. The aim was to perform a multicenter, retrospective study assessing clinical characteristics and treatment results. Methods: A standard questionnaire was uploaded to an online national database system to collect data on children with hypercalcemia (serum calcium level >10.5 mg/dL) due to vitamin D intoxication [serum 25-hydroxyvitamin D (25(OH)D) level >150 ng/mL] who were treated in pediatric endocrinology clinics. Results: Seventy-four children [median (range) age 1.06 (0.65-1.60) years, 45 males (61%) from 11 centers] were included. High-dose vitamin D intake was evident in 77% of the cases. At diagnosis, serum calcium, phosphorus, alkaline phosphatase, 25(OH)D and parathyroid hormone concentrations were 15±3.2 mg/dL, 5.2±1.2 mg/dL, 268±132 IU/L, 322 (236-454) ng/mL, and 5.5 (3-10.5) pg/mL, respectively. Calcium levels showed moderate correlation with 25(OH)D levels (rs=0.402, p<0.001). Patients were designated into five groups according to the initial specific treatment regimens (hydration-only, prednisolone, alendronate, pamidronate, and combination). Need for another type of specific drug treatment was higher in children who initially received prednisolone (p<0.001). Recurrence rate of hypercalcemia was significantly lower in children who were treated with pamidronate (p=0.02). Conclusion: Prednisolone is less effective in the treatment of children with severe hypercalcaemia secondary to vitamin D intoxication and timely implementation of other treatment regimens should be considered.

Effect of a nurse-led intervention programme on professional quality of life and post-traumatic growth in oncology nurses.

AIM: To evaluate the effects of a nurse-led intervention programme on compassion fatigue, compassion satisfaction, and burnout, which are indicators of the professional quality of life and post-traumatic growth of oncology nurses. METHOD: The study was designed in a single group with pre-test and post-test comparisons. The nurse-led intervention programme was carried out in two face-to-face sessions and two counselling follow-up sessions by phone with 43 nurses who care for oncology patients at a university hospital. The nurse-led intervention sessions consisted of a lecture on a relevant topic, background reading, baksi dance and mandala painting; motivational text messages and counselling. The Professional Quality of Life-IV Scale and the Post-Traumatic Growth Inventory were used, and data were evaluated using the "paired groups t test" analysis. Data for the study were acquired between March and April 2016. RESULTS: The evaluation carried out before and 5 weeks after the intervention showed that compassion fatigue and burnout decreased, while compassion satisfaction and all subscales scores of post-traumatic growth inventory increased. CONCLUSION: This nurse-led intervention programme was effective in improving the professional quality of life and post-traumatic growth of oncology nurses.

Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolines.

Herein, we describe a catalytic fluorooxygenation of readily accessible N-allylcarboxamides via an I(I)/I(III) manifold to generate 2-oxazolines containing a fluoromethyl group. Catalysis is conditional on the oxidation competence of Selectfluor®, whilst HF serves as both a fluoride source and Brønsted acid activator. The C(sp3)-F bond of the mono-fluoromethyl unit and the C(sp3)-O bond of the ring are aligned in a synclinal relationship thereby engaging in stabilising hyperconjugative interactions with vicinal, electron-rich σ-bonds (σC-C→σ*C-F and σC-H→σ*C-O). This manifestation of the stereoelectronic gauche effect was established by X-ray crystallographic analysis of a representative example. Given the importance of fluorine in drug discovery, its ability to modulate conformation, and the prevalence of the 2-oxazoline scaffold in Nature, this strategy provides a rapid entry into an important bioisostere class.

Acoustic Radiation Force Impulse Quantification in the Evaluation of Thyroid Elasticity in Pediatric Patients With Hashimoto Thyroiditis.

OBJECTIVES: To evaluate the parenchymal elasticity of the thyroid gland with acoustic radiation force impulse imaging in pediatric patients with Hashimoto thyroiditis and to compare it with healthy volunteers. METHODS: Twenty-six patients with Hashimoto thyroiditis and 26 healthy volunteers between 6 and 17 years were included. The shear wave velocity (SWV) values of both thyroid lobes in both groups were evaluated. RESULTS: The age and sex characteristics of the controls and patients with Hashimoto thyroiditis were similar. The SWV of the thyroid gland in patients with Hashimoto thyroiditis (mean ± SD, 1.67 ± 0.63 m/s) was significantly higher than that in the control group (1.30 ± 0.13 m/s; P < .001). There was no significant difference between the thyroid lobes in both groups. A receiver operating characteristic curve analyses showed an optimal cutoff value of 1.41 m/s, with 73.1% sensitivity, 80.8% specificity, a 79.2 % positive predictive value, and a 75.0% negative predictive value (area under the curve, 0.806; P < .001). In patients with Hashimoto thyroiditis, there was a positive correlation between the SWV values versus anti-thyroperoxidase (Pearson r = 0.46; P = .038). There were no correlations between age, body mass index, thyroid function test results, and anti-thyroglobulin values and versus SWV values. Also, no significant differences were seen between the groups for gland size, gland vascularity, and l-thyroxine treatment. CONCLUSIONS: Acoustic radiation force impulse elastography showed a significant difference in the stiffness of the thyroid gland between children with Hashimoto thyroiditis and the healthy group. Using acoustic radiation force impulse elastography immediately after a standard ultrasound evaluation may predict chronic autoimmune thyroiditis.

Acoustic Radiation Force Impulse Elastography in Determining the Effects of Type 1 Diabetes on Pancreas and Kidney Elasticity in Children.

OBJECTIVE: The aim of this study is to determine the effects of type 1 diabetes on pancreas and kidney elasticity in children, using acoustic radiation force impulse ultrasound elastography. SUBJECTS AND METHODS: Sixty autoantibody-positive patients with type 1 diabetes (45% girls; mean [± SD] age, 11.7 ± 4.4 years; range, 1.9-19.3 years) admitted to the pediatric endocrinology outpatient clinic and 32 healthy children (50% girls; mean age, 10.2 ± 3.8 years; range, 2.1-17.3 years) were included in the study. Acoustic radiation force impulse elastography measurements were performed of the kidneys and pancreas in both groups. Body mass index, duration of diabetes, HbA1c levels, and insulin dosage of patients with type 1 diabetes were recorded. RESULTS: The mean shear-wave velocities of the pancreas were 0.99 ± 0.25 m/s in patients with type 1 diabetes and 1.09 ± 0.22 m/s in healthy control subjects; the difference was not significant (p = 0.08). The median shear-wave velocities of the right and left kidneys in patients with type 1 diabetes were 2.43 ± 0.29 and 2.47 ± 0.25 m/s, respectively. There were no significant differences in the shear-wave velocities of the right and left kidneys between the patients with type 1 diabetes and the healthy control subjects (p = 0.91 and p = 0.73, respectively). Correlation analysis showed no correlation between the shear-wave velocities of the pancreas and kidney versus HbA1c level, duration of diabetes, insulin dosage, height, weight, and body mass index of the patients with type 1 diabetes. CONCLUSION: The current study showed no significant difference in the shear-wave velocity of kidneys in children with type 1 diabetes with normoalbuminuria compared with the healthy control subjects. We also observed that the shear-wave velocity of the pancreas in children with type 1 diabetes and healthy control subjects did not differ significantly.

Clinical, biochemical and genetic features with nonclassical 21-hydroxylase deficiency and final height.

BACKGROUND: The clinical, laboratory, genetic properties and final height of a large cohort of patients with nonclassical 21-hydroxylase deficiency (NC21OHD) in Turkey were analyzed. METHODS: This multicenter, nationwide web-based study collected data. RESULTS: The mean age was 9.79±4.35 years (229 girls, 29 boys). The most common symptoms were premature pubarche (54.6%) and hirsutism (28.6%). The peak cortisol was found below 18 µg/dL in three (15.45%) patients. A mutation was detected in the CYP21A2 gene of 182 (87.5%) patients. The most common mutation was V281L. Final height in female patients who were diagnosed and treated before attaining final height or near final height was found to be shorter than the final height in female patients who were diagnosed after attaining final height or near final height. CONCLUSIONS: The final height of the patients who were treated during childhood was found to be shorter than the final height of patients during the adolescent period.