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12 (0.04, 0.20)) and 0.08 (0.01, 0.15)). Seropositivity for CMV in the absence of seropositivity for EBV was associated with an increased risk of inhalant allergic sensitization (OR (95% CI) 1.31 (1.02, 1.68)). All effect estimates attenuated into non-significant mainly after adjustment for child's ethnicity. Seropositivity for EBV or CMV was not associated with asthma. CONCLUSIONS AND CLINICAL RELEVANCE Associations of EBV and CMV infections in early childhood with school-age lung function and inhalant allergic sensitization are explained by ethnicity, or sociodemographic and lifestyle-related factors. © 2020 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.AIM To explore the phenotype and response to growth hormone in patients with heterozygous mutations in the insulin-like growth factor I receptor gene (IGF1R). METHODS Children with short stature, microcephaly, born SGA combined with biochemical sign of IGF-I insensitivity were analysed for IGF1R mutations or deletions using Sanger sequencing and Multiple ligation-dependent probe amplification analysis. RESULTS In two families, a novel heterozygous non-synonymous missense IGF1R variant was identified. In family 1, c.3364G > T, p.(Gly1122Cys) was found in the proband and co-segregated perfectly with the phenotype in three generations. In family 2, a de novo variant c.3530G > A, p.(Arg1177His) was detected. Both variants were rare, not present in the GnomAD database. Three individuals carrying IGF1R mutations have received rhGH treatment. The average gain in height SDS during treatment was 0.42 (range 0.26-0.60) and 0.64 (range 0.32-0.86) after 1 and 2 years of treatment, respectively. CONCLUSION Our study presents two heterozygous IGF1R mutations causing pre- and postnatal growth failure and microcephaly and also indicates that individuals with heterozygous IGF1R mutations can respond to rhGH treatment. The findings highlight that sequencing of the IGF1R should be considered in children with microcephaly and short stature due to pre- and postnatal growth failure. © 2020 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.Data from three completed cardiovascular outcome trials (CVOTs), EMPA-REG OUTCOME, CANVAS Program and DECLARE-TIMI 58, add to the evidence supporting the potential renoprotective effects of sodium-glucose linked transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes. Despite recommendations in recent guidelines, it is difficult to support a view that definitive evidence for renoprotection exists from these SGLT2 inhibitor CVOT results. To date, the only dedicated trial to report definitive data on the renal impact of SGLT2 inhibition is CREDENCE. Notably, the total number of patient-relevant renal endpoint events (dialysis, transplant or renal death) observed in CREDENCE was significantly higher than the total for all three CVOTs collectively (183 events/4401 patients vs. 69 events/34 322 patients, respectively), which shows the increased statistical power of CREDENCE for these renal endpoints. Treatment with canagliflozin was associated with a 30% relative risk reduction (RRR) in the primary composite endpoint of end-stage kidney disease, doubling of serum creatinine, or death from renal or cardiovascular causes and a 34% RRR for the renal-specific elements of this primary endpoint (P less then 0.001). Canagliflozin has therefore become the first US-approved SGLT2 inhibitor to include an indication for RRR, in addition to type 2 diabetes glycaemic control and cardiovascular risk reduction. While confirmatory of the exploratory data from CVOTs, CREDENCE provides the first robust data on the effects of canagliflozin on patient-relevant renal endpoints. Extrapolation to a conclusion of a SGLT2 inhibitor class effect cannot be made until additional renal trials with other SGLT2 inhibitors are reported. © 2020 John Wiley & Sons Ltd.BACKGROUND Associations of cardiorespiratory fitness in childhood and adulthood with adult cardiometabolic risk factors are poorly understood, not least because of the paucity of studies. OBJECTIVES We investigated associations between nonexercise testing cardiorespiratory fitness (NETCRF) in childhood/adulthood and cardiometabolic risk factors in adulthood. METHODS Based on an established algorithm comprising gender, age, body mass index, resting heart rate, and self-reported physical activity at age 10, we computed NETCRF. Risk factors were assessed at age 46 in 5009 participants when NETCRF was again calculated. Linear regression was used to summarize associations between NETCRF in childhood and risk factors in adulthood and, additionally, the relationship between NETCRF in adulthood and risk factors in adulthood after adjusting for childhood NETCRF. RESULTS Inconsistent associations were observed between childhood NETCRF and adult risk factors. NETCRF in adulthood was associated with blood pressure [-5.8 (-6.7, -4.9)], glycated hemoglobin [-3.41 (-4.06, -2.76)], total cholesterol [-0.16 (-0.24, -0.08)], HDL cholesterol [0.19 (0.16, 0.22)], triglycerides [-0.68 (-0.85, -0.50)], and C-reactive protein [-0.29 (-0.35, -0.22)] in adult males. Similar associations were observed in adult females. Compared to those with low estimated fitness in both childhood and adulthood, participants with low fitness in childhood and high fitness in adulthood had a lower risk of two or more cardiometabolic risk factors (odds ratio 0.25; 95% confidence interval 0.19, 0.31). MK-0991 inhibitor CONCLUSION Associations between estimated fitness and risk factors are stronger in adulthood than from childhood to adulthood. Adults with previously sedentary childhoods may still gain benefits from improving their fitness. © 2020 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.OBJECTIVE To evaluate the feasibility and effect of mesureteral preservation on urinary complications in the context of total mesometrial resection (TMMR), a surgical treatment for cervical cancer. DESIGN Retrospective cohort study with historic control. SETTING Single tertiary academic centre. POPULATION Women older than 18 with primary cervical cancer staged FIGO IB1-IIB enrolled in the prospective Leipzig School MMR study and underwent total mesometrial resection (TMMR) without adjuvant radiation. METHOD We retrospectively analysed 100 consecutive TMMR procedures which were performed for cancer of the uterine cervix and in which the mesureter was preserved (intervention group, 01/2014-06/2017). We compared this group with the previous 100 consecutive TMMRs, which were performed before the introduction of mesureteral preservation (control group, 09/2010-01/2014). MAIN OUTCOME MEASURES The occurrence of urological and specifically ureteral complications. RESULTS Mesureteral preservation was feasible and was associated with a significant decrease in ureteral complications (11% without mesureteral preservation versus 3% with mesureteral preservation, P = 0.

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