Early age at menarche and the risk of gestational diabetes mellitus: a cohort study.

PURPOSE: To evaluate whether there is an association between age at menarche (AAM) and the risk of gestational diabetes mellitus (GDM). METHODS: A retrospective cohort study was conducted, including 5390 pregnant women who were screened for GDM at Alexandra Hospital in Athens, Greece over a 15-year period (2000-2014). Maternal age, pre-pregnancy body mass index (BMI), height, family history of type 2 diabetes mellitus, parity, educational and smoking status, and AAM were recorded. The results were expressed as odds ratios (OR) with a 95% confidence interval (95% CI). RESULTS: Pregnant women with GDM experienced earlier menarche compared to normoglycemic women (12.9 ± 1.5 vs 13.1 ± 1.6, p < 0.001, respectively). The OR for a woman with AAM <12 years to develop GDM was 1.08 (95% CI 1.03-1.14), while the OR to be obese was 1.70 (95% CI 1.50-1.90). The multivariate logistic regression analysis showed that AAM is a risk factor for GDM. However, that effect was lost after adjusting for BMI. CONCLUSION: Early AAM may be associated with an increased risk of GDM. Therefore, it can be used to identify high-risk women and implement preconception interventions for GDM prevention. Future studies should be conducted to confirm these findings.

Prognostic factors in high-grade pediatric osteosarcoma among children and young adults: Greek Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) data along with a systematic review and meta-analysis.

The 5-year overall survival of children and adolescents with osteosarcoma has been in plateau during the last 30 years. The present systematic review (1976-2023) and meta-analysis aimed to explore factors implicated in the prognosis of children and young adults with high-grade osteosarcoma. Original studies including patients ≤30 years and the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) data (2010-2021) referred to children ≤14 years were analysed. Individual participant data (IPD) and summary estimates were used to assess the n-year survival rates, as well as the association of risk factors with overall survival (OS) and event-free survival (EFS). IPD and the n-year survival rates were pooled using Kaplan-Meier and Cox regression models, and random effects models, respectively. Data from 8412 patients, including 46 publications, NARECHEM-ST data, and 277 IPD from 10 studies were analysed. The summary 5-year OS rate was 64% [95% confidence interval (95%CI): 62%-66%, 37 studies, 6661 patients] and the EFS was 52% (95%CI: 49%-56%, 30 studies, 5010 patients). The survival rates generally differed in the pre-specified subgroups. Limb-salvage surgery showed a higher 5-year OS rate (69%) versus amputation (47%). Good responders had higher OS rates at 3 years (94%) and 5 years (81%), compared to poor responders at 3 years (66%), and 5 years (56%). Patients with metastatic disease had a higher risk of death [Hazard Ratio (HR): 3.60, 95%CI: 2.52, 5.15, 11 studies]. Sex did not have an impact on EFS (HR females/males: 0.90, 95%CI: 0.54, 1.48, 3 studies), whereas age>18 years seems to adversely affect EFS (HR 18+/<10 years: 1.36, 95%CI: 1.09, 1.86, 3 studies). Our results summarize the collective experience on prognostic factors of high-grade osteosarcoma among children and young adults. Poor response to neoadjuvant chemotherapy and metastatic disease at diagnosis were confirmed as primary risk factors of poor outcome. International collaboration of osteosarcoma study groups is essential to improve survival.

Menopausal Hormone Therapy in Women with Type 2 Diabetes Mellitus: An Updated Review.

Menopause is accompanied by several metabolic adaptations, which are related to insulin resistance, increased total body fat mass, and central abdominal fat accumulation, predisposing women to type 2 diabetes mellitus (T2DM) development. Metabolic syndrome has a high prevalence in postmenopausal women, indicating the loss of estrogen protection on metabolic and cardiovascular health. Moreover, earlier age at menopause has been related to increased risk of T2DM. Menopausal hormone therapy (MHT) has favorable results in glucose metabolism. Indeed, it reduces the risk of T2DM in women without this condition and improves glycemic control in women with T2DM. Before MHT initiation in women with clinical indications, it is imperative to assess their cardiovascular disease (CVD) risk, using official electronic algorithms for score calculation. The latter will determine regimen, dose, and administration route of MHT. Oral estrogens are preferable in women with low CVD risk, while transdermal administration is indicated in those with moderate and high CVD risk, as the risk of stroke and venous thromboembolism (VTE) is increased with oral administration. Oral 17ß-estradiol is usually preferred in women with T2DM, as this route has more beneficial effects on glucose metabolism. Oral estrogens are also suggested in perimenopausal or recently postmenopausal women with low CVD risk. Although oral estrogens have favorable effects when indicated, the risk of VTE or stroke should always be considered. Micronized progesterone, dydrogesterone, and transdermal norethisterone are the progestogens used in postmenopausal women with T2DM and intact uterus. MHT should not be initiated in women > 60 years or > 10 years in menopause, as there is an increased thromboembolic risk in women with established atherosclerosis and no additional cardiovascular benefit in women without atherosclerosis. In conclusion, MHT administration in postmenopausal women with T2DM can be safe and effective as long as the therapeutic regimen has been properly selected according to their cardiovascular, metabolic, and fracture risk.

Sleep disorders during pregnancy: an underestimated risk factor for gestational diabetes mellitus.

Sleep disorders are highly prevalent during pregnancy and significantly affect women's health and quality of life. Gestational diabetes mellitus (GDM) is one of the most common metabolic complications during pregnancy and constitutes a significant risk factor for both mother and fetus in the short and the long term. While the association between sleep disorders and type 2 diabetes mellitus (T2DM) is indisputable, it is not clear whether there is a link between sleep disorders and GDM. The aim of this article was to investigate the association between sleep disorders and GDM and whether the treatment of sleep disorders may prevent GDM development. Insomnia, obstructive sleep apnea (OSA), restless legs syndrome (RLS), and narcolepsy were the most common sleep disorders identified during pregnancy and were related to poor sleep quality and short or prolonged sleep duration. They were all associated with an increased risk of GDM. The ideal sleep duration for pregnant women was determined at 8-9 h daily. In conclusion, sleep disorders constitute a risk factor for GDM. It is imperative that prospective studies be conducted to evaluate the effect of the early management of sleep disorders on GDM manifestation and control. Healthcare providers should highlight the importance of sufficient sleep to reinforce pregnancy outcomes.

Efficacy and safety of metformin during pregnancy: an update.

During the last decades, gestational diabetes mellitus (GDM) prevalence has been on the rise. While insulin remains the gold standard treatment for GDM, metformin use during pregnancy is controversial. This review aimed to comprehensively assess the available data on the efficacy and safety of metformin during pregnancy, both for the mother and the offspring. Metformin has been validated for maternal efficacy and safety, achieving comparable glycemic control with insulin. Additionally, it reduces maternal weight gain and possibly the occurrence of hypertensive disorders. During the early neonatal period, metformin administration does not increase the risk of congenital anomalies or other major adverse effects, including lower APGAR score at 5 min, neonatal intensive care unit admissions, and respiratory distress syndrome. Several studies have demonstrated a reduction in neonatal hypoglycemia. Metformin has been associated with an increase in preterm births and lower birth weight, although this effect is controversial and depends on the indication for which it was administered. Evidence indicates possible altered fetal programming and predisposition to childhood obesity and metabolic syndrome during adulthood after use of metformin in pregnancy. With critical questions still requiring a final verdict, ongoing research on the field must be conducted.

Smoking during pregnancy and gestational diabetes mellitus: a systematic review and meta-analysis.

PURPOSE: To investigate whether maternal cigarette smoking during pregnancy is a risk factor for developing GDM. METHODS: MEDLINE, Scopus, CENTRAL and Google Scholar databases were searched from inception to December 2022 to identify eligible original articles. A systematic review and meta-analysis (weighted data, random-effects model) were performed. The primary outcome was the development of GDM in pregnant women. The results were expressed as odds ratios (OR) with 95% confidence interval (CI) (inverse variance method). Subgroup analysis was planned according to the maternal smoking status and GDM diagnostic criteria. Statistical heterogeneity was checked with the Chi-squared (Chi2) test and the I2 index was used to quantify it. The studies were evaluated for publication bias. RESULTS: Thirty-five studies, including 23,849,696 pregnant women, met the inclusion criteria. The pooled OR of smoking during pregnancy compared with non-smoking (never smokers and former smokers) was 1.06 (95% CI 0.95-1.19), p = 0.30; I2 = 90%; Chi2 = 344; df=34; p < 0.001. Subgroup analysis was performed according to the two-step Carpenter-Coustan diagnostic criteria, due to the high heterogeneity among the other applied methods. The pooled OR for the Carpenter-Coustan subgroup was 1.19 (95% CI 0.95-1.49), p = 0.12; I2 = 63%; Chi2 = 27; df=10; p < 0.002. Further subgroup analysis according to maternal smoking status was not performed due to missing data. CONCLUSION: There is no evidence to support an association between maternal cigarette smoking during pregnancy and the risk for GDM. Universally accepted diagnostic criteria for GDM must be adopted to reduce heterogeneity and clarify the association between smoking and GDM.

Safety and efficacy of insulin detemir versus NPH in the treatment of diabetes during pregnancy: Systematic review and meta-analysis of randomized controlled trials.

AIMS: To compare the safety and efficacy of insulin detemir versus neutral protamine Hagedorn (NPH) in pregnant women with diabetes. METHODS: MEDLINE, CENTRAL, Google Scholar databases, and ClinicalTrials.gov registry were searched from inception to December 2021 to identify randomized controlled trials (RCTs) concerning adult women with singleton pregnancies, gestational or pregestational diabetes, and the need for insulin therapy. A systematic review and a meta-analysis (weighted data, random-effects model) were performed. Continuous outcomes were expressed as mean difference (MD) with 95% confidence interval (CI) (inverse variance method); dichotomous outcomes were expressed as risk ratio (RR) with 95% CI (Mantel-Haenszel method). Heterogeneity was quantified using the I2 index. RESULTS: Five RCTs involving 1450 participants met the inclusion criteria. Outcomes that showed significant results in favor of insulin detemir over NPH were maternal hypoglycemic events (RR 0.64, 95% CI 0.48-0.86, p = 0.003; I2 = 0%) and gestational age at delivery (MD 0.48, 95% CI 0.16-0.81, p = 0.003; I2 = 0%). CONCLUSIONS: Insulin detemir was associated with less maternal hypoglycemic events and decreased risk for prematurity compared with NPH insulin. More research should be conducted to reach a safe conclusion about the optimal insulin regimen for women with diabetes in pregnancy.

G6PD deficiency and Harilaou variant in a newborn: Intrauterine haemolysis and meconium aspiration syndrome.

G6PD deficiency is one of the most commonly inherited enzymopathies with a hallmark of an X-linked pattern. G6PD has more than 300 unique variants with different enzyme activity. The G6PD Mediterranean variant is prevalent in Greece and associated with asymptomatic patients who may experience haemolysis under specific circumstances. G6PD Harilaou is a new variant that was first described in Greece in an eight-year-old boy who suffered chronic haemolysis demanding multiple transfusions. We present a new case of the G6PD Harilaou variant in a Greek male neonate who suffered severe intrauterine haemolysis and passed away 39 hours after birth. To our knowledge, it is the second reported G6PD Harilaou case.

Can we predict the behavior of the scoliotic curve after bracing in adolescent idiopathic scoliosis? Τhe prognostic value of apical vertebra rotation.

PURPOSE: We aimed to recognize radiographic and clinical prognostic factors of scoliotic curve behaviour after bracing. METHODS: Our prognostic study was based on the 25 years outcomes of a Boston braced AIS cohort between 1978 and 1993 that were previously reported. All patients were followed-up during bracing, at short term and 25 years post-bracing. We evaluated the impact of socio-demographic, clinical and radiological parameters on the loss of curve correction after bracing. RESULTS: Seventy-seven patients were reevaluated at 25 years post-brace. The mean scoliotic curve was significantly increased after bracing until the 25 years follow-up (p < 0.001). The mean loss of curve correction between the end of bracing and long-term follow-up was independent on the curve type, apical vertebra, premenarcheal status at bracing, time and duration of bracing, Cobb angle before or after bracing. The mean apical vertebral rotation after bracing was significantly related to the loss of curve correction (Spearman ρ = 0.2, p = 0.049). Apical vertebral rotation (Perdriolle method) greater than 20° post-bracing had a three times higher chance of progression > 5° compared with lesser apical vertebral rotation (OR 3.071, CI 0.99-9.51). The rotation of the apical vertebra, type and magnitude of the scoliotic curve after bracing explained 27.4% of the variance in the loss of curve correction post-bracing (R square = 0.274, p < 0.001). CONCLUSION: A scoliotic curve is expected to lose some correction after bracing. The apical vertebral rotation post-bracing mainly affected the long-term curve behaviour. Adolescents with apical vertebral rotation greater than 20° after bracing may need further attention. LEVEL OF EVIDENCE: Prognostic study, Level II.

Pulmonary Infectious Complications in Children with Hematologic Malignancies and Chemotherapy-Induced Neutropenia.

Infections frequently complicate the treatment course in children with hematologic malignancies undergoing chemotherapy. Febrile neutropenia (FN) remains a major cause of hospital admissions in this population, and respiratory tract is often proven to be the site of infection even without respiratory signs and symptoms. Clinical presentation may be subtle due to impaired inflammatory response. Common respiratory viruses and bacteria are widely identified in these patients, while fungi and, less commonly, bacteria are the causative agents in more severe cases. A detailed history, thorough clinical and basic laboratory examination along with a chest radiograph are the first steps in the evaluation of a child presenting signs of a pulmonary infection. After stratifying patient's risk, prompt initiation of the appropriate empirical antimicrobial treatment is crucial and efficient for the majority of the patients. High-risk children should be treated with an intravenous antipseudomonal beta lactam agent, unless there is suspicion of multi-drug resistance when an antibiotic combination should be used. In unresponsive cases, more invasive procedures, including bronchoalveolar lavage (BAL), computed tomography (CT)-guided fine-needle aspiration or open lung biopsy (OLB), are recommended. Overall mortality rate can reach 20% with higher rates seen in cases unresponsive to initial therapy and those under mechanical ventilation.

Successful treatment of rhinoorbital mucormycosis due to Rhizopus arrhizus with liposomal amphotericin B, posaconazole and surgical debridement in a child with neuroblastoma.

Mucormycosis is a rare but potentially mortal opportunistic infection caused by Mucorales. We present a case of rhinoorbital mucormycosis in an 11-year old male with neuroblastoma successfully treated with aggressive surgical debridement and antifungal combination of liposomal amphotericin B and posaconazole. Our patient developed signs of paranasal sinus infection and culture of fine needle biopsy grew Rhizopus arrhizus. Prompt treatment and drastic surgical resection led to complete clinical and radiological recovery without evidence of mucormycosis relapse.