Plasma Adrenomedullin level in Egyptian children and Adolescents with type 1 diabetes mellitus: relationship to microvascular complications

<p>Abstract</p> <p>Background</p> <p>Adrenomedullin (AM) is known to be elevated in different clinical situations including diabetes mellitus (DM), but its potential role in the pathogenesis of vascular complications in diabetic children and adolescents is to be clarified. Hence, the study aimed at assessment of plasma adrenomedullin levels in children and adolescents with type 1 DM and correlation of these levels with metabolic control and diabetic microvascular complications (MVC).</p> <p>Methods</p> <p>The study was performed in the Diabetes Specialized Clinic, Children's Hospital of Ain Shams University in Cairo, Egypt. It included 55 diabetic children and adolescents (mean age 13.93 ± 3.15 years) who were subdivided into 40 with no MVC and 15 with MVC. Thirty healthy subjects, age-and sex- matched were included as control group (mean age 12.83 ± 2.82 years). Patients and controls were assessed for glycosylated hemoglobin (HbA1c) and plasma adrenomedullin assay using ELISA technique.</p> <p>Results</p> <p>Mean plasma AM levels were significantly increased in patients with and without MVC compared to control group, (110.6 pg/mL, 60.25 pg/mL and 39.2 pg/mL respectively) (P < 0.01) with higher levels in those with MVC (P < 0.05). Plasma AM levels were positively correlated with both duration of diabetes (ρ = 0.703, P < 0.001) and glycemic control (HbA1c) (ρ = 0.453, P < 0.001).</p> <p>Conclusion</p> <p>Higher plasma AM levels in diabetics particularly in those with MVC & its correlation with diabetes duration and metabolic control may reflect the role of AM in diabetic vasculopathy in the pediatric age group.</p

High dose intravenous immunoglobulin in Rh and ABO hemolytic disease of Egyptian neonates

Background: Despite advances made in the use of phototherapy, and in order to avoid sequelae of kernicterus, the treatment of hyperbilirubinemia may require one or several exchange transfusions, an invasive therapy which is not without risk. Intravenous immune globulin treatment in isoimmune hyperbilirubinemia has been shown to be effective, but the response to treatment is variable. Objective: To evaluate effectiveness of high dose Intravenous immune globulin (HD-IVIG) in reducing the need for exchange transfusion, duration of phototherapy and/or hospitalization in neonates with isoimmune hemolytic disease due to Rh or ABO incompatibility. Methods: The study included 116 direct Coombs' test positive neonates delivered at Gynecology and Obstetrics Hospital of Ain Shams University, Cairo, Egypt. They were randomly assigned to receive phototherapy with HD-IVIG in a single dose of 1 gm/kg (60 neonates, intervention group) or phototherapy (56 neonates, control group). Results: Nine neonates in the intervention group (15%) and 23 (41%) in the control group required single exchange transfusion (p&lt; 0.001). Multiple exchange transfusion was indicated in 15 neonates (26.8%) in the control group versus none in the intervention group (p&lt; 0.001). Compared with control group, neonates in the intervention group had shorter mean duration of intensive phototherapy (9.97 versus 35.5 hours, p&lt;0.001) and hospital stay (27.9 versus 103.5 hours, p&lt; 0.001). No adverse effects of HD-IVIG administration were noted. Conclusion: HD-IVIG effectively reduced the requirement for exchange transfusion and duration of phototherapy and hospitalization in isoimmune hemolytic disease of the newborn.Keywords: Hemolytic disease of newborn; hyperbilirubinemia; exchange transfusion; high dose intravenous immunoglobulin

The COVID-19 Pandemic Affects Seasonality, With Increasing Cases of New-Onset Type 1 Diabetes in Children, From the Worldwide SWEET Registry

Objective: To analyze whether the coronavirus disease 2019 (COVID-19) pandemic increased the number of cases or impacted seasonality of new-onset type 1 diabetes (T1D) in large pediatric diabetes centers globally. Research design and methods: We analyzed data on 17,280 cases of T1D diagnosed during 2018-2021 from 92 worldwide centers participating in the SWEET registry using hierarchic linear regression models. Results: The average number of new-onset T1D cases per center adjusted for the total number of patients treated at the center per year and stratified by age-groups increased from 11.2 (95% CI 10.1-12.2) in 2018 to 21.7 (20.6-22.8) in 2021 for the youngest age-group, <6 years; from 13.1 (12.2-14.0) in 2018 to 26.7 (25.7-27.7) in 2021 for children ages 6 to <12 years; and from 12.2 (11.5-12.9) to 24.7 (24.0-25.5) for adolescents ages 12-18 years (all P < 0.001). These increases remained within the expected increase with the 95% CI of the regression line. However, in Europe and North America following the lockdown early in 2020, the typical seasonality of more cases during winter season was delayed, with a peak during the summer and autumn months. While the seasonal pattern in Europe returned to prepandemic times in 2021, this was not the case in North America. Compared with 2018-2019 (HbA1c 7.7%), higher average HbA1c levels (2020, 8.1%; 2021, 8.6%; P < 0.001) were present within the first year of T1D during the pandemic. Conclusions: The slope of the rise in pediatric new-onset T1D in SWEET centers remained unchanged during the COVID-19 pandemic, but a change in the seasonality at onset became apparent.info:eu-repo/semantics/publishedVersio

MYC functions are specific in biological subtypes of breast cancer and confers resistance to endocrine therapy in luminal tumours.

BACKGROUND: MYC is amplified in approximately 15% of breast cancers (BCs) and is associated with poor outcome. c-MYC protein is multi-faceted and participates in many aspects of cellular function and is linked with therapeutic response in BCs. We hypothesised that the functional role of c-MYC differs between molecular subtypes of BCs. METHODS: We therefore investigated the correlation between c-MYC protein expression and other proteins involved in different cellular functions together with clinicopathological parameters, patients' outcome and treatments in a large early-stage molecularly characterised series of primary invasive BCs (n=1106) using immunohistochemistry. The METABRIC BC cohort (n=1980) was evaluated for MYC mRNA expression and a systems biology approach utilised to identify genes associated with MYC in the different BC molecular subtypes. RESULTS: High MYC and c-MYC expression was significantly associated with poor prognostic factors, including grade and basal-like BCs. In luminal A tumours, c-MYC was associated with ATM (P=0.005), Cyclin B1 (P=0.002), PIK3CA (P=0.009) and Ki67 (P<0.001). In contrast, in basal-like tumours, c-MYC showed positive association with Cyclin E (P=0.003) and p16 (P=0.042) expression only. c-MYC was an independent predictor of a shorter distant metastases-free survival in luminal A LN+ tumours treated with endocrine therapy (ET; P=0.013). In luminal tumours treated with ET, MYC mRNA expression was associated with BC-specific survival (P=0.001). In ER-positive tumours, MYC was associated with expression of translational genes while in ER-negative tumours it was associated with upregulation of glucose metabolism genes. CONCLUSIONS: c-MYC function is associated with specific molecular subtypes of BCs and its overexpression confers resistance to ET. The diverse mechanisms of c-MYC function in the different molecular classes of BCs warrants further investigation particularly as potential therapeutic targets

Mediator complex (MED) 7: a biomarker associated with good prognosis in invasive breast cancer, especially ER+ luminal subtypes

Background: Mediator complex (MED) proteins have a key role in transcriptional regulation, some interacting with the oestrogen receptor (ER). Interrogation of the METABRIC cohort suggested that MED7 may regulate lymphovascular invasion (LVI). Thus MED7 expression was assessed in large breast cancer (BC) cohorts to determine clinicopathological significance. Methods: MED7 gene expression was investigated in the METABRIC cohort (n = 1980) and externally validated using bc-GenExMiner v4.0. Immunohistochemical expression was assessed in the Nottingham primary BC series (n = 1280). Associations with clinicopathological variables and patient outcome were evaluated. Results: High MED7 mRNA and protein expression was associated with good prognostic factors: low grade, smaller tumour size, good NPI, positive hormone receptor status (p < 0.001), and negative LVI (p = 0.04) status. Higher MED7 protein expression was associated with improved BC-specific survival within the whole cohort and ER+/luminal subgroup. Pooled MED7 gene expression data in the external validation cohort confirmed association with better survival, corroborating with the protein expression. On multivariate analysis, MED7 protein was independently predictive of longer BC-specific survival in the whole cohort and Luminal A subtype (p < 0.001). Conclusions: MED7 is an important prognostic marker in BC, particularly in ER+luminal subtypes, associated with improved survival and warrants future functional analysis

Novel immunohistochemistry-based signatures to predict metastatic site of triple-negative breast cancers

Background: Although distant metastasis (DM) in breast cancer (BC) is the most lethal form of recurrence and the most commonunderlying cause of cancer related deaths, the outcome following the development of DM is related to the site of metastasis.Triple negative BC (TNBC) is an aggressive form of BC characterised by early recurrences and high mortality. Athough multiplevariables can be used to predict the risk of metastasis, few markers can predict the specific site of metastasis. This study aimed atidentifying a biomarker signature to predict particular sites of DM in TNBC.Methods: A clinically annotated series of 322 TNBC were immunohistochemically stained with 133 biomarkers relevant to BC, todevelop multibiomarker models for predicting metastasis to the bone, liver, lung and brain. Patients who experienced metastasisto each site were compared with those who did not, by gradually filtering the biomarker set via a two-tailed t-test and Coxunivariate analyses. Biomarker combinations were finally ranked based on statistical significance, and evaluated in multivariableanalyses.Results: Our final models were able to stratify TNBC patients into high risk groups that showed over 5, 6, 7 and 8 times higher riskof developing metastasis to the bone, liver, lung and brain, respectively, than low-risk subgroups. These models for predictingsite-specific metastasis retained significance following adjustment for tumour size, patient age and chemotherapy status.Conclusions: Our novel IHC-based biomarkers signatures, when assessed in primary TNBC tumours, enable prediction of specificsites of metastasis, and potentially unravel biomarkers previously unknown in site tropism

Impact of diabetes mellitus and its control on pulmonary functions and cardiopulmonary exercise tests

Background: Diabetes mellitus (DM) is a leading public health problem with increasing incidence and long term complications. These complications are mainly a consequence of macrovascular and microvascular damages of the target organs. The presence of an extensive microvascular circulation and abundant connective tissue in the lungs, raises the possibility that lung tissue may be a target organ in diabetic patients. Objectives: To study the impact of DM and its control on pulmonary function and cardiopulmonary exercise tests. Methodology: This is a cross-sectional study carried out on diabetic mellitus patients (type I or type II n = 30) group II divided into two subgroups (group IIA) controlled diabetes (HbA1c < 7%) (n = 15) and uncontrolled diabetes (group IIB) (HbA1c ⩾ 7% (n = 15). The control group (group I) was non diabetic healthy (n = 15). The following pulmonary function parameters were recorded: Forced Expiratory Volume in the first second (FEV1), Forced Expiratory Volume percent (FEV1/FVC %), Forced Expiratory Flow 25–75% (FEF 25–75%), peak expiratory flow (PEF) and MVV. Also maximum aerobic power (VO2 max) using cardiopulmonary exercise test was measured. Results: The mean FEV1, FEV1/FVC%, PEF, FEF 25–75%, MVV and VO2 max values were low in diabetics (p value <0.05) compared to non-diabetics. Also, uncontrolled diabetics show a greater decrease in these values than controlled diabetics. Conclusion: The findings of the present study suggest that, the lung is a target organ for damage in DM and diabetics show a decrease in PFTs and VO2 max compared to non-diabetics. And this deterioration is exaggerated in uncontrolled diabetics