Can we Predict Incipient Diabetes Mellitus in Patients with Transfusion Dependent ß-Thalassemia (ß-TDT) Referred with a History of Prediabetes?

Background: Prediabetes and diabetes mellitus (DM) are complications in adult patients with transfusion-dependent ß-thalassemia (ß-TDT), with their incidence increasing with age. Objective: This retrospective observational study describes the glycemic trajectories and evaluates predictive indices of ß-cell function and insulin sensitivity/resistance in ß-TDT patients with prediabetes, both in a steady state and during 3-h oral glucose tolerance test (OGTT), in order to identify patients at high risk for incipient diabetes. Setting: The study was mainly conducted at the Pediatric and Adolescent Outpatient Clinic, Quisisana Hospital, Ferrara (Italy), in collaboration with thalassemia referring centers across Italy. Patients: The study included 11 ß-TDT (aged 15.11-31.10 years) with prediabetes. Methods: The ADA criteria for the diagnosis of glucose dysregulation were adopted. Investigations included evaluating plasma glucose levels and insulin secretion, analyzing glycemic trajectories and indices of ß-cell function, and insulin sensitivity/resistance assessed in steady state and during OGTT. Results: The duration of progression from prediabetes to DM, expressed in years, showed a positive direct correlation with corrected insulin response (CIR-30 = r: 0.7606, P: 0.0065), insulinogenic index (IGI 0-120 = r: 0.6121, P:0.045), oral disposition index (oDI = r: 0.7119, P:0.013), insulin growth factor-1 (IGF-1= r: 0.6246, P: 0.039) and an inverse linear correlation with serum ferritin (SF = r: -0.7197, P: 0.012). The number of patients with 1-hour post-load PG value ≥ 155 mg/dL ( ≥ 8.6 mmol/L) was at -4 years: 4/9 (44.4%); -3 years: 8/9 (88.8%); - 2 years: 7/10 (70 %) and at -1 year: 11/11 (100%) (PG range:162-217 mg/dL). Conclusions: A progressive increase in 1-hour PG in response to OGTT is associated with progressive ß-cell failure, peripheral resistance to insulin action, and reduced oDI and may be considered a relevant marker for incipient DM in ß-TDT patients with prediabetes.

Saccharomyces cerevisiae supplemented diets mitigate the effects of waterborne cadmium toxicity on gilthead seabream (Sparus aurata L.): growth performance, haemato-biochemical, stress biomarkers, and histopathological investigations.

Yeast, Saccharomyces cerevisiae, has been utilized as a probiotic in aqua-feeds to promote growth and alleviate the stress in aquatic animals. On the other hand, cadmium (Cd) toxicity causes serious retardation of growth and welfare status of aquatic animals. The present study was conducted to evaluate the protective role of dietary yeast in mitigating the waterborne Cd toxicity effects on the growth, haemato-biochemical, stress biomarkers, and histopathological investigations of gilthead seabream (Sparus aurata L.). In a 3 × 3 factorial design, the acclimated fish (20-24 g) were randomly distributed into nine treatments in triplicates where they were fed on 0.0% (control), 0.5%, and 1.0% of yeast along with exposure to 0.0, 1.0, and 2.0 mg Cd/L for 60 days. All growth parameters and mRNA expressions of IGF-1 and GH genes as well as haematological parameters were markedly increased with the increase of dietary yeast levels; meanwhile these variables were significantly retarded with Cd exposure. Contradictory effects on the above-mentioned variables were observed with Cd toxicity. In contrast, blood cortisol, glucose, total cholesterol, and triglyceride, lactate dehydrogenase, alanine transaminase, aspartate transaminase, alkaline phosphatase, in addition to DNA fragments % were noticeably increased with Cd toxicity especially at the treatment of 2.0 mg Cd/L, while decreasing with increasing dietary yeast levels. Compared with the control fish group, Cd concentrations in the gill, liver, and muscle tissues of gilthead seabream were higher in Cd-exposed treatments, especially at the treatment of 2.0 mg Cd/L. Deposition of Cd in fish liver was higher than that in gill tissues but lowest Cd residue was observed in muscle tissues. No significant changes in Cd residues in fish organs were observed in yeast-fed fish with no Cd exposure. The Cd exposure negatively affected histological status of gill, liver, and kidney tissues of S. aurata; while feeding Cd-exposed fish on yeast diets lowered the Cd residues in fish organs and recovered the adverse effects of Cd toxicity. Hence, this study recommends the addition of bakery yeast (1.0%) to fish diets to improve the performance, overall welfare, and histopathological status of gilthead seabream, S. aurata.

A prospective guide for clinical implementation of selected OGTT- derived surrogate indices for the evaluation of ß- cell function and insulin sensitivity in patients with transfusion-dependent ß- thalassaemia.

The gold standard for the measurement of insulin secretion is the hyperglycemic clamp and for insulin sensitivity the hyperinsulinemic euglycemic clamp, respectively. A number of surrogate indices, derived from plasma glucose and insulin levels at a fasting state or after oral glucose load, have been proposed to estimate ß-cell response, and the ability of ß-cells to compensate for changes of insulin sensitivity by modulating insulin secretion (disposition index). Starting from the current recommendations for the annual screening of glucose dysregulation in patients with transfusion dependent ß-thalassemia (ß-TDT), this article summarizes the most frequently used indirect indices of insulin secretion and resistance derived from the oral glucose tolerance test (OGTT) and discusses the strengths and weaknesses of selected indices and the basic concepts underlying each method for the appropriate evaluation of glucose regulation. Basal indices for ß-cell function and insulin sensitivity, albeit simple and cheap, have limited usefulness due to a high coefficient variation and the lack of data about response to glucose load. Therefore, measurement of indices during an OGTT, despite being costly and time-consuming, is suggested since it can detect, even subtle, dynamic changes in insulin secretion and glucose handling. In patients with ß-TDT, the indices derived from OGTT may offer an additional factor to evaluate the efficiency of iron chelation therapy and detect patients who may need intensification of iron chelation therapy and/or pharmacological intervention.

Long-term health consequences of central precocious/early puberty (CPP) and treatment with Gn-RH analogue: a short update.

BACKGROUND: The relationship between precocious or early puberty and its treatment has received significant research attention, yielding diverse outcomes. This short review aims to comprehensively analyze and summarize research articles to elucidate the potential link between precocious or early pubertal onset (CPP) and crucial health factors. METHODS: We conducted a systematic review of studies published from -January 2000 to March 2023, sourced from databases of Medline, PubMed, Google Scholar and Web of Science. We assessed the relationship between CPP and final adult height (FHt), bone health, reproductive function, body mass index, metabolic and cardiovascular abnormalities, and increased cancer risk. RESULTS: Upon reviewing and analyzing selected studies, the following key findings emerged: (a) treating CPP in girls before age 6-7 and in boys before age 9 improves FHt; (b) bone mineral density (BMD) decreases during GnRHa treatment but normalizes afterward, with no lasting effects on peak bone mass during puberty; (c) GnRH treatment does not negatively affect menstrual cycles; however, untreated CPP increases the risk of premature or early-onset menopause; (d) the incidence of PCOS/hyperandrogenemia may be slightly elevated in women with a history of CPP, but overall reproductive function remains largely unaffected; (e) earlier thelarche and menarche may enhance susceptibility to breast carcinogenesis; (f) CPP contributes to an increased risk of obesity and type 2 diabetes in both genders; (g) early menarche may slightly increase the risk of coronary heart disease and ischemic strokes and (h) early pubertal timing increases the risk of depression and anxiety disorders. CONCLUSION: Monitoring and early diagnosis of these conditions are of paramount importance for successful management.

A retrospective study of glucose homeostasis, insulin secretion, sensitivity/resistance in non- transfusion-dependent ß-thalassemia patients (NTD- ß Thal): reduced ß-cell secretion rather than insulin resistance seems to be the dominant defect for glucose dysregulation (GD).

AIMS: Non-transfusion - dependent ß-thalassemias (NTD-ßThal) can cause iron overload and serious iron-related organ complications as endocrine dysfunction, including glucose dysregulation (GD). PATIENTS AND METHODS: We retrieved data of all NTD- ß Thal patients referred consecutively to a single Outpatient Italian Clinic from October 2010 to April 2023. All patients underwent a standard 3-h oral glucose tolerance test (OGTT) for analysis of glucose homeostasis, insulin secretion and sensitivity/resistance (IR), using conventional surrogate indices derived from the OGTT. The collected data in NTD- ß Thal patients were compared to 20 healthy subjects. RESULTS: Seventeen of 26 (65.3 %) NTD- ß Thal patients (aged: 7.8 -35.1 years) had normal glucose tolerance, 1/26 (3.8 %) had impaired fasting glucose (IFG), 5/26 (19.2 %) impaired glucose tolerance (IGT), 1/26 (3.8%) IFG plus IGT and 2/26 (7.6%) plasma glucose (PG) level ≥155 mg/dL 1-h after glucose load. GD was observed exclusively in young adult patients; none of them had diabetes mellitus (DM). These findings were associated with a low insulinogenic index (IGI) and oral disposition index. HOMA-IR and QUICKI were not significantly different compared to controls. Interestingly, in young adult patients, ISI-Matsuda index was statistically higher compared to the control group, suggesting an increased insulin sensitivity. CONCLUSIONS: This study reported a high prevalence of GD in young adults with NTD- ß Thal. The documented reduction of IGI rather than the presence of IR, indicates reduced insulin secretory capacity as the pathophysiological basis of dysglycemia that may represent a novel investigational path for future studies on the mechanism(s) responsible for GD in NTD- ß Thal patients.

A Multicenter ICET-A Study on Age at Menarche and Menstrual Cycles in Patients with Transfusion-Dependent Thalassemia (TDT) who Started Early Chelation Therapy with Different Chelating Agents.

Introduction: To evaluate the effect of early chelation therapy (≤ 3 years) with a variety of chelating agents on age at menarche and menstrual characteristics in patients with transfusion-dependent thalassemia (TDT). Design: A retrospective multicenter study promoted by the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A). Setting: Eight of 13 International Thalassemia Centers (61.5%) in the ICET-A Network participated. Patients: Fifty-seven female TDT patients, aged 11 to 26 years, and with early iron chelation therapy, were eligible for the present study. They were enrolled from one center from Iran (33 patients), 3 centers from Bulgaria (9), 1 from Greece (8), one from Oman (4), 1 from Cyprus (2), and 1 from Italy (1). Seven patients were excluded, four still prepubertal (age 12-14 years) and 3 with primary amenorrhea. Therefore 50 patients were finally enrolled. Results: All fifty TDT patients developed spontaneous menarche at a mean age of 14.2 ± 2.24 years (range 9 - 20). A significant positive correlation was observed between age at menarche and serum ferritin levels (r: 0. 41, p=0.005). Regular menstrual cycles were reported from 32 (64%) patients, of whom 28 (83.3%) get menarche at age ≤ 14 years. Complications were more frequent in patients older than 14 years at menarche and in those with secondary amenorrhea. Conclusions: Age at menarche greater than 14 years was a forerunner of menstrual irregularities and associated complications in 36% of patients despite precocious chelation therapy. The poor adherence to treatment, to be demonstrated in future studies, could explain the finding.

Efficacy and Safety of Remdesivir in Hospitalized Pediatric COVID-19: A Retrospective Case-Controlled Study.

Introduction: While most children experience mild coronavirus disease 2019 (COVID-19) infections, a minority of cases progress to severe or critical illness. This study aimed to assess the efficacy and safety of Remdesivir (RDV) therapy in children with moderate to severe COVID-19, enhancing clinical decision-making and expanding our understanding of antiviral treatments for pediatric patients. Methods: The study included 60 patients, 38 receiving RDV treatment and 22 serving as the control group. Data was collected retrospectively from January 2021 to January 2022 through electronic hospital records. Results: Regarding the main clinical symptoms reported, most patients experienced Upper Respiratory Tract Infections (93.3%), indicating respiratory involvement. Additional symptoms included Central Nervous System (11.7%) and Gastrointestinal (10.0%). Among the 38 cases in the RDV group included in the study, the adverse effects associated with using RDV: Hypoalbuminemia in 19 cases (50.0%) and anemia in 18 cases (47.4%), making them the most common adverse effects. Only one case in the RDV group experienced non-RDV-related death with a different clinical diagnosis. The results showed that RDV treatment was well-tolerated in pediatric patients, with no significant differences in hospital stay and oxygen treatment compared to the control group with P values (0.2, 0.18), respectively. Conclusion: The outcomes indicate that Remdesivir may represent a safe and therapeutic choice for children with coronavirus disease 2019 (COVID-19).

The effects of excess weight on glucose homeostasis in young adult females with ß-thalassemia major (ß-TM): a preliminary retrospective study.

BACKGROUND: With the rising prevalence of obesity worldwide, it is becoming imperative to detect disturbed glucose metabolism as early as possible in order to prevent type 2 diabetes (T2D) development. STUDY DESIGN: The present retrospective observational study aimed to evaluate the relationship between BMI and glucose metabolism, insulin secretion and sensitivity indices, derived from glucose tolerance test (OGTT), in ß -TM female patients who were overweight (BMI 25-29.9 kg/m2) and follow its outcome over time. SUBJECTS AND METHODS: Eleven overweight and 11 females with ideal weight and ß -TM, matched for age, were recruited. OGTT was undertaken and different indices for ß-cell function, insulin sensitivity and insulin secretion were calculated. RESULTS: At first evaluation, 7 of 11 overweight ß -TM patients (63.6%) and 3 of 11 normal weight ß-TM patients (27.2%) had glucose dysregulation (GD) during OGTT. Overweight patients with ß-TM had increased HOMA-IR and QUICKI indices associated with decreased Matsuda WBISI index. The mean ± SD duration of follow-up was 4.5 ± 1.2 years. At last observation, 2/11 overweight patients had developed T2D (18.1%). In patients with normal weight, GD increased from 3/11 (27.2%) to 5/11 (45.4%), but none developed T2DM. The difference between SF at first and last observation (1,220 ± 702 vs.1,091 ± 454 ng/mL; P: 0.61) was not significant. CONCLUSION: Overweight seems to be an additional risk factor for the development of GD in ß-TM patients. This is particularly important in clinical practice, due to the lack of appropriate guidelines dedicated to this group of patients.

Clinical and epidemiological features and therapeutic options of avascular necrosis in patients with sickle cell disease (SCD): a cross-sectional study.

BACKGROUND: Avascular necrosis (AVN) is a debilitating complication in sickle cell disease (SCD) patients, and its management is usually challenging. This study aims to evaluate the clinical and epidemiological features and therapeutic options of AVN in sickle cell patients in Qatar. PATIENTS AND METHODS: A cross-sectional study was conducted on a 49 SCD patients who were diagnosed with AVN and attended the hematology clinic at the National Center for Cancer care & research, Hamad Medical Corporation, Qatar between Jan-2011 to Jan2021.  Results: Forty-nine adult patients with SCD who were diagnosed with AVN were studied. The median age of the study population is 32 years, and the median age at the first AVN diagnosis was 26 years (range: 11-44 yr.). 37 (75.5%) patients suffered from multiple joints AVN while 12(24.5%) had single joint involvement. 31 (63.3%) patients had bilateral hip AVN and 18 (36.7%) had shoulder involvement. 30 patients (61%) were on Hydroxyurea treatment. Based on FICAT and Alert classification of AVN, 57 % of patients had stage III and above at first diagnosis. 20 (40.8%) were managed with a conservative approach, 11 (22.4%) received hyperbaric oxygen with good response, 6(12.2%) underwent hip core decompression and 12(24.5%) underwent hip replacement surgery. CONCLUSION: In SCD patients, AVN occurred more during the 3rd and 4th decades of life. The majority of AVN represented with advanced stage and had multiple joint involvements. We recommend adopting a low threshold of joint imaging for early detection and prevention of further complications.

Effect of Hydroxyurea Therapy on Growth Parameters in Older Children (6-15 Year-Old) with Sickle Cell Disease: Low Dose Versus High Dose.

Growth impairment is a known complication of sickle cell disease (SCD). Few studies explored the potential effects of hydroxyurea (HU) on growth in children with SCD in relation to HU dose and response. This is a prospective study conducted at Sultan Qaboos University Hospital, Oman, and included 91 SCD patients with age below 16 years when started on HU, aiming to explore the potential effect/s of HU on growth parameters of older children with SCD in relation to their clinical improvement and the dose required for this improvement. Weight, height, and body mass index (BMI) were collected at baseline, 6 and 18 months after initiation. Anthropometric data were compared to WHO standards. Initial height and BMI Z scores (HAZ and WAZ) were lower compared to WHO norms. HAZ and WAZ did not change significantly after 6 and 18 months on HU therapy. However, BMI Z-scores improved significantly after 6 and 18 months of follow-up (p value 0.044 and 0.028 respectively). No significant changes were observed in WAZ or HAZ among patients on low dose versus those on high dose. BMI Z score improved significantly after 18 months of low dose group (p = 0.014) but did not change in those on high dose HU. In conclusion, HU therapy did not adversely affect weight and height growth in older children with SCD. BMI Z scores improved at 18 months in patients on low dose but not in those on high dose (p = 0.014).

Retrospective study on long-term effects of hormone replacement therapy (HRT) and iron chelation therapy on glucose homeostasis and insulin secretion in female ß- thalassemia major (ß-TM) patients with acquired hypogonadotropic- hypogonadism (AHH).

BACKGROUND AND AIM: Hypogonadism and abnormalities of glucose homeostasis, resulting from iron-induced pituitary and pancreatic ß-cell dysfunction respectively, are the most frequently reported endocrine abnormalities in patients with ß-thalassemia major (ß-TM), also identified as transfusion-dependent thalassemia (TDT). STUDY DESIGN AND PATIENTS: The aim of the present retrospective study was to evaluate the long-term effects of hormone replacement therapy (HRT) on glucose metabolism and insulin secretion/sensitivity during 3-h oral glucose tolerance test (OGTT) in adolescent and young ß-TM women with acquired hypogonadototropic -hypogonadism (AHH).Twelve hypogonadal ß-TM females with AHH on HRT were followed for 8.26 ± 1.49 years. RESULTS: At baseline, 10 patients (83.3%) had normal OGTT, 1 patient presented with impaired glucose tolerance (IGT) and 1 patient had an isolated PG level of 165 mg/dL at 1-h during OGTT (H-NGT). At last evaluation, 7 patients (58.4 %) had normal OGTT, while 5 patients (41.6%) had abnormal OGTT. Reduced insulin sensitivity and impaired first-phase insulin secretion were also documented. Three of 4 ß-TM patients on treatment with estradiol hemihydrate MX 50 patches plus oral medroxyprogesterone acetate (MPA), associated with a very effective iron chelation therapy, maintained normal glucose tolerance from baseline to last evaluation. Significant adverse events due to HRT or additional endocrine complications were not documented in any cases during the follow-up. CONCLUSION: Deterioration of glycemia (dysglycemia) occurred in 45.4% (5/11) of thalassemic females on long-term HRT. Additional studies are needed to elucidate the validity of our preliminary observations.

Qatar population-specific centile charts of placental weight in 80 722 newborns: relation to maternal age, gestational age, newborn birth weight, and gender, between the 37 th and 42 nd weeks of gestation.

BACKGROUND: Data about placental weight (PW) in relation to birth weight (BW) and gestational age (GA) are lacking in Arabic countries. AIMS OF THE STUDY: (a) to find out the national PW standards for babies born between 37th and 42nd weeks of gestation in male and female babies born in Qatar; (b) to study the relation, if any, between PW and maternal age, gestational age (GA), birth weight (BW), and gender of the newborn. MATERIALS AND METHODS: A National population-based retrospective chart review study was conducted between 1-2016 to 12-2019 (n = 80 722). Data of gestational age (GA) at delivery (in weeks), newborn birth weight (BW), PW, and gender at birth, were collected from singleton babies born between 37 th and 42nd weeks of gestation. RESULTS: The PW ranged from 440 to 860 grams (g) with a mean of 682 ± 96 g. at term for boys and 673 ± 94 g. for girls. The mean BW was 3 036 ± 448 g and BW/PW ratio was 0.203 ± 0.026. The PW continued to increase through 41 weeks' gestation, in boys and girls with a significant decrease at the 42nd week of gestation. PW was significantly correlated with BW (r = 0.596, P: < 0.001) and GA (r = 0.15, P: <0.001) and accounted for 43.4% of the explained variability in birth weight. CONCLUSIONS: PW was a significant predictor of BW with a consistent increase in PW until the 41st week of gestation in boys and girls and a positive correlation with BW and GA.

Nutritional studies in patients with ß-thalassemia major: A short review.

BACKGROUND: Patients with ß-thalassemia major (BTM) had variable prevalence of undernutrition and abnormal body composition.  Methods: We performed an electronic search in PubMed, Scopus, Research gate, and Web of Sciences to evaluate the prevalence of nutritional disorders in patients with BTM worldwide in relation to their body composition and possible etiological factors. In addition, we reviewed the published nutritional intervention studies.  Results: 22 studies on the prevalence of undernutrition (12 countries) and 23 nutritional intervention studies were analyzed.  Undernutrition occurred in a considerable number of patients but varied greatly among different countries (from 5.2% to 70%). The lower middle income (LMI) countries (India, Pakistan, Iran, Egypt) had higher prevalence, while (high -middle and high income (Turkey, Greece, North America, USA, Canada) had lower prevalence.  Even in patients with normal BMI, abnormalities of body composition are common with decreased muscle mass, lean-body mass, and bone mineral density. 65% to 75% of them had lower energy intake with low levels of circulating nutrients, minerals (zinc, selenium, and copper), and vitamins (D, E) versus controls. Increased macro and micronutrient requirements decreased absorption and /or increased loss or excretion are etiologic factors. Undernutrition was associated with short stature and lower quality of life (QOL). High prevalence of endocrinopathies, poor transfusion regimen (tissue hypoxia), improper chelation, and lack of maternal education, represented important risk factors in the production of poor growth in weight and stature. CONCLUSIONS: Timely detection of undernutrition in patients with BTM and proper nutritional intervention could prevent growth delay and comorbidities.

Assessment of glucose homeostasis in young adult female ß-thalassemia major patients (ß-TM) with acquired hypogonadotropic hypogonadism (AHH) never treated with sex steroids compared to eugonadal ß-TM patients with spontaneous menstrual cycles.

BACKGROUND: Acquired ypogonadotropic hypogonadism (AHH) is the most prevalent endocrine complication in thalassemia major (TM). STUDY DESIGN: Considering the detrimental effect of estrogen deficiency on glucose metabolism, the ICET-A Network promoted a retrospective study on the long-term effects of estrogen deficiency on glucose homeostasis in female ß-TM patients with HH without hormonal replacement therapy (HRT). PATIENTS AND METHODS: Seventeen ß-TM patients with AHH (4 had arrested puberty; Tanners' breast stage 2-3), never treated with sex steroids, and 11 eugonadal ß-TM patients with spontaneous menstrual cycles at the time of referral were studied. A standard 3-h OGTT was performed in the morning, after an overnight fast. Six-point plasma glucose and insulin level determinations, indices of insulin secretion and sensitivity, early-phase insulin insulinogenic index (IGI), HOMA-IR and ß-cell function (HOMA-ß), oral disposition index (oDI), glucose and insulin areas under the OGTT curves were evaluated. RESULTS: Abnormal glucose tolerance (AGT) or diabetes was observed in 15 (88.2%) of 17 patients with AHH and 6 (54.5%) of 11 patients with eumenorrhea. The difference between the two groups was statistically significant (P: 0.048). However, the group of eugonadal patients was younger compared to AHH patients (26.5 ± 4.8 years vs. 32.6 ± 6.2 years ; P: 0.010). Advanced age,  severity of iron overload, splenectomy, increased ALT levels and reduced IGF-1 levels were the main clinical and laboratory risk factors for glucose dysregulation observed in ß-TM with AHH compared to eugonadal ß-TM patients with spontaneous menstrual cycles. CONCLUSION: These data further support the indication for an annual assessment of OGTT in patients with ß-TM. We believe that a registry of subjects with hypogonadism is necessary for a better understanding of the long-term consequences of this condition and  refining treatment options.

Insulin-induced lipodystrophy and predisposing factors in children and adolescents with type 1 diabetes mellitus (T1DM) in a tertiary care Egyptian center.

BACKGROUND: Lipodystrophy (LH) is one of the most common complications of subcutaneous insulin injection. Many factors are incriminated in the evolution of LH in children with diabetes type 1 (T1DM). LH may affect insulin absorption in the skin areas involved, resulting in a negative impact on blood glucose levels and glycemic variability. PATIENTS AND METHODS: We calculated and evaluated the prevalence of LH in relation to possible clinical factors associated with the development of LH in a cohort of children (n =115) with T1DM using insulin pens or syringes and we studied possible predisposing factors including their age, duration of T1DM, injection technique, insulin dose/kg, degree of pain perception, and HbA1c level. RESULTS: In our cross-sectional study, 84% of patients were using pens for insulin injection and 52.2 % of them were rotating the site of injection on daily basis. 27 % did not experience pain during an injection while 6 % had the worst hurt. 49.5 % had clinically detectable LH. Those with LH had higher HbA1c levels and more unexplained hypoglycemic events compared to those without LH (P: 0.058). The hypertrophied site was related to the preferred site of injection which was the arms in 71.9 % of the cases. Children who had LH were older with a longer duration of T1DM, rotating sites of injection less frequently, and were more frequently reusing needles compared to children without LH (P: < 0.05). CONCLUSION: Improper insulin injection technique, older age, and longer duration of T1DM were associated with LH. Proper education of patients and their parents must include correct injection techniques, rotating injection sites, and minimal reuse of needles.

Applications of Artificial Intelligence in Thalassemia: A Comprehensive Review.

Thalassemia is an autosomal recessive genetic disorder that affects the beta or alpha subunits of the hemoglobin structure. Thalassemia is classified as a hypochromic microcytic anemia and a definitive diagnosis of thalassemia is made by genetic testing of the alpha and beta genes. Thalassemia carries similar features to the other diseases that lead to microcytic hypochromic anemia, particularly iron deficiency anemia (IDA). Therefore, distinguishing between thalassemia and other causes of microcytic anemia is important to help in the treatment of the patients. Different indices and algorithms are used based on the complete blood count (CBC) parameters to diagnose thalassemia. In this article, we review how effective artificial intelligence is in aiding in the diagnosis and classification of thalassemia.

Comparison Between Pulsed and Continuous Accelerated Corneal Cross-Linking Protocols.

Purpose: To compare between two accelerated corneal cross-linking (A-CXL) protocols in the management of keratoconus (KC) as regard to the extent of corneal treatment. Methods: This retrospective, comparative study included patients having mild to moderate, progressive KC. The study population was divided into two groups; group 1 enrolled 103 eyes of 62 patients who received pulsed light A-CXL (pl-CXL) at a power of 30 mW/cm2 with an irradiation time of 4 minutes, while group 2 comprised 87 eyes of 51 patients who received continuous light A-CXL (cl-CXL) at a power of 12 mW/cm2 with an irradiation time of 10 minutes. Recordings of the central and peripheral demarcation line depths (DD), and the maximum (DDmax) and minimum (DDmin) DD, using anterior segment optical coherence tomography, were compared between the two studied groups one month after the treatment protocol. Treatment stability was also evaluated pre and postoperatively (one year following surgery) by comparing the refractive and keratometric outcomes in both groups. Results: The differences between the preoperative corneal thickness (minimum and central) and the epithelial thickness measurements between both groups were not statistically significant. Although group 1 had slightly larger central DD (223.4 ± 62.3 um), DDmax (240.4 ± 61.8 um), and DDmin (201 ± 54 um) than those of group 2 (221.8 ± 37 um, 229.1 ± 38.4 um, and 212 ± 37.2 um, respectively), the differences between both groups' measurements were not statistically significant. Also, the two groups showed statistically insignificant differences regarding the subjective refraction and the average and maximum keratometry pre and postoperatively, denoting visual, refractive, and keratometric stability in both groups. Conclusion: Longer duration cl-CXL seems to be as effective as pl-CXL regarding both postoperative stability and the extent of corneal tissue penetration by the ultraviolet treatment.

Unilateral breast enlargement in males during adolescence (10-19 years): Review of current literature and personal experience.

Idiopathic unilateral breast enlargement (UBE) in males is a, commonly overlooked, diagnosis of exclusion that requires careful history, meticulous physical examination, and pertinent laboratory studies to exclude the possible pathologic causes. The aims of the present update are to review the current literature on UBE in subjects during adolescent age (10-19 years) in 18 cases, and to report the personal experience in 13 adolescents referred to our unit during the last four decades. In total, our survey and personal experience include 31 UBE cases, 10 of whom (32.2 %) being idiopathic or familial gynecomastia (GM). In 3/31 (9.6%) UBE was due to breast sarcoma/ carcinoma; one patient (11-years old) had a 5-year history of painless lump in the right breast, which increased gradually in size followed by bloody nipple discharge. In the personal cases of 13 adolescents, a moderate to marked UBE was secondary to: treatment with androgens (2 ß-thalassemic patients with hypogonadism), high estrogen/androgen ratio in 2 Klinefelter syndrome patients, peripheral aromatization of androgens in 1 patient with non-classical 21-hydroxylase deficiency (NC-21-OH-D). One patient had subareolar hematoma due to injury. In 2 patients (15,3%) marked UBE was due to cystic lymphangioma (histologically proved). Furthermore, 5 patients were characterized as idiopathic UBE In clinical practice, the persistence of UBE for long period before diagnosis necessitates attention and further evaluation. Underlying causes should be treated, when possible, while surgery can be offered to patients with persistent or atypical signs and/or symptoms of UBE. For the optimal management of this condition, better collaboration between primary care physician and specialists is mandatory.

Longitudinal study of ICET-A on glucose tolerance, insulin sensitivity and ß-cell secretion in eleven ß-thalassemia major patients with mild iron overload.

BACKGROUND: Iron chelation therapy (ICT) is the gold standard for treating patients with iron overload, though its long-term effects are still under evaluation. According to current recommendations regarding  transfusion-dependent  (TD)  ß-thalassemia major (ß-TM) patients, their serum ferritin (SF) levels should be maintained below 1,000 ng/mL and ICT should be discontinued when the levels are <500 ng/mL in two successive tests. Alternatively, the dose of chelator could be considerably reduced to maintain a balance between iron input and output of  frequent transfusions. STUDY DESIGN: Due to the paucity of information on long-term effects of ICT  in ß-TM with low SF levels on glucose homeostasis, the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescence Medicine (ICET-A) promoted a retrospective and an ongoing prospective observational study with the primary aim to address the long-term effects of ICT on glucose tolerance and metabolism (ß-cell function and peripheral insulin sensitivity) in adult ß-TM patients with persistent SF level below 800 ng/mL. PATIENTS AND METHODS: 11 ß-TM patients (mean age: 35.5 ± 5.5 years; SF range: 345-777 ng/mL) with normal glucose tolerance test (OGTT) or abnormal glucose tolerance (AGT) for a median of 5.3(1.1-8.3) years. RESULTS: Abnormal glucose tolerance (AGT) was observed in 7 patients (63.6%) at first observation and ) persisted in 6 patients (54.5%) at last observation. None of them developed diabetes mellitus. AGT was reversed in two patients. One patient with NGT developed early glucose intolerance (1-h PG ≥155 and 2-h PG <140 mg/dL). Three out of  5 patients with isolated impaired glucose tolerance presented a variation of  ATG. Stabilization of low indices for ß-cell function and insulin sensitivity/resistance was observed. One patient developed hypogonadotrophic hypogonadism. Three out of 6 patients with SF below 500 ng/dL had hypercalciuria. CONCLUSION: Despite low SF level, the burden of endocrine complications remains a challenge in ß-TM patients. The ability to keep iron at near "normal" level with acceptable risks of toxicity remains to be established.

Analysis of the Outcomes of the Screen-Time Reduction in Computer Vision Syndrome: A Cohort Comparative Study.

Purpose: To analyze the outcomes of screen-time reduction on the foveal responses that associates computer vision syndrome (CVS) using multifocal electroretinogram (mfERG) examination. Methods: This prospective multicenter cohort comparative study included 49 eyes of 49 medical students divided into two groups. Group A (control group) included 25 eyes with no CVS diagnosis while group B (CVS group) included 24 eyes with CVS diagnosis. All students responded to the valid and reliable CVS-Form 3 (CVS-F3) questionnaire and underwent complete ophthalmic and mfERG examinations twice at the time recruitment in the study and four weeks after strict reduction of the daily screen-hours to ≤1 screen-hour daily to document associated foveal responses. Results: We documented statistically significant reduction in foveal responses in CVS versus control groups in mean mfERG Rings 1, 2, and 5 with Quadrants 1, 2, and 4 (P=<0.0001, 0.0001, 0.0003, 0.001, 0.002, and 0.006, respectively). Following the screen-time reduction, the second mfERG examination revealed significant post-reduction improvements in foveal responses in CVS group particularly in mean mfERG Rings 1, 2, 3, and 5 with Quadrants 1 and 4 (P=<0.0001, <0.0001, 0.0005, 0.02, <0.0001, and 0.04, respectively). Conclusion: This study documented the screen-induced foveal dysfunction that associates CVS using mfERG examination, which revealed remarkable significant improvements in foveal responses in the 4 weeks following strict screen-time reduction. These improvements were also associated with corresponding improvements in the visual performances. We suggest that the potential screen-induced foveal dysfunction outcomes might be reversible with strict screen-time reduction. We also recommend that educational institutional policies should limit online education-hours and redesign the mandated computer system use program to guard against visual sequelae of CVS. Clinical Trials Registration: ClinicalTrials.gov (ID: NCT04405648).