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.

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.

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.

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.

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.

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.

Etiology of Pediatric Uveitis in a Tertiary Pediatric Eye Hospital in Egypt.

PURPOSE: To report the causes of childhood-onset uveitis in a tertiary pediatric ophthalmology hospital in Egypt. METHODS: Retrospective study of the medical records of all uveitis patients following up at a tertiary pediatric ophthalmology hospital in Egypt from January 2017 to December 2020. RESULTS: The present study included 388 patients. The most common anatomical category was intermediate uveitis (30.4%), and around half of these children had pars planitis. This was followed by panuveitis (25.5%), posterior uveitis (23.5%), and anterior uveitis (20.6%), in decreasing frequency. Juvenile idiopathic arthritis, toxoplasmosis, and Vogt-Koyanagi-Harada syndrome were the most common causes of anterior uveitis, posterior uveitis, and panuveitis respectively. Cataract (40.5%), glaucoma (33.8%), and cystoid macular edema (31.6%) were the most frequent ocular complications. CONCLUSION: The present report provides the relative prevalence of the different anatomical types of uveitis, as well as their main causes in a cohort of Egyptian patients with childhood-onset uveitis.

Growth and Metabolic Syndrome (MetS) criteria in young children with classic Congenital Adrenal Hyperplasia (CAH) treated with corticosteroids (CS).

BACKGROUND: Treatment of children with congenital adrenal hyperplasia (CAH) with corticosteroids (CS) may increase the risk for developing different components of metabolic syndrome (MetS).  Aim: We assessed the occurrence of cardiometabolic risk factors in children with CAH on treatment with CS since early infancy. METHODS: Data of 30 children with CAH were analyzed retrospectively. They have received hydrocortisone (HC; n = 11) or prednisolone (P; n= 19) and fludrocortisone (0.1- 0.15 mg once daily) since early infancy. The different cardiometabolic criteria including blood pressure (BP), fasting glucose, low-density lipoprotein (LDL), and serum cholesterol concentrations were studied and compared with the data for 66 age-matched obese children. RESULTS: Children with CAH on treatment for > 5 years had a high rate of obesity and overweight (60%) and short stature (23.3%), respectively. They had higher occurrences of abnormal cardio-metabolic components including high LDL and triglyceride and BP as well as increased carotid intima-media thickness (CIMT). Females had higher body mass index (BMI) and BP compared to males. The less controlled group was older and had faster linear growth compared to the controls. In the CAH group, BP and CIMT were correlated significantly with BMI-SDS and weight-standard deviation score (Wt-SDS). Neither the level of 17-hydroxy-Progesterone (17-OHP), nor the HC dose was correlated with BP, CIMT or BMI. CONCLUSION: These findings suggest the role played by excessive weight gain on the increased cardiometabolic risk factors in children with CAH on treatment with CS.

A Short Review on Growth and Endocrine Long-term Complications in Children and Adolescents with ß-Thalassemia Major: Conventional Treatment versus Hematopoietic Stem Cell Transplantation.

The conventional treatment of ß-thalassemia (ß-TM) patients is based on the correction of anemia through regular blood transfusions and iron chelation therapy. However, allogeneic hematopoietic stem cell transplantation (HSCT) remains the only currently available technique that has curative potential. Variable frequency and severity of long-term growth and endocrine changes after conventional treatment as well as after HSCT have been reported by different centers. The goal of this mini-review is to summarize and update knowledge about long-term growth and endocrine changes after HSCT in patients with ß-TM in comparison to those occurring in ß-TM patients on conventional treatment. Regular surveillance, early diagnosis, treatment, and follow-up in a multi-disciplinary specialized setting are suggested to optimize the patient's quality of life (www.actabiomedica.it).

Blood transfusion and iron overload in patients with Sickle Cell Disease (SCD): Personal experience and a short update of diabetes mellitus occurrence.

The conventional treatment of ß-thalassemia (ß-TM) patients is based on the correction of anemia through regular blood transfusions and iron chelation therapy. However, allogeneic hematopoietic stem cell transplantation (HSCT) remains the only currently available technique that has curative potential. Variable frequency and severity of long-term growth and endocrine changes after conventional treatment as well as after HSCT have been reported by different centers. The goal of this mini-review is to summarize and update knowledge about long-term growth and endocrine changes after HSCT in patients with ß-TM in comparison to those occurring in ß-TM patients on conventional treatment. Regular surveillance, early diagnosis, treatment, and follow-up in a multi-disciplinary specialized setting are suggested to optimize the patient's quality of life (www.actabiomedica.it).

Neutropenia and Lymphocytopenia Among Arab Females with Iron Deficiency Anemia (IDA) and their Response to Iron therapy.

. INTRODUCTION: The link between iron deficiency anemia (IDA) and neutropenia/ lymphocytopenia is not well established in the literature. This study aims at assessing the prevalence and clinical characteristics of neutropenia and lymphocytopenia in IDA patients considering the impact of iron replacement on the total and differential WBCs' count. SUBJECTS AND METHODS: The records of all female patients with IDA who attended our hematology clinic (Jan 2018 to Jan 2020) were retrospectively reviewed. Patients with systemic or chronic diseases were excluded. Age, BMI, CBC, and iron parameters were collected before and after IV iron therapy. Results: Out of 1,567 adult females with IDA, 80 patients had leukopenia (5.1%), 64 had neutropenia (4.0%), and 20 had lymphocytopenia (1.2%). After iron therapy, their mean leukocytes, neutrophils, and lymphocytes increased significantly to 4.38 ± 1.82 ×103/L, 2.3 ±1.56 ×109/L and 1.76 ± 0.48 ×103/L, respectively. About 67% of women with IDA and neutropenia had increased ANC in response to iron therapy. However, no significant correlation was found between leukocytes, ANC, or lymphocytes with TIBC or serum iron concentration. CONCLUSIONS: Neutropenia and/or lymphocytopenia may occur in patients with IDA and are reversible with iron therapy. Iron therapy led to the correction of anemia in 100% and increased ANC in 67%. Therefore, neutropenic women with IDA should be treated, initially only with iron, and observed for their Hb and ANC responses before starting any other treatment.

The Prevalence and Significance of Leukopenia Induced by Intravenous Iron Therapy in a Large Cohort of Females with Iron Deficiency Anemia (IDA).

INTRODUCTION: Iron deficiency anemia (IDA) is the most common cause of anemia in both developed and developing countries. Leukopenia is an infrequent side effect of iron therapy reported in the literature as sporadic cases. OBJECTIVE: To assess the prevalence of leukopenia, neutropenia and/or lymphocytopenia and its possible clinical impact if any, after intravenous iron therapy in adult patients with IDA. PATIENTS AND METHODS: This is a retrospective study conducted in Hamad Medical Corporation, Doha (Qatar). The clinical and biochemical data of 1.567 females (mean age: 29.5 years) with IDA who attended the Hematology Clinic and were treated with intravenous (i.v.) iron therapy were collected and analysed. Complete and differential blood counts and iron profile were studied before and after i.v. iron therapy. In addition, cases who developed infections during the time of leukopenia were noted and checked for possible complications. RESULTS: 30 cases (1.91%) developed leukopenia,15 cases (0.95%) developed neutropenia and 12 cases (0.76%) developed lymphocytopenia. All had normal white blood cell counts before treatment. Two patients (6.66%) had infection. One had upper respiratory tract infection and the other had urinary tract infection, the latter was treated with antibiotics. There was no reported other infection during or after i.v. iron therapy. CONCLUSIONS: Leukopenia in form of neutropenia or lymphocytopenia may occur as a side effect of i.v. iron therapy, however, its clinical significance appears to be limited.

Extramedullary haematopoiesis in patients with transfusion dependent ß-thalassaemia (TDT): a systematic review.

INTRODUCTION: Around 5% of the world's population is expected to have some degree and type of thalassaemia. Beta thalassaemia (BT) occurs due to a deficient production of the beta-globin chain of haemoglobin. Extramedullary haematopoiesis (EMH) is one of the complications of BT, mainly observed in minor/intermedia subtypes. EMH is the production of blood cells outside the marrow as a compensatory response to longstanding hypoxia. Due to chronic transfusions, it is not expected in patients with beta-thalassaemia major (BTM). However, there are increasingly reported cases of EMH in BTM. The incidence of EMH in BTM is thought to be <1%. We aim to pool the available data and provide cumulative evidence on the occurrence of EMH in BTM patients. METHODS: This is a systematic review of case reports, series, and retrospective studies that presented data on the occurrence of EMH in BTM patients. Data were recorded and analyzed in Microsoft Excel 2016 and SPSS 26. The protocol has been registered in PROSPERO: CRD42021242943. RESULTS: Data from 253 cases of EMH in BTM patients were extracted with a mean age of 35.3 years. Mean haemoglobin at presentation with EMH was 8.2 mg/dL. Lower limb weakness was the most common presenting feature (N = 23) (paraspinal EMH). Magnetic resonance imaging (MRI) was the most widely used diagnostic modality (226). Overall, blood transfusion was the commonest reported treatment (30), followed by radiotherapy (20), surgery (15), hydroxyurea (12), steroids (6), and exchange transfusion (2). An outcome was reported in 20% of patients, all recovered, except one who died as a result of nosocomial infection. CONCLUSION: EMH is rare in BTM and can occur in any organ system with varied clinical features. MRI can effectively diagnose EMH, and conservative management has similar results compared to invasive treatments. Larger studies, focussing on outcomes may enhance guidelines on preventive and therapeutic strategies for managing EMH in BTM.KEY MESSAGESExtramedullary haematopoiesis is a rare complication in beta thalassaemia. Although it is more common in non-transfusion dependent thalassaemia, increasingly reported cases suggest a higher prevalence of EMH in TDT than what is known before.There are no clear guidelines on the management of EMH in TDT, with reported patients showing similar outcomes with conservative invasive treatment modalities.More extensive and preferably prospectively designed studies are required focussing on the management of EMH and its outcomes in patients with TDT to formulate evidence-based guidelines.

Growth, bone maturation and ovarian size in girls with early and fast puberty (EFP) and effects of three years treatment with GnRH analogue (GnRHa).

INTRODUCTION: Early puberty (EP) in girls is defined as the onset of thelarche that begins after 6 years and before 8 years and/or acceleration in the tempo of pubertal development. The stage of puberty and the ovarian volume at presentation and the effect of treatment with GnRH analogue (GnRHa) on final adult height are still debated. PATIENTS AND METHODS: We analyzed the data of 22 girls, who presented early and fast puberty (FEP). The clinical stage of puberty, hormonal levels and the ovarian volume (OV) (measured by ovarian ultra-sonography) at presentation were studied. We recorded the effects of 3 years treatment with GnRHa on their growth in relation to their mid parental height, pubertal progression, and bone maturation. RESULTS AND CONCLUSION: GnRHa therapy decreased the fast progress of puberty, skeletal maturation, and GV/year. It was successful in increasing the predicted final adult height comparable to or surpassing their mid-parenteral height. A larger OV at presentation was associated with reduced Ht-SDS after 3 years of GnRHa treatment. Clearly, a definitive evaluation of the efficacy of GnRHa as treatment for EFP in girls will require expanded and concerted studies.

Effects of Two Chlorine Gas Attacks on Hospital Admission and Clinical Outcomes in Kafr Zita, Syria.

Background In 2014, Hama Governorate was exposed twice to chlorine gas, with 15 patients presenting to Kafr Zita Hospital in Northwest Syria. This study aimed to describe clinical manifestations of chlorine gas exposure to identify factors leading to facility admission and the need for ICU/intubation in conflict-affected areas with limited healthcare infrastructure. Methods We conducted a case-series study, using medical records of suspected chlorine-exposed patients presenting at Kafr Zita Hospital on either 11 April or 22 May 2014. Data on age, sex, initial clinical presentation, therapeutic management, and outcome were compared by hospital admission/non-admission and attack date. All patients provided verbal informed consent. Results Fifteen patients with signs of chlorine gas exposure had detailed medical records. The mean age was 25.7 years (range 2-59), eight were male (53%), and three (20%) were under age 16. At initial presentation, all experienced respiratory distress, due to severe airway inflammation confirmed by nonspecific pulmonary infiltrates on chest x-ray, and similar intestinal, neurological, dermatological, ophthalmological, and psychological signs and symptoms. Acute management consisted of oxygen and bronchodilators for all patients, hydrocortisone (93%), antiemetics (80%), and dexamethasone (13%). Seven (47%) made a rapid symptomatic recovery and were discharged the same day and eight (53%) were admitted for a median of two days (range 1-6 days), one of whom required intubation and later died. The only significant associations found were higher mean pulse rate (i.e. 138 versus 124; p=0.043) and body temperature (37.0 versus 36.5; p=0.019) among admitted patients compared to non-admitted. Conclusion Our results demonstrated that even in low-resource humanitarian settings the survival rate for chlorine gas exposed patients is fair. Despite the small sample, this study provides insight into the clinical presentation, management, and outcomes of weaponized chlorine gas exposure, though further research is required to understand any chronic consequences.

The Effects of Treatment with Blood Transfusion, Iron Chelation and Hydroxyurea on Puberty, Growth and Spermatogenesis in Sickle Cell Disease (SCD): A short update.

Sickle cell disease (SCD) is traditionally associated with growth failure and delayed puberty. Wasting and stunting are still prevalent in children and adolescents with SCD, especially in developing countries. In addition, sperm abnormalities are frequent in males with SCD, with high rates of low sperm density, low sperm counts, poor motility, and increased abnormal morphology.  Severe anemia, vaso-occlusive attacks with ischemic injury to different organs including the pituitary gland and testis, and nutritional factors are incriminated in the pathogenesis of defective growth, puberty, and spermatogenesis. There is great phenotypic variability among patients with SCD. The variability in the clinical severity of SCA can partly be explained by genetic modifiers, including HbF level and co-inheritance of α-thalassemia. In the past, severe disease led to early mortality. Advancements in treatment have allowed patients with SCD to have a longer and better quality of life. For most patients, the mainstays of treatment are preventive and supportive. For those with severe SCD, three major therapeutic options are currently available: erythrocyte transfusion or exchange, hydroxyurea, and hematopoietic stem cell transplantation. In this mini-review, the authors tried to recognize, delineate, and update knowledge on abnormalities due to SCD from those created by the use of different treatment modalities.

A rare case of Ovarian Juvenile Granulosa Cell Tumor in an Infant with Isosexual Pseudo Puberty and a Revision of Literature.

Juvenile ovarian granulosa cell tumors (JGCTs) are described infrequently in pediatrics, and their finding in infants is exceptional. We highlight the presenting symptoms, radiologic images, operative management, and histopathologic findings of a 9-month-old female with isosexual pseudopuberty. An updated revision of literature in infants below the age of 12 months is also reported.

Priapism in Patients with Chronic Myeloid Leukemia (CML): A Systematic Review.

BACKGROUND: Priapism is defined as a penile erection that persists four or more hours and is unrelated to sexual stimulation. Priapism resulting from hematologic malignancy is most likely caused by venous obstruction from microemboli/thrombi and hyperviscosity caused by the increased number of circulating leukocytes in mature and immature forms. In patients with leukemia, 50% of cases of priapism are due to Chronic Myeloid Leukemia (CML). We present a systematic review of priapism in CML. Acquisition of evidence: An extensive literature research was carried out in PubMed, Google Scholar, SCOPUS, and Science Citation Index databases... The search included cases up to 4th August 2020. Synthesis of evidence: A total of 68 articles were found and included in our review, including 3 reviews from three different centers.  We found 68 articles (102 patients; figure 1) and several case reports on priapism in CML. Priapism was noticed in some patients at the first presentation of CML. However, it was infrequently reported during the start of treatment, following the stop of medication and post-splenectomy. The mean age at presentation was 27.4 years, and the mean time from onset of priapism to the time to get medical attention (presentation) was 78.2 hours. The mean white blood cell count associated with priapism was 321.29x109/L, and the mean platelet count was 569 x10 9/L. The chronic phase of CML was the most common phase where priapism occurred. Most patients were Asian (>50%). Nearly a quarter of patients (27.4%) developed permanent erectile dysfunction. CONCLUSIONS: Priapism is a urological emergency requiring urgent multidisciplinary management to prevent erectile dysfunction. Because of the relatively rare occurrence of priapism in CML patients, there is no standard treatment protocol.