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Introduction: Angelman syndrome (AS) is a rare, genetic, neurodevelopmental disorder characterized by severe impairments in speech, cognition, and motor skills accompanied by unique behaviors, distinct facial features, and high prevalence of epilepsy and sleep problems. Despite some reports of short stature among AS patients, this feature is not included in the clinical criteria defined in 2005. We investigated growth patterns among AS patients with respect to mutation type, growth periods, family history, and endocrine abnormalities. Methods: Data were collected from patients' medical files in AS National Clinic. Mutation subtypes were divided to deletion and non-deletion. Four growth periods were defined: preschool, childhood, peak height velocity, and final height. Results: The cohort included 88 individuals (46 males), with 54 (61.4%) carrying deletion subtype. A median of 3 observations per individual produced 280 data points. Final height SDS was significantly lower compared to general population (−1.23 ± 1.26, p < 0.001), and in deletion group versus non-deletion (−1.67 ± 1.3 vs. −0.65 ± 0.96, p = 0.03). Final height SDS was significantly lower compared to height SDS in preschool period (−1.32 vs. −0.47, p = 0.007). Patient's final height SDS was significantly lower than the parents' (∆final-height SDS = 0.94 ± 0.99, p = 0.002). IGF1-SDS was significantly decreased compared to general population (−0.55 ± 1.61, p = 0.04), with lower values among deletion group (−0.70 ± 1.44, p = 0.01). Conclusions: AS patients demonstrate specific growth pattern with deceleration during childhood and adolescence, resulting in significantly decreased final height compared to normal population, and even lower among deletion subgroup, which could be attributed to reduced IGF1 levels. We propose adding short stature to the clinical criteria and developing adjusted growth curves for AS population. [ABSTRACT FROM AUTHOR]

Aims: Assess the effectiveness of virtual reality (VR) technology, in reducing pain and anxiety, and improving adherence and glycemic control among children with type 1 diabetes (T1D). Methods: Children with T1D, managed with continuous glucose monitoring and insulin pumps, were recruited for a randomized cross-over trial. Children were randomized to one of two interventions for diabetes management: group 1 used VR glasses first and group 2 listened to vocal-guided affective imagery first (audio). After 1 month, the interventions were crossed over. The outcome measures included pain and anxiety assessment, adherence, glycemic control, and patient-reported outcome measures (PROMs) of VR satisfaction and effectiveness. Results: Forty children, mean age 11.4 ± 1.8 years, were participated. During the VR part, the monthly mean pain score compared to the baseline improved in both groups by 30% (p = 0.03). A 14% reduction in the state anxiety score was observed from baseline to 1 month in both groups (p = 0.009). Glycemic control measures including time in range, time above range, and glucose management indicator improved in both groups during VR part (p < 0.004 for all), compared to audio part. After one month, the patient-reported outcome measure (PROM) of satisfaction and effectiveness was sixfold higher after 1 month in group 1 compared to group 2 (p = 0.002). Adherence improved for both groups. Conclusions: VR was shown to be effective in reducing pain and anxiety, improving adherence, PROM, and glycemic control among children with T1D. We suggest incorporating VR technology in pediatric diabetes clinics to facilitate and improve coping and management of diabetes. Trial registration: Trial registration number and date of registration for prospectively registered trials:ClinicalTrials.gov Identifier: NCT05883267, May 10th, 2023. [ABSTRACT FROM AUTHOR]

Aim. The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the pediatric occurrence of type 1 diabetes (T1D) is inconclusive. We aimed to assess associations between seroprevalences of the distinct anti-SARS-CoV-2 antibodies and T1D occurrence in children and adolescents. Methods. This multicenter prospective observational cohort comprised children diagnosed with T1D between October 2020 and July 2022 and unrelated children who performed endocrine tests (control group) in a 1 : 3 ratio. Anti-SARS-CoV-2 antibodies, including anti-S, anti-N, and neutralizing antibodies, were assessed in each group. Results. The cohort included 51 children with T1D and 182 children in the control group. The median (interquartile range) age was 11.4 (8.2, 13.3) years, with 45% being female. Increases were not observed in the seroprevalence of any of the anti-SARS-CoV-2 antibodies among the children with new-onset T1D compared to the control group. Among the T1D group, anti-S seroprevalence was higher among those without diabetic ketoacidosis (DKA) than in those with DKA upon T1D diagnosis (72% vs. 42%, p = 0.035). After adjustment to vaccination status, this difference was not statistically significant. Additionally, anti-N antibodies and neutralizing antibodies did not differ between the DKA and the non-DKA groups. None of the anti-SARS-CoV-2 antibodies were associated with any of the glycemic parameters. Conclusions. This study is the first to assess several distinct anti-SARS-CoV-2 antibodies in new-onset T1D, and our findings do not support an association between SARS-CoV-2 infection and the occurrence of T1D in children and adolescents. Since autoimmunity may emerge years after a viral infection, we recommend conducting follow-up epidemiological studies to assess whether there is a change in the incidence of T1D following the SARS-CoV-2 pandemic. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion Low‐carbohydrate (LC) diets have gained popularity. We compared glycaemic and metabolic parameters following an LC versus a Mediterranean (MED) diet in adolescents and youths with type 1 diabetes.In a six‐month, open‐label, randomised trial, 40 individuals were assigned to either diet. Glycaemic outcomes, based on continuous glucose monitoring, included per cent time of blood glucose in the range [3.9–10.0 mmol/L (70–180 mg/dL)] and haemoglobin A1c (HbA1c).Twenty‐eight (70%) were females. The median age was 18 years. After 6 months, the median time in range increased from 47% to 58% in the LC and from 52% to 64% in the MED diet group (p = 0.98). The delta values for the time in range were 16% and 7% for the respective groups (p = 0.09). The percentage of time >13.9 mmol/L (>250 mg/dL) improved more in the LC diet than in the MED diet group: −10% vs. −2% (p = 0.005). The percentage of time <3.0 mmol/L (<54 mg/dL) was comparable. The delta HbA1c improved in both groups: −0.7% vs. −0.1% (p = 0.02). Changes in BMI Z‐score and lipid levels were similar.Both diets improved glycaemic outcomes in adolescents and youths with type 1 diabetes, without increasing hypoglycaemia or cardiovascular risk factors, indicating comparable safety and efficacy. [ABSTRACT FROM AUTHOR]

Fragile X syndrome (FXS) is the most prevalent known genetically inherited cause for autism and intellectual disability. Premutation state can cause several clinical disorders as well. We aimed to perform a nesting approach to acquire data with regard to first degree relatives of index fragile X cases at the largest child development center in Israel in order to map characteristics of Israeli FXS permutation women carriers. Seventy-nine women were referred due to a related fragile X syndrome patient, mainly an offspring or sibling. General information regarding demographics, ethnicity, and associated medical conditions were collected using interviews and structured questionnaires. Thirteen (17 %) of the women who were referred as 'carrier' were proven to be actually full mutation. The mean years of education were 14 (±1.51, range 12-17). Twenty-one women (27 %) originated from Tunisia (mainly from the island of Djerba). Ten women (13 %) reported delivery of their affected offspring beyond 41 gestational weeks. Twenty-two percent of women with premutation reported symptoms consistent with learning difficulties, mainly dyscalculia, and 14 % reported ADHD symptoms. Awareness about clinical disorders of the carriers was existent only in 25 % of the patients. Increased awareness and knowledge dissemination concerning premutation symptomatology and associated medical conditions are warranted. We suggest a national registry to be installed in different countries in order to identify fragile X premutation carriers at increased risk for various medical complications. [ABSTRACT FROM AUTHOR]

Aims: Diabetic ketoacidosis (DKA) at diabetes diagnosis is a dangerous yet potentially preventable condition. Young age, low socioeconomic status, and low parental education have been found to be associated with increased risk of DKA. We aimed to evaluate the impact of religious affiliation on presentation with DKA at type 1 diabetes mellitus (T1DM) diagnosis in Jewish children. Methods: The study comprised an analysis of medical records of all consecutive patients with new-onset T1DM who were admitted to one tertiary medical center from January 2007 to January 2014. DKA was defined as venous pH <7.3 or HCO < 15 mmol/l, and severe DKA as pH <7.1 or HCO < 5 mmol/l. Results: Of 81 patients with new-onset T1DM (38 females, mean ± SD age at diagnosis 9.9 ± 4.2 years), 34 (42 %) presented with DKA: 21 of 60 (35 %) of patients from secular families and 13 of 21 (62 %) from ultra-orthodox families. Children from ultra-orthodox families had a 3.5-fold increased risk of presenting with DKA than children from secular families (95 % CI 1.2-10.1, p = 0.02) and a 3.8-fold risk to be admitted with severe DKA (95 % CI 1.1-12.6, p = 0.02). Other factors that were found to be associated with an increased risk of DKA were younger age, an absence of maternal academic education, and residence in an area of low socioeconomic status. Conclusions: DKA and severe DKA at diabetes diagnosis were more common among religious ultra-orthodox than among secular Jewish children. Awareness of the symptoms and dangers of DKA in new-onset T1DM should be directed to particularly high-risk population groups. [ABSTRACT FROM AUTHOR]

Aims: Frequent glucose testing is required for optimal management of type 1 diabetes (T1D). Limited data are available regarding real-world experience of the novel technology for monitoring by continuous interstitial fluid glucose (IFG), using flash glucose-sensing technology (FSL-CGM). We aimed to assess the effect of FSL-CGM in a real-life clinical setting on glycemic control parameters, compliance, and adverse events among pediatric and young adult T1D patients.Methods: This observational multi-center study assessed FSL-CGM use (6-12 months) in T1D patients (mean ± SD age 13.4 ± 4.9 years) who purchased the device out-of-pocket. Outcome measures included HbA1c, mean IFG levels, CGM metrics [time in hypoglycemia (< 54 mg/dL; < 3 mmol/L), in target range (70-180 mg/dL; 3.9-10 mmol/L), and in hyperglycemia > 240 mg/dL; > 13.3 mmol/L)], frequency of self-monitoring of blood glucose, acute complications, skin reactions, and reasons for initiation/discontinuation.Results: Among patients with regular use of the FSL-CGM (n = 59), mean HbA1c decreased from 8.86 ± 0.23 to 8.05 ± 0.2% (73.3-64.5 mmol/mol) in 3 months (p = 0.0001) and plateaued thereafter. A clinically significant reduction in HbA1c (defined as a decrease of ≥ 0.5%) was associated with shorter diabetes duration. Of 71 patients who initiated use of the FSL-CGM, 12 (16.9%) discontinued during the study period. No statistically significant changes were found after FSL-CGM use, in mean and standard deviation IFG levels, and in time of glucose levels in target, hypoglycemia, and hyperglycemia ranges. One patient with hypoglycemia unawareness was found dead-in-bed while using FSL-CGM.Conclusions: Real-life observational data in a self-selected young T1D population demonstrated a significant and sustained reduction in HbA1c with FSL-CGM in one-third of the participants. Surveillance of glucose monitoring should be individualized, especially for patients with hypoglycemia unawareness. [ABSTRACT FROM AUTHOR]

Can ovarian reserve parameters predict the outcome of ovarian tissue cryopreservation (OTCP) in patients ≤18 years with non-iatrogenic premature ovarian insufficiency (POI)? Retrospective cohort analysis carried out in a single tertiary hospital between August 2010 and January 2020. Thirty-seven patients ≤18 years with non-iatrogenic POI (27 with Turner syndrome, six with POI of unknown aetiology, three with galactosemia and one with blepharophimosis, ptosis, epicanthus inversus syndrome) were included. Three parameters were used to evaluate ovarian reserve: anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH) and transabdominal antral follicle count. Fertility preservation (most commonly OTCP) was offered if ovarian reserve was diminished and one or more parameters was positive. Follicles were counted in ovarian samples obtained at the time of OTCP. Ovarian reserve was diminished in 34 patients and 19 of them had one or more positive parameter. Fourteen (11 aged ≥12 years and 3 aged <12) underwent OTCP, one (14 years old) underwent ovarian stimulation and oocyte cryopreservation and four declined fertility preservation. Follicles were detected in 11 of 14 patients who underwent OTCP with one or more positive parameters (79%), and in all those (100%) who had two or three positive parameters. The median number of follicles was 27 (range 5–64) and 48 (range 21–75) in patients ≥12 years and those <12 years, respectively. This study shows that if OTCP is performed in patients with one or more positive parameters of ovarian activity, a 79% positive predictive value is achieved for the detection of follicles. The incorporation of this criterion for OTCP will minimize the risk of harvesting ovarian tissue with a low number of follicles. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have demonstrated an association between gut microbiota composition and type 1 diabetes (T1D) pathogenesis. However, little is known about the composition and function of the gut microbiome in adults with longstanding T1D or its association with host glycemic control.Research Design and Methods: We performed a metagenomic analysis of the gut microbiome obtained from fecal samples of 74 adults with T1D, 14.6 ± 9.6 years following diagnosis, and compared their microbial composition and function to 296 age-matched healthy control subjects (1:4 ratio). We further analyzed the association between microbial taxa and indices of glycemic control derived from continuous glucose monitoring measurements and blood tests and constructed a prediction model that solely takes microbiome features as input to evaluate the discriminative power of microbial composition for distinguishing individuals with T1D from control subjects.Results: Adults with T1D had a distinct microbial signature that separated them from control subjects when using prediction algorithms on held-out subjects (area under the receiver operating characteristic curve = 0.89 ± 0.03). Linear discriminant analysis showed several bacterial species with significantly higher scores in T1D, including Prevotella copri and Eubacterium siraeum, and species with higher scores in control subjects, including Firmicutes bacterium and Faecalibacterium prausnitzii (P < 0.05, false discovery rate corrected for all). On the functional level, several metabolic pathways were significantly lower in adults with T1D. Several bacterial taxa and metabolic pathways were associated with the host's glycemic control.Conclusions: We identified a distinct gut microbial signature in adults with longstanding T1D and associations between microbial taxa, metabolic pathways, and glycemic control indices. Additional mechanistic studies are needed to identify the role of these bacteria for potential therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objective: Despite technological advances, results from various clinical trials have repeatedly shown that many individuals with type 1 diabetes (T1D) do not achieve their glycemic goals. One of the major challenges in disease management is the administration of an accurate amount of insulin for each meal that will match the expected postprandial glycemic response (PPGR). The objective of this study was to develop a prediction model for PPGR in individuals with T1D.Research Design and Methods: We recruited individuals with T1D who were using continuous glucose monitoring and continuous subcutaneous insulin infusion devices simultaneously to a prospective cohort and profiled them for 2 weeks. Participants were asked to report real-time dietary intake using a designated mobile app. We measured their PPGRs and devised machine learning algorithms for PPGR prediction, which integrate glucose measurements, insulin dosages, dietary habits, blood parameters, anthropometrics, exercise, and gut microbiota. Data of the PPGR of 900 healthy individuals to 41,371 meals were also integrated into the model. The performance of the models was evaluated with 10-fold cross validation.Results: A total of 121 individuals with T1D, 75 adults and 46 children, were included in the study. PPGR to 6,377 meals was measured. Our PPGR prediction model substantially outperforms a baseline model with emulation of standard of care (correlation of R = 0.59 compared with R = 0.40 for predicted and observed PPGR respectively; P < 10-10). The model was robust across different subpopulations. Feature attribution analysis revealed that glucose levels at meal initiation, glucose trend 30 min prior to meal, meal carbohydrate content, and meal's carbohydrate-to-fat ratio were the most influential features for the model.Conclusions: Our model enables a more accurate prediction of PPGR and therefore may allow a better adjustment of the required insulin dosage for meals. It can be further implemented in closed loop systems and may lead to rationally designed nutritional interventions personally tailored for individuals with T1D on the basis of meals with expected low glycemic response. [ABSTRACT FROM AUTHOR]

Background: Data regarding glycemic control in children and adolescents with a dual diagnosis of type 1 diabetes mellitus (T1DM) and attention‐deficit/hyperactivity disorder (ADHD) are limited. Objective: To compare various aspects of diabetes control among youth with T1DM, between those with and without ADHD. Methods: In this cross‐sectional study of youth with T1DM, 39 had ADHD (mean age 14.1 ± 2.8 years) and 82 did not (control group, mean age 12.6 ± 3.3 years). Health‐related quality of life was assessed by a Diabetes Quality of Life (DQOL) questionnaire submitted to their parents. Glycemic data were downloaded from glucometers, pumps, and continuous glucose monitoring systems. HbA1c levels, hospitalizations, and severe hypoglycemic and diabetes ketoacidosis events were retrieved from the medical files. Results: Compared to the control group mean HbA1c level of the ADHD group was higher: 8.3 ± 1.1% versus 7.7 ± 1.0% (p = 0.005) and the percent of time that glucose level was in the target range (70–180 mg/dl) was lower: 48 ± 17% versus 59 ± 14% (p = 0.006). Mean glucose and glucose variability were higher in the ADHD group. Youth with ADHD who were not pharmacologically treated had worse HbA1c and more hospitalizations than those who were treated. DQOL did not differ between the control group, the treated ADHD group, and the untreated ADHD‐Group. Conclusions: Dual diagnosis of T1DM and ADHD during childhood leads to worse diabetes control, which is more pronounced in the context of untreated ADHD. Healthcare providers should be aware of the difficulties facing youth with T1DM and ADHD in coping with the current intensive treatment of diabetes. [ABSTRACT FROM AUTHOR]

Background: Diabetic kidney disease (DKD) is becoming increasingly common among children. We aimed to estimate the risk of end-stage renal disease (ESKD) and mortality among adolescents with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) and normal renal function compared with non-diabetics. We hypothesized that childhood onset T1DM vs. T2DM would be associated with a different risk profile for developing ESKD and its complications. Methods: A nationwide, population-based, retrospective cohort study, including 1,500,522 adolescents examined for military service between 1967 and 1997, which were classified according to the presence and type of diabetes. Data were linked to the Israeli ESKD registry. Cox proportional-hazards models were used to estimate the hazard ratio (HR) for ESKD. Results: At study enrolment, 1183 adolescents had T1DM and 196 had T2DM. ESKD developed in 2386 non-diabetic individuals (0.2%) compared with 72 individuals (6.1%) with T1DM and 8 individuals (4.1%) with T2DM. Participants with T1DM were younger at ESKD onset than participants with T2DM (median age, 36.0 vs. 40.5 years, P < 0.05). In a multivariate model adjusted for age, sex, paternal origin, enrollment year, BMI, and blood pressure, T1DM and T2DM were associated with HR of 36.4 (95% CI 28.3–46.9) and 19.3 (95% CI 9.6–38.8) for ESKD, respectively. Stratification according to sex, ethnicity, immigration, and socioeconomic status did not materially change the HR. During the follow-up period, mortality rates were higher in T2DM as compared with T1DM and controls (8.7 %, 2.2%, and 2.7% respectively). Conclusions: T1DM and T2DM in adolescents with normal renal function confer a significantly increased risk for ESKD. T1DM is associated with younger age at ESKD onset while T2DM is associated with higher mortality rate. [ABSTRACT FROM AUTHOR]

Background: Isolated growth hormone deficiency (IGHD) is a relatively common disorder. Current diagnostic protocol requires a brain magnetic resonance imaging (MRI) study of the hypothalamus and the hypophysis to determine the cause after establishment of the diagnosis. This study aimed to examine the yield of brain MRI in the evaluation of children with IGHD and to define clinical and laboratory parameters that justify its performance. Methods: A retrospective chart review of all children (<18 years) diagnosed with IGHD was conducted at 3 pediatric endocrinology units between 2008 and 2018. Results: The study included 192 children (107 boys) with confirmed IGHD. The mean age ± standard deviation (SD) at diagnosis was 8.2 ± 3.7 years (median 8.5 years, range 0.8–15.9). The mean height SD score (SDS) at diagnosis was –2.25 ± 0.73. The mean height deficit SDS (defined as the difference between height SDS at diagnosis and mid-parental height SDS) was –1.7 ± 0.9. Fifteen children (7.8%) had pathological MRI findings. No space-occupying lesion was detected. Children with pathological MRIs had greater height deficit SDS and lower peak growth hormone levels on provocative tests compared to children with normal MRIs: –2.3 ± 1.2 vs. –1.6 ± 0.8 (p = 0.02) and 4.4 ± 1.9 vs. 5.7 ± 1.3 (p = 0.01), respectively. Conclusion: Our preliminary data indicate that most brain MRIs performed for routine evaluation of children with IGHD are not essential for determining cause. Further studies with larger cohorts are needed in order to validate this proposed revision of current protocols. [ABSTRACT FROM AUTHOR]

Unfortunately, the co-author name was misspelled as “Avivit Brenner” instead of “Avivit Brener” in the original publication and the correct author name is updated here [ABSTRACT FROM AUTHOR]

Background: The use of insulin pumps in pediatric patients with type 1 diabetes (T1D) has expanded; however, data comparing devices remain scarce. We compared glycemic control, technical difficulties, and quality of life (QOL) between pump devices of three companies.Methods: This prospective observational trial is based on clinical data retrieved during 12 months of follow-up of pediatric patients who started pump therapy as part of their clinical care in four medical centers. The devices fully reimbursed by the national health insurance are as follows: MiniMed™ 640G, MiniMed® Veo™, Animas® Vibe®, and Abbott OmniPod®. Parameters investigated included discontinuation rate, glycated hemoglobin (HbA1c), mean self-monitoring of blood glucose (SMBG), total daily dose of insulin (TDD), pump setting parameters, body mass index (BMI), frequency of technical difficulties, significant skin reactions, and QOL.Results: Of 113 children (mean age 9.1 ± 4.1 years, 46% females), 68 (60%) used Medtronic devices, 33 (29%) OmniPod, and 12 (11%) Animas devices. Twelve percent of the cohort stopped using the pump during the study period, with no difference according to device. There were no differences between groups regarding mean SMBG values (P = 0.86), insulin TDD (P = 0.24), BMI (P = 0.87), level of insertion site pain or local reaction (P = 0.51), technical problems (P = 0.66), and QOL (P = 0.38). Changes in HbA1c from study initiation to end were also not statistically significant for any of the devices: from 7.99% ± 1.14% to 7.93% ± 0.99% for Medtronic, from 7.71% ± 1.29% to 7.92% ± 1.38% for OmniPod, and from 8.75% ± 1.3% to 7.70% ± 1.33% for Animas (P = 0.63).Conclusions: Pump devices were comparable regarding glycemic control, weight gain, and satisfaction among pediatric patients with T1D. [ABSTRACT FROM AUTHOR]

Background: Disordered eating behaviors (DEBs) may lead to full blown eating disorders. Both type 1 diabetes mellitus (T1DM) and celiac disease (CD) have been linked to DEBs. Objective: To compare the presence of DEBs between adolescents and young adults with a dual diagnosis of T1DM and CD, and individuals with only one of the diagnoses. Methods: Individuals with a dual diagnosis of T1DM and CD (“T1DM + CD group” n = 39), with a diagnosis of T1DM only (“T1DM group” n = 97) and with a diagnosis of CD only (“CD group” n = 267) filled the Eating Attitude Test‐26 (EAT‐26) questionnaire. Those with T1DM completed in addition to the Diabetes Eating Problem Survey‐Revised (DEPS‐R). Results: The study population comprised of 403 individuals, of whom 65% were females. There were no statistically significant differences among the groups in distribution of sex, age, hemoglobin A1c (HbA1c) levels, age of disease diagnosis and duration. The prevalence of DEBs in the T1DM + CD group was 3‐fold higher (26.0%) than in the T1DM (8.2%) and CD (8.2%) groups (P = .003). This trend was observed for both females and males. Multivariate analysis demonstrated that the T1DM + CD group had an increased risk for DEBs (odds ratio, OR: 4.7, 95% confidence interval, CI: 1.9‐11.2, P = .001) after adjustment for age, sex, and body mass index. Additionally, being female, older and overweight increased the risk for DEBs. HbA1c values were not associated with an increased DEBs rate. Conclusions: Individuals with the dual diagnoses of T1DM and CD have an increased likelihood to develop DEBs compared to those with only one of these diagnoses. [ABSTRACT FROM AUTHOR]

A healthy four-year-old boy presented with new haemorrhagic skin lesions on his thighs and left flank (upper left image). Several hours following treatment initiation, the skin lesion progression ceased, and laboratory tests improved. Laboratory investigations showed a normal full blood count, C-reactive protein (CRP) was 27 mg/l (normal <0-5), prothrombin time (PT) was 57% (normal 75-120%) and activated partial thromboplastin time (APTT) was normal. [Extracted from the article]