Growth Responses During 3 Years of Growth Hormone Treatment in Children and Adolescents With Growth Hormone Deficiency: Comparison Between Idiopathic, Organic and Isolated Growth Hormone Deficiency, and Multiple Pituitary Hormone Deficiency.

BACKGROUND: The study aimed to compare the growth responses to 3 years of growth hormone (GH) treatment in children and adolescents with GH deficiency (GHD) according to idiopathic, organic, isolated (IGHD), and multiple pituitary hormone deficiency (MPHD). METHODS: Total 163 patients aged 2-18 years (100 males and 63 females; 131 idiopathic and 32 organic GHD; 129 IGHD and 34 MPHD) were included from data obtained from the LG Growth Study. Parameters of growth responses and biochemical results were compared during the 3-year GH treatment. RESULTS: The baseline age, bone age (BA), height (Ht) standard deviation score (SDS), weight SDS, mid-parental Ht SDS, predicted adult Ht (PAH) SDS, and insulin like growth factor-1 (IGF-1) SDS were significantly higher in the organic GHD patients than in the idiopathic GHD patients, but peak GH on the GH-stimulation test, baseline GH dose, and mean 3-year-GH dosage were higher in the idiopathic GHD patients than in the organic GHD patients. The prevalence of MPHD was higher in the organic GHD patients than in the idiopathic GHD patients. Idiopathic MPHD subgroup showed the largest increase for the ΔHt SDS and ΔPAH SDS during GH treatment, and organic MPHD subgroup had the smallest mean increase after GH treatment, depending on ΔIGF-1 SDS and ΔIGF binding protein-3 (IGFBP-3) SDS. The growth velocity and the parental-adjusted Ht gain were greater in the idiopathic GHD patients than the organic GHD patients during the 3-year GH treatment, which may have been related to the different GH dose, ΔIGF-1 SDS, and ΔIGFBP-3 SDS between two groups. Multiple linear regression analysis revealed that baseline IGF-1 SDS, BA, and MPH SDS in idiopathic group and baseline HT SDS in organic group are the most predictable parameters for favorable 3-year-GH treatment. CONCLUSION: The 3-year-GH treatment was effective in both idiopathic and organic GHD patients regardless of the presence of MPHD or underlying causes, but their growth outcomes were not constant with each other. Close monitoring along with appropriate dosage of GH and annual growth responses, not specific at baseline, are more important in children and adolescents with GHD for long-term treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01604395.

Recombinant growth hormone therapy in children with Turner Syndrome in Korea: a phase III Randomized Trial.

BACKGROUND: Short stature is the most consistent characteristic feature of Turner syndrome (TS). To improve final heights of children with TS effectively, it is important to provide them with early and appropriate treatment using growth hormone (GH). The objective of this study was to assess the efficacy and safety of a new recombinant human GH, Growtropin®-II (DA-3002, Dong-A ST Co., Ltd) versus a comparator (Genotropin®, Pfizer Inc.) for Korean children with TS. METHODS: This open-label, active-controlled, parallel-group, randomized controlled phase III trial was conducted at 11 hospitals in Korea. Eligible patients (n = 58) were randomized to two groups: 1) DA-3002 group (administrated with DA-3002 at 0.14 IU [0.0450-0.050 mg] /kg/day); and 2) comparator group (administrated with the comparator at 0.14 IU [0.0450-0.050 mg] /kg/day). RESULTS: The change from baseline in annualized height velocity (HV) after a 52-week treatment period was 4.15 ± 0.30 cm/year in the DA-3002 group and 4.34 ± 0.29 cm/year in the comparator group. The lower bound of 95% two-sided confidence interval for group difference in the change of annualized HV (- 1.02) satisfied the non-inferiority margin (- 1.5). The change in height standard deviation score (HtSDS) at 52-week was 0.70 ± 0.23 for the DA-3002 group and 0.66 ± 0.39 for the comparator group, showing no significant (p = 0.685) difference between the two groups. The change of skeletal maturity defined as change in bone age/change in chronological age between the two groups was not significantly different (1.25 ± 0.58 for the DA-3002 group and 1.47 ± 0.45 for the comparator group, p = 0.134). Changes from baseline in serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) after 52 weeks of treatment did not differ significantly between the two groups (p = 0.565 and p = 0.388, respectively) either. The occurrence of adverse events was not statistically different between groups. CONCLUSIONS: This study demonstrates that the efficacy and safety of GH treatment with DA-3002 in children with TS are comparable with those of the comparator. It is expected to analysis the long-term effect of DA-3002 on the increase of final adult height in children with TS and possible late-onset complications in the future. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov. ClinicalTrials.gov identifier: NCT01813630 (19/03/2013).

Effectiveness of negative pressure isolation stretcher and rooms for SARS-CoV-2 nosocomial infection control and maintenance of South Korean emergency department capacity.

OBJECTIVE: There are growing concerns regarding the lack of COVID-19 pandemic response capacity in already overwhelmed emergency departments (EDs), and lack of proper isolation facilities. This study evaluated the effectiveness of the negative pressure isolation stretcher (NPIS) and additional negative pressure isolation rooms (NPIRs) on the maintenance of emergency care capacity during the COVID-19 outbreak. METHODS: A before and after intervention study was performed between February 27, 2020 and March 31, 2020 at the ED of Chungbuk National University Hospital, Cheongju, South Korea. A total of 2455 patients who visited the ED during the study period were included. Interventions included the introduction of the NPIS and additional NPIRs in the ED. The main outcome of the study was frequency of medical cessation. Secondary outcomes were the average number of ED visits and lengths of stay. RESULTS: After the intervention, average frequency of medical cessation was significantly decreased from 1.6 times per day (range 0-4) in the pre-intervention period to 0.6 times per day (range 0-3) in the post-intervention period (p-value <0.01). On the other hand, the number of patients visiting the ED increased significantly from 67.2 persons per day (range 58-79) pre-intervention to 76.3 persons per day (range 61-88) post-intervention (p value <0.01). However, there were no statistically significant differences in the average ED length of stay across the study phases (p value = 0.50). CONCLUSIONS: This intervention may provide an effective way to prepare and meet the ED response needs of the COVID-19 pandemic.

The Importance of Early Recognition, Timely Management, and the Role of Healthcare Providers in Multisystem Inflammatory Syndrome in Children.

In April 2020, a pediatric report of an unusual inflammatory illness associated with coronavirus disease 2019 (COVID-19) led to similar cases in Europe and North America, which was referred to as multisystem inflammatory syndrome in children (MIS-C). Herein, we describe the case of a 12-year-old boy who had a history of polymerase chain reaction-confirmed COVID-19 and developed MIS-C approximately three weeks after an initial diagnosis of COVID-19. High fever with abdominal pain mimicking appendicitis was the initial manifestation of MIS-C, which could have been easily missed if the patient's history of COVID-19 was ignored. Intravenous immunoglobulin was administered twice, 24 hours apart, five days after the onset of MIS-C, and the patient fully recovered without any obvious sequelae. Early recognition by disease awareness and prompt management are the keys to saving the lives of children affected by MIS-C.

Bilateral Obstructive Uropathy Caused by Congenital Bladder Diverticulum Presenting as Hypertensive Retinopathy.

A congenital bladder diverticulum (CBD) is caused by inherent muscular weakness instead of obstruction of the bladder outlet. The major clinical conditions are recurrent urinary tract infection (UTI) and voiding dysfunction. This report describes a 15-year-old male adolescent who developed sudden visual disturbance resulting from hypertensive retinopathy. The cause of hypertension was bilateral obstructive uropathy caused by enlarged paraureteral bladder diverticula. After the non-functioning right kidney and ureter and the bilateral diverticula were removed, the left ureter was reimplanted in the bladder. Pathologic findings showed chronic pyelonephritis and partial loss of the bladder musculature in the diverticular wall. This observation indicates that dilated CBD can cause latent UTI, ureteral obstruction, hydronephrosis, and secondary hypertension.

Unintended Pulmonary Artery Ligation during PDA Ligation.

A 10-day-old boy was transferred to our hospital due to tachypnea. Patent ductus arteriosus (PDA), 4.8 mm in diameter, with small ASD was diagnosed on echocardiography. Surgical ligation of the ductus was performed after failure of three cycles of ibuprofen. However, the ductus remained open on routine postoperative echocardiography on the second postoperative day, and chest CT revealed inadvertent ligation of the left pulmonary artery (LPA) rather than the PDA. Emergent operation successfully reopened the clipped LPA and ligated the ductus on the same (second postoperative) day.Mechanical ventilator support was weaned on postoperative day 21, and the baby was discharged on postoperative day 47 with a normal left lung shadow.

Early discontinuation of thyroxine therapy is possible in most very low-birthweight infants with hypothyroidism detected by screening.

AIM: To determine the feasibility of discontinuing thyroid hormone treatment earlier than recommended by the current guidelines for congenital hypothyroidism. METHODS: We retrospectively reviewed the medical records of very low-birthweight (VLBW) infants born at Chungbuk National University Hospital from January 2006 to December 2010. Infants were divided into two groups--hypothyroid and normal thyroid--on the basis of the thyroid function test results. Infants in the hypothyroid group were treated with levothyroxine (L-T4) and attempts to discontinue this therapy began when they were about 2 years old. RESULTS: Of the 216 infants born during the study period, 20 died and 196 were included in the study. Of these, 46 were in the hypothyroid group and 150 were in the normal thyroid group. Thirty-nine infants were taken off L-T4 therapy at around 2 years of age. All were successfully weaned off L-T4 and retained normal thyroid function. Tc-99 m thyroid scans were performed in 32 infants, and no distinct abnormality was noted. CONCLUSION: Thyroid dysfunction in VLBW infants was common in our cohort and most cases were transient. Attempts to discontinue this therapy could begin at around the age of two or earlier when low doses of L-T4 have achieved maintenance.

Prevalence and genetic characterization of respiratory syncytial virus (RSV) in hospitalized children in Korea.

Human respiratory syncytial virus (HRSV) is the most common respiratory pathogen among infants and young children. To investigate the prevalence and genetic characteristics of HRSVs circulating in South Korea, we analyzed medical records of patients and performed molecular analysis of the G-protein gene of viruses detected from nasopharyngeal aspirates (NPA) of admitted patients at the Pediatrics Department of Chungbuk National University Hospital from April 2008 to April 2010. Epidemiological data revealed that the prevalence of HRSV infection was high during both winter seasons (October 2008 to February 2009 and November 2009 to February 2010). Of the 297 positive NPA specimens from infants or children tested, 67% were identified as HRSV-A while 33% were HRSV-B. The HRSV subgroup B was the most dominant in December 2008, but its dominance was dramatically replaced by HRSV subgroup A strains by February 2009. Phylogenetic analysis of the G protein sequences of HRSVs revealed novel genotypes within the HRSV-A (genotype CB-A) and B (genotypes BA11 and CB-B) subgroups in South Korea in addition to other strains identified in other countries. Molecular analysis also revealed genetic variability at the C-terminal end of the G proteins of the two HRSV subgroups, suggesting selection pressure in this region, which may potentially impact immune recognition. This is the first report of these HRSV variants in South Korea, indicating active genetic evolution of HRSV strains. Therefore, this study provides information on the molecular epidemiology of current HRSVs in the country and presents data for comparative analysis with other HRSV strains circulating worldwide.

Tuberculous pericarditis presenting as multiple free floating masses in pericardial effusion.

Pericarditis is a rare manifestation of tuberculosis (Tb) in children. A 14-yr-old Korean boy presented with cardiac tamponade during treatment of pulmonary tuberculosis. He developed worsening anemia and persistent fever in spite of anti-tuberculosis medications. Echocardiography found free floating multiple discoid masses in the pericardial effusion. The masses and exudates were removed by pericardiostomy. The masses were composed of pink, amorphous meshwork of threads admixed with degenerated red blood cells and leukocytes with numerous acid-fast bacilli, which were confirmed as Mycobacterium species by polymerase chain reaction. The persistent fever and anemia were controlled after pericardiostomy. This is the report of a unique manifestation of Tb pericarditis as free floating masses in the effusion with impending tamponade.

Efficacy and safety of the recombinant human growth hormone in short children born small for gestational age: A randomized, multicentre, comparative phase III trial.

OBJECTIVE: Growth hormone (GH) treatment is known to be effective in increasing stature in children with a short stature born small for gestational age (SGA). This multicentre, randomized, open-label, comparative, phase III study aimed to evaluate the efficacy and safety of Growtropin-II (recombinant human GH) and to demonstrate that the growth-promoting effect of Growtropin-II is not inferior to that of Genotropin in children with SGA (NCT ID: NCT02770157). METHODS: Seventy five children who met the inclusion criteria were randomized into 3 groups in a ratio of 2:2:1 (the study group [Growtropin-II, n = 30], control group [Genotropin, n = 30], and 26-week non-treatment group [n = 15]). The study and control groups received subcutaneous injections of Growtropin-II and Genotropin, respectively for 52 weeks, whereas the non-treatment group underwent a non-treatment observation period during weeks 0 to 26 and a dosing period during weeks 27 to 52 and additional dosing till week 78 only in re-consenting children. RESULTS: No significant differences in demographic and baseline characteristics between the groups were observed. The mean ± standard deviation change difference in annualized height velocity (aHV) (study group - control group) was 0.65 ±2.12 cm/year (95% confidence interval [CI], -0.53 to 1.83), whereas the lower limit for the 2-sided 95% CI was -0.53 cm/year. Regarding safety, treatment-emergent adverse events (TEAEs) occurred in 53.33% children in the study group and 43.33% children in the control group; the difference in the incidence of TEAEs between the 2 treatment groups was not statistically significant (P  = .4383). A total of 17 serious adverse events (SAEs) occurred in 13.33% children in the treatment groups, and no significant difference in incidence between groups (P  = .7065) was seen. Two cases of adverse drug reaction (ADR) occurred in 2 children (3.33%): 1 ADR (injection site swelling or pain) occurred in 1 child (3.33%) each in the study and control groups. CONCLUSIONS: This study demonstrates that the change in aHV from the baseline till 52 weeks with Growtropin-II treatment is non-inferior to that with Genotropin treatment in children with short stature born SGA. Growtropin-II is well-tolerated, and its safety profile is comparable with that of Genotropin over a 1-year course of treatment.

A 5-yr follow-up nerve conduction study for the detection of subclinical diabetic neuropathy in children with newly diagnosed insulin-dependent diabetes mellitus.

OBJECTIVE: To investigate the changes of peripheral nerve conduction in children with insulin-dependent diabetes mellitus (IDDM) prospectively from diagnosis and to know how those results were related to clinical risk factors. METHODS: A total of 37 patients (14 males and 23 females) aged 3-19 yr (mean 12.0 ± 3.7) with newly diagnosed IDDM underwent bilateral nerve conduction studies (NCS) of median, ulnar, posterior tibial, peroneal, and sural nerves annually for 5 yr. RESULTS: In all, 12 patients (32.4%) showed electrophysiological evidence of polyneuropathy in at least two different nerves including the sural nerve at the diagnosis of IDDM; 20 patients (54%) had multiple (≥2) abnormalities in parameters of NCS. The most common abnormal parameters at the diagnosis were conduction velocities of peroneal motor and sural nerves. In sequential NCS over 5 yr, the percentage of abnormal nerve conduction velocities rose except within the sural nerve. Poor metabolic control, height, duration of diabetes, and older age of onset were related to the changes of parameters of NCS over 5 yr. Among those risk factors, the duration of diabetes and sustained hyperglycemia affected the parameters of NCS more frequently than others. CONCLUSIONS: Children with IDDM frequently have nerve conduction abnormalities without clinical neuropathy at initial diagnosis. The frequency of abnormalities of any attribute of nerve conduction increased over the 5 yr follow-up. The duration of diabetes and poor glycemic control proved to be more important risk factors over 5 yr as related to the development of subclinical neuropathy.

Nutritional status of vitamin D and the effect of vitamin D supplementation in Korean breast-fed infants.

We investigated the vitamin D status and the effect of vitamin D supplementation in Korean breast-fed infants. The healthy term newborns were divided into 3 groups; A, formula-fed; B, breast-fed only; S, breast-fed with vitamin D supplementation. We measured serum concentrations of vitamin D (25OHD3), calcium (Ca), phosphorus (P), alkaline phosphatase (AP), intact parathyroid hormone (iPTH) and bone mineral density (BMD) at 6 and 12 months of age. Using questionnaires, average duration of sun-light exposure and dietary intake of vitamin D, Ca and P were obtained. At 6 and 12 months of age, 25OHD3 was significantly higher in group S than in group B (P<0.001). iPTH was significantly lower in group S than in group B at 6 months (P=0.001), but did not differ at 12 months. Regardless of vitamin D supplementation, BMD was lower in group B and S than in group A (P<0.05). Total intake of vitamin D differed among 3 groups (P<0.001, A>S>B), but total intake of Ca and P were higher in group A than in group B and S (P<0.001). In conclusion, breast-fed infants show lower vitamin D status and bone mineralization than formula-fed infants. Vitamin D supplementation (200 IU/day) in breast-fed infants increases serum 25-OH vitamin D(3), but not bone mineral density.

Efficacy and Safety Evaluation of Human Growth Hormone Therapy in Patients with Idiopathic Short Stature in Korea - A Randomised Controlled Trial.

BACKGROUND: This trial evaluated the efficacy and safety of growth hormone (GH) therapy (Norditropin®; Novo Nordisk, Bagsværd, Denmark) in paediatric patients with idiopathic short stature (ISS) in Korea. METHODS: This was an open-label, parallel-group, multicentre, interventional trial (ClinicalTrials.gov identifier: NCT01778023). Pre-pubertal patients (mean age 6.2 years; height, 107.1 cm) were randomised 2:1 to 12 months' GH treatment (0.469 mg/kg/week; group A, n=36) or 6 months untreated followed by 6 months' GH treatment (group B, n=18). Safety analysis was based on adverse events (AEs) in all GH-treated patients. RESULTS: After 6 months, height velocity (Ht-V), change in both height standard deviation score (Ht-SDS) and insulin-like growth factor 1 (mean difference [95% confidence interval {CI}]: 5.15 cm/year [4.09, 6.21]; 0.57 [0.43, 0.71]; 164.56 ng/mL [112.04, 217.08], respectively; all p<0.0001) were greater in group A than in group B. Mean difference in Ht-V for 0-6 months versus 6-12 months was 2.80 cm/year (95% CI 1.55, 4.04) for group A and -4.60 cm/year (95% CI -6.12, -3.09; both p<0.0001) for group B. No unexpected AEs were reported. CONCLUSIONS: During the first 6 months, height was significantly increased in GH-treated patients versus untreated patients with ISS. Safety of GH was consistent with the known safety profile.

Folate contents in human milk and casein-based and soya-based formulas, and folate status in Korean infants.

We assessed folate nutritional status from birth to 12 months in fifty-one infants who were fed human milk (HM; n 20), casein-based formula (CBF; n 12) or soya-based formula (SBF; n 19). Folate contents in ninety-five HM samples obtained from twenty mothers for the first 6-month period and twelve CBF and nineteen SBF samples were measured by bioassay after trienzyme extraction. Folate intake was estimated by weighing infants before and after feeding in the HM group and by collecting formula intake records in the formula-fed groups. After solid foods were introduced, all foods consumed were included to estimate folate intake. Serum folate and total homocysteine (tHcy) concentrations were determined at 5 and 12 months of age, and infant growth was monitored for the first 12 months. Mean HM folate contents ranged from 201 to 365 nmol/l with an overall mean of 291 nmol/l, and the contents peaked at 2 months postpartum. HM folate contents were higher than those reported in North America. Folate contents in CBF and SBF were markedly higher than those in HM and those claimed on the product labels. The overall folate intakes in formula-fed infants were significantly higher than those in HM-fed infants, and this was associated with significantly higher folate and lower tHcy in formula-fed infants than HM-fed infants at 5 months. At 12 months, serum folate was significantly higher in the SBF group than the other groups, whereas serum tHcy and overall growth were similar among all groups.

Emergence of amantadine-resistant H3N2 avian influenza A virus in South Korea.

We found a relatively high frequency of unique amantadine-resistant H3N2 and H9N2 avian influenza viruses (Val27Ile on M2 protein) isolated from live poultry markets in South Korea and confirmed that a Val27Ile single substitution in the M2 protein is enough to acquire the amantadine resistance phenotype by using reverse-genetically created human-avian reassortant viruses.

Development of multiplex rt-PCR assays for rapid detection and subtyping of influenza type A viruses from clinical specimens.

We developed multiplex RT-PCR assays that can detect and identify 12 hemagglutinin (H1-H12) and 9 neuraminidase (N1-N9) subtypes that are commonly isolated from avian, swine, and human influenza A viruses. RT-PCR products with unique sizes characteristic of each subtype were amplified by multiplex RT-PCRs, and sequence analysis of each amplicon was demonstrated to be specific for each subtype with 24 reference viruses. The specificity was demonstrated further with DNA or cDNA templates from 7 viruses, 5 bacteria, and 50 influenza A virus negative specimens. Furthermore, the assays could detect and subtype up to 105 dilution of each of the reference viruses that had an original infectivity titer of 106 EID50/ml. Of 188 virus isolates, the multiplex RT-PCR results agreed completely with individual RT-PCR subtyping results and with results obtained from virus isolations. Furthermore, the multiplex RT-PCR methods efficiently detected mixed infections with at least two different subtypes of influenza viruses in one host. Therefore, these methods could facilitate rapid and accurate subtyping of influenza A viruses directly from field specimens.

Longitudinal follow-up to near final height of auxological changes in girls with idiopathic central precocious puberty treated with gonadotropin-releasing hormone analog and grouped by pretreatment body mass index level.

PURPOSE: Reported changes in body mass index (BMI) in central precocious puberty (CPP) during and after gonadotropin-releasing hormone analog (GnRHa) treatment are inconsistent. We, therefore, investigated auxological parameters in GnRHa-treated girls with idiopathic CPP (ICPP) until attainment of near final height (NFH). METHODS: From the medical records of 59 ICPP girls who attained NFH after GnRHa therapy, auxological changes were compared between overweight (BMI≥85th percentile) and normal-weight (BMI<85th percentile) groups. BMIs were changed into standard deviation scores (BMISDSs) for subject chronologic age (BMISDS-CA) and bone age (BMISDS-BA). RESULTS: The incidence of overweight including obesity was high at the start of therapy (35.6%). The predicted adult height (PAH) at start of therapy was significantly shorter than the midparental height (MPH), whereas PAH at end of therapy approached MPH, and NFH was greater than MPH. Height velocity (HV) in the overweight group was higher during GnRHa therapy than that in the normal-weight group, but those in the two groups were not different after therapy until NFH. Both BMISDS-CA and BMISDS-BA increased significantly during therapy, but both BMISDSs decreased significantly after therapy until NFH. At NFH, neither BMISDS was different from that at baseline. In the normal-weight group, both BMISDSs increased during therapy and were maintained until NFH. In the overweight group, neither BMISDS changed during therapy, but there was a decrease after therapy until NFH. CONCLUSIONS: The different patterns of BMISDS change during and after GnRHa therapy until NFH between the 2 groups were related to the different HV during GnRHa therapy.

Modulation of store-operated calcium entry and nascent adhesion by p21-activated kinase 1.

Calcium mobilization is necessary for cell movement during embryonic development, lymphocyte synapse formation, wound healing, and cancer cell metastasis. Depletion of calcium in the lumen of the endoplasmic reticulum using inositol triphosphate (IP3) or thapsigargin (TG) is known to induce oligomerization and cytoskeleton-mediated translocation of stromal interaction molecule 1 (STIM1) to the plasma membrane, where it interacts with the calcium release-activated calcium channel Orai1 to mediate calcium influx; this process is referred to as store-operated calcium entry (SOCE). Furthermore, aberrant STIM1 or SOCE regulation is associated with cancer cell motility and metastasis. The p21-activated kinases (PAKs), which are downstream effectors of GTPases, reportedly regulate cytoskeletal organization, protrusive activity, and cell migration. Although cytoskeletal remodeling apparently contributes to calcium mobilization via SOCE, and vice versa, the mechanisms by which they regulate each other remain unclear. In this study, we aimed to characterize whether PAK1 modulates calcium mobilization and STIM1 localization. Our data demonstrate that PAK1 interacts with STIM1 in vitro and that this interaction was enhanced by treatment with a nascent adhesion inducer, such as phorbol 12,13-dibutyrate (PDBu). Under basal conditions, both proteins appeared to primarily colocalize in the cytosol, whereas treatment with PDBu induced their colocalization to vinculin-positive peripheral adhesions. Downregulation of PAK1 activity via chemical inhibitors or by PAK1 shDNA expression impaired STIM1-mediated calcium mobilization via SOCE. Based on these findings, we propose that PAK1 interacts with STIM1 to regulate calcium mobilization and the formation of cellular adhesions.

Effect of Growth Hormone Therapy on Height Velocity in Korean Children with Idiopathic Short Stature: A Phase III Randomised Controlled Trial.

BACKGROUND/AIMS: The SYNERGY (Saizen® for Your New Life and Brighter Tomorrow without Growth Deficiency) study is the first randomised multi-centre, open-label study to assess the short-term efficacy and safety of this recombinant human growth hormone (r-hGH) preparation for prepubertal children with idiopathic short stature in South Korea. METHODS: The SYNERGY study (ClinicalTrials.gov NCT01746862) was conducted at 9 centres throughout South Korea between December 2012 and March 2015. The primary endpoint was difference in height velocity from baseline to 6 months in the treatment and control arms. RESULTS: 97 children were screened; 90 were randomly assigned: 60 children to 0.067 mg/kg/day r-hGH for 12 months (treatment) and 30 children to 6 months of no treatment followed by 0.067 mg/kg/day r-hGH for 6 months (control). The 6-month mean height velocity in the treatment group increased from 5.63 cm/year (SD 1.62) to 10.08 cm/year (SD 1.92) (p < 0.0001) and from 4.94 cm/year (SD 1.91) to 5.92 cm/year (SD 2.01) (p = 0.0938) in the control group (between-group difference 3.47 cm/year, 95% CI 2.17-4.78; p < 0.0001). Adherence was > 90% throughout the study. The safety profile was consistent with that already known for r-hGH. CONCLUSION: Treatment with r-hGH in the SYNERGY study demonstrated a statistically significant increase in height velocity at 6 months.

Once-Weekly Administration of Sustained-Release Growth Hormone in Korean Prepubertal Children with Idiopathic Short Stature: A Randomized, Controlled Phase II Study.

BACKGROUND/AIMS: To determine the optimal dose of LB03002, a sustained-release, once-weekly formulation of recombinant human growth hormone (rhGH), and to compare its efficacy and safety with daily rhGH in children with idiopathic short stature (ISS). METHODS: This multicenter, randomized, open-label, phase II study included GH-naïve, prepubertal children with ISS, randomized to receive daily rhGH 0.37 mg/kg/week (control, n = 16), LB03002 0.5 mg/kg/week (n = 14), or LB03002 0.7 mg/kg/week (n = 16). The primary endpoint was height velocity (HV) change at week 26. RESULTS: At week 26, the least square (LS) means for HV change (cm/year) with control, LB03002 0.5 mg/kg/week, and LB03002 0.7 mg/kg/week were 5.08, 3.65, and 4.38, and the LS means for the change in height standard deviation score were 0.65, 0.49, and 0.58, respectively. The lower bound of the 90% confidence interval for the difference between LB03002 0.7 mg/kg/week and the control in the LS mean for HV change (-1.72) satisfied the noninferiority margin (-1.75). Adverse events were generally mild and short-lived. CONCLUSION: A once-weekly regimen of LB03002 0.7 mg/kg demonstrated noninferiority to the daily regimen of rhGH 0.37 mg/kg/week in terms of HV increments. LB03002 was well tolerated and its safety profile was comparable with that of daily rhGH.