Long-term exposure to air pollution and precocious puberty in South Korea.

BACKGROUND AND AIM: The increasing prevalence of precocious puberty (PP) has emerged as a significant medical and social problem worldwide. However, research on the relationship between long-term air pollution exposure and PP has been relatively limited. We thus investigated the association between long-term air pollution exposure and the onset of PP in South Korea. METHODS: We investigated a retrospective cohort using the Korea National Health Insurance Database. Six-year-old children born from 2007 to 2009 were examined (2013-2015). We included boys ≤10 years and girls aged ≤9 years who visited hospitals for early pubertal development, were diagnosed with PP per the ICD-10 (E228, E301, and E309), and received gonadotropin-releasing hormone agonist treatment. We analyzed data for boys up until 10 years old (60-month follow-up) and for girls up to 9 years old (48-month follow-up). We assessed the association between long-term air pollution exposure and the onset of PP using a Cox proportional hazard model. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) per 1 µg/m3 increase in fine particulate matter (PM2.5) and particulate matter (PM10) and per 1 ppb increase in sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3). RESULTS: This study included 1,205,784 children aged six years old between 2013 and 2015. A positive association was found between the 48-month moving average PM2.5 (HR: 1.019; 95% CI: 1.012, 1.027), PM10 (HR: 1.009; 95% CI: 1.006, 1.013), SO2 (HR: 1.037; 95% CI: 1.018, 1.055), and O3 (HR: 1.006; 95% CI: 1.001, 1.010) exposure and PP in girls but not boys. CONCLUSIONS: This study provides valuable insights into the harmful effects of air pollution during childhood and adolescence, emphasizing that air pollution is a risk factor that should be managed and reduced.

A Case of Chromosome 17q12 Deletion Syndrome with Type 2 Mayer-Rokitansky-Küster-Hauser Syndrome and Maturity-Onset Diabetes of the Young Type 5.

Chromosome 17q12 deletion syndrome (OMIM #614527) is a rare genetic disorder associated with a heterozygous 1.4-1.5 Mb deletion at chromosome 17q12, leading to a spectrum of clinical manifestations, including kidney abnormalities, neurodevelopmental delay, maturity-onset diabetes of the young type 5 (MODY5), and Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. We present the case of a 14-year-old Korean female diagnosed with chromosome 17q12 deletion syndrome, confirmed by chromosomal microarray analysis. The patient exhibited MODY5 with pancreatic agenesis, MRKH syndrome, dysmorphic facial features, developmental delay, kidney rotation anomaly, portal vein thrombosis with liver hypoplasia, short stature, and scoliosis. Management involved the initiation of multiple daily insulin injections for diabetes control, gynecological evaluation for MRKH syndrome, and multidisciplinary care for associated complications. This case highlights the complexity and varied organ involvement in chromosome 17q12 deletion syndrome. A comprehensive and multidisciplinary approach is crucial for the management of affected individuals, including regular monitoring, tailored interventions across various medical specialties, and providing psychosocial support.

Association between Thyroid Function and Insulin Resistance Indices in Korean Adolescents: Findings from the 2014-2015 Korea National Health and Nutrition Examination Survey.

AIM: This study investigated the sex-specific association between thyroid function and various insulin resistance (IR) indices, including noninsulin-based IR indices, in euthyroid adolescents. METHODS: A total of 465 adolescents (aged 12-18 years; 255 boys and 210 girls) based on data from the 2014-2015 Korea National Health and Nutrition Examination Survey were included. Serum thyrotropin (thyroid-stimulating hormone [TSH]) and free thyroxine (fT4) were used to assess thyroid function, whereas the homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin-sensitivity check index (QUICKI), glucose/insulin ratio (GIR), triglyceride-glucose (TyG) index, and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio were used to assess IR. The relationship between thyroid function and IR was analyzed using multiple linear regressions stratified by sex, considering obesity status. RESULTS: The relationship between thyroid function and IR varied depending on sex and was more pronounced in the overweight/obesity subgroup for both boys and girls. In overweight and obese boys and girls, fT4 was significantly associated with HOMA-IR and QUICKI with conflicting association directions. TSH was also positively associated with the TyG index in both sexes. CONCLUSIONS: The findings suggest that the relationship between thyroid function and IR in adolescents might vary depending on sex, and the degree of association was significant in obese adolescents.

A Korean male with Kleefstra syndrome presented with micropenis.

Kleefstra syndrome is caused by chromosome 9q34.3 deletion or heterozygous mutations in the euchromatin histone methyl transferase 1 (EHMT1) gene. It can be accompanied by intellectual disability, distinctive facial features, microcephaly, psychiatric disorders, hypotonia in childhood, hearing loss, heart defects, renal defects, epilepsy, speech anomalies, and obesity. Furthermore, genital anomalies are present in 30%-40% of male patients with Kleefstra syndrome, but their mechanisms have not been elucidated. Herein, we report a patient with Kleefstra syndrome presenting with micropenis. The patient was transferred to Kyungpook National University Children's Hospital for management of imperforate anus on the day of birth. Physical examination revealed micropenis with stretched penile length of 0.9 cm and facial dysmorphisms, including hypertelorism and anteverted nares. Chromosomal microarray revealed 424-kb heterozygous deletion at chromosome 9q34.3 (arr[hg19] 9q34.3 (140,234,315-140,659,055)x1). Among the involved main OMIM genes, phenotypically relevant genes were EHMT1 and NSMF. Endocrinological investigation showed low basal gonadotropin and testosterone levels. Anterior pituitary hormones and steroid hormone levels were in the normal range. Testicular function was normal based on human chorionic gonadotropin stimulation test. The patient experienced improvement in penile length growth with intramuscular testosterone enanthate injection initiated at 4 months of age. The purpose of this study is to describe the etiology, endocrine laboratory tests, and treatment of micropenis in Kleefstra syndrome.

A novel compound variant in GNRHR causing congenital idiopathic hypogonadotropic hypogonadism in a young male Korean patient.

Idiopathic hypogonadotropic hypogonadism (IHH) is a disease that shows symptoms of no or incomplete sexual maturation after 18 years old. The mutation of gonadotropin releasing hormone receptor gene (GNRHR) has been reported as the cause in 16% of total IHH patients. An 18-year-old adolescent was referred to endocrinology department for hypogonadism. He was born with cryptorchidism, had small testes at the age of 7 years, and showed low testosterone levels. Management of his hypogonadism was delayed due to his uncontrolled nephrotic syndrome. There were no abnormal findings on the brain MRI; atrophied testes discovered on his pelvis MRI; low levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were observed. In the HCG simulation test, testosterone levels showed no significant increase, rising from 1.11 to 1.15 ng/dL. The patient harbored a novel compound heterozygous variant of c.514G>A (p.Gly172Arg) and c.113G>A (p.Arg38Gln) in the GNRHR gene. Here, we report a case of new GNRHR compound variant c.514G>A (p.Gly172Arg) and c.113G>A (p.Arg38Gln) in a Korean adolescent for hypogonadotropic hypogonadism.

Metanephrine Negative Pheochromocytoma: A rare case report of dopamine-secreting tumor in an adolescent patient with NF1.

Pheochromocytoma (PCC) occurs in 4% of pediatric neurofibromatosis type 1 (NF1) patients and is mostly characterized by epinephrine and norepinephrine secretion. Herein, we report the first case of a dopamine-secreting PCC in a 13-year-old patient with NF1, in whom a left adrenal mass was incidentally found on abdominal computed tomography (CT) during hypertension workup. Fractionated 24-h urine metanephrine excretion was normal but urine dopamine level was elevated. On 123I-metaiodobenzylguanidine (MIBG) single photon emission tomography/CT (SPECT/CT), focal MIBG uptake was observed. Our multidisciplinary team determined that surgery would be difficult to perform because the tumor was small and the symptoms were vague, with only increased dopamine level. After six months, the tumor increased in size on abdominal CT, with focal significant uptake of the lesion on 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine (18F-FDOPA) PET/CT. Laparoscopic resection was performed, and the mass was histologically confirmed as PCC. Currently, the vital signs of the patient are stable, urine dopamine levels are normal, and there is no abnormal uptake of 18F-FDOPA PET/CT. This study reports a case of a rare dopamine-secreting PCC. When metanephrine is negative in patients at high risk of PCC, focused examination and multidisciplinary approach are needed.

Increase in blood glucose level and incidence of diabetic ketoacidosis in children with type 1 diabetes mellitus in the Daegu-Gyeongbuk area during the coronavirus disease 2019 (COVID-19) pandemic: a retrospective cross-sectional study.

BACKGRUOUND: The coronavirus disease 2019 (COVID-19) outbreak in the Daegu-Gyeongbuk area in 2020 has caused difficulties in the daily life and hospital care of children with type 1 diabetes mellitus (T1DM). We detected an increase in blood sugar levels in these children and the number of patients hospitalized with more severe diabetic ketoacidosis (DKA) compared to those before COVID-19. METHODS: This single-center study was conducted at Kyungpook National University Children's Hospital. The following patient groups were included; 45 returning patients diagnosed with T1DM and undergoing insulin treatment for more than 2 years and 20 patients newly diagnosed with T1DM before and after COVID-19 were selected by age matching. Returning patients before and after the outbreak were selected, and changes in hemoglobin A1c (HbA1c) levels were retrospectively reviewed. The HbA1c levels and severity of symptoms in newly diagnosed patients during hospitalization were examined. RESULTS: HbA1c levels in returning patients with T1DM were significantly increased after COVID-19 (before, 7.70%±1.38% vs. after, 8.30%±2.05%; p=0.012). There were 10 and 10 newly diagnosed patients before and after COVID-19, respectively. The proportion of patients with drowsiness and dyspnea at the time of admission was higher after COVID-19 than before (before, 2 of 10 vs. after, 4 of 10). The HbA1c levels were higher in newly diagnosed patients hospitalized after COVID-19 than before (before, 11.15% vs. after, 13.60%; p=0.036). CONCLUSION: Due to COVID-19 in the Daegu-Gyeongbuk area, there was an increase in blood glucose levels in children with T1DM and in the incidence of severe DKA in newly diagnosed diabetes mellitus patients.

Infantile hypercalcemia with novel compound heterozygous mutation in SLC34A1 encoding renal sodium-phosphate cotransporter 2a: a case report.

Idiopathic infantile hypercalcemia is characterized by hypercalcemia, dehydration, vomiting, and failure to thrive, and it is due to mutations in 24-hydroxylase (CYP24A1). Recently, mutations in sodium-phosphate cotransporter (SLC34A1) expressed in the kidney were discovered as an additional cause of idiopathic infantile hypercalcemia. This report describes a female infant admitted for evaluation of nephrocalcinosis. She presented with hypercalcemia, hypercalciuria, low intact parathyroid hormone level, and high 1,25-dihydroxyvitamin D3 level. Exome sequencing identified novel compound heterozygous mutations in SLC34A1 (c.1337G>A, c.1483C>T). The patient was treated with fluids for hydration, furosemide, a corticosteroid, and restriction of calcium/vitamin D intake. At the age of 7 months, the patient's calcium level was within the normal range, and hypercalciuria waxed and waned. Renal echogenicity improved on the follow-up ultrasonogram, and developmental delay was not noted. In cases of hypercalcemia with subsequent hypercalciuria, DNA analysis for SLC34A1 gene mutations and CYP24A1 gene mutations should be performed. Further studies are required to obtain long-term data on hypercalciuria and nephrocalcinosis.

Increased EMRSA-15 health-care worker colonization demonstrated in retrospective review of EMRSA hospital outbreaks.

BACKGROUND: Health care worker (HCW) colonization with methicillin resistant Staphylococcus aureus (MRSA) is a documented cause of hospital outbreaks and contributes to ongoing transmission. At Royal Perth Hospital (RPH) it had been anecdotally noted that the increasing prevalence of EMRSA-15 appeared to be associated with increased HCW colonization compared with Aus2/3-EMRSA. Hence we compared HCW colonization rates during outbreaks of EMRSA-15 and Aus2/3-EMRSA at a single institution. METHODS: We performed a retrospective review of EMRSA-15 and Aus2/3-EMRSA outbreaks from 2000-2009 at RPH, a quaternary hospital in Western Australia. Outbreak files were reviewed and relevant data extracted. RESULTS: Ten EMRSA-15 outbreaks were compared with seven Aus2/3 outbreaks. The number of patients colonized was similar between EMRSA-15 and Aus2/3-EMRSA outbreaks (median 7 [range 3-20] and 11 [5-26], respectively; P = 0.07) but the number of HCWs colonized was significantly higher in EMRSA-15 outbreaks compared to Aus2/3-EMRSA outbreaks (median 4 [range 0-15] and 2 [1-3], respectively; P = 0.013). The percentage of HCWs colonized was also higher in EMRSA-15 outbreaks versus Aus2/3-EMRSA outbreaks (median 3.4% [range 0-5.5%] and 0.81% [0.56-2.2%], respectively; P = 0.013). CONCLUSIONS: This study demonstrates a higher level of HCW colonization during EMRSA-15 outbreaks compared with Aus2/3-EMRSA outbreaks. This finding suggests that MRSA vary in their ability to colonize HCWs and contribute to outbreaks. MRSA type should be determined during outbreaks and future research should investigate the mechanisms by which EMRSA-15 contributes to increased HCW colonization.

Eradication of a large outbreak of a single strain of vanB vancomycin-resistant Enterococcus faecium at a major Australian teaching hospital.

OBJECTIVE: To demonstrate that nosocomial transmission of vancomycin-resistant enterococci (VRE) can be terminated and endemicity prevented despite widespread dissemination of an epidemic strain in a large tertiary-care referral hospital. INTERVENTIONS: Two months after the index case was detected in the intensive care unit, 68 patients became either infected or colonized with an epidemic strain of vanB vancomycin-resistant Enterococcus faecium despite standard infection control procedures. The following additional interventions were then introduced to control the outbreak: (1) formation of a VRE executive group; (2) rapid laboratory identification (30 to 48 hours) using culture and polymerase chain reaction detection of vanA and vanB resistance genes; (3) mass screening of all hospitalized patients with isolation of carriers and cohorting of contacts; (4) environmental screening and increased cleaning; (5) electronic flagging of medical records of contacts; and (6) antibiotic restrictions (third-generation cephalosporins and vancomycin). RESULTS: A total of 19,658 patient and 24,396 environmental swabs were processed between July and December 2001. One hundred sixty-nine patients in 23 wards were colonized with a single strain of vanB vancomycin-resistant E. faecium. Introducing additional control measures rapidly brought the outbreak under control. Hospital-wide screening found 39 previously unidentified colonized patients, with only 7 more nonsegregated patients being detected in the next 2 months. The outbreak was terminated within 3 months at a cost of dollar 2.7 million (Australian dollars). CONCLUSION: Despite widespread dissemination of VRE in a large acute care facility, eradication was achievable by a well-resourced, coordinated, multifaceted approach and was in accordance with good clinical governance.

Screening and electronic labelling of ward contacts of vancomycin-resistant Enterococcus faecium vanB carriers during a single-strain hospital outbreak and after discharge from hospital.

A large single-strain outbreak of vancomycin-resistant Enterococcus faecium (VREF) vanB occurred in Royal Perth Hospital from July to December 2001. When a VREF-carrying patient was discovered on a ward, all patients on the ward were screened with rectal swabs. A total of 172 patients were colonised, four with infections, but no deaths were attributable to VREF. The number of rectal swabs required to detect each carrier was recorded. On average four rectal swabs, each collected on separate days, were needed to detect more than 90 per cent of the 172 VREF carriers who were epidemiologically linked to the Royal Perth Hospital outbreak. An electronic alert system (Micro-Alert) was used to identify ward contacts of VREF carriers and enabled those who had not been screened before discharge to be followed-up and screened. Ninety-six contacts were actively followed-up in October 2001 and 32 (33.3%) were found to be VREF carriers. From 28 September 2001 to 30 April 2002, a total of 1,977 ward contacts were screened after discharge from hospital and 54 (2.73%) were found to be carrying VREF. We conclude that during single-strain outbreaks of vancomycin-resistant enterococci in hospitals, patient contacts need to be screened on more than three occasions in order to detect most of the carriers and control the outbreak. Secondly, electronic labelling and active follow-up of ward contacts of VREF carriers resulted in a significant number of carriers being detected who otherwise posed a risk of initiating further outbreaks in hospitals if they were readmitted.

A review of the Royal Perth Hospital Bali experience: an infection control perspective.

Thirty five patients were transferred to Royal Perth Hospital (RPH) after the Bali bombings. The patients had severe burn injuries and were considered to be at high-risk of both the carriage and acquisition of multi-resistant organisms (MROs). Whilst seeking to protect the Bali patients with a comprehensive infection control response, we also sought to protect other high-risk patients from nosocomial acquisition of MROs. MROs were detected from 25 (82%) of the 29 Bali patients admitted to RPH. Bali patients were colonised, or infected, with one or more of the following MROs: multi-resistant Acinetobacter baumannii (MRAB) (19 patients), extended-spectrum ß-lactamase (ESBL) producing Gram-negative bacteria (15 patients), vancomycin-resistant enterococci (VRE) (nine patients), multi-resistant Pseudomonas aeruginosa (MRPA) (six patients), multi-resistant Chryseobacterium sp. (four patients), and methicillin-resistant Staphylococcus aureus (MRSA) (three patients). Five Bali patients developed a total of eight bacteraemic episodes, with MRPA sepsis contributing to death in two patients. Since the Bali bombings horizontal transmission of Bali MROs has occurred in 41 non-Bali patients in RPH. MRPA has had the greatest clinical impact. Eight non-Bali patients developed a total of 11 bacteraemic episodes, with MRPA sepsis contributing to death in four patients. However, apart from MRPA, we have now controlled transmission of the other MROs in RPH. The emergency response to the Bali disaster required strong leadership, good communication and multi-disciplinary teamwork. The infection control strategy contributed to good outcomes for most Bali bombing patients. However, many patients within the Bali cohort were heavily colonised with MROs, and some developed invasive infection. Subsequent nosocomial transmission of these MROs to non-Bali patients has been a legacy of the Bali tragedy.