ABSTRACT
Purpose@#GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a). @*Materials and Methods@#Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study. @*Results@#RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0). @*Conclusion@#GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.
ABSTRACT
Background@#This study investigated the effectiveness of a social networking site (SNS)-based automatic mobile message providing system on glycemic control in patients with type 2 diabetes mellitus (T2DM). @*Methods@#A 3-month, randomized, open-label, controlled, parallel-group trial was conducted. One hundred and ten participants with T2DM were randomized to a mobile message system (MMS) (n=55) or control group (n=55). The MMS group received protocolbased automated messages two times per day for 10 weeks regarding diabetes self-management through KakaoTalk SNS messenger. The primary outcome was the difference in the change in glycated hemoglobin (HbA1c) levels (%) from baseline to week 12. @*Results@#HbA1c levels were more markedly decreased in the MMS group (8.4%±0.7% to 8.0%±1.1%) than in the control group (8.5%±0.8% to 8.4%±0.8%), resulting in a significant between-group difference (P=0.027). No differences were observed in changes in fasting glucose levels, lipid profiles, and the number of participants who experienced hypoglycemia, or in changes in lifestyle behavior between groups. However, the self-monitoring of blood glucose frequency was significantly increased in the MMS group compared to the control group (P=0.003). In addition, sleep duration was increased in the MMS group, but was not changed in the control group. @*Conclusion@#An SNS-based automatic mobile message providing system was effective in improving glycemic control in patients in T2DM. Studies which based on a more individualized protocol, and investigate longer beneficial effect and sustainability will be required in the future.
ABSTRACT
Objective@#This study aimed to identify predictive factors for suspected intestinal ischemia (II) when compared with those of acute gastroenteritis (AGE) in the emergency department (ED). @*Methods@#This single-center retrospective case-control study included 71 patients with II and 355 with AGE who visited the ED from 2014 to 2021. We attempted to compare the initial clinical presentation and laboratory examination findings of the II and AGE patients. The data in this study were analyzed using the chi-square test, Student t-test, and logistic regression analysis. @*Results@#The analyses showed that patients with II accounted for only about 0.018% of patients visiting the ED. The logistic regression analysis results revealed that age >51 years (odds ratio [OR], 9.75; 95% confidence interval [CI], 3.84-24.75), onset-to-visit time 51 years; onset-to-visit time is <48 hours; symptoms of lower abdominal pain and hematochezia are present, there is PMHx of A-fib, hyperglycemia, and hypoalbuminemia; and diarrhea, febrile feeling/chill, and fever are absent.
ABSTRACT
Purpose@#Survivors of childhood leukemia are at risk of growth impairment due to intensive chemotherapy and radiation treatments. This study investigated the auxological and biochemical characteristics of childhood leukemia survivors diagnosed with growth hormone deficiency (GHD) and the changes in these parameters after 1 year of growth hormone (GH) treatment. @*Methods@#A total of 24 children diagnosed with GHD after leukemia treatment was analyzed. Clinical and biochemical data were collected retrospectively at leukemia diagnosis, GHD diagnosis, and 1 year after GH treatment. Standard deviation score (SDS) was calculated based on the age- and gender-adjusted population. @*Results@#Of the 24 children included in this study, 19 received GH treatment. The median age at GHD diagnosis was 12.3 years, and the median delay in bone age was 1.46 years. Height SDS decreased from -0.69 at leukemia diagnosis to -2.58 at GHD diagnosis (P<0.001). The change in height SDS with and without GH for 1 year was 0.35 and -0.21, respectively (P=0.044). In regression analyses, higher height SDS at GHD diagnosis and a smaller decrease of the height SDS between leukemia and GHD diagnoses were positively correlated with height SDS after GH treatment. @*Conclusion@#GH treatment could be beneficial and safe for improving height in childhood leukemia survivors with GHD. Height SDS at GHD diagnosis and reduction of height SDS between leukemia and GHD diagnosis could be potential factors in predicting the therapeutic effects. Close auxological monitoring is recommended for any childhood leukemia survivors who experience posttreatment height decline.
ABSTRACT
Purpose@#This study aimed to investigate the clinical factors associated with bone mineral density (BMD) among children and adolescents with osteoporosis secondary to treatment for underlying clinical conditions. @*Methods@#We retrospectively reviewed the medical records of patients aged 10–18 years and evaluated them for lumbar spine BMD (LSBMD) after treatment for underlying diseases, including hemato-oncologic, rheumatologic system, and inflammator y bowel diseases. LSBMD measured by dual-energy x-ray absorptiometry (DXA) performed from March 2019 to March 2021 was evaluated. We analyzed 117 patients who underwent initial DXA after treatment for underlying diseases. @*Results@#Subjects in this study had multiple underlying diseases: hemato-oncologic (78.6%), rheumatologic (11.1%), and inflammatory bowel diseases (10.3%). There was no significant association between the z-score and bone metabolic markers (P>0.05). However, higher cumulative glucocorticoid (GC) dose significantly reduced LSBMD z-score (P=0.029). Moreover, the association between cumulative dose of GC and initial z-score of LSBMD was significant in logarithmic regression analysis (P=0.003, R2=0.149). GC accumulation was a significant risk factor for vertebral fracture when the initial BMD was evaluated after treatment (P=0.043). Bone metabolic markers did not significantly influence the risk of vertebral fracture. @*Conclusion@#Initial bone mass density of the lumbar spine evaluated after long-term GC use for underlying diseases is a predictor of further vertebral fractures.
ABSTRACT
Purpose@#Preclinical data indicate that response to radiotherapy (RT) depends on DNA damage repair. In this study, we investigated the role of mutations in genes related to DNA damage repair in treatment outcome after RT. @*Materials and Methods@#Patients with solid tumor who participated in next generation sequencing panel screening using biopsied tumor tissue between October 2013 and February 2019 were reviewed and 97 patients that received RT were included in this study. Best response to RT and the cumulative local recurrence rate (LRR) were compared according to absence or presence of missense, nonsense, and frameshift mutations in ATM and/or BRCA1/2. @*Results@#Of the 97 patients, five patients harbored mutation only in ATM, 22 in only BRCA1/2, and six in both ATM and BRCA1/2 (ATMmtBRCAmt). Propensity score matching was performed to select the control group without mutations (ATMwtBRCAwt, n=33). In total, 90 RT-treated target lesions were evaluated in 66 patients. Highest objective response rate of 80% was observed in ATMmtBRCAmt lesions (p=0.007), which was mostly durable. Furthermore, the cumulative 1-year LRR was the lowest in ATMmtBRCAmt lesions and the highest in ATMwtBRCAwt lesions (0% vs. 47.9%, p=0.008). RT-associated toxicities were observed in 10 treatments with no significant difference among the subgroups (p=0.680). @*Conclusion@#Tumors with ATM and BRCA1/2 mutations exhibited superior tumor response and local control after RT compared to tumors without these mutations. The results are hypothesis generating and suggest the need for integrating the tumor mutation profile of DNA repair genes during treatment planning.
ABSTRACT
Background@#Despite the extraordinary speed of mass vaccination efforts, an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delta variant in a vaccinee with coronavirus disease 2019 (COVID-19) mRNA vaccine was identified in an adult day service center (ADSC) of Jeju, South Korea. The primary objective of this study was to investigate the epidemiologic features in infection-vulnerable facilities with a high vaccination rate of BNT162b2 mRNA COVID-19 vaccine. The second was to estimate the secondary transmission prevention effect of the vaccine in the household members by vaccination status. @*Methods@#We included all ADSC participants, staff and their household members. All COVID-19 infected cases were confirmed by reverse transcriptase polymerase chain reaction.We calculated attack rate in ADSC and the secondary attack rate (SAR) in household members by vaccination status. @*Results@#Among a total of 42 participants and 16 staff, of which 96.6% were fully vaccinated with BNT162b2 mRNA COVID-19 vaccine, 12 symptomatic cases and 13 asymptomatic confirmed cases of COVID-19 were found. The attack rate was 43.1%, with 13 isolates identified as SARS-CoV-2 virus, delta variant. The SAR in unvaccinated and partially vaccinated household members were 27.8% (5/18) and 25.0% (5/20), respectively, while the SAR in fully vaccinated household members was 12.5% (1/8). @*Conclusion@#We describe a SARS-CoV-2 delta variant outbreak in ADSC with high vaccine coverage rate, characterized by high infection rate, high transmissibility, and low clinical severity. The outbreak proceeded to unvaccinated or partially vaccinated household members, emphasizing the need for immunizing close contacts of high-risk groups.
ABSTRACT
Background@#Discontinuing growth hormone (GH) treatment during the transition to adulthood has been associated with adverse health outcomes in patients with childhood-onset growth hormone deficiency (CO-GHD). This study investigated the metabolic changes associated with interrupting GH treatment in adolescents with CO-GHD during the transition period. @*Methods@#This study included 187 patients with CO-GHD who were confirmed to have adult GHD and were treated at six academic centers in Korea. Data on clinical parameters, including anthropometric measurements, metabolic profiles, and bone mineral density (BMD) at the end of childhood GH treatment, were collected at the time of re-evaluation for GHD and 1 year after treatment resumption. @*Results@#Most patients (n=182, 97.3%) had organic GHD. The median age at treatment discontinuation and re-evaluation was 15.6 and 18.7 years, respectively. The median duration of treatment interruption was 2.8 years. During treatment discontinuation, body mass index Z-scores and total cholesterol, low-density lipoprotein, and non-high-density lipoprotein (HDL) cholesterol levels increased, whereas fasting glucose levels decreased. One year after GH treatment resumption, fasting glucose levels, HDL cholesterol levels, and femoral neck BMD increased significantly. Longer GH interruption (>2 years, 60.4%) resulted in worse lipid profiles at re-evaluation. The duration of interruption was positively correlated with fasting glucose and non-HDL cholesterol levels after adjusting for covariates. @*Conclusion@#GH treatment interruption during the transition period resulted in worse metabolic parameters, and a longer interruption period was correlated with poorer outcomes. GH treatment should be resumed early in patients with CO-GHD during the transition period.
ABSTRACT
Childhood adrenocortical carcinoma (ACC) is a rare disease that is mostly linked to familial cancer syndrome. Although the prevalence of ACC is extremely low in children, it is clinically important to diagnose ACC early because age and tumor stage are closely related to prognosis. From this perspective, understanding the underlying genetics and possible symptoms of ACC is crucial in managing ACC with familial cancer syndromes. In this report, we present the case of a 3-year-old girl who initially presented with symptoms of precocious puberty and was later found to have ACC by imaging analysis. On genetic analysis, the patient was found to have a MEN1 gene mutation. MEN1 mutations are found in patients with multiple endocrine neoplasia type 1 (MEN1), usually precipitating multiple endocrine tumors, including pituitary adenoma, parathyroid hyperplasia, and adrenal tumors. Although MEN1 mutation is usually inherited in an autosomal dominant manner, neither of the patient’s parents had the same mutation, making hers a case of sporadic MEN1 mutation with initial presentation of ACC. The clinical course and further investigations of this patient are discussed in detail in this report.
ABSTRACT
Neonatal diabetes mellitus can be categorized as transient, permanent, or syndromic, and approximately half of the cases are transient. We present a case involving a term newborn who showed overt progression of transient neonatal diabetes mellitus, with complete remission within 6 months. On the second day of life, the patient presented with tachypnea, hyperglycemia, and decreased serum levels of C-peptide and insulin. Continuous subcutaneous infusion of insulin and continuous glucose monitoring were well tolerated. The patient showed a normal growth pattern, with no hyperglycemic or hypoglycemic episodes at 6 months of age. As it is rare and often asymptomatic, hyperglycemia may be attributed to various factors, including intrauterine environment, perinatal stress, and diverse genetic background. Therefore, consistent blood glucose monitoring and prompt early insulin therapy are crucial for any term newborns with persistent hyperglycemia, to prevent further diabetic complications. Moreover, continuous subcutaneous insulin infusion and the utilization of continuous glucose monitoring devices are the most effective and practical management strategies.
ABSTRACT
Background/Aims@#Although people with diabetes have been shown to have higher mortality than people without diabetes, there is a lack of data on the association between fasting plasma glucose (FPG) levels and cause-specific mortality rates in the general population. @*Methods@#A total of 326,547 Korean adults over 20 years of age, who had received a health checkup between 2006 and 2008 were selected from the Korean National Health Insurance Service sample cohort dataset and followed until 2015. We estimated hazard ratios (HRs) of all-cause mortality and cause-specific mortality relative to various range of FPG levels. All causes of death were classified according to International Classification of Diseases (ICD)-10 codes. @*Results@#During follow-up (mean, 8.5 years), a total of 13,536 deaths (mortality rate 4.89/1,000 person-year) occurred; 4,916 deaths from cancer, 2,133 from cardiovascular disease, 762 from infectious disease, 199 from renal disease, and 5,526 from other causes. The overall mortality rate increased with an increase in FPG category (HR, 1.78; 95% confidence interval, 1.65 to 1.92; in the ≥ 160 mg/dL). In addition, a J-shaped associations was found between FPG levels and all-cause mortality after adjustment for age, sex, smoking, drinking, physical activity, body mass index, diabetes mellitus medication, hypertension, and dyslipidemia. In particular, the risk of cancer-mortality with high FPG levels was increased for men but not women. @*Conclusions@#The risk of all-cause and cause-specific mortality showed the tendency to increase when the FPG level was outside of the normal range, indicating a J-shaped relationship, in both men and women.
ABSTRACT
Purpose@#The aim of this study is to evaluate the effect of body mass index (BMI) on peak serum growth hormone (GH) level after GH stimulation test in children with short stature. @*Methods@#Data were obtained from retrospective medical record reviews of those who visited the pediatric endocrine clinic at St. Vincent’s Hospital of Catholic University for short stature from January 2010 to June 2019. A total of 115 children (66 boys and 49 girls) whose height was less than the third percentile according to age and sex underwent GH stimulation testing. @*Results@#Of the 115 subjects, 47 were diagnosed with GH deficiency (GHD) and 68 were diagnosed with idiopathic short stature (ISS). In patients with GHD, weight standard deviation score (SDS) (P<0.001) and BMI SDS (P≤0.001) were higher, and free thyroxine (T4) level (P=0.012) was lower than those in the ISS group. In total subjects, peak serum GH level after GH stimulation test showed negative correlations with weight SDS (r=-0.465, P<0.001), BMI SDS (r=-0.398, P<0.001), and thyroid stimulating hormone (r=-0.248, P=0.008) and a positive correlation with free T4 (r=0.326, P<0.001). In multiple regression analysis, BMI SDS (P=0.003) was negatively associated with peak serum GH level in GH stimulation testing after adjusting for age, sex, pubertal status, and type of pharmacological stimulus. @*Conclusion@#The BMI SDS influences peak serum GH level after GH stimulation testing. We should consider BMI factors when interpreting the results of GH stimulation testing.
ABSTRACT
Neonatal diabetes mellitus can be categorized as transient, permanent, or syndromic, and approximately half of the cases are transient. We present a case involving a term newborn who showed overt progression of transient neonatal diabetes mellitus, with complete remission within 6 months. On the second day of life, the patient presented with tachypnea, hyperglycemia, and decreased serum levels of C-peptide and insulin. Continuous subcutaneous infusion of insulin and continuous glucose monitoring were well tolerated. The patient showed a normal growth pattern, with no hyperglycemic or hypoglycemic episodes at 6 months of age. As it is rare and often asymptomatic, hyperglycemia may be attributed to various factors, including intrauterine environment, perinatal stress, and diverse genetic background. Therefore, consistent blood glucose monitoring and prompt early insulin therapy are crucial for any term newborns with persistent hyperglycemia, to prevent further diabetic complications. Moreover, continuous subcutaneous insulin infusion and the utilization of continuous glucose monitoring devices are the most effective and practical management strategies.
ABSTRACT
Background/Aims@#Although people with diabetes have been shown to have higher mortality than people without diabetes, there is a lack of data on the association between fasting plasma glucose (FPG) levels and cause-specific mortality rates in the general population. @*Methods@#A total of 326,547 Korean adults over 20 years of age, who had received a health checkup between 2006 and 2008 were selected from the Korean National Health Insurance Service sample cohort dataset and followed until 2015. We estimated hazard ratios (HRs) of all-cause mortality and cause-specific mortality relative to various range of FPG levels. All causes of death were classified according to International Classification of Diseases (ICD)-10 codes. @*Results@#During follow-up (mean, 8.5 years), a total of 13,536 deaths (mortality rate 4.89/1,000 person-year) occurred; 4,916 deaths from cancer, 2,133 from cardiovascular disease, 762 from infectious disease, 199 from renal disease, and 5,526 from other causes. The overall mortality rate increased with an increase in FPG category (HR, 1.78; 95% confidence interval, 1.65 to 1.92; in the ≥ 160 mg/dL). In addition, a J-shaped associations was found between FPG levels and all-cause mortality after adjustment for age, sex, smoking, drinking, physical activity, body mass index, diabetes mellitus medication, hypertension, and dyslipidemia. In particular, the risk of cancer-mortality with high FPG levels was increased for men but not women. @*Conclusions@#The risk of all-cause and cause-specific mortality showed the tendency to increase when the FPG level was outside of the normal range, indicating a J-shaped relationship, in both men and women.
ABSTRACT
Purpose@#The aim of this study is to evaluate the effect of body mass index (BMI) on peak serum growth hormone (GH) level after GH stimulation test in children with short stature. @*Methods@#Data were obtained from retrospective medical record reviews of those who visited the pediatric endocrine clinic at St. Vincent’s Hospital of Catholic University for short stature from January 2010 to June 2019. A total of 115 children (66 boys and 49 girls) whose height was less than the third percentile according to age and sex underwent GH stimulation testing. @*Results@#Of the 115 subjects, 47 were diagnosed with GH deficiency (GHD) and 68 were diagnosed with idiopathic short stature (ISS). In patients with GHD, weight standard deviation score (SDS) (P<0.001) and BMI SDS (P≤0.001) were higher, and free thyroxine (T4) level (P=0.012) was lower than those in the ISS group. In total subjects, peak serum GH level after GH stimulation test showed negative correlations with weight SDS (r=-0.465, P<0.001), BMI SDS (r=-0.398, P<0.001), and thyroid stimulating hormone (r=-0.248, P=0.008) and a positive correlation with free T4 (r=0.326, P<0.001). In multiple regression analysis, BMI SDS (P=0.003) was negatively associated with peak serum GH level in GH stimulation testing after adjusting for age, sex, pubertal status, and type of pharmacological stimulus. @*Conclusion@#The BMI SDS influences peak serum GH level after GH stimulation testing. We should consider BMI factors when interpreting the results of GH stimulation testing.
ABSTRACT
Background@#The risk of weight gain as a consequence of school closure in children during the coronavirus disease-2019 (COVID-19) pandemic has been recognized. This study was performed to investigate changes in anthropometric and metabolic parameters in children following a 6-month period of social distancing and school closure due to the pandemic. @*Methods@#This retrospective cohort study was conducted in school-aged children that were on routine follow-up at the Growth Clinic of Seoul St. Mary's Hospital. Changes in body mass index (BMI) standard deviation scores (z-scores), lipid profiles, and vitamin D levels were investigated. The 1-year period prior to school closure was defined as “pre-COVID-19 period,” and the subsequent 6-month period as “COVID-19 period.” @*Results@#Overall, 226 children between 4 to 14 years old without comorbidities were assessed. On average, their BMI z-scores increased by 0.219 (95% confidence interval [CI], 0.167–0.271; P < 0.001) in the COVID-19 period compared to the pre-COVID-19 period, and the proportion of overweight or obesity increased from 23.9% in the pre-COVID-19 period to 31.4% in the COVID-19 period. The number of days after school closure ( P = 0.004) and being in the normoweight category in the pre-COVID-19 period ( P = 0.017) were factors associated with an increased BMI in the COVID-19 period. The mean triglyceride (105.8 mg/dL vs. 88.6 mg/dL, P < 0.001) and low-density lipoprotein-cholesterol (100.2 mg/dL vs. 94.0 mg/dL, P = 0.002) levels were higher, whereas the calcidiol level (18.9 mg/dL vs. 23.8 mg/dL, P < 0.001) was lower in the COVID-19 period compared to the pre-COVID-19 period. @*Conclusion@#Within 6 months, increased childhood obesity and vitamin D deficiencies were observed. The duration of school closure was significantly associated with an increased BMI and being normoweight does not exclude the risks for gaining weight.
ABSTRACT
Purpose@#To evaluate the effect of a ptosis correction operation on eyebrow position of senile upper lid ptosis patients. @*Methods@#A retrospective study of 140 eyes of 70 patients who had a ptosis correction operation between June 2011 and July 2018 was conducted. Marginal reflex distance 1 and brow height were measured preoperatively and at 1 month and 3 months postoperatively. Patients were divided into two groups, according to whether brow height asymmetry was symmetrized (≤1 mm) or not after the operation. @*Results@#The average brow height decreased after the operation (19.3-18.3 mm, p = 0.00), as did the brow height symmetricity (2.7-2.3 mm, p = 0.01). The symmetric group were older and had a higher female ratio than the asymmetric group, as well as a smaller preoperative brow symmetricity. @*Conclusions@#Brow height and brow asymmetry were reduced by ptosis correction of senile upper lid ptosis patients. The symmetrization rate was higher in patients who were older, female, and who had smaller preoperative brow symmetricity.
ABSTRACT
Background/Aims@#We examined the concordance rate among fasting plasma glucose (FPG), 2-hour post-challenge glucose (2hr PG), and hemoglobin A1c (HbA1c) in the diagnosis of diabetes in a population with a high-risk for type 2 diabetes mellitus (T2DM) in Korea. @*Methods@#Among the participants from the Korean Diabetes Prevention Study, individuals with FPG ≥ 100 mg/dL, body mass index (BMI) ≥ 23.0 kg/m2, and no previous history of T2DM were consecutively enrolled after a 75 g glucose tolerance test. We analyzed the differences in the clinical characteristics in subjects with stage 1 (FPG, 100 to 109 mg/dL) and stage 2 (FPG, 110 to 125 mg/dL) impaired fasting glucose (IFG). @*Results@#Of 1,637 participants, 27.2% had T2DM and 59.3% had IFG and/or impaired glucose tolerance (IGT). The mean age was 55.0 ± 8.1 years and the mean BMI was 26.3 ± 2.7 kg/m2. Based on FPG criteria, 515 (31.4%) and 352 (21.5%) subjects were classified as having stage 1 and stage 2 IFG, respectively. The 19.0% of stage 1 and 43.5% of stage 2 subjects showed 2hr PG levels in the diabetic range. Even for those in the normal FPG range, 63 (9.5%) participants showed a 2hr PG level of ≥ 200 mg/dL. Of 446 subjects with newly-diagnosed diabetes, 340 (76.2%) showed FPG levels < 126 mg/dL. @*Conclusions@#The oral glucose tolerance test should be actively considered for Korean adults who are overweight or obese with the IFG range (FPG, 100 to 125 mg/ dL) to allow for early detection of diabetes and prompt intervention.
ABSTRACT
BackgroundHypoxia can occur in pancreatic islets in type 2 diabetes mellitus. Pancreatic stellate cells (PSCs) are activated during hypoxia. Here we aimed to investigate whether PSCs within the islet are also activated in hypoxia, causing β-cell injury.MethodsIslet and primary PSCs were isolated from Sprague Dawley rats, and cultured in normoxia (21% O2) or hypoxia (1% O2). The expression of α-smooth muscle actin (α-SMA), as measured by immunostaining and Western blotting, was used as a marker of PSC activation. Conditioned media (hypoxia-CM) were obtained from PSCs cultured in hypoxia.ResultsIslets and PSCs cultured in hypoxia exhibited higher expressions of α-SMA than did those cultured in normoxia. Hypoxia increased the production of reactive oxygen species. The addition of N-acetyl-L-cysteine, an antioxidant, attenuated the hypoxia-induced PSC activation in islets and PSCs. Islets cultured in hypoxia-CM showed a decrease in cell viability and an increase in apoptosis.ConclusionPSCs within the islet are activated in hypoxia through oxidative stress and promote islet cell death, suggesting that hypoxia-induced PSC activation may contribute to β-cell loss in type 2 diabetes mellitus.
ABSTRACT
Acute lymphoblastic leukemia (ALL), currently the most common pediatric leukemia, has a high curability rate of up to 90%. Endocrine disorders are highly prevalent in children with ALL, and skeletal morbidity is a major issue induced by multiple factors associated with ALL. Leukemia itself is a predominant risk factor for decreased bone formation, and major bone destruction occurs secondary to chemotherapeutic agents. Glucocorticoids are cornerstone drugs used throughout the course of ALL treatment that exert significant effects on demineralization and osteoclastogenesis. After completion of treatment, ALL survivors are prone to multiple hormone deficiencies that eventually affect bone mineral accrual. Dual-energy X-ray absorptiometry, the most widely used method of measuring bone mineral density, is used to determine the presence of childhood osteoporosis and vertebral fracture. Supplementation with calcium and vitamin D, administration of pyrophosphate analogues, and promotion of mobility and exercise are effective options to prevent further bone resorption and fracture incidence. This review focuses on addressing bone morbidity after pediatric ALL treatment and provides an overview of bone pathology based on skeletal outcomes to increase awareness among pediatric hemato-oncologists and endocrinologists.
