OBJECTIVE: To summarize the clinical and genetic characteristics of a child with 46,XX Ovotesticular disorder of sex development (46,XX OTDSD) due to copy number variation of SOX3 gene. METHODS: A 46,XX male patient presented at the Capital Center for Children's Health, Capital Medical University in November 2024 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples were taken from the child and his parents and subjected to trio whole-genome sequencing. Skewed X-chromosome inactivation was tested in the child and his mother. A literature review was carried out on 46,XX males associated with mutations of the SOX3 gene. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: SHERLL2025056). RESULTS: The 10-year-old boy presented with hypospadias and cryptorchidism at birth. Chromosome analysis at one year and a half revealed a 46,XX karyotype. Gonadal biopsy showed testicular tissue, while ultrasound at the age of 10 detected ovotesticular tissue. Whole-genome sequencing identified a 660 kb duplication in the Xq27.1 region, which was derived from his mother. X-chromosome inactivation testing showed random inactivation in the child and mild non-random inactivation in the mother. Literature review has found 11 publications involving 15 patients (including our case), among whom 14 had a male social gender. They had primarily presented with hypospadias at birth but had no significant endocrine abnormalities. Most patients had experienced testicular failure after puberty. SOX3 related 46,XX males are mainly caused by de novo duplications, although a few maternal carriers had been discovered. CONCLUSION Duplication of the SOX3 gene probably underlay the pathogenesis is this 46,XX male. Individuals with 46,XX SRY negative male phenotypes should be routinely screened for SOX3 gene variants. Structural variations of the SOX3 gene can lead to complete or partial sex reversal in 46,XX individuals with minimal impact on intellectual and motor development, as well as other endocrine hormones.
Child ; Humans ; Male ; 46, XX Disorders of Sex Development/genetics* ; DNA Copy Number Variations ; Gene Duplication ; Phenotype ; SOXB1 Transcription Factors/genetics*

INTRODUCTION

Patients with diabetes are at higher risk of developing severe COVID-19 infection with a two-fold increased risk of mortality. This study described the risk factors affecting clinical outcomes of confirmed COVID-19 patients with diabetes mellitus at the University of Santo Tomas Hospital, Manila, Philippines.

This retrospective study included 204 patients with COVID-19 (34 with known type 2 diabetes and 2 with new-onset diabetes) from March to October 2020. Clinical characteristics and laboratory parameters were collected and analyzed in subjects with diabetes. A univariate logistic regression was used to calculate the odds ratios and 95% confidence interval (CI) for the patient’s risk factors associated with mortality or poor prognosis.

Moderate COVID-19 infection occurred in 52.8% of type 2 diabetes mellitus (T2DM) patients and critical COVID-19 infection in 27.8%. All patients with critical COVID-19 infection presented with acute respiratory distress syndrome, half had concomitant septic shock and respiratory failure was observed in 27.8%. The average length of hospital stay was approximately 17.5 days. T2DM patients with established atherosclerotic cardiovascular disease (ASCVD) are 5.1 times (95% CI 1.2 to 21.4) more likely to develop severe or critical COVID-19 infection, and more likely to stay in the hospital for more than 14 days. HbA1c >8.5% is a potential risk (OR = 3.7, 0.6 to 21.6) for severe to critical disease. T2DM patients with concomitant coronary artery disease are 7.6 times (95% CI 1.3 to 43.4) more likely to stay longer (more than 14 days) as compared to those without existing coronary artery disease. Prior statin use was a significant risk factor for ICU admission (p-value 0.0341). Other potential risk factors affecting clinical outcomes are obesity (OR 3, 0.4 to 22.7), prior use of thiazolidinedione (OR 7.8, 0.5 to 126.7) or sodium-glucose transporter 2 (SGLT2) inhibitors (OR 7.5, 0.4 to 145) and prior use of anti-thrombotic (OR 4.6, 0.4 to 56.8). The recovery rate of T2DM patients hospitalized for COVID-19 infection was 86.1%.

Patients with T2DM are more vulnerable to COVID-19 infection. The presence of established ASCVD increases the likelihood of severe COVID-19 disease as well as longer length of hospital stay for more than 14 days. Early recognition and prompt treatment led to a favorable recovery rate.

INTRODUCTION

Administration of antenatal corticosteroids (ACS) between 24 and 36 weeks of gestation is recommended to pregnant women at risk of preterm delivery to decrease the risk of respiratory distress syndrome, intra-ventricular hemorrhage and neonatal death. However, it may worsen glycemic profile primarily in those with gestational diabetes mellitus (GDM).

To determine the effects of ACS on maternal glycemia in Filipino women with GDM and to analyze the factors associated with insulin use or increased insulin requirement.

A retrospective study of the medical records of Filipino women with GDM who were admitted and received ACS treatment (betamethasone) between 24- and 36-weeks age of gestation (AOG) for fetal lung maturity from 2017-2019. Clinical characteristics (age, parity, completed ACS dose, AOG at ACS administration and mode of delivery) and glycemic control were retrieved and compared before and after ACS treatment. Data collection began the day or on the day before steroids were given and continued until discharge or delivery.

Included were 42 pregnant women with GDM. Of these, 28 women with GDM were treated by diet alone (Group A) while 14 women with GDM were started on insulin in addition to diet (Group B). After betamethasone therapy was initiated, only three (Group A1; n=3/28) patients had good glycemic control with diet alone and the rest were given insulin treatment (Group A2; n=25/28). In this subpopulation of Group A2, insulin requirement within 24 hours after ACS was at 0.3 units per kg of body weight. There was a steady increase with maximum requirement observed on day 4 and decreased thereafter to 0.33 units per kg of body weight on day 5. For GDM women in Group B, only three maintained their insulin dose (Group B1; n=3/14) while 11 (Group B2; n=11/14) women with GDM previously on insulin, required further increase in insulin from day 1-2 reaching 140% increase in insulin dose on day 2. Thereafter, there was a gradual decrease of insulin dose almost returning to initial dose on day 5.

Insulin initiation was observed among GDM diet-controlled mothers (Group A) who were given ACS therapy at ≥31 weeks age of gestation. Age, parity, family history of diabetes and mode of delivery did not have significant effects on insulin use nor increased insulin requirement. Fasting capillary glucose (FCG) and one-hour post-prandial capillary glucose (PPCG) were elevated within 24 hours after administration of corticosteroid (betamethasone) in 60%-70% of our population. The FCG values remained elevated on day 2-3 in about 70% of patients. While the first hour PPCG was elevated in 85% of patients on day 2 and remained elevated in 70% of women on day 3-4, it reached 53% on day 5. Insulin requirement among Group B2 reached to 140% increase in insulin dose on day 2 followed by a gradual decrease of insulin dose almost returning to initial dose on day 5.

ACS administration caused maternal hyperglycemia in Filipino women with GDM during the first 24 hours and lasting up to five days. Both fasting glucose and post-prandial glucose were elevated, hence intensified monitoring of maternal glucose levels and temporary addition or increase of insulin doses may be necessary. The timing (≥31 weeks AOG) of administration of ACS on GDM women was associated with subsequent insulin initiation but only on patients initially controlled on diet alone.

BACKGROUND

Type 2 diabetes is the most common type of diabetes in the Philippines. Diabetic foot complications represent a prevalent and significant chronic concern for individuals with type 2 diabetes. This poses an immediate community health concern, as diabetic complications may threaten an individual's well-being.

This study intends to cross-culturally adapt the Diabetic Foot Knowledge Subscale (DFKS) and Foot Self-Care Behavior Scale (FSCBS) questionnaires into the Filipino language as an assessment tool among Filipinos with diabetes.

The study employed a psychometric research design, where it entailed Phase A and Phase B. Phase A involved the forward translation of the DFKS and FSCBS questionnaires, followed by the synthesis of the translations and backward translation. Subsequently, an expert committee reviewed the translations and concluded the final version. The final translated versions of the questionnaires ensured that it can be understood by an individual who has a Grade 6 level of reading proficiency. Phase B entailed the validity testing with the evaluation of the expert committee, and reliability testing of the said questionnaires with a sample size of 30 participants. A wash-out period of 24 hours was given for the test-retest reliability, followed by data analysis. The validity and reliability of the questionnaires were measured using the item and scale content validity indices and the internal consistency and test-retest reliability, respectively, to ensure their accuracy and appropriateness. The content validity of the questionnaires was evaluated individually by the experts using a Likert scale from 1-4, with 4 being the highest meaning the item was very relevant and succinct. Scores per item were between 3 and 4, which indicate that the translated version of the items were relevant and succinct or were relevant but needed minor revisions.

The validity scores for the translated DFKS and FSCBS questionnaires were obtained using the Scale Content Validity Index (S-CVI) with a score of 0.96 and 0.92, respectively. Moreover, all items in the questionnaires obtained an Item Content Validity Index (I-CVI) of 0.88-1.00. The DFKS also has an acceptable internal consistency with a Cronbach’s alpha of 0.72, while the FSCBS has a good internal consistency with a Cronbach’s alpha of 0.85. The test-retest reliability shows an acceptable Spearman’s correlation at 0.76 for the DFKS and a strong positive Pearson correlation coefficient at 0.73 for the FSCBS.

The validity of the two questionnaires was acceptable and the test-retest reliability showed a strong positive correlation among the items thereby making the cross-cultural adaptation of the questionnaires successful. The Filipino versions of the DFKS and FSCBS questionnaires accurately measure the knowledge and behavior of individuals with type 2 diabetes, respectively.

INTRODUCTION: Premature ovarian insufficiency (POI) refers to loss of ovarian activity before the age 40 years. POI has significant detrimental effects on health (infertility, cardiovascular diseases, type 2 diabetes, reduced bone density, dementia), well-being and longevity. This summary is a practical toolkit for health-care professionals (HCPs) looking after women with POI. METHOD: A workgroup comprising specialists in gynaecology, reproductive medicine, endocrinology, genetics and family medicine reviewed relevant guidelines and literature on POI to establish recom-mendations for the diagnosis and management of POI in Singapore. RESULTS: A summary to assist HCPs manage POI was produced, outlining: (1) the aetiology and conse-quences of POI; (2) making the diagnosis; (3) hormone therapy (HT) prescribing options including for those with additional medical conditions; (4) counselling women with POI about HT; and (5) long-term management of POI. CONCLUSION Timely diagnosis and management of POI is vital to prevent long-term adverse consequences, except infertility. HT is the mainstay of treatment and there are no alternatives as effective. Contraindications are very few; estrogen-sensitive cancer is the main contraindication, and caution in prescribing may be needed with established coexisting cardiovascular disease. Estrogen dosage is higher than when treating normal menopause, and as a result, the patient might require more progestogen for endometrial protection. Minimising cardiovascular risk factors by following a healthy lifestyle is important. POI is a significant public health issue and it is imperative that women have affordable access to appropriate HT. Large-scale research on POI in Asian women is needed.
Humans ; Primary Ovarian Insufficiency/drug therapy* ; Female ; Estrogen Replacement Therapy ; Singapore ; Adult

BACKGROUND: Poly adenosine-diphosphate-ribose polymerase (PARP) inhibitors (PARPi) have been approved to act as first-line maintenance (FL-M) therapy and as platinum-sensitive recurrent maintenance (PSR-M) therapy for ovarian cancer in China for >5 years. Herein, we have analyzed the clinical-application characteristics of olaparib and niraparib in ovarian cancer-maintenance therapy in a real-world setting to strengthen our understanding and promote their rational usage. METHODS: A retrospective chart review identified patients with newly diagnosed or platinum-sensitive recurrent ovarian cancer, who received olaparib or niraparib as maintenance therapy at Sichuan Cancer Hospital between August 1, 2018, and December 31, 2021. Patient medical records were reviewed. We grouped and analyzed patients based on the type of PARPi they used (the olaparib group and the niraparib group) and the line of PARPi maintenance therapy (the FL-M setting and the PSR-M setting). The primary endpoint was the 24-month progression-free survival (PFS) rate. RESULTS: In total, 131 patients (olaparib: n = 67, 51.1%; niraparib: n = 64, 48.9%) were enrolled. Breast cancer susceptibility genes ( BRCA ) mutations ( BRCA m) were significantly less common in the niraparib group than in the olaparib group [9.4% (6/64) vs . 62.7% (42/67), P <0.001], especially in the FL-M setting [10.4% (5/48) vs . 91.4% (32/35), P <0.001]. The 24-month progression-free survival (PFS) rates in the FL-M and PSR-M settings were 60.4% and 45.7%, respectively. In patients with BRCA m, the 24-month PFS rates in the FL-M and PSR-M settings were 62.2% and 72.7%, respectively. CONCLUSIONS Olaparib and niraparib were effective in patients with ovarian cancer without any new safety signals except for skin pigmentation. In patients with BRCA m, the 24-month PFS of the PARPi used in the PSR-M setting was even higher than that used in the FL-M setting.
Humans ; Female ; Ovarian Neoplasms/drug therapy* ; Piperazines/therapeutic use* ; Middle Aged ; Retrospective Studies ; Phthalazines/therapeutic use* ; Piperidines/therapeutic use* ; Indazoles/therapeutic use* ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use* ; Adult ; Aged ; China ; Neoplasm Recurrence, Local/drug therapy* ; Progression-Free Survival

BACKGROUND: The role of inflammation in the development of gestational diabetes mellitus (GDM) has recently become a focus of research. The systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI), novel indices, reflect the body's chronic immune-inflammatory state. This study aimed to investigate the associations between the SII or SIRI and GDM. METHODS: A prospective birth cohort study was conducted at Beijing Obstetrics and Gynecology Hospital from February 2018 to December 2020, recruiting participants in their first trimester of pregnancy. Baseline SII and SIRI values were derived from routine clinical blood results, calculated as follows: SII = neutrophil (Neut) count × platelet (PLT) count/lymphocyte (Lymph) count, SIRI = Neut count × monocyte (Mono) count/Lymph count, with participants being grouped by quartiles of their SII or SIRI values. Participants were followed up for GDM with a 75-g, 2-h oral glucose tolerance test (OGTT) at 24-28 weeks of gestation using the glucose thresholds of the International Association of Diabetes and Pregnancy Study Groups (IADPSG). Logistic regression was used to analyze the odds ratios (ORs) (95% confidence intervals [CIs]) for the the associations between SII, SIRI, and the risk of GDM. RESULTS: Among the 28,124 women included in the study, the average age was 31.8 ± 3.8 years, and 15.76% (4432/28,124) developed GDM. Higher SII and SIRI quartiles were correlated with increased GDM rates, with rates ranging from 12.26% (862/7031) in the lowest quartile to 20.10% (1413/7031) in the highest quartile for the SII ( Ptrend <0.001) and 11.92-19.31% for the SIRI ( Ptrend <0.001). The ORs (95% CIs) of the second, third, and fourth SII quartiles were 1.09 (0.98-1.21), 1.21 (1.09-1.34), and 1.39 (1.26-1.54), respectively. The SIRI findings paralleled the SII outcomes. For the second through fourth quartiles, the ORs (95% CIs) were 1.24 (1.12-1.38), 1.41 (1.27-1.57), and 1.64 (1.48-1.82), respectively. These associations were maintained in subgroup and sensitivity analyses. CONCLUSION The SII and SIRI are potential independent risk factors contributing to the onset of GDM.
Humans ; Female ; Pregnancy ; Diabetes, Gestational/immunology* ; Prospective Studies ; Adult ; Inflammation/immunology* ; Glucose Tolerance Test ; Birth Cohort

BACKGROUND: Approximately 40% of individuals with diabetes worldwide are at risk of developing diabetic kidney disease (DKD), which is not only the leading cause of kidney failure, but also significantly increases the risk of cardiovascular disease, causing significant societal health and financial burdens. This study aimed to describe the burden of DKD and explore its cross-country epidemiological status, predict development trends, and assess its risk factors and sociodemographic transitions. METHODS: Based on the Global Burden of Diseases (GBD) Study 2021, data on DKD due to type 1 diabetes (DKD-T1DM) and type 2 diabetes (DKD-T2DM) were analyzed by sex, age, year, and location. Numbers and age-standardized rates were used to compare the disease burden between DKD-T1DM and DKD-T2DM among locations. Decomposition analysis was used to assess the potential drivers. Locally weighted scatter plot smoothing and Frontier analysis were used to estimate sociodemographic transitions of DKD disability-adjusted life years (DALYs). RESULTS: The DALYs due to DKD increased markedly from 1990 to 2021, with a 74.0% (from 2,227,518 to 3,875,628) and 173.6% (from 4,122,919 to 11,278,935) increase for DKD-T1DM and DKD-T2DM, respectively. In 2030, the estimated DALYs for DKD-T1DM surpassed 4.4 million, with that of DKD-T2DM exceeding 14.6 million. Notably, middle-sociodemographic index (SDI) quintile was responsible for the most significant DALYs. Decomposition analysis revealed that population growth and aging were major drivers for the increased DKD DALYs in most regions. Interestingly, the most pronounced effect of positive DALYs change from 1990 to 2021 was presented in high-SDI quintile, while in low-SDI quintile, DALYs for DKD-T1DM and DKD-T2DM presented a decreasing trend over the past years. Frontiers analysis revealed that there was a negative association between SDI quintiles and age-standardized DALY rates (ASDRs) in DKD-T1DM and DKD-T2DM. Countries with middle-SDI shouldered disproportionately high DKD burden. Kidney dysfunction (nearly 100.0% for DKD-T1DM and DKD-T2DM), high fasting plasma glucose (70.8% for DKD-T1DM and 87.4% for DKD-T2DM), and non-optimal temperatures (low and high, 5.0% for DKD-T1DM and 5.1% for DKD-T2DM) were common risk factors for age-standardized DALYs in T1DM-DKD and T2DM-DKD. There were other specific risk factors for DKD-T2DM such as high body mass index (38.2%), high systolic blood pressure (10.2%), dietary risks (17.8%), low physical activity (6.2%), lead exposure (1.2%), and other environmental risks. CONCLUSIONS DKD markedly increased and varied significantly across regions, contributing to a substantial disease burden, especially in middle-SDI countries. The rise in DKD is primarily driven by population growth, aging, and key risk factors such as high fasting plasma glucose and kidney dysfunction, with projections suggesting continued escalation of the burden by 2030.
Humans ; Global Burden of Disease ; Risk Factors ; Male ; Female ; Disability-Adjusted Life Years ; Diabetic Nephropathies/epidemiology* ; Middle Aged ; Diabetes Mellitus, Type 2/epidemiology* ; Adult ; Diabetes Mellitus, Type 1/complications* ; Aged ; Adolescent ; Young Adult ; Quality-Adjusted Life Years

BACKGROUND: Alpha-glucosidase inhibitors or dipeptidyl peptidase-4 inhibitors are both hypoglycemia agents that specifically impact on postprandial hyperglycemia. We compared the effects of acarbose and sitagliptin add on to metformin on time in range (TIR) and glycemic variability (GV) in Chinese patients with type 2 diabetes mellitus through continuous glucose monitoring (CGM). METHODS: This study was a randomized, open-label, active-con-trolled, parallel-group trial conducted at 15 centers in China from January 2020 to August 2022. We recruited patients with type 2 diabetes aged 18-65 years with body mass index (BMI) within 19-40 kg/m 2 and hemoglobin A1c (HbA1c) between 6.5% and 9.0%. Eligible patients were randomized to receive either metformin combined with acarbose 100 mg three times daily or metformin combined with sitagliptin 100 mg once daily for 28 days. After the first 14-day treatment period, patients wore CGM and entered another 14-day treatment period. The primary outcome was the level of TIR after treatment between groups. We also performed time series decomposition, dimensionality reduction, and clustering using the CGM data. RESULTS: A total of 701 participants received either acarbose or sitagliptin treatment in combination with metformin. There was no statistically significant difference in TIR between the two groups. Time below range (TBR) and coefficient of variation (CV) levels in acarbose users were significantly lower than those in sitagliptin users. Median (25th percentile, 75th percentile) of TBR below target level <3.9 mmol/L (TBR 3.9 ): Acarbose: 0.45% (0, 2.13%) vs . Sitagliptin: 0.78% (0, 3.12%), P = 0.042; Median (25th percentile, 75th percentile) of TBR below target level <3.0 mmol/L (TBR 3.0 ): Acarbose: 0 (0, 0.22%) vs . Sitagliptin: 0 (0, 0.63%), P = 0.033; CV: Acarbose: 22.44 ± 5.08% vs . Sitagliptin: 23.96 ± 5.19%, P <0.001. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV (group with small wave, moderate wave and big wave). No significant difference was found in the complexity of glucose time series index (CGI) between acarbose users and sitagliptin users. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV. CONCLUSIONS: Acarbose had slight advantages over sitagliptin in improving GV and reducing the risk of hypoglycemia. Time series analysis of CGM data may predict GV and the risk of hypoglycemia. TRIAL REGISTRATION Chinese Clinical Trial Registry: ChiCTR2000039424.
Humans ; Metformin/therapeutic use* ; Sitagliptin Phosphate/therapeutic use* ; Acarbose/therapeutic use* ; Diabetes Mellitus, Type 2/blood* ; Middle Aged ; Male ; Female ; Adult ; Blood Glucose/drug effects* ; Hypoglycemic Agents/therapeutic use* ; Aged ; Glycated Hemoglobin/metabolism* ; Adolescent ; Young Adult ; China ; East Asian People

Noncoding RNAs (ncRNAs) are a class of RNA molecules with little or no protein-coding potential. Emerging evidence indicates that ncRNAs are frequently dysregulated and play pivotal roles in the pathogenesis of pancreatic cancer. Their aberrant expression can arise from chromosomal abnormalities, dysregulated transcriptional control, and epigenetic modifications. ncRNAs function as protein scaffolds or molecular decoys to modulate interactions between proteins and other biomolecules, thereby regulating gene expression and contributing to pancreatic cancer progression. In this review, we summarize the mechanisms underlying ncRNA dysregulation in pancreatic cancer, emphasize the biological significance of ncRNA-protein interactions, and highlight their clinical relevance. A deeper understanding of ncRNA-protein interactions is essential to elucidate molecular mechanisms and advance translational research in pancreatic cancer.
Humans ; Pancreatic Neoplasms/metabolism* ; RNA, Untranslated/metabolism* ; Gene Expression Regulation, Neoplastic/genetics*