BACKGROUND

Cyanotic congenital heart disease (CHD) accounts for 20% of all cardiac malformations with an estimated incidence of 2.5–3 per 1,000 live births. An increasing number of patients now survive into adolescence, with or without intervention, forming a unique group requiring specialized care.

OBJECTIVE

To determine factors influencing survival among adolescents with unrepaired cyanotic CHD.

METHODOLOGY

This single-center case-control study was conducted from 2017 to 2022 in a specialized tertiary center in the Philippines. Sample size was based on a 2.6% total fatality rate among infants who underwent CHD operations. Binary logistic regression was used to identify significant predictors of survival, with pRESULTS

Among 125 subjects, 58% (72/125) were males with a median age of 16 years. The median age at diagnosis was 1 year and 1 month; 73% resided outside Metro Manila. Most patients were New York Heart Association (NYHA) Class I (49%), with Tetralogy of Fallot as the most common diagnosis (52%) and 26% had palliative procedures. Predictors of survival included place of origin (OR 0.38, 95% CI 0.15–0.95, p = 0.039), oxygen saturation (OR 1.12, 95% CI 1.06–1.17, pCONCLUSION

Optimizing oxygenation, improving access to care and strengthening targeted interventions are crucial for enhancing survival among adolescents with unrepaired cyanotic CHD.

Human ; Male ; Female ; Adolescent: 13-18 Yrs Old ; Adolescent ; Heart Defects, Congenital ; Survival

BACKGROUND

Cyanotic congenital heart disease (CHD) accounts for 20% of all cardiac malformations with an estimated incidence of 2.5–3 per 1,000 live births. An increasing number of patients now survive into adolescence, with or without intervention, forming a unique group requiring specialized care.

OBJECTIVE

To determine factors influencing survival among adolescents with unrepaired cyanotic CHD.

METHODOLOGY

This single-center case-control study was conducted from 2017 to 2022 in a specialized tertiary center in the Philippines. Sample size was based on a 2.6% total fatality rate among infants who underwent CHD operations. Binary logistic regression was used to identify significant predictors of survival, with pRESULTS

Among 125 subjects, 58% (72/125) were males with a median age of 16 years. The median age at diagnosis was 1 year and 1 month; 73% resided outside Metro Manila. Most patients were New York Heart Association (NYHA) Class I (49%), with Tetralogy of Fallot as the most common diagnosis (52%) and 26% had palliative procedures. Predictors of survival included place of origin (OR 0.38, 95% CI 0.15–0.95, p = 0.039), oxygen saturation (OR 1.12, 95% CI 1.06–1.17, pCONCLUSION

Optimizing oxygenation, improving access to care and strengthening targeted interventions are crucial for enhancing survival among adolescents with unrepaired cyanotic CHD.

Human ; Male ; Female ; Adolescent: 13-18 Yrs Old ; Adolescent ; Heart Defects, Congenital ; Survival

BACKGROUND

The survival advantage of HER2-positive breast cancer from targeted treatment is commonly undermined by catastrophic health expenditure (CHE), particularly in resource-limited areas. Recognizing that financial catastrophe leads to non-adherence to treatment and dissaving practices, we examined the out-of-pocket (OOP) expenses of patients with HER2-positive breast cancer.

OBJECTIVE

The study aimed to estimate the median total per-cycle out-of-pocket expenditure of HER2-positive breast cancer treatment from the patient perspective, in public and private clinics, evaluate the association of catastrophic health expenditure with non-adherence to treatment, and describe dissaving practices.

METHODS

This was a cross-sectional micro-costing analysis of the treatment of HER2-positive breast cancer from the patient perspective from a tertiary cancer center and select private clinics in the Philippines. Random sampling of patients with HER2-positive breast cancer was done. Using a validated questionnaire, a guided interview was administered. Catastrophic health expenditure was estimated as having OOP of >20% of the household income. OOP costs were assessed retrospectively from the time of confirmed HER2 diagnosis up to the date of survey, while household income referred to the corresponding period. The proportion of patients experiencing catastrophic health expenditure was computed. Fisher's exact was used to assess for any association between CHE and non-adherence to treatment. Descriptive statistics were used to report dissaving practices. All statistical analyses were performed using Stata analytical software version 12.

RESULTS

A total of 101 patients participated in the study. The mean age of participants from the tertiary cancer center and private clinics were 52 and 58 years old respectively. Patients from the private clinics had a median total OOP expenditure of PhP 54,737.06 (IQR = PhP 102,670.00), compared with patients from tertiary cancer center who had a median total OOP expenditure of PhP 13,920.66 (IQR = PhP 20,830.00). The overall prevalence of CHE (90.9%, 95% CI 0.81, 0.95) and nonadherence to treatment with trastuzumab (79%, 95% CI 0.70, 0.87) were high, and similar in both groups. A number of dissaving practices such as resignation from work, borrowing money from friends, selling assets were observed.

CONCLUSION

The high rate of CHE and treatment delay among patients with HER2-positive breast cancer were not addressed by the existing cancer programs. Most OOP expenditure was for trastuzumab. Current cancer support programs have potential to address the financial impact of their treatment.

Human ; Therapeutics ; Survival ; Patients ; Neoplasms ; Philippines ; Health Expenditures ; Breast Neoplasms

BACKGROUND

Early-stage endometrial cancer often presents with favorable survival rates, but high-risk factors, including TP53 mutations and high-grade serous pathology, can lead to recurrence and poor prognosis. The standard primary treatment for endometrial cancer is surgical staging, and lymph node metastases significantly impact adjuvant therapy decisions. The subgroup of p53-abnormal (p53abn) indicates the worst prognosis and potential benefits from adjuvant chemotherapy. Molecular classification, while recommended, faces practical challenges due to resource constraints.

OBJECTIVES

The study aimed to assess the incidence of p53 abnormal expression in clinical stage 1 endometrial cancer cases that underwent surgery at a government tertiary hospital, and assess its relationship with clinicopathologic factors and pelvic and paraaortic lymph node metastasis (LNM).

METHODS

A cross-sectional retrospective analysis was conducted on clinical early-stage endometrial cancer cases that underwent surgical primary treatment between January 2018 and December 2022. Patient records were reviewed to gather demographics, surgical information, and pathological evaluations. Preoperative clinical staging was determined through imaging, and surgical staging involved comprehensive lymphadenectomy. Immunohistochemistry studies for p53 were carried out on formalin-fixed paraffin-embedded tissue samples.

RESULTS

A total of 233 endometrial cancer cases were included. The mean age at diagnosis was 53.7 years. Common comorbidities included hypertension (47.2%) and dyslipidemia (20.6%). Most cases were endometrioid histology (82.8%) and low-grade tumors (85.8%). Tumor grade (p=0.010), myometrial invasion (p<0.001) and lymphovascular space invasion (p<0.001) significantly correlated with lymph node metastasis. However, tumor size and p53abn were not significantly associated with lymph node metastasis. p53abn overexpression was significantly associated with non-endometrioid histology at 33% and Grade 3 tumors at 23%. Preoperative grading demonstrated moderate reliability (0.51) with postoperative grading, with an agreement of 65.4%.

CONCLUSION

Tumor grade, myometrial invasion, and LVSI were all significantly associated with lymph node involvement. While p53 immunohistochemical stains show promise in predicting metastasis and has been associated with tumor aggressiveness, this should still be correlated with clinicopathological parameters to carry out a more accurate risk stratification of early-stage patients.

Therapeutics ; Survival Rate ; Risk Factors ; Recurrence ; Prognosis ; Pathology ; Endometrial Neoplasms ; Immunohistochemistry ; Tumor Suppressor Protein P53 ; Lymph Node Excision ; Risk Assessment

OBJECTIVE: To assess the carrier frequency of spinal muscular atrophy (SMA) in women of childbearing age in Chongqing and to evaluate prenatal diagnostic outcomes in high-risk couples. METHODS: A total of 17 926 women of childbearing age attending Chongqing Health Center for Women and Children between May 2021 and November 2023 were enrolled, including 3 398 pre-pregnant women and 14 528 pregnant women, all of whom had no clinical phenotype or family history of SMA or related neuromuscular disorders. Real-time quantitative PCR (RT-qPCR) was used to determine the copy number variations in exons 7 and 8 (E7, E8) of the SMN1 gene. High-risk carriers were identified based on the genetic screening results. Multiplex ligation-dependent probe amplification (MLPA) was employed for prenatal diagnosis of fetuses from high-risk couples. This study was approved by the Medical Ethics Committee of Chongqing Health Center for Women and Children (Ethics No.2021-RGI-02). RESULTS: Among the 17 926 women of childbearing age, 298 (1.66%) were identified as heterozygous carriers, including 278 (1.55%) with concurrent deletions of E7 and E8, and 20 (0.11%) with isolated deletions of E7. Seven high-risk couples were identified, six of whom were prenatal couples. Of the two fetuses from these high-risk pregnancies, both exhibited heterozygous deletions of E7 and E8 in the SMN1 gene, while four fetuses showed no abnormalities. CONCLUSION This study provides a comprehensive assessment of the carrier frequency of SMA among women of childbearing age in Chongqing, offering valuable data for the primary and secondary prevention of SMA-related birth defects in the region.
Humans ; Female ; Muscular Atrophy, Spinal/diagnosis* ; Pregnancy ; Prenatal Diagnosis/methods* ; Adult ; Survival of Motor Neuron 1 Protein/genetics* ; Genetic Carrier Screening/methods* ; DNA Copy Number Variations/genetics* ; China ; Genetic Testing ; Heterozygote

OBJECTIVE: To investigate the steady-state mechanism of interconversion between the SMN1 and SMN2 genes in a normal population. METHODS: Fluorescence PCR capillary electrophoresis was employed to assess gene conversion and copy number variation of SMN1 and SMN2 in a cohort of 1,133 healthy individuals (including 256 males and 877 females) recruited between 2019 and 2023. This study was approved by the Ethics Committee of Henan Provincial People's Hospital (Ethics No.: 2019-134). RESULTS: No significant gender difference was observed in the single copy carrying rate of SMN1. The probability of conversion from SMN1 to SMN2 was determined to be 3.2% for females, 2.7% for males, and 3.1% for the overall population. The probability of conversion from SMN2 to SMN1 was found to be 5.5% for females, 6.3% for males, and 5.6% for the overall population. No statistically significant difference was found in the conversion probability between different genders (P > 0.05). Among the 99 cases of gene conversion, the SMN1 gene predominantly exhibited a copy number of 2 (97.0%), with the remainder having 3 copies (3%). The SMN2 gene primarily showed a copy number of 2 (72.7%), with the rest having 1 copy (27.3%). CONCLUSION Gene conversion tends to normalize the copy numbers of both SMN1 and SMN2 genes towards 2. However, SMN1 exhibited a higher priority over SMN2, causing the copy numbers approaching two.
Humans ; Male ; Female ; Survival of Motor Neuron 2 Protein/genetics* ; Survival of Motor Neuron 1 Protein/genetics* ; Gene Conversion ; DNA Copy Number Variations/genetics* ; Adult ; Middle Aged ; Gene Dosage

Anastasis is a phenomenon described as a cellular escape from ethanol-induced cell death. Although the relevant mechanism has not yet been fully elucidated, anastasis is thought to play a role in drug resistance in cancer cells. To date, the regulation of anastasis in normal and cancerous cells has not been clarified. The current cancer treatment strategies are expected to selectively attack cancer cells without negatively affecting normal cell proliferation. Inspired by the anti-cancer potential of bee venom, this study is the first to evaluate whether bee venom has similar selectivity in producing an anastatic effect. The results indicated that bee venom induces anastasis in normal cells (Michigan Cancer Foundation-10A (MCF10A), Adult Retinal Pigment Epithelium cell line-19 (ARPE-19), and National Institutes of Health 3T3 cell line (NIH3T3)) but causes irreversible cell death in breast cancer cells (M.D. Anderson-Metastatic Breast-231 (MDA-MB-231) and Michigan Cancer Foundation-7 (MCF7)). Liver cancer (HepG2) cells were moderately more resistant to permanent cell death after bee venom treatment compared to breast cancer cells. However, cisplatin caused permanent non-selective cell death in both normal and cancerous cells. The selectivity indices after bee venom treatment were higher compared to cisplatin. Taken together, bee venom was shown to induce selective anastasis only in normal cells, not in cancer cells, which suggests that bee venom has significant potential in selective cancer therapy, especially for breast cancer, via promoting the recovery and maintenance of viability of normal cells.
Bee Venoms/pharmacology* ; Humans ; Animals ; Mice ; Cell Survival/drug effects* ; Breast Neoplasms/pathology* ; Female ; Cell Line, Tumor ; NIH 3T3 Cells ; Antineoplastic Agents/pharmacology* ; Cisplatin/pharmacology* ; Cell Death/drug effects* ; Hep G2 Cells ; MCF-7 Cells

OBJECTIVES: To analyze the differences in the prognosis of gastric signet ring cell carcinoma (SRCC) among different races using the US Surveillance Epidemiology and End Results (SEER) database and The Cancer Genome Atlas (TCGA) database. METHODS: We analyzed the data of patients with gastric SRCC from the SEER database from 2000 to 2020, and divided the patients into cohorts of whites, blacks, Asians or Pacific Islanders, American Indians/Alaska Natives according to their race. The prognosis and treatment of the cohorts were evaluated using baseline demographic analysis, Kamplan-Meier survival curve, and nomogram analysis. RESULTS: We analyzed the data of a total of 2058 patients, including 8.6% blacks, 72.4% whites, 16.6% Asians or Pacific Islanders, 1.0% American Indians/Alaska Natives, and 1.4% other races. The tumor grade varied among different races, and the prevalence and survival rates of patients differed significantly across races. The differences in the white cohort were the most prominent, and all the differences were statistically significant (P<0.05). Racial differences were also noted in patient management and prognosis. CONCLUSIONS There are racial differences in tumor grades and prognosis of gastric SRCC, and these differences provide evidence for optimizing clinical diagnosis and treatment strategies for this malignancy.
Aged ; Female ; Humans ; Male ; Middle Aged ; Carcinoma, Signet Ring Cell/therapy* ; Databases, Factual ; Prognosis ; Racial Groups ; SEER Program ; Stomach Neoplasms/therapy* ; Survival Rate ; United States/epidemiology* ; White ; Asian American Native Hawaiian and Pacific Islander ; American Indian or Alaska Native ; Black or African American

OBJECTIVES: To evaluate the protective effect of Lycium barbarum polysaccharides (LBP) against cisplatin-induced ovarian granulosa cell injury and investigate its possible mechanisms. METHODS: Human granulosa-like tumor cell line (KGN) were treated with 2.5 µg/mL cisplatin for 24 h, followed by treatment with 100, 500, and 1000 mg/L LBP, and the changes in cell viability, apoptosis, level of anti-Müllerian hormone (AMH), and cell ultrastructure were detected with CCK-8 assay, flow cytometry, ELISA and transmission electron microscopy. The cellular expressions of Bax, caspase-3, Bcl-2, and the PI3K/AKT pathway proteins were analyzed using Western blotting, and the expression of miR-23a was detected with RT-qPCR. KGN cell models with lentivirus-mediated miR-23a overexpression or knockdown were used to verify the therapeutic mechanism of LBP. RESULTS: Cisplatin treatment significantly inhibited cell viability, induced apoptosis, decreased AMH level, caused ultrastructural abnormalities, increased Bax and caspase-3 expression, and lowered Bcl-2 expression in KGN cells. Cisplatin also suppressed the activation of the PI3K/AKT signaling pathway and upregulated miR-23a expression in the cells. LBP intervention obviously alleviated cisplatin-induced injuries in KGN cells, and in particular, LBP treatment at the medium dose for 24 h significantly improved KGN cell viability, reduced apoptosis, enhanced their endocrine function, and ameliorated ultrastructural abnormalities. Mechanistically, medium-dose LBP obviously activated the PI3K/AKT pathway by downregulating miR-23a in cisplatin-treated cells, subsequently inhibiting Bax and caspase-3 while upregulating Bcl-2. Overexpression of miR-23a weakened while knockdown of miR-23a significantly enhanced the protective effects of LBP. CONCLUSIONS LBP alleviates cisplatin-induced apoptosis in KGN cells by inhibiting miR-23a expression and activating the PI3K/AKT pathway, suggesting a potential therapeutic strategy for ovarian function preservation.
Humans ; Cisplatin/adverse effects* ; MicroRNAs/genetics* ; Female ; Granulosa Cells/cytology* ; Apoptosis/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Down-Regulation ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Cell Line, Tumor ; Cell Survival/drug effects*

Xerostomia (dry mouth) is frequently experienced by patients treated with radiotherapy for head and neck cancers or with Sjögren's syndrome, with no permanent cure existing for this debilitating condition. To this end, in vitro platforms are needed to test therapies directed at salivary (fluid-secreting) cells. However, since these are highly differentiated secretory cells, the maintenance of their differentiated state while expanding in numbers is challenging. In this study, the efficiency of three reversible thermo-ionically crosslinked gels: (1) alginate-gelatin (AG), (2) collagen-containing AG (AGC), and (3) hyaluronic acid-containing AG (AGHA), to recapitulate a native-like environment for human salivary gland (SG) cell expansion and 3D spheroid formation was compared. Although all gels were of mechanical properties comparable to human SG tissue (~11 kPa) and promoted the formation of 3D spheroids, AGHA gels produced larger (>100 cells/spheroid), viable (>93%), proliferative, and well-organized 3D SG spheroids while spatially and temporally maintaining the high expression of key SG proteins (aquaporin-5, NKCC1, ZO-1, α-amylase) for 14 days in culture. Moreover, the spheroids responded to agonist-induced stimulation by increasing α-amylase secretory granules. Here, we propose alternative low-cost, reproducible, and reversible AG-based 3D hydrogels that allow the facile and rapid retrieval of intact, highly viable 3D-SG spheroids.
Humans ; Hydrogels/chemistry* ; Acinar Cells/cytology* ; Spheroids, Cellular/cytology* ; Salivary Glands/cytology* ; Gelatin/chemistry* ; Collagen/chemistry* ; Alginates/chemistry* ; Cell Culture Techniques/methods* ; Hyaluronic Acid/chemistry* ; Cell Proliferation ; Cell Survival ; Cells, Cultured