Estradiol Levels and Chemotherapy in Breast Cancer Patients: A Prospective Clinical Study.

Background: Breast cancer remains a global health issue, including in Indonesia, which has a relatively high incidence of breast cancer. Several theories have proved the role of estrogen in breast cancer carcinogenesis, but there is yet to be a preventive measure against breast cancer. Chemotherapy is one of the therapeutic modalities for breast cancer that disturbs ovarian function in producing estrogen due to damaged ovarian granulosa cells. Chemotherapy becomes an alternative option to decreasing circulating estradiol levels through interventions in ovarian functions, either by surgery, such as oophorectomy, or medications that disturb the ovarian functions. This study aimed to observe the estradiol levels in breast cancer patients before and after chemotherapy. Methods: This was a prospective cohort study. We observed the estradiol levels before and after adjuvant chemotherapy in breast cancer patients. Subjects' characteristics are presented in mean ± standard deviation, distribution frequency, and percentage. Subjects' characteristics based on chemotherapy were tested using an independent t-test, Mann-Whitney U, and Chi-square/Fisher exact test. Effects of chemotherapy on estrogen levels were tested using the Wilcoxon rank test and Kruskal-Wallis test. Results: A total of 194 research subjects were included. There were changes in estradiol levels before and after therapy. The decrease of estradiol levels in patients who did not receive chemotherapy was -6.9% (P > 0.05). Patients who received anthracycline cyclophosphamide (AC) regimen, paclitaxel and anthracycline (TA) regimen, paclitaxel, anthracycline and trastuzumab (TA + H) regimen, and platinum regimen experienced a significant decrease in estradiol levels (-21.4% (P < 0.05), -20.2% (P < 0.001), -31.7% (P < 0.01), and -23.7% (P < 0.05), respectively). Among chemotherapy groups, the estradiol levels before and after chemotherapy did not have significant differences (P = 0.937 and P = 0.730, respectively). Conclusion: There are no significant differences in estradiol levels between chemotherapy and hormonal therapy groups. Patients in both groups have decreased estradiol levels after therapy, although patients in hormonal therapy do not experience as much decrease as those in chemotherapy.

Association between prognostic factors and the clinical deterioration of preterm neonates with necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is responsible for most morbidity and mortality in neonates. Early recognition of the clinical deterioration in newborns with NEC is essential to enhance the referral and management and potentially improve the outcomes. Here, we aimed to identify the prognostic factors and associate them with the clinical deterioration of preterm neonates with NEC. We analyzed the medical records of neonates with NEC admitted to our hospital from 2016 to 2021. We ascertained 214 neonates with NEC. The area under the receiver operating characteristic (ROC) curve and cut-off level of age at onset, C-reactive protein (CRP), leukocyte count, and platelet count for the clinical deterioration of preterm neonates with NEC was 0.644 and 10.5 days old, 0.694 and 4.5 mg/L, 0.513 and 12,200/mm3, and 0.418 and 79,500/mm3, respectively. Late-onset, history of blood transfusion, thrombocytopenia, and elevated CRP were significantly associated with the clinical deterioration of neonates with NEC (p = < 0.001, 0.017, 0.001, and < 0.001, respectively), while leukocytosis, gestational age, and birth weight were not (p = 0.073, 0.274, and 0.637, respectively). Multivariate analysis revealed that late-onset and elevated CRP were strongly associated with the clinical deterioration of neonates with NEC, with an odds ratio of 3.25 (95% CI = 1.49-7.09; p = 0.003) and 3.53 (95% CI = 1.57-7.95; p = 0.002), respectively. We reveal that late-onset and elevated CRP are the independent prognostic factor for the clinical deterioration of preterm neonates with NEC. Our findings suggest that we should closely monitor preterm neonates with NEC, particularly those with late-onset of the disease and those with an elevated CRP, to prevent further clinical deterioration and intervene earlier if necessary.

The COVID-19 pandemic impact on pediatric surgery residency programs.

BACKGROUND: The residency program as a part of the clinical services itself has been influenced by the COVID-19 outbreak. Several reports have been published regarding the impact of COVID-19 on the residency programs; however, all studies were performed in developed countries or did not comprehensively analyze what residents think about the COVID-19 impact on their residency program. We investigated the impact of the COVID-19 pandemic on the pediatric surgery residency program in our institution as an important part of hospital medical services. METHODS: We developed and distributed a questionnaire to pediatric surgery residents in our institution who were registered from January 2015-July 2020. The questionnaire was consisting of 24 questions: a) the perspectives of residents about COVID-19 infection during their residency program; b) the learning process; c) academic evaluations; and d) residents' suggestions to improve the quality of their residency program during the outbreak. RESULTS: Most (82.6%) pediatric surgery residents agreed that elective surgeries should be postponed during the pandemic. Before the outbreak, almost all (82.6%) residents used textbooks and journals as their primary sources of learning, while during the outbreak, 69.5% of residents shifted to use online lectures either from the school or Association of Pediatric Surgeons. Interestingly, 91.3% of participants agreed that they had more time to complete their academic assignments during the pandemic. CONCLUSIONS: The pandemic has had a significant impact on the development of pediatric surgery residency programs. Moreover, the responses to the questionnaire are affected by the seniority and sex of the residents. A comprehensive approach is needed to maintain the high standard of competence of pediatric surgery without compromising our safety from the COVID-19 infection risk.

Comparison of metamizole and paracetamol effects on colonic anastomosis and fibroblast activities in Wistar rats.

BACKGROUND: Leakage following colorectal anastomosis surgery causes various complications associated with high morbidity and mortality, especially in pediatric patients. It might be caused by the use of non-steroidal anti-inflammatory drugs (NSAIDs) as postoperative analgesics. This study aimed to compare the effect of metamizole and paracetamol on colonic anastomosis and fibroblast activities, including proliferation, migration, and collagen synthesis, in Wistar rats. METHODS: Rats were divided into control, paracetamol and metamizole groups. The colonic anastomosis was evaluated by determining the integrity of the muscle layers, the formation of granulation tissue, and mucosal anastomosis. Fibroblast activities were analyzed by measuring the proliferation, migration, and collagen synthesis. RESULTS: Metamizole caused more damage to muscle layer integrity, more inhibition of granulation tissue formation in the anastomosis area and lower mucosal anastomosis compared with paracetamol and control groups. Metamizole had a higher cytotoxic effect than paracetamol, which suppressed the proliferation and migration of fibroblasts. Furthermore, both drugs did not affect the synthesis of collagen. CONCLUSION: Metamizole shows worse effects on the integrity of muscle layers, inhibition of granulation tissue formation, mucosal anastomosis, fibroblast proliferation, and migration, but not collagen synthesis, than paracetamol in Wistar rat intestines following colonic anastomosis. These findings might indicate that paracetamol is safer than metamizole as analgesic following colonic anastomosis.

Effects of SEMA3 polymorphisms in Hirschsprung disease patients.

PURPOSE: Recently, genetic markers within a locus on 7q21.11 containing the SEMA3A, SEMA3C, and SEMA3D genes were reported to be associated with Hirschsprung disease (HSCR). Here, we investigated three polymorphisms, rs1583147, rs12707682, and rs11766001, at this locus to determine their potential contributions to the susceptibility of Indonesian HSCR patients. METHODS: Three variants were analyzed in 60 non-syndromic HSCR patients and 118 ethnicity-matched controls for association studies by genotyping. RESULTS: The risk allele frequencies of SEMA3 rs12707682 (allele C) and rs1583147 (allele T) is higher in cases, 53 and 23 %, than in controls, at 42 and 13 %, respectively. However, these frequency differences were not statistically significant with p value of 0.06 and 0.023, respectively. These findings were consistent with transmission disequilibrium test results with p values of 0.041 and 0.11 for rs12707682 and rs1583147, respectively. Furthermore, the frequencies of SEMA3 rs11766001 risk allele in HSCR cases and controls were 1.7 and 0.8 %, respectively. CONCLUSIONS: SEMA3 rs12707682 and rs1583147 variants are not common risk factors for HSCR in Indonesia. The rarity of the SEMA3 rs11766001 polymorphism in Indonesian population might be due to a founder effect.