Cardiopulmonary functional capacity in Taiwanese children with atrial septal defects.

BACKGROUND: Most existing studies measure atrial septal defect (ASD) outcomes based on morbidity rates such as atrial arrhythmias and heart failure rather than the functional assessment of physical capacity postprocedure. Few studies have evaluated cardiopulmonary function in ASD children. This study represents the largest sample population in the current research, encompassing a total of 122 Taiwanese children with ASD who had undergone treatment, to evaluate cardiopulmonary functional capacity through the implementation of cardiopulmonary exercise testing (CPET), and to investigate whether variations in treatment may impact their cardiopulmonary function. METHODS: This is a retrospective cohort study with the data collected from January 2010 to December 2021. All patients and controls (age-, sex-, and body mass index-matched) underwent CPET and pulmonary function testing. RESULTS: In total, 122 ASD patients (surgically closed ASDs 27, transcatheter-closed ASDs 48, and follow-up unrepaired ASD 47) and 244 healthy controls were recruited. The ASD group exhibited lower peak metabolic equivalent (MET), peak oxygen consumption (VO 2 , p < 0.001), and peak minute ventilation ( p = 0.028) along with MET and VO 2 at the anaerobic threshold (AT) ( p = 0.012) compared to the control group. No statistically significant differences were observed in the pulmonary function test. Among surgically closed, transcatheter closed and unrepaired ASD subgroups, no significant variances were seen in CPET and pulmonary function tests. CONCLUSION: Taiwanese ASD children exhibited diminished exercise capacity and cardiopulmonary performance compared to their healthy counterparts. Differences among specific ASD treatments in cardiopulmonary tests were non-significant.

Cardiopulmonary functional capacity in Taiwanese children with ventricular septal defects.

BACKGROUND: Children with ventricular septal defects (VSDs) are considered to have no difference in cardiopulmonary functional capacity with healthy children of the same age; however, studies have shown contradictory findings. The aim of this study was to assess whether Taiwanese children with VSDs exhibited cardiopulmonary deficits. METHODS: This is a retrospective cohort study with the data collected from January 2010 to December 2021. All patients and controls (age-, sex-, and body mass index -matched) underwent cardiopulmonary exercise testing (CPET) and pulmonary function test. RESULTS: In total, 157 VSD patients (80 patients with surgically closed VSDs, 77 patients with unrepaired VSDs) and 157 healthy controls were recruited. Pulmonary function test showed significant among-group differences in maximal voluntary ventilation (MVV) (p = 0.015). The surgically closed group had lower MVV compared to the control group. Regarding CPET, we found VSD patients had lower peak oxygen uptake than the controls (surgically closed group: 30.84 ± 6.27 ml/kg/min; unrepaired group: 32.00 ± 5.95 ml/kg/min; control group: 36.76 ± 6.50 ml/kg/min, p < 0.001). There was also significant among-group differences in aerobic capacity (surgically closed group: 21.20 ± 4.39 ml/kg/min; unrepaired group: 21.68 ± 4.47 ml/kg/min; control group: 26.25 ± 4.33 ml/kg/min, p < 0.001). In addition, the surgically closed group had lower heart rate average at anaerobic threshold than the control group (surgically closed group: 138.11 ± 16.42 bpm; control group: 145.78 ± 15.53 bpm, p = 0.002). CONCLUSION: Taiwanese children with VSD, whether surgically closed or not, have poorer cardiopulmonary performance than age-matched healthy children, and the results of the surgically closed group were even worse.

Effects of photobiomodulation as an adjunctive treatment in chronic obstructive pulmonary disease: a narrative review.

Chronic obstructive pulmonary disease (COPD) is a disease characterized by chronic airway inflammation and remodeling and lung parenchymal inflammation and destruction, which result in many pulmonary and extrapulmonary manifestations. The anti-inflammatory effect of photobiomodulation (PBM) has been reported in previous studies. This review was conducted to evaluate the direct effect of PBM on lung inflammation in COPD. The other effects of PBM on modulation of peripheral and respiratory muscle metabolism and angiogenesis in lung tissues were also discussed. The databases of PubMed, Cochrane Library, and Google Scholar were searched to find the relevant studies. Keywords included PBM and related terms, COPD-related signs, and lung inflammation. A total of 12 articles were selected and reviewed in this study. Based on the present review, PBM is helpful in reducing lung inflammation through decreasing the inflammatory cytokines and chemokines at multiple levels and increasing anti-inflammatory cytokines. In addition, PBM also improves both peripheral and respiratory muscle metabolism and promote angiogenesis. This review demonstrated that PBM is a promising adjunctive treatment modality for COPD management which merits further validation.

The breast graded prognostic assessment is associated with the survival outcomes in breast cancer patients receiving whole brain re-irradiation.

INTRODUCTION: Whole brain (WB) re-irradiation for breast cancer patients with progressive brain metastasis after first-course WB radiotherapy (WBRT) is controversial. In this study, we sought to investigate the association between the molecular sub-classifications and breast-specific Graded Prognostic Assessment (GPA, which includes the Karnofsky performance status, molecular subtypes, and age as its indices) and the outcomes of breast cancer patients who received WB re-irradiation. METHODS: Twenty-three breast cancer patients who received WB re-irradiation for relapsed and progressive intracranial lesions after first-course WBRT between 2004 and 2016 were retrospectively reviewed. Patients were divided according to the 4 molecular subtypes of luminal A/B (hormone receptor [HR]+/human epidermal growth factor receptor 2 [HER2]-), luminal HER2 (HR+/HER2+), HER2 (HR-/HER2+), and triple negative (HR-/HER2-). The clinical and radiological responses and survival rates after WB re-irradiation were analyzed. RESULTS: At 1 month after WB re-irradiation, 13 of 23 patients (56.5%) exhibited disappearance or alleviation of neurological symptoms. The median survival time after WB re-irradiation was 2.93 months (95% confidence interval [CI], 1.79-4.08). After WB re-irradiation, patients with HER2-negative tumors had poorer median survival times than those with HER2-positive tumors (2.23 vs. 3.0 months, respectively; p = 0.022). Furthermore, patients with high breast GPA scores (2.5-4.0, n = 11) had longer median survivals than those with low-scores (0-2.0, n = 12) after WB re-irradiation (4.37 vs. 1.57 months, respectively; p < 0.005). CONCLUSIONS: WB re-irradiation may be a feasible treatment option for certain breast cancer patients who develop brain metastatic lesions after first-course WBRT when these lesions are ineligible for radiosurgery or surgery.

CYP19 genetic polymorphism haplotype AASA is associated with a poor prognosis in premenopausal women with lymph node-negative, hormone receptor-positive breast cancer.

Given the critical role of CYP19 in estrogen synthesis, we investigated the influence of CYP19 gene polymorphisms on the clinical outcome of lymph node- (LN-) negative, hormone receptor- (HR-) positive early breast cancers. Genotyping for the CYP19 polymorphisms rs4646 (A/C), rs1065779 (A/C), CYP19 (TTTA)n (short allele/long (S/L) allele using the 7 TTTA repeat polymorphism as the cut-off), and rs1870050 (A/C) was performed on 296 patients with LN-negative, HR-positive breast cancers. All patients received adjuvant hormonal therapy. Associations were examined between these 4 genotypes and 6 common haplotypes of CYP19 and distant disease-free survival (DDFS), disease-free survival (DFS), and overall survival (OS). Patients were divided into the 6 subhaplotypes of CCLA (41.1%), AASA (17.1%), CASA (11.9%), CCLC (8.9%), CCSA (7.5%), AASC (8.9%), and others (4.6%). In premenopausal patients, haplotype AASA was significantly associated with a poor DDFS (adjusted hazard ratio (aHR), 3.3; P = 0.001), DFS (aHR, 2.5; P = 0.0008), and OS (aHR, 2.9; P = 0.0004) after adjusting for age, tumor size, tumor grade, estrogen receptor status, progesterone receptor status, chemotherapy, pathology, adjuvant hormone therapy, menopausal status, and radiotherapy. Furthermore, haplotype AASA remained a negative prognostic factor for premenopausal patients receiving adjuvant chemotherapy in terms of DDFS (aHR, 4.5; P = 0.0005), DFS (HR, 3.2; P = 0.003), and OS (HR, 6.4; P = 0.0009). However, in postmenopausal patients, haplotype AASA was not associated with a poor prognosis, whereas the AASC haplotype was significantly associated with a poor DFS (aHR, 3.1; P = 0.03) and OS (aHR, 4.4; P = 0.01). Our results indicate that, in patients with LN-negative, HR-positive breast cancers, genetic polymorphism haplotype AASA is associated with poor survival of premenopausal women but does not affect survival of postmenopausal women.

Lack of compensatory pAKT activation and eIF4E phosphorylation of lymphoma cells towards mTOR inhibitor, RAD001.

mTOR (mammalian target of rapamycin) inhibitors were recently found to be effective in the treatment of various human non-Hodgkin's lymphomas (NHLs). We recently reported that RAD001, an mTOR inhibitor, suppressed the growth of lymphoma cells at concentrations much lower than those required for carcinomas. However, the basis for the enhanced sensitivity to RAD001 is unknown. Seven aggressive NHL cell lines and seven carcinoma cell lines were used in this study. Cell cycle was analysed by flow cytometry. pAKT (phosphorylated AKT) (Ser(473) and Thr(308)), p-p70S6K, p-4E-BP1, p-mTOR, p-eIF4E (phosphorylated eIF4E), cyclin A, cyclin E, cyclin D3, c-Myc and insulin receptor substrate-1 (IRS-1) protein expression were assessed by immunoblotting. The PI3K/AKT/mTOR (phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin) signalling pathway was constitutively expressed in all seven lymphoma cell lines. RAD001 down-regulated p-mTOR, p-p70S6K, p-4E-BP1, cyclin A, cyclin E, cyclin D3, and c-Myc, but did not affect IRS-1. In parallel with RAD001-induced inhibition of cell viability, a dose- and schedule- dependent down-regulation of pAKT and p-eIF4E expressions was demonstrated. In contrast, a compensatory activation of pAKT and p-eIF4E, was observed in seven carcinoma cells. These findings indicate that the basis for enhanced activity of mTOR inhibitors in NHL may be the lack of compensatory activation of AKT and eIF4E phosphorylation in lymphoma cells.

The CYP19 TTTA repeat polymorphism is related to the prognosis of premenopausal stage I-II and operable stage III breast cancers.

PURPOSE: Given the critical role of the CYP19 gene, encoding aromatase, in estrogen synthesis and the association of the estrogen level with its TTTA repeat polymorphism, the potential influence of this polymorphism on breast cancer survival, and hence management, deserves further study. METHODS: Genotyping for the CYP19 TTTA repeat polymorphism was performed on 482 stage I-II and operable stage III Taiwanese breast cancer patients. Patients with more than seven TTTA repeats in either allele of CYP19 were defined as having the long allele. We correlated clinical variables and CYP19 genotypic polymorphism with outcome. RESULTS: In hormone receptor (HR)-positive breast cancers, premenopausal patients with the long allele of the CYP19 polymorphism had a significantly higher overall survival (OS) rate (8-year, 89% versus 68%; p= .003) than those without it. This difference was further demonstrated by a multivariate analysis (OS hazard ratio, 1.53; p= .041). In postmenopausal women or patients with HR-negative breast cancer, there was no significant difference in OS between patients with or without the long allele. In premenopausal women with HR-positive cancers, adequate intensity adjuvant chemotherapy did not achieve a greater OS rate than suboptimal chemotherapy in patients with the long allele, but it resulted in a significantly higher OS rate (p= .011) than suboptimal chemotherapy in women without the long allele. CONCLUSIONS: The CYP19 TTTA repeat polymorphism is associated with survival in premenopausal women, but not in postmenopausal women, with HR-positive breast cancers. Premenopausal women with the long allele have a greater survival rate and may not gain benefit from adjuvant chemotherapy.