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South Asian Journal of Cancer Apr 2024S. Shanthala Immunophenotypic discordance of receptors between primary and metastatic sites significantly impacts treatment outcomes. Current international guidelines...
S. Shanthala Immunophenotypic discordance of receptors between primary and metastatic sites significantly impacts treatment outcomes. Current international guidelines recommend rebiopsy of accessible metastatic lesions to reassess tissue biomarkers. While existing literature on biomarker changes is conflicting and heterogeneous, similar studies on the Indian cohort of breast cancer patients are lacking. In this context, we aimed to evaluate the frequencies of biomarker changes between biopsies from primary and recurrent sites, and their association with various clinicopathological characteristics, including the type of metastasis and treatment in metastatic breast cancer (MBC) patients. This is an ambispective study performed at a single center. Immunohistochemical (IHC) expression of paired primary and recurrence samples of MBC patients was reviewed for the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and Ki-67. Concordance, loss, and gain of receptors were assessed based on the Allred scores for ER, PR, and HER2. Ki-67 was assessed based on a 14% cutoff. Further, receptor changes were studied in relation to age, menopausal status, morphology, grade, stage, metastatic sites, interval between biopsies, and treatment. At progression, biopsies were obtained from 41.18% of locoregional recurrence and 58.82% of metastatic sites. Despite high discordance of 47% for ER and 68.6% for PR, true receptor conversion was observed in 9.8%, 21.56%, and 5.88% for ER, PR, and HER2, respectively. There was a significant correlation between age and ER discordance ( = 0.029). Loss in PR significantly correlated with a gain in Ki-67. Of all the metastatic sites, the lung was significantly associated with PR and Ki-67 concordance ( = 0.008 and = 0.0425, respectively). Discordance of receptors was neither related to the sites of biopsy (local recurrence or metastatic site) nor to the time interval between biopsies, prior chemotherapy, or hormone therapy. In conclusion, metastatic progression of the disease is accompanied by age-dependent discordance of ER. Unparalleled changes in PR in relation to ER suggest that ER-independent pathways may influence PR expression in MBC. Furthermore, the concurrence of PR loss with Ki-67 gain indicates an aggressive phenotype with disease progression. Hence, follow-up testing of samples for receptor expression is beneficial in determining prognosis and guiding therapeutic decisions.
PubMed: 38919661
DOI: 10.1055/s-0043-1775807 -
Risk Management and Healthcare Policy 2024The aim of this study was to investigate the risk factors of postmenopausal special uterine leiomyoma pathological types or leiomyosarcoma and to develop a nomogram for...
Development and Validation of a Nomogram to Predict the Risk of Special Uterine Leiomyoma Pathological Types or Leiomyosarcoma in Postmenopausal Women: A Retrospective Study.
PURPOSE
The aim of this study was to investigate the risk factors of postmenopausal special uterine leiomyoma pathological types or leiomyosarcoma and to develop a nomogram for clinical risk assessment, ultimately to reduce unnecessary surgical interventions and corresponding economic expenses.
METHODS
A total of 707 patients with complete information were enrolled from 1 August 2012 to 1 August 2022. Univariate and multivariate logistic regression models were used to analyse the association between variables and special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients. A nomogram for special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients was developed and validated by bootstrap resampling. The calibration curve was used to assess the accuracy of the model and receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were compared with the clinical experience model.
RESULTS
The increasing trend after menopause, the diameter of the largest uterine fibroid, serum carcinoembryonic antigen 125 concentration, Serum neutrophil to lymphocyte ratio, and Serum phosphorus ion concentration were independent risk factors for special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients. We developed a user-friendly nomogram which showed good diagnostic performance (AUC=0.724). The model was consistent and the calibration curve of our cohort was close to the ideal diagonal line. DCA indicated that the model has potential value for clinical application. Furthermore, our model was superior to the previous clinical experience model in terms of ROC and DCA.
CONCLUSION
We have developed a prediction nomogram for special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients. This nomogram could serve as an important warning signal and evaluation method for special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients.
PubMed: 38919406
DOI: 10.2147/RMHP.S461773 -
Microbiology Resource Announcements Jun 2024Reported here are the sequences for 11 and four strains isolated from post-menopausal women with a recurrent urinary tract infection. Each of the strains were...
Reported here are the sequences for 11 and four strains isolated from post-menopausal women with a recurrent urinary tract infection. Each of the strains were isolated along with an strain. This provides a resource of high-quality complete genomes from polymicrobial infections.
PubMed: 38916300
DOI: 10.1128/mra.00147-24 -
Cureus May 2024Introduction Menopause is an important milestone in the lives of women. Despite it being a natural phenomenon, menopause brings a lot of changes in a woman's life,...
Introduction Menopause is an important milestone in the lives of women. Despite it being a natural phenomenon, menopause brings a lot of changes in a woman's life, which significantly affects their health and well-being. Menopause involves the cessation of hormone production necessary for menstrual cycles and fertility of females. The absence of these hormones may disturb the homeostasis of minerals, blood glucose, and lipid parameters and predispose women to several health conditions affecting different organs. Obesity has been identified as one of the several conditions that influence the health of women. Therefore, assessing women's health before menopause may improve understanding of their well-being and predict problems during and after menopause. The present study evaluated the activities of calcium, magnesium, phosphorous, fasting blood glucose (FBG), and lipid parameters in obese and nonobese premenopausal women. Methods The present study included 90 obese and 110 nonobese premenopausal women attending the General Medicine and Obstetrics and Gynaecology Departments of Gandhi Medical College and Hospital (GMC&H), Secunderabad, Telangana, India. The body mass index (BMI) was measured in all the study participants to put them under obese and nonobese categories. Blood samples were collected from all the study participants for the estimation of the activities of minerals like calcium, magnesium, phosphorous, FBG, and lipid parameters including total cholesterol (TC), triglycerides (TG), very low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). Results The results demonstrated a significant difference in the activities of lipid parameters (TC-obese (158.90 ± 20.20 mg/dl) versus nonobese (148.7 ± 18.6 mg/dl), p < 0.05; TG-obese (143.1 ± 58.2 mg/dl) versus nonobese (118.40 ± 55.80 mg/dl), p < 0.01; VLDL-obese (28.30 ± 11.50 mg/dl) versus nonobese (23.30 ± 11 mg/dl), p < 0.05; LDL-obese (92 ± 30.30 mg/dl) versus nonobese (73.90 ± 26.10 mg/dl), p < 0.01; HDL-obese (61.60 ± 12.50) versus nonobese (65.30 ± 11.25 mg/dl), p < 0.01), FBG (obese (106.80 ± 32.20 mg/dl) versus nonobese (88.50 ± 42.60 mg/dl); p < 0.01)), and magnesium (obese (1.79 ± 0.36 mg/dl) versus nonobese (2.42 ± 0.67 mg/dl); p < 0.01)). However, the activities of calcium (obese (9 ± 0.54 mg/dl) vs. nonobese (8.9 ± 0.58); p > 0.05)) and phosphorous (obese (3.84 ± 0.53 mg/dl) versus nonobese (3.75 ± 0.46 mg/dl); p > 0.05)) was found to be similar in obese and nonobese premenopausal women. Conclusions The results suggest that obese premenopausal women revealed lowered activities of magnesium that can predispose them to chronic diseases like cardiovascular diseases. In addition, obese women showed higher activities of FBG that predisposes them to type 2 diabetes mellitus (T2DM). There was significant variation in the lipid parameters among obese and nonobese women. However, serum calcium and phosphorous were similar in obese and nonobese premenopausal women.
PubMed: 38916014
DOI: 10.7759/cureus.60995 -
Frontiers in Nutrition 2024Cardiovascular disease (CVD) is the leading cause of death in women, with increased risk following menopause. Dietary intake of beetroot juice and other plant-based...
Seven-day dietary nitrate supplementation clinically significantly improves basal macrovascular function in postmenopausal women: a randomized, placebo-controlled, double-blind, crossover clinical trial.
INTRODUCTION
Cardiovascular disease (CVD) is the leading cause of death in women, with increased risk following menopause. Dietary intake of beetroot juice and other plant-based nitrate-rich foods is a promising non-pharmacological strategy for increasing systemic nitric oxide and improving endothelial function in elderly populations. The purpose of this randomized, placebo-controlled, double-blind, crossover clinical trial was to determine the effects of short-term dietary nitrate (NO ) supplementation, in the form of beetroot juice, on resting macrovascular endothelial function and endothelial resistance to whole-arm ischemia-reperfusion (IR) injury in postmenopausal women at two distinct stages of menopause.
METHODS
Early-postmenopausal [1-6 years following their final menstrual period (FMP), = 12] and late-postmenopausal (6+ years FMP, = 12) women consumed nitrate-rich (400 mg NO /70 mL) and nitrate-depleted beetroot juice (approximately 40 mg NO /70 mL, placebo) daily for 7 days. Brachial artery flow-mediated dilation (FMD) was measured pre-supplementation (Day 0), and approximately 24 h after the last beetroot juice (BR) dose (Day 8, post-7-day BR). Consequently, FMD was measured immediately post-IR injury and 15 min later (recovery).
RESULTS
Results of the linear mixed-effects model revealed a significantly greater increase in resting FMD with 7 days of BR compared to BR (mean difference of 2.21, 95% CI [0.082, 4.34], = 0.042); however, neither treatment blunted the decline in post-IR injury FMD in either postmenopausal group. Our results suggest that 7-day BR-mediated endothelial protection is lost within the 24-h period following the final dose of BR.
CONCLUSION
Our findings demonstrate that nitrate-mediated postmenopausal endothelial protection is dependent on the timing of supplementation in relation to IR injury and chronobiological variations in dietary nitrate metabolism.
CLINICAL TRIAL REGISTRATION
https://classic.clinicaltrials.gov/ct2/show/NCT03644472.
PubMed: 38915856
DOI: 10.3389/fnut.2024.1359671 -
Frontiers in Pharmacology 2024The increasing prevalence of depression is a major societal burden. The etiology of depression involves multiple mechanisms. Thus, the outcomes of the currently used... (Review)
Review
The increasing prevalence of depression is a major societal burden. The etiology of depression involves multiple mechanisms. Thus, the outcomes of the currently used treatment for depression are suboptimal. The anti-depression effects of traditional Chinese medicine (TCM) formulations have piqued the interest of the scientific community owing to their multi-ingredient, multi-target, and multi-link characteristics. According to the TCM theory, the functioning of the kidney is intricately linked to that of the brain. Clinical observations have indicated the therapeutic potential of the kidney-tonifying formula (EXD) in depression. This review aimed to comprehensively search various databases to summarize the anti-depression effects of EXD, explore the underlying material basis and mechanisms, and offer new suggestions and methods for the clinical treatment of depression. The clinical and preclinical studies published before 31 August 2023, were searched in PubMed, Google Scholar, China National Knowledge Infrastructure, and Wanfang Database. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Clinical studies have demonstrated that EXD exhibits therapeutic properties in patients with menopausal depression, depression, and maintenance hemodialysis-associated depression. Meanwhile, preclinical studies have reported that EXD and its special chemical markers exert anti-depression effects by modulating monoamine neurotransmitter levels, inhibiting neuroinflammation, augmenting synaptic plasticity, exerting neuroprotective effects, regulating the hypothalamic-pituitary-adrenal axis, promoting neurogenesis, and altering cerebrospinal fluid composition. Thus, the anti-depression effects of EXD are mediated through multiple ingredients, targets, and links. However, further clinical and animal studies are needed to investigate the anti-depression effects of EXD and the underlying mechanisms and offer additional evidence and recommendations for its clinical application. Moreover, strategies must be developed to improve the quality control of EXD. This review provides an overview of EXD and guidance for future research direction.
PubMed: 38915473
DOI: 10.3389/fphar.2024.1377079 -
Frontiers in Pharmacology 2024To comprehensively analyze the ADRs associated with Denosumab (Prolia) in the treatment of osteoporosis using data from the FAERS database, and gain a better...
OBJECTIVE
To comprehensively analyze the ADRs associated with Denosumab (Prolia) in the treatment of osteoporosis using data from the FAERS database, and gain a better understanding of the potential risks and side effects of Denosumab (Prolia) therapy.
METHODS
Data of Denosumab (Prolia) were collected from the FAERS database covering the period from first quarter of 2010 to the third quarter of 2023. Disproportionality analysis was performed by calculating the reporting odds ratios (ROR), proportional reporting ratio (PRR), and Bayesian analysis confidence propagation neural network (BCPNN) to detect positive signals.
RESULTS
Totally, 17,985,365 reports were collected from the FAERS database, 1,97,807 reports of Denosumab (Prolia) were identified as the "primary suspected (PS)" ADRs. Denosumab (Prolia) induced ADRs occurred in 27 organ systems. 38 significant disproportionality PTs satisfying with the three algorithms were retained at the same time. Unexpected significant ADRs such as bone density abnormal and immobile also occur. The majority of the ADRs occurred within the first 30 days after Denosumab (Prolia) initiation.
CONCLUSION
Based on the American FAERS database, the high frequency ADRs of Denosumab (Prolia) were hypocalcaemia, bone density abnormal, eczema, rebound effect, spinal deformity, etc. Clinical use of this drug should focus on this part of ADRs. Attention should also be paid to newly discovered ADRs, such as immobile, menopausal symptoms, etc., to avoid more serious consequences. Cohort studies, more detailed and comprehensive case information, and long-term clinical investigations are needed to confirm these results and to further understand the safety profile of Denosumab (Prolia).
PubMed: 38915470
DOI: 10.3389/fphar.2024.1358592 -
BMC Women's Health Jun 2024The purpose of this study was to predict the risk factors for residual lesions in patients with high-grade cervical intraepithelial neoplasia who underwent total...
BACKGROUND
The purpose of this study was to predict the risk factors for residual lesions in patients with high-grade cervical intraepithelial neoplasia who underwent total hysterectomy.
METHODS
This retrospective study included 212 patients with histologically confirmed high-grade cervical intraepithelial neoplasia (CIN2-3) who underwent hysterectomy within 6 months after loop electrosurgical excision procedure (LEEP). Clinical data (e.g., age, menopausal status, HPV type, and Liquid-based cytology test(LCT) type), as well as pathological data affiliated with endocervical curettage (ECC), colposcopy, LEEP and hysterectomy, were retrieved from medical records. A logistic regression model was applied to estimate the relationship between the variables and risk of residual lesions after hysterectomy.
RESULTS
Overall, 75 (35.4%) patients had residual lesions after hysterectomy. Univariate analyses revealed that positive margin (p = 0.003), glandular involvement (p = 0.017), positive ECC (p < 0.01), HPV16/18 infection (p = 0.032) and vaginal intraepithelial neoplasia (VaIN) I-III (p = 0.014) were factors related to the presence of residual lesions after hysterectomy. Conversely, postmenopausal status, age ≥ 50 years, ≤ 30 days from LEEP to hysterectomy, and LCT type were not risk factors for residual lesions. A positive margin (p = 0.025) and positive ECC (HSIL) (p < 0.001) were identified as independent risk factors for residual lesions in multivariate analysis.
CONCLUSIONS
Our study revealed that positive incisal margins and ECC (≥ CIN2) were risk factors for residual lesions, while glandular involvement and VaIN were protective factors. In later clinical work, colposcopic pathology revealed that glandular involvement was associated with a reduced risk of residual uterine lesions. 60% of the patients with residual uterine lesions were menopausal patients, and all patients with carcinoma in situ in this study were menopausal patients. Therefore, total hysterectomy may be a better choice for treating CIN in menopausal patients with positive margins and positive ECC.
Topics: Humans; Female; Uterine Cervical Dysplasia; Hysterectomy; Retrospective Studies; Middle Aged; Risk Factors; Adult; Uterine Cervical Neoplasms; Neoplasm, Residual; Papillomavirus Infections; Margins of Excision; Electrosurgery; Aged
PubMed: 38915002
DOI: 10.1186/s12905-024-03212-x -
BMC Public Health Jun 2024Hormone therapy (HT) use among menopausal women declined after negative information from the 2002 Women's Health Initiative (WHI) HT study. The 2017 post-intervention...
BACKGROUND
Hormone therapy (HT) use among menopausal women declined after negative information from the 2002 Women's Health Initiative (WHI) HT study. The 2017 post-intervention follow-up WHI study revealed that HT did not increase long-term mortality. However, studies on the effects of the updated WHI findings are lacking. Thus, we assessed the impact of the 2017 WHI findings on HT use in Taiwan.
METHODS
We identified 1,869,050 women aged 50-60 years, between June and December 2017, from health insurance claims data to compare HT use in the 3 months preceding and following September 2017. To address the limitations associated with interval-censored data, we employed an emulated repeated cross-sectional design. Using logistic regression analysis, we evaluated the impact of the 2017 WHI study on menopausal symptom-related outpatient visits and HT use. In a scenario analysis, we examined the impact of the 2002 trial on HT use to validate our study design.
RESULTS
Study participants' baseline characteristics before and after the 2017 WHI study were not significantly different. Logistic regressions demonstrated that the 2017 study had no significant effect on outpatient visits for menopause-related symptoms or HT use among women with outpatient visits. The scenario analysis confirmed the negative impact of the 2002 WHI trial on HT use.
CONCLUSIONS
The 2017 WHI study did not demonstrate any impact on either menopause-related outpatient visits or HT use among middle-aged women in Taiwan. Our emulated cross-sectional study design may be employed in similar population-based policy intervention studies using interval-censored data.
Topics: Humans; Female; Cross-Sectional Studies; Middle Aged; Taiwan; Women's Health; Estrogen Replacement Therapy; Menopause; Hormone Replacement Therapy
PubMed: 38914983
DOI: 10.1186/s12889-024-19089-2 -
Gynecological Endocrinology : the... Dec 2024Female sexual interest and arousal disorder (FSIAD) is the most prevalent female sexual dysfunction in the postmenopause. (Review)
Review
INTRODUCTION
Female sexual interest and arousal disorder (FSIAD) is the most prevalent female sexual dysfunction in the postmenopause.
OBJECTIVE
The aim of this review is to provide a summary of the currently available evidence on the use of testosterone in the treatment of FSIAD in postmenopausal women.
METHODS
A narrative review on the topic was performed. Only randomized controlled trials (RCTs) and systematic reviews and meta-analysis were considered. 123 articles were screened, 105 of them assessed for eligibility, and finally 9 were included in qualitative synthesis following the PRISMA declaration.
RESULTS
Current evidence recommends, with moderate therapeutic benefit, the use of systemic transdermal testosterone within the premenopausal physiological range in postmenopausal women with Hypoactive Sexual Desire Disorder (HSDD), the previous entity for low desire dysfunction, not primarily related to modifiable factors or comorbidities such as relationship or mental health problems. The available evidence is based on studies with heterogeneity on their design (different testosterone doses, routes of administration, testosterone use in combination and alone, sexual instruments of measurement). There is no data indicating severe short-term adverse effects, although long-term safety data is lacking.
CONCLUSIONS
Despite having testosterone as a valuable tool, therapeutic strategies are lacking in the pharmacological field of HSDD/FSIAD. Neuroimaging studies could provide valuable information regarding the sexual desire substrate and suggest the potential application of already approved drugs for women with a good safety profile. The use of validated instruments for HSDD in postmenopausal women, considering the level of distress, is necessary to be able to draw robust conclusions on the evaluated treatments.
Topics: Humans; Female; Testosterone; Sexual Dysfunctions, Psychological; Postmenopause; Libido
PubMed: 38913119
DOI: 10.1080/09513590.2024.2364220