UNASSIGNED: To examine the specific time frame and identify associated risk factors from commencement of hormonal therapy to the onset of castration-resistant prostate cancer among patients who have developed biochemical recurrence following radical prostatectomy.
UNASSIGNED: We retrospectively reviewed the records of 92 patients who developed biochemical recurrence and received hormonal therapy as initial salvage treatment after radical prostatectomy for high-risk localized prostate cancer from 2005 to 2021. The castration-resistant prostate cancer-free survival rates from the commencement of salvage hormonal therapy were analyzed using log-rank methods. Cox proportional hazard regression was performed to analyze the risk factors associated with acquiring castration resistance. The patients were stratified based on those risk factors.
UNASSIGNED: During a median follow-up duration of 57 months, 24 (26.1%) patients developed castration-resistant prostate cancer. The 5- and 10-year castration-resistant prostate cancer-free survival rates were 73.6% and 54.5%, respectively. A multivariate analysis showed that Grade Group of 5 and prostate-specific antigen doubling time at biochemical recurrence of ≤3 months were independent predictors of castration-resistant prostate cancer. The 5-year castration-resistant prostate cancer-free survival rates in the low- and high-risk groups, stratified according to the aforementioned factors, were 85.4% and 47.6%, respectively.
UNASSIGNED: Patients in high Grade Group and short prostate-specific antigen doubling time after radical prostatectomy are more likely to develop resistance to salvage hormonal therapy.

暂无摘要。

Data on uterine preservation in the management of low grade endometrial stromal sarcoma (LGESS) is scarce due to rarity of this tumor type. Standard management of LGESS involves extrafascial hysterectomy with bilateral salpingo-oophorectomy with debulking of any extrauterine metastatic disease. High estrogen and progesterone receptor expression facilitates adjuvant hormone therapy post-surgery. LGESS frequently affects young women, thus fertility preservation is an important issue in management. Here we describe uterine preservation in two young women diagnosed with LGESS followed by GnRH analogue therapy with favorable outcome. The first case was diagnosed with recurrent endometrial polyp invading myometrium requiring wedge resection of uterus with free margins. Second case presented with a vaginal mass arising from cervix and excision was done through vaginal route. Both patients were prescribed GnRH analogue therapy for six months post-surgery and are currently on follow-up. These case reports add to literature on feasibility of uterine preservation in the management of LGESS.

The treatment of metastatic castration-sensitive prostate cancer (mCSPC) has seen remarkable breakthroughs over the last few years. Diagnostic and therapeutic advances have given rise to debates about risk stratification and optimal first-line treatment selection, as well as to concerns about potential overtreatment in a disease state with a highly heterogeneous clinical behavior. Here, we use case reports from our practice to review the clinical trials exploring intensified triplet regimens combining androgen deprivation therapy with second-generation androgen receptor signaling inhibitors and docetaxel, and we offer our recommendations on how to best select candidates for these novel combinations. Furthermore, the growing adoption of PET imaging with increasingly sensitive and prostate tissue-specific tracers replacing conventional staging technologies has led to the identification of a subset of low-volume mCSPC with nodal metastases which would otherwise not be considered abnormal by RECIST criteria. We describe our PSA-adapted approach to treatment in this unique population with non-measurable low-volume mCSPC which has not been specifically investigated in any phase III clinical trials. We also discuss ongoing clinical trials evaluating treatment de-escalation strategies. Finally, we review how local treatment modalities directed at the prostate or distant sites of disease in oligometastatic CSPC may benefit patients, and how we incorporate metastasis-directed therapy in the management of mCSPC.

UNASSIGNED: Female sex is associated with an increased prevalence of dementia. Menopause may have a role to play in explaining sex differences in cognition, and possibly the risk of future dementia. We aimed to determine if the rate of cognitive decline differed between stages of the menopausal transition.
UNASSIGNED: Women with data on menopause and longitudinal cognitive function from the UK Biobank study were stratified into three groups: premenopausal, perimenopausal and postmenopausal. We studied associations of these menopause groups with rate of change in reaction time, verbal-numeric reasoning, prospective memory, visual memory and attention/working memory, adjusted for age, education, ethnicity and APOEε4 genotype. We also explored the effect of menopausal hormonal therapy (MHT) use and cross-sectional brain magnetic resonance imaging (MRI) volumes on these models.
UNASSIGNED: We included 15,486 women (baseline mean age 52 years) over a mean duration of 8 years. An interaction between menopausal group status and time was found for reaction time (p < 0.01). Compared with premenopausal women, the rate of increase (worsening) in reaction time was least in postmenopausal women (β = -1.07, p for interaction = 0.02). In general, compared with premenopausal women, perimenopausal and postmenopausal women had overall poorer performance in fluid intelligence and memory over the study duration, with no difference in rates of change. The models were unaffected by MHT use and brain volume measures.
UNASSIGNED: Perimenopause and post-menopause are associated with cognitive changes. Psychomotor speed appears to be most sensitive to the menopause transition, whereas other cognitive functions may be less susceptible. More sensitive structural or functional brain imaging may be required to understand the underlying neural basis for these findings.

OBJECTIVE: Aromatase inhibitors (AI) block estrogen synthesis and are used as long-term adjuvant treatment for breast cancer in postmenopausal women. AI use can be associated with weight gain that can lead to increased cardiometabolic risk. The response to anti-obesity medications (AOM) in patients using AI has yet to be studied. We sought to investigate weight loss outcomes of AOM in patients taking AI for breast cancer treatment.
METHODS: This is a matched retrospective cohort study of breast cancer survivors on AI using AOM (AOM/AI group). We compared their weight loss outcomes with a group of female patients with obesity, without a history of breast cancer or AI use, on AOM (AOM group). The primary endpoint was total body weight loss percentage (TBWL %) at the last follow-up. We performed mixed linear regression models, including diabetes status at baseline, to assess associations between use of AOM with/without AI with total body weight loss percentage (TBWL%).
RESULTS: We included 124 patients: 62 in the AOM/AI group (63.6 ± 10 years, body mass index [BMI] 34.3 ± 7.1 kg/m2) and 62 in the AOM group (62.8 ± 9.9 years, BMI 34.6 ± 6.5 kg/m2). The mean time of follow up was 9.3 ± 3.5 months, with no differences among the two groups. The AOM/AI group had a lower TBWL% compared to the AOM group at the last follow-up -5.3 ± 5.0 vs. -8.2 ± 6.3 (p = 0.005). The results remained significant after adjusting for diabetes status (p = 0.0002). At 12 months, the AOM/AI group had a lower TBWL% compared to the AOM group 6.4 ± 0.8% vs. 9.8 ± 0.9% (p = 0.04). The percentage of patients achieving ≥ 5%, ≥ 10%, and ≥ 15% of weight loss at 12 months was greater in the AOM compared to the AOM/AI group. Although the weight loss response was suboptimal, patients in the AOM/AI group had improvement in fasting glucose, glycated hemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol.
CONCLUSIONS: The use of AI in breast cancer survivors is associated with less weight loss response to AOM compared to patients without breast cancer history and who do not take AI. Studies are needed to assess the mechanisms behind the differential weight loss response to AOM in women taking AI.

OBJECTIVE: The increasing use of fertility-preserving treatments in reproductive-aged patients with early-stage endometrial cancer necessitates robust evidence on the effectiveness of oral progestins and levonorgestrel-releasing intrauterine device. We conducted a systematic review and meta-analysis to examine the outcomes following these 2 primary progestin-based therapies in reproductive-aged patients with early-stage endometrial cancer.
METHODS: We conducted a systematic review of observational studies and randomized controlled trials following the Cochrane Handbook guidance. We conducted a literature search of 5 databases and 1 trial registry from inception of the study to April 16, 2024.
METHODS: Studies reporting complete response within 1 year in reproductive-aged patients with clinical stage IA endometrioid cancer undergoing progestin therapy treatment were included. We used data from both observational and randomized controlled studies.
METHODS: The primary exposure assessed was the type of progestational treatment (oral progestins or LNG-IUD). The primary outcome was the pooled proportion of the best complete response (CR) within 1 year of primary progestational treatment. We performed a proportional meta-analysis to estimate the treatment response. Sensitivity analyses were performed by removing studies with extreme effect sizes or removing grade 2 tumors. The risk of bias was assessed in each study using the Joanna Briggs Institute critical appraisal checklist.
RESULTS: Our analysis involved 754 reproductive-aged patients diagnosed with endometrial cancer, with 490 receiving oral progestin and 264 receiving levonorgestrel-releasing intrauterine device as their primary progestational treatment. The pooled proportion of the best complete response within 12 months of oral progestin and levonorgestrel-releasing intrauterine device treatment were 66% (95% CI, 55-76) and 86% (95% CI, 69-95), respectively. After removing outlier studies, the pooled proportion was 66% (95% CI, 57-73) for the oral progestin group and 89% (95% CI, 75-96) for the levonorgestrel-releasing intrauterine device group, showing reduced heterogeneity. Specifically, among studies including grade 1 tumors, the pooled proportions were 66% (95% CI, 54-77) for the oral progestin group and 83% (95% CI, 50-96) for the levonorgestrel-releasing intrauterine device group. The pooled pregnancy rate was 58% (95% CI, 37-76) after oral progestin treatment and 44% (95% CI, 6-90) after levonorgestrel-releasing intrauterine device treatment.
CONCLUSIONS: This meta-analysis provides valuable insights into the effectiveness of oral progestins and levonorgestrel-releasing intrauterine device treatment within a 12-month timeframe for patients with early-stage endometrial cancer who desire to preserve fertility. These findings have the potential to assist in personalized treatment decision-making for patients.

UNASSIGNED: There is no consensus regarding the therapeutic approach of breast neuroendocrine carcinomas (NECs). As most NECs are hormone receptor positive and HER-2 negative, we suggest that endocrine-based strategies may play a leading role. Here, we report a new treatment strategy by incorporating CDK4/6 inhibitors in the therapeutic armamentarium.
UNASSIGNED: Primary neuroendocrine neoplasms of the breast constitute a rare entity. They are characterized by predominant neuroendocrine differentiation and are further divided into well-differentiated neuroendocrine tumors and poorly differentiated (high-grade) neuroendocrine carcinomas (NECs). Regarding their therapeutic approach, there are no standardized guidelines. Herein, we present the first case ever reported, concerning a female patient with de novo metastatic breast NEC who received hormonal therapy, a combination of a CDK4/6 inhibitor palbociclib with letrozole and triptorelin, as first-line treatment with significant clinical and radiological response. As most NECs are estrogen receptor and/or progesterone receptor positive and HER-2 negative, we suggest that hormonal therapy may play a leading role even in the first-line setting. The present report provides a new treatment strategy by incorporating CDK4/6 inhibitors in the therapeutic armamentarium of breast NECs.

Patient portal messages often relate to specific clinical phenomena (e.g., patients undergoing treatment for breast cancer) and, as a result, have received increasing attention in biomedical research. These messages require natural language processing and, while word embedding models, such as word2vec, have the potential to extract meaningful signals from text, they are not readily applicable to patient portal messages. This is because embedding models typically require millions of training samples to sufficiently represent semantics, while the volume of patient portal messages associated with a particular clinical phenomenon is often relatively small. We introduce a novel adaptation of the word2vec model, PK-word2vec (where PK stands for prior knowledge), for small-scale messages. PK-word2vec incorporates the most similar terms for medical words (including problems, treatments, and tests) and non-medical words from two pre-trained embedding models as prior knowledge to improve the training process. We applied PK-word2vec in a case study of patient portal messages in the Vanderbilt University Medical Center electric health record system sent by patients diagnosed with breast cancer from December 2004 to November 2017. We evaluated the model through a set of 1000 tasks, each of which compared the relevance of a given word to a group of the five most similar words generated by PK-word2vec and a group of the five most similar words generated by the standard word2vec model. We recruited 200 Amazon Mechanical Turk (AMT) workers and 7 medical students to perform the tasks. The dataset was composed of 1389 patient records and included 137,554 messages with 10,683 unique words. Prior knowledge was available for 7981 non-medical and 1116 medical words. In over 90% of the tasks, both reviewers indicated PK-word2vec generated more similar words than standard word2vec (p = 0.01).The difference in the evaluation by AMT workers versus medical students was negligible for all comparisons of tasks\' choices between the two groups of reviewers ( p = 0.774 under a paired t-test). PK-word2vec can effectively learn word representations from a small message corpus, marking a significant advancement in processing patient portal messages.

Primary amenorrhea, the absence of menstruation by age 15, can have significant implications for reproductive health and overall well-being. This retrospective study aimed to evaluate the effectiveness of various management strategies for primary amenorrhea among women of reproductive age in Saudi Arabia. Medical records of 63 eligible patients from 2018 to 2023 were analyzed, assessing diagnostic methods, treatment modalities, and associated outcomes. The findings revealed that hormonal therapy was the most commonly employed management strategy (50.0%) and demonstrated the highest rate of achieving menstrual regularity (62.5%). Surgical interventions were utilized in 28.1% of cases, with a 50.0% rate of symptom resolution. Lifestyle modifications were less frequent (21.9%) but showed a moderate rate of symptom resolution (35.7%). Logistic regression analysis identified age, underlying etiology, and management strategy as significant predictors of treatment success. Subgroup analyses highlighted the efficacy of hormonal therapy and lifestyle modifications for genetic etiologies, while surgical interventions were more effective for anatomical causes. The study underscores the importance of a comprehensive diagnostic approach and personalized treatment plans tailored to individual patient characteristics. Despite limitations, the findings contribute to the understanding of optimal management strategies for primary amenorrhea and emphasize the need for multidisciplinary collaboration in addressing this complex condition.