Use Of Replacement Therapy Research Articles

Association between the use of loop diuretics and prognosis in critically ill patients with acute kidney injury: a retrospective propensity score-matched cohort study.

The role of loop diuretics in patients with acute kidney injury (AKI) is controversial. This study examined the association between the use of loop diuretics and prognosis in critically ill patients with AKI. This study used data from the medical information mart for the intensive care IV database. Adult critically ill patients with AKI were included in the analysis. Patients were partitioned into two groups based on their use of loop diuretics in the ICU, and potentially confounding variables between the two groups were balanced using propensity score matching (PSM). We used time-dependent Cox proportional hazards regression, logistic regression, and Hodges-Lehman estimator to assess the impact of loop diuretics on all-cause mortality, renal replacement therapy (RRT) use, and the length of hospital stay, respectively. This study included a cohort of 19,671 patients. After PSM, both groups consisted of 6200 patients. The use of loop diuretics was associated with a lower risk of in-hospital mortality (HR, 0.672; 95% CI 0.597-0.757; P < 0.001), lower in-ICU mortality (HR, 0.375; 95% CI 0.315-0.446; P < 0.001), and lower odds of in-hospital RRT (OR, 0.472; 95% CI 0.400-0.555; P < 0.001). A sensitivity analysis using the original cohort (HR, 0.624; 95% CI 0.561-0.693; P < 0.001) and weighted cohort (HR, 0.654; 95% CI 0.582-0.736; P < 0.001) also demonstrated lower in-hospital all-cause mortality. The use of loop diuretics is associated with a substantial reduction in mortality among critically ill patients with AKI.

Menopause Matters: Results of a National Survey of Rheumatoid Arthritis Patients in the UK.

The effects of the menopause have received a lot of attention in the press recently. Anecdotally, patients report changes in their arthritis around the menopause, either onset or aggravation of symptoms. Clearly, there are hormonal influences on arthritis with the female predominance, onset of RA around times of hormonal change and improvement during pregnancy. We were interested in exploring the patient perspective to inform future research and educational needs. A national survey was organised through the National Rheumatoid Arthritis Society (NRAS), using their database of people with RA and online community who self-selected as peri menopausal, menopausal or post-menopausal. A questionnaire was developed by the steering group seeking responses on the effects of the menopause, changes in the arthritis at the time, use of hormone replacement therapy (HRT) and any discussions they had had with their healthcare providers. Free text comments were analysed qualitatively. A total of 779 people responded during September/October 2023. Respondents were 95% Caucasian mainly in their 50s with onset of menopausal symptoms in their 40s. 80% responded that their arthritis was worse during the menopause with 10% being much worse. 47% had taken HRT. Of these, 80% experienced an improvement in their menopausal symptoms and 30% had a moderate or large improvement in their arthritis symptoms. A standout statistic was that 93% of respondents had had no medical discussion about the menopause. For those who did, this was most frequently with the GP in relation to HRT and osteoporosis. 84% of participants felt that the rheumatology team should receive more education and training about the menopause in relation to RA. The qualitative analysis revealed several themes: Discussion about the menopause only occurred if the patient raised it. There was conflicting advice about HRT. There is overlap and confusion of symptoms between RA and the menopause. Participants expressed a perceived link between menopause and onset or deterioration of their arthritis. This study was long overdue. Patients perceive a strong association between the menopause and onset or deterioration of their arthritis, with confusion over what is due to arthritis and what is being caused by the menopause. Patients would like much more discussion about the menopause, but this is not currently happening. They are getting conflicting advice on HRT. Further research is necessary to clarify the impact of the menopause on people with arthritis.

Patient-reported sexual health outcomes of cervical cancer patients treated with definitive chemoradiation and MRI-guided brachytherapy

BackgroundSexual health is an important survivorship issue in cervical cancer. We assessed patient-reported sexual health outcomes and correlations with oncologist-assessed vaginal toxicity (VT). MethodsThis was a prospective, cross-sectional study of stage IB-IVA cervical cancer patients treated with definitive chemoradiation, who completed a socio-demographic questionnaire and the following patient-reported-outcomes (PROs): Female Sexual Function Index (FSFI), Female Sexual Distress Scale-Revised (FSDS-R), Menopause Rating Scale (MRS), Hospital Anxiety and Depression Scale (HADS). VT was assessed using the CTCAE v4.0. Sociodemographic, clinical data, PROs and VT were summarized using descriptive statistics; correlations were evaluated using linear regression analyses. ResultsBetween August 2018 and April 2022, 73 patients were analyzed. Median age was 49 (range 25–81), 57.5% had vaginal involvement at diagnosis and 76.9% were partnered. Sexual dysfunction (FSFI score ≤ 26), sexual distress (FSDS-R ≥ 11), severe menopausal symptoms (MRS ≥ 17), anxiety (HAD-Anxiety >7) and depression (HAS-Depression >7) were reported in 86.3%, 54.5%, 36.2%, 46.6% and 24.7%, respectively. Grade 2+ VT was reported in 27.4%. No significant associations were found between PROs and VT. On multivariable analysis, non-partnered status, use of hormone replacement therapy, and International Commission on Radiation Units and Measurements – rectovaginal dose (ICRU-RV) >65Gy were associated with worse sexual health (p < 0.005). ConclusionCervical cancer patients self-report high rates of sexual distress, dysfunction and menopause symptoms. Discordance between oncologist-assessed VT and PROs highlights the importance of evaluating the patient's experience. Proactive treatment of menopausal symptoms and attention to radiotherapy doses to the vagina should be considered.

Ventricular assist devices as bridge to heart transplantation: minimally invasive approach with axial pumps vs sternotomy approach with centrifugal pumps: short term results

Abstract Introduction Microaxial flow ventricular assist devices (VADs) with hybrid approach could provide an advantage over centrifugal flow VADs with surgical implantation via median sternotomy as bridge to heart transplantation. Purpose We aimed to compare short-term results in intensive cardiac care unit between both groups. Methods Single-center retrospective registry comparing patients supported with microaxial flow VADs with hybrid approach (Impella 5.0 or 5.5) and surgical centrifugal flow VADs (biventricular or left univentricular CentriMag) as bridge to heart transplantation. Results Including 12 patients (January 2020-March 2022), 7 patients in hybrid approach group (2 patients with Impella 5.0-16,7% and 5 patients with Impella 5.5-41,7%) and 5 pacientes in sternotomy approach group (33.3% biventricular support and 8.3% left ventricular support). In first 48 hours after VAD implantation, worsening of renal function was greater in sternotomy approach group (Cr 2.23±0.88, 1.07±0.58;p=0.021) and there was a trend toward lower hemoglobin values (7.72±0.19, 8.9±1.35;p =0.059), with no differences in other analyzed variables (Table). A trend toward earlier respiratory weaning was observed in hybrid approach group (median 12 vs 48 hours,p=0.067). Sternotomy approach group required more frequent use of continuous renal replacement therapy (60% vs 0%,p=0.045). There were statistically non-significant differences in need for blood products or surgical reinterventions, although percentage of red blood cells transfused in first 48 hours after VAD implantation were lower in hybrid approach group than sternotomy approach group (median 4 (1.5-8) versus 8(2.5-13.5) in sternotomy approach group, p=0.309). The most common complication in sternotomy approach group was tamponade (80%- 4 patients versus 0 patients in hybrid approach) and in hybrid approach group access-related infections (28.57%, 2 patients). Ten patients received a transplant, one died for non-cardiovascular cause, and another underwent the implantation of long term VAD as bridge to transplantation. There were no differences in time from assistance implantation to heart transplantation. The most common complication after heart transplantation was primary graft failure in both groups (40%,2 patients) with no differences in mortality. Conclusions Microxial flow VADs with hybrid approach provide adequate support, with less need for continuous renal replacement therapy and shorter duration of mechanical ventilation after VAD implantation to admission in intensive cardiac care unit, a trend towards lower rates of reintervention due to bleeding was observed. The advantages of minimally invasive approach could increase its use as bridge to heart transplantation compared to VADs with sternotomy approach although small sample size may negatively influence the failure to reach statistical significance, and more studies are necessary to validate our preliminary experience.Variables analyzed 48 hours of admission

Much more than a biological phenomenon: A qualitative study of women's experiences of brain fog across their reproductive journey.

Whilst 'brain fog' is mostly considered a biological problem little is understood about an individual's experience. This qualitative study explored women's experiences of brain fog focusing on those at the start (aged 18-25; n = 10) and end (aged 45-60; n = 10) of their reproductive journey. Descriptive thematic analysis described three themes: (i) 'daily disruptions' describing cognitive dysfunctions and the main triggers; (ii) 'the cycle of impact' with a focus on women's emotional experiences and how these can exacerbate brain fog; (iii) 'taking control' highlighting the use of self-care, physical prompts and Hormonal Replacement Therapy (HRT) to manage brain fog. Transcending these themes was the notion of 'crisis of identity' illustrating the negative impact of brain fog on the women's sense of self with some older women describing acceptance and finding it less challenging. Brain fog is much more than a biological phenomenon and has broader implications for a woman's sense of self.

Hormone Replacement Therapy and Alzheimer's Disease: Current State of Knowledge and Implications for Clinical Use.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder responsible for over half of dementia cases, with two-thirds being women. Growing evidence from preclinical and clinical studies underscores the significance of sex-specific biological mechanisms in shaping AD risk. While older age is the greatest risk factor for AD, other distinct biological mechanisms increase the risk and progression of AD in women including sex hormones, brain structural differences, genetic background, immunomodulation and vascular disorders. Research indicates a correlation between declining estrogen levels during menopause and an increased risk of developing AD, highlighting a possible link with AD pathogenesis. The neuroprotective effects of estrogen vary with the age of treatment initiation, menopause stage, and type. This review assesses clinical and observational studies conducted in women, examining the influence of estrogen on cognitive function or addressing the ongoing question regarding the potential use of hormone replacement therapy (HRT) as a preventive or therapeutic option for AD. This review covers recent literature and discusses the working hypothesis, current use, controversies and challenges regarding HRT in preventing and treating age-related cognitive decline and AD. The available evidence indicates that estrogen plays a significant role in influencing dementia risk, with studies demonstrating both beneficial and detrimental effects of HRT. Recommendations regarding HRT usage should carefully consider the age when the hormonal supplementation is initiated, baseline characteristics such as genotype and cardiovascular health, and treatment duration until this approach can be more thoroughly investigated or progress in the development of alternative treatments can be made.

Sepsis associated acute kidney injury is common among Aboriginal and Torres Strait Islanders with septic shock and has poor outcomes: A nested cohort study.

Exploration of the incidence and outcomes of Acute Kidney Injury (AKI) broadly, and sepsis associated AKI specifically, in Aboriginal and Torres Strait Islander (First Nations) people has been limited. We compared a nested cohort of First Nations people drawn from a multinational randomised controlled trial of hydrocortisone in septic shock, to a cohort matched for age, sex and severity of illness. Acute Kidney Injury was defined using the Kidney Disease Improving Global Outcomes (KDIGO) criteria, as well as incident use of kidney replacement therapy (KRT). Major Adverse Kidney Events (MAKE) were described as the composite of death, new dialysis requirement or persisting kidney dysfunction at hospital discharge. A cohort of 57 Aboriginal and/or Torres Strait Islander patients with septic shock was identified. 91.2% (52) of the First Nations cohort met KDIGO criteria for Stage 1 AKI or greater and 63% (36) met Stage 3 criteria. 59.6% (34) of the First Nations required dialysis as compared to 45.6% (26) in the matched cohort. 60.7% (34) of First Nations participants met criteria for MAKE at hospital discharge. The proportions requiring dialysis at 6, 12 and 24 months were 8.3%, 9.1% and 6.9% respectively. The incidences of AKI and MAKE reported in this First Nations cohort are substantially higher than in previously published cohorts of patients with sepsis, even those that use sensitive definitions of AKI. Measures to promote better management of infectious diseases in First Nations communities are required.

12566 Adult Growth Hormone Deficiency, Replacement Therapy Use, and IGF1 Levels in Association with Physical, Psychosocial, and Neurocognitive Outcomes Among Childhood Cancer Survivors

Abstract Disclosure: T. Yoshida: None. J.L. Baedke: None. H. Wang: None. C.H. Yu: None. C.L. Wilson: None. D.A. Mulrooney: None. S.B. Dixon: None. I. Huang: None. T.M. Brinkman: None. K.R. Krull: None. S. Mostoufi-Moab: None. J. Miguel Martínez: None. K.K. Ness: None. M.M. Hudson: None. Y. Yasui: None. A. Delaney: None. Background: Adult growth hormone deficiency (aGHD) is a common and often untreated late effect among childhood cancer survivors. Untreated aGHD likely adds to the burden of health outcomes in survivors already experiencing cancer treatment related late toxicities. As comprehensive data on the consequences of untreated aGHD in survivors are scarce, we assessed the clinical impact of untreated aGHD among survivors, together with socioeconomic factors as potential contributing factors, utilizing a large, clinically characterized cohort of childhood cancer survivors. Methods: 3902 five-year survivors ≥ 18 years old [median (25th-75th percentile) age, 31.7y (25.2-40.0); age at cancer diagnosis 8.1y (3.5-13.6); 47.5% female] were examined. We assessed the: 1) proportion of survivors with aGHD on GH therapy (GHT); 2) association between GHT and socioeconomic factors (e.g., household income, area deprivation index) by multivariable logistic regression; and 3) associations between age- and sex-adjusted insulin-like growth factor 1 (IGF1) z-score and prevalence of clinically-assessed (i.e., body composition, metabolic/cardiovascular factors, neurocognitive function) and self-reported [i.e., quality of life (QoL), emotional symptom] outcomes by multivariable logistic regression with trend test, adjusting for potential confounders (e.g., radiation to the hypothalamic-pituitary region). Results: aGHD was observed in 9.1% (354/3902) of survivors; among them, 9.0% (32/354) were on GHT. Survivors on GHT were more likely to have higher household income, hold health insurance, and reside in less socioeconomically disadvantaged neighborhoods, compared to survivors with untreated aGHD. Socioeconomic factors had significant independent associations with GHT use in multivariable analysis [e.g., annual household income &amp;lt;$40,000 vs. ≥$80,000, adjusted odds ratio (aOR) of GHT use, 0.28; 95% confidence interval (CI), 0.08-0.86]. Lower IGF1 z-score (IGF1 z-score ≤ -2, vs. IGF1 z-score &amp;gt;0) was associated with a higher prevalence of various outcomes (aOR, 95% CI), such as abdominal obesity (2.56, 1.98-5.26), weak handgrip strength (2.49, 1.65-3.73), hypertension (1.47, 1.06-2.04), abnormal glucose metabolism (2.07, 1.49-2.86), impaired health-related QoL (e.g., physical functioning, 1.97, 1.35-2.86), depression (1.58, 1.06-2.33), and impairment in multiple neurocognitive functions (e.g., verbal reasoning, a global measure of intelligence, 2.22, 1.49-3.30) with a dose-response relationship. Conclusions: Our data support a negative impact of untreated aGHD on physical, psychosocial, and neurocognitive outcomes among survivors and suggest the potential of GHT to improve QoL of survivors with aGHD. As lower socioeconomic status may affect survivors’ access to GHT, this disparity should be considered in interventions evaluating GHT for survivors with aGHD. Presentation: 6/3/2024

6700 Risk Of Dementia According To The Reproductive Factors In Postmenopausal Women With Diabetes

Abstract Disclosure: J. Yu: None. K. Han: None. J. Yun: None. S. Lee: None. Risk of dementia according to the reproductive factors in postmenopausal women with diabetes Jin Yu[1], Kyungdo Han[2], Jae-Seung Yun[3], Seung-Hwan Lee[1],[4] [1]Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea[2]Department of Statistics and Actuarial Science, Soongsil University[3]Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea[4]Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Background: Previous studies have suggested a possible association between endogenous estrogen exposure and decreased risk of cognitive impairment or dementia. We aimed to investigate the impact of reproductive factors on the risk of dementia in women with diabetes. Methods:166,245 postmenopausal women with type 2 diabetes aged over 40 who underwent health examination in 2009 were identified from the National Health Information Database. Information regarding reproductive factors were collected through self-administered questionnaires. Incident dementia was defined using diagnosis codes and anti-dementia drug prescription. Cox proportional hazards regression analyses were performed to evaluate the risk of all-cause dementia, Alzheimer’s disease, and vascular dementia according to reproductive factors including age at menarche, age at menopause, reproductive lifespan, parity, and use of hormone replacement therapy (HRT). Results: The mean age and reproductive lifespan were 64.5 ± 8.0 and 33.4 ± 4.7 years, respectively. During the median follow-up of 8.3 years, 25,330 cases of any dementia, including 20,817 cases of Alzheimer's disease and 2,756 cases of vascular dementia were developed. The hazard ratios (95% CI) of all-cause dementia were 1.28 (1.06-1.56) for age at menarche &amp;gt;16 years compared with ≤12 years, 0.71 (0.66-0.77) for age at menopause ≥55 years compared with &amp;lt;40 years, and 0.72 (0.68-0.76) for reproductive lifespan ≥40 years compared with &amp;lt;30 years, respectively. The risk of all-cause dementia was decreased by 11% in women with parity ≥2 compared with 0, and by 16% in women with HRT for more than 5 years compared without HRT. Similar findings were observed for Alzheimer’s disease and vascular dementia. Conclusion: Longer reproductive lifespan was associated with lower risk of dementia in postmenopausal women with diabetes. Presentation: 6/2/2024

7407 Normosmic Idiopathic Hypogonadotropic Hypogonadism in Women: A Case Report and Comprehensive Review

Abstract Disclosure: E.G. Bustamante: None. M. Sulehri: None. I. Patoli: None. A. Karunakaran: None. Normosmic Idiopathic Hypogonadotropic Hypogonadism (nIHH) in Women: A Case Report and Literature ReviewIntroduction: IHH is a rare genetic disorder affecting gonadotropic-releasing hormone (GnRH) production and/or action, resulting in diminished sex steroid levels. Characterized by the absence of spontaneous pubertal development. In women, it manifests with normal adrenarche but absent thelarche and menarche. Our case highlight a late diagnosis of IHH in a 34-year-old woman with primary amenorrhea. Case report: A 34 year old lady with a history of primary amenorrhea sought evaluation. At age 16, she underwent assessment for short stature and primary amenorrhea, denying anosmia, headache, visual disturbances. Evaluation revealed bone age concordant with chronological age and normal MRI Brain. Pelvic ultrasound (US) showed small premenarchal uterus and ovaries. She initiated oral contraceptive pills (OCP) and experienced regular menses. Seeking fertility assistance at age 24, a normal Hysterosalpingogram was followed by successful delivery of twins after ovarian stimulation. Post-delivery menses did not resume and OCP was not restarted. Family history revealed a sister with irregular periods requiring OCP.Subsequently workup at age 30 showed Estradiol 22 pg/ml, FSH/LH 4.1/2.3 mUI/mL; normal PRL, TFT, DHEAS, 17OHP. Repeat Pelvic US showed normal uterus, endometrial stripe normal at 0.24 cm and non-visualized ovaries. PCOS testing negative for hyperandrogenism. Progesterone challenge resulted in no withdrawal bleeding. Brain MRI demonstrated a 2.2 x 1.3 mm hypoenhancing ovoid mass in the pars Intermedia of the pituitary gland suggestive of pituitary microadenoma. Pituitary axis hormonal testing was normal. Karyotype revealed 46 XX (normal female). Genetic evaluation identified a pathogenic variant (p.R35C) in GNRH1 gene. Her final diagnosis: nIHH. Discussion HH is diagnosed in 5% of all women with primary amenorrhea and is divided into 2 major categories: Kallmann syndrome and nIHH. The majority of known causes of HH can be attributed to mutations in KAL1, FGFR1, or GNRHR. The p.R35C variant has been associated with autosomal dominant nIHH. Diagnosis involves clinical suspicious, low LH/FSH and sex steroid levels, normal hypothalamic–pituitary imaging, and exclusion of differentials.Treatment goal for female focus on regular breast and uterine development, as well as the capability to conceive. Use of hormonal replacement therapy and/or gonadotropins or pulsatile GnRH for ovarian stimulation are essential. ConclusionWhile IHH predominantly affects men, limited literature explores its manifestation in women and its impact on fertility. The identification of a GNRH1-related nIHH variant highlights the role of genetic testing in specific HH diagnoses. Failure to diagnose in adolescence may compromise women overall well-being Presentation: 6/1/2024

Clinical Pharmacology Of Selective Oestrogen Receptor Modulators In The Prevention Of Breast Cancer, Osteoporosis, Coronary Heart Disease, Alzheimer's Disease, Use In Hormone Replacement Therapy, Cholesterol Metabolism

Oestrogen is the key regulatory hormone for the development and maintenance of reproductive functions and affects various physiological systems, including the skeletal, cardiovascular, and central nervous systems. oestrogen replacement therapy (ERT) is highly effective in postmenopausal women, addressing menopausal symptoms and providing beneficial effects on osteoporosis and coronary heart disease. However, ERT is associated with significant side effects, such as an increased risk of breast cancer. To mitigate these risks, selective oestrogen receptor modulators (SERMs) have been developed. SERMs are a growing class of synthetic nonsteroidal compounds that act as oestrogen receptor agonists or antagonists in a tissue-specific manner. They can selectively activate or inhibit oestrogen receptors in different tissues throughout the body. SERMs are used to treat a variety of conditions, including ER-positive breast cancer, osteoporosis, coronary heart disease, Alzheimer’s disease, and cholesterol metabolism disorders in postmenopausal women. Specific SERMs are employed for different conditions: raloxifene for osteoporosis, tamoxifen and toremifene for breast cancer, clomiphene for the induction of ovulation, and ormeloxifene for oral contraception. Arzoxifene is used for altering cholesterol metabolism. Each SERM forms a unique complex with oestrogen receptors, influencing target tissues and resulting in a tissue-selective pharmacological profile. This unique mechanism of action translates into specific safety and efficacy profiles for each SERM. The surprising pharmacology of SERMs has sparked interest in developing new selective medications, allowing for precise treatment of various diseases. This article reviews the pharmacological properties of SERMs and explains how they differ from oestrogen in their actions.

Call to quit: Results of a remote, longitudinal tobacco cessation program.

356 Background: Tobacco cessation counseling remains suboptimal for patients with cancer. The current iteration of the Dana-Farber Cancer Institute Tobacco Cessation Program was established in 2021 to provide virtual, longitudinal tobacco session counseling to patients with cancer. Here, we report the Program’s experience. Methods: The DFCI Tobacco Cessation Program data from 2021 to 2023 was analyzed. Descriptive statistics summarized demographics and tobacco cessation experiences from baseline and follow-up visits. Results: Of 227 patients referred to the Program and included in the analysis (Table 1), 161 declined participation. 63 participants attended a baseline visit, of whom the median age for first cigarette was 15 years (range: 10-32) and the median age for regular tobacco use was 17 years (range: 10-61). Prior to baseline, most participants (n=43) indicated using tobacco daily; the median number of daily cigarettes was 11-15. Many (n=41) reported smoking within 30 minutes of waking up, and most considered tobacco use to be an addiction (n=50). Though a considerable number of participants (n=27) reported quitting smoking to be extremely important to them, confidence in quitting varied; the most frequently selected confidence level was 5/10 (n=14). Past use of tobacco cessation drugs was reported by one-third of participants (n=22); past use of nicotine replacement therapy was reported by nearly half (n=30). The most frequently reported perceived benefit of quitting smoking was better health (n=48). 51 participants had at least one follow-up visit (median: 4, range: 1-23). At the time of first follow-up, 10 reported decreasing the number of cigarettes smoked per day, 20 reported no change, and 3 reported an increase. However, among 24 participants who attended a fifth visit, 8 reported a decrease and 6 reported no change. Of 11 patients who had attended at least 10 visits, 5 reported decreasing their number of daily cigarettes. 13/63 (20.6%) of all participants reported quitting smoking after enrolling, with a median time from baseline assessment to smoke-free status of 34 days. Conclusions: Remote, longitudinal tobacco cessation programs provide an effective way to increase access to tobacco cessation counseling for patients with cancer. However, limitations include high decline rates and loss to follow up. Future analysis of our program will help better understand tobacco cessation efforts. Demographics Approached (n=227) Attended Baseline (n=63) Median Age 60 62 Sex Female 130 (57.3%) | Male 94 (41.4%) |Prefer not to say/Unknown 3 (1.3%) Female 36 (57.1%) |Male 26 (41.3%) |Prefer not to say 1 (1.6%) Cancer Lung 80 (35.2%) |Breast 46 (20.3%) |Head &amp; Neck 27 (11.9%) |GI 24 (10.6%) Lung 22 (34.9%) |Breast 9 (14.3%) |Head &amp; Neck 11 (17.5%) |Lymphoma 6 (9.5%) Race: White 191 (84.1%) 52 (82.5%) Black 17 (7.5%) 4 (6.3%) Asian 4 (1.8%) 1 (1.6%) Other/Prefer not to say 15 (6.6%) 6 (9.5%) Hispanic 8 (3.6%) 3 (5.1%)

Reproductive factors and mammographic density within the International Consortium of Mammographic Density: A cross-sectional study

BackgroundElevated mammographic density (MD) for a woman’s age and body mass index (BMI) is an established breast cancer risk factor. The relationship of parity, age at first birth, and breastfeeding with MD is less clear. We examined the associations of these factors with MD within the International Consortium of Mammographic Density (ICMD).MethodsICMD is a consortium of 27 studies with pooled individual-level epidemiological and MD data from 11,755 women without breast cancer aged 35–85 years from 22 countries, capturing 40 country-& ethnicity-specific population groups. MD was measured using the area-based tool Cumulus. Meta-analyses across population groups and pooled analyses were used to examine linear regression associations of square-root (√) transformed MD measures (percent MD (PMD), dense area (DA), and non-dense area (NDA)) with parity, age at first birth, ever/never breastfed and lifetime breastfeeding duration. Models were adjusted for age at mammogram, age at menarche, BMI, menopausal status, use of hormone replacement therapy, calibration method, mammogram view and reader, and parity and age at first birth when not the association of interest.ResultsAmong 10,988 women included in these analyses, 90.1% (n = 9,895) were parous, of whom 13% (n = 1,286) had ≥ five births. The mean age at first birth was 24.3 years (Standard deviation = 5.1). Increasing parity (per birth) was inversely associated with √PMD (β: − 0.05, 95% confidence interval (CI): − 0.07, − 0.03) and √DA (β: − 0.08, 95% CI: − 0.12, − 0.05) with this trend evident until at least nine births. Women who were older at first birth (per five-year increase) had higher √PMD (β:0.06, 95% CI:0.03, 0.10) and √DA (β:0.06, 95% CI:0.02, 0.10), and lower √NDA (β: − 0.06, 95% CI: − 0.11, − 0.01). In stratified analyses, this association was only evident in women who were post-menopausal at MD assessment. Among parous women, no associations were found between ever/never breastfed or lifetime breastfeeding duration (per six-month increase) and √MD.ConclusionsAssociations with higher parity and older age at first birth with √MD were consistent with the direction of their respective associations with breast cancer risk. Further research is needed to understand reproductive factor-related differences in the composition of breast tissue and their associations with breast cancer risk.

Correlation between Hearing Impairment and the Triglyceride Glucose Index in Middle-Aged Female Based on a Korean National Health and Nutrition Examination Survey

Background and Objectives: This study aimed to investigate the association between insulin resistance, as measured by the triglyceride–glucose index (TyG index), and hearing impairment in middle-aged women in Korea. Materials and Methods: This cross-sectional survey utilized data from the Korea National Health and Nutrition Examination Survey (KNHANES) IV (2007–2009), specifically from the period after July 21, 2009, when hearing test results became available, and from the KNHANES V (2010–2012). This study was conducted on 5416 women aged 40 to 69 who had completed both the health examination survey and audiometric tests, excluding those with missing data on menopausal status and the use of hormone replacement therapy. Results: In the study group, the prevalence of high-frequency hearing loss according to the TyG index was significantly higher in the mild hearing loss group (OR = 1.29; 95% CI: 1.12, 1.49, p &lt; 0.001) and the moderate hearing loss group (OR = 1.27; 95% CI: 1.09, 1.48, p = 0.002). Conversely, the prevalence of low-frequency hearing loss did not show a significant difference in either the mild hearing loss group (OR = 1.17; 95% CI: 0.99, 1.37, p = 0.065) and the moderate hearing loss group (OR = 1.13; 95% CI: 0.94, 1.35, p = 0.199) Conclusions: Since diabetes can induce hearing impairment in women, it is recommended that women with a high TyG index undergo early hearing tests

Hemodynamic management of acute kidney injury.

To discuss the role of hemodynamic management in critically ill patients with acute kidney injury. Acute kidney injury (AKI) may be associated with persistent alterations in renal perfusion, even when cardiac output and blood pressure are preserved. The effects of interventions aiming at increasing renal perfusion are best evaluated by renal Doppler or contrast enhance ultrasound. However, limited data have been acquired with these techniques and the essential of the literature is based on surrogates of renal function such as incidence of use of renal replacement therapy. Fluids may increase renal perfusion but their effects are quite unpredictable and can be dissociated from their impact on cardiac output and arterial pressure. Inotropes can also be used in selected conditions. At the de-escalation phase, fluid withdrawal should be considered. Safe fluid withdrawal may be achieved when applied in selected patients with preserved tissue perfusion presenting signs of fluid intolerance. When applied, stopping rules should be set. Dobutamine, milrinone and levosimendan increase renal perfusion in AKI associated with cardiac failure or after cardiac surgery. However, the impact of these agents in sepsis is not well defined. Regarding vasopressors, norepinephrine is the first-line vasopressor agent, but vasopressin derivative may limit the requirement of renal replacement therapy. Angiotensin has promising effects in a limited size post-Hoc analysis of a RCT, but these data need to be confirmed. While correction of severe hypotension is associated with improved renal perfusion and function, the optimal mean arterial pressure (MAP) target level remains undefined, Systematic increase in MAP results in variable changes in renal perfusion. It sounds reasonable to individualize MAP target, paying attention to central venous and intraabdominal pressures, as well as to the response to an increase in MAP. Recent studies have refined the impact of the various hemodynamic interventions on renal perfusion and function in critically ill patients with AKI. Though several of these interventions improve renal perfusion, their impact on renal function is more variable.

THE IMPACT OF HOP EXTRACT ACTIVE COMPONENTS ON METABOLIC DISTURBANCES IN ESTROGEN DEFICIENT FEMALE RATS WITH PREDIABETES

A number of studies have shown a greater cardiovascular risk in women with type 2 diabetes compared to men. The latter may be due to more excessive manifestations of metabolic disorders in women, in particular postmenopausal, that develop even at the stage of prediabetes. Since the use of hormone replacement therapy in women after menopause had adverse results on the progression of cardiovascular events, an alternative method of reducing cardiovascular risk in postmenopausal women with prediabetes may be the use of phytoestrogens, which possess estrogen-like activity without negative side effects specific to exogenous estrogens. The aim of our study was to evaluate the effect of hop extract on metabolic disturbances in female rats with prediabetes under estrogen deficiency. Materials and methods. The study was conducted on three-month-old intact and ovariectomized Wistar rats with metabolic syndrome (MS) induced by high calorie diet (15% lard, 25% sucrose, 1% bile salts, 59% standard feed) for eight weeks. The test substances were administered intragastrically once per day in a dose of 20 μg/kg or 200 μg/kg b.w. in recalculation on 8-prenylnaringenin for hop extract and 200 μg/kg b.w. in recalculation on estradiol for the reference drug, from the fifth week after induction of metabolic syndrome. Results. It was revealed that administration of hop extract in a dose of 200 μg/kg, similar to estradiol, led to improvement in glucose tolerance and decrease in insulin resistance (p˂0.05) in estrogen deficient rats with MS. In contrast to estradiol, hop extract had no effect on the mass of uterus in ovariectomized animals. The use of hop extract only in the dose of 200 μg/kg, similar to estradiol, was accompanied by a significant decrease in body weight gain and visceral fat, as well as normalization of the total lipids content in serum of experimental animals (p˂0.05). It is of note, that hop extract resulted in decrease of hypertriglyceridemia (p˂0.05), but did not affect the level of total cholesterol, while estradiol reduced the concentration of total cholesterol (p˂0.05), and had no effect on the level of triglycerides. Hop extract in a dose of 200 μg/kg, as well as estradiol, led to a decrease in the intensity of lipid peroxidation induced by MS under estrogen deficiency, as evidenced by reduced concentration of conjugated dienes in serum (p˂0.05). At the same time, the total antioxidant activity of serum in these animals remained elevated compared to intact group. In rats with MS and hypoestrogenia, hop extract in the highest dose and estradiol resulted in complete normalization (p˂0.05) of the decreased level of NO stable metabolites in serum and the reduced activity of NO-synthase in heart. Conclusions. The revealed cardioprotective effect of hop extract that is realized due to the improved lipid profile and reduced insulin resistance, visceral obesity, oxidative stress and endothelial dysfunction in estrogen deficient female rats with MS indicates the prospects of its use for prevention and treatment of cardiovascular complications in postmenopausal women with prediabetes.

Evaluation of the Diagnostic Utility of Urine Biomarkers Tissue Inhibitor of Metalloproteinases-2 (TIMP-2) and Insulin-like Growth Factor Binding Protein-7 (IGFBP-7) in Predicting Acute Kidney Injury and Short-term Outcomes among High-risk, Critically Ill Patients in a Tertiary Government Hospital in the Philippines.

Acute kidney injury (AKI) is a common complication of critical illness that often leads to increased mortality and morbidity. Biomarkers detect AKI earlier, providing a window of opportunity for timely intervention. Of the recent biomarkers in literature, the cell cycle arrest biomarkers tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7) were found to be superior in predicting AKI. Our study aimed to evaluate the diagnostic performance of urine TIMP-2/IGFBP-7 in its ability to predict AKI and major adverse kidney events within 30 days (MAKE30) among high-risk patients for AKI. MAKE30 is a composite outcome comprised of all-cause mortality, use of renal replacement therapy (RRT), or persistent renal dysfunction at hospital discharge truncated at 30 days. We conducted a prospective, cross-sectional study which included 135 adult, non-COVID ICU patients. Baseline urine TIMP-2/IGFBP-7 results were used to dichotomize the population into low risk (<0.3 ng/mL) or high risk (≥0.3 ng/mL) for AKI. Participants were then observed for 30 days and monitored for MAKE30 outcomes. ROC curves were created to calculate the sensitivity, specificity, NPV, PPV, and the AUC of the 0.3 ng/mL cut-off to predict the AKI and MAKE30. Urine TIMP-2/IGFBP-7 cutoff of 0.3 ng/mL predicted AKI with a sensitivity of 82.4%, specificity of 79.2%, PPV of 57.1%, NPV of 93% and AUC of 0.81. MAKE30 was detected with a sensitivity of 62.8%, specificity of 76.1%, PPV of 55.1%, NPV of 81.4% and AUC of 0.69. Elevated levels of urine TIMP-2/IGFBP-7 were found to be associated with AKI (p<0.01), MAKE30 (p<0.01) and all of its subcomponents. Survival or discharge after 30 days were found to be associated with lower urine TIMP-2/IGFBP-7 levels (p<0.01). Urine TIMP-2/IGFBP-7, at its current cut-off at 0.3 ng/mL, can predict the likelihood of developing AKI and major adverse kidney events among high-risk patients for AKI. It can serve as a useful adjunct to existing methods, such as serum creatinine, in the early diagnosis and prognosis of acute kidney injury and expanding the therapeutic window to prevent disease progression and improve outcomes.

Assessment of the Workflow and Time to Antibiotic Dose Adjustment for Critically Ill Patients Starting Continuous Renal Replacement Therapy.

Background: Acute kidney injury (AKI) remains a common sequela of sepsis necessitating use of continuous renal replacement therapy (CRRT). In the setting of AKI, renally adjusted antimicrobials (eg, β-lactams) are dose reduced to prevent toxicity; however, the extracorporeal clearance of CRRT may lead to subtherapeutic exposures of dose reduced antimicrobials. The present study sought to evaluate the time to dose adjustment to CRRT appropriate doses of antimicrobials after initiation of CRRT. Methods: A retrospective cohort study of patients on CRRT and anti-pseudomonal β-lactams was conducted. CRRT was conducted as continuous veno-venous hemodialysis (CVVHD) per institutional standards. Baseline characteristics were collected including dialysate flow rate. The primary outcome was time to CRRT appropriate dose adjustment. Secondary outcomes included the pharmacist shift (ie, day, evening, or night shift) that CRRT was ordered and initiated. Continuous data were reported as median (IQR). Results: Forty-four patients were included in the analysis. The median dialysate flow rate was 2.3 L/hour (2, 3.1). Of included patients, 75% received cefepime therapy while 25% received meropenem. The median time to CRRT appropriate dosing was 13 hours (6, 20). CRRT was most commonly ordered during day shift (68%) but not started until evening (59%). The observed delay in appropriate dose adjustment may predispose patients to suboptimal antimicrobial exposure and subsequently therapeutic failure. CRRT was often ordered during the day shift but not initiated until evening which led to identification of potential procedural improvements. Conclusions: These data led to the initiation of a pharmacy in basket consult to alert pharmacists in real time of CRRT orders so that once CRRT was started, doses could be appropriately adjusted. Future studies to assess the impact of this process change on both time to appropriate dose and clinical outcomes are warranted.

СОСТОЯНИЕ ГИПОТАЛАМО-ГИПОФИЗАРНО-ГОНАДНОЙ СИСТЕМЫ У ВОЕННОСЛУЖАЩИХ. ОБЗОР ЛИТЕРАТУРЫ

This review paper provides an analysis of publications on change and misfunctioning of the hypothalamic-pituitary-gonadal system through the prism of the factors accompanying military service. The detectable decrease in testosterone levels as a result of the effects of those factors, as well as the use of testosterone replacement therapy in military personnel, are considered in detail in this paper and, certainly, need further study.

P225 RISK FACTORS FOR CEREBROVASCULAR DISEASE IN WOMEN ADMITTED TO THE INTERNAL MEDICINE SERVICE OF THE EMERGENCY DEPARTMENT OF THE CENTRAL HOSPITAL IN SAN CRISTOBAL (TACHIRA, VENEZUELA)

Background and objective: Cerebrovascular disease is a leading cause of mortality and disability worldwide. Research has focused on determining the risk factors for cerebrovascular disease independent of gender; however, it has been important to differentiate between men and women due to the variety of causes that occur in the latter. Therefore, the aim was to determine the risk factors for cerebrovascular disease in women admitted to the internal medicine service of the Central Hospital of San Cristóbal (Táchira, Venezuela). Methods: A case-control study was performed. Cases were female patients diagnosed with acute cerebrovascular disease (24 to 72 hours after symptom onset). Controls were hospitalized or community-based female subjects without pathologies associated with cardiovascular disorders. The case-control ratio was 1:2, of equal age or ± 5 years. All participants signed the informed consent form and completed the data collection form. Odds ratios (OR) were calculated, with 95% confidence intervals. Results: In the period between February 2 to July 15, 2020, 111 female participants entered the study, 37 cases (26 with ischemic cerebrovascular disease and 11 with hemorrhagic cerebrovascular disease) and 74 controls. Of the risk factors studied: arterial hypertension, diabetes mellitus, dyslipidemia, physical inactivity, smoking, alcohol consumption, overweight, obesity, atrial fibrillation, use of oral contraceptives, use of hormone replacement therapy, autoimmune diseases, only association was found between atrial fibrillation (OR 9.1736, 95% CI 3.3638-25.0173), autoimmune diseases (OR 9.1736, 95% CI 3.3638-5.0173) and ischemic cerebrovascular disease. No association was found with any risk factor and hemorrhagic cerebrovascular disease. Conclusions: The risk factors for cerebrovascular disease in the female population are modifiable and treatable, being pertinent to determine their presence and carry out the necessary actions to reduce morbimortality in this population group.