Large Cohort Study Research Articles

Effectiveness and safety of the ablative fractional 2940-nm Er: YAG laser for the treatment of androgenetic alopecia.

Laser sources have established their potential effect in inducing hair regrowth. No large cohort study has evaluated the effect of ablative fractional 2940-nm erbium yttrium aluminum garnet (Er: YAG) laser in the treatment of androgenetic alopecia (AGA). To investigate the efficacy and safety of the ablative fractional 2940-nm Er: YAG laser in combination with medication therapy for the treatment of AGA. We performed a retrospective study between first July 2021 to 30th December 2021. All included patients received oral finasteride and topical minoxidil, or combined with six sessions of Er: YAG laser at 2-week intervals. Patients were divided into medication or combined therapy groups. The efficacy of the two therapies was evaluated by the investigator's Global Assessment (IGA) scores and the patient's Likert satisfaction scale at week 12 and week 24. Changes in total, terminal and villous hair count, total and terminal hair diameter, and AGA grade were also recorded. Adverse events were evaluated at each follow-up. A total of 192 male patients with AGA were included, including 67 receiving combination treatment, and 125 receiving medication treatment. At week 24, the combination treatment afforded superior outcomes in the IGA score, patient's global assessment, total and terminal hair counts, and diameters (all P<0.05). No severe adverse events were reported in both groups. The combined therapy of ablative fractional Er: YAG laser and medication was superior in treating male AGA than single medication therapy without serious adverse effects.

Preoperative three-dimensional lung volumetry predicts respiratory complications in patients undergoing major liver resection for colorectal metastases

Colorectal liver metastases (CRLM) are the predominant factor limiting survival in patients with colorectal cancer and liver resection with complete tumor removal is the best treatment option for these patients. This study examines the predictive ability of three-dimensional lung volumetry (3DLV) based on preoperative computerized tomography (CT), to predict postoperative pulmonary complications in patients undergoing major liver resection for CRLM. Patients undergoing major curative liver resection for CRLM between 2010 and 2021 with a preoperative CT scan of the thorax within 6 weeks of surgery, were included. Total lung volume (TLV) was calculated using volumetry software 3D-Slicer version 4.11.20210226 including Chest Imaging Platform extension (http://www.slicer.org). The area under the curve (AUC) of a receiver-operating characteristic analysis was used to define a cut-off value of TLV, for predicting the occurrence of postoperative respiratory complications. Differences between patients with TLV below and above the cut-off were examined with Chi-square or Fisher’s exact test and Mann–Whitney U tests and logistic regression was used to determine independent risk factors for the development of respiratory complications. A total of 123 patients were included, of which 35 (29%) developed respiratory complications. A predictive ability of TLV regarding respiratory complications was shown (AUC 0.62, p = 0.036) and a cut-off value of 4500 cm3 was defined. Patients with TLV < 4500 cm3 were shown to suffer from significantly higher rates of respiratory complications (44% vs. 21%, p = 0.007) compared to the rest. Logistic regression analysis identified TLV < 4500 cm3 as an independent predictor for the occurrence of respiratory complications (odds ratio 3.777, 95% confidence intervals 1.488–9.588, p = 0.005). Preoperative 3DLV is a viable technique for prediction of postoperative pulmonary complications in patients undergoing major liver resection for CRLM. More studies in larger cohorts are necessary to further evaluate this technique.

Dyslipidemia in children with chronic kidney disease-findings from the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study.

Dyslipidemia is an important and modifiable risk factor for CVD in children with CKD. In a cross-sectional study of baseline serum lipid levels in a large prospective cohort study of children with stage 3-5 (predialysis) CKD, frequencies of abnormal lipid levels and types of dyslipidemia were analyzed in the entire cohort and in subpopulations defined by fasting status or by the presence of nephrotic range proteinuria. Associated clinical and laboratory characteristics were determined by multivariable linear regression analysis. A total of 681 patients aged 12.2 ± 3.3years with a mean eGFR of 26.9 ± 11.6ml/min/1.73 m2 were included. Kidney diagnosis was classified as CAKUT in 69%, glomerulopathy in 8.4%, and other disorders in 22.6% of patients. Nephrotic range proteinuria (defined by a urinary albumin/creatinine ratio > 1.1g/g) was present in 26.9%. Dyslipidemia was found in 71.8%, and high triglyceride (TG) levels were the most common abnormality (54.7%). Fasting status (38.9%) had no effect on dyslipidemia status. Except for a significant increase in TG in more advanced CKD, lipid levels and frequencies of dyslipidemia were not significantly different between CKD stages. Hypertriglyceridemia was associated with younger age, lower eGFR, shorter duration of CKD, higher body mass index (BMI-SDS), lower serum albumin, and higher diastolic blood pressure. Dyslipidemia involving all lipid fractions, but mainly TG, is present in the majority of patients with CKD irrespective of CKD stage or fasting status and is significantly associated with other cardiovascular risk factors.

Long-term incidence of acute cardiovascular events in transgender people - a large cohort study with national registry data

Long-term incidence of acute cardiovascular events in transgender people - a large cohort study with national registry data

Cannabinoid levels description in a cohort of patients with chronic and neuropathic pain treated with Cannabis decoction: A possible role of TDM

The phytocomplex of Cannabis is made up of approximately 500 substances: terpeno-phenols metabolites, including Δ-9-tetrahydrocannabinol and cannabidiol, exhibit pharmacological activity.Medical Cannabis has several pharmacological potential applications, in particular in the management of chronic and neuropathic pain. In the literature, a few data are available concerning cannabis pharmacokinetics, efficacy and safety.Thus, aim of the present study was the evaluation of cannabinoid pharmacokinetics in a cohort of patients, with chronic and neuropathic pain, treated with inhaled medical cannabis and decoction, as a galenic preparation.In this study, 67 patients were enrolled. Dried flower tops with different THC and CBD concentrations were used: Bedrocan® medical cannabis with THC level standardized at 19% and with a CBD level below 1%, Bediol® medical cannabis with THC and CBD level standardized at similar concentration of 6.5% and 8%, respectively.Cannabis was administered as a decoction in 47 patients and inhaled in 11 patients. The blood withdrawn was obtained before the new dose administration at the steady state and metabolites plasma concentrations were measured with an UHPLC-MS/MS method.Statistically significant differences were found in cannabinoids plasma exposure between inhaled and oral administration of medical cannabis, between male and female and cigarette smokers.For the first time, differences in cannabinoid metabolites exposures between different galenic formulations were suggested in patients. Therapeutic drug monitoring could be useful to allow for dose adjustment, but further studies in larger cohorts of patients are required in order to confirm these data.

Effect of beta-blockers and angiotensin receptor blockers in reducing the aortic growth rate in children with bicuspid aortic valve-related aortopathy

AimsThe aim of this study is to evaluate the effect of beta-blockers and angiotensin receptor blockers in reducing the aortic growth rate in children with bicuspid aortic valve (BAV)-related aortopathy and ascending phenotype. MethodsConsecutive paediatric patients (≤16 years) with BAV and ascending aorta (AsAo) dilation (z-score > 3) were enrolled in this observational retrospective cohort study. Patients receiving prophylactic treatment with either atenolol (0.5 to 1.0 mg/kg/daily) or losartan (0.7 to 1.4 mg/kg/daily) were compared with those who did not receive medical prophylaxis (control group). The primary outcome of interest was the annual rate of change in maximal AsAo diameter z-score in the treatment and control groups. ResultsFrom a cohort of 1005 patients, 120 (mean age 11.3 ± 4.5 years, 82% males) fulfilled the inclusion criteria and were included in the study. Patients in the treatment and control group had similar age, sex, family history of BAV, BAV morphology, and baseline AsAo diameter. During a median follow-up of 7.1 years (interquartile range 3.8–10.2), no differences were observed in the annual growth rate of aortic diameter z-score between patients on treatment and controls. The prevalence of aortic diameter progression was similar in the treatment and control groups, and treatment with atenolol or losartan was not associated with a lower rate of aortic disease progression. ConclusionsThe findings revealed no significant difference in the annual aortic growth rate between treated and untreated patients. Larger cohort studies or, ideally, randomized clinical controlled trials are needed to validate these findings.

Risk of gestational diabetes in women with PCOS based on body mass index: The Japan Environment and Children's Study.

Women with polycystic ovary syndrome (PCOS), which is the most common endocrine disorder in women of reproductive age, have a potentially increased risk of gestational diabetes mellitus (GDM). To examine the impact of PCOS on GDM based on maternal body mass index (BMI) using data from a large birth cohort study in Japan. Prospective observational study using data from the Japan Environment and Children's Study (JECS). Singleton pregnancies in the JECS during 2011-2014 were included. Mothers with HbA1c levels of ≥6.5% in the first trimester and history of DM or steroid use during pregnancy were excluded. Participants were categorized according to their pre-pregnancy BMIs: G1 (<18.5 kg/m2), G2 (18.5-19.99 kg/m2), G3 (20.0-22.99 kg/m2), G4 (23.0-24.99 kg/m2), and G5 (≥25.0 kg/m2). The impact of PCOS on early (Ed) and late-onset (Ld) GDM for each group was estimated using a multiple logistic regression model. We included 92774 participants, comprising 2012 PCOS(+) cases. GDM occurrence was higher in women with PCOS (p<0.001). PCOS had no effect on GDM in G1, G2, and G3. In G4, PCOS increased the risk of Ed GDM (adjusted odds ratio [aOR]: 3.27, 95% confidence interval [CI]: 1.29-8.29). In G5, PCOS increased the risk of both Ed (aOR: 2.48, 95% CI: 1.53-4.02) and Ld GDM (aOR: 1.94, 95% CI: 1.23-3.07). The impact of PCOS on GDM occurrence depended on the pre-pregnancy BMIs, which may facilitate personalized preconception counseling among women with PCOS.

Effect of religion on the course of anxiety disorders and symptoms over 9-years follow-up

BackgroundReligion can be an important aspect in life for people and may therefore be important to consider in anxiety disorders. However, there has been limited research into the longitudinal relationship between religiousness and the prevalence of anxiety disorders or anxiety severity and no such research up to date looking at specific anxiety disorders. MethodsWe made use of data from the Netherlands Study of Depression and Anxiety (NESDA), a large clinical cohort study, including 2981 participants at baseline. Based on religious affiliation, commitment to affiliation and religious attendance at baseline as demographic variables, three groups (non-affiliated; affiliated, low commitment/attendance; affiliated, higher commitment/attendance) were compared regarding the prevalence of specific anxiety disorders and anxiety severity at baseline and at two, four, six, and nine years follow-up. For the analyses, we used graphs and Linear Mixed Models. ResultsOverall, no differences were found for the prevalence of specific anxiety disorders and of comorbidity between anxiety disorders or comorbidity with depressive disorders. Furthermore, results showed no differences between the groups regarding the anxiety severity over time. LimitationsThe main limitations relate to the operationalization of religiousness based on demographic variables at baseline. ConclusionsOn a population level, being religiously affiliated with more or less commitment/attendance does not seem to protect against specific anxiety disorders or more anxiety symptoms, nor is it a risk factor. Further research should focus on more internal religious aspects, and more specifically on anxiety in specific groups of religious people or people with specific religion related anxiety.

Outcomes and management in paediatric autoimmune hepatitis presenting as acute liver failure: Individual patient data meta-analysis.

Autoimmune hepatitis (AIH) in children presenting in acute liver failure (ALF) can be fatal and often requires liver transplantation (LTx). This individual patient data meta-analysis (IPD) aims to examine management and outcomes of this population, given the lack of large cohort studies on paediatric AIH first presenting as ALF (AIH-ALF). A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses of IPD statement using PubMed and Excerpta Medica dataBASE, and included English studies published between 2000 and 2020. The study included patients under 21 years of age, diagnosed with type 1 or 2 AIH and presenting with ALF. Data extracted included clinical and biochemical characteristics, interventions, and outcomes. Three hundred and thirty eligible patients from 61 studies were identified, with an additional five patients from our institution. The majority were female (66.8%), with a median age of 10. Overall, 59.7% achieved native liver survival (NLS), 35% underwent LTx, and 5% died before LTx. The use of corticosteroids with non-steroid immunomodulators increased the likelihood of NLS by 2.5-fold compared to corticosteroids alone. AIH-1 was associated with 3.3-fold odds for NLS, compared to AIH-2. However, on multivariate analysis, only AIH-1 was identified as an independent predictor for NLS (OR 3.8 [95% CI 1.03-14.2], p = .04). While corticosteroids and non-steroid immunomodulators treatment may offer enhanced probability of achieving NLS, treatment regimens for AIH-ALF may need to consider patient-specific factors, especially AIH type. This highlights the potential for NLS in AIH-ALF and suggest a need to identify biomarkers which predict the need for combination immunosuppression to avoid LTx.

Abstract PO4-11-12: Patient Reported Outcomes from a multi-site, prospective Pivotal study evaluating pegulicianine fluorescence guided surgery (pFGS) for breast cancer lumpectomy procedures using the Lumicell Direct Visualization System (DVS)

Abstract Background: In pegulicianine fluorescence guided surgery (pFGS), a standard of care lumpectomy procedure is performed, and additional tissue is taken from cavity walls at sites of high pFGS signal. This approach been shown to reduce 2nd surgeries and remove additional tumor left by standard surgery, but may remove more tissue, potentially worsening cosmetic outcomes. Patient breast satisfaction surveys were used to assess cosmesis after pFGS. Methods: A prospective Pivotal trial of pFGS in women undergoing lumpectomy surgery for stage 0-III breast cancer was conducted at 14 US sites (NCT03686215). We assessed the safety and efficacy of the Lumicell DVS in identifying and removing residual cancer from the lumpectomy cavity in real time. Patient Reported Outcome Measures (PROM) data was collected as an exploratory endpoint. The BREAST-Q, a validated tool that measures patient perspectives after different breast procedures, was used to collect PROM data. An 11-question BREAST-Q survey was used to measure patients’ breast satisfaction at baseline (pre-surgery) and at multiple timepoints through 6-months post lumpectomy. Descriptive statistics of participating patients’ responses were collected and analyzed. Survey results were analyzed by the distribution of patient ratings for each question and the change in the distribution of ratings over time, with comparison of baseline to post-lumpectomy. Comparison of patient satisfaction with or without additional pFGS-directed tissue removal was performed with Item Response Theory assuming all items equally discriminative of responding patients. For each timeframe, responses to BREAST-Q items were used to create a response score for each patient. Scaled factor scores (0-100) were compared between groups with and without additional tissue removed during pFGS. Results: Of the 357 patients evaluated for efficacy in the primary Pivotal study analysis, 255 patients agreed to participate in the PROM surveys (71%). Approximately 60% of the participating respondents completed a pre- and initial post-lumpectomy survey while only 34% of the participating patients completed a pre- and 6-month post-lumpectomy survey. Most patients responded either “Very Satisfied” or “Somewhat Satisfied” across all surveyed timeframes. No significant difference in patient breast satisfaction was found at any time point between the groups with and without additional pFGS-guided shaves removed (p &amp;gt;0.05). There were 4 patients with scores of 3 or higher pre-surgery but 2 or lower post-surgery. Among these, 1 had no pFGS-guided shaves taken. The remaining 3 had had pFGS-guided shaves taken, but 2 required a second lumpectomy surgery and 1 underwent mastectomy, these additional surgeries likely accounting for decreased cosmetic outcomes. Discussion: Patient perspective of breast satisfaction was not decreased by the amount of extra tissue removed by pFGS. These data suggest that pFGS using the Lumicell DVS does not significantly decrease breast cosmesis. Three of 4 patients with decreased satisfaction had 2nd surgeries, confirming the importance of finding approaches to decrease 2nd surgeries. This data was collected during the COVID-19 pandemic, which may have adversely impacted the compliance rate of survey completion. Studies in larger cohorts with longer follow up are required to better assess the relative impact of 2nd surgeries, radiation, and systemic therapy on breast satisfaction PROM scores after lumpectomy. Citation Format: Kelly Hunt, Irene Wapnir, E Shelley Hwang, David Carr, Peter Blumencranz, Kate Smith, Manna Chang, Jorge Ferrer, Barbara Smith. Patient Reported Outcomes from a multi-site, prospective Pivotal study evaluating pegulicianine fluorescence guided surgery (pFGS) for breast cancer lumpectomy procedures using the Lumicell Direct Visualization System (DVS) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-11-12.

Abstract PO2-17-11: Management guidelines for epithelial atypia diagnosed in breast screening, based on an analysis of a large prospective cohort study (Sloane Project)

Abstract Background: Epithelial atypia in the breast is most frequently detected through breast screening. Internationally, guidelines differ between advising diagnostic surgical excision of screen-detected atypia versus vacuum-assisted excision (VAE), often with annual follow up surveillance mammography. Prospective data with detailed follow-up and outcomes for subsequent cancer events is lacking. We evaluated a large prospective cohort of screen-detected atypia (Sloane Project) and an expert consensus meeting to develop management recommendations. Methods: We undertook an observational analysis of women with screen-detected epithelial atypia (Atypical Ductal Hyperplasia (ADH), Flat Epithelial Atypia (FEA), Lobular In Situ Neoplasia (LISN), or mixed atypia) reported to the National Health Service (NHS) Breast Screening Programme (BSP) between 01/04/03 and 20/06/18. We estimated cumulative incidence of invasive cancers per 1000 women within 1 and 2 subsequent screening rounds using cumulative incidence functions and repeated these by women’s age, type of atypia and year of diagnosis. Flexible parametric modelling produced hazard ratios (HR). The results were presented at a consensus meeting with clinical experts, patient representation, national decision-makers and commissioners from the NHS in England. A consensus on management recommendations was reached. Results: Among 3238 women (19088 person-years of follow up) with screen-detected atypia, diagnoses increased from 2010 (n=119) to 2015 (n=502). This coincided with the introduction of digital mammography into English screening centres from 2010 and changes in biopsy technique. A total of 141 invasive breast cancers were detected up to December 2018. Cumulative incidence of invasive breast cancer per 1000 women with atypia (ADH, FEA, LISN or mixed) was 14.2 (95% CI 10.3, 19.1) and 45.0 (36.3, 55.1) at 3- and 6-years post atypia based on 40 and 94 cancers, respectively. Women diagnosed with atypia during 2013-2018 had an invasive cancer detected less frequently within 3 years than women with an atypia diagnosis between 2003-2007 or 2008-2012 (6.0 invasive cancers (3.1, 10.9) per 1000 women in 2013-2018 Vs 24.3 (13.7, 40.1) and 24.6 (14.9, 38.3) in 2003-2007 and 2008-2012), suggesting that atypia diagnosis may increasingly contribute to ‘overdiagnosis’. Cancers detected were similar to the general screening population regarding grade, size and nodal involvement. Ipsilateral and contralateral cancers were detected in equal numbers, supporting the concept that atypia represents a risk factor rather than precursor of invasive cancer in the short term. Results by age and type of atypia did not suggest a need for risk-stratified management. Considering subsequent invasive cancer, VAE appeared to be as safe as diagnostic surgical excision of atypia (HR 0.75 (0.45, 1.25)). The expert consensus considered that increased screening of women with screen-detected atypia over and above routine 3-yearly screening was not beneficial, given the overall low numbers of cancers at three years. This applied to all types of atypia and all women who received digital mammography and diagnosis of atypia on core or vacuum-assisted biopsy followed by VAE within a quality assured NHS BSP. Conclusions: Breast atypia represents a risk factor for invasive cancer and does not necessitate surgical excision. Changes to mammography (digital vs plain film) and biopsy techniques (gauge of needle and use of vacuum-assistance) may lead to detection of atypia which is then ‘over-managed’. Current recommendations for annual mammography for 5 years after a diagnosis of epithelial atypia may be overly cautious. We suggest that women with screen detected atypia should be followed up with routine screening appointments. Citation Format: Karoline Freeman, David Jenkinson, Karen Clements, Matthew Wallis, Sarah E Pinder, Elena Provenzano, Hilary Stobart, Nigel Stallard, Olive Kearins, Nisha Sharma, Abeer Shaaban, Cliona Kirwan, Bridget Hilton, Alastair Thompson, Sian Taylor-Phillips. Management guidelines for epithelial atypia diagnosed in breast screening, based on an analysis of a large prospective cohort study (Sloane Project) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-17-11.

Effect of a hypertensive response during exercise on growth rates of aortic diameters.

Aortic diameters are related to age, sex, and body size. There are a scarcity of data on the long-term sequelae of a hypertensive response to exercise (HRE) on aortic diameters. In this retrospective cohort study, we aimed to evaluate the relationship between the growth rates of the aorta in individuals with a HRE. Our analysis included follow-up data of 649 patients recruited between January 2009 and December 2014 with a HRE. Participants with known connective tissue disease or a history of acute aortic syndrome were excluded. Sinus of Valsalva (SoV) and ascending aorta (AscAo) diameters were measured by transthoracic echocardiography using leading edge to leading edge convention at end-diastole. At baseline, median age, maximum systolic blood pressure (BP), body mass index (BMI), diameter of the SoV, and AscAo were 62 years, 208 mmHg, 26.9kg/m2, 35mm, and 35mm respectively. 32% of patients were female and 67% had hypertension. After a median follow-up of 7.1 years, mean yearly growth rates (±SD) of the SoV and AscAo were 0.09 (0.41) mm and 0.13 (0.56) mm respectively. No significant associations were observed between growth rates of aortic diameters and maximum systolic and diastolic BP or when considering only individuals with a baseline diameter > 40mm. In this large cohort study, maximum systolic and diastolic BP during exercise showed no association with growth rates of aortic diameters. Furthermore, the mean growth rates of aortic diameters in this population were in line with growth rates in a normal population.

Abstract SS02-02: Hormone Replacement and Alternatives for Relief of Vasomotor Symptoms in Women at Increased Risk for Breast Cancer

Abstract 70% of women will experience vasomotor symptoms sufficient to impact their quality of life during menopause transition and the early menopause. These symptoms are thought result from neurotransmitter imbalances resulting from ovarian hormone reductions and hypersecretion of gonadotropins. Increases in gonadotropins result in neurotransmitter triggered stimulation of the neurokinin 3 (NK3) receptor and thermoregulatory imbalance. Estrogen deficiency also reduces serotonin which can also trigger increases in hot flashes, and sleep disturbances. Vasomotor symptoms last on the average for 7 years until acclimation to persistent low estrogen levels occurs. Estrogen +/- progestin replacement therapy is associated with the greatest likelihood of vasomotor symptom relief as it reduces gonadotropin and NK3 receptor signaling and increases serotonin. Progestins also increase the neuroinhibitory transmitter gamma-aminobutyric acid (GABA) which improves sleep quality. There continues to be confusion on the part of providers and patients regarding the excess risk of breast cancer and thromboembolic events as these risks are affected by type of agent, route of delivery, age, duration of treatment, and presence of obesity. The majority of placebo controlled randomized clinical trial data on hormone replacement with estrogen or estrogen + a progestin comes from the Women’s Health Initiative (WHI) for women 50-79 in which oral conjugated estrogen (CE) 0.625 mg was used as the estrogen for women without a uterus and medroxyprogesterone acetate (MPA) was added to CE for women with a uterus to protect against endometrial hyperplasia and cancer. The median age at entry to WHI that trial was 63 and a substantial proportion had previously taken hormones. Large longitudinal cohort studies have been helpful in assessing risks in women starting hormones at a more clinically relevant age (45-55) and with hormonal preparations other than oral CE and MPA. Five to seven years of estrogen alone results in minimal if any increased risk for breast cancer. However, combined estrogen+ progestin replacement for women over 50, necessary for women with a uterus, results in an ~ 30 % relative increased risk for breast cancer if taken for up to 5 years and a doubling of risk with 10 years of treatment. So called bioidentical hormones often compounded as oral troches of estradiol, progesterone, and testosterone, are also associated with increased breast cancer risk. Vaginal hormones have not been found to increase risk for breast cancer. Increased risk of thromboembolism is predominately observed in women over 50 using oral as opposed to transdermal preparations. Increased risk for stroke and dementia was observed in the WHI again with oral hormones in women over 65. In the WHI there was no increase in cancer related, cardiovascular or overall mortality with estrogen or estrogen and progestin. For high-risk peri and post-menopausal women with who would like to reduce/alleviate their vasomotor symptoms with no increase in risk for breast cancer there are several options: 1) the tissue selective estrogen complex bazedoxifene (BZA) combined with conjugated estrogen (CE) 2) the non-hormonal option of NK3 receptor antagonists such as fezolinetant ( 3) non-hormonal options of gabapentin, selective serotonin reuptake inhibitors (SSRI) and serotonin and norepinephrine uptake inhibitors (SNRI). BZA and CE and fezolinetant are reported to reduce hot flashes in 70% or more of individuals with paroxetine effectiveness reported as 50%. All three are FDA approved for reduction of vasomotor symptoms. The combination of BZA and CE is also being investigated for breast cancer risk reduction. These agents differ with respect to side effects with increased risk of blood clots for bazedoxifene and conjugated estrogen, increased risk of nausea, diarrhea, and liver dysfunction for fezolinetant and drowsiness and dry mouth for SSRIs. Drug costs may also dramatically affect insurance coverage and patient uptake of a particular strategy. A recent online perusal of a popular site for finding the lowest drug price suggested substantial differences in the cost of drugs for relief of vasomotor symptoms. The approximate cost for a 30- day supply of oral estradiol was $30, estradiol transdermal patches $35, oral progesterone $15, combined estradiol and levonorgestrel transdermal patches $240, oral CE $200, oral CE + medoxyprogesterone acetate $240, and for BZA+ CE $200. For non-hormonal therapies the cost of 30 days of gabapentin was $11, paroxetine $30 and fezolinetant $550. Crandall, Mehta, and Manson JAMA 2023 329:405-420 Collaborative Group on Hormonal Factors in Breast Cancer Lancet 2019 394: 1159-1168 Fabian et al Ca Prev Res 2019 10:711-720 Modi and Dhillo Neuroendocrinology 2019 109:242–248 Citation Format: C. Fabian. Hormone Replacement and Alternatives for Relief of Vasomotor Symptoms in Women at Increased Risk for Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr SS02-02.

Abstract PO1-02-14: Breast cancer in older women - long-term prognosis by age and subtype in a large population-based cohort

Abstract Background Compared to middle-aged women, older women have a higher risk of breast cancer death. Whether the increased risk of breast cancer death is present in all subgroups of older adults with breast cancer, or negligible in the subgroups receiving adequate surgical and oncological treatment, has been debated. We studied long-term prognosis by age and subtype, adjusting for stage, treatment, socioeconomic status and comorbidity, clarifying which subgroups of older patients that are at increased risk of breast cancer death. Methods In a nation-wide cohort of 45,949 women aged ≥60 years at diagnosis of breast cancer 1997-2014, we estimated crude probabilities of breast cancer death and from other causes using competing risk methods. Cox proportional hazards models were used to estimate adjusted hazard ratios (HR) with 95% confidence intervals (CI. Results In this large population-based cohort study of older women with breast cancer, we found an increasing risk of breast cancer death with increasing age at diagnosis, both at 5- and 10-year follow up. The strong association between age and breast cancer death was found for all breast cancer subtypes, being most prominent in Her2-positive breast cancer. The age effect was also significant in Luminal A breast cancer where treatment opportunities are not necessarily affected by age. High-risk tumors were equally common in all age groups above 60 years. In multivariable analysis, stage, subtype, grade and treatment were important explanatory variables to the age-related differences in survival, while comorbidity and socioeconomic status contributed minorly. After adjustments, older age remained an independent risk factor for both overall and breast cancer survival. Older women with triple-negative (60-79 years) or Her2-positive (60-84 years) tumors had a 5-year risk of breast cancer death exceeding the risk of death by other causes. Conclusions Older women had a significantly higher risk of breast cancer death irrespective of breast cancer subtype, also in Luminal A disease where treatment opportunities are not necessarily affected by age. Table 3. Crude probabilities of breast cancer specific death and death by other cause (competing cause of death) at 5, 10 and 15 years. Table 4. Multivariable analysis of prognostic factors affecting 15-year overall (OS) and breast cancer- specific survival (BCSS) Table 5. Multivariable analysis of prognostic factors affecting 15-year overall (OS) and breast cancer- specific survival (BCSS) by age at diagnosis and subtype. Citation Format: Amelia Chiorescu, Anna L V Johansson, Antonis Valachis, Alexios Matikas, Jan Frisell, Lars Holmberg, Irma Fredriksson. Breast cancer in older women - long-term prognosis by age and subtype in a large population-based cohort [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-02-14.

Abstract PS05-01: Accuracy and safety of fibroblast activation protein inhibitor (FAPI) PET/CT in diagnosis of axillary lymph node metastasis in early breast cancer patients: a prospective cohort study (PFB-01&amp;02 study)

Abstract Background Axillary lymph node (ALN) is the most common metastatic site of breast cancer (BC) and the status of ALN determines the staging, treatment and prognosis for BC patients. Traditional imaging techniques, including ultrasound (US), mammography, MRI, and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) were still unsatisfactory to evaluate the status of ALN non-invasively. Fibroblast activation protein (FAP) is highly expressed in cancer-associated fibroblasts and FAP inhibitor (FAPI) PET has been found quite promising in BC. Well-designed prospective large cohort study concerning the diagnostic performance and safety profile of FAPI PET/CT in detection of ALN metastasis of BC is still lacking. Furthermore, FAPI could be radio-labeled with different radio-nuclides including 68Ga and 18F, and there is yet no data concerning the 18F-labeled FAPI in BC. In this study, we investigated the accuracy of FAPI (both 68Ga-FAPI-04 and Al18F-FAPI-04) PET/CT in newly diagnosed BC patients for assessing ALN metastasis. We also compared the diagnostic performance of FAPI PET/CT with that of 18F-FDG PET/CT and US. Methods This prospective study was approved by the Peking Union Medical College Hospital Ethics Committee and was registered online at NIH ClinicalTrials.gov (NCT05574907, NCT05574920). The inclusion criteria were as follows: (1) age 18-80 years old; (2) newly diagnosed BC confirmed by biopsy or with BI-RADS category 4C or 5 lesions by US. The exclusion criteria were as follows: (1) pregnancy or lactation; (2) patients unwilling to undergo PET/CT scans. All patients received biopsy or surgery on breast lesion and ALN. Patients received FAPI and 18F-FDG PET/CT after enrollment. The safety profile of FAPI PET was monitored after injection using the Common Terminology Criteria for Adverse Events. Two experienced nuclear medicine physicians, who were blinded to the pathological diagnosis and other imaging results, assessed the PET/CT images. It was defined as visually positive if the radioactive uptake of the ALN was higher than that of the adjacent normal tissue. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each diagnostic test. The McNemar test was applied to compare the differences of sensitivity and specificity between FAPI PET/CT, 18F-FDG PET/CT, and US. All statistical tests were performed two-sided, and P&amp;lt; 0.05 was considered statistically significant. Results In total, 113 patients (27-79 years old, median age 66) were enrolled. 53 patients underwent 68Ga-FAPI-04 PET/CT, and the other 60 patients underwent Al18F-FAPI-04 PET/CT. All patients underwent 18F-FDG PET/CT and US. A total of 53/113 (46.9%) patients were finally diagnosed with ALN metastasis. The sensitivity, specificity, accuracy, PPV, and NPV were 90.6%, 90.0%, 90.3%, 88.9%, and 91.5% for FAPI PET/CT, 84.9%, 73.3%, 78.8%, 73.8%, and 84.6% for 18F-FDG PET/CT, 83.0%, 76.7%, 79.6%, 75.9%, and 83.6% for US, respectively (Table 1). The specificity of FAPI PET/CT was significantly higher than that of 18F-FDG PET/CT (P &amp;lt; 0.05) and US (P &amp;lt; 0.05). The sensitivity of FAPI PET/CT was higher than that of 18F-FDG PET/CT (P= 0.45) and US (P= 0.29). There was no significant difference of sensitivity and specificity between 18F-FDG PET/CT and US (P &amp;gt; 0.05). The sensitivity, specificity, accuracy, PPV, and NPV were 92.0%, 92.9%, 92.5%, 92.0%, and 92.9% for 68Ga-FAPI-04 PET/CT, and 89.3%, 87.5%, 88.3%, 86.2%, and 90.3% for Al18F-FAPI-04 PET/CT, respectively (Table 2). The 68Ga-FAPI-04 PET/CT and Al18F-FAPI-04 PET/CT procedures were well tolerated in all patients. The only adverse event was injection pain in 12/53 (22.6%) patients injected with 68Ga-FAPI-04, and 7/69 (10.1%) patients injected with Al18F-FAPI-04, which might relate to the ethanol in the imaging agent. Conclusion The FAPI PET/CT outperformed 18F-FDG PET/CT and US in the diagnosis of ALN metastasis among early breast cancer patients. The 68Ga-FAPI-04 and Al18F-FAPI-04 PET/CT have similar diagnostic performance. The FAPI PET/CT procedures were well tolerated in all patients. Table 1 Diagnostic performance of FAPI PET/CT, 18F-FDG PET/CT, and ultrasound in the diagnosis of ALN metastasis Table 2 Diagnostic performance of 68Ga-FAPI-04 and Al18F-FAPI-04 PET/CT in diagnosis of ALN metastasis Citation Format: Bo Pan, Zhixin Hao, Chao Ren, Lifan Zhang, Yidong Zhou, Qiang Sun, Li Huo. Accuracy and safety of fibroblast activation protein inhibitor (FAPI) PET/CT in diagnosis of axillary lymph node metastasis in early breast cancer patients: a prospective cohort study (PFB-01&amp;02 study) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS05-01.

The relationship between patient-specific factors and functional progression of COVID-19 survivors admitted to an inpatient rehabilitation facility.

Survivors of hospitalization for severe acute COVID-19 infection faced significant functional impairments necessitating discharge to inpatient rehabilitation facilities (IRFs) for intensive rehabilitation prior to discharge home. There remains a lack of large cohort studies of the functional outcomes of patients admitted to IRFs with COVID-19-related impairments and the relationship to patient-specific factors. To characterize functional outcomes of patients admitted to IRFs for COVID-19-related debility and to investigate associations between functional outcomes and patient-specific factors. Multisite retrospective cohort study. Multiple IRFs in a large urban city. Adult patients admitted to IRFs for rehabilitation after hospitalization for acute COVID-19 infection. Not applicable. Primary outcomes included change in GG Self-Care and Mobility Activities subscales and Functional Independence Measure scores from admission to discharge from inpatient rehabilitation. Linear regression analysis was used to relate functional changes to demographic, medical, and hospitalization-specific factors. Secondary outcomes included discharge destination from the IRF. The analysis included n = 362 patients admitted to IRFs for COVID-19-related rehabilitation needs. This cohort showed significant improvements in mobility, self-care, and cognition congregate scores (216.0%, 174.3%, 117.6% respectively). Patient-specific factors associated with functional improvement, included age, body mass index, premorbid employment status, history of diabetes and cardiac disease and medications received in acute care, and muscle strength upon admission to IRF. Patients admitted to inpatient rehabilitation for COVID-19-related functional deficits made significant functional improvements in mobility, self-care, and cognition. Many significant associations were found between patient-specific factors and functional improvement, which support further investigation of these factors as possible predictors of functional improvement in an IRF for COVID-19-related deficits.

Abstract PO1-20-05: SURVIVE study – a multicenter, randomized, controlled phase 3 superiority trial, evaluating liquid biopsy guided intensified follow-up surveillance in women with intermediate-to high-risk early breast cancer

Abstract Background: Current guidelines limit routine breast cancer follow-up to clinical examinations and breast imaging. This is based on the results of two large cohort studies conducted in the 1980s that showed no improvement in overall survival (OS) by an intensified screening for distant metastases. Thus, imaging for distant metastases should currently only be performed in patients with specific symptoms. To detect distant relapse in a pre-symptomatic stage, we suggest the evaluation of a liquid biopsy-guided intensified surveillance, analyzing tumor markers (CA 27.29, CA 125 and CEA), circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Trial design: Funded by the German Federal Ministry of Education and Research, the SURVIVE study is the first large, randomized breast cancer surveillance trial to investigate the potential survival benefit of a liquid biopsy guided follow-up care in intermediate- to high-risk early breast cancer patients. The trial is a German multicenter, controlled phase 3 superiority study, in which 3500 patients are randomized in a 1:1 ratio to standard vs. liquid biopsy guided intensified follow-up care. At the time of writing 150 patients have been enrolled since December 2022. The total study duration is 144 months. Stratification factors are study site as well as HR-, HER2- and nodal status at surgery. Both study arms receive standard follow-up according to national guidelines. Additional blood samples (year 1-3 every 3 months, year 4-5 every 6 months) and standardized Quality of Life (QoL) questionnaires (EORTC-QLQ-C30/PA-F12, every 6 months) will be collected. While the standard surveillance arm samples will only be stored in a biobank, samples collected in the intensive surveillance arm will be tested for standard tumor markers, CTCs and ctDNA. Pre-specified abnormal findings of any of the liquid biopsy markers indicative of minimal residual disease trigger complete staging. In the event of confirmed disease recurrence, guideline-based treatment follows, otherwise, liquid biopsy testing continues. If applicable, study participants may enter interventional trials. Eligibility criteria: Eligible patients are adult females or males with histologically confirmed primary invasive intermediate to high-risk early breast cancer, defined as an indication for (neo-)adjuvant chemotherapy, and/or large tumor size ( &amp;gt; 50 mm), and/or positive lymph nodes (≥ pN1mi), and/or high grade (≥ G3). Primary anti-tumor therapy (surgery, adjuvant chemo- or radiotherapy) must have been completed ≤ 24 months (≤ 60 months for luminal carcinoma) previously. Patient enrollment during adjuvant endocrine- or antibody-therapy, CDK4/6-/PARP- or PI3K-inhibitors and antibody-drug conjugates is allowed. Statistical methods: The two primary objectives are to determine whether intensified, liquid biopsy-guided surveillance leads to better OS or an overall lead-time effect, compared to standard surveillance. The primary endpoint OS will be analyzed in the ITT population using Kaplan Meier methods and cox regression models, the overall lead time effect is a purely descriptive composite measure. Secondary objectives include invasive disease-free survival (IDFS), distant disease-free survival (DDFS), distant recurrence free survival (DRFS), breast cancer-specific survival (BCSS) and quality of life (QoL). Specific aims: To improve OS and the QoL during breast cancer follow-up, we propose a liquid biopsy guided follow-up method, with high sensitivity and specificity for the earlier detection of distant (oligo-)metastases, to enable earlier initiation of therapy. Conclusion: The SURVIVE-study is a long-awaited trial in early breast cancer follow-up, based on promising liquid biopsy markers. If successful, the results will lead to a paradigm shift in current follow-up care of intermediate to high-risk early breast cancer survivors. Clinical trial information: NCT05658172 Citation Format: Franziska Mergel, Sophia Huesmann, Thomas Friedl, Kerstin Pfister, Tatjana Braun, Angelina Fink, Forca Mehmeti, Tanja Fehm, Volkmar Müller, Klaus Pantel, Andreas Hartkopf, Elisabeth Wiesmüller, Brigitte Rack, Wolfgang Janni. SURVIVE study – a multicenter, randomized, controlled phase 3 superiority trial, evaluating liquid biopsy guided intensified follow-up surveillance in women with intermediate-to high-risk early breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-20-05.

The Association of Psychotherapy With Burnout, Depression, and Measures of Well-Being in Residents and Fellows: A Pilot Study.

Resident physicians experience high rates of burnout and depression but rarely prioritize their well-being or seek mental health care. The Accreditation Council for Graduate Medical Education mandated that training programs prioritize resident wellness and emotional and mental health to ensure readily available and accessible mental health care. To help meet that requirement and circumvent barriers to accessing care, the University of California San Diego Healer Education Assessment & Referral (HEAR) Program offers residents and fellows short-term therapy for coping with challenges that threaten their well-being. This report describes the results of a pilot study designed to evaluate the feasibility and effectiveness of the HEAR Program's resident therapy program. The cohort included residents and fellows who completed at least 1 postbaseline assessment from January to May 2022. Measures of fulfillment, burnout, self-compassion, quality of life, depression, and suicidal ideation were assessed and compared before and up to 12 weeks after enrollment. Of the 39 residents who consented to participation, 30 completed at least 1 postbaseline assessment. Most outcomes improved after therapy, with significant increases in fulfillment (mean [SE] coefficient, 0.24 [0.08]; z score, 2.86; P = .004), self-compassion (mean [SE] coefficient, 0.37 [0.07]; z score, 5.72; P < .001), and quality of life ( P < .001) and significant reductions in burnout (Stanford burnout scale: mean [SE] coefficient, -0.27 [0.07]; z score, -4.01; P < .001; single-item burnout scale: mean [SE] coefficient, -0.34 [0.08]; z score, -4.37; P < .001) and depression severity (mean [SE] coefficient, -1.08 [0.25]; z score, -4.36; P < .001). This pilot study noted improvements in fulfillment, compassion, quality of life, and function, as well as reductions in burnout and depression severity, among resident physicians. Future studies in larger cohorts are needed to validate these findings and inform further optimization of this program.

Endothelial Dysfunction Biomarkers and CKD Incidence in the REGARDS Cohort

IntroductionChronic kidney disease (CKD) is only partly caused by traditional risk factors. Endothelial dysfunction is common in CKD and may contribute to CKD incidence. We studied the association of circulating biomarkers reflecting endothelial dysfunction with incident CKD. MethodsREGARDS is a prospective cohort of 30,239 Black or White adults aged ≥45 years. Baseline levels of ICAM-1, VCAM-1, factor VIII, and E-selectin were measured in 3,300 participants without baseline CKD or albuminuria who attended a second visit 9.4 years later. Kidney outcomes were incident CKD (eGFR <60 mL/min/1.73m2 and ≥40% decline or onset of new end stage kidney disease), incident ≥30% eGFR decline, and incident albuminuria (albumin-to-creatinine ratio (ACR) ≥30 mg/g). Sequentially adjusted logistic regression models assessed the association of biomarkers with kidney outcomes. ResultsMedian age of participants was 62, 49% were women, and 46% identified as Black. 228 (6.9%) developed CKD, 613 (18.9%) experienced ≥30% decline in eGFR, and 356 (11.4%) developed albuminuria. The adjusted odds ratios for incident CKD per 1 standard deviation increment biomarker was 1.12 for ICAM-1 (95% CI 1.02-1.22), 1.10 for VCAM-1 (95% CI 1.01-1.20), 1.15 for factor VIII (95% CI 1.06-1.24), and 1.10 for E-selectin (95% CI 1.01-1.20). Results were similar for incident ≥30% eGFR decline but not albuminuria, where only higher factor VIII was positively associated. ConclusionsHigher concentration of ICAM-1, VCAM-1, factor VIII, and E-selectin were associated with incident CKD and ≥30% eGFR decline in a large cohort study. Higher factor VIII was also associated with incident albuminuria.

Helicobacter pylori infection does not influence the progression from gastroesophageal reflux disease to Barrett's esophagus to esophageal adenocarcinoma.

We conducted a meta-analysis evaluating the overall risk of esophageal adenocarcinoma (EAC) in individuals with Helicobacter pylori infection, and a network meta-analysis to assess the role of H. pylori infection in the progression from Barrett's esophagus (BE) to EAC. The MEDLINE, EMBASE and Cochrane databases were searched between 1988 and June 2023 for observational studies of H. pylori infection and the risk of EAC. Summary odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using the DerSimonian-Laird method. I2 statistics were calculated to examine heterogeneity. Thirteen studies were included in the meta-analysis and 3 additional studies were included in the network meta-analysis. For comparisons with controls, individuals with H. pylori infection were 46% less likely to develop EAC than individuals without H. pylori infection (OR, 0.54; 95% CI: 0.46, 0.64), with low heterogeneity between studies (I2=4.4%). The magnitude of the inverse association was stronger in the two large cohort studies (OR=0.31) than in the 11 case-control studies (OR=0.55). When comparing to controls, the network meta-analysis of 6 studies showed that H. pylori infection was associated with a lower risk of GERD (OR=0.68) or BE (OR=0.59) or EAC (OR=0.54); however, H. pylori infection was not associated with risk of EAC in patients with BE (OR=0.91; 95% CI: 0.68, 1.21). This meta-analysis provides the strongest evidence yet that H. pylori infection is inversely associated with EAC. H. pylori does not appear to be associated with BE progression to EAC.