OBJECTIVE: To assess the behavior change of high-risk breast cancer patients regarding the intention to undergo risk-reducing mastectomies (RRM) before and after genetic testing results and to identify the main influencing factors in decision-making.
METHODS: Prospective cohort study conducted between November 2021 and October 2022 with women under follow-up at the high-risk outpatient clinic of the State University of Campinas (UNICAMP). Patients were referred for genetic testing, followed by counseling according to the test result.
RESULTS: A total of 373 women were included. In the pre-genetic testing analysis, 54.1% of patients intended to undergo RRMs. After testing, 42.2% opted for the procedure. Behavior change occurred in 26.2%, mainly from \"yes\" to \"no/don\'t know\" (72,6%) (p < 0.001). The genetic test result was positive (LPV or PV) in 29.7% of patients. Among the 90 patients with positive results, 62 (68.9%) agreed to RRM, while 22 (24.4%) remained unwilling to accept RRM, regardless of the positive test. Significant influencing factors for behavior change pre- and post-genetic testing (in favor of surgery) in multivariate analysis were: positive genetic test result (OR 2.94, p < 0.001), personal cancer history (OR 2.7, p = 0.008), and ages between 40 and 49 years (OR 2.07, p = 0.008) and ≥ 50 years (OR 3.47, p < 0.001).
CONCLUSIONS: In a Brazilian population at high-risk for breast cancer and users of the public health system, it was observed that most desired RRM, however, when genetic testing and counseling were performed, behavior change was observed, especially when the result was positive.

BACKGROUND: Adjuvant nivolumab reduces recurrence in patients with locoregional esophageal cancer who had pathological residual disease after neoadjuvant chemoradiotherapy and R0 resection. However, the efficacy of adjuvant anti-PD-1 therapy in patients at higher risk of recurrence remains unclear.
METHODS: This phase II trial (ClinicalTrials.gov identifier: NCT03322267) enrolled patients with locally advanced esophageal squamous cell carcinoma (ESCC) received neoadjuvant chemoradiotherapy plus esophagectomy but still had various risk factors for recurrence, such as involved or close margins (≤ 1 mm), extranodal extension of the involved lymph nodes, and the ypN2-3 stage. Patients received adjuvant therapy composed of a course of cisplatin-based chemoradiotherapy and pembrolizumab (200 mg, IV every 3 weeks) for 18 cycles. The primary endpoint was 1-year relapse-free survival (RFS) rate.
RESULTS: Twenty-five patients were enrolled. The risk factors were tumor margins of ≤ 1 mm (18 patients), extranodal extension of the involved lymph nodes (9 patients), and the ypN2-3 stage (9 patients). The median follow-up duration was 21.6 months (95% CI: 18.7-33.2). The rate of 1-year RFS was 60.0%. The median duration of RFS and overall survival was 14.3 (95% CI: 9.0-19.5) and 21.6 (95% CI: 0.0-45.5) months, respectively. Treatment-emergent adverse events of any grade and those of ≥ 3 grade occurred in 56% and 8% of all patients receiving cisplatin-based chemoradiotherapy and in 79.2% and 12.5% of those receiving pembrolizumab.
CONCLUSIONS: Adjuvant chemoradiotherapy followed by pembrolizumab is feasible and may be associated with improved 1-year RFS rate in patients at high risk of recurrence after trimodality therapy for locally advanced ESCC. Trial registration number ClinicalTrials.gov (No. NCT03322267).

UNASSIGNED: According to previous reports, very high percentages of individuals in Saudi Arabia are undiagnosed for type 2 diabetes mellitus (T2DM). Despite conducting several screening and awareness campaigns, these efforts lacked full accessibility and consumed extensive human and material resources. Thus, developing machine learning (ML) models could enhance the population-based screening process. The study aims to compare a newly developed ML model\'s outcomes with the validated American Diabetes Association\'s (ADA) risk assessment regarding predicting people with high risk for T2DM.
UNASSIGNED: Patients\' age, gender, and risk factors that were obtained from the National Health Information Center\'s dataset were used to build and train the ML model. To evaluate the developed ML model, an external validation study was conducted in three primary health care centers. A random sample (N = 3400) was selected from the non-diabetic individuals.
UNASSIGNED: The results showed the plotted data of sensitivity/100-specificity represented in the Receiver Operating Characteristic (ROC) curve with an AROC value of 0.803, 95% CI: 0.779-0.826.
UNASSIGNED: The current study reveals a new ML model proposed for population-level classification that can be an adequate tool for identifying those at high risk of T2DM or who already have T2DM but have not been diagnosed.

BACKGROUND: The results of the OlympiA study led to the approval of a PARP inhibitor (olaparib) as adjuvant treatment for early breast cancer (eBC) at high risk of relapse in patients with a germline BRCA1/2 mutation (gBRCAm). However, the proportion of patients in routine practice who meet the \"high-risk\" criteria applied in the OlympiA study, and for whom gBRCAm testing would now be mandatory, remains unknown.
METHODS: In this population-based study, we use unique data from the French specialized Côte d\'Or Breast and Gynecological Cancer Registry, to assess the real-life proportion, and long-term prognosis of patients treated for eBC between 2005 and 2015 with standard treatment, and at \"high risk\" of relapse according to the OlympiA trial criteria.
RESULTS: We included 3483 patients treated for HER2-negative eBC (N = 380 with ER-, and N = 3103 with ER + tumor). We found N = 62 (1.8 %) patients with gBRCA1/2 mutations. A total of 494 patients (14.2 %) were classified as \"high risk\" according to the Olympia criteria; 55 % with ER-tumors, and 9.1 % with ER + tumors, respectively. Despite more intensive systemic treatments in \"high risk\" patients, 10-year overall survival was much worse in these \"high risk\" patients compared to the others: 60.1 % vs 83.8 % in ER-tumors, and 55.4 % vs 84.1 % in ER + tumors. Our estimates of net survival show an even greater difference.
CONCLUSIONS: This study provides real-life insights into the prevalence and prognosis of patients with high-risk eBC, in a context where the approval of adjuvant olaparib requires careful reorganization of care, so as not to overlook a patient with gBRCAm who could benefit from adjuvant olaparib.

BACKGROUND: Chromosomal 1q gains and amplifications (+1q21) are frequently observed in patients with newly diagnosed multiple myeloma (NDMM). However, the interpretation of the high-risk (HR) prognostic implications stemming from 1q21 abnormalities remain challenging to implement effectively.
METHODS: In a comprehensive analysis of 367 consecutive patients with symptomatic MM, we assessed the prognostic significance of +1q21 using FISH with a threshold of 7.4%. The patient cohort was randomly divided into a training set (66.5%, n = 244) and a validation set (33.5%, n = 133). A multivariate Cox regression analysis was conducted to identify significant prognostic factors associated with PFS. Weight scores were assigned to each risk factor based on the β-value of the corresponding regression coefficient. A predictive risk-scoring model involving +1q21 was then developed, utilizing the total score derived from these weight scores. The model\'s discriminative ability was evaluated using the AUC in both the training and validation sets. Finally, we compared the performance of the +1q21-involved risk with the established R-ISS and R2-ISS models.
RESULTS: Upon initial diagnosis, 159 patients (43.32%) exhibited +1q21, with 94 (59.11%) having three copies, referred to as Gain(1q21), and 65 (40.89%) possessing four or more copies, referred to as Amp (1q21). Both were significantly linked to a reduced PFS in myeloma (p < 0.05), which could be effectively mitigated by ASCT. The +1q21-involved risk model, with an AUC of 0.697 in the training set and 0.725 in the validation set, was constructed including Gain(1q21), Amp(1q21), no-ASCT, and TP53 deletion. This model, termed the ultra-high-risk (UHR) model, demonstrated superior performance in predicting shorter PFS compared to the R-ISS stage 3 and R2-ISS stage 4.
CONCLUSIONS: The UHR model, which integrates the presence of +1q21 with no-ASCT and TP53 deletion, is designed to identify the early relapse subgroup among patients with +1q21 in NDMM.

BACKGROUND: Research is needed to understand and address barriers to risk management for women at high (≥20% lifetime) risk for breast cancer, but recruiting this population for research studies is challenging.
OBJECTIVE: This paper compares a variety of recruitment strategies used for a cross-sectional, observational study of high-risk women.
METHODS: Eligible participants were assigned female at birth, aged 25-85 years, English-speaking, living in the United States, and at high risk for breast cancer as defined by the American College of Radiology. Individuals were excluded if they had a personal history of breast cancer, prior bilateral mastectomy, medical contraindications for magnetic resonance imaging, or were not up-to-date on screening mammography per American College of Radiology guidelines. Participants were recruited from August 2020 to January 2021 using the following mechanisms: targeted Facebook advertisements, Twitter posts, ResearchMatch (a web-based research recruitment database), community partner promotions, paper flyers, and community outreach events. Interested individuals were directed to a secure website with eligibility screening questions. Participants self-reported method of recruitment during the eligibility screening. For each recruitment strategy, we calculated the rate of eligible respondents and completed surveys, costs per eligible participant, and participant demographics.
RESULTS: We received 1566 unique responses to the eligibility screener. Participants most often reported recruitment via Facebook advertisements (724/1566, 46%) and ResearchMatch (646/1566, 41%). Community partner promotions resulted in the highest proportion of eligible respondents (24/46, 52%), while ResearchMatch had the lowest proportion of eligible respondents (73/646, 11%). Word of mouth was the most cost-effective recruitment strategy (US $4.66 per completed survey response) and paper flyers were the least cost-effective (US $1448.13 per completed survey response). The demographic characteristics of eligible respondents varied by recruitment strategy: Twitter posts and community outreach events resulted in the highest proportion of Hispanic or Latina women (1/4, 25% and 2/6, 33%, respectively), and community partner promotions resulted in the highest proportion of non-Hispanic Black women (4/24, 17%).
CONCLUSIONS: Although recruitment strategies varied in their yield of study participants, results overall support the feasibility of identifying and recruiting women at high risk for breast cancer outside of clinical settings. Researchers must balance the associated costs and participant yield of various recruitment strategies in planning future studies focused on high-risk women.

Pancreatic cancer is a rare but lethal cancer due to its biologically aggressive nature, advanced stage at the time of diagnosis, and poor response to oncologic therapies. The risk of pancreatic cancer is significantly higher to 5% in certain high-risk individuals with inherited genetic susceptibility. Screening for pancreatic cancer in these individuals from high-risk groups can help with the early detection of pancreatic cancer as well as the detection of precursor lesions leading to early surgical resection and improved overall outcomes. The advancements in radiological imaging as well as advanced endoscopic procedures has made a significant impact on the early diagnosis, surveillance, and staging of pancreatic cancer. There is also a significant advancement in the development of biomarkers for the early detection of pancreatic cancer, which has also led to the development of liquid biopsy, allowing for microRNA detection in serum and circulating tumor cells. Various societies and organizations have provided guidelines for pancreatic cancer screening and surveillance in high-risk individuals. In this review, we aim to discuss the hereditary risk factors for developing pancreatic cancer, summarize the screening recommendations by different societies, and discuss the development of novel biomarkers and areas for future research in pancreatic cancer screening for high-risk individuals.

Unpredictable fatal outcome of COVID-19 is attributed to dysregulated inflammation. Impaired early adaptive immune response leads to late-stage inflammatory outcome. The purpose of this study was to develop biomarkers for early detection of host immune impairment at first diagnosis from leftover RNA samples, which may in turn identify high risk patients. Leftover RNA samples of COVID-19 patients at first diagnosis were stored. Following prospective follow-up, the samples were shorted and categorized into outcome groups. Impaired adaptive T cell response (severity score) and Impaired IL-10 response (undetectable IL-10 in the presence of high expression of a representative interferon response gene) were determined by RT-PCR based assay. We demonstrate that a T cell response based \'severity score\' comprising rational combination of Ct values of a target genes\' signature can predict high risk noncomorbid potentially critical COVID-19 patients with a sensitivity of 91% (95% CI 58.7-99.8) and specificity of 92.6% (95% CI 75.7-99) (AUC:0.88). Although inclusion of comorbid patients reduced sensitivity to 77% (95% CI 54.6-92.2), the specificity was still 94% (95% CI 79.8-99.3) (AUC:0.82). The same for \'impaired IL-10 response\' were little lower to predict high risk noncomorbid patients 64.2% (95% CI 35.1-87.2) and 82% (95% CI 65.5-93.2) respectively. Inclusion of comorbid patients drastically reduce sensitivity and specificity51.6% (95% CI 33.1-69.8) and 80.5% (95% CI 64.0-91.8) respectively. As best of our knowledge this is the first demonstration of a metric-based approach showing the \'severity score\' as an indicator of early adoptive immune response, could be used as predictor of severe COVID-19 outcome at the time of first diagnosis using the same leftover swab RNA. The work flow could reduce expenditure and reporting time of the prognostic test for an earliest clinical decision ensuring possibility of early rational management.

A portion of multiple myeloma (MM) patients relapse early or do not respond to first line treatment. Identification of possible clinical and or biological features of these patients remains an unmet medical need. In this study we assesed the predictive markers for early relapse MM, defined as a progressive disease that occurred within 18 months, from autologoust stem cell transplantation (ASCT) in MM patients who did not have primary refractory disease. 74 consecutive MM patients were included in the study that received intensive therapy with ASCT. The study was able to identify the main features of newly diagnosed ER MM patients eligible for ASCT identifying the IgA isotype and the R2-ISS score system as the main predictive prognostic factors for ER in this cohort of MM patients.

UNASSIGNED: People with schizophrenia and bipolar disorder are at increased risk of having comorbid somatic illness. This is partly due to lack of physical activity, which may originate from childhood. Sleep disturbances are associated with schizophrenia and bipolar disorder. We aimed to assess physical activity and sleep in children at familial high risk of schizophrenia or bipolar disorder and population-based controls.
UNASSIGNED: This study is part of The Danish High Risk and Resilience Study-VIA 11. Children aged 11 born to parents with schizophrenia (FHR-SZ) (N = 133), bipolar disorder (FHR-BP) (N = 84), or controls (C) (N = 150) were assessed by accelerometry for an average of 6.9 days.
UNASSIGNED: High-intensity physical activity was significantly lower in children at FHR-SZ and FHR-BP compared to controls, (mean hours per day for FHR-SZ: 0.29, SD 0.19, for FHR-BP: 0.27, SD 0.24, and for controls 0.38, SD 0.22, P = <.001). Sleep did not differ between the groups.
UNASSIGNED: Children at FHR-SZ or FHR-BP had less physical activity compared to controls. Our study highlights a research area that reveals a hitherto unexplored disadvantage of being born to parents with schizophrenia or bipolar disorder. Further research is needed to enhance better understanding of causal pathways and consequences of reduced physical activity in children with FHR-SZ and FHR-BP.