High-risk Subgroups Research Articles

A Prospective Cohort Study on Metamorphosis of Peptic Ulcer Dynamics: Insights into High Risk Paramedical Students Transformed Knowledge, Lifestyle and Symptoms Pattern

Background: This study explores the epidemiology of Peptic Ulcer Disease (PUD) among resident students in Komarapalayam, India, with the aim of increasing awareness, identifying influential lifestyle factors, and assessing intervention effectiveness. Methods: A comprehensive nine-month prospective cohort study involving 404 paramedical students aged 17-28 was rigorously conducted. Data collection included a meticulously validated questionnaire, high-risk subgroup identification, and the implementation of educational interventions. Statistical analyses maintained a significance threshold at p ≤ 0.05. Results: The study findings revealed a striking contrast. While the actual incidence of Peptic Ulcer Disease was lower than anticipated, the prevalence of prodromal symptoms was surprisingly high. This underscores the critical need for early symptom identification. Tailored educational interventions exhibited great promise in improving PUD comprehension. Lifestyle choices played a substantial role in susceptibility, with hostellers experiencing the highest PUD prevalence at 10.3%— the efficacy of symptom-based assessments extended beyond healthcare domains. Conclusion: This investigation underscores the urgency of early symptom recognition, personalized education, and proactive health-oriented choices to mitigate the onset of Peptic Ulcer Disease. It highlights the merit of symptom- based assessments and emphasizes the essential role of health education within tertiary institutions. This research catalyzes future initiatives aimed at enhancing the well-being of students in the context of Peptic Ulcer Disease.

Polygenic risk, aspirin and primary prevention of coronary artery disease.

Recent aspirin primary prevention trials failed to identify a net benefit of aspirin for preventing cardiovascular disease versus the harms of bleeding. This study aimed to investigate whether a high-risk subgroup, individuals with elevated genetic predisposition to coronary artery disease (CAD), might derive more benefit than harm with aspirin, compared to those with lower genetic risk. We performed genetic risk stratification of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized controlled trial using a CAD polygenic risk score (GPSMult). For 12,031 genotyped participants (5,974 aspirin, 6,057 placebo) overall, we stratified them by GPSMult quintiles (q1-5), then examined risk of CAD (composite of myocardial infarction and coronary heart disease death) and bleeding events using Cox models. During a median 4.6 years of follow-up with randomization to 100 mg/day aspirin versus placebo, 234 (1.9%) participants had CAD and 373 (3.1%) had bleeding events. In the overall cohort, aspirin resulted in higher bleeding risk (adjusted Hazard Ratio [aHR]=1.30 [1.06-1.61], P=0.01) but no significant CAD reduction (aHR=0.84 [0.64-1.09], P=0.19). However, among the highest quintile of polygenic risk (q5, top 20% of the GPSMult distribution), there was a 47% reduction in risk of CAD events with aspirin (aHR=0.53 [0.31-0.90], P=0.02) without increased bleeding risk (aHR=1.05 [0.60-1.82], P=0.88). Interaction between the GPSMult and aspirin was significant for CAD (q5 versus q1, P=0.02) but not bleeding (P=0.80). The balance between net benefit and harm on aspirin in the primary prevention setting shifts favourably in individuals with an elevated genetic predisposition.

Machine learning-based model for CD4+ conventional T cell genes to predict survival and immune responses in colorectal cancer

Globally, CRC ranks as a principal cause of mortality, with projections indicating a substantial rise in both incidence and mortality by the year 2040. The immunological responses to cancer heavily rely on the function of CD4Tconv. Despite this critical role, prognostic studies on CRC-related CD4Tconv remain insufficient. In this investigation, transcriptomic and clinical data were sourced from TCGA and GEO. Initially, we pinpointed CD4TGs using single-cell datasets. Prognostic genes were then isolated through univariate Cox regression analysis. Building upon this, 101 machine learning algorithms were employed to devise a novel risk assessment framework, which underwent rigorous validation using Kaplan-Meier survival analysis, univariate and multivariate Cox regression, time-dependent ROC curves, nomograms, and calibration plots. Furthermore, GSEA facilitated the examination of these genes’ potential roles. The RS derived from this model was also analyzed for its implications in the TME, and its potential utility in immunotherapy and chemotherapy contexts. A novel prognostic model was developed, utilizing eight CD4TGs that are significantly linked to the outcomes of patients with CRC. This model’s RS showcased remarkable predictive reliability for the overall survival rates of CRC patients and strongly correlated with malignancy levels. RS serves as an autonomous prognostic indicator, capable of accurately forecasting patient prognoses. Based on the median value of RS, patients were categorized into subgroups of high and low risk. The subgroup with higher risk demonstrated increased immune infiltration and heightened activity of genes associated with immunity. This investigation’s establishment of a CD4TGs risk model introduces novel biomarkers for the clinical evaluation of CRC risks. These biomarkers may enhance therapeutic approaches and, in turn, elevate the clinical outcomes for patients with CRC by facilitating an integrated treatment strategy.

8297 Risk Of Pancreatic Cancer In Patients With Diabetes Mellitus And Pancreatitis: A Nationwide Nested Case-Control Study

Abstract Disclosure: Y. Kim: None. H. Kim: None. M. Yu: None. C. Nam: None. E. Kang: None. Background: Despite diabetes mellitus and pancreatitis being known risk factors for pancreatic cancer, but because of their low incidence, patients with these conditions are not included in pancreatic cancer screening. This study aimed to determine the high-risk subgroup of patients with diabetes and pancreatitis that would benefit from pancreatic cancer screening. Methods: A nested case-control study was conducted using data from the national health information database of the Korean National Health Insurance Service. Patients were categorized into the following groups: type 2 diabetes only (T2D-only), pancreatitis only (PAN-only), type 2 diabetes followed by pancreatitis (T2D-PAN), post-pancreatitis DM (PPDM), and no diabetes and no pancreatitis (NDNP). Conditional logistic regression was used to determine significant associations of each group with pancreatic cancer development risk. Results: The risk of pancreatic cancer was significantly higher in the T2D-PAN (adjusted odds ratio [AOR], 4.96; 95% confidence interval [CI], 4.48-5.49) and PPDM (AOR, 4.71; 95% CI, 4.12-5.37) groups than in the NDNP group. Furthermore, the T2D-PAN and PPDM groups had a significantly higher risk of pancreatic cancer than the T2D-only and PAN-only groups. Compared to patients in the NDNP group, patients with PPDM using insulin had a 9-fold increased risk (AOR, 9.84; 95% CI, 6.77-14.29), and patients with T2D-PAN using insulin had a 6-fold increased risk (AOR, 6.62; 95% CI, 5.33-8.20). Conclusion: Patients with both diabetes and pancreatitis had a higher risk of pancreatic cancer than those with either alone, regardless of the order of occurrence, and insulin use was associated with an additional increase in pancreatic cancer risk. These results suggest that these subgroups of patients could be considered to benefit from pancreatic cancer screening. Presentation: 6/2/2024

The Association Between Depression and All-Cause, Cause-Specific Mortality in the Chinese Population - China, 2010-2022.

Depression is linked to higher all-cause and cardiovascular mortality rates, but its effects on specific subgroups and non-cardiovascular mortality in the Chinese population remain unclear. Both severe and mild to moderate depression were found to elevate mortality rates among the Chinese population. The impact was particularly notable among males, urban residents, younger individuals, and those with higher education levels. Depression exhibited a stronger connection with fatalities related to suicide and non-suicidal injuries. Individuals experiencing mild depression require healthcare attention to avoid negative consequences. Enhanced physical and psychological support is particularly crucial for high-risk subgroups.

Association between myocardial layer-specific strain and high 10-year risk of atherosclerotic cardiovascular disease in hypertension-findings from the China-PAR project study.

Myocardial layer-specific strain is a sensitive tool for detecting myocardial dysfunction. The objective of this study was to assess changes in the left ventricle (LV) function using myocardial layer-specific strain and its association with 10-year atherosclerotic cardiovascular disease risk (10Y-ASCVDR) in individuals with hypertension (HP). The parameters of LV structure, including layer-specific global longitudinal strain (GLSww, GLSendo, GLSmid, GLSepi) and layer-specific global circumferential strain (GCSww, GCSendo, GCSmid, GCSepi), were analyzed by two-dimensional speckle-tracking echocardiography in 239 hypertensive patients and 124 control subjects. In addition, participants were divided into low-risk (LR) and high-risk (HR) subgroups according to 10Y-ASCVDR scores . The correlation between myocardial layer-specific strain and 10Y-ASCVDR was further analyzed by the restricted cubic spline (RCS) function. The values of GLSww, GLSepi, GLSmid, and GLSendo were significantly lower in HP patients with HR than in HP patients with LR and controls (p < 0.05). However, no significant differences in layer-specific GCS were observed between the groups (p > 0.05). RCS analysis revealed that 10Y-ASCVDR exhibited a significant J-shaped relationship with layer-specific GLS and GCS. After adjusting for confounding factors, GLSww (β = 0.156, p = 0.042), GLSmid (β = 0.161, p = 0.032), GCSendo (β = 0.163, p = 0.024), and GCSmid (β = -0.175, p = 0.030) were identified as independent influencing factors for high 10Y-ASCVDR. In hypertensive patients, myocardial layer-specific strain, especially GLS, sensitively detected LV dysfunction and showed a significant J-shaped relationship with 10Y-ASCVDR. GCSmid may have a compensatory effect on myocardial impairment. LV myocardial layer-specific strain may help to understand the early compensatory mechanisms of the myocardium in hypertension.

Diagnostic performance of ultrasound vs. ultrasound-guided FNAc in thyroid nodules: data from the ElaTION trial.

ElaTION is a large multi-centre pragmatic randomised controlled trial, performed in 18 secondary/tertiary hospitals across England, comparing elastography ultrasound-guided fine needle aspiration cytology (EUS-FNAC) with ultrasound-guided FNAC (US-FNAC) alone in the diagnostic assessment of thyroid nodules. Secondary trial outcomes, reported here, assessed the accuracy of ultrasound-alone (US) compared with US-guided FNAC to inform and update current practice guidelines. Adults with single or multiple thyroid nodules who had not undergone previous FNAC were eligible. Radiologists assessed all thyroid nodules using US alone, thereby enabling assessment of its accuracy (sensitivity and specificity) versus US-FNAC. Of the 982 participants, a final definitive diagnosis was obtained in 688, who were included in the final analyses. The sensitivity of US-alone was the same as US-FNAC (0.91, [95% CI 0.85, 0.97] vs 0.87 [95%CI 0.80-0.95], p=0.37). US alone had statistically significant lower specificity than US-FNAC alone (0.48 vs 0.67 respectively, p<0.0001). The malignancy rate on histology in a nodule classified as benign on ultrasound (U2) was 9/263 (3.42%) and on cytology (Thy2) was 15/353 (4.25%), whereas the malignancy rate in a nodule that was benign on both (U2, Thy2) was 3/210 (1.43%). Malignancy risk for U3, U4, and U5 nodules was 68/304 (22.4%), 43/83 (51.8%), and 29/38 (76.3%) respectively (p<0.0001). Yet 80/982 (8%) patients were discharged despite having U3-U5 scans with Thy1 (non-diagnostic) FNAC and no definitive diagnosis.Malignancy risk was higher in smaller nodules: <10mm 23/60 (38.3%), 10-20mm 46/162 (28.4 %), and >20mm 80/466 (17.2%) (p<0.0001). Nodules with indeterminate cytology with atypical features (Thy3a) carried a similar malignancy risk to those with indeterminate cytology (Thy3/3f): 27/95 (28.4%) versus 42/113 (37.2%) respectively (p=0.18). Ultrasound alone appears to be an effective diagnostic modality in thyroid nodules, confirming the recommendations of recent guidelines and the BTA classification. However, findings also suggest caution regarding existing recommendations for conservative management of non-diagnostic (Thy1/Bethesda I) and atypical (Thy3a/Bethesda III) nodules. In those cases, ultrasound (U3-5) features may help identify high-risk subgroups for more proactive management.

Sequencing of cellular therapy and bispecific antibodies for the management of diffuse large B-cell lymphoma.

Historically, the management of relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) following first-line chemoimmunotherapy has been second-line chemotherapy, followed by high-dose chemotherapy and consolidative autologous hematopoietic stem cell transplantation (HSCT), resulting in durable remissions in approximately 40% of patients. In 2017, chimeric antigen receptor (CAR) T-cell therapy changed the landscape of treatment for patients with R/R DLBCL, with complete response rates ranging from 40-58% and long-term disease-free survival of >40% in the highest risk subgroups, including patients who relapsed after autologous HSCT. Since that time further studies have demonstrated improved overall response rates and survival outcomes in patients with primary refractory or early-relapsed (relapse within 1 year) DLBCL treated with CAR T-cell therapy compared with autologous HSCT, advancing CAR T-cell therapy into the second-line setting. However, >50% of patients will relapse in the post-CAR T-cell setting. In the past 2 years, two CD20 x CD3 bispecific antibodies were approved by the Food and Drug Administration for the treatment of R/R DLBCL after two or more lines of systemic therapy. These bispecific antibodies have demonstrated overall response rates exceeding 50% and durable remissions at >2 years of follow-up. Additionally, a notable treatment advantage of bispecific antibodies is their ability to be administered in the community setting, making treatment more accessible for patients. The development and advancement of these novel therapies raise questions regarding the ongoing role of HSCT in the management of R/R DLBCL and the best sequence of cellular and bispecific therapies to optimize patients' outcomes.

Lymph node ratio–based model for predicting survival and assessing the benefit of adjuvant chemotherapy in postoperative duodenal adenocarcinoma

BackgroundThis study aimed to evaluate the prognostic significance of lymph node ratio in postoperative duodenal adenocarcinoma and develop a nomogram-based model for prognosis assessment and treatment optimization. MethodsClinical information of patients with duodenal adenocarcinoma were retrieved from the Surveillance, Epidemiology, and End Results database, and prognostic factors were identified by univariate and multivariable analyses. Prognostic factors influencing patient outcomes were identified using univariate and multivariable Cox analyses. Subsequently, a novel nomogram and risk stratification system were developed based on these identified factors. ResultsA total of 943 eligible patients were included, with 656 in the training cohort and 287 in the validation cohort. Lymph node ratio ≥0.12 were associated with poorer overall survival (hazard ratio 1.562, 95% confidence interval 1.195–2.041, and P = .001 for lymph node ratio = 0.12–0.30; hazard ratio 2.431, 95% confidence interval 1.847–3.199, and P < .001 for lymph node ratio >0.30). Prognostic factors including age at diagnosis, race, T stage, lymph node ratio, and tumor size were integrated into the nomogram. Patients in the low-risk group demonstrated significantly better overall survival compared with those in the high-risk group. Additionally, adjuvant chemotherapy significantly improved overall survival in the high-risk subgroup, whereas low-risk patients might be exempt from adjuvant chemotherapy. ConclusionsThis study represented the pioneering endeavor in introducing a lymph node ratio–based nomogram model for prognosis stratification and adjuvant chemotherapy decision-making protocol for patients with duodenal adenocarcinoma, thereby guiding personalized treatment strategies and minimizing overtreatment.

Identification of m6A-related lncRNAs prognostic signature for predicting immunotherapy response in cervical cancer

BackgroundN6-methylandenosine-related long non-coding RNAs (m6A-related lncRNAs) play a crucial role in the cancer progression and immunotherapeutic efficacy. The potential function of m6A-related lncRNAs signature in cervical cancer has not been systematically clarified. MethodsRNA-seq and the clinical data of cervical cancer were extracted from The Cancer Genome Atlas. All of the patients were randomly classified into training and testing cohorts. The m6A-related lncRNAs prognostic model was constructed by LASSO regression using data in the training cohort.The predictive value of the signature was validated in the whole cohort and testing cohort. Cervical cancer patients were divided into low- and high-risk subgroups by the median value of risk scores. Kaplan-Meier analysis, principal-component analysis (PCA), functional enrichment annotation, and nomogram were used for further evaluation. We also examined the immune response and potential drug sensitivity targeting this model. ResultsSeventy-nine prognostic m6A-related lncRNAs were screened. The risk model comprising four m6A-related lncRNAs (AL139035.1, AC015922.2, AC073529.1, AC008124.1) was identified and verified as an independent prognostic predictor of cervical cancer. A nomogram based on age, tumor grade, clinical stage, TNM stage, and four m6A-related lncRNAs risk signatures was generated. It displayed good accuracy and reliability in predicting the overall survival of patients with CC. Based on our risk model, cervical cancer patients with potential immunotherapy benefits from the candidate drugs could be effectively screened. ConclusionThe four m6A-related lncRNAs signature may provide new targets and allow the prediction of immunotherapy response, which can assist developing individualized treatment for cervical cancer.

Risk Factors of Pulmonary Embolism in Long-Segment Posterior Thoracolumbar Fusion: Scoring System for Prophylactic Inferior Vena Cava Filter Placement

ObjectiveTo investigate the factors for PE development and the necessity of IVC filter placement. Specifically, propose a scoring system to identify patient populations who benefit from IVC filter placement. MethodsSingle-institution retrospective cohort study between 2010-2022. Inclusion criteria were open posterior thoracolumbar fusion, ≥ 7 segments, and adult patients ≥ 18 years old. Patients undergoing any surgical approach other than posterior were excluded. Risk factors such as smoking status, illicit drug use/type, body mass index (BMI), gender, age, anticoagulation history and status on presence of PE were reviewed. Results365 patients were identified; 170 (46.6%) patients were male, and 195 (53.4%) were female. 24 (6.6%) had IVC filters placed before the surgery. The overall rate of PE was 8 (2.2%), all in patients without IVC filter. Analysis showed that gender, age, and BMI did not affect incidence of PE. Smoking status, history of illicit drug use (cocaine/cannabis), and history of deep vein thrombosis/PE significantly increased the incidence of PE. Based on multivariate logistic regression, we developed a scoring system composed of aforementioned significant risk factors to determine risk of developing PE. Our scoring system stratified risk to low-risk (0-3 points), medium-risk (4-6 points), and high-risk (7-8 points). ConclusionRisk of PE is relatively low after long-segment posterior thoracolumbar fusion. Smoking (former and current), history of cocaine/cannabis use, and history of venous thromboembolism are risk factors in such patients. We recommend prophylactic IVC filter use only in high-risk subgroups and under discretion between physician and patient in medium-risk subgroups.

Measuring Peri-Anastomotic Pressure to Identify Patients at High-Risk for Dialysis Associated Steal Syndrome

Dialysis Access-associated Steal Syndrome (DASS) is one of the most serious complications of hemoaccess surgery. Treatment algorithms involve significant morbidity; a tool to reliably identify patients at risk who could benefit from interventions at time of operation would be useful. We present a strategy of using peri-anastomotic pressure (PAP) measurement to identify patients who may be at high risk of developing DASS. Patients who underwent dialysis access creation between January 1, 2018 and September 30, 2022 at our institution were reviewed. Beginning October 2019, we developed a strategy of measuring systolic pressure at the arterial anastomosis intra-operatively. A ratio of this value compared to the systemic systolic pressure was calculated. In patients believed to be high-risk for developing DASS based on clinical findings, selective banding of the access was performed intra-operatively to augment distal perfusion. Of 857 total patients, 36 (4.2%) developed clinically significant DASS, defined as requiring operative treatment, either intraoperatively or during follow-up (mean, 76 days; range, 0-602 days). DASS was more common for femoral-based accesses (6/12, 46.2%) compared to upper extremity accesses (30/840, 3.6%, p < 0.001). No patients who underwent radiocephalic arteriovenous fistula (AVF) or infraclavicular axillary arteriovenous graft construction developed DASS. There was no difference in DASS for upper extremity AVFs (20/576, 3.47%) vs. AV grafts (10/264, 3.79%, p = 0.82). 216 patients had PAP measured intra-operatively. Fourteen (6.5%) of these 216 patients developed DASS requiring intervention in follow-up. The mean PAP ratio of these 14 patients was 0.395 vs. 0.557 for the 202 patients who did not [CI 0.07-0.25, p = 0.001]. Seventeen patients who had low PAP ratio with poor distal perfusion underwent intra-operative banding, which improved mean PAP ratios from a mean of 0.33 to 0.58. Despite banding, 3 of these 17 (17.6%) patients in this high-risk subgroup went on to develop DASS postoperatively. The calculated mean PAP ratio in patients who either developed DASS post-operatively or underwent prophylactic banding intra-operatively was 0.37, which was significantly lower than the mean ratio of 0.57 in the control group (p = 0.001). Low PAP ratios (less than 0.50) identified patients at elevated risk for DASS, but prophylactic banding did not always prevent the occurrence of DASS in select patients. Because steal is a dynamic phenomenon, intraoperative conditions are not always going to reflect later adaptation. Nonetheless, PAP measurement may identify a subgroup warranting procedural modification or closer postoperative physiologic monitoring.

Medicación pediátrica de alto riesgo: propuesta de listado a través de la técnica de consenso interdisciplinar

IntroductionPediatric patients are more likely to experience medication-related errors and serious associated harms. The identification of high-risk medications (HRM) and their study in special populations, such as children with excess body weight, is a part of safety improvement strategies. ObjectiveTo generate, through a consensus technique structured by an interdisciplinary group of pediatricians and hospital pharmacists, an operational and updated list of HRM for hospital use in children over 2 years of age. The document was part of a collaboration project between the Spanish Society of Hospital Pharmacists and the Spanish Society of Pediatric Hospital Medicine. MethodsThe study was carried out in two sequential phases: a) preparation of a preliminary list of HRM through bibliographic review and b) subsequent application of the double-round Delphi method to agree on a definitive list of HRM. The results obtained were validated by calculating the probability of chance agreement and the modified Kappa statistic for each drug. ResultsThe original list obtained by bibliographic review included 26 pharmacological classes and 96 drugs. Of the total of 37 experts, 32 (86.4%) completed both rounds of the Delphi. The final consensus list of HRM incorporated 24 pharmacological classes and 100 drugs. The modified Kappa statistic reflected a high percent agreement (94.9%) in the consensus reached by the participants. ConclusionThis list can establish a tool for future studies and interventions to improve the safety of medications in general pediatric population, as well as in high-risk subgroups, such as pediatric patients with excess body weight.

Liquid biopsy with plasma Epstein-Barr virus DNA characterizes biological relapse for the prediction of cancer recurrence in non-disseminated nasopharyngeal carcinoma

PurposeTo investigate whether a bounce in plasma Epstein-Barr virus (EBV) DNA during posttreatment surveillance of nasopharyngeal carcinoma (NPC) informs the risk of clinical recurrence and its implication for early therapeutic intervention. Methods950 non-disseminated NPC patients with completed remission in 3 months after treatment were retrospectively screened. Detectable EBV DNA with no evidence of clinical relapse during follow-up was deemed as DNA bounce. The diagnostic and prognostic performance of EBV DNA bounce was assessed for subsequent failures. ResultsTumor recurrence occurred in 6.6 %, 10.1 % and 65.8 % in the group with persistently negative EBV DNA, single positive test and ≥ 2 positive tests, respectively. EBV DNA bounce over twice was associated with worse disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) than the other two groups. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for the prediction of recurrence were 0.56, 0.95, 0.66, 0.93 and 0.90 using two positive tests, which were hence deemed as biological relapse. Serial cutoffs (EBV DNA 1 ≥ 40 copies/ml or EBV DNA 2 ≥100 copies/ml) further defined a high-risk subgroup with an eventual recurrence rate of 77.9 % and 3-year DFS of merely 20.5 %. Prophylactic medical intervention with capecitabine or S1 significantly improved the 3-year DFS when compared to those with observation. ConclusionsThe earliest two positive tests of EBV DNA represent a biomarker of biological relapse that allows early detection of clinical recurrence in EBV-related NPC. For high-risk biological relapse, preemptive intervention provides potential survival benefits.

Men's Suicidal thoughts and behaviors and conformity to masculine norms: A person-centered, latent profile approach

BackgroundMen are up to four times more likely to die by suicide than women. At the same time, men are less likely to disclose suicidal ideation and transition more rapidly from ideation to attempt. Recently, socialized gender norms and particularly conformity to masculine norms (CMN) have been discussed as driving factors for men's increased risk for suicidal thoughts and behaviors (STBs). This study aims to examine the individual interplay between CMN dimensions and their association with depression symptoms, help-seeking, and STBs. MethodsUsing data from an anonymous online survey of 488 cisgender men, latent profile analysis was performed to identify CMN subgroups. Multigroup comparisons and hierarchical regression analyses were used to estimate differences in sociodemographic characteristics, depression symptoms, psychotherapy use, and STBs. ResultsThree latent CMN subgroups were identified: Egalitarians (58.6 %; characterized by overall low CMN), Players (16.0 %; characterized by patriarchal beliefs, endorsement of sexual promiscuity, and heterosexual self-presentation), and Stoics (25.4 %; characterized by restrictive emotionality, self-reliance, and engagement in risky behavior). Stoics showed a 2.32 times higher risk for a lifetime suicide attempt, younger age, stronger somatization of depression symptoms, and stronger unbearability beliefs. ConclusionThe interplay between the CMN dimensions restrictive emotionality, self-reliance, and willingness to engage in risky behavior, paired with suicidal beliefs about the unbearability of emotional pain, may create a suicidogenic psychosocial system. Acknowledging this high-risk subgroup of men conforming to restrictive masculine norms may aid the development of tailored intervention programs, ultimately mitigating the risk for a suicide attempt.

Systems mapping: a novel approach to national lung cancer screening implementation in Australia.

Lung cancer screening with low-dose computed tomography has been started in some high-income countries and is being considered in others. In many settings uptake remains low. Optimal strategies to increase uptake, including for high-risk subgroups, have not been elucidated. This study used a system dynamics approach based on expert consensus to identify (I) the likely determinants of screening uptake and (II) interactions between these determinants that may affect screening uptake. Consensus data on key factors influencing screening uptake were developed from existing literature and through two stakeholder workshops involving clinical and consumer experts. These factors were used to develop a causal loop diagram (CLD) of lung cancer screening uptake. The CLD comprised three main perspectives of importance for a lung cancer screening program: participant, primary care, and health system. Eight key drivers in the system were identified within these perspectives that will likely influence screening uptake: (I) patient stigma; (II) patient fear of having lung cancer; (III) patient health literacy; (IV) patient waiting time for a scan appointment; (V) general practitioner (GP) capacity; (VI) GP clarity on next steps after an abnormal computed tomography (CT); (VII) specialist capacity to accept referrals and undertake evaluation; and (VIII) healthcare capacity for scanning and reporting. Five key system leverage points to optimise screening uptake were also identified: (I) patient stigma influencing willingness to receive a scan; (II) GP capacity for referral to scans; (III) GP capacity to increase patients' health literacy; (IV) specialist capacity to connect patients with timely treatment; and (V) healthcare capacity to reduce scanning waiting times. This novel approach to investigation of lung cancer screening implementation, based on Australian expert stakeholder consensus, provides a system-wide view of critical factors that may either limit or promote screening uptake.

Real-World Outcomes of Upfront Autologous Hematopoietic Stem Cell Transplantation in Patients With Newly Diagnosed Multiple Myeloma With Deletion 17p

Despite tremendous advancements in multiple myeloma (MM) therapeutics, outcomes remain heterogeneous, heavily influenced by clinical and cytogenetic factors. Among these, deletion of the short arm of chromosome 17 (del(17p)) is a strong predictor of poor prognosis. The aim of this study was to evaluate real-world outcomes in patients with newly diagnosed MM (NDMM) with del(17p) undergoing upfront autologous hematopoietic stem cell transplantation (auto-HCT). We conducted a single-center retrospective analysis of patients with NDMM who underwent upfront auto-HCT at MD Anderson Cancer Center between 2008 and 2018. Primary endpoints were progression-free survival (PFS) and overall survival (OS), with secondary endpoints being hematological response and measurable residual disease (MRD) status postauto-HCT. MRD status in the bone marrow biopsy was evaluated using 8-color next-generation flow cytometry with a sensitivity of 1/10-5 cells. One hundred and fifteen patients were included (55% male). Median age at auto-HCT was 62 years (range 34 to 83). The median del(17p) clone size was 20%, with 51 (53%) patients having clone sizes >20% and 15 (15%) patients having clone sizes >55%. Additional high-risk cytogenetic abnormalities included t(4;14) in 15 (13%) patients, t(14;16) in 8 (7%) patients, and 1q21+ in 25 (22%) patients. After induction, 10% of patients achieved ≥ CR, and 50% achieved ≥ VGPR, with 25% having MRD-negative ≥ VGPR. Post-transplant, 42% achieved ≥ CR, and 83% achieved ≥ VGPR as best response, with 55% (48/87) having MRD-negative ≥ VGPR. With a median follow-up of 31.4 months (range 3.1 to 199.1), median PFS and OS for the entire cohort were 19.9 and 71.5 months, respectively, and 5-year OS was 53%. Concurrent del(17p) and t(4;14) were associated with significantly worse outcomes, with median PFS and OS of 11.5 and 22.4 months, respectively. In multivariable analysis (MVA), female sex was associated with worse PFS (HR [95% CI] 2.87 [1.75 to 4.72], P < .001), while MRD negative CR post-transplant (0.35 [0.18 to 0.68], P = .002) and maintenance therapy (0.46 [0.27 to 0.77], P = 0.003) were associated with better PFS. In MVA for OS, female sex (2.22 [1.18 to 4.17], P = 0.013) and the presence of t(4;14) (2.55 [1.09 to 5.95], P = 0.030) were associated with worse OS, whereas Karnofsky Performance Status of ≥90 (0.47 [0.23 to 0.94], P = 0.034) was associated with better OS. This study affirms del(17p) as a high-risk abnormality with unfavorable outcomes despite modern therapies. The co-occurrence of del(17p) and t(4;14) was associated with particularly poor outcomes. Novel approaches are needed for this high-risk subgroup.

Maximum disease diameter is associated with outcomes in stage II follicular lymphoma treated with radiation therapy alone

PurposeThe optimal management of stage II follicular lymphoma (FL) is unclear. Radiation therapy (RT) alone has been the gold standard treatment, but a proportion of patients relapse. We sought to characterize outcomes and prognostic factors for stage II FL treated with RT alone to identify a high-risk subgroup of patients who may benefit from treatment intensification. MethodsThis was a population-based, province-wide, retrospective study. Included patients had grade 1–3A, non-mesenteric, stage IIA or IIAE FL diagnosed between 1986 and 2016 and treated with curative-intent (≥20 Gy) RT alone. Results102 patients were included. Median follow-up was 10.4 years (range, 0.3–22.3). Median age was 59 years (range, 33–86). Median greatest disease diameter was 3.6 cm (range, 1.5–11.5). Freedom from progression (FFP) was 60.3% at 5 years and 40.7% at 10 years. Overall survival (OS) was 89.2% at 5 years and 81.8% at 10 years. Greatest disease diameter of >3.6 cm was associated with inferior FFP (10-year FFP 34% vs. 47%, p = 0.013) on univariable analysis and inferior FFP (hazard ratio [HR] 1.87, p = 0.019) and inferior OS (HR 2.12, p = 0.027) on multivariable analysis (MVA). Older age was associated with inferior OS (HR 1.08, unit = 1 year, p < 0.001) on MVA. Conclusions40.7% of stage II FL patients treated with RT alone remained disease-free at 10 years. Greatest disease diameter >3.6 cm was associated with inferior FFP and OS, representing a novel prognostic indicator in this population that may help in the decision-making process on whether to complement RT with systemic therapy.

A Longitudinal Study of Aggression in People with Autism and Other Neurodevelopmental Disabilities.

Aggression is common in autism and neurodevelopmental disorders, but longitudinal research on aggression is lacking. We longitudinally tracked aggression in 254 individuals from toddlerhood to emerging adulthood. Our sample included participants with a range of cognitive abilities, with 39.9% classified as more-cognitively-abled (MCA; IQ ≥ 70) and 60.1% as less-cognitively-abled (LCA; IQ < 70). Aggression Composite scores were derived from data from the autism diagnostic observation schedule, autism diagnostic interview-revised, and child behavior checklist at ages 2, 9, and 18. Fifty-four percent, 69%, and 42% of the sample showed aggression in toddlerhood, school age, and emerging adulthood, respectively. LCA individuals had higher rates of aggression in school age (80%) and emerging adulthood (58%) compared to MCA individuals (48 and 22%, respectively). Longitudinal aggression profiles revealed distinct patterns of change over time: 31% displayed persistent aggression, 25% increased, 23% decreased, and 13% never displayed aggression. Higher autism symptoms, lower VIQ, NVIQ, and less-developed adaptive skills correlated with more aggression cross-sectionally. Nonverbal IQ and repetitive behaviors related to aggression longitudinally: people in decreasing or absent profiles had higher NVIQ and fewer RRBs than those with persistent or increasing profiles. Participants with aggression at 9 were four times likelier to exhibit aggression at 18. Aggression is common in autism and NDDs, peaking around age 9, and declining in emerging adulthood. Patterns of change varied widely, with evidence that higher NVIQ and fewer RRBs may be protective. Findings have implications for clinical practices, highlighting important developmental periods and high-risk subgroups.

Long-term outcome of the Milano-HART strategy for high-risk medulloblastoma, including the impact of molecular subtype.

We applied the strategy for M+ medulloblastoma across all high-risk subgroups, including LC/A histology, TP53 mutations, MYC/MYCN amplification. Patients over 3-years-old received,after surgery,staging and histo-biological analysis,sequential high-dose-methotrexate(HD-MTX),high-dose-etoposide(HD-VP16),high-dose-cyclophosphamide(HD-Cyclo),high-dose-carboplatin(HD-Carbo).Hyperfractionated-accelerated-radiotherapy-craniospinal(HART-CSI),administered in twice daily 1.3 Gy-fractions reached a total dose tailored to the patients' age and pre-radiation response to chemotherapy(CT): 31.2 Gy if under 10-years-old and complete response(CR) or partial response(PR) obtained or absence of metastatic disease,39 Gy in other/older patients.Boosts to posterior fossa/residual metastatic(M+) deposits were given up to a total dose of 60 Gy/9 Gy,respectively,but avoided if metastatic nodules were very big or patients very young.Two courses of high-dose-thiotepa were delivered in case of not CR/PR after pre-radiotherapy(RT) phase and in all M0 patients either - pre/post HART.Subgrouping was performed where tissue was available. Eighy-nine patients were enrolled,median age 8.8 years,median follow up 136 months.Overall-survival(OS) and event-free-survival(EFS) at 5/15 years were 75.9/66.5% and 68.2/65.3%, respectively;5/28 fatal events were not related to relapse(three developed secondary malignancies).Sex,age less than 10 years,histological subtype,presence of MYC/MYCN amplification,reduction in CSI dose,omission of RT-boosts,implementation of myeloablative therapy,presence/absence of metastases did not impact prognosis.Patients progressing after pre-HART CT(14/89) and stable-disease(SD)+PD after HART(10/89) negatively affected outcome(P<0.001).Subgrouping in 66/89 patients' samples demonstrated a significantly worse EFS for patients with Sonic Hedgehog(SHH)-tumors(#15, 2 with constitutional TP53-mutations) vs. group 3 and 4(15 and 29 patients, respectively, group3/4 in 7).Patients younger than 10 received lower CSI doses if stratified according to CT response. This strategy, partly adopted in the ongoing SIOPE protocol,confirmed improved EFS and OS over previously reported outcomes in all high-risk categories;SHH tumors appeared the most aggressive.