Clinical Variables Of Interest Research Articles

Abstract PO3-06-05: Association of tumor-derived extracellular vesicles with circulating tumor DNA alterations in metastatic breast cancer patients: exploring differences in inflammatory breast cancer

Abstract Background: Liquid biopsy provides a real-time assessment of metastatic breast cancer (MBC). Recently, the complementary prognostic value of tumor-derived extracellular vesicles (tdEVs) and circulating tumor cells (CTCs) has been reported. We have previously confirmed the strong prognostic significance of CTCs and tdEVs in inflammatory breast cancer (IBC). While previous studies have reported the association of CTCs with circulating tumor DNA (ctDNA) alterations in MBC, no evidence is available for tdEVs. This study aimed to analyze the association of tdEVs with ctDNA alterations, to investigate the molecular pathways underlying their presence. Moreover, we explored potential differences of this association in patients (pts) with IBC to provide a comprehensive liquid biopsy-based portrait of this aggressive subtype of BC. Methods: Blood samples were collected from 355 pts with MBC before starting a new line of therapy at Northwestern University (Chicago, IL) between 2016 and 2021 (NU16B06 trial). For CTCs and tdEVs analysis, 7.5 mL of blood was processed with the CellSearch® system. The ACCEPT software was applied to CellSearch® images to automatically enumerate CTCs and tdEVs. Positivity cutoff was ≥5 for CTCs, while tdEV cutoff points were < 20 (low), 20-79 (intermediate), and ≥80 (high). For ctDNA analysis, matched plasma samples (± 1 month) were analyzed with the Guardant360™ NGS platform for the detection of somatic single nucleotide variants (SNVs) and copy number variations (CNVs), which were classified into oncogenic pathways based on defined profiles generated on the Cancer Genome Atlas database (p53, PI3K, ER, RTK, RAS, RAF, WNT, MYC, cell cycle, notch). Associations between ctDNA pathways alterations and tdEVs were tested in the overall population by multinomial logistic regression and corrected for significant clinical characteristics. Differences in liquid biopsy features between IBC and non-IBC subgroups were analyzed through Fisher's exact test. Results: Of the 355 MBC pts, 210 (62%) had HR+ BC, 61 (17%) had HER2+ BC, and 68 (20%) had triple-negative BC. Eighty-three (23%) had a diagnosis of IBC and had a numerically lower tdEV count. Also, lower tdEVs were detected in HER2+ BC as compared with HR+. Significantly higher tdEVs were observed among pts with lobular histology, liver, and bone metastases. CTC count was significantly associated with tdEV number. A matched plasma sample for ctDNA analysis was available for 175 pts (62 IBC and 113 non-IBC). In the overall population, SNVs in ER pathway were associated with intermediated/high levels of tdEVs (p=0.004 and 0.008). A similar association was observed for CNVs in the cell cycle pathway (p=0.008 and 0.007). Moreover, associations with ≥80 tdEVs were observed for PI3K SNVs and CNVs (p=0.039 and 0.004, respectively), RTK CNVs (p=0.023), and MYC CNVs (p=0.001). In multivariable analysis, clinical characteristics associated with higher tdEVs were lobular histology (p=0.014 for 20-79 and < 0.001 for ≥80) and bone metastases (p=0.019 for 20-79 and 0.002 for ≥80). When considering clinical variables of interest, only ER SNVs and MYC CNVs were significantly associated with intermediate (p=0.031) and high (p=0.022) tdEV counts, respectively. While the association with ER SNVs and cell cycle CNVs was significant both in the IBC and non-IBC subgroups, others were specific for a certain subgroup: higher tdEVs were significantly associated with PI3K SNVs only in non-IBC pts whereas the significant association with CNVs in PI3K and MYC pathways was observed only in pts with IBC. Conclusion: Detection of tdEVs was associated with particular genomic profiles. These alterations seem to be different in IBC further underlying a different biology of this BC subtype. Additional studies are needed to explore how to integrate different liquid-biopsy based biomarkers in the management of pts with MBC. Citation Format: Eleonora Nicolò, Lorenzo Gerratana, Lorenzo Foffano, Laura Munoz Arcos, Mara Serena Serafini, Maroua Manai, Letizia Pontolillo, Nadia Bayou, Elisabetta Molteni, Amanda Kaylan Strickland, Youbin Zhang, Paolo D’Amico, Andrew Davis, Jeannine Donahue, Huiping liu, William Gradishar, Ami Shah, Giuseppe Curigliano, Carolina Reduzzi, Massimo Cristofanilli. Association of tumor-derived extracellular vesicles with circulating tumor DNA alterations in metastatic breast cancer patients: exploring differences in inflammatory 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 PO3-06-05.

Factors Associated with Patient Education in Patients with Chronic Obstructive Pulmonary Disease (COPD) - A Primary Health Care Register-Based Study.

Patient education in chronic obstructive pulmonary disease (COPD) is recommended in treatment strategy documents, since it can improve the ability to cope with the disease. Our aim was to identify the extent of and factors associated with patient education in patients with COPD in a primary health care setting. In this nationwide study, we identified 29,692 COPD patients with a registration in the Swedish National Airway Register (SNAR) in 2019. Data on patient education and other clinical variables of interest were collected from SNAR. The database was linked to additional national registers to obtain data about pharmacological treatment, exacerbations and educational level. Patient education had been received by 44% of COPD patients, 72% of whom had received education on pharmacological treatment including inhalation technique. A higher proportion of patients who had received education were offered smoking cessation support, had performed spirometry and answered the COPD Assessment Test (CAT), compared with patients without patient education. In the adjusted analysis, GOLD grade 2 (OR 1.29, 95% CI 1.18-1.42), grade 3 (OR 1.41, 95% CI 1.27-1.57) and grade 4 (OR 1.79, 95% CI 1.48-2.15), as well as GOLD group E (OR 1.17, 95% CI 1.06-1.29), ex-smoking (OR 1.70, 95% CI 1.56-1.84) and current smoking (OR 1.45, 95% CI 1.33-1.58) were positively associated with having received patient education, while cardiovascular disease (OR 0.92, 95% CI 0.87-0.98) and diabetes (OR 0.93, 95% CI 0.87-1.00) were negatively associated with receipt of patient education. Fewer than half of the patients had received patient education, and the education had mostly been given to those with more severe COPD, ex- and current smokers and patients with fewer comorbidities. Our study highlights the need to enhance patient education at an earlier stage of the disease.

Altered Resting-State Amygdalar Functional Connectivity in Primary Angle-Closure Glaucoma Patients.

Glaucoma patients frequently present with depressive symptoms, the development of which is closely associated with amygdalar activity. However, no studies to date have documented glaucoma-related changes in the functional connectivity (FC) of the amygdala. Accordingly, resting-state functional magnetic resonance imaging (rs-fMRI) analyses were herein used to evaluate changes in amygdalar FC in primary angle-closure glaucoma (PACG) patients. In total, this study enrolled 36 PACG patients and 33 healthy controls (HCs). Complete eye exams were conducted for all PACG patients. After the preprocessing of magnetic resonance imaging (MRI) data, the bilateral amygdala was selected as a seed point, followed by the comparison of resting-state FC between the PACG and HC groups. Then, those brain regions exhibiting significant differences between these groups were identified, and relationships between the FC coefficient values for these regions and clinical variables of interest were assessed. These analyses revealed that as compared to HC individuals, PACG patients exhibited reductions in FC between the amygdala and the cerebellum_8, vermis_4_5, anterior central gyrus, supplementary motor area, paracentral lobule, putamen, middle frontal gyrus, and posterior cingulate gyrus, while enhanced FC was detected between the right and left amygdala. No significant correlations between these changes in amygdalar any any disease-related clinical parameters or disease duration were noted. Patients with PACG exhibit extensive resting state abnormalities with respect to the FC between the amygdala and other regions of the brain, suggesting that dysregulated amygdalar FC may play a role in the pathophysiology of PACG.

Efficacy of a Psychologically-Informed Physiotherapy Intervention in Patients with Chronic Low Back Pain at High Risk of Poor Prognosis: A Pilot and Feasibility Randomized Controlled Trial.

To determine the feasibility of a randomized controlled trial (RCT) testing the efficacy of psychologically-informed physiotherapy (PIPT), which includes usual physiotherapy (UP) interventions, compared with UP, and to explore the preliminary effectiveness of the interventions. People with chronic low back pain at high risk of poor prognosis (using the STarT Back screening tool) were recruited and allocated to PIPT or UP. Effectiveness of recruitment strategies, adherence to intervention, risk of contamination, and specific challenges were assessed. Functional capacity, pain, quality of life, kinesiophobia, catastrophization, central sensitization, and self-efficacy were measured at baseline, 6-, 12- and 24-week follow-ups. Forty participants were recruited mainly by diffusing through Laval University's email list, and 10 physiotherapists treated the participants recruited. The retention rate of participants at 24 weeks was 72.5%. Adherence to treatment by participants and physiotherapists was very good. The risk of contamination was low, and the specific challenges identified were modifiable. Significant improvement over time in all clinical variables of interest, except self-efficacy, was observed with no difference between groups. As most success criteria were met, conducting an RCT evaluating PIPT and PU is feasible with modifications. PIPT and UP appear to be similarly effective.

Dyadic and Individual Variation in 24-Hour Heart Rates of Cancer Patients and Their Caregivers.

Twenty-four-hour heart rate (HR) integrates multiple physiological and psychological systems related to health and well-being, and can be continuously monitored in high temporal resolution over several days with wearable HR monitors. Using HR data from two independent datasets of cancer patients and their caregivers, we aimed to identify dyadic and individual patterns of 24 h HR variation and assess their relationship to demographic, environmental, psychological, and clinical variables of interest. a novel regularized approach to high-dimensional canonical correlation analysis (CCA) was used to identify factors reflecting dyadic and individual variation in the 24 h (circadian) HR trajectories of 430 people in 215 dyads, then regression analysis was used to relate these patterns to explanatory variables. Four distinct factors of dyadic covariation in circadian HR were found, contributing approximately 7% to overall circadian HR variation. These factors, along with non-dyadic factors reflecting individual variation exhibited diverse and statistically robust patterns of association with explanatory variables of interest. Both dyadic and individual anomalies are present in the 24 h HR patterns of cancer patients and their caregivers. These patterns are largely synchronous, and their presence robustly associates with multiple explanatory variables. One notable finding is that higher mood scores in cancer patients correspond to an earlier HR nadir in the morning and higher HR during the afternoon.

Influence of Lp(a) and systemic inflammation on all-cause mortality in a primary prevention population: data from our clinic database

Abstract Background Epidemiological, pathophysiological, and genetic studies have established Lp(a) as a causal risk factor for development of cardiovascular (CVD) and valvular heart disease. However, there is controversy about how inflammation can modulate Lp(a) risk and major adverse cardiovascular events. We aim to investigate the influence of elevated Lp(a) and systemic inflammation on all-cause mortality in a primary prevention setting. Method We analyzed data obtained from the Preventive Cardiology Information System (PreCis), a database of clinical and laboratory information on 8,136 primary prevention patients seen at our clinic preventive cardiology clinic between 1st Jan 1999-12th Dec 2018. Primary prevention was defined as having no history of coronary artery disease (CAD), coronary and peripheral arterial revascularization, nor atherosclerosis. Lp(a) ≥50 mg/dL was considered as clinically elevated. The association between Lp(a) and the demographic and clinical variables of interest was examined using the student’s t-test or Chi-squared test. All-cause mortality was assessed using Kaplan-Meier estimates, and adjusted Cox proportional hazards models. All statistical analyses were conducted using SAS version 9.4. Result In the overall primary prevention population (n=8,136), the median age was 54 years, with 56.9% women and 84.8% being Caucasian. In this cohort, 21% had hypertension, and 5.5% had diabetes. The median Lp(a) was 21 mg/dL (interquartile interval 7-57 mg/dL). Lp(a) was ≥50 mg/dL in 29% of the population. Of those with elevated Lp(a) (n=2,368), 1,751 (73.9%) patients had hsCRP drawn. In this group, 782 patients (44.7%) had hsCRP <2 mg/L and 969 (55.3%) had hsCRP ≥2 mg/L. The all-cause mortality rate in individuals with elevated Lp(a) and hsCRP ≥2mg/L was 9.2% compared to 4.2% in those with elevated Lp(a) and hsCRP <2mg/L. In a multivariable Cox proportional hazard regression model adjusted for age and gender, in patients with elevated Lp(a), hsCRP ≥2 mg/L was significantly associated with all-cause mortality (HR 2.35, 95% CI (1.57-3.53), p>0.001) (Figure 1). Conclusion In a primary prevention population without established atherosclerosis, elevated Lp(a), increased systemic inflammation was associated with increased all-cause mortality. This finding supports the need for risk classification and targeted primary prevention management of higher risk patients with elevated Lp(a).

COMPORTAMENTO DE AUTOCUIDADO DE PACIENTES COM INSUFICIÊNCIA CARDÍACA: RELAÇÃO COM VARIÁVEIS SOCIODEMOGRÁFICAS E CLÍNICAS

ABSTRACT Objective: to assess self-care behavior and its relationship with the sociodemographic and clinical variables of patients with heart failure. Method: a cross-sectional and correlational study was conducted in a cardiomyopathy outpatient clinic in São Paulo, SP, Brazil. Data were collected between 2018 and 2020. The sample consisted of patients with heart failure without visual, auditory, or cognitive deficits. Self-care behavior was assessed using the European Heart Failure Self-care Behavior Scale. Sociodemographic and clinical variables were selected through a literature review. The Spearman’s correlation coefficient and the Mann-Whitney test were used for data analysis. Factors presenting p≤0.10 and the variables of clinical interest were included in the multiple analysis, and p-values ≤ 0.05 were considered significant. Results: 340 patients with a mean self-care score of 24.7 were analyzed. Those taking more medications and adhering to the pharmacological treatment tended to present improved self-care (p≤0.001). In contrast, patients without a partner (p=0.022), with a sedentary lifestyle (p<0.001), or employed (p<0.001) tended to present worse self-care scores. Conclusion: The factors related to self-care behavior were adherence to pharmacological treatment, the number of medications taken, marital status, employment, and sedentary lifestyle.

Prognostic value of procalcitonin in cancer patients with coronavirus disease 2019.

Many biomarkers have been studied to assist in the risk stratification and prognostication of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Procalcitonin (PCT), a circulating precursor of the hormone calcitonin, has been studied with mixed results as a predictor of severe coronavirus disease 2019 (COVID-19) in the general population; however, to date, no studies have focused on the utility of PCT in predicting disease severity and death from COVID-19 in the cancer population. We conducted a retrospective study of cancer patients hospitalized with COVID-19 at a comprehensive cancer center over a 10-month period who had PCT recorded on admission. We assessed associations between variables of clinical interest and the primary outcomes ofprogression of COVID-19 and death during or within 30days of hospitalization using univariable and multivariable logistic regression. The study included 209 unique patients. In the univariate analysis, elevated PCT on admission was associated with higher odds of progression of COVID-19 or death (Odds ratio [OR] 1.40, 95% CI 1.08-1.93) and mortality alone (OR 1.53, 95% CI 1.17-2.11). In multivariate regression, PCT remained significantly associated with progression or death after holding chronic kidney disease (CKD) status constant (OR 1.40, 95% CI: 1.08, 1.93, p=0.003). Similarly, the association of PCT and death remained significant after adjusting for age (OR 1.54, 95% CI: 1.17-2.15). In hospitalized COVID-19 patients with underlying cancer, initial PCT levels on admission may beassociated with prognosis, involving higher odds of progression of COVID-19 and/or mortality.

Survival benefit of adequate lymphadenectomy in patients undergoing liver resection for clinically node-negative intrahepatic cholangiocarcinoma

Lymph-nodal status is an important predictor of survival in intrahepatic cholangiocarcinoma (iCCA), but the need to perform lymphadenectomy in patients with clinically node-negative (cN0) iCCA is still under debate. The aim of this study was to determine whether adequate lymphadenectomy improves long-term outcomes in patients undergoing liver resection for cN0 iCCA. We performed a retrospective cohort study on consecutive patients who underwent radical liver resection for cN0 iCCA at five tertiary referral centers. A propensity score based on preoperative data was calculated and used to generate stabilized inverse probability of treatment weight (IPTW). Overall and recurrence-free survival of patients undergoing adequate (≥6 retrieved lymph nodes) vs. inadequate lymphadenectomy were compared. Interactions between adequacy of lymphadenectomy and clinical variables of interest were explored through Cox IPTW regression. The study includes 706 patients who underwent curative surgery for cN0 iCCA. Four-hundred and seventeen (59.1%) received adequate lymphadenectomy. After a median follow-up of 33 months (IQR 18-77), median overall survival was 39 months (IQR 23-109) and median recurrence-free survival was 23 months (IQR 8-74). After stratification according to nodal status at final pathology, node-positive patients had longer overall survival (28 vs. 23 months; hazard ratio 1.82; 95% CI 1.14-2.90; p= 0.023) and disease-free survival (13 vs. 9 months; hazard ratio 1.35; 95% CI 1.14-1.59; p= 0.008) after adequate lymphadenectomy. Adequate lymphadenectomy significantly improved survival outcomes in patients without chronic liver disease, and in patients with less-advanced tumors (solitary tumors, tumor size <5cm, carbohydrate antigen 19-9 <200 U/ml). Adequate lymphadenectomy provided better survival outcomes for patients with cN0 iCCA who were found to be node-positive at pathology, supporting the routine use of adequate lymphadenectomy for cN0 iCCA. Lymphadenectomy is essential for the surgical staging of intrahepatic cholangiocarcinoma (iCCA). While its role in patients with preoperative suspicion of nodal metastases is implicit, the impact of lymphadenectomy on survival of patients with clinically node-negative (cN0) disease is still under debate. In this large retrospective study on patients who underwent surgical resection for cN0 iCCA, we show that adequate lymphadenectomy (i.e. retrieving ≥6 lymph nodes) significantly improves survival and lowers the risk of tumor recurrence. Lymphadenectomy during surgical resection of iCCA is actually underperformed by the surgical community, resulting in inadequate staging and possibly worse long-term outcomes. The results of this study should empower surgeons and clinicians to push for adequate lymphadenectomy even for cN0 iCCA. Since patients with no chronic liver disease and with less-advanced tumors receive a significant benefit from lymphadenectomy, our results might guide decision making in patients at high-risk of postoperative complications.

S1056 Change in C-Reactive Protein 72 Hours Following Admission Associates With Inpatient and One-Year Colectomy Risk in Severe Ulcerative Colitis

Introduction: Ulcerative colitis (UC) morbidity remains high despite multiple therapeutic advances. Early identification of risk for failure of medical therapies and need for colectomy becomes pivotal to avoid unnecessary and dangerous delays in care. Many presently-validated risk appraisal scores require subjective data to inform risk. Our study aimed to determine the predictive value of the change in C-reactive protein (CRP) during hospitalization for severe UC. Methods: We designed a retrospective study including patients ≥ 18 years old with an admission for UC at a single academic center between 1/1/2013 and 4/1/2018. Cases were identified using the ICD-9 code 556.X and ICD-10 code K51.X and separately, manually verified. Clinical variables of interest and laboratory values were obtained via chart review or extracted from the electronic medical record. Data was analyzed using Wilcoxon rank-sum test for continuous variables, and Fischer’s exact test for categorical variables. Statistical analysis was conducted using JMP ® 13.1.0. Results: 122 hospitalized patients met the inclusion criteria with a median age of 30.2 (IQR: 22.8-46.9) years. 72 (59%) patients were male and 89 (73.6%) were Caucasian. 27 (22.3%) patients required inpatient colectomy and 49 (41.5%) had a colectomy within one year of index admission. Percent change in CRP between admission and 72 hours was predictive of inpatient colectomy (P=0.051), whereas the value of CRP on admission or at 72 hours was not (Table). Among patients with an increase in CRP at 72 hours, 9/21 (42.9%) required inpatient colectomy as compared to 18/101 (17.8%) without an increase in CRP (P=0.019). The percent change in CRP at 72 hours was also predictive of 1-year colectomy risk (-53.3 (50.7) vs -33.7 (49.6), P=0.003). Conclusion: Percent change in CRP between admission and 72-hours predicts both inpatient and 1-year colectomy risk in patients hospitalized with UC. Percent change better prognosticates the need for surgery compared to CRP on admission alone. Herein, we show that a reduction in CRP by 50% 72 hours from admission is an objective and easily determined measurement to risk stratify patients early in the admission for UC. Table 1. - Predictors of colectomy during inpatient admission Risk Factors: Colectomy No Colectomy P-value Age (years), mean (SD) 37.98 (18.51) 35.08 (14.3) 0.644 Male Sex, n (%) 14 (51.85) 58 (61.05) 0.506 White Race, n (%) 21 (77.78) 68 (72.34) 0.631 Presentation with Severe Colitis, n (%) 27 (100) 82 (86.32) 0.07 Prior Admission requiring IV Steroids, n (%) 17 (62.96) 34 (35.79) 0.015 Hospitalization in prior 4 weeks, n (%) 23 (39.0%) 50 (24.5%) 0.047* Biologic naïve, n (%) 7 (25.93) 50 (52.63) 0.024 Single prior biologic class 12 (44.44) 33 (34.74) Multiple prior biologic classes 8 (29.63) 12 (12.63) Steroids usage prior to Presentation, n (%) 17 (62.96) 53 (55.79) 0.66 Inpatient salvage therapy 13 (48.15) 61 (64.21) < 0.001 Laboratory Data: Mean (SD) Admission CRP 45.7 (35.1) 52.89 (56.31) 0.7 72 hour CRP 37.41 (45.03) 26.52 (34.43) 0.178 72 hour change in CRP % -26.5 (58.74) -47.19 (55.81) 0.051

Comorbidities associated with COVID‑19 mortality: A retrospective study in an intermediate care facility in Cape Town, South Africa

Background. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to place a significant burden on healthcare systems across the globe. Previous studies have shown that patients with comorbidities who contract SARS-CoV-2 develop more severe COVID‑19 disease and are at a higher risk of mortality. However, literature in the intermediate care setting is limited. Objectives. To evaluate the association between comorbidity and mortality in the intermediate care setting.Methods. A retrospective observational study was performed at Brackengate Intermediate Care Facility (BICF), a 330-bed field hospital, during the second wave of COVID‑19 in Cape Town, South Africa. Data of all adult patients admitted from 1 November 2020 to 28 February 2021 who met the inclusion criteria were analysed. Data were obtained from electronic hospital patient administration systems. Comparisons were made using χ2 or Fisher’s exact testing with a 5% level of confidence used to determine significance. Logistic regression models were used to investigate the independent association between clinical variables of interest and overall mortality.Results. A total of 2 508 patients were analysed, of whom 2 476 (98.7%) were laboratory confirmed cases of COVID‑19. The median number of admissions per day was 14. The mean age was 58 years, and 1 449 (57.8%) were female. The most prevalent comorbidities were hypertension (62.6%), diabetes (46.9%) and obesity (28.0%), while 8.0% of patients were HIV-positive. The overall mortality was 13.3% (333/2 508). Patients with at least one comorbidity were 1.4 times more likely to die (odds ratio (OR) 2.4; 95% confidence interval (CI) 1.6 - 3.5), and this risk increased significantly with cumulative comorbidities. Patients who required &gt;40% oxygen were at 5.5 (95% CI 4.3 - 7.1) times higher mortality risk. Variables independently associated with mortality were age &gt;60 years, FiO2&gt;40%, previous cerebrovascular accident, concurrent tuberculosis infection and chronic kidney disease.Conclusion. Patients with comorbidities are at an increased risk of death in COVID‑19 disease, and should be monitored closely. Oxygen requirement &gt;40% is also associated with a higher likelihood of dying. Intermediate care facilities can provide valuable relief to acute care facilities by admitting high-risk patients for closer monitoring and management.

An exploratory study of pro-inflammatory cytokines in individuals with alcohol use disorder: MCP-1 and IL-8 associated with alcohol consumption, sleep quality, anxiety, depression, and liver biomarkers.

BackgroundHigh levels of sleep disturbances reported among individuals with alcohol use disorder (AUD) can stimulate inflammatory gene expression, and in turn, may alter pro-inflammatory cytokines levels. We aimed to investigate associations between pro-inflammatory cytokine markers with subjective measures of sleep quality, psychological variables and alcohol consumption among individuals with AUD.MethodsThis exploratory study is comprised of individuals with AUD (n = 50) and healthy volunteers (n = 14). Spearman correlation was used to investigate correlations between plasma cytokine levels and clinical variables of interest (liver and inflammatory markers, sleep quality, patient reported anxiety/depression scores, and presence of mood and/or anxiety disorders (DSM IV/5); and history of alcohol use variables.ResultsThe AUD group was significantly older, with poorer sleep quality, higher anxiety/depression scores, and higher average drinks per day as compared to controls. Within the AUD group, IL-8 and MCP-1 had positive significant correlations with sleep, anxiety, depression and drinking variables. Specifically, higher levels of MCP-1 were associated with poorer sleep (p = 0.004), higher scores of anxiety (p = 0.006) and depression (p < 0.001), and higher number of drinking days (p = 0.002), average drinks per day (p < 0.001), heavy drinking days (p < 0.001) and total number of drinks (p < 0.001). The multiple linear regression model for MCP-1 showed that after controlling for sleep status and heavy drinking days, older participants (p = 0.003) with more drinks per day (p = 0.016), and higher alkaline phosphatase level (p = 0.001) had higher MCP-1 level.ConclusionThis exploratory analysis revealed associations with cytokines MCP-1 and IL-8 and drinking consumption, sleep quality, and anxiety and depression in the AUD group. Furthermore, inflammatory and liver markers were highly correlated with certain pro-inflammatory cytokines in the AUD group suggesting a possible relationship between chronic alcohol use and inflammation. These associations may contribute to prolonged inflammatory responses and potentially higher risk of co-morbid chronic diseases.

Statistical challenges in longitudinal microbiome data analysis.

The microbiome is a complex and dynamic community of microorganisms that co-exist interdependently within an ecosystem, and interact with its host or environment. Longitudinal studies can capture temporal variation within the microbiome to gain mechanistic insights into microbial systems; however, current statistical methods are limited due to the complex and inherent features of the data. We have identified three analytical objectives in longitudinal microbial studies: (1) differential abundance over time and between sample groups, demographic factors or clinical variables of interest; (2) clustering of microorganisms evolving concomitantly across time and (3) network modelling to identify temporal relationships between microorganisms. This review explores the strengths and limitations of current methods to fulfill these objectives, compares different methods in simulation and case studies for objectives (1) and (2), and highlights opportunities for further methodological developments. R tutorials are provided to reproduce the analyses conducted in this review.

Impact of the COVID-19 pandemic on maternal anxiety during pregnancy: A prevalence study

AimTo assess the impact of the coronavirus SARS-CoV-2 pandemic on the level of anxiety in low-risk pregnant women. Material and methodEpidemiological, descriptive, prevalence study. A total of 74 patients who underwent low risk antenatal controls during the state of alarm because of COVID-19, were included. They filled in the Hamilton Anxiety Rating Scale and a specific document about the pandemic. Clinical histories and different variables of clinical interest were reviewed and compiled, respectively. ResultsMean age was 34.05 years with average amenorrhoea of 28.17 weeks. A total of 77% of the sample presented symptoms and signs compatible with anxiety. Of these, 44.6% and 32.4% presented minor and major anxiety, respectively. Concern over the time of the birth and postpartum and fear of being at greater risk because of possible infection was present in 95.9% and 94.6% of the sample, respectively. A total of 93.2% of the sample was afraid of intrauterine virus transmission; 94.5% admitted fear over the neonatal consequences of infection. ConclusionsThe pregnant women assessed had three times more anxiety during the COVID-19 pandemic. This incidence is independent of most study variables.

Are there clinical and sociodemographic differences between bipolar i and ii disorders?

IntroductionBipolar disorder is a serious mental disorder. Although bipolar disorder I (BDI) might seem to have a more complex evolution and severe prognosis than bipolar disorder II (BDII) because of cross-sectional symptom severity, BDII has a high episode frequency, high rates of psychiatric comorbidities and recurrent suicidal behaviours that impair functioning and quality of life.ObjectivesTo explore whether there are differences between patients with BDI and BDII concerning sociodemographic and clinical variables of interest.MethodsA sample of 407 euthymic patients with bipolar disorder (307 BDI and 100 BDII) being age 18 or older was recruited from the Bipolar and Depressive Disorders Unit of the Hospital Clinic of Barcelona. Sociodemographic and clinical variables were collected through the administration of semi-structured interview and clinical scales. Differences between groups in these variables were analysed using the Mann-Whitney U and Chi-square tests, as appropriate. The level of significance was set at p &lt;0.05.ResultsWe found statistically significant differences between both groups. Patients with BD II were older (p&lt;0.001), presented a longer illness duration (p=0,001) and a greater subsyndromal depressive symptomatology (p=0,010). Patients with BDI had a higher number of previous hospitalizations (p&lt;0,001) and higher rates of psychotic symptoms (p&lt;0,001) even during the first episode (p&lt;0,001).ConclusionsOur data suggests that clinical differences exist between both bipolar subtypes. The episodes may be more serious, with a greater presence of a history of psychosis, and require more hospitalizations in BDI patients. In the BDII group, persistent subsyndromal symptoms may predominate, especially of the depressive pole.DisclosureNo significant relationships.

A Weakly Supervised Clustering Method for Cancer Subgroup Identification

Identifying subgroups of cancer patients is important as it opens up possibilities for targeted therapeutics. A widely applied approach is to group patients with unsupervised clustering techniques based on molecular data of tumor samples. The patient clusters are found to be of interest if they can be associated with a clinical outcome variable such as the survival of patients. However, these clinical variables of interest do not participate in the clustering decisions. We propose an approach, WSURFC (Weakly Supervised Random Forest Clustering), where the clustering process is weakly supervised with a clinical variable of interest. The supervision step is handled by learning a similarity metric with features that are selected to predict this clinical variable. More specifically, WSURFC involves a random forest classifier-training step to predict the clinical variable, in this case, the survival class. Subsequently, the internal nodes are used to derive a random forest similarity metric among the pairs of samples. In this way, the clustering step utilizes the nonlinear subspace of the original features learned in the classification step. We first demonstrate WSURFC on hand-written digit datasets, where WSURFC is able to capture salient structural similarities of digit pairs. Next, we apply WSURFC to find breast cancer subtypes using mRNA, protein, and microRNA expressions as features. Our results on breast cancer show that WSURFC could identify interesting patient subgroups more effectively than the widely adopted methods.

Prophylactic surgical treatment using CT-based rigidity analysis vs. after the fact fracture treatment of pathologic femoral lesions.

Accurate comparison of prophylactic surgical treatment (PST) to after fracture treatment (AF) of patients with femoral metastatic disease requires more accurately identifying patients for impending fracture, such as with CT-based structural rigidity analysis (CTRA). This study compares a more accurately defined PST group (of impending fractures defined by CTRA) to AF for metastatic femoral disease. PST patients were enrolled and treated by the PI in a longitudinal multicenter study of impending pathologic fractures evaluated for accuracy by CTRA. The AF patients were also treated by the senior author and were identified by retrospective chart review. Fifty-five patients were treated surgically for metastatic femoral lesions and were divided into three groups for the purpose of this study: Group I (AF), Group II (PST-high), and Group III (PST-low). Demographic information, comorbidities, and clinical variables of interest were collected by retrospective chart review; cost data was collected by collaboration with our hospital financial personnel (office of the Chief Financial Officer). Survival showed statistically significant differences favoring Group II. Transfusions in Group I were nearly twice those of Groups II and III, but there was no statistically significant (NS) difference between groups. Estimated blood loss (EBL) was generally with NS difference. Similarly, there were NS differences in LOS between groups. Discharge disposition showed statistically significant differences between groups (P=0.012, global). Discharge to home was highest in Group II (76%) and lowest in Group I (27%). Discharge to rehab was lowest in Group II (24%) and highest in Group I (47%). There were no discharges to hospice or morgue in Group II, while both occurred in Group I. Mean direct and total costs were highest in Group I ($18,837 and $31,997, respectively) and lowest in Group II ($16,094 and $27,357) but the differences were NS. This study shows benefits of PST over AF in a group of PST patients more accurately defined to have impending pathologic fractures by CTRA definition.

Population Pharmacokinetics of Cotadutide in Subjects with Type 2 Diabetes.

Cotadutide is a balanced dual glucagon-like peptide-1/glucagon receptor agonist under development for the treatment of nonalcoholic steatohepatitis and chronic kidney disease with type 2 diabetes. The objectives of the analysis were to characterize the population pharmacokinetics of cotadutide following daily subcutaneous injection in subjects with type 2 diabetes and to evaluate the effect of demographic and clinical variables of interest on cotadutide pharmacokinetics. This study analyzed 8834 plasma concentrations of cotadutide from 759 subjects with type 2 diabetes who received daily subcutaneous doses from 20 to 600 μg from six clinical studies. The impact of covariates on cotadutide pharmacokinetics was quantified, and body weight effect on cotadutide exposure was further evaluated using a simulation approach. The model performance was evaluated through prediction-corrected visual predictive checks. A one-compartment model with first-order absorption and elimination described cotadutide pharmacokinetic data well. The mean values for cotadutide apparent clearance, apparent distribution volume, absorption rate constant, and half-life were 1.04 L/h (interindividual variability [IIV]: 26.5%), 18.7 L (IIV: 28.7%), 0.343 h-1 (IIV: 38.6%), and 12.9 h, respectively. Higher body weight, lower albumin, and higher alanine aminotransferase were associated with an increase in cotadutide clearance, while an increase in anti-drug antibody titers was associated with a decrease in cotadutide clearance. These statistically significant effects were not considered clinically significant and did not warrant dose adjustment. Effects of other tested baseline covariates (age, sex, body mass index, hemoglobin A1c, renal function, duration of diabetes) were not found to statistically significantly affect cotadutide pharmacokinetics. Cotadutide pharmacokinetics was adequately described by a one-compartment linear model with first-order absorption and elimination. Body weight-based dosing is not necessary for cotadutide based on the simulation using the final population pharmacokinetic modeling. This model will be used to evaluate exposure-response relationships for efficacy and safety in different indications that are being studied for cotadutide.

Differences in Clinical Features and Comorbid Burden between HLA-C∗06:02 Carrier Groups in >9,000 People with Psoriasis

The identification of robust endotypes-disease subgroups of clinical relevance-is fundamental to stratified medicine. We hypothesized that HLA-C∗06:02 status, the major genetic determinant of psoriasis, defines a psoriasis endotype of clinical relevance. Using two United Kingdom-based cross-sectional datasets-an observational severe-psoriasis study (Biomarkers of Systemic Treatment Outcomes in Psoriasis; n= 3,767) and a large population-based bioresource (UK Biobank, including n= 5,519 individuals with psoriasis)-we compared demographic, environmental, and clinical variables of interest in HLA-C∗06:02-positive (one or two copies of the HLA-C∗06:02 allele) with those in HLA-C∗06:02‒negative (no copies) individuals of European ancestry. We used multivariable regression analyses to account for mediation effects established a priori. We confirm previous observations that HLA-C∗06:02-positive status is associated with earlier age of psoriasis onset and extend findings to reveal an association with disease expressivity in females (Biomarkers of Systemic Treatment Outcomes in Psoriasis: P= 2.7× 10-14, UK Biobank: P= 1.0× 10-8). We also show HLA-C∗06:02-negative status to be associated with characteristic clinical features (large plaque disease, OR for HLA-C∗06:02= 0.73, P= 7.4× 10-4; nail involvement, OR= 0.70, P= 2.4× 10-6); higher central adiposity (Biomarkers of Systemic Treatment Outcomes in Psoriasis: waist circumference difference of 2.0 cm, P= 8.4× 10-4; UK Biobank: waist circumference difference of 1.4 cm, P= 1.5× 10-4), especially in women; and a higher prevalence of other cardiometabolic comorbidities. These findings extend the clinical phenotype delineated by HLA-C∗06:02 and highlight its potential as an important biomarker to consider in future multimarker stratified medicine approaches.

Factors related to hospital readmission of patients with acute coronary syndrome: a prospective cohort study

Abstract Background Hospital readmissions of patients with acute coronary syndrome (ACS) are frequent and associated with poor clinical outcomes and increased costs to the healthcare services. Identifying factors that might be associated with hospital readmission is important to support preventive interventions. Purpose To identify factors related to hospital readmission of patients with ACS. Methods A prospective cohort study. Patients hospitalized with ACS for the first time were included in the study. The outcome, hospital readmission for ACS, was assessed at 30 days, 6 months and 1 year after index discharge. Modifiable cardiovascular risk factors (arterial hypertension, dyslipidemia, diabetes mellitus, smoking, degree of addiction to smoking, use of alcohol, physical inactivity, obesity, stress, depression, excessive daytime sleepiness, obstructive sleep apnea syndrome, hormone replacement) and non-modifiable risk factors (age, race, family history of coronary heart disease) were evaluated as potential predictors of the outcome. Other variables that might have contributed to readmission were also included: marital status, family income, occupation, education, adherence to medication and type of treatment (clinical, percutaneous coronary intervention or coronary artery bypass grafting). The association between hospital readmission and potential predictors was assessed using the Log-Rank test and Cox's simple regression model. Factors whose associations had a p-value of less than 0.20 in the simple regression and other variables of clinical interest were evaluated in a Cox multiple regression model, with p&amp;lt;0.05 considered significant. The study was approved by two Research Ethics Committees. Results 216 patients were included and the incidence of readmission was 15.7%. Most of the patients were male, white, married, had an income between two and four minimum wages, and a mean age of 60 years. Half of the patients had high adherence to medication. The cardiovascular risk factors identified in most patients were sedentary lifestyle (79.6%), arterial hypertension (63.4%) and obstructive sleep apnea (51.9%). The only independent predictor for readmission was surgical treatment (p=0.026). Conclusions Participants had several cardiovascular risk factors and the predictor of hospital readmission was surgical treatment. Identifying the predictive factors of a given population helps nurses in planning and guiding hospital discharge. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Conselho Nacional de Desenvolvimento Científico e Tecnolόgico (CNPq)