Baseline Clinical Measures Research Articles

Development of Self‐Reported Reward Responsiveness and Inhibitory Control and the Role of Clinical and Neural Predictors

ABSTRACTObjectiveUnderstanding the development of adolescent reward responsiveness and inhibitory control is important as they are implicated in key outcomes, such as depression. However, relatively few studies have examined the self‐reported experience of this development longitudinally, and past findings have been mixed. Here, we examined the longitudinal development of self‐reported reward responsiveness and inhibitory control in youth, as well as clinical and neural measures as predictors of these longitudinal trajectories.MethodWe assessed 223 youth aged 9–17 across 36 months. We modeled growth trajectories of several measures of reward responsiveness and inhibitory control using multilevel models. We tested reward‐related functional connectivity, depression symptoms, and parental risk for psychopathology as moderators of longitudinal growth.ResultsSelf‐reported inhibitory control increased linearly across adolescence. However, contrary to hypotheses and common models of adolescent development, self‐reported reward responsiveness decreased linearly across adolescence. Baseline functional connectivity and clinical risk measures did not significantly moderate trajectories.ConclusionResults suggest that within‐person changes in the phenomenological experience of reward responsiveness may not match developmental expectations based on cross‐sectional and neuroimaging studies. More attention is needed to the longitudinal study of subjective experience of reward responsiveness.

A prediction model for the walking and balance milestone in Parkinson's disease

BackgroundWalking and balance impairments, represented by freezing of gait and falls, are significant contributors to disability in advanced Parkinson's disease (PD) patients. However, the composite measure of the Walking and Balance Milestone (WBMS) has not been thoroughly investigated. MethodsThis study included 606 early-stage PD patients from the Parkinson's Progression Markers Initiative (PPMI) database, with a disease duration of less than 2 years and no WBMS at baseline. Patients were divided into a model development cohort (70 %) and a validation cohort (30 %) according to the enrollment site. Longitudinal follow-up data over a period of 12 years were analyzed. ResultsAmong all 606 patients, the estimated probability of being WBMS-free at the 5th and 10th year was 88 % and 60 %, respectively. Five clinical variables (Age, Symbol Digit Modalities Test (SDMT), postural instability and gait difficulty (PIGD) score, Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part I (MDS-UPDRS-I) score, and REM Sleep Behavior Disorder (RBD) were used to construct the Cox predictive model. The C-index of the model was 0.75 in the development cohort and 0.76 in the validation cohort. By optimizing the PIGD and MDS-UPDRS-I variables, an easy-to-use model was achieved with comparable predictive performance. ConclusionA predictive model based on five baseline clinical measures (Age, SDMT, PIGD score, MDS-UPDRS-I score, RBD) could effectively estimate the risk of the WBMS in early PD patients. This model is valuable for prognostic counseling and clinical intervention trials for gait and balance impairment.

Intragallbladder versus intravenous indocyanine green (ICG) injection for enhanced bile duct visualization by fluorescent cholangiography during laparoscopic cholecystectomy: a retrospective cohort study.

Iatrogenic bile duct injuries (BDIs) prevention during laparoscopic cholecystectomy (LC) relies on meticulous anatomical dissections through direct visualization. Near-infrared fluorescence (NIRF) with indocyanine green (ICG) improves the visualization of extrahepatic biliary structures. Although ICG can be administered either intravenously or intragallbladder, there remains uncertainty regarding the optimal method for different patient populations. This study sought to assess the suitability of each method for specific patient groups. Between October 2021 and May 2022, 59 consecutive patients underwent fluorescence-guided LC at West China Hospital of Sichuan University. Among them, 32 patients received an intravenous injection of ICG (10 mg) 10 to 12 hours prior to surgery (Group A: the intravenous group), while 27 patients received an intragallbladder injection of ICG (10 mg) (Group B: the intragallbladder group). Baseline clinical factors, inclusion criteria, and measurements of parameters and complications were assessed. Data were retrospectively collected and analyzed to evaluate the comparability of the two groups and the clinical outcomes. Groups A and B included 32 patients (18 males, 14 females), and 27 patients (13 men, 14 women), respectively. In our statistical analysis, significant differences were observed in preoperative diagnoses between the two groups (P=0.041), but the majority of other baseline clinical factors were comparable. Notably, no statistically significant differences were found in complication rates. However, Group A had a shorter operative time (60.38±9.35 vs. 66.78±9.88 min, P=0.01) and superior bile duct fluorescence (P=0.04) than Group B. Interestingly, fluorescence was not observed in impacted gallbladder stones in Group B. Additionally, patients with cirrhosis (P=0.008) and fatty liver (P=0.005) in Group B had higher common bile duct-to-liver ratios (BLRs) than those in Group A. ICG fluorescence cholangiography allows to visualize extrahepatic biliary anatomical structures with both administration methods. However, the efficacy of bile duct fluorescence varies with different administration routes in diverse patient populations. Hence, appropriate administration route selection for ICG should be tailored to individual patients.

Acupuncture Modulation of Chronic Neuropathic Pain and Its Association With Brain Functional Properties

Chronic neuropathic pain has been one of the prominent causes of disability, and acupuncture has shown promise in treatment. The present study aimed to characterize acupuncture modulation of chronic neuropathic pain and explore the related functional brain changes. Sixty chronic sciatica patients were divided into acupuncture- or sham acupuncture groups and received 10 sessions of treatment during 4 weeks. The visual analog scale for leg pain, oswestry disability index (ODI), and resting-state functional magnetic resonance images were assessed at baseline and after treatment. Then, fractional amplitudes of low-frequency fluctuations (fALFF) and support vector regression analyses were performed. Compared with sham acupuncture, acupuncture significantly improved symptoms, including visual analog scale for leg pain and ODI. In addition, acupuncture exhibited increased fALFF of the right superior parietal lobule (SPL) and right postcentral gyrus. Furthermore, the actual 4-week ODI values were positively correlated with the support vector regression-predicted values based on the right SPL fALFF and baseline clinical measurements. These results indicate that the spontaneous neural activity of the right SPL and right postcentral gyrus may be involved in the modulation of acupuncture in chronic neuropathic pain. In addition, the spontaneous neural activity of the right SPL might be used as the predictor of response to acupuncture therapy. PerspectiveThis clinical neuroimaging study elucidated the neural basis of acupuncture in chronic sciatica. Neurological indicators and clinical measurements could be used as potential predictors of acupuncture response. This study combines neuroimaging and artificial intelligence techniques to highlight the potential of acupuncture for the treatment of chronic neuropathic pain. Trial registration numberChinese Clinical Trial Registry, ChiCTR2100044585, http://www.chictr.org.cn.

SomaLogic proteomics reveals new biomarkers and provides mechanistic, clinical insights into Acetyl coA Carboxylase (ACC) inhibition in Non-alcoholic Steatohepatitis (NASH)

Non-alcoholic Fatty Liver Disease (NAFLD) and Non-alcoholic Steatohepatitis (NASH) are major metabolic diseases with increasing global prevalence and no approved therapies. There is a mounting need to develop biomarkers of diagnosis, prognosis and treatment response that can effectively replace current requirements for liver biopsies, which are invasive, error-prone and expensive. We performed SomaLogic serum proteome profiling with baseline (n = 231) and on-treatment (n = 72, Weeks 12 and 16, Placebo and 25 mg PF-05221304) samples from a Phase 2a trial (NCT03248882) with Clesacostat (PF-05221304), an acetyl coA carboxylase inhibitor (ACCi) in patients with NAFLD/NASH. SomaSignal NASH probability scores and expression data for 7000+ analytes were analyzed to identify potential biomarkers associated with baseline clinical measures of NAFLD/NASH [Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF), alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] as well as biomarkers of treatment response to ACCi. SomaSignal NASH probability scores identified biopsy-proven/clinically defined NIT-based (Presumed) NASH classification of the cohort with > 70% agreement. Clesacostat-induced reduction in steatosis probability scores aligned with observed clinical reduction in hepatic steatosis based on MRI-PDFF. We identify a set of 69 analytes that robustly correlate with clinical measures of hepatic inflammation and steatosis (MRI-PDFF, ALT and AST), 27 of which were significantly reversed with ACC inhibition. Clesacostat treatment dramatically upregulated Wnt5a protein and Apolipoproteins C3 and E, with drug-induced changes significantly correlating to changes on MRI-PDFF. Our data demonstrate the utility of SomaLogic- analyte panel for diagnosis and treatment response in NAFLD/NASH and provide potential new mechanistic insights into liver steatosis reduction, inflammation and serum triglyceride elevation with ACC inhibition. (Clinical Trial Identifier: NCT03248882).

Effectiveness of peer-delivered sleep health education and social support in increasing OSA evaluation among at-risk blacks.

To assess the effectiveness of culturally and linguistically tailored, peer-delivered obstructive sleep apnea education and of social support to increase adherence to physician-recommended obstructive sleep apnea evaluation among blacks. In a two-arm randomised controlled trial, we ascertained the effectiveness of peer-delivered obstructive sleep apnea education in increasing obstructive sleep apnea evaluation among 319 blacks at risk of obstructive sleep apnea (intervention = 159 and control = 160); their average age was 47 ± 12.9 years, and 41% were male. Obstructive sleep apnea risk was assessed with the Apnea Risk Evaluation System questionnaire, administered in community venues. Participants in the intervention arm received tailored obstructive sleep apnea education during a 6 month period; those in the control arm received standard sleep and healthy lifestyle information. Analysis focussed on the effectiveness of peer-delivered obstructive sleep apnea education on adherence to obstructive sleep apnea evaluation, but also considered the role of psychosocial factors. The results showed no significant differences in baseline demographic and clinical measures when contrasting participants in the study arms. The adherence rates for home-based obstructive sleep apnea evaluation in the intervention and control arms were 45.9% and 45.6%, respectively. Overall, participants in both study arms (adherers) who underwent obstructive sleep apnea evaluations were likely to experience a greater level of social support (8.2 ± 2.4 vs. 7.3 ± 2.4; p = 0.06). Moreover, adherers showed greater psychosocial scores (i.e., Dysfunctional Beliefs and Attitudes about Sleep scale, Apnea Beliefs Scale (ABS) (and Apnea Knowledge) compared with non-adherers (6.0 ± 1.8 vs. 4.9 ± 2.2; p = 0.02; 77.0 ± 7.1 vs. 73.2 ± 7.4; p = 0.04, and 6.4 ± 3.1 vs. 7.6 ± 2.4; p = 0.06, respectively). The results of the present randomised controlled trial favoured a potential role of peer-based social support and psychosocial factors, associated with obstructive sleep apnea adherence behaviour.

Combined Treatment of Peri-Implantitis in Patients with Type 2 Diabetes Mellitus

Objective: To evaluate the outcome of combined therapy of peri-implantitis in patients with type 2 diabetes mellitus. Methods: Study included 46 patients with type 2 diabetes mellitus diagnosed peri-implantis. 24 implants with early peri-implantitis, 18 implants with moderate peri-implantitis. The diagnostic parameters used for assessing peri-implantitis include clinical indices, Probing Pocket Depth (PPD), Bleeding on Probing (BOP), peri-implant radiography, data at the re-examination were retrospectively compared to baseline data. Patients underwent treatment with HbA1c levels <7.2% or less than 154 mg/Dl. Results: A statistical significant reduction in both PPD and BOP were seen at all-time points as compared with the baseline clinical measurements. Stable clinical measurements PPD and BOP were demonstrated after 1 year the initial treatment, remaining stable during the following three years. The mean BOP in patients before treatment of peri-implantitis was 2.5 ± 0.31, after 6 months treatment month treatment 0.6 ± 0.1. The mean PPD in patients before treatment of peri- implantitis was 5.2 ± 0.24, after 6-month treatment pocket was 3.2 ± 0.1. Conclusion: Conservative treatment with systemic antibiotics, pocket elimination was an effective therapy in peri-implant mucositis and еarly periimplantitis, when peri-implantitis category moderate surgical treatment combined conservative therapy effective method in patients with type 2 diabetes mellitus.

Predictors for early-onset psychotic symptoms in patients newly diagnosed with Parkinson's disease without psychosis at baseline: A 5-year cohort study.

To investigate the risk factors for early-onset psychosis in Parkinson's disease (PD) in a cohort of patients from the Parkinson's Progression Markers Initiative. Longitudinal data on motor and non-motor features, dopamine transporter (DAT) imaging, and cerebrospinal fluid (CSF) measurements were collected. The survival probability of psychotic symptoms, potential risk factors for psychosis development over a 5-year follow-up period, and the performance of the prediction model were evaluated. Among the 338 newly diagnosed patients with PD, 83 developed psychotic symptoms. Gastrointestinal autonomic dysfunction, presence of probable rapid-eye-movement sleep behavior disorder, and the ratio Aβ42: total-tau could independently predict onset of psychosis in PD (hazard ratio (HR) = 1.157, 95% confidence interval (CI) 1.022-1.309, p = 0.021, HR = 2.596, 95% CI 1.287-5.237, p = 0.008, and HR = 0.842, 95% CI 0.723-0.980, p = 0.027, respectively). The combined model integrating baseline clinical predictors, DAT imaging, and CSF measurements achieved better sensitivity than the clinical predictors alone (area under the curve = 0.770 [95% CI 0.672-0.868] vs. 0.714 [95% CI 0.625-0.802], p = 0.098). We identified clinical and CSF predictors of early-onset psychosis in patients with PD. Our study provides evidence and implications for prognostic stratification and therapeutic approaches for PD psychosis.

Remaining Between the Cracks - The Long-Term Effect of Different Suicide Risk Exclusion Criterion on Outcomes of an Online Intervention for Depression.

Background: Previous studies have demonstrated that excluding individuals at risk of suicide from online depression interventions can impact recruited sample characteristics. Aim: To determine if a small change in suicide risk exclusion criterion led to differences in the usage and effectiveness of an Internet depression intervention at 6 months of follow-up. Method: A partial sample of a recently completed online depression intervention trial was divided into two groups: those with no risk of suicide versus those with some risk. The two groups were compared for baseline demographic and clinical measures, as well as intervention uptake and treatment success across 6 months. Results: Overall, individuals with less risk of suicide at baseline reported significantly less severe clinical symptoms. Both groups interacted with the intervention at the same rate, but specific use of modules was different. Finally, the impact of intervention usage on outcomes over time did not vary by group. Limitations: While different suicide risk exclusion criteria can change recruited sample characteristics, it remains unclear how these differences impact intervention uptake and success. Conclusion: Overall, the findings suggest that researchers should exercise caution when excluding individuals at risk of suicide, as they greatly benefit from web-based interventions.

Evaluation of the Relationship Between Vitamin D Deficiency and Subclinical Cardiac Dysfunction Using 2D/3D Strain Echocardiography in Healthy People.

Vitamin D deficiency has a high prevalence in the population and is highly associated with cardiovascular diseases. The aim of this study was to evaluate subclinical left ventricular (LV) function using strain analysis in healthy individuals with vitamin D deficiency. 113 healthy volunteers were enrolled in the study (age, 44.1±7 yrs, 34 male). All volunteers underwent two-dimensional (2D) and three-dimensional (3D) speckle tracking echocardiography after conventional echocardiographic evaluation. The subjects were divided into two groups according to their vitamin D concentrations. 61 subjects with vitamin D less than 20 ng / ml were included in the vitamin D deficiency group. The baseline clinical characteristics, laboratory measurements, echocardiographic data, including 2D and 3D global longitudinal strain (GLS) values, were compared between the groups. The 2D GLS values of the subjects with vitamin D deficiency were lower (mathematically less negative) than subjects with normal vitamin D (-16.1±3.4 vs -19.3±4.2, p<0.001). Similarly, the 3D GLS results were lower in subjects with vitamin D deficiency (-18.3±5.2 vs -24.1±6.9, p<0.001). A significant correlation was detected between the vitamin D concentrations and the 2D and 3D GLS measurements. (r=0.765 and r=0.628, respectively, p<0.001). Vitamin D was found to be an independent predictor of impaired 2D and 3D LV GLS (p=0.031, p=0.023, respectively). Subclinical LV dysfunction in healthy individuals with vitamin D deficiency was demonstrated by 3D and 2D strain analysis. Due to potential negative effects of vitamin D deficiency on cardiac function, more attention should be paid to healthy individuals with vitamin D deficiency.

Exploration of differential responses to FODMAPs and gluten in people with irritable bowel syndrome- a double-blind randomized cross-over challenge study

IntroductionThere is large variation in response to diet in irritable bowel syndrome (IBS) and determinants for differential response are poorly understood.ObjectivesOur aim was to investigate differential clinical and molecular responses to provocation with fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) and gluten in individuals with IBS.MethodsData were used from a crossover study with week-long interventions with either FODMAPs, gluten or placebo. The study also included a rapid provocation test. Molecular data consisted of fecal microbiota, short chain fatty acids, and untargeted plasma metabolomics. IBS symptoms were evaluated with the IBS severity scoring system. IBS symptoms were modelled against molecular and baseline questionnaire data, using Random Forest (RF; regression and clustering), Parallel Factor Analysis (PARAFAC), and univariate methods.ResultsRegression and classification RF models were in general of low predictive power (Q2 ≤ 0.22, classification rate < 0.73). Out of 864 clustering models, only 2 had significant associations to clusters (0.69 < CR < 0.73, p < 0.05), but with no associations to baseline clinical measures. Similarly, PARAFAC revealed no clear association between metabolome data and IBS symptoms.ConclusionDifferential IBS responses to FODMAPs or gluten exposures could not be explained from clinical and molecular data despite extensive exploration with different data analytical approaches. The trial is registered at www.clinicaltrials.gov as NCT03653689 31/08/2018.

Factors Associated with Transition to Serious Mental Illness.

There is increasing interest in early intervention and detection strategies for youth at-risk of developing a serious mental illness (SMI). Little is known about early factors that may be related to the later development of a SMI; thus, the aim of this study was to determine what clinical factors might relate to the development of in this study psychosis, bipolar disorder and severe or recurrent major depression in at-risk youth. The sample consisted of 162 youth aged 12-26 years at different stages of risk. Thirty-one participants developed a SMI during the study. Those who made a transition were compared on a range of baseline clinical and functional measures with those who did not make the transition. A Cox regression model was used to assess the association between measures and later development of a SMI. Female sex, attenuated psychotic symptoms as assessed with the Scale of Psychosis-Risk Symptoms (SOPS) and ratings on the K-10 Distress Scale, were found to be significantly associated with the later transition to mental illness. Females were 2.77 times more likely to transition compared to males. For the SOPS and K-10 scales, there is a 14% increase in the transition rate relative to a one-scale increase in SOPS and a 7% increase in the transition rate relative to a one-point increase in the K-10. Results from these longitudinal data provide further insight into the specific clinical measures that may be pertinent in early detection of mental illnesses.

Cognitive inflexibility and immunome biomarkers in children with autism spectrum disorder

Cognitive inflexibility is a transdiagnostic endophenotype that presents across a range of disorders, including autism spectrum disorder (ASD), which is maintained through adulthood, and encompasses both cognitive and behavioral rigidity. There is evidence for immune dysfunction in a subgroup of ASD, including systemic inflammation, cytokine dysregulation and anti-brain autoantibodies. Although immunome pathways are involved in ASD pathophysiology, there is little known about how they relate to symptom domains or symptom severity, and whether such biomarkers may be useful in optimizing future clinical trials. We correlated baseline clinical measures of cognitive inflexibility and resultant irritability with immunome biomarker levels in children with ASD, aged 5–18 years with ABC-I scores ≥18, CGI-S scores ≥4 and SRS-2 scores ≥66T, at Albert Einstein College of Medicine (AECOM). Non-parametric Spearman correlations and estimated multivariable regression analyses adjusting for potential confounders, including other clinical variables, race, sex, and age were completed. Strong positive correlations (rs > .70) were found between the Montefiore Einstein Rigidity Scale – Revised (MERS-R) Total Score and the pro-inflammatory cytokines IL-6 (rs=.80), granulocyte-colony stimulating factor (GCSF; rs =.72), macrophage inflammatory protein-1 alpha (MIP-1a; rs =.71). The MERS-R subscales also had moderate and strong correlations with the immunome biomarkers. The MERS-R Total Rigidity Subscale Score had a strong positive relationship with IL-6 (rs = 0.7856). Using multivariable regression analyses significant relationships were found between the MERS-R Total Rigidity Subscale Score and proinflammatory cytokine IL-18 (p = 0.02), and a nonsignificant trend was found between it and IFN-alpha2 (β = −4.982, p = 0.058). The ABC-I was significantly correlated with pro-inflammatory cytokine IL-18 (p = .013), IFN-alpha2 (p = 0.039), the anti-inflammatory cytokine IL-10 (p = 0.02), and adaptive immunity cytokine IL-2 (p = 0.041). This preliminary data is the first to examine the relationship of clinical measures of cognitive inflexibility and immunome biomarkers in children with ASD, and may provide a framework for better understanding the relationship between immunome mechanisms, cognitive inflexibility, and ASD symptomatology. Clinicaltrials.gov: NCT03202303.

Abstract C013: Importance of statistical considerations in multi-center, transatlantic cancer disparity studies: Lessons learned from the CaPTC prostate cancer familial cohort study

Abstract The CaPTC prostate cancer (CaP) Familial Cohort study (CaPFCS) was launched in 2017 to explore the CaP risk factors of African Black men (ABM). The study design is a prospective study that observes and follows healthy ABM and ABM diagnosed with CaP. Aim: The specific aim is to provide recommendations on statistical considerations for cohort studies focused on cancer disparities, based on lessons learned from the CaPTC CaPFCS. Methodology: Study participants were ABM in Cameroon, Nigeria, and the US. Using validated measures, data were collected mostly by self-administered or research assistant administered survey using paper survey (especially in Cameroon and Nigeria) with the responses transferred to REDCap by research coordinators. The statistical analysis for the CaPTC CaPFCS focused on the baseline epidemiological, behavioral, clinical and anthropometric measures of Black men. A total of 819 participants were included in the analyses. Statistical analyses included descriptive statistics (sample median, range, frequency and percentages) and unadjusted logistic regression models. Results: Data collection for the CaPTC CaPFCS were by multiple investigators/research coordinators at multiple sites in Cameroon, Nigeria, and the US. In preparation for the data analyses, we noted data entry errors and/or misinterpretation of data entry, which required extensive cleaning of the database prior to the analyses. The biostatisticians spent significant effort cleaning and ensuring data validity prior to the analyses. Confounding variables is another statistical consideration for cohort studies, such as the CaPTC CaPFCS. There was variability observed across age, education levels, employment status, household income and CaP diagnosis based on country of residence. CaP diagnosis was not reported by any of the ABM in the US, which may be due to the fact that they were all recruited within the community and no recruitment took place in the clinic. Finally, the CaPTC CaPFCS has several variables. Performing a lot of statistical tests may result in false-positive findings at P&amp;lt;0.05.Conclusion: The advantage of the CaPFCS is that it allows the CaPTC investigators to study epidemiological, behavioral, clinical and anthropometric variables associated with CaP over time. Being a longitudinal cohort study, investigators can track the changes in exposure and outcomes over time.However, statistical considerations need to be at the fore-front of multi-center, transatlantic cancer disparity studies such as the CaPTC CaPFCS, from data collection to data entry. The use of web-based survey with the ability to enter data directly into REDCaP will significantly reduce (if not totally eliminate) the need for database cleaning. There are multiple strategies that can be used to reduce confounder effect, including statistical adjustment and multivariate analysis to adjust for the confounders. The use of propensity score methods have especially been found to be effective in controlling baseline confounding factors. Citation Format: Daniel Lee, CaPTC Investigators, Jennifer Crook, Ruth Enuka, Fathi Parisa, Emeka Iweala Iweala, Oluwole Kukoyi, Ernest Kaninjing, Oluwaseyi Toye, Paul Jibrin, Folakemi Odedina. Importance of statistical considerations in multi-center, transatlantic cancer disparity studies: Lessons learned from the CaPTC prostate cancer familial cohort study [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C013.

Adult Cervical Deformity Patients Have Higher Baseline Frailty, Disability, and Comorbidities Compared With Complex Adult Thoracolumbar Deformity Patients: A Comparative Cohort Study of 616 Patients.

Multicenter comparative cohort. Studies have shown markedly higher rates of complications and all-cause mortality following surgery for adult cervical deformity (ACD) compared with adult thoracolumbar deformity (ATLD), though the reasons for these differences remain unclear. Our objectives were to compare baseline frailty, disability, and comorbidities between ACD and complex ATLD patients undergoing surgery. Two multicenter prospective adult spinal deformity registries were queried, one ATLD and one ACD. Baseline clinical and frailty measures were compared between the cohorts. 616 patients were identified (107 ACD and 509 ATLD). These groups had similar mean age (64.6 vs 60.8years, respectively, P = .07). ACD patients were less likely to be women (51.9% vs 69.5%, P < .001) and had greater Charlson Comorbidity Index (1.5 vs .9, P < .001) and ASA grade (2.7 vs 2.4, P < .001). ACD patients had worse VR-12 Physical Component Score (PCS, 25.7 vs 29.9, P < .001) and PROMIS Physical Function Score (33.3 vs 35.3, P = .031). All frailty measures were significantly worse for ACD patients, including hand dynamometer (44.6 vs 55.6 lbs, P < .001), CSHA Clinical Frailty Score (CFS, 4.0 vs 3.2, P < .001), and Edmonton Frailty Scale (EFS, 5.15 vs 3.21, P < .001). Greater proportions of ACD patients were frail (22.9% vs 5.7%) or vulnerable (15.6% vs 10.9%) based on EFS (P < .001). Compared with ATLD patients, ACD patients had worse baseline characteristics on all measures assessed (comorbidities/disability/frailty). These differences may help account for greater risk of complications and all-cause mortality previously observed in ACD patients and facilitate strategies for better preoperative optimization.

Rates of diabetic retinopathy among cluster analysis—identified type 2 diabetic mellitus subgroups

PurposeTo determine whether phenotypic clustering of patients with diabetes mellitus (DM) is associated with more advanced diabetic retinopathy (DR).MethodsRetrospective cohort study of 495 patients with no prior DR treatment seen at a tertiary care clinic 2014–2020. Four previously identified clusters from Ahlqvist’s 2018 paper were reproduced utilizing baseline hemoglobin A1c, body mass index, and age at DM diagnosis. Age-adjusted Cox proportional hazard ratios were used to compare clusters with reference as the lowest risk cluster.ResultsAll four type 2 DM clusters were replicated with our cohort. There was a significant difference in racial distribution among clusters (p = 0.018) with severe insulin-resistant diabetes (SIRD) having the higher percentage of Caucasians and lower percentage of Hispanics compared to other groups and a higher percentage of African Americans comprising the severe insulin-deficient diabetes (SIDD) cluster than other groups. Rates of proliferative diabetic retinopathy were higher in mild obesity-related diabetes (MOD) (28%), SIDD (24%), mild age-related diabetes (MARD) (20%), and lowest in SIRD (7.9%), overall p = 0.004. Rates of vitreous hemorrhage were higher in MOD (p = 0.032) and MARD (0.005) compared to SIRD.ConclusionBaseline clinical measures may be useful in risk stratifying patients for progression to retinopathy requiring intervention.

Identification of characteristics predictive of long-term survival with durvalumab or durvalumab plus tremelimumab in metastatic urothelial carcinoma

BackgroundThis retrospective analysis of data from clinical trials in metastatic urothelial carcinoma (mUC) was conducted to determine baseline patient characteristics associated with long-term survival (LTS) following treatment with immune checkpoint inhibitors.MethodsData for this analysis were from patients with platinum-refractory mUC who received durvalumab or durvalumab plus tremelimumab in phase 1/2 studies. The primary outcome measure was LTS. Patients were categorised as overall survival (OS) ≥ 2 years (from first dose) or OS < 2 years. A univariable analysis assessed independent associations with LTS and multivariable logistic regression was employed including each variable with P ≤ 0.05 as covariates.ResultsAmong 360 patients, 88 (24.4%) had OS ≥ 2 years and 272 (75.6%) had OS < 2 years. In univariable analysis, several baseline characteristics and laboratory measurements were associated with LTS including sex, ECOG PS, PD-L1 expression, prior surgery, time from initial diagnosis, lymph node-only involvement, visceral disease, haemoglobin level, absolute neutrophil count, neutrophil–lymphocyte ratio and lactate dehydrogenase level. In multivariable analysis, LTS was significantly associated with ECOG PS, PD-L1 expression, haemoglobin level and absolute neutrophil count.ConclusionsSeveral baseline clinical characteristics and laboratory measurements were associated with LTS for patients with platinum-refractory mUC treated with durvalumab or durvalumab plus tremelimumab.

Pre- and post-vaccination characteristics and risk factors for COVID-19 outcomes in a Swedish population-based cohort of COPD patients.

Evidence on risk factors for Coronavirus disease 2019 (COVID-19) outcomes among patients with COPD in relation to COVID-19 vaccination remains limited. The objectives of the present study were to characterise determinants of COVID-19 infection, hospitalisation, intensive care unit (ICU) admission and death in COPD patients in their unvaccinated state compared to when vaccinated. We included all COPD patients in the Swedish National Airway Register (SNAR). Events of COVID-19 infection (test and/or healthcare encounter), hospitalisation, ICU admission and death were identified from 1 January 2020 to 30 November 2021. Using adjusted Cox regression, associations between baseline sociodemographics, comorbidities, treatments, clinical measurements and COVID-19 outcomes, during unvaccinated and vaccinated follow-up time, were analysed. The population-based COPD cohort included 87 472 patients, among whom 6771 (7.7%) COVID-19 infections, 2897 (3.3%) hospitalisations, 233 (0.3%) ICU admissions and 882 (1.0%) COVID-19 deaths occurred. During unvaccinated follow-up, risk of COVID-19 hospitalisation and death increased with age, male sex, lower education, non-married status and being foreign-born. Comorbidities increased risk of several outcomes, e.g. respiratory failure for infection and hospitalisation (adjusted hazard ratios (HR) 1.78, 95% CI 1.58-2.02 and 2.51, 2.16-2.91, respectively), obesity for ICU admission (3.52, 2.29-5.40) and cardiovascular disease for mortality (2.80, 2.16-3.64). Inhaled COPD therapy was associated with infection, hospitalisation and death. COPD severity was also associated with COVID-19, especially hospitalisation and death. Although the risk factor panorama was similar, COVID-19 vaccination attenuated HRs for some risk factors. This study provides population-based evidence on predictive risk factors for COVID-19 outcomes and highlights the positive implications of COVID-19 vaccination for COPD patients.

MP-453089-1 DIGOXIN AND RISK OF VENTRICULAR TACHYARRHYTHMIA AND DEATH IN ICD RECIPIENTS

Digoxin continues to be used in patients with heart failure with reduced ejection fraction (HFrEF), especially among those with atrial fibrillation (AF) with difficult to control ventricular response. However, some studies have shown digoxin use to be associated with adverse outcomes including increased mortality. There are limited data on whether digoxin use is associated with increased risk of ventricular tachycardia/ventricular fibrillation (VT/VF) in implantable cardioverter defibrillator (ICD) recipients. We sought to assess whether digoxin use would be associated with increased risk of VT/VF in patients with HFrEF who were implanted with a primary prevention ICD in landmark clinical trials. Our study cohort consisted of patients with an ICD or cardiac resynchronization therapy-defibrillator (CRT-D) who were enrolled in the four landmark MADIT trials. Propensity score for digoxin at baseline was developed using a wide variety of baseline clinical measures with a logistic regression model stepwise variable selection approach. All potential variables which met a significance level <0.10 were included in the propensity score model. Additionally, a multivariate proportional hazards regression model was developed for the endpoint of VT/VF. This multivariate model was used along with propensity score quintile stratification for the endpoints of VT/VF, death and VT/VF/death. At baseline, 1155 of 4499 patients were on digoxin (26%). Propensity score variables are shown in Table 1. From statistical models using both multivariate adjustment and propensity score quintile stratification, patients prescribed digoxin exhibited a statistically significant 28% increased risk of VT/VF [HR 1.28 (1.10-1.50); p=0.002; Figure 1A], 38% increased risk of the composite of VT/VF or death [HR 1.38 (1.21-1.58); p<0.0001; Figure 1B]; and a 64% increased risk of death [HR 1.64; (1.32-2.04); p<0.0001]. Our findings suggest that digoxin use is associated with a significant increased risk of ventricular tachyarrhythmic events and death among ICD recipients. This adds to the growing evidence that digoxin use is associated with adverse outcomes in certain groups of patients and suggest a need for reconsideration on use of digoxin in HFrEF patients with an ICD.

Associations of striatal dopamine transporter binding with motor and non-motor symptoms in early Parkinson's disease.

Dopamine transporter (DAT) imaging is an in vivo tool to assess presynaptic dopaminergic function in the clinical practices of Parkinson's disease (PD). Current clinical practices focused on qualitatively visual interpretation of DAT imaging, whereas quantitative analyses are potentially more helpful when monitoring the progression of PD. Previous cross-sectional studies indicated certain motor and non-motor features were associated with striatal DAT binding, whereas limited data were reported in terms of the longitudinal correlation between clinical features of PD with striatal DAT binding. The purpose of our study is to clarify current and longitudinal correlations between striatal DAT binding and clinical measures. A total of 352 untreated PD individuals and 167 healthy controls with complete baseline clinical measures and neuroimaging data were identified from the Parkinson's Progression and Markers Initiative (PPMI) database. Patients with PD underwent DAT imaging at the screening visit and following months 12, 24, and 48. Multiple linear regression models and linear mixed-effect models were respectively conducted to investigate the cross-sectional and longitudinal correlation between clinical characteristics and DAT binding. Associations between changes in clinical characteristics and changes in DAT binding were further evaluated and the Spearman rank correlation coefficients were reported. In the cross-sectional analysis, baseline striatal DAT binding was significantly associated with the Hoehn and Yahr scale, the Movement Disorder Society-Sponsored Revision of the Unified Parkinson Disease Rating Scale (MDS-UPDRS) scores, the rigidity scores, and the axial scores in PD individuals (false discovery rate [FDR]-adjusted p=0.0017 for all above). Patients who developed freezing of gait had lower striatal DAT binding (FDR-adjusted p=0.0161). Healthy controls who had higher tremor scores and suffered more severe olfactory dysfunction had lower striatal DAT binding (FDR-adjusted p=0.0257 for all above). Longitudinal analysis indicated that baseline severity of rapid-eye-movement sleep behavior disorder was significantly associated with longitudinal striatal DAT binding in patients with PD (FDR-adjusted p=0.0120). Furthermore, changes in MDS-UPDRS scores and the State-Trait Anxiety Inventory (STAI) scores demonstrated significant correlations with changes in striatal DAT binding over 4 years (p=0.005 and p=0.032, respectively). Our findings clarified quantitative associations between certain motor and non-motor features with current and future striatal dopamine binding, suggesting the feasibility of using DAT images as a progression predictive marker for PD. Further studies are needed to investigate correlations between different regional dopamine binding with specific clinical features.