Distinct Patient Profiles Research Articles

Deciphering Popliteal Artery Aneurysm Patient Diversity: Insights From a Cluster Analysis of the POPART Registry.

Popliteal artery aneurysms (PAAs) are the most common peripheral aneurysm. However, due to its rarity, the cumulative body of evidence regarding patient patterns, treatment strategies, and perioperative outcomes is limited. This analysis aims to investigate distinct phenotypical patient profiles and associated treatment and outcomes in patients with a PAA by performing an unsupervised clustering analysis of the POPART (Practice of Popliteal Artery Aneurysm Repair and Therapy) registry. A cluster analysis (using k-means clustering) was performed on data obtained from the multicenter POPART registry (42 centers from Germany and Luxembourg). Sensitivity analyses were conducted to explore validity and stability. Using 2 clusters, patients were primarily separated by the absence or presence of clinical symptoms. Within the cluster of symptomatic patients, the main difference between patients with acute limb ischemia presentation and nonemergency symptomatic patients was PAA diameter. When using 6 clusters, patients were primarily grouped by comorbidities, with patients with acute limb ischemia forming a separate cluster. Despite markedly different risk profiles, perioperative complication rates appeared to be positively associated with the proportion of emergency patients. However, clusters with a higher proportion of patients having any symptoms before treatment experienced a lower rate of perioperative complications. The conducted analyses revealed both an insight to the public health reality of PAA care as well as patients with PAA at elevated risk for adverse outcomes. This analysis suggests that the preoperative clinic is a far more crucial adjunct to the patient's preoperative risk assessment than the patient's epidemiological profile by itself.

Current developments in small cell lung cancer

Small cell lung cancer (SCLC), often associated with smoking, is characterized by its aggressive biology and potential for early metastasis. It accounts for approximately 15% of all lung cancer patients. The combination of platinum-based chemotherapy and etoposide has been used for many years in the treatment of SCLC. The prognosis for patients with SCLC who are treated as a single group is still quite poor. Recent research has provided a new perspective on the biology of SCLC. A survival benefit has been demonstrated by adding immune checkpoint inhibitors to chemotherapy in patients with extensive stage SCLC. The study of the molecular, biological, and immunological properties of the heterogeneous structure of SCLC is a promising area of research for the future. Identification of distinct gene expression profiles (ASCL1, NEUROD1, POU2F3, and YAP1) of SCLC patients may form the basis of the most effective and individualized therapeutic treatments in disease management. More research is needed to identify SCLC subtypes and develop effective treatments for this group of patients who have a poor prognosis.

Investigating oral somatosensory perception and oral symptoms of head and neck cancer patients: insights on eating behaviour.

Sensory alterations and oral manifestations are prevalent among head and neck cancer (HNC) patients. While taste and smell alterations have been thoroughly investigated, studies on their oral somatosensory perception remain limited. Building upon our previous publication that primarily focused on objective somatosensory measurements, the present work examined self-reported sensory perception, including somatosensation and oral symptoms, in HNC patients and evaluated their link with eating behaviour. A cross-sectional study was conducted using self-reported questionnaires on sensory perception, oral symptoms, sensory-related food preference, and eating behaviour among HNC patients (n = 30). Hierarchical clustering analysis was performed to categorise patients based on their sensory perception. Correlations between oral symptoms score, sensory perception, sensory-related food preference, and eating behaviour were explored. Two distinct sensory profiles of patients were identified: no alteration (n = 14) and alteration (n = 16) group. The alteration group showed decreased preference towards several sensory modalities, especially the somatosensory. Concerning eating behaviour, more patients in the alteration group agreed to negatively connotated statements (e.g. having food aversion and eating smaller portions), demonstrating greater eating difficulties. In addition, several oral symptoms related to salivary dysfunction were reported. These oral symptoms were correlated with sensory perception, sensory-related food preference, and eating behaviour. This study presented evidence demonstrating that sensory alterations in HNC patients are not limited to taste and smell but cover somatosensory perception and are linked to various aspects of eating. Moreover, patients reported experiencing several oral symptoms. Those with sensory alterations and oral symptoms experienced more eating difficulties.

Routine biomarker profile for the prediction of clinical phenotypes of adult-onset Still's disease using unsupervised clustering algorithm.

This study addresses the challenge of predicting the course of Adult-onset Still's disease (AoSD), a rare systemic autoinflammatory disorder of unknown origin. Precise prediction is crucial for effective clinical management, especially in the absence of specific laboratory indicators. We assessed the effectiveness of combining traditional biomarkers with the k-medoids unsupervised clustering algorithm in forecasting the various clinical courses of AoSD-monocyclic, polycyclic, or chronic articular. This approach represents an innovative strategy in predicting the disease's course. The analysis led to the identification of distinct patient profiles based on accessible biomarkers. Specifically, patients with elevated ferritin levels at diagnosis were more likely to experience a monocyclic disease course, while those with lower erythrocyte sedimentation rate could present with any of the clinical courses, monocyclic, polycyclic, or chronic articular, during follow-up. The study demonstrates the potential of integrating traditional biomarkers with unsupervised clustering algorithms in understanding the heterogeneity of AoSD. These findings suggest new avenues for developing personalized treatment strategies, though further validation in larger, prospective studies is necessary.

Toward Individual Treatment in Cervical Artery Dissection: Subgroup Analysis of the TREAT-CAD Randomized Trial.

Uncertainty remains regarding antithrombotic treatment in cervical artery dissection. This analysis aimed to explore whether certain patient profiles influence the effects of different types of antithrombotic treatment. This was a post hoc exploratory analysis based on the per-protocol dataset from TREAT-CAD (NCT02046460), a randomized controlled trial comparing aspirin to anticoagulation in patients with cervical artery dissection. We explored the potential effects of distinct patient profiles on outcomes in participants treated with either aspirin or anticoagulation. Profiles included (1) presenting with ischemia (no/yes), (2) occlusion of the dissected artery (no/yes), (3) early versus delayed treatment start (</>median), and (4) intracranial extension of the dissection (no/yes). Outcomes included clinical (stroke, major hemorrhage, death) and magnetic resonance imaging outcomes (new ischemic or hemorrhagic brain lesions) and were assessed for each subgroup in separate logistic models without adjustment for multiple testing. All 173 (100%) per-protocol participants were eligible for the analyses. Participants without occlusion had decreased odds of events when treated with anticoagulation (odds ratio [OR] = 0.28, 95% confidence interval [CI] = 0.07-0.86). This effect was more pronounced in participants presenting with cerebral ischemia (n = 118; OR = 0.16, 95% CI = 0.04-0.55). In the latter, those with early treatment (OR = 0.26, 95% CI = 0.07-0.85) or without intracranial extension of the dissection (OR = 0.34, 95% CI = 0.11-0.97) had decreased odds of events when treated with anticoagulation. Anticoagulation might be preferable in patients with cervical artery dissection presenting with ischemia and no occlusion or no intracranial extension of the dissection. These findings need confirmation. ANN NEUROL 2024;95:886-897.

Distinct Spectral Profiles of Awake Resting EEG in Disorders of Consciousness: The Role of Frequency and Topography of Oscillations.

The prolonged disorders of consciousness (PDOC) pose a challenge for an accurate clinical diagnosis, mainly due to patients' scarce or ambiguous behavioral responsiveness. Measurement of brain activity can support better diagnosis, independent of motor restrictions. Methods based on spectral analysis of resting-state EEG appear as a promising path, revealing specific changes within the internal brain dynamics in PDOC patients. In this study we used a robust method of resting-state EEG power spectrum parameter extraction to identify distinct spectral properties for different types of PDOC. Sixty patients and 37 healthy volunteers participated in this study. Patient group consisted of 22 unresponsive wakefulness patients, 25 minimally conscious patients and 13 patients emerging from the minimally conscious state. Ten minutes of resting EEG was acquired during wakefulness and transformed into individual power spectra. For each patient, using the spectral decomposition algorithm, we extracted maximum peak frequency within 1-14Hz range in the centro-parietal region, and the antero-posterior (AP) gradient of the maximal frequency peak. All patients were behaviorally diagnosed using coma recovery scale-revised (CRS-R). The maximal peak frequency in the 1-14Hz range successfully predicted both neurobehavioral capacity of patients as indicated by CRS-R total score and PDOC diagnosis. Additionally, in patients in whom only one peak within the 1-14Hz range was observed, the AP gradient significantly contributed to the accuracy of prediction. We have identified three distinct spectral profiles of patients, likely representing separate neurophysiological modes of thalamocortical functioning. Etiology did not have significant influence on the obtained results.

Serum and Urine Metabolomic Profiling of Newly Diagnosed Treatment-Naïve Inflammatory Bowel Disease Patients.

Inflammatory bowel disease (IBD) is a prevalent chronic noncurable disease associated with profound metabolic changes. The discovery of novel molecular indicators for unraveling IBD etiopathogenesis and the diagnosis and prognosis of IBD is therefore pivotal. We sought to determine the distinctive metabolic signatures from the different IBD subgroups before treatment initiation. Serum and urine samples from newly diagnosed treatment-naïve IBD patients and age and sex-matched healthy control (HC) individuals were investigated using proton nuclear magnetic resonance spectroscopy. Metabolic differences were identified based on univariate and multivariate statistical analyses. A total of 137 Crohn's disease patients, 202 ulcerative colitis patients, and 338 HC individuals were included. In the IBD cohort, several distinguishable metabolites were detected within each subgroup comparison. Most of the differences revealed alterations in energy and amino acid metabolism in IBD patients, with an increased demand of the body for energy mainly through the ketone bodies. As compared with HC individuals, differences in metabolites were more marked and numerous in Crohn's disease than in ulcerative colitis patients, and in serum than in urine. In addition, clustering analysis revealed 3 distinct patient profiles with notable differences among them based on the analysis of their clinical, anthropometric, and metabolomic variables. However, relevant phenotypical differences were not found among these 3 clusters. This study highlights the molecular alterations present within the different subgroups of newly diagnosed treatment-naïve IBD patients. The metabolomic profile of these patients may provide further understanding of pathogenic mechanisms of IBD subgroups. Serum metabotype seemed to be especially sensitive to the onset of IBD.

Prognosis-telling by the neurologist: Two distinct patient profiles in functional neurological disorders

Prognosis-telling by the neurologist: Two distinct patient profiles in functional neurological disorders

Resemblances and differences between osteoradionecrosis of the jaw and medication-related osteonecrosis of the jaw.

The aim of this retrospective study was to identify the clinical, radiological, and histological characteristics of patients diagnosed with osteonecrosis of the jaw (ONJ) and treated at the Oral and Maxillo-Facial Surgery Clinic of the Emergency Clinical County Hospital of Targu Mures between 2017 and 2022. The study aimed to analyze correlations between patient characteristics, particularly their history of bone modifying agent use or local radiotherapy during cancer treatment, in order to identify specific patient profiles that could aid in evaluating treatment response and guide individualized treatment strategies. Fifty-two patients diagnosed with ONJ were included in the study. The patients were divided into two groups based on their medical history: the bone modifying agent use group and the radiotherapy group. Clinical, radiological, and histological data were collected and analyzed. Statistical analysis, including p-values, was performed to compare patient characteristics between the two groups. Patients in the radiotherapy group were significantly older than those in the bone modifying agent use group (66 years vs. 56.9 years, p=0.001). There was a higher proportion of males in the radiotherapy group compared to the bone modifying agent use group (90% vs. 22%, p<0.001). Jaw involvement was more prevalent in the radiotherapy group compared to the bone modifying agent use group (95% vs. 66%, p=0.018). Histological analysis showed a similar frequency of Actinomyces species in both groups (50% vs. 34%, p=0.264). The findings of this study suggest the existence of two distinct patient profiles based on their treatment history (bone modifying agent use vs. radiotherapy) in ONJ. Patients in the radiotherapy group were older, predominantly male, and exhibited a higher prevalence of jaw involvement. Histological analysis revealed no significant differences in Actinomyces species frequency between the two groups. These distinct patient profiles may indicate different responses to treatment, emphasizing the need for individualized treatment strategies tailored to specific patient characteristics. Further research is warranted to validate these findings and develop personalized approaches for managing ONJ.

Label-free quantitative proteomics reveals aberrant expression levels of LRG, C9, FN, A1AT and AGP1 in the plasma of patients with colorectal cancer

BackgroundColorectal cancer (CRC) is one of the major causes of cancer-related death worldwide. Although commercial biomarkers of CRC are currently available, they are still lacking in terms of sensitivity and specificity; thus, searching for reliable blood-based biomarkers are important for the primary screening of CRC.MethodsPlasma samples of patients with non-metastatic (NM) and metastatic (M) CRC and healthy controls were fractionated using MARS-14 immunoaffinity chromatography. The flow-through and elute fractions representing low- and high-abundant proteins, respectively, were analyzed by label-free quantitative proteomics mass spectrometry. The functional analysis of the proteins with greater than 1.5-fold differential expression level between the CRC and the healthy control groups were analyzed for their biological processes and molecular functions. In addition, the levels of plasma proteins showing large alterations in CRC patients were confirmed by immunoblotting using two independent cohorts. Moreover, receiver operating characteristic (ROC) curve analysis was performed for individual and combinations of biomarker candidates so as to evaluate the diagnostic performance of biomarker candidates.ResultsFrom 163 refined identifications, five proteins were up-regulated and two proteins were down-regulated in NM-CRC while eight proteins were up-regulated and three proteins were down-regulated in M-CRC, respectively. Altered plasma proteins in NM-CRC were mainly involved in complement activation, while those in M-CRC were clustered in acute-phase response, complement activation, and inflammatory response. Results from the study- and validation-cohorts indicate that the levels of leucine-rich alpha-2-glycoprotein-1(LRG), complement component C9 (C9), alpha-1-acid glycoprotein 1 (AGP1), and alpha-1-antitrypsin (A1AT) were statistically increased, while fibronectin (FN) level was statistically decreased in CRC patients compared to healthy controls, with most alterations found in a metastatic stage-dependent manner. ROC analysis revealed that FN exhibited the best diagnostic performance to discriminate CRC patients and healthy controls while AGP1 showed the best discrimination between the disease stages in both cohorts. The combined biomarker candidates, FN + A1AT + AGP1, exhibited perfect discriminatory power to discriminate between the CRC population and healthy controls whereas LRG + A1AT + AGP1 was likely to be the best panel to discriminate the metastatic stages in both cohorts.ConclusionsThis study identified and quantified distinct plasma proteome profiles of CRC patients. Selected CRC biomarker candidates including FN, LRG, C9, A1AT, and AGP1 may be further applied for screening larger cohorts including disease groups from other types of cancer or other diseases.

Exploring the intersectionality of characteristics among those who experienced opioid overdoses: A cluster analysis.

As Canada continues to experience an opioid crisis, it is important to understand the intersection between the demographic, socioeconomic and service use characteristics of those experiencing opioid overdoses to better inform prevention and treatment programs. The Statistics Canada British Columbia Opioid Overdose Analytical File (BCOOAF) represents people's opioid overdoses between January 2014 and December 2016 (n = 13,318). The BCOOAF contains administrative health data from British Columbia linked to Statistics Canada data, including on health, employment, social assistance and police contacts. Cluster analysis was conducted using the k-prototypes algorithm. The results revealed a six-cluster solution, composed of three groups (A, B and C), each with two distinct clusters (1 and 2). Individuals in Group A were predominantly male, used non-opioid prescription medications and had varying levels of employment. Individuals in Cluster A1 were employed, worked mostly in construction, had high incomes and had a high rate of fatal overdoses, while individuals in Cluster A2 were precariously employed and had varying levels of income. Individuals in Group B were predominantly female; were mostly taking prescription opioids, with about one quarter or less receiving opioid agonist treatment (OAT); mostly had precarious to no employment; and had low to no income. People in Cluster B1 were primarily middle-aged (45 to 65 years) and on social assistance, while people in Cluster B2 were older, more frequently used health services and had no social assistance income. Individuals in Group C were primarily younger males aged 24 to 44 years, with higher prevalence of having experienced multiple overdoses, were medium to high users of health care services, were mostly unemployed and were recipients of social assistance. Most had multiple contacts with police. Those in Cluster C1 predominantly had no documented use of prescription opioid medications, and all had no documented OAT, while all individuals in Cluster C2 were on OAT. The application of machine learning techniques to a multidimensional database enables an intersectional approach to study those experiencing opioid overdoses. The results revealed distinct patient profiles that can be used to better target interventions and treatment.

The Usefulness of Pre-Operative Extra-Cranial Imaging in Radiologically Suspicious Glioblastoma Multiforme in the West of Scotland: and a Proposal of an Imaging Diagnostic Pathway

Abstract AIMS Objective: a CT chest, abdomen and pelvis (CT CAP) is probably unnecessary if a glioblastoma multiforme (GBM) is detected on initial CT brain (CTB) prior to definitive MRI. We audited its frequency to develop a management pathway METHOD Methods: 12-month retrospective case series from 2018 of patients having an initial CTB suspicious for GBM. We dichotomised patients into two groups a) tissue proven and b) non-tissue proven, due to these representing distinct patient profiles. We quantified frequencies of plain and contrast CTBs, CT CAPs and extra-cranial malignancy. RESULTS Results: Group 1 (total n=84 [mean age 59 years]): 64% had a CT CAP. Plain CTB occurred in 24% and contrast CTB in 76%. Extra-cranial malignancy was 8% and 12%. Group 2 (total n=47 [mean age 73 years]): 85% had a CT CAP. Plain CTB occurred in 22% and contrast CTB in 78%. Extra-cranial malignancy was 33% and 23%. Negative CT CAPs in ~88% of CTBs in Group 1 and ~75% of CTBs in Group 2. CONCLUSION Conclusions: patients having a contrast CTB as their initial imaging modality, being suggestive of GBM, prior to definitive MRI, and managed surgically, having no history of extra-cranial malignancy, do not need a CT CAP unless MRI is non-diagnostic.

OS09.4.A Cognitive functioning of patients with diffuse glioma during stable disease

Abstract Background Glioma patients often experience cognitive problems, which are associated with decreased functional independence and health-related quality of life. However, the prevalence and nature of cognitive impairment in these patients is relatively underreported, particularly during stable disease. In this study we determine the prevalence of cognitive deficits and explore distinct cognitive profiles of patients with diffuse glioma at least two months after tumor treatment. Material and Methods A total of 112 patients (mean age: 43 years) without clinical or radiological progression with a grade II-IV glioma were included in this observational cohort study. Cognitive functioning was assessed in five cognitive domains (attention, information processing speed, verbal memory, working memory, and executive functioning). Cognitive impairment was defined as a z-score of 1.5 SD below that of healthy controls. Hierarchical cluster analysis was used to examine cognitive profiles. Results In total, 46 patients (41%) had cognitive impairment. More than one domain was impaired in 25 of these patients (54%). The domains were affected in decreasing order of frequency: working memory in 31%, information processing speed in 22%, attention in 19%, verbal memory in 12%, and executive functioning in 11% of the patients. A clustered heatmap revealed three prominent cognitive clusters with an increasing number of cognitive domains impaired. The first cluster displayed patients with only working memory deficits, patients in the second cluster also had deficits in information processing speed, and the last cluster showed patients with impairments across all domains. Conclusion Cognitive impairment is highly prevalent in patients with diffuse glioma during stable disease. Working memory and information processing speed are most frequently affected. Importantly, our analyses show evidence for three subgroups in cognitively impaired glioma patients. Working memory seems an important driver in cognitive impairment given the involvement in all subgroups.

Comorbidity profiles of patients experiencing homelessness: A latent class analysis.

Individuals experiencing homelessness are known to have increased rates of healthcare utilization when compared to the average patient population, often attributed to their complex health care needs and under or untreated comorbid conditions. With increasing focus on hospital readmissions among acute care settings, a better understanding of these comorbidity patterns and their impacts on acute care utilization could help improve quality of care. This study aims to identify distinct comorbidity profiles of homeless patients, and to explore the correlates of the identified comorbidity profiles and their impact on hospital readmission. This is a retrospective analysis using electronic health records (EHR) of patients experiencing homelessness encountered in the hospitals of ChristianaCare from 2015 to 2019 (N = 3445). Latent class analysis (LCA) was used to identify the comorbidity profiles of homeless patients. The mean age of the study population was 44-year, and the majority were male (63%). The most prevalent comorbid conditions were tobacco use (77%), followed by depression (58%), drug use disorder (56%), anxiety disorder (50%), hypertension (44%), and alcohol use disorder (43%). The LCA model identified 4 comorbidity classes—“relatively healthy” class with 31% of the patients, “medically-comorbid with SUD” class with 15% of the patients, “substance use disorder (SUD)” class with 39%, and “Medically comorbid” class with 15% of the patients. The Kaplan-Meir curves of probability of readmission against time from the index visits were significantly different for the four classes (p<0.001). The multivariable Cox proportional hazard model adjusted for age, sex, race, ethnicity, and insurance type showed that the hazard for readmission among patients in medically comorbid with SUD class is 3.16 (CI: 2.72, 3.67) times higher than the patients in the relatively healthy class.

Latent Profile/Class Analysis Identifying Differentiated Intervention Effects.

The randomized clinical trial is generally considered the most rigorous study design for evaluating overall intervention effects. Because of patient heterogeneity, subgroup analysis is often used to identify differential intervention effects. In research of behavioral interventions, such subgroups often depend on a latent construct measured by multiple correlated observed variables. The purpose of this article was to illustrate latent class analysis/latent profile analysis as a helpful tool to characterize latent subgroups, conduct exploratory subgroup analysis, and identify potential differential intervention effects using clinical trial data. After reviewing different approaches for subgroup analysis, latent class analysis/latent profile analysis was chosen to identify heterogeneous patient groups based on multiple correlated variables. This approach is superior in this specific scenario because of its ability to control Type I error, assess intersection of multiple moderators, and improve interpretability. We used a case study example to illustrate the process of identifying latent classes as potential moderators based on both clinical and perceived risk scores and then tested the differential effects of health coaching in improving health behavior for patients with elevated risk of developing coronary heart disease. We identified three classes based on one clinical risk score and four perceived risk measures for individuals with high risk of developing coronary heart disease. Compared to other classes we assessed, individuals in the class with low clinical risk and low perceived risk benefit most from health coaching to improve their physical activity levels. Latent class analysis/latent profile analysis offers a person-centered approach to identifying distinct patient profiles that can be used as moderators for subgroup analysis. This offers tremendous opportunity to identify differential intervention effects in behavioral research.

Differences in the Biomarker Profile of De Novo Acute Heart Failure versus Decompensation of Chronic Heart Failure.

The perception of acute heart failure (AHF) as a single entity is increasingly outdated, as distinct patient profiles can be discerned. Key heart failure (HF) studies have previously highlighted the difference in both the course and prognosis of de novo AHF and acute decompensated chronic HF (ADHF). Accordingly, distinct AHF profiles with differing underlying pathophysiologies of disease progression can be shown. We compared a range of selected biomarkers in order to better describe the profile of de novo AHF and ADHF, including the inter alia—serum lactate, bilirubin, matrix metallopeptidase 9 (MMP-9), follistatin, intercellular adhesion molecule 1 (ICAM-1), lipocalin and galectin-3. The study comprised 248 AHF patients (de novo = 104), who were followed up for one year. The biomarker data of the de novo AHF and ADHF profiles was then compared in order to link biomarkers to their prognosis. Our study demonstrated that, although there are similarities between each patient profile, key biomarker differences do exist—predominantly in terms of NTproBNP, serum lactate, bilirubin, ICAM-1, follistatin, ferritin and sTfR (soluble transferrin receptor). ADHF tended to have compromised organ function and higher risks of both one-year mortality and composite endpoint (one-year mortality or rehospitalization for heart failure) hazard ratios (HR) (95% CI): 3.4 (1.8–6.3) and 2.8 (1.6–4.6), respectively, both p < 0.0001. Among the biomarkers of interest: sTfR HR (95% CI): 1.4 (1.04–1.8), NGAL(log) (neutrophil gelatinase-associated lipocalin) HR (95% CI): 2.0 (1.3–3.1) and GDF-15(log) (growth/differentiation factor-15) HR (95% CI): 4.0 (1.2–13.0) significantly impacted the one-year survival, all p < 0.05.

Distinct clinical and immunological profiles of patients with evidence of SARS-CoV-2 infection in sub-Saharan Africa

Although the COVID-19 pandemic has left no country untouched there has been limited research to understand clinical and immunological responses in African populations. Here we characterise patients hospitalised with suspected (PCR-negative/IgG-positive) or confirmed (PCR-positive) COVID-19, and healthy community controls (PCR-negative/IgG-negative). PCR-positive COVID-19 participants were more likely to receive dexamethasone and a beta-lactam antibiotic, and survive to hospital discharge than PCR-negative/IgG-positive and PCR-negative/IgG-negative participants. PCR-negative/IgG-positive participants exhibited a nasal and systemic cytokine signature analogous to PCR-positive COVID-19 participants, predominated by chemokines and neutrophils and distinct from PCR-negative/IgG-negative participants. PCR-negative/IgG-positive participants had increased propensity for Staphylococcus aureus and Streptococcus pneumoniae colonisation. PCR-negative/IgG-positive individuals with high COVID-19 clinical suspicion had inflammatory profiles analogous to PCR-confirmed disease and potentially represent a target population for COVID-19 treatment strategies.

Identifying Clusters of Adherence to Cardiovascular Risk Reduction Behaviors and Persistence with Medication in New Lipid-Lowering Drug Users. Impact on Healthcare Utilization.

We sought to identify specific profiles of new lipid-lowering drug users based on adherence to a healthy lifestyle and persistence with medication, and to characterize co-morbidities, co-treatments, and healthcare utilization for each of the profiles identified. Observational study in 517 participants in the Aragon Workers’ Health Study (AWHS) without previous cardiovascular disease (CVD) and who initiated lipid-lowering therapy. Data were collected from workplace medical examinations and administrative health databases (2010–2018). Using cluster analysis, we identified distinct patient profiles based on persistence with therapy and lifestyle. We then compared characteristics, morbidity, and healthcare utilization across clusters. Participants were aggregated into four clusters based on persistence with therapy, smoking status, adherence to Mediterranean diet, and physical activity. In cluster 1 (n = 113), comprising those with a healthiest lifestyle (14.2% smokers, 84.0% with medium-high adherence to Mediterranean diet, high physical activity), 16.8% were persistent. In cluster 3 (n = 108), comprising patients with the least healthy lifestyle (100% smokers, poor adherence to the Mediterranean diet, low level of physical activity), all were non-persistent. Clusters 2 (n = 150) and 4 (n = 146) both comprised patients with intermediate lifestyle behaviors, but differed in terms of persistence (100 and 0%, respectively). Compared with other clusters, the burden of morbidity, cardiovascular score, and healthcare utilization were lower in cluster 1. The healthy adherer effect was only observed in new lipid-lowering drug users of certain profiles. Furthermore, we found that differences in adherence to lifestyle and medication recommendations for CVD prevention influenced morbidity burden and healthcare utilization.

Dissection of the Pre-Germinal Center B-Cell Maturation Pathway in Common Variable Immunodeficiency Based on Standardized Flow Cytometric EuroFlow Tools.

IntroductionCommon Variable Immunodeficiency (CVID) is characterized by defective antibody production and hypogammaglobulinemia. Flow cytometry immunophenotyping of blood lymphocytes has become of great relevance for the diagnosis and classification of CVID, due to an impaired differentiation of mature post-germinal-center (GC) class-switched memory B-cells (MBC) and severely decreased plasmablast/plasma cell (Pb) counts. Here, we investigated in detail the pre-GC B-cell maturation compartment in blood of CVID patients.MethodsIn this collaborative multicentric study the EuroFlow PID 8-color Pre-GC B-cell tube, standardized sample preparation procedures (SOPs) and innovative data analysis tools, were used to characterize the maturation profile of pre-GC B-cells in 100 CVID patients, vs 62 age-matched healthy donors (HD).ResultsThe Pre-GC B-cell tube allowed identification within pre-GC B-cells of three subsets of maturation associated immature B-cells and three subpopulations of mature naïve B-lymphocytes. CVID patients showed overall reduced median absolute counts (vs HD) of the two more advanced stages of maturation of both CD5+ CD38+/++ CD21het CD24++ (2.7 vs 5.6 cells/µl, p=0.0004) and CD5+ CD38het CD21+ CD24+ (6.5 vs 17 cells/µl, p<0.0001) immature B cells (below normal HD levels in 22% and 37% of CVID patients). This was associated with an expansion of CD21-CD24- (6.1 vs 0.74 cells/µl, p<0.0001) and CD21-CD24++ (1.8 vs 0.4 cells/µl, p<0.0001) naïve B-cell counts above normal values in 73% and 94% cases, respectively. Additionally, reduced IgMD+ (21 vs 32 cells/µl, p=0.03) and IgMD- (4 vs 35 cells/µl, p<0.0001) MBC counts were found to be below normal values in 25% and 77% of CVID patients, respectively, always together with severely reduced/undetectable circulating blood pb. Comparison of the maturation pathway profile of pre-GC B cells in blood of CVID patients vs HD using EuroFlow software tools showed systematically altered patterns in CVID. These consisted of: i) a normally-appearing maturation pathway with altered levels of expression of >1 (CD38, CD5, CD19, CD21, CD24, and/or smIgM) phenotypic marker (57/88 patients; 65%) for a total of 3 distinct CVID patient profiles (group 1: 42/88 patients, 48%; group 2: 8/88, 9%; and group 3: 7/88, 8%) and ii) CVID patients with a clearly altered pre-GC B cell maturation pathway in blood (group 4: 31/88 cases, 35%).ConclusionOur results show that maturation of pre-GC B-cells in blood of CVID is systematically altered with up to four distinctly altered maturation profiles. Further studies, are necessary to better understand the impact of such alterations on the post-GC defects and the clinical heterogeneity of CVID.

Whole-genome sequencing of cholangiocarcinoma to reveal distinct profiles of patients with underlying cirrhosis or inflammatory disorders.

340 Background: Cholangiocarcinoma (CCA) is a lethal malignancy with limited treatment options. Molecular profiling of these tumours has revealed a number of actionable mutations and four clusters have been defined through integrative genomic analysis. We sought to explore whole genome sequencing (WGS) data in 20 patients enriched for CCA arising in the setting of cirrhosis or inflammatory disorders. Methods: A previously established Biliary Tract Cancer (BTC) database at the Princess Margaret Cancer Centre (PMCC)/University Health Network (UHN) was used to identify patients of clinical interest including long-term survivors, those with germ-line mutations, and those with chronic inflammatory disorders. WGS and bioinformatic analyses were performed at the Ontario Institute for Cancer Research. Results: The 20 resected samples included 12 patients (pts) with intrahepatic CCA, 7 perihilar CCA, and 1 distal CCA. 8 pts were alive &gt; 8 years post resection and one patient harboured a germline MLH1 pathogenic variant (MLH1 G67R). 3 pts had documented cirrhosis (hepatitis B n = 2, haemochromatosis n = 1); other inflammatory disorders (n = 4) included ulcerative colitis (UC) without documented PSC (n = 1), PSC alone (n = 1), UC with PSC (n = 1), and ankylosing spondylitis (n = 1). The remaining cases were randomly selected. The predominant COSMIC single base substitution (SBS) mutational signatures were 1, 8 and 5, and the median TMB was 1.75 mutations per MB (0.73-33.23). The pt with an MLH1 mutation exhibited a TMB of 33.23 with predominance of SBS26. Actionable variants were enriched in the 8 pts who are alive and disease free including 2 predicted FGFR fusions and mutations in IDH1 (n = 1), BRAF V600E (n = 1), and BAP1 (n = 1). TP53 mutations (n = 7) were present exclusively in patients with cirrhosis or inflammatory disorders and the median survival in the group was 12 months (3 -21 months). Although SBS signatures were similar in this group, in the two cases of UC, SBS17 (unknown etiology) was evident. SBS17 was also dominant in one case where the TMB was 13 mutations per MB and the patient died within 3 months of diagnosis. A somatic case of homologous recombination deficiency, with no causative genetic alteration identified, was evident in a further patient receiving maintenance rituximab for a coexisting stage 4 mantle cell lymphoma. Conclusions: WGS may provide additional biological information in CCA particularly in patients with underlying inflammatory disorders, where TP53 mutations are prevalent and mutational signatures are distinct.