Worse Disease Outcomes Research Articles

Prevention of Radiographic Progression in Higher-Risk Patients with Rheumatoid Arthritis Using Filgotinib in PhaseIII Studies: Narrative Review of PostHoc Analyses.

Filgotinib is an oral preferential Janus kinase1 inhibitor that demonstrated significant reductions in radiographic progression, with an acceptable tolerability and safety profile, vs placebo in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX-IR; FINCH1) and vs MTX in MTX-naïve patients with RA (FINCH3). International treatment guidelines identify multiple poor prognostic factors (PPFs) associated with worse disease outcomes among patients with RA. However, questions remain both about the clinical utility of considering PPFs and about which PPFs should drive treatment decisions. Additionally, the role of radiographic findings in clinical practice continues to be discussed and to evolve. This review examines radiographic results from posthoc analyses of phase3 trials of filgotinib that examined subgroups with 4PPFs or with baseline estimated rapid radiographic progression (e-RRP). In MTX groups, there were trends toward greater progression among patients with 4PPFs or e-RRP, suggesting these subgroups may comprise a higher-risk population. Results show general consistency for the efficacy of filgotinib 200mg plus MTX vs placebo plus MTX/MTX monotherapy on radiographic assessments, including change from baseline in modified total Sharp score and proportions without radiographic progression, even among MTX-IR or MTX-naïve patients with 4PPFs or e-RRP who may be at higher risk of bone damage. Multivariate analysis identified multiple factors associated with baseline e-RRP status. This summary of the current understanding of benefits associated with filgotinib on radiographic progression and the relevance of baseline factors to these benefits may help inform treatment decisions for patients facing high risk of radiographic progression.

Metabolic Associated Fatty Liver Disease (MAFLD) and COVID-19 Infection: An Independent Predictor of Poor Disease Outcome?

Background and Objectives: Early reports on COVID-19 infection suggested that the SARS-CoV-2 virus solely attacks respiratory tract cells. As the pandemic spread, it became clear that the infection is multiorganic. Metabolic associated fatty liver disease (MAFLD) is a chronic liver disease strongly associated with insulin resistance and diabetes. The aim of this study was to assess a possible interplay between MAFLD and COVID-19 infection and its implication in COVID-19 outcome. Materials and Methods: A retrospective observational study, including 130 COVID-19 positive patients was conducted. MAFLD diagnosis was made based on the International Consensus criteria. Patients were divided into two groups, group A (MAFLD) and group B (nonMAFLD). Anthropometric and laboratory analysis were obtained. COVID-19 severity was assessed using the NEWS2 score. Disease outcome was threefold and regarded as discharged, patients who required mechanical ventilation (MV), and deceased patients. Results: MAFLD prevalence was 42%, 67% of patients were discharged, and 19% needed MV. Mortality rate was 14%. MAFLD patients were significantly younger (p < 0.001), and had higher body mass index (p < 0.05), respiratory rate (p < 0.05) and systolic blood pressure (p < 0.05) than nonMAFLD patients. Regarding metabolic syndrome and inflammatory markers: group A had significantly higher glycemia at admission (p = 0.008), lower HDL-c (p < 0.01), higher triglycerides (p < 0.01), CRP (p < 0.001), IL-6 (p < 0.05) and ferritin (p < 0.05) than group B. MAFLD was associated with more prevalent type 2 diabetes (p = 0.035) and hypertension (p < 0.05). MAFLD patients had a more severe disease course (NEWS2 score, 6.5 ± 0.5 vs. 3 ± 1.0, p < 0.05). MAFLD presence was associated with lower patient discharge (p < 0.01) and increased need for MV (p = 0.024). Multiple regression analysis showed that BMI (p = 0.045), IL-6 (p = 0.03), and MAFLD (p < 0.05) are significant independent risk factors for a poor COVID-19 outcome. Conclusions: The prevalence of MAFLD is relatively high. MAFLD patients had a more severe COVID-19 clinical course and worse disease outcome. Our results imply that early patient stratification and risk assessment are mandatory in order to avoid poor outcomes.

D-dimer in Coronavirus 2019: An Acute Phase Reactant?

D-dimers are released following the breakdown of blood clots, essentially representing a byproduct of the degradation of fibrin by plasmin activity. Normal values are less than 0.50 mg/L (in fibrinogen equivalent units), and the negative predictive values of D-dimer measurements are excellent to rule out pulmonary embolism, deep vein thrombosis, and disseminated intravascular coagulation, since it would otherwise increase substantially in those settings. However, the D-dimer assay only represents a screening test and should be interpreted in the context of the patient’s clinical signs and symptoms.[1] Overt coagulation abnormalities are common in patients with coronavirus disease 2019 (COVID-19) and have led to an increase in requests of laboratory biomarkers, such as blood cell counts, acute phase reactants, coagulation tests, and platelet function assays, as aids in the clinical decision-making processes throughout the pandemic.[2] [3] D-dimer levels are among the most frequently and thoroughly studied, and the International COVID-19 Thrombosis Biomarkers Colloquium concluded that they were associated with patient prognosis and were helpful in clinical decision-making in patients requiring imaging studies, in the administration of thromboprophylaxis, and to detect and prevent complications.[4] While the consensus suggests that an elevated D-dimer is associated with worse disease outcomes,[5] the literature is not consistent in terms of whether the increase in D-dimer in COVID-19 can predict thrombotic events. Moreover, some issues have been identified in various publications, whereby comparisons between studies reporting D-dimer levels in different hospital units only reach confusing conclusions on their clinical significance.[6]

P237 Stenotrophomonas maltophilia isolates from cystic fibrosis patients eliminate competitor bacteria

Lung disease represents the primary cause of death in cystic fibrosis (CF) patients and bacterial infections are recognized as major contributors to worsening lung functions. Polymicrobial infections where more than one bacterial pathogen colonizes the lungs of CF patients are associated with worse disease outcomes. During these polymicrobial infections, cooperative and antagonistic interactions between different bacteria can impact microbial communities and affect disease progression. Stenotrophomonas maltophilia is a broadly distributed emerging bacterial pathogen that infects approximately 10–40% of all CF patients. Infections are difficult to treat because S. maltophilia isolates are resistant to many antibiotics. CF patients infected with S. maltophilia have a higher risk to require a lung transplant and have an increased risk of death. In both the environment and during polymicrobial infections, S. maltophilia must engage in antagonistic interactions with other bacteria to survive. It is currently unknown how CF S. maltophilia isolates compete against other bacteria.

The longitudinal course and determinants of apathy in UK care home residents with dementia

AbstractBackgroundApathy in dementia is a common and troubling symptom associated with worse disease outcomes but its longitudinal course is unclear We aimed to 1) describe the prevalence and persistence of clinically‐significant apathy in UK care home residents with dementia, 2) investigate the association of other neuropsychiatric symptoms in people with clinically‐significant apathy, and 3) identify sociodemographic and disease related factors associated with worse apathy trajectory.MethodProspective cohort study of residents with dementia recruited from 86 voluntary, state or private UK care homes. At baseline, and 4, 8, 12, and 16 months, care home staff rated apathy using the Neuropsychiatric Inventory (clinically‐significant apathy if score ≥4, sub‐clinical if 1‐3). Staff also rated dementia severity using the Clinical Dementia Rating scale, and provided other sociodemographic information about each participant. We examined the prevalence and persistence of apathy and, in mixed linear models, its association with time, age, sex, dementia severity, antipsychotic use, and baseline apathy and other neuropsychiatric symptoms.ResultsOf 1419 included participants (mean age 85 years (SD 8.5), 975 (68.7%) women), 30% had mild dementia, 33% moderate, and 37% severe. The point prevalence of clinically‐significant apathy was 21.4% (n = 304) and the period prevalence during 16 months follow‐up was 47.3% (n = 671). The point‐prevalence and 16‐month period prevalence of any apathy was 33.3% and 85.1% respectively. The longitudinal course is shown in the figure. Of participants who had follow‐up data, 45 (3.8%) were always clinically‐significantly apathetic, 3 (0.3%) were always sub‐clinically apathetic, and 420 (36.2%) were never apathetic until death or end of follow‐up. In adjusted models, apathy increased over time and was associated with having more severe dementia, worse baseline apathy and other neuropsychiatric symptoms.ConclusionMost people with dementia are not apathetic but it is common and frequently fluctuates in its course. It is important for clinicians to know that most people with dementia do not develop apathy and it is not an inevitable symptom and often remits. People with more severe dementia and other neuropsychiatric symptoms are more likely to have an adverse apathy course, so may be a priority group for current and future treatments.

Activation of Inflammasome complex in nasopharyngeal epithelial cells from patients with Coronavirus disease 2019 contributes to inflammatory state and worse disease outcomes.

Pathogenesis of Coronavirus disease 2019 (COVID-19) has been associated with dysregulation of both adaptive and innate immune systems. Hence, we determined the contribution of inflammasome in the nasopharyngeal epithelial cells isolated from COVID-19 subjects to disease pathogenesis and outcomes. Epithelial cells from 150 COVID-19 patients and 150 healthy controls were yielded through nasopharyngeal swab sampling. Patients were categorized into three groups of those with clinical presentations/need hospitalization, with clinical presentations/no need hospitalization and cases without clinical symptoms/no need hospitalization. Finally, the transcriptional amount of inflammasome related genes were assessed in the nasopharyngeal epithelial cells using qPCR. There was a significant upregulation of nod-like receptor (NLR) family pyrin domain containing 1 (NLRP1), nod-like receptor (NLR) family pyrin domain containing 3 (NLRP3), Apoptosis-associated speck-like protein containing a CARD (ASC) and Caspase-1 mRNA expressions in patients compared to controls. NLRP1, NLRP3, ASC and Caspase-1 were upregulated in epithelial cells of patients with clinical symptoms/need hospitalization and cases with clinical symptoms/no need hospitalization when compared to controls. There was a correlation between expression of inflammasome-related genes and clinicopathological features. Abnormal expression of inflammasome-related genes in the nasopharyngeal epithelial cells obtained from COVID-19 patients may be of prognostic value to determine the intensity of the disease's outcomes and requirement for alternative supports in hospitals.

Suboptimally controlled asthma in patients treated with inhaled ICS/LABA: prevalence, risk factors, and outcomes

This observational claims-linked survey study assessed the prevalence of and risk factors for suboptimal asthma control and healthcare utilization in adults with asthma receiving fixed-dose combination (FDC) inhaled corticosteroid/long-acting β2-agonist (ICS/LABA). Commercially insured adults from the Optum Research Database were invited to complete the Asthma Control Test (ACT) and Asthma Control Questionnaire-6 (ACQ-6). Among participants (N = 428), 36.4% (ACT-assessed) and 55.6% (ACQ-6-assessed) had inadequately controlled asthma. Asthma-related quality of life was worse and asthma-related healthcare resource utilization was higher in poorly controlled asthma. Factors associated with ACT-defined suboptimal asthma control in multivariate analysis included: frequent short-acting β2-agonist (SABA) use, asthma-related outpatient visits, lower treatment adherence, and lower education levels. During follow-up, factors associated with asthma exacerbations and/or high SABA use included: inadequately controlled asthma (ACT-assessed), body mass index ≥30 kg/m2, and high-dose ICS/LABA. Approximately 35–55% of adults with asthma were inadequately controlled despite FDC ICS/LABA; poor control was associated with worse disease outcomes.

A pan-cancer analysis of the role of WDFY2 in human tumors

ABSTRACT WDFY2 is a protein that may provide valuable insights into the mechanisms underlying human tumors and aid in the development of novel therapies. Despite its potential importance, the role of WDFY2 in pan-cancer has not been systematically investigated. In this study, we comprehensively explored the expression pattern and function of WDFY2 across 33 cancers using various databases, including TCGA, CPTAC and GEO datasets. Our results indicate that WDFY2 is downregulated in most cancer types, including BRCA, KIRP, KICH, LUAD, KIRC, PCPG, PRAD, THCA, ACC, OV, TGCT and UCS, while it is upregulated in CESC, CHOL, COAD, HNSC, LUSC, READ, STAD and UCEC. Prognostic analyses showed that higher levels of WDFY2 were associated with worse disease outcomes in ACC, BLCA, COAD, READ, SARC, MESO and OV. WDFY2 mutations were most frequent in colorectal cancer but were not associated with disease prognosis. We also found that WDFY2 expression correlated with monocyte infiltration status in SKCM, endothelial cell infiltration in COAD, KIRC, MESO, OV and THCA, and cancer-associated fibroblast infiltration in COAD, LUAD and OV. Additionally, functional enrichment analysis revealed that WDFY2 is involved in metabolism. Overall, our comprehensive analysis sheds light on the role of WDFY2 in various cancers, providing a better understanding of its role in tumorigenesis.

Type 2 Diabetes Mellitus and Asthma: Pathomechanisms of Their Association and Clinical Implications.

Type 2 diabetes mellitus (T2DM) and asthma are chronic illnesses concomitantly present in a significant percentage of the population. Their comorbidity is associated with poor disease control and lower quality of life, thus imposing a substantial medical and economic burden worldwide. This review investigates the association between asthma and T2DM, in terms of pathogenesis, clinical outcomes, and therapeutic opportunities. Our review found an increased risk of asthmaamong diabetics, and vice versa. Having diabetes and poor glycemic control is associated with an increased rate of asthma exacerbations and increased mortality among those hospitalized for asthma exacerbations. The mechanisms postulated for the diabetes-asthma association include chronic low-grade inflammation, obesity, hyperinsulinemia, and possibly diabetic pneumopathy. Usage of metformin, which is the first-line drug for type 2 diabetes, was found to be associated with a decreased asthma occurrence, asthma exacerbations, and asthma-related hospitalizations.Glucagon-like peptide 1 receptor agonists were also found to be associated with a lower occurrence of asthma exacerbations. Thiazolidinediones are also associated with lower rates of asthma exacerbations, but their clinical efficacy for the same was suggested to be limited. This literature review supports a partly causative association between asthma and diabetes. This comorbidity leads to poor patient compliance, worse disease outcomes, and poor quality of life. Thus, further studies are warranted to explore the prognostic implications, therapeutic opportunities, and specific clinical practice algorithms for patients with concurrent asthma and type 2 diabetes mellitus.

Ki67 increase after core needle biopsy associated with worse disease outcome in HER2-negative breast cancer patients

Ki67 would change after core needle biopsy (CNB) in invasive breast cancer. However, whether Ki67 alteration (ΔKi67) influences disease outcomes remains unclear. Here we aim to evaluate the prognostic value of ΔKi67. Patients with paired CNB and open excision biopsy (OEB) samples between January 2009 and June 2016 were retrospectively analyzed. ΔKi67 was calculated as the absolute difference between Ki67 level in CNB and OEB samples, and the median value of 5% was adopted to category patients into high- and low ΔKi67 groups. Disease-free survival (DFS) and overall survival (OS) were compared between different ΔKi67 groups. Overall, 2173 invasive breast cancer patients were included. Median Ki67 was higher in OEB than CNB samples: 25.00% versus 20.00% (P < 0.001). Axillary nodal status, STI, histological grading, and molecular subtype were independently associated with ΔKi67 (P < 0.05). In the whole population, patients with low ΔKi67 showed superior 5-year DFS (89.6% vs 87.0%, P = 0.026), but similar OS (95.8% vs 94.3%, P = 0.118) compared to those with high ΔKi67. HER2 status at surgery was the only significant factor interacting with ΔKi67 on both DFS (P = 0.026) and OS (P = 0.007). For patients with HER2-negative disease, high ΔKi67 was associated with worse 5-year DFS (87.2% vs 91.2%, P = 0.004) as well as impaired 5-year OS (93.9% vs 96.8%, P = 0.010). ΔKi67 had no significant impact on survival of HER2-positive patients. Ki67 increase after CNB was significantly associated with worse disease outcomes in HER2-negative, but not in HER2-positive patients, which warrants further study.

Multimorbidity and SARS-CoV-2-Related Outcomes: Analysis of a Cohort of Italian Patients.

Since the outbreak of the COVID-19 pandemic, identifying the main risk factors has been imperative to properly manage the public health challenges that the pandemic exposes, such as organizing effective vaccination campaigns. In addition to gender and age, multimorbidity seems to be 1 of the predisposing factors coming out of many studies investigating the possible causes of increased susceptibility to SARS-CoV-2 infection and adverse outcomes. However, only a few studies conducted have used large samples. The objective is to evaluate the association between multimorbidity, the probability to be tested, susceptibility, and the severity of SARS-CoV-2 infection in the Piedmont population (Northern Italy, about 4 million inhabitants). For this purpose, we considered 5 main outcomes: access to the swab, positivity to SARS-CoV-2, hospitalization, intensive care unit (ICU) admission, and death within 30 days from the first positive swab. Data were obtained from different Piedmont health administrative databases. Subjects aged from 45 to 74 years and infections diagnosed from February to May 2020 were considered. Multimorbidity was defined both with the Charlson Comorbidity Index (CCI) and by identifying patients with previous comorbidities, such as diabetes and oncological, cardiovascular, and respiratory diseases. Multivariable logistic regression models (adjusted for age and month of infection and stratified by gender) were performed for each outcome. Analyses were also conducted by separating 2 age groups (45-59 and 60-74 years). Of 1,918,549 subjects, 85,348 (4.4%) performed at least 1 swab, of whom 12,793 (14.9%) tested positive for SARS-CoV-2. Of these 12,793 subjects, 4644 (36.3%) were hospitalized, 1508 (11.8%) were admitted to the ICU, and 749 (5.9%) died within 30 days from the first positive swab. Individuals with a higher CCI had a higher probability of being swabbed but a lower probability of testing positive. We observed the same results when analyzing subjects with previous oncological and cardiovascular diseases. Moreover, especially in the youngest group, we identified a greater risk of being hospitalized and dying. Among comorbidities considered in the study, respiratory diseases seemed to be the most likely to increase the risk of having a positive swab and worse disease outcomes. Our study shows that patients with multimorbidity, although swabbed more frequently, are less likely to get infected with SARS-CoV-2, probably due to greater attention on protective methods. Moreover, a history of respiratory diseases is a risk factor for a worse prognosis of COVID-19. Nonetheless, whatever comorbidities affect the patients, a strong dose-response effect was observed between an increased CCI score and COVID-19 hospitalization, ICU admission, and death. These results are important in terms of public health because they help in identifying a group of subjects who are more prone to worse SARS-CoV-2 outcomes. This information is important for promoting targeted prevention and developing policies for the prioritization of public health interventions.

Blood transcriptome responses in patients correlate with severity of COVID-19 disease.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infected individuals display a wide spectrum of disease severity, as defined by the World Health Organization (WHO). One of the main factors underlying this heterogeneity is the host immune response, with severe COVID-19 often associated with a hyperinflammatory state. Our current study aimed to pinpoint the specific genes and pathways underlying differences in the disease spectrum and outcomes observed, through in-depth analyses of whole blood transcriptomics in a large cohort of COVID-19 participants. All WHO severity levels were well represented and mild and severe disease displaying distinct gene expression profiles. WHO severity levels 1-4 were grouped as mild disease, and signatures from these participants were different from those with WHO severity levels 6-9 classified as severe disease. Severity level 5 (moderate cases) presented a unique transitional gene signature between severity levels 2-4 (mild/moderate) and 6-9 (severe) and hence might represent the turning point for better or worse disease outcome. Gene expression changes are very distinct when comparing mild/moderate or severe cases to healthy controls. In particular, we demonstrated the hallmark down-regulation of adaptive immune response pathways and activation of neutrophil pathways in severe compared to mild/moderate cases, as well as activation of blood coagulation pathways. Our data revealed discrete gene signatures associated with mild, moderate, and severe COVID-19 identifying valuable candidates for future biomarker discovery.

Axial Spondyloarthritis and Diagnostic Challenges: Over-diagnosis, Misdiagnosis, and Under-diagnosis.

This article aims to review the challenges in axial spondyloarthritis diagnosis and identify the possible contributing factors. The inability to reach an accurate diagnosis in a timely fashion can lead to treatment delays and worse disease outcomes. The lack of validated diagnostic criteria and the misuse of the currently available classification criteria could be contributing. There is also significant inter-reader variability in interpreting images, and the radiologic definitions of axial spondyloarthritis continue to be re-defined to improve their positive predictive value. The role of inflammatory back pain features, serologic biomarkers, genetics, and their diagnostic contribution to axial spondyloarthritis continues to be investigated. There is still a significant amount of delay in the diagnosis of axial spondyloarthritis. Appreciating the factors that contribute to this delay is of utmost importance to close the gap. It is similarly important to recognize other conditions that may present with symptoms that mimic axial spondyloarthritis so that misdiagnosis and wrong treatment can be avoided.

Association of serum lipid levels and clinical outcomes in early breast cancer patients.

The association between dyslipidaemia and breast cancer remains controversial, especially regarding the dynamic changes in lipid levels. This study aimed to elucidate the role of serum lipid levels and the changes in disease outcomes in patients with breast cancer. The lipid profiles of patients with breast cancer who underwent surgery between 2013 and 2017 were retrospectively reviewed. The lipid profiles comprised triglyceride (TG), total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein. Serum lipid levels were categorized into three groups based on the tertiles. The Wilcoxon test was used to compare changes in serum lipid levels during follow-up. Hazard ratios (HRs) for survival outcomes were estimated using a multivariate Cox regression analysis. A total of 3499 women diagnosed with nonmetastatic invasive breast cancer were included in this study, with a median follow-up of 60.4 months. We confirmed that each 1-tertile increased TG at baseline [HR = 1.19, 95% confidence interval (CI) 1.02-1.39] and 1-year follow-up (HR = 1.46, 95% CI 1.07-1.98) led to worse relapse-free survival (RFS). A lower risk of disease relapse was observed with each 1-tertile upregulation in HDL at 1-year follow-up (HR = 0.72, 95% CI 0.56-0.92). Receiving systemic therapies tends to induce an elevation in plasma lipid levels 1 year after surgery, especially in terms of TG. Regarding the prognostic value of dynamic changes in lipid levels, patients with sustained high levels of TG had poorer RFS (HR = 1.90, 95% CI 1.16-3.11), whereas maintaining high levels of HDL led to better survival (HR = 0.60, 95% CI 0.37-0.97). High TG at baseline and during follow-up was associated with worse disease outcome in early breast cancer patients. Systemic treatment would lead to an elevation of serum lipid levels. Patients with sustained high HDL level at 1-year follow-up after surgery had a superior prognosis, warranting further clinical evaluation.

Unexpected Photocatalytic Degeneration of NAD + for Inducing Apoptosis of Hypoxia Cancer Cells

Unexpected Photocatalytic Degeneration of NAD ⁺ for Inducing Apoptosis of Hypoxia Cancer Cells

Association of Vitamin D Polygenic Risk Scores and Disease Outcome in People With Multiple Sclerosis.

Observational studies suggest low levels of 25-hydroxyvitamin D (25[OH]D) may be associated with increased disease activity in people with multiple sclerosis (PwMS). Large-scale genome-wide association studies (GWAS) suggest 25(OH)D levels are partly genetically determined. The resultant polygenic scores (PGSs) could serve as a proxy for 25(OH)D levels, minimizing potential confounding and reverse causation in analyses with outcomes. Herein, we assess the association of genetically determined 25(OH)D and disease outcomes in MS. We generated 25(OH)D PGS for 1,924 PwMS with available genotyping data pooled from 3 studies: the CombiRx trial (n = 575), Johns Hopkins MS Center (n = 1,152), and Immune-Mediated Inflammatory Diseases study (n = 197). 25(OH)D-PGS were derived using summary statistics (p < 5 × 10-8) from a large GWAS including 485,762 individuals with circulating 25(OH)D levels measured. We included clinical and imaging outcomes: Expanded disability status scale (EDSS), timed 25-foot walk (T25FW), nine-hole peg test (9HPT), radiologic activity, and optical coherence tomography-derived ganglion cell inner plexiform layer (GCIPL) thickness. A subset (n = 935) had measured circulating 25(OH)D levels. We fitted multivariable models based on the outcome of interest and pooled results across studies using random effects meta-analysis. Sensitivity analyses included a modified p value threshold for inclusion in the PGS (5 × 10-5) and applying Mendelian randomization (MR) rather than using PGS. Initial analyses demonstrated a positive association between generated 25(OH)D-PGS and circulating 25(OH)D levels (per 1SD increase in 25[OH]D PGS: 3.08%, 95% CI: 1.77%, 4.42%; p = 4.33e-06; R2 = 2.24%). In analyses with outcomes, we did not observe an association between 25(OH)D-PGS and relapse rate (per 1SD increase in 25[OH]D-PGS: 0.98; 95% CI: 0.87-1.10), EDSS worsening (per 1SD: 1.05; 95% CI: 0.87-1.28), change in T25FW (per 1SD: 0.07%; 95% CI: -0.34 to 0.49), or change in 9HPT (per 1SD: 0.09%; 95% CI: -0.15 to 0.33). 25(OH)D-PGS was not associated with new lesion accrual, lesion volume or other imaging-based outcomes (whole brain, gray, white matter volume loss or GCIPL thinning). The results were similarly null in analyses using other p value thresholds or those applying MR. Genetically determined lower 25(OH)D levels were not associated with worse disease outcomes in PwMS and raises questions about the plausibility of a treatment effect of vitamin D in established MS.

Endothelial Progenitor Cells in Neurovascular Disorders—A Comprehensive Overview of the Current State of Knowledge

Endothelial progenitor cells (EPCs) are a population of cells that circulate in the blood looking for areas of endothelial or vascular injury in order to repair them. Endothelial dysfunction is an important component of disorders with neurovascular involvement. Thus, the subject of involvement of EPCs in such conditions has been gaining increasing scientific interest in recent years. Overall, decreased levels of EPCs are associated with worse disease outcome. Moreover, their functionalities appear to decline with severity of disease. These findings inspired the application of EPCs as therapeutic targets and agents. So far, EPCs appear safe and promising based on the results of pre-clinical studies conducted on their use in the treatment of Alzheimer’s disease and ischemic stroke. In the case of the latter, human clinical trials have recently started to be performed in this subject and provided optimistic results thus far. Whereas in the case of migraine, existing findings pave the way for testing EPCs in in vitro studies. This review aims to thoroughly summarize current knowledge on the role EPCs in four disorders with neurovascular involvement, which are Alzheimer’s disease, cerebral small vessel disease, ischemic stroke and migraine, with a particular focus on the potential practical use of these cells as a treatment remedy.

Relationships among illness understanding, information preferences, and adherence to oral anticancer therapy.

250 Background: Patients prescribed oral anticancer therapy receive less support for adherence and symptom monitoring from oncologists compared to infusional cancer therapy, which can result in lower quality care and worse disease outcomes. Identifying factors related to adherence can guide efforts to develop patient-centered interventions. The goal of this analysis was to examine associations among patients’ illness understanding, information preferences, and oral anticancer therapy adherence. Methods: We conducted a secondary analysis of a randomized trial testing the efficacy of a mobile application to improve assessment of symptoms and treatment adherence. Eligible patients included adults diagnosed with cancer prescribed oral anticancer therapy. To assess adherence, participants stored their medication for three months in a Medication Event Monitoring System (MEMS) bottle that electronically records the date and time the bottle is opened. At baseline, participants completed the Prognosis and Treatment Perceptions Questionnaire, which assesses patients’ illness understanding and information preferences in communicating with oncologists. We conducted linear regression to examine associations among patients’ illness understanding, information preferences, and medication adherence. Results: The study included 181 patients prescribed oral anticancer therapy (Mean age = 53.30 years; 53.6% female; 87.8% white). The most common cancer types were hematologic (33.1%), lung (18.2%), and breast (14.4%) malignancies. Two-thirds (66.9%) were prescribed oral targeted therapies, and 35.5% self-identified as terminally ill. Controlling for intervention effects, patients who reported wanting as many details as possible related to their cancer and treatment had higher MEMS adherence over the three-month study period (B = 12.84, 95%CI: 3.65, 22.03, p =.006) versus those who preferred to know fewer details. Also, patients who reported that it was extremely important for them to know their prognosis had higher adherence (B = 9.93, 95%CI: 1.73, 18.13, p =.018) versus those who rated knowing about prognosis as less important, though this relationship was moderated by illness understanding. Specifically, in the subgroup of patients reporting that they were not terminally ill, the association between wanting to know about prognosis and MEMS adherence remained significant (p =.006), which was not the case for patients identifying as terminally ill (p =.776). Conclusions: In this sample, patients’ desire for information about their cancer and prognosis was strongly associated with higher adherence to oral anticancer therapy over the following three months. Yet, this association may be stronger among those who do not identify as terminally ill. Targeted interventions that support patients who prefer fewer details about their illness and prognosis may improve medication adherence.

Assessment of inhaler techniques and the impact of critical errors on clinical outcomes

Introduction: The use of inhaled medications remained as the pillar in pharmacological management of asthma and chronic obstructive pulmonary disease. Incorrect inhalation technique can impact drug delivery to the lung, compromised bronchodilation and lead to deteriorated disease control and worse disease outcomes. However, devices for inhaled medications can be difficult to learn and prone to mishandling despite presence of newer and more user-friendly inhalers. Objectives: This study aimed to assess and compare between patients’ self-rated confidence with their actual technique in using inhalers This study also aimed to determine factors associated with incorrect inhalation technique and impact of inhaler critical errors on clinical outcomes. Methodology: This was a cross-sectional study among patients with chronic respiratory disease who were users of inhalers, who visited outpatient pharmacy department and respiratory clinic, Serdang Hospital from 15th July to 15th August 2019. The patients were screened using convenient sampling according to inclusion and exclusion criteria. Pertinent data and inhalation techniques were identified during interview sessions. Results and discussion: Nearly a third of the patients who were confident with their inhalation technique had incorrect inhalation techniques and performed critical errors.

Cervical Cancer Outcome and Tumor-Associated Macrophages: Research Evidence

Inflammation is a key factor in cancer promotion. Tumor-associated macrophages (TAMs), as part of the tumor microenvironment, are often associated with the progression of tumors and a worse prognosis in many cancers, namely on cervical cancer. This work exhaustively summarizes the conclusions of the different studies published concerning TAMs function in cervical cancer, from in vitro studies using cancer cell lines to the clinical perspective (histological samples-based studies). Most studies have led to the conclusion that TAMs increased density is directly related to increased severity of a malignant cervical lesion. Additionally, TAMs are normally polarized into an M2 phenotype, benefiting and promoting tumor progression, resulting in a worse disease outcome. The tumor microenvironment is also a highly critical contributor that not only influences tumor natural history but also modulates the specific immune response.