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1.
Cardiovasc Diabetol ; 23(1): 257, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39026226

RESUMO

BACKGROUND: Diabetes mellitus (DM) and Lp(a) are well-established predictors of coronary artery disease (CAD) outcomes. However, their combined association remains poorly understood. OBJECTIVE: To investigate the relationship between elevated Lp(a) and DM with CAD outcomes. METHODS: Retrospective analysis of the MGB Lp(a) Registry involving patients ≥ 18 years who underwent Lp(a) measurements between 2000 and 2019. Exclusion criteria were severe kidney dysfunction, malignant neoplasms, and prior atherosclerotic cardiovascular disease (ASCVD). The primary outcome was a combination of cardiovascular death or myocardial infarction (MI). Elevated Lp(a) was defined as > 90th percentile (≥ 216 nmol/L). RESULTS: Among 6,238 patients who met the eligibility criteria, the median age was 54, 45% were women, and 12% had DM. Patients with DM were older, more frequently male, and had a higher prevalence of additional cardiovascular risk factors. Over a median follow-up of 12.9 years, patients with either DM or elevated Lp(a) experienced higher rates of the primary outcome. Notably, those with elevated Lp(a) had a higher incidence of the primary outcome regardless of their DM status. The annual event rates were as follows: No-DM and Lp(a) < 90th% - 0.6%; No-DM and Lp(a) > 90th% - 1.3%; DM and Lp(a) < 90th% - 1.9%; DM and Lp(a) > 90th% - 4.7% (p < 0.001). After adjusting for confounders, elevated Lp(a) remained independently associated with the primary outcome among both patients with DM (HR = 2.66 [95%CI: 1.55-4.58], p < 0.001) and those without DM (HR = 2.01 [95%CI: 1.48-2.74], p < 0.001). CONCLUSIONS: Elevated Lp(a) constitutes an independent and incremental risk factor for CAD outcomes in patients with and without DM.


Assuntos
Biomarcadores , Doença da Artéria Coronariana , Diabetes Mellitus , Fatores de Risco de Doenças Cardíacas , Lipoproteína(a) , Sistema de Registros , Humanos , Masculino , Feminino , Lipoproteína(a)/sangue , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/sangue , Idoso , Biomarcadores/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Adulto , Fatores de Tempo , Prognóstico , Incidência , Regulação para Cima , Prevalência , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade
2.
Clin Rheumatol ; 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39052143

RESUMO

Psoriatic arthritis (PsA) is associated with obesity and other related comorbidities, which impose an additional burden on disease activity and response to treatment. We investigated the impact of Mediterranean diet, and exercise on the presentation and severity of PsA. Three hundred fifty-five patients with PsA (n = 279) and psoriasis (PsO) (n = 76) were included in a cross-sectional study. Demographic and clinical characteristics and dietary and exercise patterns were recorded. Patients were grouped into (i) high, moderate, and low Mediterranean diet adherence and (ii) high, medium, and low activity level. Levels of diet and exercise were correlated with disease activity indices. PsA patients had more comorbidities than their PsO counterparts (42.7% vs. 26.3%, p = .038). The majority showed a low exercise pattern (total = 71.3%, PsA = 72.4%, PsO = 67.1%). Approximately half (total = 44.2%, PsA = 43.4%, PsO = 47.4%) did not follow a Mediterranean diet. Disease Activity in Psoriatic Arthritis Score (DAPSA) (p = .004), tender (p = .003) and swollen (p = .015) joint counts, erythrocyte sedimentation rate (ESR) (p = .001), and Psoriasis Area and Severity Index (PASI) (p = .015) had an inverse correlation with exercise. Higher Mediterranean diet adherence was associated with reduced ESR (p = .056), PASI (p = .011), and body surface area (BSA) (p = .009) indices. After adjusting for body mass index (BMI), exercise retained its positive correlation with PsA disease activity, but diet showed significant correlation only with enthesitis (p = 0.015). Uptake of a Mediterranean diet and exercise have positive effects on PsA activity, independently of BMI. These findings support lifestyle recommendations to supplement conventional treatment for improvement in disease outcomes. Key points • Diet and lifestyle are important influencers of health-related outcomes in PsA. • In this cross-sectional study of 355 patients with psoriatic disease, we found that Med Diet and exercise improve outcomes in PsA independently of weight loss. • Our results suggest that diet and lifestyle modifications should supplement conventional medical treatments.

4.
Patient Prefer Adherence ; 18: 1077-1094, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38854480

RESUMO

Objective: Chronic diseases hold the potential to worsen the overall health of patients by limiting their functional status, productivity, and capacity to live well, affecting their overall health-related quality of life (HRQoL). The purpose of the study was to assess the HRQoL of individuals with chronic diseases residing in the Al-Jouf region of Saudi Arabia. Furthermore, the current study also sought to ascertain the impact of multimorbidity and the duration of illness on HRQoL. Material and Methods: A cross-sectional study was conducted among the residents of Al-Jouf region for a period of 6 months. A self-administered EuroQoL (EQ-5D-5L) study tool was used. Appropriate statistical analysis was conducted to ascertain the relationship between various variables and HRQoL. Results: A total of 500 out of 562 participants completed the study, with a response rate of 88.97%. Participants had a mean age of 46.15 ± 16.79 years, and the majority were female (n = 299; 59.80%). A mean HRQoL score of 0.82 ± 0.20 was reported, poorest in patients with kidney failure (0.65 ± 0.26) and highest in hepatitis. However, nearly half of the participants had diabetes mellitus type II (n = 205, 39.20%). Patients aged <30 years (OR: 0.109; p = 0.002), male participants (OR: 0.053; p < 0.001), no disability (OR: 0.143; p = 0.002), and <2 comorbid diseases (0.84 ± 0.18; p < 0.001) reported better QoL. Additionally, comorbid conditions such as DM, prolong the duration of the overall illness (14.19 ± 7.67 years). Overall, imperfect health (n = 390, 78%) was reported by the study participants. Conclusion: The present study provided preliminary data about the current HRQoL status of individuals with imperfect health and lower HRQoL. In the future, large-scale longitudinal studies are required to investigate the most prevalent chronic diseases, their associations, and change in HRQoL, as there is a dearth of information in the Saudi population.

5.
Hum Pathol ; 146: 66-74, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38608782

RESUMO

OBJECTIVES: To evaluate the International Society of Urological Pathology (ISUP) 5-tier grade grouping (GG) system of prostate cancers as well as previously proposed optimizations. PATIENTS AND METHODS: The PROCURE biobank is a prospective cohort study of patients with localized prostate cancer who underwent radical prostatectomy in Quebec province between 2005 and 2013. Surgical specimens were graded by experienced genitourinary pathologists using 2019 ISUP criteria. Follow-up was conducted until November 2021. The current 5-tier and a proposed 6-tier GG system were evaluated, the latter having two changes: 1) Gleason 3 + 4 and 4 + 3 tumors with minor/tertiary Gleason 5 patterns were upgraded to GG 3 and 4, respectively; and 2) patients in GG5 were separated based on primary Gleason pattern (4 or 5). Cox proportional hazards models and Harrell's concordance (C) indices were used for statistical analyses. RESULTS: 2003 patients were included (median follow-up: 8.7 years). The current 5-tier GG system predicted time to recurrence (hazard ratio [HR] 2.12, 95% confidence interval [95%CI] 1.99-2.25, C 0.717), androgen-deprivation therapy (HR 2.58, 95%CI 2.38-2.80, C 0.790), metastasis (HR 2.48, 95%CI 2.17-2.83, C 0.806), castration-resistant prostate cancer (HR 2.67, 95%CI 2.28-3.13, C 0.829), and cancer-specific mortality (HR 2.80, 95%CI 2.27-3.44, C 0.835). Goodness-of-fit further improved with the proposed 6-tier GG system, with Harrell's C of 0.733, 0.807, 0.827, 0.853, and 0.853, respectively. CONCLUSIONS: The 5-tier GG system predicted short- and long-term outcomes for patients with localized prostate cancer, and the proposed 6-tier GG system further improved its accuracy.


Assuntos
Gradação de Tumores , Prostatectomia , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/patologia , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Recidiva Local de Neoplasia/patologia , Fatores de Tempo
6.
J Clin Lab Anal ; 38(1-2): e25005, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38251811

RESUMO

BACKGROUND: The COVID-19 pandemic has had a profound global impact, with variations in susceptibility, severity, and mortality rates across different regions. While many factors can contribute to the spread and impact of the disease, specifically human leukocyte antigen (HLA) genetic variants have emerged as potential contributors to COVID-19 outcomes. METHODS: In this comprehensive narrative review, we conducted a thorough literature search to identify relevant studies investigating the association between HLA genetic variants and COVID-19 outcomes. Additionally, we analyzed allelic frequency data from diverse populations to assess differences in COVID-19 incidence and severity. RESULTS: Our review provides insights into the immunological mechanisms involving HLA-mediated responses to COVID-19 and highlights potential research directions and therapeutic interventions. We found evidence suggesting that certain HLA alleles, such as HLA-A02, may confer a lower risk of COVID-19, while others, like HLA-C04, may increase the risk of severe symptoms and mortality. Furthermore, our analysis of allele frequency distributions revealed significant variations among different populations. CONCLUSION: Considering host genetic variations, particularly HLA genetic variants, is crucial for understanding COVID-19 susceptibility and severity. These findings have implications for personalized treatment and interventions based on an individual's genetic profile. However, further research is needed to unravel the precise mechanisms underlying the observed associations and explore the potential for targeted therapies or preventive measures based on HLA genetic variants.


Assuntos
COVID-19 , Humanos , COVID-19/genética , SARS-CoV-2/genética , Pandemias , Frequência do Gene/genética
7.
Prev Med Rep ; 37: 102569, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38186661

RESUMO

This study examined associations between established cigar use and prevalence and incidence of cardiovascular diseases (CVD; congestive heart failure, stroke, or heart attack/needed bypass surgery) among U.S. adults, 40 years or older. Using Waves 1-5 (2013-2019) of the Population Assessment of Tobacco and Health (PATH) Study, incidence (Nindividuals (Nind) = 6,692; Nobservations (Nobs) = 23,738) and prevalence (Nind = 7,819; Nobs = 33,952) of CVD outcomes were examined using weighted generalized estimating equations (WGEEs) among adults who were exclusive current/former established cigar smokers (ever cigar smokers who have smoked fairly regularly), exclusive current/former established cigarette smokers (lifetime smokers of 100 or more cigarettes), dual current/former established cigarette and cigar smokers compared with never smokers of cigars or cigarettes, adjusting for covariates. The population-averaged incidence of CVD from one wave to next among exclusive current/former established cigar smokers during a six-year period based on WGEEs was low (overall average rate of 3.0 %; 95 % CI: 1.2, 7.0). Compared with never users, exclusive current/former established cigar smokers (OR = 1.67, 95 % CI: 1.11, 2.51) and exclusive current/former established cigarette smokers (OR = 2.12, 95 % CI: 1.45, 3.09) were more likely to have any CVD outcome in unadjusted analyses. When adjusted for covariates, only exclusive current/former established cigarette use was associated with CVD outcomes (AOR = 1.60, CI: 1.07, 2.40). Results suggest that exclusive established use of cigars or duration of exclusive cigar use was not associated with lifetime CVD prevalence compared with never cigar or cigarette smokers, which is important in understanding health outcomes in cigar users.

8.
Dig Dis Sci ; 69(2): 410-418, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38087127

RESUMO

BACKGROUND: Inflammatory Bowel Disease (IBD) is one of the most serious chronic diseases affecting the global population. Clinical team members involved in the care of individuals with IBD should have sufficient knowledge about IBD. AIMS: The study aim was to assess IBD knowledge among four health care professional groups in New Zealand: nurses, medical students, dietitians, and pharmacists. METHODS: All four groups completed surveys on demographics, work experience, and contact with patients with IBD. All completed a validated IBD knowledge assessment questionnaire (IBD-KID2), and percentage scores with standard deviation (SD) for each group calculated and compared. RESULTS: Participants included 200 nurses, 196 medical students, 45 dietitians, and 28 pharmacists. Mean IBD-KID2 percentage scores were nurses 69.7% (SD 14.7), medical students 77.6% (SD 14.5), dietitians 87.4% (SD 8.3), and pharmacists 83.4% (SD 10.1). Nurses scored lower than other HCP (P < 0.001). Independent variables were associated (P < 0.05) with higher scores for nurses having first degree relative with IBD, access to IBD guidelines, worked with children with IBD; medical students in their clinical years of study; and dietitians with IBD-specific education. Specific items scored poorly: growth, food triggers, heritability of IBD, and nutrient absorption. CONCLUSIONS: Knowledge gaps exist among HCP that may be addressed with targeted education. Improvements in the knowledge of those caring for people with IBD may optimize patient outcomes.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Doenças Inflamatórias Intestinais , Criança , Humanos , Doenças Inflamatórias Intestinais/terapia , Doenças Inflamatórias Intestinais/complicações , Pessoal de Saúde , Inquéritos e Questionários , Escolaridade
10.
Pediatr Cardiol ; 45(2): 426-432, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37853163

RESUMO

Neonates who require surgery for congenital heart disease (CHD) frequently have difficulty with oral feeds post-operatively and may require a feeding tube at hospital discharge. The purpose of this study was to determine the effect of oral or nasal intubation route on feeding method at hospital discharge. This was a non-blinded randomized control trial of 62 neonates who underwent surgery for CHD between 2018 and 2021. Infants in the nasal (25 patients) and oral (37 patients) groups were similar in terms of pre-operative risk factors for feeding difficulties including completed weeks of gestational age at birth (39 vs 38 weeks), birthweight (3530 vs 3100 g), pre-operative PO intake (92% vs 81%), and rate of pre-operative intubation (22% vs 28%). Surgical risk factors were also similar including Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery category (3.9 vs 4.1), shunt placement (32% vs 41%), cardiopulmonary bypass time (181 vs 177 min), and cross-clamp time (111 vs 105 min). 96% of nasally intubated patients took full oral feeds by discharge as compared with 78% of orally intubated infants (p = 0.05). Nasally intubated infants reach full oral feeds an average of 3 days earlier than their orally intubated peers. In this cohort of patients, nasally intubated infants reach oral feeds more quickly and are less likely to require supplemental tube feeding in comparison to orally intubated peers. Intubation route is a potential modifiable risk factor for oral aversion and appears safe in neonates. The study was approved by the University of Virginia Institutional Review Board for Health Sciences Research and was retrospectively registered on clinicaltrials.gov (NCT05378685) on May 18, 2022.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Cardiopatias Congênitas , Cirurgia Torácica , Recém-Nascido , Lactente , Humanos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Cardiopatias Congênitas/cirurgia , Cardiopatias Congênitas/etiologia , Intubação Gastrointestinal/efeitos adversos , Nutrição Enteral/métodos
11.
J Invest Dermatol ; 144(6): 1251-1261.e13, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38147960

RESUMO

Fibroblasts constitute a heterogeneous population of cells. In this study, we integrated single-cell RNA-sequencing and bulk RNA-sequencing data as well as clinical information to study the role of individual fibroblast populations in systemic sclerosis (SSc). SSc skin demonstrated an increased abundance of COMP+, COL11A1+, MYOC+, CCL19+, SFRP4/SFRP2+, and PRSS23/SFRP2+ fibroblasts signatures and decreased proportions of CXCL12+ and PI16+ fibroblast signatures in the Prospective Registry of Early Systemic Sclerosis and Genetics versus Environment in Scleroderma Outcome Study cohorts. Numerical differences were confirmed by multicolor immunofluorescence for selected fibroblast populations. COMP+, COL11A1+, SFRP4/SFRP2+, PRSS23/SFRP2+, and PI16+ fibroblasts were similarly altered between normal wound healing and patients with SSc. The proportions of profibrotic COMP+, COL11A1+, SFRP4/SFRP2+, and PRSS23/SFRP2+ and proinflammatory CCL19+ fibroblast signatures were positively correlated with clinical and histopathological parameters of skin fibrosis, whereas signatures of CXCL12+ and PI16+ fibroblasts were inversely correlated. Incorporating the proportions of COMP+, COL11A1+, SFRP4/SFRP2+, and PRSS23/SFRP2+ fibroblast signatures into machine learning models improved the classification of patients with SSc into those with progressive versus stable skin fibrosis. In summary, the profound imbalance of fibroblast subpopulations in SSc may drive the progression of skin fibrosis. Specific targeting of disease-relevant fibroblast populations may offer opportunities for the treatment of SSc and other fibrotic diseases.


Assuntos
Fibroblastos , Escleroderma Sistêmico , Pele , Humanos , Escleroderma Sistêmico/patologia , Escleroderma Sistêmico/genética , Escleroderma Sistêmico/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patologia , Feminino , Pele/patologia , Pele/metabolismo , Masculino , Pessoa de Meia-Idade , Adulto , Fibrose , Estudos Prospectivos , Análise de Célula Única , Cicatrização
12.
Parasitol Int ; 99: 102846, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38110172

RESUMO

Amoebiasis, caused by the enteric parasite Entamoeba histolytica has differential disease outcomes. The association of parasite genotypes with outcomes of amoebic infection is still a paradox and requires to be explored. The genetic information of infecting strains from endemic settings of different geographical regions is essential to evaluate the relation. Comparative genetics of E. histolytica clinical isolates from different disease outcomes have been explored based on two tRNA-linked STR loci (STGA-D and A-L). All of the repeat patterns in the A-L locus were newly identified and unique to Indian isolates. The majority of newly identified repeat patterns in STGA-D locus have outcome-specific distributions, predicting the emergence of disease-specific mutations in this target locus. Statistical analysis further reinforces this observation, as identified repeat patterns only from STGA-D but not A-L locus were significantly associated with disease outcomes. Phylogenetic analysis indicates independent segregation and divergence of tRNA-linked STR arrays for each STR locus.


Assuntos
Entamoeba histolytica , Entamoeba , Entamebíase , Animais , Entamoeba histolytica/genética , Entamebíase/epidemiologia , Entamebíase/parasitologia , Marcadores Genéticos , Filogenia , Repetições de Microssatélites , RNA de Transferência/genética , Entamoeba/genética
13.
Front Aging Neurosci ; 15: 1240971, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37842125

RESUMO

Background: The severity, progression, and outcomes of motor and non-motor symptoms in Parkinson's disease (PD) are quite variable. Following PD cohorts holds promise for identifying predictors of disease severity and progression. Methods: PD patients (N = 871) were enrolled at five sites. Enrollment occurred within 5 years of initial motor symptom onset. Disease progression was assessed annually for 2-to-10 years after onset. Group-based trajectory modeling was used to identify groups differing in disease progression. Models were developed for UPDRS-III scores, UPDRS-III tremor and bradykinesia-rigidity subscores, Hoehn & Yahr (H&Y) stage, Mini-Mental Status Exam (MMSE) scores, and UPDRS-III, H&Y and MMSE scores considered together. Predictors of trajectory-group membership were modeled simultaneously with the trajectories. Kaplan-Meier survival analysis evaluated survival free of PD outcomes. Results: The best fitting models identified three groups. One showed a relatively benign, slowly progressing trajectory (Group 1), a second showed a moderate, intermediately progressing trajectory (Group 2), and a third showed a more severe, rapidly progressing trajectory (Group 3). Stable trajectory-group membership occurred relatively early in the disease course, 5 years after initial motor symptom. Predictors of intermediate and more severe trajectory-group membership varied across the single variable models and the multivariable model jointly considering UPDRS-III, H&Y and MMSE scores. In the multivariable model, membership in Group 2 (28.4% of patients), relative to Group 1 (50.5%), was associated with male sex, younger age-at-onset, fewer education-years, pesticide exposure, absence of reported head injury, and akinetic/rigid subtype at initial presentation. Membership in Group 3 (21.3%), relative to Group 1, was associated with older age-at-onset, fewer education-years, pesticide exposure, and the absence of a tremor-predominant subtype at initial presentation. Persistent freezing, persistent falls, and cognitive impairment occurred earliest and more frequently in Group 3, later and less frequently in Group 2, and latest and least frequently in Group 1. Furthermore, autonomic complications, dysphagia, and psychosis occurred more frequently in Groups 2 and 3 than in Group 1. Conclusion: Modeling disease course using multiple objective assessments over an extended follow-up duration identified groups that more accurately reflect differences in PD course, prognosis, and outcomes than assessing single parameters over shorter intervals.

15.
Ann Gastroenterol ; 36(4): 423-429, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37396005

RESUMO

Background: The etiology of inflammatory bowel disease (IBD) is multifactorial and thought to be influenced by inappropriate activation of the gut mucosal immune system. As the only immunoglobulin G (IgG) subclass unable to activate the classical complement cascade, the role of IgG4 in IBD pathophysiology as an immunomodulator is controversial. This study aimed to determine the association of low, normal and high IgG4 levels with the outcomes of IBD patients. Methods: This was a retrospective study of a multisite tertiary care center database evaluating patients with IBD who had an IgG4 level drawn between 2014 and 2021. Subjects were divided into low, normal, and high IgG4 level groups for evaluation of demographic and clinical indicators of IBD activity and severity. Results: Of 284 patients with IBD, 22 had low (7.7%), 16 high (5.6%), and 246 (86.6%) normal IgG4 levels. There was no difference in IBD subtype, mean age, age at IBD diagnosis, or smoking between the 3 groups. There was no difference in number of hospitalizations (P=0.20), C-reactive protein levels, need for intestinal resection (P=0.85), or presence of primary sclerosing cholangitis (P=0.15), pancreatitis (P=0.70), or perianal disease (P=0.68) between the groups. Significantly more patients in the low IgG4 group had previous exposure to vedolizumab compared to the other groups and more patients in the low IgG4 group received vedolizumab (P=0.04), azathioprine (P=0.04) and prednisone (P=0.03) during the 5-year follow up. Conclusion: In this study, a low serum IgG4 level was associated with higher rates of vedolizumab, azathioprine, and steroid use.

16.
Adv Exp Med Biol ; 1426: 215-235, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37464123

RESUMO

The application of mathematical and computational analysis, together with the modelling of biological and physiological processes, is transforming our understanding of the pathophysiology of complex diseases. This systems biology approach incorporates large amounts of genomic, transcriptomic, proteomic, metabolomic, breathomic, metagenomic and imaging data from disease sites together with deep clinical phenotyping, including patient-reported outcomes. Integration of these datasets will provide a greater understanding of the molecular pathways associated with severe asthma in each individual patient and determine their personalised treatment regime. This chapter describes some of the data integration methods used to combine data sets and gives examples of the results obtained using single datasets and merging of multiple datasets (data fusion and data combination) from several consortia including the severe asthma research programme (SARP) and the Unbiased Biomarkers Predictive of Respiratory Disease Outcomes (U-BIOPRED) consortia. These results highlight the involvement of several different immune and inflammatory pathways and factors in distinct subsets of patients with severe asthma. These pathways often overlap in patients with distinct clinical features of asthma, which may explain the incomplete or no response in patients undergoing specific targeted therapy. Collaboration between groups will improve the predictions obtained using a systems medicine approach in severe asthma.


Assuntos
Asma , Transtornos Respiratórios , Humanos , Proteômica , Biologia de Sistemas , Asma/diagnóstico , Asma/genética , Biomarcadores/metabolismo
17.
Cancer Immunol Immunother ; 72(10): 3217-3228, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37428196

RESUMO

BACKGROUND: The clinical implications of the third dose of coronavirus disease 2019 (COVID-19) vaccines in patients receiving immune checkpoint inhibitors are currently unknown. We performed a prospective analysis of the Vax-On-Third study to investigate the effects of antibody response on immune-related adverse events (irAEs) and disease outcomes. METHODS: Recipients of the booster dose of SARS-CoV-2 mRNA-BNT162b2 vaccine who had received at least one course of an anti-PD-1/PD-L1 treatment before vaccination for an advanced solid malignancy were eligible. RESULTS: The current analysis included 56 patients with metastatic disease (median age: 66 years; male: 71%), most of whom had a lung cancer diagnosis and were being treated with pembrolizumab- or nivolumab-based regimens. The optimal cut-point antibody titer of 486 BAU/mL allowed a dichotomization of recipients into low-responders (Low-R, < 486 BAU/mL) or high-responders (High-R, ≥ 486 BAU/mL). After a median follow-up time of 226 days, 21.4% of patients experienced moderate to severe irAEs without any recrudescence of immune toxicities preceding the booster dose. The frequencies of irAE before and after the third dose did not differ, but an increase in the cumulative incidence of immuno-related thyroiditis was observed within the High-R subgroup. On multivariate analysis, an enhanced humoral response correlated with a better outcome in terms of durable clinical benefit, which resulted in a significant reduction in the risk of disease control loss but not mortality. CONCLUSIONS: Our findings would strengthen the recommendation not to change anti-PD-1/PD-L1 treatment plans based on current or future immunization schedules, implying that all these patients should be closely monitored.


Assuntos
Vacina BNT162 , COVID-19 , Humanos , Masculino , Idoso , Inibidores de Checkpoint Imunológico , Antígeno B7-H1 , SARS-CoV-2 , COVID-19/prevenção & controle , Recidiva Local de Neoplasia , RNA Mensageiro
18.
World J Cardiol ; 15(5): 262-272, 2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37274374

RESUMO

BACKGROUND: A limited number of studies have been conducted to test the magnitudes of the association between apparent treatment resistant hypertension (aTRH) and risk of cardiovascular disease (CVD). AIM: To investigate the association between aTRH and risk of CVD and examine whether sex and age modify this association. METHODS: We applied an observational analysis study design using data from the United States Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). ALLHAT recruited participants (n = 25516) from 625 primary care settings throughout the United States, Canada, Puerto Rico, and United States Virgin Islands, aged 55 and older with hypertension and at least one additional risk factor for heart disease. aTRH was assessed from the year 2 visit. CVD event was defined as one of the following from the year 2 follow-up visit: Fatal or non-fatal myocardial infarction, coronary revascularization, angina, stroke, heart failure, or peripheral artery disease. Cox proportional hazards regression was used to examine the effect of aTRH on CVD risk. Potential modifications of sex and age on this association were examined on the multiplicative scale by interaction term and additive scale by joint effects and relative excess risk for interaction. RESULTS: Of the total study participants (n = 25516), 5030 experienced a CVD event during a mean of 4.7 years follow-up. aTRH was associated with a 30% increase in risk of CVD compared to non-aTRH [hazards ratio (HR) = 1.3, 95%CI: 1.19-1.42]. Sex and age modified this relationship on both multiplicative and additive scales independently. Stratified by sex, aTRH was associated with a 64% increase in risk of CVD (HR = 1.64, 95%CI: 1.43-1.88) in women, and a 13% increase in risk of CVD (HR = 1.13, 95%CI: 1.01-1.27) in men. Stratified by age, aTRH had a stronger impact on the risk of CVD in participants aged < 65 (HR = 1.53, 95%CI: 1.32-1.77) than it did in those aged ≥ 65 (HR = 1.18, 95%CI: 1.05-1.32). Significant two-way interactions of sex and aTRH, and age and aTRH on risk of CVD were observed (P < 0.05). The observed joint effect of aTRH and ages ≥ 65 years (HR = 1.85, 95%CI: 1.22-2.48) in males was less than what was expected for both additive and multiplicative models (HR = 4.10, 95%CI: 3.63-4.57 and 4.88, 95%CI: 3.66-6.31), although three-way interaction of sex, age, and aTRH on the risk of CVD and coronary heart disease did not reach a statistical significance (P > 0.05). CONCLUSION: aTRH was significantly associated with an increased risk of CVD and this association was modified by both sex and age. Further studies are warranted to test these mechanisms.

19.
Crohns Colitis 360 ; 5(3): otad021, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37162798

RESUMO

Background: In the absence of targeted empirical evidence on effective clinical communication in inflammatory bowel disease (IBD), a broad overview of existing evidence on effective communication in healthcare and available recommendations for communication in telehealth is provided and mapped onto IBD research and practice. Methods: A narrative literature review was conducted using Pubmed and Scopus databases and snowballing literature search. Results: Evidence-based relationship building strategies include communicating emotions, acknowledging and addressing patients' hesitancy, and ensuring continued support. A particular recommendation regarding telehealth interaction is to avoid long stretches of talk. Effective informational strategies include facilitating and supporting information exchange and considering patients' preferences in decision-making. In teleconsultations, clinicians should ask direct questions about patients' emotional state, clarify their understanding of patients' concerns and check patients' understanding, address at least one patient-reported outcome when discussing the recommended treatment, and shorten the consultation where possible. Strategies for maximizing effective clinical communication in the spoken communicative mode include using infographics and simple language, and assessing adherence at the beginning of the consultation. For teleconsultations, clinicians are advised to allow patients to explain the reason for their call at the beginning of the teleconsultation, probe additional concerns early and before ending the teleconsultation, and be mindful of technical issues such as voice delays. Conclusions: Use of question prompt lists, decision aids, micro-lessons, and communication training interventions for clinicians could be beneficial in IBD care. Further research into the implementation of such interventions as well as clinical communication concerns specific to IBD is warranted.

20.
Vaccine ; 41(20): 3258-3265, 2023 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-37085449

RESUMO

OBJECTIVES: To investigate how BBIBP-CorV vaccination affecting antibody responses upon heterologous Omicron infection. METHODS: 440 Omicron-infected patients were recruited in this study. Antibodies targeting SARS-CoV-2 spike protein receptor binding domain (RBD) and nucleoprotein of both wild-type (WT) and Omicron were detected by ELISA. The clinical relevance was further analyzed. RESULTS: BBIBP-CorV vaccinated patients exhibited higher anti-RBD IgG levels targeting both WT and Omicron than non-vaccinated patients at different stages. By using a 3-day moving average analysis, we found that BBIBP-CorV vaccinated patients exhibited the increases in both anti-WT and Omicron RBD IgG from the onset and reached the plateau at Day 8 whereas those in non-vaccinated patients remained low during the disease. Significant increase in anti-WT RBD IgA was observed only in vaccinated patients. anti-Omicron RBD IgA levels remained low in both vaccinated and non-vaccinated patients. Clinically, severe COVID-19 only occurred in non-vaccinated group. anti-RBD IgG and IgA targeting both WT and Omicron were negatively correlated with virus load, hospitalization days and virus elimination in vaccinated patients. CONCLUSIONS: BBIBP-CorV vaccination effectively reduces the severity of Omicron infected patients. The existence of humoral memory responses established through BBIBP-CorV vaccination facilitates to induce rapid recall antibody responses when encountering SARS-CoV-2 variant infection.


Assuntos
Antivirais , COVID-19 , Humanos , Anticorpos Antivirais , Formação de Anticorpos , China , COVID-19/prevenção & controle , Imunoglobulina A , Imunoglobulina G , SARS-CoV-2 , Vacinação , Estudos Retrospectivos
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