| 1. |
- Bobbio, Emanuele, et al.
(författare)
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Clinical Outcomes and Predictors of Long-Term Survival in Patients With and Without Previously Known Extracardiac Sarcoidosis Using Machine Learning: A Swedish Multicenter Study.
- 2023
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 12:15
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Tidskriftsartikel (refereegranskat)abstract
- Background Cardiac involvement can be an initial manifestation in sarcoidosis. However, little is known about the association between various clinical phenotypes of cardiac sarcoidosis (CS) and outcomes. We aimed to analyze the relation of different clinical manifestations with outcomes of CS and to investigate the relative importance of clinical features influencing overall survival. Methods and Results A retrospective cohort of 141 patients with CS enrolled at 2 Swedish university hospitals was studied. Presentation, imaging studies, and outcomes of de novo CS and previously known extracardiac sarcoidosis were compared. Survival free of primary composite outcome (ventricular arrhythmias, heart transplantation, or death) was assessed. Machine learning algorithm was used to study the relative importance of clinical features in predicting outcome. Sixty-two patients with de novo CS and 79 with previously known extracardiac sarcoidosis were included. De novo CS showed more advanced New York Heart Association class (P=0.02), higher circulating levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) (P<0.001), and troponins (P<0.001), as well as a higher prevalence of right ventricular dysfunction (P<0.001). During a median (interquartile range) follow-up of 61 (44-77) months, event-free survival was shorter in patients with de novo CS (P<0.001). The top 5 features predicting worse event-free survival in order of importance were as follows: impaired tricuspid annular plane systolic excursion, de novo CS, reduced right ventricular ejection fraction, absence of β-blockers, and lower left ventricular ejection fraction. Conclusions Patients with de novo CS displayed more severe disease and worse outcomes compared with patients with previously known extracardiac sarcoidosis. Using machine learning, right ventricular dysfunction and de novo CS stand out as strong overall predictors of impaired survival.
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| 2. |
- Darlington, Pernilla
(författare)
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Studies of different clinical manifestations of Sarcoidosis and the role of genetic factors
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Sarcoidosis is a systemic disease of unknown etiology characterized by the formation of non-necrotizing granulomas in the affected organs. Engagement of the lungs and/or thoracic lymph nodes (LN) are found in more than 90 % of all cases, but almost any organ such as the eyes, skin, heart and nervous system can be involved. Genetic factors influence the risk for disease as well as the clinical picture seen in sarcoidosis and especially the genes localized to the human leukocyte antigen (HLA) region on chromosome six are believed to be of importance. For example, the HLA-DRB1*0301 allele is found to be strongly associated with Löfgren’s syndrome (LS). Characteristic for LS is an acute onset usually with fever, bilateral ankle arthritis and/or erythema nodosum and bilateral hilar lymphadenopathy with in some cases parenchymal infiltrates. The HLA-DRB1*0301 allele is also associated with an accumulation of T cells expressing the T cell receptor variable gene segment AV2S3 in bronchoalveolar lavage fluid (BALF) of sarcoidosis patients. The aim of this thesis has been to identify risk factors for different clinical manifestations in sarcoidosis as well as markers of importance for the inflammatory cell response seen in sarcoidosis. The results show that HLA-DRB1*04 positive sarcoidosis patients had an increased risk for the three organ engagements associated with Heerfordt´s syndrome. Heerfordt´s syndrome is a phenotype of sarcoidosis that in its complete form consists of uveitis, parotid and/or salivary gland enlargement and cranial nerve palsy. In comparison to BALF where a high CD4/CD8-ratio is strongly associated with sarcoidosis, the CD4/CD8-ratio in the affected LNs of sarcoidosis patients had no diagnostic value. Further, in HLA-DRB1*03 positive patients the associated accumulation of AV2S3+ T cells was strictly compartmentalized in BALF. This finding indicates an airborne antigen as the triggering factor in sarcoidosis. The risk for cardiac sarcoidosis (CS) was significantly higher in patients with an abnormal electrocardiography (ECG) compared to those with a normal ECG. The risk for CS was highest in patients who had a pathologic ECG in combination with cardiac related symptoms. Further, non-LS was associated with an increased risk for CS. In LS patients was the absence of HLA-DRB1*03 a risk factor for extra-pulmonary manifestations (erythema nodosum and ankle arthritis excluded). Another risk marker in all patients was HLA-DRB1*04/*15 where half of the patients had extra-pulmonary manifestations. In conclusion, the HLA-DRB1*04 allele is associated with an increased risk for involvement of the eyes, parotid and/or salivary glands and cranial nerves in sarcoidosis patients. Moreover, an increased CD4/CD8-ratio in enlarged LNs is not diagnostic for sarcoidosis in comparison to BALF where a high ratio is strongly associated with sarcoidosis. Further, a pathologic ECG is a risk marker for CS in sarcoidosis patients. Finally, not only the single HLA-DRB1 alleles are of importance for the risk of extra-pulmonary manifestations in sarcoidosis, but also the allele combinations and where especially the combination HLA-DRB1*04/*15 calls for an increased awareness and a more intensive follow-up.
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| 3. |
- Eldhagen, Per, et al.
(författare)
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Phenotypic and HLA-DRB1 allele characterization of Swedish cardiac sarcoidosis patients.
- 2022
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Ingår i: International journal of cardiology. - : Elsevier BV. - 1874-1754 .- 0167-5273. ; 359, s. 108-112
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Tidskriftsartikel (refereegranskat)abstract
- Early detection and initiation of treatment in cardiac sarcoidosis (CS) is believed to be crucial to reduce morbidity and mortality. The diagnosis of CS is challenging, especially in isolated CS (ICS). Certain human leukocyte antigen (HLA-DRB1) alleles associate with different phenotypes of sarcoidosis. Phenotypic and genotypic characterization of patients with CS may improve our ability to identify patients being at risk for developing CS.87 patients with CS, identified at two Swedish university hospitals were included. Phenotypic characteristics were extracted from the medical records and the patients were HLA-DRB1 typed.Median age at diagnosis was 55years, 37% were women. HLA-DRB1 distribution was similar to a general sarcoidosis population. A majority of patients (51/87) had CS as the first sarcoidosis presentation. They were younger (p=0.04), more often presenting with ventricular tachycardia (VT) or atrioventricular block (AVB) grade II or III (p<0.001), had lower left ventricular ejection fraction (LVEF) (p=0.002), lower serum angiotensin converting enzyme (s-ACE) (p=0.025), and fewer extra cardiac manifestations (ECM) (p=0.02) than those presenting with CS later.Of Swedish CS patients, 59% presented with cardiac involvement as first manifestation. They had more severe cardiac symptoms than patients presenting with CS later. This phenotype disclosed less ECM and lower s-ACE thus diagnosis can be missed or delayed. We did not observe significant differences in HLA-DRB1 allele frequency between patients with CS compared to sarcoidosis in general. Awareness of CS as a primary manifestation can enable early detection and adequate intervention.
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| 4. |
- Håkansson, Anders, et al.
(författare)
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Cognitive Behavioral Therapy and Acceptance and Commitment Therapy (CBT-ACT) vs. Standard Care After Critical Illness Due to COVID-19 : Protocol for a Pilot Randomized Controlled Trial
- 2022
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Ingår i: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Post-covid syndrome is an emerging condition involving a wide range of symptoms, including high rates of poor mental health. The diagnostic relevance and clinical severity of these symptoms are largely unknown, and evidence for treatment of post-covid mental health symptoms is lacking. This protocol describes a pilot randomized clinical trial, primarily aiming to assess feasibility, participant adherence and satisfaction in a novel phycho-therapeutic intervention on post-covid anxiety and depression symptoms ≥1 year after critically ill COVID-19. Whether the intervention may generate improvements in post-covid depression, anxiety, post-traumatic stress and health-related quality of life (HRQoL) will be addressed in a following larger trial. Methods: A multicenter, investigator-initiated randomized controlled trial (Clinical Trial Identifier number NCT05119608) including Intensive Care Unit (ICU)-treated COVID-19 survivors, who display symptoms of anxiety and/or depression at follow-up 12 months after hospitalization (Hospital Anxiety and Depression Scale ≥8 for depression or anxiety). Eligible individuals are referred to a psychiatrist for structured diagnostic assessment and inclusion in the trial. Participants will be randomized to either a 10-week cognitive behavioral therapy intervention with added acceptance and commitment therapy (CBT-ACT) or standard care (primary care referral). Primary study outcome measure is feasibility and patient adherence, defined as the proportion of participants who consent to randomization and remain in the study including follow-up. Secondary outcome measures include reduced symptoms in the HADS depression/anxiety subscales, post-traumatic symptoms, HRQoL and user satisfaction at 3 months after the intervention. Discussion: This protocol describes a pilot trial to assess feasibility and preliminary effects of a structured psycho-therapeutic intervention to ameliorate mental health in a population severely affected by COVID-19, where evidence for structured psycho-therapy is lacking.
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| 5. |
- van Leeuwen, Marieke, et al.
(författare)
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Phase III study of the European Organisation for Research and Treatment of Cancer Quality of Life cancer survivorship core questionnaire
- 2023
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Ingår i: Journal of Cancer Survivorship. - : Springer Science and Business Media LLC. - 1932-2259 .- 1932-2267. ; 17:4, s. 1111-1130
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this study is to develop a European Organisation for Research and Treatment of Cancer Quality of Life Group (EORTC QLG) questionnaire that captures the full range of physical, mental, and social health-related quality of life (HRQOL) issues relevant to disease-free cancer survivors. In this phase III study, we pretested the provisional core questionnaire (QLQ-SURV111) and aimed to identify essential and optional scales. Methods: We pretested the QLQ-SURV111 in 492 cancer survivors from 17 countries with one of 11 cancer diagnoses. We applied the EORTC QLG decision rules and employed factor analysis and item response theory (IRT) analysis to assess and, where necessary, modify the hypothesized questionnaire scales. We calculated correlations between the survivorship scales and the QLQ-C30 summary score and carried out a Delphi survey among healthcare professionals, patient representatives, and cancer researchers to distinguish between essential and optional scales. Results: Fifty-four percent of the sample was male, mean age was 60 years, and, on average, time since completion of treatment was 3.8 years. Eleven items were excluded, resulting in the QLQ-SURV100, with 12 functional and 9 symptom scales, a symptom checklist, 4 single items, and 10 conditional items. The essential survivorship scales consist of 73 items. Conclusions: The QLQ-SURV100 has been developed to assess comprehensively the HRQOL of disease-free cancer survivors. It includes essential and optional scales and will be validated further in an international phase IV study. Implications for Cancer Survivors: The availability of this questionnaire will facilitate a standardized and robust assessment of the HRQOL of disease-free cancer survivors.
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