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- Thorlacius, Guðný Ella, et al.
(författare)
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Genetic and clinical basis for two distinct subtypes of primary Sjögren's syndrome
- 2021
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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 60:2, s. 837-848
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesClinical presentation of primary Sjögren’s syndrome (pSS) varies considerably. A shortage of evidence-based objective markers hinders efficient drug development and most clinical trials have failed to reach primary endpoints.MethodsWe performed a multicentre study to identify patient subgroups based on clinical, immunological and genetic features. Targeted DNA sequencing of 1853 autoimmune-related loci was performed. After quality control, 918 patients with pSS, 1264 controls and 107 045 single nucleotide variants remained for analysis. Replication was performed in 177 patients with pSS and 7672 controls.ResultsWe found strong signals of association with pSS in the HLA region. Principal component analysis of clinical data distinguished two patient subgroups defined by the presence of SSA/SSB antibodies. We observed an unprecedented high risk of pSS for an association in the HLA-DQA1 locus of odds ratio 6.10 (95% CI: 4.93, 7.54, P=2.2×10−62) in the SSA/SSB-positive subgroup, while absent in the antibody negative group. Three independent signals within the MHC were observed. The two most significant variants in MHC class I and II respectively, identified patients with a higher risk of hypergammaglobulinaemia, leukopenia, anaemia, purpura, major salivary gland swelling and lymphadenopathy. Replication confirmed the association with both MHC class I and II signals confined to SSA/SSB antibody positive pSS.ConclusionTwo subgroups of patients with pSS with distinct clinical manifestations can be defined by the presence or absence of SSA/SSB antibodies and genetic markers in the HLA locus. These subgroups should be considered in clinical follow-up, drug development and trial outcomes, for the benefit of both subgroups.
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| 2. |
- Andresen, Amanda K H, et al.
(författare)
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Radiographic features in 2D imaging as predictors for justified CBCT examinations of canine-induced root resorption.
- 2021
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Ingår i: Dento-Maxillo-Facial Radiology. - : British Institute of Radiology. - 0250-832X .- 1476-542X. ; 51:1
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This retrospective observational study aimed to evaluate the diagnostic accuracy of two-dimensional radiographs on canine-induced root resorption (CIRR) in lateral incisors and identify predictors of CIRR in patients with impacted maxillary canines (IMC).METHODS: Ninety-nine patients aged 9-17 years, with 156 IMCs, were included in the study. All had CBCT-volumes and two-dimensional radiographs consisting of at least one panoramic radiograph. Two radiologists jointly viewed all cases twice. First, radiographic features related to the IMC and possible CIRR were recorded from two-dimensional radiographs. Then, CIRR was determined from CBCT and according to position and extension classified as mild, moderate and severe.RESULTS: CIRRs was detected in 80% of lateral incisors (mild: 45%; moderate: 44%; severe: 11%). The sensitivity was generally low at mild and moderate cut-offs (29 and 29%), and somewhat higher for severe (50%). Corresponding specificities were 48%, 63% and 68%. Canine cusp-tip superimposing the lateral incisor's middle third and root/crown ratio >1 was positively associated with mild CIRR, with an odds ratio (OR) of 3.8 and 6.7, respectively. In addition, the root development stage was positively associated with moderate/severe CIRR when the canine root was nearly or fully developed (OR = 3.1).CONCLUSIONS: The diagnostic accuracy of two-dimensional radiographs was inadequate for detecting CIRR amongst patients referred for CBCT examinations. Based on our results, none of the suggested two-dimensional radiographic features could predict moderate/severe CIRR except for root development stage. IMC in a later stage of root development seems to be associated with a higher risk of moderate/severe CIRR.
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| 3. |
- Hallingström, Maria, et al.
(författare)
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Mid-trimester amniotic fluid proteome’s association with spontaneous preterm delivery and gestational duration
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 15:5
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Tidskriftsartikel (refereegranskat)abstract
- Background Amniotic fluid is clinically accessible via amniocentesis and its protein composition may correspond to birth timing. Early changes in the amniotic fluid proteome could therefore be associated with the subsequent development of spontaneous preterm delivery. Objective The main objective of this study was to perform unbiased proteomics analysis of the association between mid-trimester amniotic fluid proteome and spontaneous preterm delivery and gestational duration, respectively. A secondary objective was to validate and replicate the findings by enzyme-linked immunosorbent assay using a second independent cohort. Methods Women undergoing a mid-trimester genetic amniocentesis at Sahlgrenska University Hospital/Östra between September 2008 and September 2011 were enrolled in this study, designed in three analytical stages; 1) an unbiased proteomic discovery phase using LC-MS analysis of 22 women with subsequent spontaneous preterm delivery (cases) and 37 women who delivered at term (controls), 2) a validation phase of proteins of interest identified in stage 1, and 3) a replication phase of the proteins that passed validation using a second independent cohort consisting of 20 cases and 40 matched controls. Results Nine proteins were nominally significantly associated with both spontaneous preterm delivery and gestational duration, after adjustment for gestational age at sampling, but none of the proteins were significant after correction for multiple testing. Several of these proteins have previously been described as being associated with spontaneous PTD etiology and six of them were thus validated using enzyme linked immunosorbent assay. Two of the proteins passed validation; Neutrophil gelatinase-associated lipocalin and plasminogen activator inhibitor 1, but the results could not be replicated in a second cohort. Conclusions Neutrophil gelatinase-associated lipocalin and Plasminogen activator inhibitor 1 are potential biomarkers of spontaneous preterm delivery and gestational duration but the findings could not be replicated. The negative findings are supported by the fact that none of the nine proteins from the exploratory phase were significant after correction for multiple testing.
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| 4. |
- Wadell, M., et al.
(författare)
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Challenges imposed by the COVID-19 pandemic on the Obstetrics and Gynecology residency program: a mixed-methods Swedish survey in the COPE Staff cohort study
- 2022
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Ingår i: Bmc Medical Education. - : Springer Science and Business Media LLC. - 1472-6920. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background To outline how the training program and work situation of residents in Obstetrics and Gynecology (OB-GYN) was affected by the pandemic and to illuminate how residents experienced these changes. Methods As part of the COVID-19 in Pregnancy and Early Childhood Staff (COPE Staff) cohort study, between January and May 2021, all participating residents were invited to answer a 28-question online Resident Survey focusing on their specialist education, work situation and experiences during the COVID-19 pandemic. Descriptive statistics were given in percentages for categorical variables and means and standard deviations (SD) for continuous variables. Univariate comparative analyses were performed with the use of the Pearson's Chi-2-test for dichotomous data. The association between residents' worry about the quality and length of their specialist training, with extra clinical hours and transfer to other healthcare institutions were assessed by multivariate logistic regression. Free text responses were analyzed by content analysis. Results Of the 162 participating OB-GYN residents, 69% expressed concern that the pandemic would have a negative impact on their training. Ninety-five (95%) reported cancellation/postponement of educational activities, 70% performed fewer surgeries and 27% had been transferred to other healthcare institutions where about half reported having gained more general knowledge as a physician. Working extra clinical hours was reported by 69% (7.4 +/- 5.3 hours per week) and 14% had considered changing their profession due to the pandemic. Senior residents, compared to junior residents, more often experienced cancelled/postponed clinical rotations (30% vs 15%, P=0.02) and reported performing fewer surgeries (P=0.02). The qualitative analysis highlighted the lack of surgical procedural training as a major concern for residents. Conclusion The COVID-19 pandemic has strongly impacted the training program and work situation of OB-GYN residents in Sweden. Residents were concerned over the negative impact of the pandemic on their training program and senior residents reported more missed educational opportunities as compared to junior residents. Program directors, head of institutions and clinical supervisors can use the problem areas pinpointed by this study to support residents and compensate for missed educational opportunities. While hands-on-training and operating time cannot be compensated for, the authors hope that the findings of the study can help develop new strategies to minimize the negative impact of the current and future pandemics on resident education and work situation.
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