| 1. |
- Ranebo, Mats, 1970-
(författare)
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Rotator Cuff Tears : Short- and long-term aspects on treatment outcome
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rotator cuff tear is a common disorder and there is a lack of knowledge of appropriate treatment and consequences of different treatment modalities. The overall aim of this thesis was to examine short- and long-term results of rotator cuff tear treatment.In Paper I we did a retrospective 21 to 25-year follow-up of a consecutive series of patients with partial and full-thickness rotator cuff tears, treated with acromioplasty without cuff repair. The cuff status had been documented in a specific perioperative protocol in all patients at the index operation. We did x-ray, ultrasonography and clinical scores with Constant score and Western Ontario Rotator Cuff index (WORC) at follow-up. We identified 111 patients with either a partial or a full-thickness tear, but at follow-up 21 were deceased and 11 were too ill from medical conditions unrelated to their shoulder. Out of the remaining 78 eligible patients, 69 were examined (follow-up rate 88 %) and they had a mean age at the index operation of 49 years (range 19-69 years). Forty-five had a partial tear and 24 a full-thickness tear at the index operation. At follow-up, 74% of patients with full-thickness tear had cuff tear arthropathy grade 2 or more according to the arthropathy classification of Hamada (grade 1 to 5) and 87% had developed tear progression (i.e. a larger tear). Corresponding numbers in those with a partial tear was 7 % arthropathy and 42 % tear progression, and the differences between the full-thickness group and the partial tear group was significant for both outcome measures (P<0.001 for both analyses). In those with arthropathy, the mean Constant score was 47 (standard deviation [SD], 23), the mean age and gender-adjusted Constant score 62 (SD, 27) and the mean WORC 58 % (SD, 26). Patients with a partial tear at follow-up had mean Constant score and WORC within the normal range. In multivariable analysis with logistic regression, having a full-thickness tear at the index operation was a risk factor for arthropathy (odds ratio [OR] 37.8; 95% confidence interval [CI], 8.2-175.0) and for tear progression (OR 6.09; 95% CI, 1.41-26.29).In Paper II we examined the contralateral shoulder in the same patients as in paper I and with the same methodology. Sixty-one patients were examined and 38 had had a partial tear at the index operation 21-25 years ago and 23 a full-thickness tear. The overall rate of contralateral full-thickness tears was 50.8 %, which is higher than the 16-35 % rate found in previous studies of newly diagnosed cuff patients. The rate of contralateral full-thickness tear ranged from 13.6 % in patients with a partial tear in the index shoulder at follow-up, to 90 % in patients with a full-thickness tear and arthropathy in the index shoulder. There was a significant correlation regarding conditions between shoulders in the same patient, with a Spearman coefficient of 0.72 for the number of ten-dons with a full-thickness tear, 0.31 for Hamada grade of arthropathy and 0.65 for Constant score. The number of tendons with a full-thickness tear in the index shoulder at follow-up was a risk factor for a contralateral full-thickness tear (OR 3.28; 95% CI, 1.67-6.44) in a multi-variable logistic regression model. We also found that cuff tear arthropathy was significantly more common in patients who had undergone an acromioplasty (P<0.001), a finding which is not confirmatory but may generate a hypothesis.Paper III addressed 17 to 20-year results after operation with a synthetic interposition graft for irreparable cuff tears. We used X-ray, ultrasonography and clinical scores at follow-up. We identified a consecutive series of 13 patients, one of whom was deceased at follow-up. Ten of the remaining 12 participated in a complete follow-up and 2 did only x-ray examination. Nine out of 12 (75 %; 95% CI, 43-95 %) had cuff tear arthropathy Hamada grade 2 or more in the index shoulder at follow-up. The mean Constant score was 46 (SD, 26) and the mean WORC 59 % (SD, 20). Seven out of 12 had contralateral cuff tear arthropathy, and the difference in frequency of arthropathy between shoulders was not statistically significant (P=0.667).In Paper IV we tested whether early repair of small cuff tears, involving mainly supraspinatus, would give a superior clinical result com-pared to physiotherapy without repair in a prospective randomised trial with 12 months follow-up. We used Constant score as the primary out-come, and WORC, EQ-VAS and Numerical Rating Scale for pain (NRS) as secondary outcomes. We also aimed at assessing the rate of tear progression in unrepaired shoulders and the healing rate in repaired shoulders by Magnetic Resonance Imaging (MRI) performed at 12 months. With a high grade of follow-up (100 % for 12 months Constant score and 95 % for 12 months MRI), the repair group had a 12 months median Constant score of 83 (Quartile range [QR], 25) and the conservative group 78 (QR, 22). This between-group difference in medians of 4.5 (95% CI,-5 to 9; P=0.68) was not statistically significant and we did not detect any significant differences in the secondary outcomes at 12 months. The retear rate was 6.5 % in repaired patients and 29 % of unrepaired patients had a tear enlargement >5 mm.The results in this thesis indicate that patients with small, traumatic, full-thickness tears of mainly supraspinatus have no clinical benefit of early surgical repair compared to physiotherapy alone, but in the long-term, patients with full-thickness tears have an increased risk of tear progression, cuff tear arthropathy and low clinical scores. These results are especially important in the treatment decision of repair or not in younger patients. Having a full-thickness tear is also a risk factor for having a contralateral cuff tear, a phenomenon that underlines the importance of endogenous factors in the development of rotator cuff tears. If a cuff tear is not repairable to bone, the addition of a synthetic inter-position graft does not seem to prevent cuff tear arthropathy.
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| 2. |
- Kanberg, Nelly, et al.
(författare)
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Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19.
- 2020
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Ingår i: Neurology. - 1526-632X .- 0028-3878. ; 95:12, s. e1754-e1759
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Tidskriftsartikel (refereegranskat)abstract
- To test the hypothesis that coronavirus disease 2019 (COVID-19) has an impact on the CNS by measuring plasma biomarkers of CNS injury.We recruited 47 patients with mild (n = 20), moderate (n = 9), or severe (n = 18) COVID-19 and measured 2 plasma biomarkers of CNS injury by single molecule array, neurofilament light chain protein (NfL; a marker of intra-axonal neuronal injury) and glial fibrillary acidic protein (GFAp; a marker of astrocytic activation/injury), in samples collected at presentation and again in a subset after a mean of 11.4 days. Cross-sectional results were compared with results from 33 age-matched controls derived from an independent cohort.The patients with severe COVID-19 had higher plasma concentrations of GFAp (p = 0.001) and NfL (p < 0.001) than controls, while GFAp was also increased in patients with moderate disease (p = 0.03). In patients with severe disease, an early peak in plasma GFAp decreased on follow-up (p < 0.01), while NfL showed a sustained increase from first to last follow-up (p < 0.01), perhaps reflecting a sequence of early astrocytic response and more delayed axonal injury.We show neurochemical evidence of neuronal injury and glial activation in patients with moderate and severe COVID-19. Further studies are needed to clarify the frequency and nature of COVID-19-related CNS damage and its relation to both clinically defined CNS events such as hypoxic and ischemic events and mechanisms more closely linked to systemic severe acute respiratory syndrome coronavirus 2 infection and consequent immune activation, as well as to evaluate the clinical utility of monitoring plasma NfL and GFAp in the management of this group of patients.
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| 3. |
- Stråvik, Mia, 1994, et al.
(författare)
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Maternal Intake of Cow's Milk during Lactation Is Associated with Lower Prevalence of Food Allergy in Offspring
- 2020
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643 .- 2072-6643. ; 12:12, s. 1-19
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Tidskriftsartikel (refereegranskat)abstract
- Maternal diet during pregnancy and lactation may affect the propensity of the child to develop an allergy. The aim was to assess and compare the dietary intake of pregnant and lactating women, validate it with biomarkers, and to relate these data to physician-diagnosed allergy in the offspring at 12 months of age. Maternal diet during pregnancy and lactation was assessed by repeated semi-quantitative food frequency questionnaires in a prospective Swedish birth cohort (n = 508). Fatty acid proportions were measured in maternal breast milk and erythrocytes. Allergy was diagnosed at 12 months of age by a pediatrician specialized in allergy. An increased maternal intake of cow's milk during lactation, confirmed with biomarkers (fatty acids C15:0 and C17:0) in the maternal blood and breast milk, was associated with a lower prevalence of physician-diagnosed food allergy by 12 months of age. Intake of fruit and berries during lactation was associated with a higher prevalence of atopic eczema at 12 months of age. Our results suggest that maternal diet modulates the infant's immune system, thereby influencing subsequent allergy development.
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| 4. |
- Robertson, Josefina, et al.
(författare)
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Serum neopterin levels in relation to mild and severe COVID-19
- 2020
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Ingår i: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, is rapidly spreading worldwide. There is limited information about prognostic markers that could help clinicians to identify COVID-19 patients with a poor prognosis. Serum levels of the immune activation marker neopterin has shown to be of prognostic value in patients with SARS. The aim of this study was to investigate whether serum neopterin is associated with the severity of COVID-19. Methods: We included 34 patients with confirmed COVID-19 between March 3 and March 30, 2020. Fifteen patients had mild disease and did not require hospitalization, whereas 19 patients developed severe COVID-19 requiring intensive care. Concentrations of serum neopterin, tryptophan, and kynurenine were measured at and repeatedly after inclusion. Results: We found a more than two-fold higher mean concentration of neopterin in severely ill patients (mean value 42.0 nmol/L (SD 18.2)) compared to patients with mild symptoms (16.9 nmol/L (SD 11.0)). All of the severe cases had elevated neopterin concentrations (> 9.1 nmol/L) at the initial sampling with values ranging from 17.2 to 86.7 nmol/L. In comparison, 10 of 15 patients with mild disease had neopterin levels above 9.1 nmol/L, with concentrations in the range from 4.9 to 31.6 nmol/L. Neopterin levels gradually decreased during the course of COVID-19, but severe cases maintained elevated levels for a longer period. Moreover, lower levels of tryptophan and higher levels of kynurenine, indicating an increased tryptophan catabolism, were seen in the group with severe cases. Conclusions: In conclusion, we found that serum neopterin levels are associated with the severity of COVID-19. Our findings suggest that neopterin could be used as a prognostic marker, but further studies are needed to elucidate how it can be used in the clinic.
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| 5. |
- Waldenström, Jesper, 1985, et al.
(författare)
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The relation of 25-hydroxy vitamin D concentrations to liver histopathology, seasonality and baseline characteristics in chronic hepatitis C virus genotype 2 or 3 infection
- 2020
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 15:8
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Tidskriftsartikel (refereegranskat)abstract
- Background and objectives The hydroxylation to 25-hydroxy vitamin D (25(OH)D) occurs in the liver and the impact of liver disease on vitamin D is unclear. This study evaluated the relationship between vitamin D concentrations and hepatic histopathology, seasonality and patient characteristics in well-characterized patients having undergone a liver biopsy. Method 25(OH)D was measuredpost-hocin pre-treatment serum from 331 North European patients with chronic HCV genotype 2 or 3 infection (NORDynamIC study). Liver biopsies were scored for fibrosis and inflammation according to the Ishak protocol, and graded for steatosis. Non-invasive markers of hepatic fibrosis as well as baseline viral and host characteristics, including genetic polymorphisms rs2228570, rs7975232, and rs10877012 were also evaluated. Results Mean 25(OH)D concentration was 59 +/- 23 nmol/L, with 41% having values <50 nmol/L and 6% were <30 nmol/L. 25(OH)D correlated with fibrosis (r = -0.10, p <= 0.05) in univariate but not in multivariate analyses. No association was observed between 25(OH)D and hepatic inflammation, but with steatosis in HCV genotype 2 infected patients. None of the genetic polymorphisms impacted on 25(OH)D levels or fibrosis. 25(OH)D levels were significantly inversely correlated to BMI (r = -0.19, p = 0.001), and was also associated with season and non-Caucasian ethnicity. Conclusion Fibrosis was not independently associated with 25(OH)D concentration and no association was seen with hepatic inflammation, but HCV genotype 2 infected patients with moderate-to-severe steatosis had lower 25(OH)D levels compared to those without steatosis. A high percentage had potential risk of 25(OH)D deficiency, and BMI, seasonality and ethnicity were independently associated with 25(OH)D as previously reported.
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| 6. |
- Zhang, C., et al.
(författare)
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The acute effect of metabolic cofactor supplementation: a potential therapeutic strategy against non-alcoholic fatty liver disease
- 2020
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Ingår i: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 16:4
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of non-alcoholic fatty liver disease (NAFLD) continues to increase dramatically, and there is no approved medication for its treatment. Recently, we predicted the underlying molecular mechanisms involved in the progression of NAFLD using network analysis and identified metabolic cofactors that might be beneficial as supplements to decrease human liver fat. Here, we first assessed the tolerability of the combined metabolic cofactors including l-serine, N-acetyl-l-cysteine (NAC), nicotinamide riboside (NR), and l-carnitine by performing a 7-day rat toxicology study. Second, we performed a human calibration study by supplementing combined metabolic cofactors and a control study to study the kinetics of these metabolites in the plasma of healthy subjects with and without supplementation. We measured clinical parameters and observed no immediate side effects. Next, we generated plasma metabolomics and inflammatory protein markers data to reveal the acute changes associated with the supplementation of the metabolic cofactors. We also integrated metabolomics data using personalized genome-scale metabolic modeling and observed that such supplementation significantly affects the global human lipid, amino acid, and antioxidant metabolism. Finally, we predicted blood concentrations of these compounds during daily long-term supplementation by generating an ordinary differential equation model and liver concentrations of serine by generating a pharmacokinetic model and finally adjusted the doses of individual metabolic cofactors for future human clinical trials.
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| 7. |
- Sigurdsson, Gudmundur Vignir, 1985, et al.
(författare)
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Altered body composition profiles in young adults with childhood-onset inflammatory bowel disease
- 2020
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 55:2, s. 169-177
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with inflammatory bowel disease (IBD) often develop alterations in body composition in terms of their proportions of lean mass and fat mass, as well as reduced bone mineral density (BMD). However, there are limited data on the skeletal muscle index (SMI) and percentage fat (fat %) for young adults with childhood-onset IBD. Our aim was to investigate the body compositions of these patients, with the focus on SMI and fat %. Methods: Body composition was estimated by dual x-ray absorptiometry for 94 young adults with childhood-onset IBD aged 18–27 years, 65 of whom had ulcerative colitis. The Z-scores for SMI, fat %, and BMD were calculated using the normative data from 1,289 individuals with corresponding age. Based on the SMI and fat % Z-scores, each patient was classified as having a body composition profile that was: (i) normal; (ii) obese (fat % Z-score >1); (iii) myopenic (SMI Z-score < −1); or (iv) myopenic-obese. Results: A higher proportion of young adults with childhood-onset IBD had a body composition profile classified as myopenic (24%) or myopenic-obese (9%), as compared to the controls (myopenic [16%, p =.016]; myopenic-obese [2%, p =.002]). Patients with the myopenic or myopenic-obese profile had significantly lower total body BMD Z-scores (−1.3 ± 0.7 and −1.4 ± 0.9, respectively) than patients with the normal profile (−0.2 ± 1.1; p <.001 and p =.004, respectively). Diagnosis of IBD in childhood represented an additional risk for low BMD, regardless of SMI Z-score. Conclusion: Young adults with childhood-onset IBD have a high risk for having altered body composition traits.Summary Young adults with childhood-onset IBD carry a high risk for altered body composition traits. The myopenic and myopenic-obese body composition profiles were more frequently observed in patients with IBD than controls, and these profiles were strongly associated with low BMD.
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| 8. |
- Marklund, Emelie, et al.
(författare)
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Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders.
- 2020
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 15:10
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Tidskriftsartikel (refereegranskat)abstract
- To accurately interpret COVID-19 seroprevalence surveys, knowledge of serum-IgG responses to SARS-CoV-2 with a better understanding of patients who do not seroconvert, is imperative. This study aimed to describe serum-IgG responses to SARS-CoV-2 in a cohort of patients with both severe and mild COVID-19, including extended studies of patients who remained seronegative more than 90 days post symptom onset.SARS-CoV-2-specific IgG antibody levels were quantified using two clinically validated and widely used commercial serological assays (Architect, Abbott Laboratories and iFlash 1800, YHLO), detecting antibodies against the spike and nucleocapsid proteins.Forty-seven patients (mean age 49 years, 38% female) were included. All (15/15) patients with severe symptoms and 29/32 (90.6%) patients with mild symptoms of COVID-19 developed SARS-CoV-2-specific IgG antibodies in serum. Time to seroconversion was significantly shorter (median 11 vs. 22 days, P = 0.04) in patients with severe compared to mild symptoms. Of the three patients without detectable IgG-responses after >90 days, all had detectable virus-neutralizing antibodies and in two, spike-protein receptor binding domain-specific IgG was detected with an in-house assay. Antibody titers were preserved during follow-up and all patients who seroconverted, irrespective of the severity of symptoms, still had detectable IgG levels >75 days post symptom onset.Patients with severe COVID-19 both seroconvert earlier and develop higher concentrations of SARS-CoV-2-specific IgG than patients with mild symptoms. Of those patients who not develop detectable IgG antibodies, all have detectable virus-neutralizing antibodies, suggesting immunity. Our results showing that not all COVID-19 patients develop detectable IgG using two validated commercial clinical methods, even over time, are vital for the interpretation of COVID-19 seroprevalence surveys.
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| 9. |
- Trolle Lagerros, Ylva, et al.
(författare)
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Risk of Delayed Discharge and Reoperation of Gastric Bypass Patients with Psychiatric Comorbidity : a Nationwide Cohort Study
- 2020
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Ingår i: Obesity Surgery. - : Springer Science and Business Media LLC. - 0960-8923 .- 1708-0428. ; 30:7, s. 2511-2518
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundGastric bypass (GBP) surgery is considered a safe and effective treatment for obesity. However, there is uncertainty regarding the impact of preexisting psychiatric comorbidity on GBP complications. We have investigated whether a psychiatric diagnosis before GBP surgery is associated with delayed discharge (the odds of being in the 90th percentile of length of stay) and rate of reoperation in a nationwide Swedish cohort.MethodsPatients undergoing GBP surgery during 2008–2012 were identified and followed up through the National Patient Register and the Prescribed Drug Register. Logistic regression models were fitted to the studied outcomes.ResultsAmong the 22,539 patients identified, a prior diagnosis of bipolar disorder, schizophrenia, depression, neurotic disorders, ADHD (attention deficit hyperactivity disorder), substance use disorder, eating disorder, personality disorder, or self-harm since 1997 (n = 9480) was found to be associated with delayed discharge after GBP surgery (odds ratio [OR] = 1.47, confidence interval [CI] 1.34–1.62), especially in patients with psychiatric hospitalization exceeding 1 week in the 2 years preceding GBP surgery (OR = 2.06, CI 1.30–3.28), compared with those not hospitalized within psychiatry. Likewise, patients with a prior psychiatric diagnosis were more likely to be reoperated within 30 days (OR = 1.25, CI 1.11–1.41), with twice the likelihood OR 2.23 (CI 1.26–3.92) for patients with psychiatric hospitalization of up to a week in the 2 years preceding GBP surgery, compared with patients who had not been hospitalized within psychiatry.ConclusionsA psychiatric diagnosis before GBP surgery was associated with delayed discharge and increased likelihood of reoperation within 30 days. Patients with a prior psychiatric diagnosis may, therefore, need additional attention and support.
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| 10. |
- Tyrberg, Tobias, et al.
(författare)
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Serum and cerebrospinal fluid neurofilament light chain in patients with central nervous system infections caused by varicella-zoster virus.
- 2020
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Ingår i: Journal of neurovirology. - : Springer Science and Business Media LLC. - 1538-2443 .- 1355-0284. ; 26:5, s. 719-726
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Tidskriftsartikel (refereegranskat)abstract
- Varicella-zoster virus (VZV) is a common cause of viral central nervous system (CNS) infection, and patients may suffer from severe neurological sequelae. The biomarker neurofilament light chain (NFL) is used for assessment of neuronal damage and is normally measured in cerebrospinal fluid (CSF). Novel methods have given the possibility to measure NFL in serum instead, which could be a convenient tool to estimate severity of disease and prognosis in VZV CNS infections. Here, we investigate the correlation of serum and CSF NFL in patients with VZV CNS infection and the association of NFL levels in serum and CSF with different VZV CNS entities. NFL in serum and CSF was measured in 61 patients who were retrospectively identified with neurological symptoms and VZV DNA in CSF detected by PCR. Thirty-three herpes zoster patients and 40 healthy blood donors served as control groups. NFL levels in serum and CSF correlated strongly in the patients with VZV CNS infection. Encephalitis was associated with significantly higher levels of NFL in both serum and CSF compared with meningitis and Ramsay Hunt syndrome. Surprisingly, herpes zoster controls had very high serum NFL levels, comparable with those shown in encephalitis patients. We show that analysis of serum NFL can be used instead of CSF NFL for estimation of neuronal injury in patients with VZV CNS infection. However, high levels of serum NFL also in patients with herpes zoster, without signs of CNS involvement, may complicate the interpretation.
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