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2.
  • Aleman, Soo, et al. (author)
  • Health check-ups and family screening allow detection of hereditary hemochromatosis with less advanced liver fibrosis and survival comparable with the general population
  • 2011
  • In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 46:9, s. 1118-1126
  • Journal article (peer-reviewed)abstract
    • Objective. The information concerning the morbidity and mortality of hereditary hemochromatosis is based primarily on clinical cohorts of symptomatic patients. The major aim of this study was to analyze the long-term prognosis for Swedish patients with this condition, with respect to both clinical features and survival, in relation to the route by which the disease was detected. Patients and methods. 373 patients with hemochromatosis detected through routine health checkups (n = 153), family screening (n = 44), symptoms of arthralgia (n = 23), investigation of other diseases/symptoms (n = 108) or signs of liver disease (n = 45) were monitored for a mean period of 11.9 +/- 5.8 years. The degree of liver fibrosis and survival were analyzed. Results. Overall survival among these patients was not significantly different from that of a matched normal population. The patients diagnosed through health check-ups and family screening were detected at an earlier age and had the highest rate of survival. Liver biopsy at the time of diagnosis revealed cirrhosis in 9% of those detected through the health check-ups and 5% in the case of family screening, compared with 13% for the group with arthralgia, 17% for other diseases/symptoms and 42% for liver disease. Conclusion. Health check-ups and family screening allow detection of hereditary hemochromatosis at an earlier age and with less advanced liver fibrosis, although a few of these patients have already developed cirrhosis. Our study indicates that iron indices should be included in health check-ups, and if abnormal, should lead to further investigation.
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  • Ekstedt, Mattias, et al. (author)
  • Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up
  • 2015
  • In: Hepatology. - : John Wiley & Sons. - 0270-9139 .- 1527-3350. ; 61:5, s. 1547-1554
  • Journal article (peer-reviewed)abstract
    • Background and rationale for the study: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, strongly associated with insulin resistance and the metabolic syndrome. Nonalcoholic steatohepatitis, i.e. fatty liver accompanied by necroinflammatory changes, is mostly defined by the NAFLD activity score (NAS). The aim of the current study was to determine disease-specific mortality in NAFLD, and evaluate the NAS and fibrosis stage as prognostic markers for overall and disease-specific mortality. Methods: In a cohort study, data from 229 well-characterized patients with biopsy-proven NAFLD were collected. Mean follow-up was 26.4 (± 5.6, range 6-33) years. A reference population was obtained from the National Registry of Population, and information on time and cause of death were obtained from the Registry of Causes of Death. Main results: NAFLD patients had an increased mortality compared with the reference population (HR 1.29, CI 1.04-1.59, p=0.020), with increased risk of cardiovascular disease (HR 1.55, CI 1.11-2.15, p=0.01), hepatocellular carcinoma (HR 6.55, CI 2.14-20.03, p=0.001), infectious disease (HR 2.71, CI 1.02-7.26, p=0.046), and cirrhosis (HR 3.2, CI 1.05-9.81, p=0.041). Overall mortality was not increased in patients with NAS 5-8 and fibrosis stage 0-2 (HR 1.41, CI 0.97-2.06, p=0.07), whereas patients with fibrosis stage 3-4, irrespective of NAS, had increased mortality (HR 3.3, CI 2.27-4.76, p<0.001). Conclusions: NAFLD patients have increased risk of death, with a high risk of death from cardiovascular disease and liver-related disease. The NAS was not able to predict overall mortality, whereas fibrosis stage predicted both overall and disease-specific mortality.
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5.
  • Elmberg, Maria, et al. (author)
  • Increased Mortality Risk in Patients With Phenotypic Hereditary Hemochromatosis But Not in Their First-Degree Relatives
  • 2009
  • In: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 137:4, s. 1301-1309
  • Journal article (peer-reviewed)abstract
    • BACKGROUND & AIMS: Hereditary hemochromatosis (HH) is an autosomal-recessive disorder characterized by iron overload. Relatives of HH patients were screened and those with HH-associated mutations and an increased iron load were identified. However, little is known about their mortality or strategies for their management. We assessed mortality among Swedish patients with HH and their first-degree relatives using health and census registers. METHODS: We performed a matched population-based cohort study of 3832 patients with HH and their 14,496 first-degree relatives using data collected from 1990 through 2007. Mortality data from these groups were compared with that of 38,969 population controls and their 143,349 first-degree relatives using Cox regression analyses. RESULTS: Patients identified on the basis of hospitalization with HH had an increased risk (relative risk [RR]) for death (RR, 2.45; 95% confidence interval [CI], 2.27-2.64; 857 deaths). Patients identified through other means had a mortality risk that was lower than those identified in the hospital but higher than controls (RR, 1.15; 95% CI, 1.00-1.33; 216 deaths). Their first-degree relatives had only a marginally increased mortality risk (RR, 1.05; 95% CI, 1.01-1.10); this RR was similar to that of patients' spouses (RR, 1.09; 95% CI, 0.86-1.38; 82 deaths). Patients with HH who also had a family history of HH did not have an increased mortality risk compared with other groups (RR, 1.05; 95% CI 0.67-1.62; 21 deaths). CONCLUSIONS: Patients with HH have a modestly increased mortality risk compared with controls. The mortality of relatives is increased marginally compared with controls, and is similar among biological and nonbiological relatives.
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  • Hagstrom, Hannes, et al. (author)
  • Accuracy of Noninvasive Scoring Systems in Assessing Risk of Death and Liver-Related Endpoints in Patients With Nonalcoholic Fatty Liver Disease
  • 2019
  • In: Clinical Gastroenterology and Hepatology. - : Saunders Elsevier. - 1542-3565 .- 1542-7714. ; 17:6, s. 1148-1156.e4
  • Journal article (peer-reviewed)abstract
    • Background and AimsSeveral non-invasive scoring systems have been developed to determine risk of advanced fibrosis in non-alcoholic fatty liver disease (NAFLD). We examined the association between 4 scoring systems and incident severe liver disease and overall mortality in a large cohort of patients with biopsy-proven NAFLD.MethodsWe performed a retrospective analysis of data from 646 patients with biopsy-proven NAFLD, recruited from 2 hospitals in Sweden, from 1971 through 2009. The NAFLD fibrosis score (NFS), FIB-4, APRI, and BARD scores were calculated at the time of the liver biopsy. Based on each score, patients were assigned to categories of low, intermediate, or high risk for advanced fibrosis. Overall mortality and severe liver disease (cirrhosis, decompensated liver disease, liver failure, or hepatocellular carcinoma) were ascertained through linkage with national registers until the end of 2014. Cox regression, area under the receiver operating characteristic (AUROC) curve, and C-statistic analyses were used to study the predictive capacity of each scoring system.ResultsDuring a mean follow-up time of 19.9±8.7 years, there were 214 deaths and 76 cases of severe liver disease. For overall mortality, AUROC curve values were: NFS, 0.72 (95% CI, 0.68–0.76); FIB-4, 0.72 (95% CI, 0.68–0.76); BARD, 0.62 (95% CI, 0.58–0.66); and APRI, 0.52 (95% CI, 0.47–0.57). For severe liver disease, AUROC curve values were: NFS, 0.72 (95% CI, 0.66–0.78); FIB-4, 0.72 (95% CI, 0.66–0.79); BARD, 0.62 (95% CI, 0.55–0.69); APRI, 0.69 (95% CI, 0.63–0.76). C-statistics for all scores were of moderate capacity to predict outcomes.ConclusionsIn a retrospective analysis of data from 646 patients with biopsy-proven NAFLD, we found the NFS and the FIB-4 scores to most accurately determine risk of overall death or severe liver disease. However, the AUROC values for these scoring systems are not high enough for use in the clinic; new systems are needed to determine prognoses of patients with NAFLD.
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  • Hagström, Hannes, et al. (author)
  • Elevated serum ferritin is associated with increased mortality in non-alcoholic fatty liver disease after 16 years of follow-up
  • 2016
  • In: Liver international (Print). - : John Wiley & Sons. - 1478-3223 .- 1478-3231. ; 36:11, s. 1688-1695
  • Journal article (peer-reviewed)abstract
    • BACKGROUND AND AIMS: High levels of ferritin in patients with non-alcoholic fatty liver disease (NAFLD) are associated with significant fibrosis and higher NAFLD activity score (NAS). It is unclear if this association has an impact on mortality. We investigated if high levels of ferritin, with or without iron overload, were associated with an increased mortality in NAFLD.METHODS: We included 222 patients between 1979 and 2009 with biopsy-proven NAFLD and available serum ferritin concentrations. The cohort was divided into "high" (n = 89) and "normal" (n = 133) ferritin values, using a cut-point of 350 μg/L in males, and 150 μg/L in females, and stratified upon iron overload status. Data on mortality was obtained from a national, population based register. Poisson regression was used to estimate hazard ratios for mortality. The estimates were adjusted for age at biopsy, sex, smoking, BMI, diabetes, hypertension, cardiovascular disease and fibrosis stage at the time of biopsy.RESULTS: The median follow-up time was 15.6 years (range: 0.5-34.2). Patients with high ferritin had more advanced fibrosis and higher NAS than patients with normal ferritin (p < 0.05). Fifteen years after diagnosis, and after adjusting for confounders, the high-ferritin group showed an increasingly higher mortality that was statistically significant (Hazard ratio = 1.10 per year, 95% Confidence interval 1.01-1.21, p < 0.05). There was no difference in mortality between patients with different iron overload patterns.CONCLUSIONS: High levels of ferritin are associated with a long-term increased risk of death. This article is protected by copyright. All rights reserved.
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  • Hagström, Hannes, et al. (author)
  • Health Care Costs of Patients With Biopsy-Confirmed Nonalcoholic Fatty Liver Disease Are Nearly Twice Those of Matched Controls
  • 2020
  • In: Clinical Gastroenterology and Hepatology. - : ELSEVIER SCIENCE INC. - 1542-3565 .- 1542-7714. ; 18:7, s. 1592-
  • Journal article (peer-reviewed)abstract
    • BACKGROUND & AIMS: Data on healthcare resource use and costs associated with nonalcoholic fatty liver disease (NAFLD) in clinical practice are lacking. We compared real-life healthcare costs of patients with NAFLD to matched controls. METHODS: We performed a retrospective study of 646 patients with biopsy-proven NAFLD in Sweden from 1971 through 2009. Each patient was matched for age, sex, and county of residence with 10 persons from the general population (controls). We retrieved all healthcare contacts through Dec 31, 2014 from national registers. Unit costs were assigned to arrive at a total healthcare cost (in USD [$]) per study subject. RESULTS: During a mean follow-up of 19.9 years, we recorded a mean of 0.27 hospitalizations per year for patients with NAFLD vs 0.16 for controls (P <.001). This corresponded to an incremental cost of $635 per year for patients with NAFLD. Patients with NAFLD had a higher mean use of outpatient care visits: 1.46 contacts per year compared with 0.86 per year in controls, corresponding to $255 in additional costs (P <.001). Total costs incurred by patients with stage 3-4 fibrosis were higher than by patients with fibrosis stage 0-2 (mean annual costs, $4397 vs $629). Cumulative costs were higher for all stages of fibrosis compared to controls. CONCLUSIONS: Healthcare costs are nearly twice as high in patients with NAFLD than in matched controls. This is mostly attributable to higher costs for hospitalizations, but also to more outpatient visits. Patients with advanced fibrosis had the highest costs.
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  • Hagström, Hannes, et al. (author)
  • Low to moderate lifetime alcohol consumption is associated with less advanced stages of fibrosis in non-alcoholic fatty liver disease
  • 2017
  • In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 52:2, s. 159-165
  • Journal article (peer-reviewed)abstract
    • Background and aim: Moderate alcohol consumption has been associated with a lower risk of disease severity in non-alcoholic fatty liver disease (NAFLD). It is unclear if this reflects current or lifetime drinking, or can be attributed to confounders such as diet and exercise. We evaluated the impact of lifetime alcohol consumption on fibrosis severity in NAFLD. Methods: We prospectively enrolled 120 subjects with biopsy-proven NAFLD and through detailed questionnaires examined lifetime alcohol consumption, diet and physical activity. Main outcome measures were odds ratios (OR) for fibrosis stage, calculated through ordinal regression after adjustment for body mass index, diabetes mellitus type 2, smoking and age at biopsy. A biomarker for recent alcohol consumption, phosphatidyl ethanol (PEth) was sampled. Results: An increase in median weekly alcohol consumption to a maximum of 13 drinks per week was associated with lower fibrosis stage (adjusted OR for each incremental unit, 0.86; 95% CI, 0.76-0.97; p = .017). The lowest risk for fibrosis was found with the lowest odds seen in the top quartile of alcohol consumption (aOR 0.23; 95% CI 0.08-0.66; p = .006). Adding soft drink and coffee consumptions, and physical activity to the model did not change the estimates. Subjects with PEth >= 0.3 mu mol/L had higher ORs for a higher fibrosis stage (aOR 2.77; 95% CI 1.01-7.59; p = .047). Conclusion: Lifetime alcohol consumption with up to 13 units per week is associated with lower fibrosis stage in NAFLD. Elevated PEth is associated with higher stages of fibrosis.
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  • Hagström, Hannes, et al. (author)
  • Overweight in late adolescence predicts development of severe liver disease later in life : A 39 years follow-up study
  • 2016
  • In: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 65:2, s. 363-368
  • Journal article (peer-reviewed)abstract
    • BACKGROUND & AIMS: The increased prevalence of overweight has been suggested to contribute to the worldwide increase in liver diseases. We investigated if body mass index (BMI) in late adolescence predicts development of severe liver disease later in life.METHODS: We performed a cohort study using data from 44,248 men (18-20years) conscribed to military service in Sweden between 1969 and 1970. Outcome data were collected from national registers to identify any diagnosis of severe liver disease (i.e., diagnosis of decompensated liver disease, cirrhosis or death in liver disease) until the end of 2009. A Cox regression model was applied using BMI as independent variable. The model was adjusted for use of alcohol, use of narcotics, smoking, high blood pressure and cognitive ability at time of conscription.RESULTS: During a follow-up period of a mean of 37.8years, 393 men were diagnosed with severe liver disease (mean time to diagnosis 24.7years). BMI (Hazard ratio [HR]=1.05 for each unit increase in BMI, 95% confidence interval [CI]: 1.01-1.09, p=0.008) and overweight (HR=1.64 for BMI 25-30 compared to BMI 18.5-22.5, 95% CI: 1.16-2.32, p=0.006) were associated with an increased risk of development of severe liver disease.CONCLUSIONS: Being overweight in late adolescence is a significant predictor of severe liver disease later in life in men.LAY SUMMARY: We investigated close to 45,000 Swedish men in their late teens enlisted for conscription in 1969-1970. After almost 40years of follow-up, we found that being overweight was a risk factor for developing severe liver disease, independent of established risk factors such as alcohol consumption.
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  • Hagström, Hannes, et al. (author)
  • Risk for development of severe liver disease in lean patients with nonalcoholic fatty liver disease : A long-term follow-up study.
  • 2018
  • In: Hepatology communications. - : John Wiley & Sons. - 2471-254X. ; 2:1, s. 48-57
  • Journal article (peer-reviewed)abstract
    • Most patients with nonalcoholic fatty liver disease (NAFLD) are overweight or obese. However, a significant proportion of patients have a normal body mass index (BMI), denoted as lean NAFLD. The long-term prognosis of lean NAFLD is unclear. We conducted a cohort study of 646 patients with biopsy-proven NAFLD. Patients were defined as lean (BMI < 25.0), overweight (BMI 25.0-29.9), or obese (BMI ≥ 30.0) at the time of biopsy. Each case was matched for age, sex, and municipality to 10 controls. Overall mortality and development of severe liver disease were evaluated using population-based registers. Cox regression models adjusted for age, sex, type 2 diabetes, and fibrosis stage were used to examine the long-term risk of mortality and liver-related events in lean and nonlean NAFLD. Lean NAFLD was seen in 19% of patients, while 52% were overweight and 29% were obese. Patients with lean NAFLD were older, had lower transaminases, lower stages of fibrosis, and lower prevalence of nonalcoholic steatohepatitis at baseline compared to patients with a higher BMI. During a mean follow-up of 19.9 years (range 0.4-40 years) representing 12,631 person years and compared to patients who were overweight, patients with lean NAFLD had no increased risk for overall mortality (hazard ratio 1.06; P =  0.73) while an increased risk for development of severe liver disease was found (hazard ratio 2.69; P =  0.007). Conclusion: Although patients with lean NAFLD have lower stages of fibrosis, they are at higher risk for development of severe liver disease compared to patients with NAFLD and a higher BMI, independent of available confounders. (Hepatology Communications 2018;2:48-57).
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  • Johansson, Henrik J, et al. (author)
  • Proteomics profiling identify CAPS as a potential predictive marker of tamoxifen resistance in estrogen receptor positive breast cancer
  • 2015
  • In: Clinical Proteomics. - : Springer Science and Business Media LLC. - 1542-6416 .- 1559-0275. ; 12:1, s. 8-
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Despite the success of tamoxifen since its introduction, about one-third of patients with estrogen (ER) and/or progesterone receptor (PgR) - positive breast cancer (BC) do not benefit from therapy. Here, we aim to identify molecular mechanisms and protein biomarkers involved in tamoxifen resistance.RESULTS: Using iTRAQ and Immobilized pH gradient-isoelectric focusing (IPG-IEF) mass spectrometry based proteomics we compared tumors from 12 patients with early relapses (<2 years) and 12 responsive to therapy (relapse-free > 7 years). A panel of 13 proteins (TCEAL4, AZGP1, S100A10, ALDH6A1, AHNAK, FBP1, S100A4, HSP90AB1, PDXK, GFPT1, RAB21, MX1, CAPS) from the 3101 identified proteins, potentially separate relapse from non-relapse BC patients. The proteins in the panel are involved in processes such as calcium (Ca(2+)) signaling, metabolism, epithelial mesenchymal transition (EMT), metastasis and invasion. Validation of the highest expressed proteins in the relapse group identify high tumor levels of CAPS as predictive of tamoxifen response in a patient cohort receiving tamoxifen as only adjuvant therapy.CONCLUSIONS: This data implicate CAPS in tamoxifen resistance and as a potential predictive marker.
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  • Lindberg, Daniel, 1976- (author)
  • Generation sociala problem. En studie av hur unga vuxna ackumulerar sociala problem
  • 2016
  • Doctoral thesis (other academic/artistic)abstract
    • Young people is at the center of many of the rapid changes taking place in contemporary society and has to deal with the uncertainties that follows. One uncertainty is linked to the transition between leaving full time studies and entering employment were unemployment has become a natural step in becoming an adult. Hence the "becoming" has become a longer period of time in young people’s lives. The economic crisis in many European countries in recent years are the cause of many problems young people experience today. In relation to this brief background the thesis examines how social problems i.e. unemployment, deprivation, dependent on social welfare, low education and disability (affecting a person’s ability to work) is accumulated over time. The thesis point of departure is what Merton (1968) described in terms of The Matthew effect according to the Gospel of St. Matthew:For unto every one that hath shall be given, and he shall have abundance: but from him that hath not shall be taken away even that which he hath.It is the last part of this “effect” that is the center of attention. The research questions are: is there such a thing as the Matthew effect and if so how this process can be understood. Theoretically the study at hand elaborates the accumulation process by drawing on the concept of marginalization and social exclusion.By analyzing changes over time (3 years) in the five social problems described above (unemployment, deprivation etc.) for 64236 young people in the age of 19 to 25 years living in Sweden it is possible to describe patterns of social problem and how and why one specific problem or social problems in combination may lead to the accumulation of problem over time. These results are also combined with data from in-depth interviews whit young people that have accumulated social problem over time. It is argued that the combination of research methods gives a better understanding to the phenomenon at hand.The theoretical contribution relates to a better understanding of the process of accumulation of social problems for young people and to a better understanding of different steps in the accumulation process as well as central fault lines in this process. These findings can be used in practice for pinpointing groups of young adults in need of more as well as less support in handling and overcoming social problem and the transition from school to work.
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  • Lindberg, Odd, 1948-, et al. (author)
  • Om mammors livssituation
  • 1990
  • In: Anhörig. - Stockholm : Riksförbundet Föräldraföreningen mot narkotika. - 0280-512X. ; :4, s. 20-25
  • Journal article (other academic/artistic)
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  • Lindman, Rolf, et al. (author)
  • Abnormal palatopharyngeal muscle morphology in sleep-disordered breathing
  • 2002
  • In: Journal of the Neurological Sciences. - : Elsevier. - 1878-5883 .- 0022-510X. ; 195:1, s. 11-23
  • Journal article (peer-reviewed)abstract
    • The aim of the present study was to investigate whether histopathological changes can be detected in two soft palate muscles, the palatopharyngeus and the uvula, in 11 patients with long duration of sleep-disordered breathing (SDB). Muscle samples were collected froth patients undergoing uvulo-palatopharyngoplasty (UPPP). Reference samples from the corresponding areas were obtained at autopsy froth five previously healthy subjects. Muscle morphology, fibre type and myosin heavy chain (MyHC) compositions were analysed with enzyme-histochemical, immunohistochemical and biochemical techniques. The muscle samples from the patients, and especially those from the palatopharyngeus, showed several morphological abnormalities. The most striking findings were (i) increased amount of connective tissue, (ii) abnormal variability in fibre size, (iii) increased proportion of small-sized fibres, (iv) alterations in fibre type and MyHC compositions, (v) increased frequency of fibres containing developmental MyHC isoforms. Our findings point towards a pathological process of denervation and degeneration in the patient samples. Conclusively. the morphological abnormalities suggest a neuromuscular disorder of the soft palate in SDB patients. (C) 2002 Elsevier Science B.V. All rights reserved.
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18.
  • Lindman, Rolf, et al. (author)
  • Morphological characterization of the levator veli palatini muscle in children born with cleft palates
  • 2001
  • In: The Cleft Palate-Craniofacial Journal. - 1055-6656 .- 1545-1569. ; 38:5, s. 438-448
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: The aim of this study was to analyze, morphologically and biochemically, one of the soft palate muscles, the levator veli palatini (LVP), in children born with cleft palate.SUBJECTS AND METHODS: Biopsies were obtained from nine male and three female infants in connection with the early surgical repair of the hard and soft palate. Samples from five adult normal LVP muscles were used for comparison. The muscle morphology, fiber type and myosin heavy chain (MyHC) compositions, capillary supply, and content of muscle spindles were analyzed with different enzyme-histochemical, immunohistochemical, and biochemical techniques.RESULTS: Compared with the normal adult subjects, the LVP muscle from the infantile subjects with cleft had a smaller mean fiber diameter, a larger variability in fiber size and form, a higher proportion of type II fibers, a higher amount of fast MyHCs, and a lower density of capillaries. No muscle spindles were observed. Moreover, one-third of the biopsies from the infantile subjects with cleft LVP either lacked muscle tissue or contained only a small amount.CONCLUSIONS: The LVP muscle from children with cleft palate has a different morphology, compared with the normal adult muscle. The differences might be related to different stages in maturation of the muscles, changes in functional demands with growth and age, or a consequence of the cleft. The lack of contractile tissue in some of the cleft biopsies offers one possible explanation to a persistent postsurgical velopharyngeal insufficiency in some patients, despite a successful surgical repair.
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  • Shang, Ying, et al. (author)
  • Non-alcoholic fatty liver disease does not increase dementia risk although histology data might improve risk prediction
  • 2021
  • In: JHEP Reports. - : Elsevier. - 2589-5559. ; 3:2
  • Journal article (peer-reviewed)abstract
    • Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is common in the general population, but its association with dementia is unclear. We aimed to assess the risk of dementia related to NAFLD, and to determine whether histological parameters could improve the predictive capacity of a conventional risk model for dementia in patients with biopsy-proven NAFLD. Methods: A retrospective matched cohort study of 656 NAFLD patients underwent liver biopsy at 2 hospitals between 1971 and 2009. Up to 10 individuals (controls) from the general population (n = 6,436) were matched for age, sex, and municipality to each patient. Dementia was ascertained from National registers until 2014. Using Cox regression, we estimated hazard ratios for dementia with 95% confidence intervals. In the biopsy cohort, the discriminative power of adding histological markers to a conventional risk model was assessed by Harrells C-index and compared with a likelihood-ratio test. Results: During a mean follow-up of 19.7 +/- 8.7 years, 3.3% of the NAFLD patients and 4.9% of the controls developed dementia (p = 0.07). Overall, NAFLD was not significantly associated with incident dementia. In the biopsy cohort, the model of conventional risk factors (age, sex, hypertension, and cardiovascular diseases) had a C-index of 0.912 to predict incident dementia. Adding individual histological parameters significantly increased the prediction of dementia, with the most pronounced improvement for fibrosis stage (C-index = 0.938, p <0.05). Conclusions: Although NAFLD was not associated with the risk of dementia, we found that adding histological markers to a conventional risk model for dementia enhanced the predictive capacity, indicating a shared metabolic origin. Lay summary: Both non-alcoholic fatty liver disease (NAFLD) and dementia are increasing in prevalence because of a more sedentary lifestyle, increased prevalence of obesity and population ageing. However, the link between these 2 diseases is not well studied. We investigated the association between NAFLD and the risk of dementia and found no association. However, liver histology parameters, especially fibrosis, could significantly improve the prediction of dementia risk. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).
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  • Stål, Per, et al. (author)
  • Capillary supply of the soft palate muscles is reduced in long-term habitual snorers
  • 2009
  • In: Respiration. - : S. Karger AG. - 0025-7931 .- 1423-0356. ; 77:3, s. 303-310
  • Journal article (peer-reviewed)abstract
    • Background: Snoring and obstructive sleep apnea (OSA) cause vibration and stretch of the upper airway tissues that may result in neuromuscular damage and changes in the microcirculation. Objectives: The aim of this investigation was to test whether long-term snoring affects capillary supply in soft palate muscles. Methods: Samples from the palatopharyngeus (PP) and uvula (UV) muscles were collected from 8 patients undergoing uvulo-palatopharyngoplasty because of habitual snoring and OSA. Control samples were obtained at autopsy. The muscles were analyzed using immunohistochemistry and morphometry. Results: The patients' palate muscles had a lower capillary density (PP 443 vs. 711 capillaries/mm(2), p < 0.001, and UV 452 vs. 624 capillaries/mm(2), p = 0.009), a lower number of capillaries related to an individual muscle fiber (PP 1.3 vs. 2.7, p = 0.003, and UV 1.0 vs. 1.9, p = 0.03) and a lower number of capillaries related to the fiber size (PP 0.9 vs. 2.1, p = 0.001, and UV 0.6 vs. 1.9, p = 0.002). Conclusions: Our results indicate that reduced capillary supply of palate muscles plays a pathophysiological role in long-term snorers and OSA. The cause of the low capillary supply is unclear, but neuromuscular injury due to repeated vibratory and stretch trauma of the soft palate during snoring is a plausible mechanism.
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