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1.
  • Björkman, Kristoffer, et al. (author)
  • Clinical course of patients with single large-scale mtDNA deletions and childhood onset anemia
  • 2022
  • In: 14th European Paediatric Neurology Society Congress, Glasgow, UK (ISBN 978-3-00-072065-9).
  • Conference paper (other academic/artistic)abstract
    • Objective: To add to our knowledge of the clinical spectrum of patients with single large-scale mitochondrial DNA (mtDNA) deletion and childhood onset anemia. Methods: Retrospective collection of clinical data from medical records for patients, both living and deceased, with a single large-scale mtDNA deletion from seven mitochondrial disease centers in five countries. Statistical analysis with descriptive methods and Kaplan-Meier survival analysis. Results: Seventeen patients matching the genetic criterium and with anemia onset before six years of age. Exocrine pancreatic insufficiency was only seen in five patients in this group. Multiple organs were involved in all patients, with the most common non-hematologic ones being skeletal muscle, central nervous system, endocrine, eyes, gastrointestinal system, kidneys, hearing, liver and heart. Psychomotor retardation was seen in ten patients, hearing impairment in nine patients, failure to thrive in eight patients. Eight later developed Kearns-Sayre syndrome. Eleven patients were deceased, with a median age at death of 7.5 years. Conclusions: The classically described phenotype of patients with large-scale mtDNA deletions and early onset anemia is Pearson marrow-pancreas syndrome, characterized by sideroblastic anemia and exocrine pancreas dysfunction. Only a minority of our patients fulfill the original criteria of Pearson syndrome though. Involvement of other organs than the pancreas is more common. The clinical course vary, but multi-system impact is the rule and life-expectancy is low. Early onset anemia in patients with large-scale mtDNA deletions is most frequently not associated with exocrine pancreas dysfunction. Better knowledge of the phenotype is helpful for diagnosis and more accurate prognosis.
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2.
  • Strömland, Kerstin, 1934, et al. (author)
  • Oculo-auriculo-vertebral spectrum: associated anomalies, functional deficits and possible developmental risk factors.
  • 2007
  • In: American Journal of Medical Genetics. Part A. - : Wiley. - 1552-4825 .- 1552-4833. ; 143A:12, s. 1317-1325
  • Journal article (peer-reviewed)abstract
    • Swedish patients with the oculo-auriculo-vertebral (OAV) spectrum participated in a prospective multidisciplinary investigation. The aims of the study were to describe their systemic and functional defects, especially autism spectrum disorders, and to search for possible etiologic risk factors. Available medical records were studied and the mothers answered a questionnaire on history of prenatal events. A clinical examination evaluating systemic findings, vision, hearing, speech, oral and swallowing function, and neuropsychiatric function, especially autism, was made. Eighteen patients, (11 males, 7 females) aged 8 months to 17 years with OAV were studied. Most frequent systemic malformations included, ear abnormalities (100%), ocular malformations (72%), vertebral deformities (67%), cerebral anomalies (50%), and congenital heart defects (33%). Functional defects consisted of hearing impairment (83%), visual impairment (28%), both visual and hearing impairment (28%), difficulties in feeding/eating (50%), speech (53%), mental retardation (39%), and severe autistic symptoms (11%). Three children were born following assisted fertilization (two intracytoplasmatic sperm injection, one in vitro fertilization), two mothers reported early bleedings, and six (33%) mothers had smoked during pregnancy.
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3.
  • Nordanstig, Joakim, et al. (author)
  • Vascular Quality of Life Questionnaire-6 facilitates health-related quality of life assessment in peripheral arterial disease
  • 2014
  • In: Journal of Vascular Surgery. - : Elsevier BV. - 0741-5214 .- 1097-6809. ; 59:3, s. 700-U492
  • Journal article (peer-reviewed)abstract
    • Background: Most commonly used outcome measures in peripheral arterial disease (PAD) provide scarce information about achieved patient benefit. Therefore, patient-reported outcome measures have become increasingly important as complementary outcome measures. The abundance of items in most health-related quality of life instruments makes everyday clinical use difficult. This study aimed to develop a short version of the 25-item Vascular Quality of Life Questionnaire (VascuQoL-25), a PAD-specific health-related quality of life instrument. Methods: The study recruited 129 individuals with intermittent claudication and 71 with critical limb ischemia from two university hospitals. Participants were a mean age of 70 +/- 9 years, and 57% were men. All patients completed the original VascuQoL when evaluated for treatment, and 127 also completed the questionnaire 6 months after a vascular procedure. The VascuQoL-25 was reduced based on cognitive interviews and psychometric testing. The short instrument, the VascuQoL-6, was tested using item-response theory, exploring structure, precision, item fit, and targeting. A subgroup of 21 individuals with intermittent claudication was also tested correlating the results of VascuQoL-6 to the actual walking capacity, as measured using global positioning system technology. Results: On the basis of structured psychometric testing, the six most informative items were selected (VascuQoL-6) and tested vs the original VascuQoL-25. The correlation between VascuQoL-25 and VascuQoL-6 was r = 0.88 before intervention, r = 0.96 after intervention, and the difference was r = 0.91 (P < .001). The Cronbach alpha for the VascuQoL-6 was .85 before and .94 after intervention. Cognitive interviews indicated that the responders considered all six items to be relevant and comprehensible. Rasch analysis was used to reduce response options from seven (VascuQoL-25) to four (VascuQoL-6). VascuQol-6 was shown to have high precision and discriminative properties. Item fit was excellent, with both "infit" and "outfit" between 0.7 and 1.3 for all six items. The standardized response mean after intervention was 1.15, indicating good responsiveness to clinical change. VascuQoL-6 results correlated strongly (r = 0.72; P < .001) with the actual measured walking ability (n = 21). Conclusions: VascuQoL-6 is a valid and responsive instrument for the assessment of health-related quality of life in PAD. The main advantage is the compact format that offers a possibility for routine use in busy clinical settings.
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4.
  • Anesäter, Erik, et al. (author)
  • The influence on wound contraction and fluid evacuation of a rigid disc inserted to protect exposed organs during negative pressure wound therapy.
  • 2011
  • In: International Wound Journal. - 1742-481X. ; 8, s. 393-399
  • Journal article (peer-reviewed)abstract
    • The use of a rigid disc as a barrier between the wound bed and the wound filler during negative pressure wound therapy (NPWT) has been suggested to prevent damage to exposed organs. However, it is important to determine that the effects of NPWT, such as wound contraction and fluid removal, are maintained during treatment despite the use of a barrier. This study was performed to examine the effect of NPWT on wound contraction and fluid evacuation in the presence of a rigid disc. Peripheral wounds were created on the backs of eight pigs. The wounds were filled with foam, and rigid discs of different designs were inserted between the wound bed and the foam. Wound contraction and fluid evacuation were measured after application of continuous NPWT at -80 mmHg. Wound contraction was similar in the presence and the absence of a rigid disc (84 ± 4% and 83 ± 3%, respectively, compared with baseline). Furthermore, the rigid disc did not affect wound fluid removal compared with ordinary NPWT (e.g. after 120 seconds, 71 ± 4 ml was removed in the presence and 73 ± 3 ml was removed in the absence of a disc). This study shows that a rigid barrier may be placed under the wound filler to protect exposed structures during NPWT without affecting wound contraction and fluid removal, which are two crucial features of NPWT.
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6.
  • Pivodic, Aldina, 1978, et al. (author)
  • Individual Risk Prediction for Sight-Threatening Retinopathy of Prematurity Using Birth Characteristics
  • 2020
  • In: JAMA Ophthalmology. - : American Medical Association (AMA). - 2168-6165 .- 2168-6173. ; 138:1, s. 21-29
  • Journal article (peer-reviewed)abstract
    • Importance: To prevent blindness, repeated infant eye examinations are performed to detect severe retinopathy of prematurity (ROP), yet only a small fraction of those screened need treatment. Early individual risk stratification would improve screening timing and efficiency and potentially reduce the risk of blindness. Objectives: To create and validate an easy-to-use prediction model using only birth characteristics and to describe a continuous hazard function for ROP treatment. Design, Setting, and Participants: In this retrospective cohort study, Swedish National Patient Registry data from infants screened for ROP (born between January 1, 2007, and August 7, 2018) were analyzed with Poisson regression for time-varying data (postnatal age, gestational age [GA], sex, birth weight, and important interactions) to develop an individualized predictive model for ROP treatment (called DIGIROP-Birth [Digital ROP]). The model was validated internally and externally (in US and European cohorts) and compared with 4 published prediction models. Main Outcomes and Measures: The study outcome was ROP treatment. The measures were estimated momentary and cumulative risks, hazard ratios with 95% CIs, area under the receiver operating characteristic curve (hereinafter referred to as AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: Among 7609 infants (54.6% boys; mean [SD] GA, 28.1 [2.1] weeks; mean [SD] birth weight, 1119 [353] g), 442 (5.8%) were treated for ROP, including 142 (40.1%) treated of 354 born at less than 24 gestational weeks. Irrespective of GA, the risk for receiving ROP treatment increased during postnatal weeks 8 through 12 and decreased thereafter. Validations of DIGIROP-Birth for 24 to 30 weeks' GA showed high predictive ability for the model overall (AUC, 0.90 [95% CI, 0.89-0.92] for internal validation, 0.94 [95% CI, 0.90-0.98] for temporal validation, 0.87 [95% CI, 0.84-0.89] for US external validation, and 0.90 [95% CI, 0.85-0.95] for European external validation) by calendar periods and by race/ethnicity. The sensitivity, specificity, PPV, and NPV were numerically at least as high as those obtained from CHOP-ROP (Children's Hospital of Philadelphia-ROP), OMA-ROP (Omaha-ROP), WINROP (weight, insulinlike growth factor 1, neonatal, ROP), and CO-ROP (Colorado-ROP), models requiring more complex postnatal data. Conclusions and Relevance: This study validated an individualized prediction model for infants born at 24 to 30 weeks' GA, enabling early risk prediction of ROP treatment based on birth characteristics data. Postnatal age rather than postmenstrual age was a better predictive variable for the temporal risk of ROP treatment. The model is an accessible online application that appears to be generalizable and to have at least as good test statistics as other models requiring longitudinal neonatal data not always readily available to ophthalmologists.
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8.
  • Johansson, Björn (author)
  • Opacification of anterior part of hydrophilic acrylic IOL or a prelenticular inflammatory membrane?
  • 2012
  • In: Journal of cataract and refractive surgery. - Philadelphia : Elsevier. - 0886-3350 .- 1873-4502. ; 38:6, s. 1115-1116
  • Journal article (peer-reviewed)abstract
    • In their recent case report, Park and Chuck1 describe the bilateral appearance of an opacification at the plane of the anterior surface of the hydrophilic acrylic Akreos MI60 intraocular lens (IOL) (Bausch & Lomb). The patient's general history of diabetes mellitus, proliferative retinopathy, and iris rubeosis explains the limited pupil dilation preventing visualization of the capsulorhexis opening in their slitlamp images.
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9.
  • Chung, Jou Ku, et al. (author)
  • Development and verification of a pharmacokinetic model to optimize physiologic replacement of rhIGF-1/rhIGFBP-3 in preterm infants
  • 2017
  • In: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 81:3, s. 504-510
  • Journal article (peer-reviewed)abstract
    • Background:rhIGF-1/rhIGFBP-3 is being investigated for prevention of retinopathy of prematurity in extremely preterm infants.Methods:A population pharmacokinetic model was developed using data from phase I/II (Sections A-C) trials of rhIGF-1/rhIGFBP-3 and additional studies in preterm infants to predict optimal dosing to establish/maintain serum IGF-1 within physiological intrauterine levels. In Section D of the phase II study, infants (gestational age (GA) (wk+d) 23+0 to 27+6) were randomized to rhIGF-1/rhIGFBP-3, administered at the model-predicted dose of 250 μg/kg/d continuous i.v. infusion up to postmenstrual age (PMA) 29 wk+6 d or standard of care. An interim pharmacokinetic analysis was performed for the first 10 treated infants to verify dosing.Results:Serum IGF-1 data were reviewed for 10 treated/9 control infants. Duration of therapy in treated infants ranged 1-34.5 d. At baseline (before infusion and <24 h from birth), mean (SD) IGF-1 was 19.2 (8.0) μg/l (treated) and 15.4 (4.7) μg/l (controls). Mean (SD) IGF-1 increased to 45.9 (19.6) μg/l at 12 h in treated infants, and remained within target levels for all subsequent timepoints. For treated infants, 88.8% of the IGF-1 measurements were within target levels (controls, 11.1%).Conclusion:Through the reported work, we determined appropriate rhIGF-1/rhIGFBP-3 dosing to achieve physiological intrauterine serum IGF-1 levels in extremely preterm infants.
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10.
  • Holmström, Gerd E, et al. (author)
  • Ophthalmologic Outcome at 30 Months Corrected Age of a Prospective Swedish Cohort of Children Born Before 27 Weeks of Gestation The Extremely Preterm Infants in Sweden Study
  • 2014
  • In: JAMA OPHTHALMOLOGY. - : American Medical Association (AMA). - 2168-6165 .- 2168-6173. ; 132:2, s. 182-189
  • Journal article (peer-reviewed)abstract
    • IMPORTANCE Follow-up at 30 months corrected age reveals eye and visual problems in one-third of children born extremely prematurely (less than27 weeks gestation). OBJECTIVE To investigate the ophthalmologic outcome of extremely preterm children at 30 months corrected age. DESIGN, SETTING, AND PARTICIPANTS A prospective, population-based follow-up study (Extremely Preterm Infants in Sweden Study [EXPRESS]) was conducted in Sweden. The population included extremely preterm infants (less than27 weeks gestation) born in Sweden between 2004 and 2007, of whom 491 survived until age 2.5 years. Screening for retinopathy of prematurity (ROP) was performed in the neonatal period. At 30 months corrected age, an ophthalmologic assessment was performed in 411 of 491 children (83.7%). MAIN OUTCOMES AND MEASURES Visual acuity, manifest strabismus, and refractive errors were evaluated. RESULTS Visual impairment was identified in 3.1% of the children, and 1.0% were blind. Refractive errors, defined as myopia less than -3 diopters (D), hypermetropia greater than +3 D, astigmatism 2 D or more, and/or anisometropia 2 D or more, were found in 25.6% of the children, and 14.1% had manifest strabismus. There were significant associations between visual impairment and treated ROP (P = .02), cognitive disability (P less than .001), and birth weight (P = .02). Multiple regression analyses revealed significant associations between strabismus and treated ROP (P less than .001), cognitive disability (P less than .01), and cerebral palsy (P = .02). Refractive errors were significantly correlated with severity of ROP (right eye, P less than .001; left eye, P less than .01). Children who had been treated for ROP had the highest frequency (69.0%) of eye and visual abnormalities. CONCLUSIONS AND RELEVANCE One-third of the extremely prematurely born children in this study had some kind of eye or visual problems, such as visual impairment, strabismus, or major refractive error. Despite being born extremely preterm, the present cohort has a similar prevalence of blindness and visual impairment as in previous Swedish cohorts of children born less prematurely.
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11.
  • Holmström, Gerd, 1951-, et al. (author)
  • New modifications of Swedish ROP guidelines based on 10-year data from the SWEDROP register
  • 2020
  • In: British Journal of Ophthalmology. - : BMJ. - 0007-1161 .- 1468-2079. ; 104:7, s. 943-949
  • Journal article (peer-reviewed)abstract
    • BACKGROUND/AIMS:During the last decade, improved neonatal care has resulted in increased survival of the most immature infants and improved health of more mature infants. We hypothesise that this has affected incidence and treatment of retinopathy of prematurity (ROP), enabling guidelines for screening to be modified.METHODS: In Sweden, all infants with gestational age (GA) at birth ≤30 weeks are screened for ROP. Results are registered in a web-based register, Swedish National ROP Register, with a coverage rate of 97%. Incidence of ROP and frequency of treatment, aspects on natural course of ROP and number of examinations, are calculated in relation to GA at birth in infants born during 2008-2017.RESULTS: Of 7249 infants, 31.9% (2310) had ROP and 6.1% (440) were treated. No infant with GA 30 weeks was treated. Incidence of ROP remained similar, but frequency of treatment increased (p=0.023). Over time, GA and birth weight were reduced in infants with ROP and with treated ROP. In the most immature infants, postmenstrual age was lower and postnatal age was higher when any ROP and stage 3 ROP were first detected (p<0.001). At treatment, postmenstrual but not postnatal age of the infant was associated with GA (p<0.001). During the 10-year period, 46 038 examinations were performed.CONCLUSION: Modification of Swedish guidelines is proposed, including only infants with a GA of <30 weeks and postponing the first examination with 1 week in infants with GA 26-29 weeks. This would spare many infants from stressful examinations and reduce eye examinations with at least 20%.
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12.
  • Källén, Karin, et al. (author)
  • Ophthalmologic Outcome of Extremely Preterm Infants at 6.5 Years of Age Extremely Preterm Infants in Sweden Study (EXPRESS)
  • 2016
  • In: Jama Ophthalmology. - : American Medical Association (AMA). - 2168-6165 .- 2168-6173. ; 134:5, s. 555-562
  • Journal article (peer-reviewed)abstract
    • IMPORTANCE This follow-up study of extremely preterm (EPT) children (<27 weeks' gestational age [GA] at birth) revealed major eye and visual problems in 37.9%(147 of 388) of all EPT infants and in 55.4%(67 of 121) of the most immature subgroups at 6.5 years of age. These major eye and visual problems were strongly associated with treatment-requiring retinopathy of prematurity (ROP). OBJECTIVES To investigate the ophthalmologic outcome of a national cohort of EPT children at 6.5 years of age and to evaluate the impact of prematurity and ROP. DESIGN, SETTING, AND PARTICIPANTS All surviving EPT children born in Sweden between April 1, 2004, and March 31, 2007, were included and compared with a matched term control group, as part of a prospective national follow-up study. MAIN OUTCOMES AND MEASURES Visual acuity, refraction in cycloplegia, and manifest strabismus were evaluated and compared with GA at birth and with treatment-requiring ROP. RESULTS The study cohort comprised 486 participants. The mean (SD) GA of the children who were included was 25 (1) weeks, and 45.7%(222 of 486) were female. At a median age of 6.6 years, 89.3%(434 of 486) of eligible EPT children were assessed and compared with 300 control group children. In the EPT group, 2.1%(9 of 434) were blind, 4.8%(21 of 434) were visually impaired according to the World Health Organization criteria, and 8.8% (38 of 434) were visually impaired according to the study criteria. Strabismus was found in 17.4% (68 of 390) and refractive errors in 29.7%(115 of 387) of the EPT children compared with 0% (0 of 299) and 5.9% (17 of 289), respectively, of the control children (P<.001). Altogether at 6.5 years of age, 37.9%(147 of 388) of the EPT children had some ophthalmologic abnormality compared with 6.2%(18 of 290) of the matched control group (95% CI of the difference, 26.1%-37.2%). When treatment-requiring ROP was adjusted for, no significant association between GA and visual impairment could be detected. For refractive errors, the association with GA remained after adjustment for treatment-requiring ROP (odds ratio, 0.72; 95% CI, 0.58-0.91 for each 1-week increment). CONCLUSIONS AND RELEVANCE In a Swedish national cohort of EPT children at 6.5 years of age, major eye and visual problems were frequently found. Treatment-requiring ROP was a stronger impact factor than GA on visual impairment and strabismus, but not on refractive errors, as a whole. In modern neonatal intensive care settings, ophthalmologic problems continue to account for a high proportion of long-term sequelae of prematurity.
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13.
  • Larsson, Eva, et al. (author)
  • Peripheral and central visual fields in 11-year-old children who had been born prematurely and at term
  • 2004
  • In: Journal of pediatric ophthalmology and strabismus. - : SLACK, Inc.. - 0191-3913 .- 1938-2405. ; 41, s. 39-
  • Journal article (peer-reviewed)abstract
    • PURPOSE: To examine the peripheral and central visual fields in children who had been born prematurely and at term. METHODS: Four groups of 11-year-old children were examined: group 1 included 24 children who had been born at term (control group); group 2 included 20 children who had been born prematurely without ROP; group 3 included 22 children who had been born prematurely with untreated ROP (stages 2 and 3); and group 4 included 21 children who had been born prematurely and underwent cryotreatment for severe ROP. Their peripheral visual fields were examined with Goldmann perimetry. Static high-pass resolution perimetry was used to evaluate their central visual fields within 30 degrees. RESULTS: The peripheral visual fields were constricted in children who had undergone cryotreatment (group 4), as compared with the other groups (1 to 3). We found no difference between the groups of children who had been born prematurely with or without ROP (groups 2 and 3) and the control group. The function of the central visual fields, expressed as neural capacity, was reduced in the children who had been born prematurely compared with the controls, significantly in their left eyes only. The children who underwent cryotreament did not differ from the other children who had been born prematurely in this respect. CONCLUSIONS: The peripheral visual fields were constricted in children who had undergone cryotreatment. It is uncertain whether this was caused by the treatment or by severe ROP. The central visual fields showed a tendency of reduced neural capacity in the children who had been born prematurely, reflecting a reduced density of retinocortical neural channels. However, this was not related to ROP or cryotreatment.
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14.
  • Borgquist, Ola, et al. (author)
  • Individualizing the Use of Negative Pressure Wound Therapy for Optimal Wound Healing: A Focused Review of the Literature
  • 2011
  • In: Ostomy - Wound Management. - 0889-5899. ; 57:4, s. 44-44
  • Research review (peer-reviewed)abstract
    • Currently available research suggests that negative pressure wound therapy (NPWT) creates a moist wound healing environment, drains exudate, reduces tissue edema, contracts the wound edges, mechanically stimulates the wound bed, and influences blood perfusion at the wound edge, which may lead to angiogenesis and the formation of granulation tissue. Although no clear evidence is available that NPWT accelerates wound healing compared to other interventions or that one form of NPWT is better than another, preclinical research suggests that the most commonly used dressings, level of negative pressure, and application mode (continuous, intermittent, or variable) may not be optimal for all patients. To summarize available literature related to these NPWT choices, pertinent literature published between 2005 and 2010 was reviewed. Preclinical study results suggest that the maximal biological effect of NPWT at the wound edge often can be achieved at -80 mm Hg and that foam dressings may be advantageous for large defect wounds, whereas gauze dressings may be more suitable for smaller wounds or when scar formation or pain is a concern. Preclinical research results also suggest that intermittent or variable pressure application has a better effect on granulation tissue formation than continuous application. The variable pressure mode maintains a negative pressure environment at lower pressure settings without dramatic fluctuations inherent to intermittent (on-and-off) pressure. Prospective, controlled clinical studies are needed to compare NPWT to other advanced wound care protocols of care and to ascertain the effect of various NPWT methods and regimens on outcomes of care.
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15.
  • Borgquist, Ola, et al. (author)
  • Tissue Ingrowth Into Foam but Not Into Gauze During Negative Pressure Wound Therapy
  • 2009
  • In: Wounds. - 1044-7946. ; 21:11, s. 302-309
  • Journal article (peer-reviewed)abstract
    • Background. Foam and gauze are two types of wound fillers used for negative pressure wound therapy (NPWT). Differences in the wound healing effects of foam and gauze have been observed clinically. The aim of the present study was to examine the effects of NPWT on the wound bed using foam and gauze. Methods. A porcine peripheral wound model was treated with NPWT at 0, -75 mmHg, or -125 mmHg for 72 hours. The effects of foam and gauze on the wound bed were compared, and the force required to remove the dressings was measured. Sections of biopsies from the wound bed with an overlying dressing were stained with hematoxylin-eosin and Giemsa and were examined histologically. Results. The force ratio needed to remove the wound filler from the wound bed after treatment with negative pressure was greater for foam than for gauze. NPWT caused the wound bed tissue to grow into the foam, while there was I no such ingrowth into gauze. Furthermore, beneath the foam there was more leukocyte infiltration, tissue disorganization, disruption of contact among cells, and differences in size among cells. The results were similar regardless of the level of negative pressure. Conclusion. More force was required to remove foam compared to gauze following NPWT, which may have been due to greater ingrowth into foam. These findings may explain the patient discomfort and wound bed disruption upon removal of foam. The observed differences in wound bed tissue morphology under foam and gauze are in accordance with the clinically observed differences in quality of granulation tissue formation.
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18.
  • Holmström, Gerd, 1951-, et al. (author)
  • Increased frequency of retinopathy of prematurity over the last decade and significant regional differences
  • 2018
  • In: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 96:2, s. 142-148
  • Journal article (peer-reviewed)abstract
    • Purpose: Retinopathy of prematurity (ROP) causes childhood blindness globally in prematurely born infants. Although increased levels of oxygen supply lead to increased survival and reduced frequency of cerebral palsy, increased incidence of ROP is reported. Methods: With the help of a Swedish register for ROP, SWEDROP, national and regional incidences of ROP and frequencies of treatment were evaluated from 2008 to 2015 (n = 5734), as well as before and after targets of provided oxygen changed from 85-89% to 91-95% in 2014. Results: Retinopathy of prematurity (ROP) was found in 31.9% (1829/5734) of all infants with a gestational age (GA) of <31 weeks at birth and 5.7% of the infants (329/5734) had been treated for ROP. Analyses of the national data revealed an increased incidence of ROP during the 8-year study period (p = 0.003), but there was no significant increase in the frequency of treatment. There were significant differences between the seven health regions of Sweden, regarding both incidence of ROP and frequency of treatment (p < 0.001). Comparison of regional data before and after the new oxygen targets revealed a significant increase in treated ROP in one region [OR: 2.24 (CI: 1.11-4.49), p = 0.024] and a borderline increase in one other [OR: 3.08 (CI: 0.99-9.60), p = 0.052]. Conclusion: The Swedish national ROP register revealed an increased incidence of ROP during an 8-year period and significant regional differences regarding the incidence of ROP and frequency of treatment.
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19.
  • Lindstedt Ingemansson, Sandra, et al. (author)
  • C-reactive protein and leucocyte counts drop faster using the HeartShield® device in patients with DSWI.
  • 2015
  • In: International Wound Journal. - : Wiley. - 1742-481X .- 1742-4801. ; 12:2, s. 189-194
  • Journal article (peer-reviewed)abstract
    • Right ventricular heart rupture is a devastating complication associated with negative pressure wound therapy (NPWT) in cardiac surgery. The use of a rigid barrier disc (HeartShield™) has been suggested to offer protection against this lethal complication by preventing the heart from being drawn up by the negative pressure and damaged by the sharp sternum bone edges. Seven patients treated with conventional NPWT and seven patients treated with NPWT with a protective barrier disc (HeartShield) were compared with regard to bacterial clearance and infection parameters including C-reactive protein levels and leucocyte counts. C-reactive protein levels and leucocyte counts dropped faster and bacterial clearance occurred earlier in the HeartShield® group compared with the conventional NPWT group. Negative biopsy cultures were shown after 3·1 ± 0·4 NPWT dressing changes in the HeartShield group, and after 5·4 ± 0·6 NPWT dressing changes in the conventional NPWT group (P < 0·001). All patients were followed up with clinical check-up after 3 months. None of the patients in the HeartShield group had any signs of reinfection such as deep sternal wound infection (DSWI) or sternal fistulas, whereas in the conventional NPWT group, two patients had signs of sternal fistulas that demanded hospitalisation. HeartShield hiders the right ventricle to come into contact with the sharp sternal edges during NPWT and thereby protects from heart damage. This study shows that using HeartShield is beneficial in treating patients with DSWI. Improved wound healing by HeartShield may be a result of the efficient drainage of wound effluents from the thoracic cavity.
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20.
  • Lindstedt Ingemansson, Sandra, et al. (author)
  • Effects on drainage of the mediastinum and pleura during negative pressure wound therapy when using a rigid barrier to prevent heart rupture.
  • 2011
  • In: International Wound Journal. - 1742-481X. ; 8, s. 454-458
  • Journal article (peer-reviewed)abstract
    • Right ventricular heart rupture is a devastating complication associated with negative pressure wound therapy (NPWT) following cardiac surgery. The use of a rigid disc has been suggested to offer protection against this lethal complication by preventing the heart from being drawn up towards, and damaged by, the sharp sternum edges. The aim of the present study was to compare the wound fluid evacuation from the pericardium and the left pleura when using NPWT with such a disc between the sternal edges and the heart, and when using conventional NPWT. Six pigs underwent median sternotomy followed by NPWT at -120 mmHg, using foam, with or without a rigid plastic disc between the heart and the sternal edges. A 250 ml saline was infused into the pericardium, and the time required for fluid evacuation was measured. A 500 ml saline was infused into the left pleura and the time for fluid evacuation measured. The pericardium was effectively drained of 250 ml fluid in both cases [conventional NPWT: 24 ± 0·7 seconds, NPWT with the disc: 25 ± 1·1 seconds (n.s.)]. The left pleura was effectively drained when using NPWT with the disc, but was not drained at all when using conventional NPWT. The left pleura could be effectively drained of 500 ml fluid when a rigid perforated plastic disc was inserted between the sternal edges and the heart during NPWT. Significantly less drainage of the left pleura was possible when using conventional NPWT without the disc. The pericardium was equally good drained using NPWT with or without the disc.
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21.
  • Lindstedt Ingemansson, Sandra, et al. (author)
  • Haemodynamic effects of negative pressure wound therapy when using a rigid barrier to prevent heart rupture.
  • 2011
  • In: International Wound Journal. - 1742-481X. ; 8, s. 385-392
  • Journal article (peer-reviewed)abstract
    • Right ventricular heart rupture is a devastating complication associated with negative pressure wound therapy (NPWT) in cardiac surgery. The use of a rigid barrier has been suggested to offer protection against this lethal complication by preventing the heart from being drawn up and damaged by the sharp sternum bone edges. The aim of this study was to investigate the haemodynamic effects of placing a rigid barrier over the heart to protect it from rupture during NPWT. Eight pigs underwent median sternotomy followed by NPWT at -70 and -120 mmHg, using foam, with or without a rigid plastic disc between the heart and the sternal edges. The heart frequency, cardiac output, mean systemic arterial pressure, mean pulmonary artery pressure, central venous pressure and left atrial pressure were recorded. Cardiac output was not affected by NPWT, regardless of whether a rigid barrier was used. Heart frequency decreased during NPWT without a disc, and showed a tendency towards a decrease when using a rigid disc. The blood pressure decreased during NPWT without a disc, and showed only a tendency towards a decrease when a disc was inserted between the heart and the sternum. In conclusion, the results of this haemodynamic study show that a rigid disc can safely be placed over the heart during NPWT, to prevent heart rupture. The haemodynamic effects of NPWT in sternotomy wounds are slightly reduced by the presence of the rigid disc.
  •  
22.
  • Malmsjö, Malin, et al. (author)
  • Comparison of bacteria and fungus-binding mesh, foam and gauze as fillers in negative pressure wound therapy - pressure transduction, wound edge contraction, microvascular blood flow and fluid retention.
  • 2013
  • In: International Wound Journal. - 1742-481X. ; 10:5, s. 597-605
  • Journal article (peer-reviewed)abstract
    • Bacteria- and fungus-binding mesh binds and inactivates bacteria and fungus, which makes it interesting, alternative, wound filler for negative pressure wound therapy (NPWT). This study was conducted to compare the performance of pathogen-binding mesh, foam and gauze as wound fillers in NPWT with regard to pressure transduction, fluid retention, wound contraction and microvascular blood flow. Wounds on the backs of 16 pigs were filled with pathogen-binding mesh, foam or gauze and treated with NPWT. The immediate effects of 0, -40, -60, -80 and -120 mmHg, on pressure transduction and blood flow were examined in eight pigs using laser Doppler velocimetry. Wound contraction and fluid retention were studied during 72 hours of NPWT at -80 and -120 mmHg in the other eight pigs. Pathogen-binding mesh, gauze and foam provide similar pressure transduction to the wound bed during NPWT. Blood flow was found to decrease 0·5 cm laterally from the wound edge and increase 2·5 cm from the wound edge, but was unaltered 5·0 cm from the wound edge. The increase in blood flow was similar with all wound fillers. The decrease in blood flow was more pronounced with foam than with gauze and pathogen-binding mesh. Similarly, wound contraction was more pronounced with foam, than with gauze and pathogen-binding mesh. Wound fluid retention was the same in foam and pathogen-binding mesh, while more fluid was retained in the wound when using gauze. The blood flow 0·5-5 cm from the wound edge and the contraction of the wound during NPWT were similar when using pathogen-binding mesh and gauze. Wound fluid was efficiently removed through the pathogen-binding mesh, which may explain previous findings that granulation tissue formation is more rapid under pathogen-binding mesh than under gauze. This, in combination with its pathogen-binding properties, makes this mesh an interesting wound filler for use in NPWT.
  •  
23.
  • Malmsjö, Malin, et al. (author)
  • Green foam, black foam or gauze for NWPT: effects on granulation tissue formation.
  • 2011
  • In: Journal of Wound Care. - 0969-0700. ; 20:6, s. 294-299
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To compare the effects of green foam with black foam and gauze during negative pressure wound therapy (NPWT), with regard to wound bed appearance and granulation tissue formation, and monitoring of wound exudate. METHOD: Wounds on the backs of eight pigs underwent 72 hours of NPWT plus either green polyurethane foam with an open pore structure, black polyurethane foam with an open pore structure or saline-moistened AMD gauze. Sections of biopsies from the wound bed, including the overlying dressing, were examined histologically with regard to microdeformation of the wound bed and granulation tissue formation. The force required to remove the wound fillers was measured. RESULTS: Wound exudate and bleeding could be easily seen when using gauze and green foam, but were not visible under the black foam. Such visibility facilitates monitoring of the wound status. No difference was found in the quantity or characteristics of the granulation tissue formed under the green foam or black foam. Both green foam and black foam resulted in more pronounced granulation tissue formation than gauze under negative pressure. There was also more leucocyte infiltration and tissue disorganisation under green foam and black foam than under gauze. All three wound fillers created microdeformation within the wound bed surface. Similar forces were required to remove green foam and black foam (5.0 ± 0.6 N for green foam and 4.0 ± 0.4 N for black foam), while less force was needed for gauze (2.1 ± 0.2 N). This may be a result of tissue ingrowth into the foam (357 ± 12µm for green foam and 362 ± 14µm for black foam), but not into gauze (0µm), as shown by examination of biopsy sections from the wound bed. CONCLUSION: Green foam and black foam have similar biological effects on the wound bed. Bleeding and exudate can be more easily monitored when using green foam or gauze. Differences in the wound bed tissue morphology when using foam or gauze plus NPWT support clinical observations that granulation tissue under foam is thick but fragile, whereas that under foam is thinner but denser. CONFLICT OF INTEREST: The study was supported by Mölnlycke Health Care AB
  •  
24.
  • Malmsjö, Malin, et al. (author)
  • Influence on pressure transduction when using different drainage techniques and wound fillers (foam and gauze) for negative pressure wound therapy.
  • 2010
  • In: International Wound Journal. - 1742-481X. ; 7, s. 406-412
  • Journal article (peer-reviewed)abstract
    • Pressure transduction to the wound bed in negative pressure wound therapy (NPWT) is crucial in stimulating the biological effects ultimately resulting in wound healing. In clinical practice, either foam or gauze is used as wound filler. Furthermore, two different drainage techniques are frequently employed. One involves the connection of a non-perforated drainage tube to the top of the dressing, while the other involves the insertion of perforated drains into the dressing. The aim of this study was to examine the efficacy of these two different wound fillers and drainage systems on pressure transduction to the wound bed in a challenging wound (the sternotomy wound). Six pigs underwent median sternotomy. The wound was sealed for NPWT using different wound fillers (foam or gauze) and drainage techniques (see earlier). Pressures between 0 and -175 mmHg were applied and the pressure in the wound was measured using saline-filled catheters sutured to the bottom of the wound (over the anterior surface of the heart) and to the side of the wound (on the thoracic wall). The negative pressure on the wound bed increased linearly with the negative pressure delivered by the vacuum source. In a dry wound, the pressure transduction was similar when using the different wound fillers (foam and gauze) and drainage techniques. In a wet wound, pressure transduction was better when using a perforated drainage tube inserted into the wound filler than a non-perforated drainage tube connected to the top of the dressing (-116 +/- 1 versus -73 +/- 4 mmHg in the wound at a delivered pressure of -125 mmHg for foam, P < 0.01), regardless of the type of wound filler. Gauze and foam are equally effective at delivering negative pressure to the wound bed. Perforated drainage tubes inserted into the wound filler are more efficient than a non-perforated drainage tubes connected to the top of the dressing. The choice of drainage technique may be particularly important in wounds with a large volume of exudate.
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25.
  • Malmsjö, Malin, et al. (author)
  • Negative Pressure Wound Therapy-associated Tissue Trauma and Pain: A Controlled In vivo Study Comparing Foam and Gauze Dressing Removal by Immunohistochemistry for Substance P and Calcitonin Gene-related Peptide in the Wound Edge.
  • 2011
  • In: Ostomy - Wound Management. - 0889-5899. ; 57:12, s. 30-35
  • Journal article (peer-reviewed)abstract
    • Pain upon negative pressure wound therapy (NPWT) dressing removal has been reported and is believed to be associ- ated with the observation that granulation tissue grows into foam. Wound tissue damage upon removal of the foam may cause the reported pain. Calcitonin gene-related peptide (CGRP) and substance P are neuropeptides that cause inflam- mation and signal pain and are known to be released when tissue trauma occurs. The aim of this controlled in vivo study was to compare the expression of CGRP and substance P in the wound bed in control wounds and following NPWT and foam or gauze dressing removal. Eight pigs with two wounds each were treated with open-pore structure polyurethane foam or AMD gauze and NPWT of 0 (control) or -80 mm Hg for 72 hours. Following removal of the wound filler, the ex- pression of CGRP and substance P was measured, using arbitrary units, in sections of biopsies from the wound bed using immunofluorescence techniques. Substance P and CGRP were more abundant in the wound edge following the removal of foam than of gauze dressings and least abundant in control wounds. The immunofluorescence staining of the wound edge for CGRP was 52 ± 3 au after the removal of gauze and 97 ± 5 au after the removal of foam (P <0.001). For substance P, the staining was 55 ± 3 au after gauze removal and 95 ± 4 au after foam removal (P <0.001). CGRP and substance P staining was primarily located to nerves and leukocytes. The increase in CGRP and substance P immuno- fluorescence was especially prominent in the dermis but also was seen in subcutaneous and muscle tissue. Using gauze may be one way of reducing NPWT dressing change-related pain. New wound fillers designed to optimize granulation tissue formation and minimize pain issues presumably will be developed in the near future.
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26.
  • Mokhtari, Arash, et al. (author)
  • Haemodynamic effects of -75 mmHg negative pressure therapy in a porcine sternotomy wound model.
  • 2009
  • In: International Wound Journal. - 1742-481X. ; 6:1, s. 48-54
  • Journal article (peer-reviewed)abstract
    • Previous research has shown -125 mmHg to be the optimal negative pressure for creating an environment that promotes wound healing, and this has therefore been adopted as a standard pressure for patients with deep sternal wound infection. However, it has not yet been clearly shown that -125 mmHg is the optimal pressure from a haemodynamic point of view. Furthermore, there have been reports of cardiac rupture during -125 mmHg negative pressure therapy. We therefore studied the effects of a lower pressure: -75 mmHg. Twelve pigs were used. After median sternotomy, sealed negative pressure therapy of -75 mmHg was applied. Baseline measurements were made and continuous recording of the cardiac output, end-tidal CO(2) production, mean arterial pressure, mean pulmonary pressure (pulmonary artery pressure), systemic vascular resistance, pulmonary vascular resistance, left atrial pressure and central venous pressure was started. Six pigs served as controls. No statistically significant difference was observed in any of the haemodynamic parameters studied, compared with the controls. The present study shows that, with a suitable foam application technique, -75 mmHg can be applied without compromising the central haemodynamics.
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27.
  • Nyström, Alf, et al. (author)
  • The Swedish National Pediatric Cataract Register (PECARE): incidence and onset of postoperative glaucoma
  • 2020
  • In: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 98:7, s. 654-661
  • Journal article (peer-reviewed)abstract
    • Purpose The aim was to report cumulative incidence and time of onset of postoperative glaucoma in a paediatric early cataract surgery cohort. Methods Data were retrieved from the Pediatric Cataract Register (PECARE), a prospective register of Swedish cataract operations before 8 years of age. All eyes with surgery between January 2007 and December 2014 and a registered follow-up were included. Cataracts caused by uveitis, trauma or coexisting congenital glaucoma were excluded. Glaucoma was defined as early onset if diagnosed within a year after surgery and late onset if diagnosed later. Results The study included 288 eyes in 207 children (106 girls), 81 with bilateral and 126 with unilateral cataracts, with a mean follow-up of 3.31 +/- 1.77 years. Of the 288, 168 (58.3%) had surgery before 3 months of age; most of these 92.3% (155/168) were defined as dense, 208 (72.2%) were below 1 year of age. Cumulative incidence of surgically treated glaucoma among individuals was 23.7% (49/207). Median time to glaucoma onset was 0.91 years (range: 0.05-4.97 years) for eyes. Early-onset glaucoma was found in 98 % (63/64), and late onset in 2% (1/64). Conclusion In this paediatric cataract cohort, a majority of eyes had surgery before 3 months of age (58.3%). Secondary glaucoma-onset peaked within the first postoperative year, with a cumulative incidence of 23.7%. Surgery performed after the first month of life, resulted in a lower glaucoma rate. Long-term follow-up will reveal whether the low rate of late-onset glaucoma with early surgery will last, and if so, the consequences.
  •  
28.
  • Runkel, N., et al. (author)
  • Evidence-based recommendations for the use of Negative Pressure Wound Therapy in traumatic wounds and reconstructive surgery: Steps towards an international consensus
  • 2011
  • In: Injury. - 1879-0267. ; 42:Suppl. 1, s. 1-12
  • Journal article (peer-reviewed)abstract
    • Negative pressure wound therapy (NPWT) has become widely adopted over the last 15 years and over 1000 peer reviewed publications are available describing its use. Despite this, there remains uncertainty regarding several aspects of usage. In order to respond to this gap a global expert panel was convened to develop evidence-based recommendations describing the use of NPWT. In this paper the results of the study of evidence in traumatic wounds (including soft tissue defects, open fractures and burns) and reconstructive procedures (including flaps and grafts) are reported. Evidence-based recommendations were obtained by a systematic review of the literature, grading of evidence, drafting of the recommendations by a global expert panel, followed by a formal consultative consensus development program in which 422 independent healthcare professionals were able to agree or disagree with the recommendations. The criteria for agreement were set at 80% approval. Evidence and recommendations were graded according to the SIGN (Scottish Intercollegiate Guidelines Network) classification system. Twelve recommendations were developed in total; 4 for soft tissue trauma and open fracture injuries, 1 for burn injuries, 3 for flaps and 4 for skin grafts. The present evidence base is strongest for the use of NPWT on skin grafts and weakest as a primary treatment for burns. In the consultative process, 11/12 of the proposed recommendations reached the 80% agreement threshold. The development of evidence-based recommendations for NPWT with direct validation from a large group of practicing clinicians offers a broader basis for consensus than work by an expert panel alone. (C) 2011 Elsevier Ltd. All rights reserved.
  •  
29.
  • Teär Fahnehjelm, Kristina, et al. (author)
  • Visual perceptual skills and visual motor integration in children and adolescents after allogeneic hematopoietic stem cell transplantation
  • 2018
  • In: Pediatric Transplantation. - : Wiley. - 1397-3142 .- 1399-3046. ; 22:2
  • Journal article (peer-reviewed)abstract
    • The aim of the study was to study visual acuity, visual perceptual, and VMI skills in patients after HSCT in childhood. Tests of visual perceptual skills, VMI, and visual acuity were performed in 102 children/adolescents (age range 4.3-20.9years). Mean time from HSCT to testing was 6.0years (0.9-17.5years). Visual acuity was median 1.0 decimal (range 0.16-1.6). Visual perceptual skills (memory, form constancy, visual sequential memory) and VMI were low compared to age-equivalent normative data with, respectively, 36%, 45%, 60%, and 46% of all patients performing below the 25 percentile. All patients performed significantly lower than the 50 percentile in the reference material in visual sequential memory, P<.001 (boys P<.001 and girls P<.05). All patients also performed significantly lower than the 50 percentile in VMI (P<.01) (boys P<.05). Pretransplant conditioning regimen did not affect outcome if the results were corrected for age at HSCT. Visual perceptual skill problems and VMI problems frequently occur in patients after HSCT in childhood. Age at HSCT and original diagnosis influence the outcome. Neuropsychological assessment including visual perception is recommended in children after HSCT.
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30.
  • Vig, S., et al. (author)
  • Evidence-based recommendations for the use of negative pressure wound therapy in chronic wounds: Steps towards an international consensus
  • 2011
  • In: Journal of Tissue Viability. - : Elsevier BV. - 1876-4746 .- 0965-206X. ; 20, s. 1-18
  • Research review (peer-reviewed)abstract
    • Aim: Negative Pressure Wound Therapy (NPWT) has become widely adopted over the last 15 years and over 1000 peer-reviewed publications are available describing its use. Despite this, there remains uncertainty regarding several aspects of usage. In order to respond to this gap a global expert panel was convened to develop evidence-based recommendations describing the use of NPWT. In this communication the results of the study of evidence in chronic wounds including pressure ulcers, diabetic foot ulcers (DFU), venous leg ulcers (VLU), and ischaemic lower limb wounds are reported. Methods: Evidence-based recommendations were obtained by a systematic review of the literature, grading of evidence, drafting of the recommendations by a global expert panel followed by a formal consultative consensus development program in which 422 independent healthcare professionals were able to agree or disagree with the recommendations. The criteria for agreement were set at 80% agreement. Evidence and recommendations were graded according to the SIGN (Scottish Intercollegiate Guidelines Network) classification system. Results: The primary treatment goal of NPWT in most chronic wounds is to achieve wound closure (either by secondary intention or preparing the wound for surgical closure). Secondary goals commonly include: to reduce wound dimensions, and to improve the quality of the wound bed. Thirteen evidence based recommendations were developed in total to address these treatment goals; 4 for pressure ulcers, 4 for DFU, 3 for ischaemic lower limb wounds and 2 for VLU. Conclusion: The present evidence base is strongest for the use of NPWT in non-ischaemic DFU and weakest in VLU. The development of evidence-based recommendations for NPWT with direct validation from a large group of practicing clinicians offers a broader basis for consensus than work by an expert panel alone. (c) 2011 Published by Elsevier Ltd on behalf of Tissue Viability Society.
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31.
  • Åkebrand, Rebecka, et al. (author)
  • Ophthalmological characteristics in children with Leigh syndrome : A long-term follow-up
  • 2016
  • In: Acta Ophthalmologica. - : John Wiley & Sons. - 1755-375X .- 1755-3768. ; 94:6, s. 609-617
  • Journal article (peer-reviewed)abstract
    • PURPOSE: To describe ophthalmological characteristics in children with Leigh syndrome (LS), an inherited, progressive, mitochondrial encephalomyopathy, at diagnosis and over time, and relate the results to causative genetic mutations.METHODS: Forty-four children with LS (19 females), with a median age of 2.4 years (range: 0.6-14.2 years) at diagnosis, were studied at the Queen Silvia Children's Hospital, Gothenburg, Sweden. Twenty-eight children had known genetic defects. The children underwent an ophthalmological examination, including visual acuity (VA), eye motility, refraction, slit lamp examination, ophthalmoscopy and a full-field electroretinogram (ff-ERG). Seventeen children were available for follow-up over a mean time of 5.4 years (range: 0.3-14.8 years). The results of these children were compared with an age- and sex-matched reference group of healthy children (n = 119).RESULTS: Altogether 36/44 of the children (82%) had ophthalmological abnormalities. The most common findings were refractive errors (n = 16/25), low VA (n = 9/36), strabismus (n = 8/42), reduced eye motility (n = 8/40), optic atrophy (n = 7/41), retinal pigmentation (n = 6/40) and nystagmus (n = 6/42). Several ophthalmological manifestations appeared over time. In 5/22 children, ff-ERG showed retinal dystrophy. No significant correlation between phenotype and genotype was found. The children with LS had significantly lower VA (p < 0.0001, Mantel-Haenszel chi-square exact test), more astigmatism (p = 0.012, Fisher's exact test) and higher incidence of strabismus (p = 0.0002) compared to controls at follow-up.CONCLUSIONS: In this unique cohort of children with LS, the vast majority showed ophthalmological findings at diagnosis, which increased over time. Therefore, we recommend that all children diagnosed with LS should be followed up with regular ophthalmological examinations.
  •  
32.
  • Hallengren, Bengt, et al. (author)
  • Normal visual fields as assessed by computerized static threshold perimetry in patients with untreated primary hypothyroidism
  • 1989
  • In: Acta Endocrinologica. - 0001-5598. ; 121:4, s. 495-500
  • Journal article (peer-reviewed)abstract
    • In this prospective study, 25 consecutive patients with untreated primary hypothyroidism were tested with a highly sensitive perimetric technique, since a high prevalence of visual field defects has been described in this condition. All patients had clinical hypothyroidism, a serum TSH value greater than 20 mU/l (reference range 0.4-4.0) and decreased/low normal serum total T4 concentration. Visual fields were tested with fully automated threshold-measuring computerized perimetry of the central 30 degrees field. Interpretation of fields included computer-assisted analysis provided by a perimetric statistical programme package. In 23 patients, conventional inspection and computer-assisted analysis showed no visual field defects. Two patients were excluded from the latter analysis: one patient who did not respond adequately at computerized perimetry and in whom manual field tests were entirely normal: one patient who had low sensitivity values in the uppermost parts of both visual fields owing to markedly swollen upper eye lids. In conclusion, although pituitary hyperplasia has been well documented in primary hypothyroidism, the present prospective study clearly indicates that visual field defects are not a common finding in patients with this disease.
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33.
  • Huang, X. F., et al. (author)
  • Genomewide Association Study of Acute Anterior Uveitis Identifies New Susceptibility Loci
  • 2020
  • In: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 61:6
  • Journal article (peer-reviewed)abstract
    • PURPOSE. Acute anterior uveitis (AAU) is a common intraocular inflammatory disease. AAU occurs in 30% to 50% of patients with ankylosing spondylitis (AS), and both conditions are strongly associated with human leukocyte antigen (HLA)-B 27 , implying a shared etiology. This study aims to apply genomewide association study (GWAS) to characterize the genetic associations of AAU and their relationship to the genetics of AS. METHODS. We undertook the GWAS analyses in 2752 patients with AS with AAU (cases) and 3836 patients with AS without AAU (controls). There were 7,436,415 single-nucleotide polymorphisms (SNPs) available alter SNP microarray genotyping, imputation, and quality-control filtering. RESULTS. We identified one locus associated with AAU at genomewide significance: rs9378248 (P = 2.69 x 10(-8), odds ratio [OR] = 0.78), lying close to HLA-B. Suggestive association was observed at 11 additional loci, including previously reported AS loci ERAP1 (rs27529, P = 2.19 x 10(-7), OR = 1.22) and NOS2 (rs2274894, P = 8.22 x 10(-7), OR = 0.83). Multiple novel suggestive associations were also identified, including MERTK (rsl0171979, P = 2.56 x 10(-6), OR = 1.20), KIFAP3 (rs508063, P = 5.64 x 10(-7), OR = 1.20), CLCN7 (rs67412457, P = 1.33 x 10(-6), OR = 1.25), ACAA2 (rs9947182, P = 9.70 x 10(-7), OR = 1.37), and 5 intergenic loci. The SNP-based heritability is approximately 0.5 for AS alone, and is much higher (approximately 0.7) for AS with AAU. Consistent with the high heritability, a genomewide polygenic risk score shows strong power in identifying individuals at high risk of either AS with AAU or AS alone. CONCLUSIONS. We report here the first GWAS for AAU and identify new susceptibility loci. Our findings confirm the strong overlap in etiopathogenesis of AAU with AS, and also provide new insights into the genetic basis of AAU.
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34.
  • Lagali, Neil, et al. (author)
  • Dendritic cell maturation in the corneal epithelium with onset of type 2 diabetes is associated with tumor necrosis factor receptor superfamily member 9
  • 2018
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1
  • Journal article (peer-reviewed)abstract
    • Type 2 diabetes mellitus is characterized by a low-grade inflammation; however, mechanisms leading to this inflammation in specific tissues are not well understood. The eye can be affected by diabetes; thus, we hypothesized that inflammatory changes in the eye may parallel the inflammation that develops with diabetes. Here, we developed a non-invasive means to monitor the status of inflammatory dendritic cell (DC) subsets in the corneal epithelium as a potential biomarker for the onset of inflammation in type 2 diabetes. In an age-matched cohort of 81 individuals with normal and impaired glucose tolerance and type 2 diabetes, DCs were quantified from wide-area maps of the corneal epithelial sub-basal plexus, obtained using clinical in vivo confocal microscopy (IVCM). With the onset of diabetes, the proportion of mature, antigen-presenting DCs increased and became organized in clusters. Out of 92 plasma proteins analysed in the cohort, tumor necrosis factor receptor super family member 9 (TNFRSF9) was associated with the observed maturation of DCs from an immature to mature antigen-presenting phenotype. A low-grade ocular surface inflammation observed in this study, where resident immature dendritic cells are transformed into mature antigen-presenting cells in the corneal epithelium, is a process putatively associated with TNFRSF9 signalling and may occur early in the development of type 2 diabetes. IVCM enables this process to be monitored non-invasively in the eye.
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35.
  • Akerblom, H., et al. (author)
  • Association of Gastric Bypass Surgery With Risk of Developing Diabetic Retinopathy Among Patients With Obesity and Type 2 Diabetes in Sweden: An Observational Study
  • 2021
  • In: Jama Ophthalmology. - : American Medical Association (AMA). - 2168-6165 .- 2168-6173. ; 139:2, s. 200-205
  • Journal article (peer-reviewed)abstract
    • IMPORTANCE Knowledge of the incidence and progression of diabetic retinopathy (DR) after gastric bypass surgery (GBP) in patients with obesity and diabetes could guide the management of these patients. OBJECTIVE To investigate the incidence of diabetic ocular complications in patients with type 2 diabetes after GBP compared with the incidence of diabetic ocular complications in a matched cohort of patients with obesity and diabetes who have not undergone GBP. DESIGN, SETTING, AND PARTICIPANTS Data from 2 nationwide registers in Sweden, the Scandinavian Obesity Surgery Registry and the National Diabetes Register, were used for this cohort study. A total of 5321 patients with diabetes from the Scandinavian Obesity Surgery Registry who had undergone GBP from January 1, 2007, to December 31, 2013, were matched with 5321 patients with diabetes from the National Diabetes Register who had not undergone GBP, based on sex, age, body mass index (BMI), and calendar time (2007-2013). Follow-up data were obtained until December 31, 2015. Statistical analysis was performed from October 5, 2018, to September 30, 2019. EXPOSURE Gastric bypass surgery. MAIN OUTCOMES AND MEASURES Incidence of new DR and other diabetic ocular complications. RESULTS The study population consisted of 5321 patients who had undergone GBP (3223 women [60.6%]; mean [SD] age, 49.0 [9.5] years) and 5321 matched controls (3395 women [63.8%]; mean [SD] age, 47.1 [11.5] years). Mean (SD) follow-up was 4.5 (1.6) years. The mean (SD) BMI and hemoglobin A1c concentration at baseline were 42.0 (5.7) and 7.6%(1.5%), respectively, in the GBP group and 40.9 (7.3) and 7.5%(1.5%), respectively, in the control group. The mean (SD) duration of diabetes was 6.8 (6.3) years in the GBP group and 6.4 (6.4) years in the control group. The risk for new DR was reduced in the patients who underwent GBP (hazard ratio, 0.62 [95% CI, 0.49-0.78]; P <.001). The dominant risk factors for development of DR at baseline were diabetes duration, hemoglobin A1c concentration, use of insulin, glomerular filtration rate, and BMI. CONCLUSIONS AND RELEVANCE This nationwide matched cohort study suggests that there is a reduced risk of developing new DR associated with GBP, and no evidence of an increased risk of developing DR that threatened sight or required treatment. (c) 2021 American Medical Association. All rights reserved.
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36.
  • Brock, Christina, et al. (author)
  • The Retinal Nerve Fiber Layer Thickness Is Associated with Systemic Neurodegeneration in Long-Term Type 1 Diabetes
  • 2023
  • In: Translational Vision Science & Technology. - : Association for Research in Vision and Ophthalmology (ARVO). - 2164-2591. ; 12:6
  • Journal article (peer-reviewed)abstract
    • Purpose: To determine whether the retinal nerve fiber layer thickness can be used as an indicator for systemic neurodegeneration in diabetes.Methods: We used existing data from 38 adults with type 1 diabetes and established polyneuropathy. Retinal nerve fiber layer thickness values of four scanned quadrants (superior, inferior, temporal, and nasal) and the central foveal thickness were extracted directly from optical coherence tomography. Nerve conduction velocities were recorded using standardized neurophysiologic testing of the tibial and peroneal motor nerves and the radial and median sensory nerves, 24-hour electrocardiographic recordings were used to retrieve time- and frequency-derived measures of heart rate variability, and a pain catastrophizing scale was used to assess cognitive distortion.Results: When adjusted for hemoglobin A1c, the regional thickness of the retinal nerve fiber layers was (1) positively associated with peripheral nerve conduction velocities of the sensory and motor nerves (all P < 0.036), (2) negatively associated with time and frequency domains of heart rate variability (all P < 0.033), and (3) negatively associated to catastrophic thinking (all P < 0.038).Conclusions: Thickness of the retinal nerve fiber layer was a robust indicator for clinically meaningful measures of peripheral and autonomic neuropathy and even for cognitive comorbidity.Translational Relevance: The findings indicate that the thickness of the retinal nerve fiber layer should be studied in adolescents and people with prediabetes to determine whether it is useful to predict the presence and severity of systemic neurodegeneration.
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37.
  •  
38.
  • Dominguez-Vicent, A, et al. (author)
  • Agreement of different OCT scan directions for individual retinal-layer thickness measurements in multiple sclerosis subjects with prior unilateral optic neuritis
  • 2022
  • In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1, s. 566-
  • Journal article (peer-reviewed)abstract
    • The similarities between horizontal and vertical Optical Coherence Tomography (OCT) scans for the individual retinal layer thickness measurements in the macula was evaluated. Two volumetric scans (B-scans oriented horizontally and vertically) were performed in 64 multiple sclerosis subjects with history of unilateral optic neuritis and 64 healthy controls. The agreement between the thickness measurements with horizontal and vertical OCT scans was evaluated in 3 groups of eyes: healthy controls, eyes with history of optic neuritis and the fellow eyes. The mean difference in individual layer thickness between the scans was smaller than the instrument’s axial resolution in all 3 groups. The limit of agreement (LoA) varied among the different layers and sectors analyzed and this trend was similar in all the groups. For the inner retinal layers (retinal nerve fiber layer to inner nuclear layer), the inner macular sectors had a larger LoA compared to the corresponding outer sectors. In the outer plexiform and nuclear layers, the central and inner sectors (except inner temporal) had LoA larger than the other sectors and layers. The larger LoA seen for different layers and sectors suggests that the scan direction must be same for the follow-up OCT measurements and in clinical studies.
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39.
  • Gustavsson, Carin, et al. (author)
  • Vascular cellular adhesion molecule-1 (VCAM-1) expression in mice retinal vessels is affected by both hyperglycemia and hyperlipidemia.
  • 2010
  • In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:9
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Inflammation has been proposed to be important in the pathogenesis of diabetic retinopathy. An early feature of inflammation is the release of cytokines leading to increased expression of endothelial activation markers such as vascular cellular adhesion molecule-1 (VCAM-1). Here we investigated the impact of diabetes and dyslipidemia on VCAM-1 expression in mouse retinal vessels, as well as the potential role of tumor necrosis factor-α (TNFα). METHODOLOGY/PRINCIPAL FINDINGS: Expression of VCAM-1 was examined by confocal immunofluorescence microscopy in vessels of wild type (wt), hyperlipidemic (ApoE(-/-)) and TNFα deficient (TNFα(-/-), ApoE(-/-)/TNFα(-/-)) mice. Eight weeks of streptozotocin-induced diabetes resulted in increased VCAM-1 in wt mice, predominantly in small vessels (<10 µm). Diabetic wt mice had higher total retinal TNFα, IL-6 and IL-1β mRNA than controls; as well as higher soluble VCAM-1 (sVCAM-1) in plasma. Lack of TNFα increased higher basal VCAM-1 protein and sVCAM-1, but failed to up-regulate IL-6 and IL-1β mRNA and VCAM-1 protein in response to diabetes. Basal VCAM-1 expression was higher in ApoE(-/-) than in wt mice and both VCAM-1 mRNA and protein levels were further increased by high fat diet. These changes correlated to plasma cholesterol, LDL- and HDL-cholesterol, but not to triglycerides levels. Diabetes, despite further increasing plasma cholesterol in ApoE(-/-) mice, had no effects on VCAM-1 protein expression or on sVCAM-1. However, it increased ICAM-1 mRNA expression in retinal vessels, which correlated to plasma triglycerides. CONCLUSIONS/SIGNIFICANCE: Hyperglycemia triggers an inflammatory response in the retina of normolipidemic mice and up-regulation of VCAM-1 in retinal vessels. Hypercholesterolemia effectively promotes VCAM-1 expression without evident stimulation of inflammation. Diabetes-induced endothelial activation in ApoE(-/-) mice seems driven by elevated plasma triglycerides but not by cholesterol. Results also suggest a complex role for TNFα in the regulation of VCAM-1 expression, being protective under basal conditions but pro-inflammatory in response to diabetes.
  •  
40.
  • Hanner, P, et al. (author)
  • Clinical observations of effects on central nervous system in patients with acute facial palsy.
  • 1987
  • In: Archives of otolaryngology--head & neck surgery. - 0886-4470. ; 113:5, s. 516-20
  • Journal article (peer-reviewed)abstract
    • Twenty-eight consecutive patients with acute unilateral facial palsy were examined with special reference to clinical signs of central nervous system involvement. The clinical investigation in the acute stage of the disease showed that only seven patients had solitary facial nerve dysfunction, while the remaining patients had evidence of more widespread disease involvement. The most frequent finding was a trigeminal dysfunction of the paretic side, as shown by paresthesia and sensibility disturbance corresponding to the sensoritrigeminal area, as well as a dysfunction of the trigeminal component of the corneal reflex of the paretic side. Three patients showed migrating symptoms that were suggestive of a brain-stem disorder. In addition, four patients had an optic neuropathy, while an abnormal brain-stem audiometry response was demonstrated in five patients. The outcome of acute facial palsy one to two years after onset, however, could not be predicted from the clinical central nervous system signs. The degree of the palsy in the acute stage of the disease still seemed to be one of the most important prognostic factors. It is concluded that acute facial palsy is not a single entity, but rather a feature of different neurologic conditions.
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41.
  • Hellström, Ann, 1959, et al. (author)
  • 20 000 barn blir blinda eller svårt synskadade varje år av prematuritets-retinopati
  • 2016
  • In: Läkartidningen. - 0023-7205. ; 113:38
  • Journal article (peer-reviewed)abstract
    • Retinopathy of prematurity is a neurovascular disorder which yearly makes 20 000 infants blind or severely visually impaired worldwide. Hyperoxia is a crucial risk factor in settings with uncontrolled oxygen supplementation, while insufficient nutrient assimilation is a general contributing factor. ROP is a two phase disease with general as well as retinal neurovascular growth arrest after birth and later uncontrolled retinal neovascularization. Laser therapy prevents retinal detachment in most cases. Screening programs need to have inclusion criteria suited for the actual level of neonatal care. With less advanced care, more mature infants are affected by ROP. Risk of severe ROP can be calculated based on neonatal weight gain, especially in high quality care settings. Control of oxygen supplementation can save the sight of many infants in developing countries. Research should focus on prevention of ROP promoting postnatal growth and development. Current off-label use of anti-VEGF treatment is worrying since evidence for e.g. safety is lacking. © 2016, Swedish Medical Association. All rights reserved.
  •  
42.
  • Jacobson, Lena, et al. (author)
  • Retinal ganglion cell topography predicts visual field function in spastic cerebral palsy
  • 2020
  • In: Developmental Medicine and Child Neurology. - : Wiley. - 0012-1622 .- 1469-8749. ; 62:9, s. 1100-1106
  • Journal article (peer-reviewed)abstract
    • The aim of this study was to evaluate the use of optical coherence tomography (OCT) to identify and assess visual field defects caused by primary damage to the optic radiation in individuals with spastic cerebral palsy (CP). Ten individuals with spastic CP (six females, four males, with a median age of 21 years [range 17–38y]) had their brain lesions documented with conventional magnetic resonance imaging (MRI) and diffusion-weighted MRI fibre tractography. Their macular ganglion cell layer (GCL) and inner plexiform layer (IPL) were examined with OCT and their visual fields were plotted. All participants had good visual acuity and were able to cooperate with the MRI and OCT examinations, as well as undergoing reliable perimetry. We found focal thinning of the GCL+IPL and corresponding homonymous visual field defects in individuals with brain damage affecting the optic radiation. We used GCL+IPL sector asymmetry as a sensitive OCT parameter to identify focal visual field defects. We observed no such sector asymmetry in GCL+IPL, or focal visual field defects, in individuals with normal MRI optic radiation imaging. Lesions affecting the optic radiation cause retrograde trans-synaptic degeneration of retinal ganglion cells. OCT examination of the GCL in the macula identified corresponding focal damage to the optic radiation in individuals with spastic CP and can be used to predict focal visual field defects. What this paper adds: Spastic cerebral palsy (CP) may be associated with damage to the optic radiation. Damage to the optic radiation causes retrograde trans-synaptic degeneration (RTSD). RTSD can be mapped using optical coherence tomography. Ganglion cell topography can predict visual field defects in individuals with spastic CP.
  •  
43.
  • Karimi, Annette, et al. (author)
  • Brain MRI findings and their association with visual impairment in young adolescents born very preterm
  • 2024
  • In: Neuroradiology. - : Springer. - 0028-3940 .- 1432-1920. ; 66:1, s. 145-154
  • Journal article (peer-reviewed)abstract
    • PurposeVery preterm birth increases risk for neonatal white matter injury, but there is limited data on to what extent this persists into adolescence and how this relates to ophthalmological outcomes. The aim of this study was to assess brain MRI findings in 12-year-old children born very preterm compared to controls and their association with concurrent ophthalmological outcomes.MethodsWe included 47 children born very preterm and 22 full-term controls (gestational age <32 and >37 weeks, respectively). Brain MRI findings were studied in association with concurrent ophthalmological outcomes at 12-year follow-up.ResultsEvans index (0.27 vs 0.25, p<0.001) and a proposed “posterior ventricle index” (0.47 vs 0.45, p=0.018) were increased in children born very preterm. Higher gestational age associated with larger corpus callosum area (β=10.7, 95%CI 0.59–20.8). Focal white matter lesions were observed in 15 (32%) of very preterm children and in 1 (5%) of full-term controls. Increased posterior ventricle index increased risk for visual acuity ≤1.0 (OR=1.07×1011, 95%CI=7.78–1.48×1021) and contrast sensitivity <0.5 (OR=2.6×1027, 95%CI=1.9×108–3.5×1046). Decreased peritrigonal white matter thickness associated with impaired visual acuity (β=0.04, 95%CI 0.002–0.07).ConclusionMore white matter lesions and evidence of lower white matter volume were found in children born very preterm compared with full-term controls at 12-year follow-up. The association between larger posterior ventricle index and reduced visual acuity and contrast sensitivity suggests disturbances of the posterior visual pathway due to diffuse white matter lesions.
  •  
44.
  • Konstantinou, Konstantinos, 1993, et al. (author)
  • Statistical modeling of diabetic neuropathy: Exploring the dynamics of nerve mortality
  • 2023
  • In: Statistics in Medicine. - 0277-6715 .- 1097-0258. ; 42:23, s. 4128-4146
  • Journal article (peer-reviewed)abstract
    • Diabetic neuropathy is a disorder characterized by impaired nerve function and reduction of the number of epidermal nerve fibers per epidermal surface. Additionally, as neuropathy related nerve fiber loss and regrowth progresses over time, the two-dimensional spatial arrangement of the nerves becomes more clustered. These observations suggest that with development of neuropathy, the spatial pattern of diminished skin innervation is defined by a thinning process which remains incompletely characterized. We regard samples obtained from healthy controls and subjects suffering from diabetic neuropathy as realisations of planar point processes consisting of nerve entry points and nerve endings, and propose point process models based on spatial thinning to describe the change as neuropathy advances. Initially, the hypothesis that the nerve removal occurs completely at random is tested using independent random thinning of healthy patterns. Then, a dependent parametric thinning model that favors the removal of isolated nerve trees is proposed. Approximate Bayesian computation is used to infer the distribution of the model parameters, and the goodness-of-fit of the models is evaluated using both non-spatial and spatial summary statistics. Our findings suggest that the nerve mortality process changes as neuropathy advances.
  •  
45.
  • Kulik, U, et al. (author)
  • Long-term results after primary intraocular lens implantation in children with juvenile idiopathic arthritis-associated uveitis
  • 2019
  • In: European journal of ophthalmology. - : SAGE Publications. - 1724-6016 .- 1120-6721. ; 29:5, s. 494-498
  • Journal article (peer-reviewed)abstract
    • To evaluate the long-term outcome after cataract surgery with primary intraocular lens implantation in children with juvenile idiopathic arthritis–associated uveitis. Methods: The medical records of all 24 children (34 eyes) with chronic juvenile idiopathic arthritis–associated uveitis who underwent cataract surgery between 1990 and 2013 were reviewed retrospectively. Primary intraocular lens implantation was performed in all patients. Results: Median age at diagnosis of uveitis in the first eye was 5.3 years (range: 2.7–9.4 years) and median age at the time of cataract surgery in the first eye was 9.7 years (range: 4.1–16.9 years). Postoperative follow-up time ranged from 1 to 23.1 years, with a median of 10.9 years. Best corrected visual acuity at the last follow-up was good (⩾20/40) in 65% of the eyes. Postoperatively, glaucoma developed in 8 eyes (24%), posterior capsular opacification and secondary membrane formation requiring surgery in 15 eyes (44%), macular oedema in 5 eyes (15%) and phthisis in 2 eyes (6%). Conclusion: This study shows a favourable visual outcome in most of the cases. Primary intraocular lens implantation may be considered in juvenile idiopathic arthritis–associated uveitis complicated by cataract in patients with well-controlled inflammation.
  •  
46.
  • Lundgren, Pia, 1967-, et al. (author)
  • WINROP identifies severe retinopathy of prematurity at an early stage in a nation-based cohort of extremely preterm infants
  • 2013
  • In: PLOS ONE. - San Francisco : Public Library of Science, PLoS. - 1932-6203. ; 8:9
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To evaluate the ability of a postnatal weight-gain algorithm (WINROP) to identify sight-threatening retinopathy of prematurity (ROP type 1) in a nation-based extremely preterm infant cohort.METHODS: This study enrolled all 707 live-born extremely preterm (gestational age [GA] <27 weeks) infants, born 2004-2007 in Sweden; the Extremely preterm Infants in Sweden Study (EXPRESS). WINROP analysis was performed retrospectively in 407 of the infants using weekly weight gain to assess the preterm infant's risk of developing ROP type 1 requiring treatment. GA, birthweight (BW), and weekly postnatal weight measurements were entered into WINROP. WINROP signals with an alarm to indicate if the preterm infant is at risk for ROP type 1.RESULTS: In this extremely preterm population, WINROP correctly identified 96% (45/47) of the infants who required treatment for ROP type 1. The median time from alarm to treatment was 9 weeks (range, 4-20 weeks).CONCLUSIONS: WINROP, an online surveillance system using weekly weight gain, identified extremely preterm infants at risk for ROP type 1 requiring treatment at an early stage and with high sensitivity in a Swedish nation-based cohort.
  •  
47.
  • Martin-Boglind, Lene, et al. (author)
  • The effect of topical antiglaucoma drugs on the results of high-pass resolution perimetry
  • 1991
  • In: American Journal of Ophthalmology. - 0002-9394 .- 1879-1891. ; 11:6, s. 711-714
  • Journal article (peer-reviewed)abstract
    • We conducted a randomly assigned, double-masked, crossover study of the effects of betaxolol, epinephrine, pilocarpine, and timolol on the high-passresolution perimetry results in normal subjects. The influence of topical administration of these intraocular pressure reducing drugs was negligible, which confirmed the reliability of high-pass resolution perimetry results. The method seems appropriate for the diagnosis of glaucoma and the follow-up ofpatients with glaucoma.
  •  
48.
  • Martin, Lene, et al. (author)
  • Visual function in young adults following intrauterine growth retardation
  • 2004
  • In: J Pediatr Ophthalmol Strabismus. - : SLACK, Inc.. ; 41:4, s. 212-8
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Intrauterine growth retardation (IUGR) resulting in infants born small for gestational age is a known risk factor for neurologic deficits and may predispose to poor cognitive development later in life. We recently found an association between IUGR and a reduced neuroretinal rim area at 18 years of age. We evaluated the possible association between IUGR and visual function. SUBJECTS AND METHODS: We studied 26 subjects who had been born small for gestational age and 20 subjects whose birth weights were appropriate for gestational age (controls) using letter acuity thresholds, color vision testing, full-threshold frequency doubling technology perimetry, and rarebit perimetry at 18 years of age. gestational age had a rarebit hit rate below the normal range as compared with none of the controls (P = .006). These 8 subjects had a significantly smaller rim-disc ratio compared with the subjects who were small for gestational age who had a normal rarebit hit rate (P = .047). The frequency doubling technology indices did not differ significantly between the control group and the group that was small for gestational age, nor did the visual acuity, refraction, and color vision test results. CONCLUSION: These data indicate that IUGR is associated with an increased rate of impaired visual function, which can be detected by using rarebit perimetry but not frequency doubling technology perimetry, visual acuity, or color vision tests.
  •  
49.
  • Mofors, J., et al. (author)
  • Infections increase the risk of developing Sjögren's syndrome
  • 2019
  • In: Journal of Internal Medicine. - : Wiley-Blackwell. - 0954-6820 .- 1365-2796. ; 285:6, s. 670-680
  • Journal article (peer-reviewed)abstract
    • Objective: Environmental factors have been suggested in the pathogenesis of rheumatic diseases. We here investigated whether infections increase the risk of developing primary Sjögren's syndrome (pSS).Methods: Patients with pSS in Sweden (n = 945) and matched controls from the general population (n = 9048) were included, and data extracted from the National Patient Register to identify infections occurring before pSS diagnosis during a mean observational time of 16.0 years. Data were analysed using conditional logistic regression models. Sensitivity analyses were performed by varying exposure definition and adjusting for previous health care consumption.Results: A history of infection associated with an increased risk of pSS (OR 1.9, 95% CI 1.6–2.3). Infections were more prominently associated with the development of SSA/SSB autoantibody‐positive pSS (OR 2.7, 95% CI 2.0–3.5). When stratifying the analysis by organ system infected, respiratory infections increased the risk of developing pSS, both in patients with (OR 2.9, 95% CI 1.8–4.7) and without autoantibodies (OR 2.1, 95% CI 1.1–3.8), whilst skin and urogenital infections only significantly associated with the development of autoantibody‐positive pSS (OR 3.2, 95% CI 1.8–5.5 and OR 2.7, 95% CI 1.7–4.2). Furthermore, a dose–response relationship was observed for infections and a risk to develop pSS with Ro/SSA and La/SSB antibodies. Gastrointestinal infections were not significantly associated with a risk of pSS.Conclusions: Infections increase the risk of developing pSS, most prominently SSA/SSB autoantibody‐positive disease, suggesting that microbial triggers of immunity may partake in the pathogenetic process of pSS.
  •  
50.
  • Oohashi, T, et al. (author)
  • Mouse ten-m/Odz is a new family of dimeric type II transmembrane proteins expressed in many tissues
  • 1999
  • In: Journal of Cell Biology. - 0021-9525. ; 145:3, s. 563-577
  • Journal article (peer-reviewed)abstract
    • The Drosophila gene ten-m/odz is the only pair rule gene identified to date which is not a transcription factor. In an attempt to analyze the structure and the function of ten-m/odz in mouse, we isolated four murine ten-m cDNAs which code for proteins of 2,700-2, 800 amino acids. All four proteins (Ten-m1-4) lack signal peptides at the NH2 terminus, but contain a short hydrophobic domain characteristic of transmembrane proteins, 300-400 amino acids after the NH2 terminus. About 200 amino acids COOH-terminal to this hydrophobic region are eight consecutive EGF-like domains. Cell transfection, biochemical, and electronmicroscopic studies suggest that Ten-m1 is a dimeric type II transmembrane protein. Expression of fusion proteins composed of the NH2-terminal and hydrophobic domain of ten-m1 attached to the alkaline phosphatase reporter gene resulted in membrane-associated staining of the alkaline phosphatase. Electronmicroscopic and electrophoretic analysis of a secreted form of the extracellular domain of Ten-m1 showed that Ten-m1 is a disulfide-linked dimer and that the dimerization is mediated by EGF-like modules 2 and 5 which contain an odd number of cysteines. Northern blot and immunohistochemical analyses revealed widespread expression of mouse ten-m genes, with most prominent expression in brain. All four ten-m genes can be expressed in variously spliced mRNA isoforms. The extracellular domain of Ten-m1 fused to an alkaline phosphatase reporter bound to specific regions in many tissues which were partially overlapping with the Ten-m1 immunostaining. Far Western assays and electronmicroscopy demonstrated that Ten-m1 can bind to itself.
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