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Hakelius, Malin
Publications (10 of 11) Show all publications
Tillman, K. K., Hakelius, M., Höijer, J., Ramklint, M., Ekselius, L., Nowinski, D. & Papadopoulos, F. (2018). Increased Risk for Neurodevelopmental Disorders in Children With Orofacial Clefts. Journal of the American Academy of Child and Adolescent Psychiatry, 57(11), 876-883
Open this publication in new window or tab >>Increased Risk for Neurodevelopmental Disorders in Children With Orofacial Clefts
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2018 (English)In: Journal of the American Academy of Child and Adolescent Psychiatry, ISSN 0890-8567, E-ISSN 1527-5418, Vol. 57, no 11, p. 876-883Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Children with orofacial clefts (OFC) may have an increased risk of poor mental health. This study aimed to investigate the risk of psychiatric diagnoses in individuals with OFC, stratified by cleft type.

METHOD: A nationwide register-based cohort of all individuals born with nonsyndromic OFC in Sweden between 1973 and 2012 (n = 7,842) was compared to a matched cohort (n = 78,409) as well as to their unaffected siblings (n = 9,637). The risk of psychiatric diagnoses, suicide attempts, and suicides was examined by crude and adjusted Cox regression models. Effect modification by sex was investigated with interaction terms in the models.

RESULTS: Children with cleft lip (CL) had a significantly higher risk of any psychiatric disorder, intellectual disability, and language disorders; children with cleft lip and palate (CLP) had, in addition, an increased risk of autism spectrum disorder (ASD). Children with cleft palate only (CPO) had risk increases for the same diagnoses as children with CL and CLP, but with higher hazard ratios, and also for psychotic disorders, attention-deficit/hyperactivity disorder (ADHD), and other behavioral or emotional disorders in childhood. Sex stratification indicated higher risk increases among females in CL and CLP but not in CPO. Siblings without OFC were less likely to be diagnosed with any psychiatric disorder, intellectual disability, language disorder, ASD, or ADHD compared to their siblings with OFC.

CONCLUSION: Children with nonsyndromic clefts had a significantly higher risk of neurodevelopmental disorders. This risk is unlikely to be explained by familial influences such as inherited genetic or shared environmental factors.

Keywords
epidemiology, neurodevelopmental disorders, nonsyndromic clefts, psychiatric comorbidity
National Category
Psychiatry Neurology
Identifiers
urn:nbn:se:uu:diva-368474 (URN)10.1016/j.jaac.2018.06.024 (DOI)000453802900013 ()30392629 (PubMedID)
Available from: 2018-12-05 Created: 2018-12-05 Last updated: 2019-02-06Bibliographically approved
Jabbari, F., Wiklander, L., Reiser, E., Thor, A., Hakelius, M. & Nowinski, D. (2018). Secondary Alveolar Bone Grafting in Patients Born With Unilateral Cleft Lip and Palate: A 20-Year Follow-up. The Cleft Palate-Craniofacial Journal, 55(2), 173-179
Open this publication in new window or tab >>Secondary Alveolar Bone Grafting in Patients Born With Unilateral Cleft Lip and Palate: A 20-Year Follow-up
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2018 (English)In: The Cleft Palate-Craniofacial Journal, ISSN 1055-6656, E-ISSN 1545-1569, Vol. 55, no 2, p. 173-179Article in journal (Refereed) Published
Abstract [en]

Objective: To identify factors of oral health important for the final outcome, after secondary alveolar bone grafting in patients born with unilateral cleft lip and palate and compare occlusal radiographs with cone beam computed tomography (CBCT) in assessment of alveolar bone height. Design: Observational follow-up study. Setting: Cleft Lip and Palate Team, Craniofacial Center, Uppsala University Hospital, Sweden. Patients: 40 nonsyndromic, Caucasian patients with unilateral complete cleft lip and palate. Interventions: Clinical examination, CBCT, and occlusal radiographs. Main Outcome Measurements: Alveolar bone height was evaluated according to Bergland index at a 20-year follow-up. Results: The alveolar bone height in the cleft area was significantly reduced compared to a previously reported 10-year follow-up in the same cohort by total (P = .045) and by subgroup with dental restoration (P = .0078). This was positively correlated with the gingival bleeding index (GBI) (r = 0.51, P = .0008) and presence of dental restorations in the cleft area (r = 0.45, P = .0170). There was no difference in the Bergland index generated from scoring the alveolar bone height on occlusal radiographs as with the equivalent index on CBCT. Conclusion: Patients rehabilitated with complex dental restoration seems to be at higher risk for progression of bone loss in the cleft area. Supportive periodontal therapy should be implemented after complex dental restorations in cleft patients. Conventional occlusal radiographs provide an adequate image for evaluating postoperative bone height in clinical follow-up.

Keywords
alveolar bone grafting, dental restoration, unilateral cleft lip and palate
National Category
Dentistry
Identifiers
urn:nbn:se:uu:diva-348925 (URN)10.1177/1055665617726999 (DOI)000426011700003 ()29351042 (PubMedID)
Available from: 2018-04-26 Created: 2018-04-26 Last updated: 2018-04-26Bibliographically approved
Falk Delgado, A., Lang, A., Hakelius, M., Skoog, V. & Nowinski, D. (2018). The Skoog Lip Repair for Unilateral Cleft Lip Deformity: The Uppsala Experience. Plastic and reconstructive surgery (1963), 141(5), 1226-1233
Open this publication in new window or tab >>The Skoog Lip Repair for Unilateral Cleft Lip Deformity: The Uppsala Experience
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2018 (English)In: Plastic and reconstructive surgery (1963), ISSN 0032-1052, E-ISSN 1529-4242, Vol. 141, no 5, p. 1226-1233Article in journal (Refereed) Published
Abstract [en]

Background: The Uppsala Craniofacial Center has been treating patients with unilateral cleft lip deformity using the lip repair technique described by Tord Skoog. The aim of this study was to determine complications after lip surgery and the incidence and indications for lip revisions in all patients born with unilateral cleft lip from 1960 to 2004.

Methods: All patients who were born from 1960 to 2004 with unilateral cleft lip, cleft lip and alveolus, or cleft lip and palate and underwent lip repair were studied retrospectively. The timing, indication, complications of the primary procedure, and type of secondary surgery were recorded. Kruskal-Wallis and Fisher’s exact tests were used, with Bonferroni correction.

Results: The study included 443 patients. The total rate of early surgical complications was 6 percent (n = 26). Secondary surgery for short upper lip was performed in 3.8 percent (n = 17), 8.4 percent (n = 37) underwent reduction of excess vermillion, 8.6 percent (n = 38) underwent scar revision, 11 percent (n = 51) underwent revision for incongruent vermillion-cutaneous border, and 10 percent (n = 45) underwent revision for other indications. Altogether, 45 percent had no secondary revisions.

Conclusion: In conclusion, the Skoog lip repair is associated with a low total revision rate, and a short-lip deformity is rare.

CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-357583 (URN)10.1097/PRS.0000000000004321 (DOI)000433322900058 ()29697619 (PubMedID)
Available from: 2018-08-17 Created: 2018-08-17 Last updated: 2018-08-17Bibliographically approved
Jabbari, F., Hakelius, M., Thor, A., Reiser, E., Skoog, V. & Nowinski, D. (2017). Skoog Primary Periosteoplasty versus Secondary Alveolar Bone grafting in Unilateral Cleft Lip and Alveolus: Long.term effects on alveolar Bone Formation and Maxillary Growth. Plastic and reconstructive surgery (1963), 139(1), 137-148
Open this publication in new window or tab >>Skoog Primary Periosteoplasty versus Secondary Alveolar Bone grafting in Unilateral Cleft Lip and Alveolus: Long.term effects on alveolar Bone Formation and Maxillary Growth
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2017 (English)In: Plastic and reconstructive surgery (1963), ISSN 0032-1052, E-ISSN 1529-4242, Vol. 139, no 1, p. 137-148Article in journal (Refereed) Published
Abstract [en]

Background: Clefts involving the alveolus are treated using one of two strategies: primary periosteoplasty at the time of lip repair or secondary alveolar bone grafting at mixed dentition. Most teams favor secondary alveolar bone grafting because of its high success rate, and concerns have been raised that primary periosteoplasty may interfere with maxillary growth. However, primary periosteoplasty may obviate the need for future bone grafting and is still practiced in some centers. Few studies compare the long-term outcomes of these two strategies.

Methods: Fifty-seven consecutive patients born with unilateral cleft lip and alveolus were studied retrospectively. All patients underwent primary lip repair using Skoog's method; 28 patients underwent primary periosteoplasty at the time of lip repair and the remaining 29 underwent secondary alveolar bone grafting at mixed dentition. Occlusal radiographs obtained at ages 10 and 16 years were analyzed for alveolar bone height. Cephalometric analysis assessed growth at ages 5, 10, and 18 years.

Results: Seventeen of 28 patients treated using primary periosteoplasty required later secondary bone grafting, and the bone height at age 16 years was lower in the primary periosteoplasty group (p < 0.0001). There was a more pronounced decrease in maxillary protrusion from ages 5 to 10 years in the primary periosteoplasty group (p < 0.03). However, at age 18 there was no significant difference in maxillary growth between the two groups.

Conclusion: Primary periosteoplasty did not seem to inhibit long-term maxillary growth but was ineffective as a method of reconstructing the alveolar cleft.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-282017 (URN)10.1097/PRS.0000000000002910 (DOI)000394051100011 ()28027239 (PubMedID)
Available from: 2016-04-01 Created: 2016-04-01 Last updated: 2017-04-20Bibliographically approved
Jabbari, F., Reiser, E., Thor, A., Hakelius, M. & Nowinski, D. (2016). Correlations between initial cleft size and dental anomalies in unilateral cleft lip and palate patients after alveolar bone grafting. Upsala Journal of Medical Sciences, 121(1), 33-37
Open this publication in new window or tab >>Correlations between initial cleft size and dental anomalies in unilateral cleft lip and palate patients after alveolar bone grafting
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2016 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 121, no 1, p. 33-37Article in journal (Refereed) Published
Abstract [en]

Objective To determine in individuals with unilateral cleft lip and palate the correlation between initial cleft size and dental anomalies, and the outcome of alveolar bone grafting. Methods A total of 67 consecutive patients with non-syndromic unilateral complete cleft lip and palate (UCLP) were included from the cleft lip and palate-craniofacial center, Uppsala University Hospital, Sweden. All patients were operated by the same surgeon and treated according to the Uppsala protocol entailing: lip plasty at 3 months, soft palate closure at 6 months, closure of the residual cleft in the hard palate at 2 years of age, and secondary alveolar bone grafting (SABG) prior to the eruption of the permanent canine. Cleft size was measured on dental casts obtained at the time of primary lip plasty. Dental anomalies were registered on radiographs and dental casts obtained before bone grafting. Alveolar bone height was evaluated with the Modified Bergland Index (mBI) at 1 and 10-year follow-up. Results Anterior cleft width correlated positively with enamel hypoplasia and rotation of the central incisor adjacent to the cleft. There was, however, no correlation between initial cleft width and alveolar bone height at either 1 or 10 years follow-up. Conclusions Wider clefts did not seem to have an impact on the success of secondary alveolar bone grafting but appeared to be associated with a higher degree of some dental anomalies. This finding may have implications for patient counseling and treatment planning.

Keywords
unilateral cleft lip and palate, initial cleft size, Dental status
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-283801 (URN)10.3109/03009734.2015.1134733 (DOI)000372123700005 ()26923345 (PubMedID)
Available from: 2016-04-20 Created: 2016-04-14 Last updated: 2017-11-30Bibliographically approved
Hakelius, M., Reyhani, V., Rubin, K., Gerdin, B. & Nowinski, D. (2016). Normal oral keratinocytes and head and neck squamous carcinoma cells induce an innate response in fibroblasts. Anticancer Research, 36(5), 2131-2137
Open this publication in new window or tab >>Normal oral keratinocytes and head and neck squamous carcinoma cells induce an innate response in fibroblasts
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2016 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 36, no 5, p. 2131-2137Article in journal (Other academic) Published
Abstract [en]

Background: Tumor stroma is similar to the connective tissue of chronic inflammation. The extracellular matrix of tumors is formed by cancer-associated fibroblasts that also modulate the inflammatory response. Materials and Methods: We studied the ability of oral keratinocytes (NOK) and oral squamous cell carcinoma cells (SCC) to induce an innate immune response in fibroblasts. Co-cultures with fibroblasts in collagen gels and keratinocytes in inserts were used. Pentraxin 3 (PTX3) was used as an indicator of an innate immune response. Results: SCC and NOK up-regulated fibroblast mRNA expression and protein release of PTX3. mRNA levels were more pronounced in cultures with malignant cells. The induction of PTX3 was abrogated by an interleukin-1 receptor antagonist Conclusion: Keratinocytes have the capacity to induce an interleukin-1-dependent innate immune response by fibroblasts in vitro. This could be important for subsequent fibroblast modulation of the inflammatory reaction in non-malignant and malignant disease processes.

Keywords
co-culture, pentraxin-3, extracellular matrix, interleukin-1 alpha, tumor stroma
National Category
Surgery Cancer and Oncology
Research subject
Plastic Surgery
Identifiers
urn:nbn:se:uu:diva-221123 (URN)000375456200010 ()27127114 (PubMedID)
Available from: 2014-03-26 Created: 2014-03-25 Last updated: 2017-12-05Bibliographically approved
Jabbari, F., Skoog, V., Reiser, E., Hakelius, M. & Nowinski, D. (2015). Optimization of Dental Status Improves Long-Term Outcome After Alveolar Bone Grafting in Unilateral Cleft Lip and Palate. The Cleft Palate-Craniofacial Journal, 52(2), 210-218
Open this publication in new window or tab >>Optimization of Dental Status Improves Long-Term Outcome After Alveolar Bone Grafting in Unilateral Cleft Lip and Palate
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2015 (English)In: The Cleft Palate-Craniofacial Journal, ISSN 1055-6656, E-ISSN 1545-1569, Vol. 52, no 2, p. 210-218Article in journal (Refereed) Published
Abstract [en]

Objective : To evaluate the importance of dental status for long-term outcome after alveolar bone grafting in patients with unilateral cleft lip and palate. Design : Retrospective longitudinal study. Setting : Cleft lip and palate-craniofacial center, Uppsala University Hospital, Sweden. Patients : A total of 67 consecutive patients with unilateral complete cleft lip and palate. Interventions : Secondary alveolar bone grafting, prior to the eruption of the permanent canine, was performed at the average age of 10.0 years (range, 8.5 to 12.0 years). Main Outcome Measures : Alveolar bone height was evaluated with the modified Bergland index at 1 and 10 years after surgery. Results : Of the patients, 97% had modified Bergland index grade I and the remaining 3% had modified Bergland index grade II at 1 year after surgery. At 10 years' follow-up, 43% showed modified Bergland index grade I; 55%, modified Bergland index grade II; and 2% (one patient), modified Bergland index grade III. The degree of dental anomalies in the cleft area, such as enamel hypoplasia, incisor rotation, incisor inclination, canine inclination, and oral hygiene registered preoperatively, all correlated negatively to the modified Bergland index at 10 years after surgery. Enamel hypoplasia (ρ = 0.70195, P < .0001), followed by canine inclination (ρ = 0.55429, P < .0001), showed the strongest correlation to reduced bone height in the cleft area. Conclusions : In patients with unilateral cleft lip and palate, excellent results from secondary alveolar bone grafting in terms of bone height in the alveolar cleft tend to decrease with time. This seems to be correlated with factors that might to some extent be treated preoperatively through adequate planning and execution of the orthodontic treatment.

National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-245024 (URN)10.1597/13-118 (DOI)000352143500013 ()24568558 (PubMedID)
Available from: 2015-02-24 Created: 2015-02-24 Last updated: 2017-12-04Bibliographically approved
Hakelius, M., Koskela, A., Ivarsson, M., Grenman, R., Rubin, K., Gerdin, B. & Nowinski, D. (2013). Keratinocytes and Head and Neck Squamous Cell Carcinoma Cells Regulate Urokinase-type Plasminogen Activator and Plasminogen Activator Inhibitor-1 in Fibroblasts. Anticancer Research, 33(8), 3113-3118
Open this publication in new window or tab >>Keratinocytes and Head and Neck Squamous Cell Carcinoma Cells Regulate Urokinase-type Plasminogen Activator and Plasminogen Activator Inhibitor-1 in Fibroblasts
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2013 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 33, no 8, p. 3113-3118Article in journal (Refereed) Published
Abstract [en]

Background: To investigate possible differences in the effects of soluble factors from oral squamous cell carcinoma (SCC) cells (UT-SCC-87) and normal oral keratinocytes (NOK) on fibroblast expression of genes involved in tumor stroma turnover. Materials and Methods: Transwell co-cultures with fibroblasts in collagen gels, and SCC cells or NOK in inserts were carried out. Fibroblast gene expression was measured with real-time polymerase chain reaction (PCR). Results: The expression of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) was up-regulated in co-cultures with SCC cells but not with NOK. In contrast, both SCC cells and NOK regulated matrix metalloproteinase-1 (MMP1) and -3, and tissue inhibitor of metalloproteinases-2 (TIMP2) and -3 to a similar extent, while MMP2 and TIMP1 were largely unaffected. Interleukin 1 alpha (IL1 alpha) up-regulated both MMP1 and MMP3 and down-regulated PAI-1, TIMP2 and -3. Conclusion: SCC and NOK regulate fibroblast expression of genes involved in tumor stroma turnover differentially in vitro. These observations may contribute to a better understanding of the mechanisms behind extracellular matrix turnover in tumors.

Keywords
Head and neck cancer, keratinocytes, differential regulation, PAI-1, uPA
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-206561 (URN)000322559300018 ()
Available from: 2013-09-02 Created: 2013-09-02 Last updated: 2017-12-06Bibliographically approved
Svee, A., Frykholm, P., Linder, A., Hakelius, M., Skoog, V. & Nowinski, D. (2012). Early Release of Interalveolar Synechiae Under General Anesthesia Through Fiberscopic Nasal Intubation. The Journal of craniofacial surgery (Print), 23(4), E299-E302
Open this publication in new window or tab >>Early Release of Interalveolar Synechiae Under General Anesthesia Through Fiberscopic Nasal Intubation
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2012 (English)In: The Journal of craniofacial surgery (Print), ISSN 1049-2275, E-ISSN 1536-3732, Vol. 23, no 4, p. E299-E302Article in journal (Refereed) Published
Abstract [en]

This article presents a treatment strategy for early release of interalveolar synechiae, aiming to facilitate early oral feeding and prevent temporomandibular joint ankylosis. The treatment results of 2 patients with van der Woude syndrome were retrospectively studied. Both patients underwent early surgical release of interalveolar synechiae under general anesthesia through fiberscopic nasal intubation. The 2 patients were treated at the ages of 6 and 14 days, respectively. The interincisival distances increased from 5 and 6 mm preoperatively to 11 and 10 mm immediately after surgery. This was increased further to 25 and 20 mm at long-term follow-up (6 and 24 months). In conclusion, synechiae between the upper and lower jaws can be safely treated at a very early age under general anesthesia with fiberscopic nasotracheal intubation. The purpose of early intervention in these cases is to facilitate oral feeding and prevent temporomandibular joint ankylosis.

Keywords
Syngnathia, management, temporomandibular joint ankylosis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-179932 (URN)10.1097/SCS.0b013e318252f314 (DOI)000306710200012 ()
Available from: 2012-08-27 Created: 2012-08-27 Last updated: 2017-12-07Bibliographically approved
Hakelius, M., Koskela, A., Reyhani, V., Ivarsson, M., Grenman, R., Rubin, K., . . . Nowinski, D. (2012). Interleukin-1-mediated effects of normal oral keratinocytes and head and neck squamous carcinoma cells on extracellular matrix related gene expression in fibroblasts. Oral Oncology, 48(12), 1236-1241
Open this publication in new window or tab >>Interleukin-1-mediated effects of normal oral keratinocytes and head and neck squamous carcinoma cells on extracellular matrix related gene expression in fibroblasts
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2012 (English)In: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 48, no 12, p. 1236-1241Article in journal (Refereed) Published
Abstract [en]

Objectives: The composition of tumor stroma and the activity of tumor associated fibroblasts are important for tumor growth. Interactions between carcinoma cells and fibroblasts regulate the turnover of extracellular matrix (ECM). Here, the in vitro effects of oral squamous cell carcinoma (SCC) cells (UT-SCC-30 and UT-SCC-87) on fibroblast expression of genes for ECM components and connective tissue growth factor (CTGF/CCN2), were compared to those of normal oral keratinocytes (NOK). Materials and Methods: Cocultures with fibroblasts in collagen gels and keratinocytes with the two cell types separated by a semi permeable membrane were used, and relative gene expression was measured with real-time PCR. Results: All investigated genes were regulated by NOK and the SCCs. The downregulation of pro-collagens alpha 1(I) and alpha 1(III) was more pronounced in cocultures with NOK, while the expression of CCN2 and fibronectin was downregulated by both NOK and the SCCs to a similar extent. UT-SCC-87, but not UT-SCC-30, secreted significantly more IL-1 alpha than NOK. A recombinant interleukin-1 receptor antagonist reversed many of the observed effects on fibroblast gene expression suggesting involvement of IL-1 in cocultures with NOK as well as with SCCs. Conclusion: The observed differential effects on fibroblast gene expression suggest that NOK are more antifibrotic compared to UT-SCC-30 and UT-SCC-87. These findings may contribute to a better understanding of the mechanisms behind ECM turnover in tumors.

Keywords
Cocultures, Extracellular matrix, Interleukin-1 alpha, Tumor stroma
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-188413 (URN)10.1016/j.oraloncology.2012.06.013 (DOI)000311151200007 ()
Available from: 2012-12-17 Created: 2012-12-17 Last updated: 2017-12-06Bibliographically approved
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