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1.
  • Isaksson, Rita, et al. (author)
  • Oral health and oral implant status in edentulous patients with implant-supported dental prostheses who are receiving long-term nursing care
  • 2009
  • In: Gerodontology. - : Wiley Intersience. - 0734-0664 .- 1741-2358. ; 26:4, s. 245-249
  • Journal article (peer-reviewed)abstract
    • AIM: The aim of this study was to investigate oral health and oral implant status in a group of edentulous patients receiving long-term residential or nursing care (LTC), all of whom had implant-supported fixed or removable dental prostheses. MATERIAL AND METHODS: A dental examination was performed on a total of 3310 patients receiving LTC and from this population 35 edentulous patients in whom dental implants had been placed formed the cohort for this study. All examinations were performed by a specialist in hospital dentistry and took place in the patients' own home environment. Oral health was assessed by means of a protocol which evaluated oral hygiene status, possible oral mucosal inflammation and oral mucosal friction levels. Any problems with the implant-supported prosthesis, implant mobility or other complications were also assessed. In addition, patients were asked about any oral symptoms and their usual oral hygiene procedures. RESULTS: About half of the subjects (17/35) were registered as having no/mild inflammation with 18 of 35 having moderate/severe inflammation. Twelve of the 35 patients had good/acceptable oral hygiene and 23 of 35 had poor/bad oral hygiene. Twenty-one of the 35 patients depended on help from the nursing personnel for their daily oral hygiene procedures. Obvious problems with food impaction were noted in 11 patients. A total of 229 implants had been placed in 43 jaws supporting 40 full arch-fixed prostheses and three implant-borne overdentures. There was no evidence of mobility or fractures of either the implants or the prostheses. Fifteen implants showed some exposed screw threads. Pus was exuding from one implant site and general peri-implant gingival hyperplasia was noted in two patients. Twenty-four patients were completely satisfied with the function and appearance of their implant-supported prostheses. Two patients were totally dissatisfied. CONCLUSION: This study indicates that oral implant therapy can be considered as a treatment of choice in elderly patients, even if oral hygiene is sub-optimal.
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2.
  • Cabrita, Rita, et al. (author)
  • Tertiary lymphoid structures improve immunotherapy and survival in melanoma
  • 2020
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 577:7791, s. 561-565
  • Journal article (peer-reviewed)abstract
    • Checkpoint blockade therapies that reactivate tumour-associated T cells can induce durable tumour control and result in the long-term survival of patients with advanced cancers1. Current predictive biomarkers for therapy response include high levels of intratumour immunological activity, a high tumour mutational burden and specific characteristics of the gut microbiota2,3. Although the role of T cells in antitumour responses has thoroughly been studied, other immune cells remain insufficiently explored. Here we use clinical samples of metastatic melanomas to investigate the role of B cells in antitumour responses, and find that the co-occurrence of tumour-associated CD8+ T cells and CD20+ B cells is associated with improved survival, independently of other clinical variables. Immunofluorescence staining of CXCR5 and CXCL13 in combination with CD20 reveals the formation of tertiary lymphoid structures in these CD8+CD20+ tumours. We derived a gene signature associated with tertiary lymphoid structures, which predicted clinical outcomes in cohorts of patients treated with immune checkpoint blockade. Furthermore, B-cell-rich tumours were accompanied by increased levels of TCF7+ naive and/or memory T cells. This was corroborated by digital spatial-profiling data, in which T cells in tumours without tertiary lymphoid structures had a dysfunctional molecular phenotype. Our results indicate that tertiary lymphoid structures have a key role in the immune microenvironment in melanoma, by conferring distinct T cell phenotypes. Therapeutic strategies to induce the formation of tertiary lymphoid structures should be explored to improve responses to cancer immunotherapy.
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3.
  • Cabrita, Rita, et al. (author)
  • Tertiary lymphoid structures improve immunotherapy and survival in melanoma.
  • 2020
  • In: Nature. - : Nature Publishing Group. - 1476-4687 .- 0028-0836. ; 577:7791, s. 561-565
  • Journal article (peer-reviewed)abstract
    • Checkpoint blockade therapies that reactivate tumour-associated T cells can induce durable tumour control and result in the long-term survival of patients with advanced cancers1. Current predictive biomarkers for therapy response include high levels of intratumour immunological activity, a high tumour mutational burden and specific characteristics of the gut microbiota2,3. Although the role of T cells in antitumour responses has thoroughly been studied, other immune cells remain insufficiently explored. Here we use clinical samples of metastatic melanomas to investigate the role of B cells in antitumour responses, and find that the co-occurrence of tumour-associated CD8+ T cells and CD20+ B cells is associated with improved survival, independently of other clinical variables. Immunofluorescence staining of CXCR5 and CXCL13 in combination with CD20 reveals the formation of tertiary lymphoid structures in these CD8+CD20+ tumours. We derived a gene signature associated with tertiary lymphoid structures, which predicted clinical outcomes in cohorts of patients treated with immune checkpoint blockade. Furthermore, B-cell-rich tumours were accompanied by increased levels of TCF7+ naive and/or memory T cells. This was corroborated by digital spatial-profiling data, in which T cells in tumours without tertiary lymphoid structures had a dysfunctional molecular phenotype. Our results indicate that tertiary lymphoid structures have a key role in the immune microenvironment in melanoma, by conferring distinct T cell phenotypes. Therapeutic strategies to induce the formation of tertiary lymphoid structures should be explored to improve responses to cancer immunotherapy.
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4.
  • Cabrita, Rita, et al. (author)
  • The Role of PTEN Loss in Immune Escape, Melanoma Prognosis and Therapy Response
  • 2020
  • In: Cancers. - : MDPI AG. - 2072-6694. ; 12:3
  • Journal article (peer-reviewed)abstract
    • Checkpoint blockade therapies have changed the clinical management of metastatic melanoma patients considerably, showing survival benefits. Despite the clinical success, not all patients respond to treatment or they develop resistance. Although there are several treatment predictive biomarkers, understanding therapy resistance and the mechanisms of tumor immune evasion is crucial to increase the frequency of patients benefiting from treatment. The PTEN gene is thought to promote immune evasion and is frequently mutated in cancer and melanoma. Another feature of melanoma tumors that may affect the capacity of escaping T-cell recognition is melanoma cell dedifferentiation characterized by decreased expression of the microphtalmia-associated transcription factor (MITF) gene. In this study, we have explored the role of PTEN in prognosis, therapy response, and immune escape in the context of MITF expression using immunostaining and genomic data from a large cohort of metastatic melanoma. We confirmed in our cohort that PTEN alterations promote immune evasion highlighted by decreased frequency of T-cell infiltration in such tumors, resulting in a worse patient survival. More importantly, our results suggest that dedifferentiated PTEN negative melanoma tumors have poor patient outcome, no T-cell infiltration, and transcriptional properties rendering them resistant to targeted- and immuno-therapy.
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5.
  • Isaksson, Rita, et al. (author)
  • Evaluation of an oral health education program for nursing personnel in special housing facilities for the elderly. Part II : Clinical aspects
  • 2000
  • In: Special Care in Dentistry. - Hoboken, NJ : Wiley-Blackwell Publishing Inc.. - 0275-1879 .- 1754-4505. ; 20:3, s. 109-113
  • Journal article (peer-reviewed)abstract
    • In Sweden, efforts are being made to create strategies for evaluating realistic dental treatment needs among the elderly, who are retaining more natural teeth. These strategies focus on the importance of maintaining adequate oral hygiene. Elderly in long-term-care facilities often depend on nursing personnel for carrying out daily oral hygiene procedures. Therefore, the nursing personnel’s knowledge about and attitudes toward oral health make oral health education for health care professionals an important concern. The purpose of this study was to evaluate the clinical oral health outcome in residents after their caregivers had undergone a one-session, four-hour oral health education program. The study consisted of an intervention with a pre- and a post-test and was carried out in three municipalities in the southwestern part of Sweden. A newly developed oral health screening protocol was carried out for 170 subjects living in long-term-care facilities both before and 3-4 months after nursing personnel had attended an oral health education program. Following the Intervention, a statistically significant improvement was recorded for changes In oral mucosal color, a modified plaque index which measured oral hygiene status, and a mucosal index which recorded mucosal inflammation. This study indicated that a limited, one-session, four-hour oral health education, offered to caregivers within long-term-care facilities, had a positive impact on the oral health status of residents.
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6.
  • Isaksson, Rita, et al. (author)
  • Oral status and treatment needs among elderly within municipal long-term care 2002-2004
  • 2007
  • In: Swedish Dental Journal. - : Swedish Dental Association. - 0347-9994. ; 31:1, s. 45-52
  • Journal article (peer-reviewed)abstract
    • A supplementary regulation in the Swedish National Dental Health Care Insurance stipulates an increased economic support to those, who are dependent permanently due to disease or handicap. Once enlisted to care, they are entitled to an annual dental examination and individual prophylactic advice free of charge, and to necessary dental treatment, offered within the ordinary medical care, regulated and funded by the county council. A population of persons, > or = 65 years of age and enrolled in municipal long-term care (LTC) in a county in the south of Sweden, was followed regarding changes in oral status and treatment needs for two years. The number of persons examined the year 2002 was 2416 and the corresponding figure for 2004 was 2846. Totally 1170, i.e. 48.4%, of those examined 2002 were deceased two years after the initial examination. Only 914, assessed in 2002, were available for assessment with full data at follow up 2004 and the results are based upon assessments in this group. Analyzing the assessed variables (dental status, oral hygiene status, oral mucosal inflammation, oral mucosal friction) revealed a change during these two years. Significant impairments were recognised, regarding mucosal inflammation and mucosal friction. Regarding treatment needs assessed by a dentist and a dental hygienist, there was a maintained and even increased need for extensive treatment, both by the dentist and, to a greater extent, by the dental hygienist. In sum, prevention efforts both from the dental profession and from other care providers are important to achieve and maintain acceptable oral status.
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7.
  • Isaksson, Rita (author)
  • Oral Treatment Intention and Realistic Oral Treatment Need for Patients in Long-term Care in Sweden, 2003
  • 2003
  • Licentiate thesis (other academic/artistic)abstract
    • A new regulation within the Swedish National Dental Health Care Insurance was introduced in 1999. It stipulates increased economic support for dental care to persons, who, due to disease or handicap, are depending on the aid from nursing personnel for their daily activities. The support is intended for those receiving long term care either living in nursing homes/homes for the elderly (NH) or those enlisted in municipal care in their own dwellings, home care (HC), with extensive and permanent assistance from mobile nursing personnel. Being enrolled in such care to a great extent entitles the care receivers to get an annual, free-of-charge, oral health examination on a voluntary basis. This population group is also entitled to receive what is considered necessary dental treatment on the same economic terms as medical treatment, with a set, low fee. There were two aims of this thesis. The first aim was to evaluate the clinical oral health outcome in care receivers, by using an oral health screening protocol, after the caregivers had undergone a one-session, four-hour oral health education program. The second aim was to evaluate the realistic oral treatment need, taking into consideration the treatment intention. The first study was performed at a smaller scale; 170 subjects enrolled in municipal long term care were included, available for examination both before and 3-4 months after education to the caregivers. The second study was performed at a larger scale; a sample, of 866 persons was selected to be examined; i.e. every third person included in long term care in three municipalities. The results showed that a limited oral health education, offered to caregivers within longterm care facilities, had a positive impact on residents´ oral health status. Further, it showed that the realistic oral treatment need, guided by the examiners´estimation of the appropriate treatment intention, was quite modest in this population, as 61% not only had a need for an oral health evaluation but also a need for additional oral/dental treatment, 31% to be accomplished by prophylactics and 30% by reparative/urgent measures. Of the latter group, about half were judged as needing prophylactics beside dentist´s treatment. Only one per cent were estimated to be in urgent need. In conclusion, the first study indicates that a limited oral health education of the caregivers combined with screening and prophylactic measures, will benefit the care-receivers in long term care.The second study indicates that when considering the treatment intention, the realistic treatment need among patients in long term care is quite modest, but prophylactic measures are important. The different levels of intention do not always aim at achieving complete oral health, but rather at facilitating a realistic oral treatment and an acceptable oral comfort.
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8.
  • Isaksson, Rita, et al. (author)
  • Oral treatment need and oral treatment intention in a population enrolled in long-term care in nursing homes and home care
  • 2003
  • In: Acta Odontologica Scandinavica. - : Informa UK Limited. - 0001-6357 .- 1502-3850. ; 61:1, s. 11-18
  • Journal article (peer-reviewed)abstract
    • The aim of the study was to evaluate the realistic oral treatment need in a population in southern Sweden enrolled in long-term care (LTC), in nursing homes (NH), or home care (HC), taking into consideration treatment intention. Every third individual enrolled in LTC was selected after proportionally stratifying a total of 866 subjects according to gender. Of these, 732 (85%) were available for a simple clinical oral health evaluation in their own homes. Dental status, oral mucosal status, oral hygiene status, oral mucosal inflammation, and oral mucosal friction were assessed by observational examinations; suspected malignancies were also noted. Oral treatment need was expressed in accordance with the Treatment Need Index (TNI) as no, minor, major, or urgent, while treatment intention was expressed in accordance with the Treatment Intention Index (TII) as the aim to relieve, delay, maintain, or improve. The rationale for using the TII is to offer subjects in this generally frail population oral treatment at an appropriate level, taking their medical condition into consideration. It was found that 61% of the sample had a need not just for an oral health evaluation but also for additional dental treatment, 31% to be accomplished by prophylactic and 30% by reparative or emergency measures; only l % were estimated to be in urgent need. Furthermore, one manifest and one suspected oral malignancy were found. The results indicate that realistic oral treatment need, guided by the examiner’s estimation of the appropriate treatment intention, is modest in this population, but that regular oral screening is mandatory.
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9.
  • Mitra, Shamik, et al. (author)
  • Analysis of DNA methylation patterns in the tumor immune microenvironment of metastatic melanoma
  • 2020
  • In: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 14:5, s. 933-950
  • Journal article (peer-reviewed)abstract
    • The presence of immune cells in the tumor microenvironment has been associated with response to immunotherapies across several cancer types, including melanoma. Despite its therapeutic relevance, characterization of the melanoma immune microenvironments remains insufficiently explored. To distinguish the immune microenvironment in a cohort of 180 metastatic melanoma clinical specimens, we developed a method using promoter CpG methylation of immune cell type-specific genes extracted from genome-wide methylation arrays. Unsupervised clustering identified three immune-methylation clusters with varying levels of immune CpG methylation that are related to patient survival. Matching protein and gene expression data further corroborated the identified epigenetic characterization. Exploration of the possible immune exclusion mechanisms at play revealed likely dependency on MITF protein level and PTEN loss-of-function events for melanomas unresponsive to immunotherapies (immune-low). To understand if melanoma tumors resemble other solid tumors in terms of immune-methylation characteristics, we explored 15 different solid tumor cohorts from TCGA. Low-dimensional projection based on immune cell type-specific methylation revealed grouping of the solid tumors in line with melanoma immune-methylation clusters rather than tumor types. Association of survival outcome with immune cell type-specific methylation differed across tumor and cell types. However, in melanomas immune-cell type-specific methylation was associated with inferior patient survival. Exploration of the immune-methylation patterns in a pan-cancer context suggested that specific immune-microenvironments might occur across the cancer spectrum. Together, our findings underscore the existence of diverse immune microenvironments, which may be informative for future immunotherapeutic applications.
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10.
  • Nederfors, Tommy, et al. (author)
  • Ability to estimate oral health status and treatment need in elderly receiving home nursing : a comparison between a dental hygienist and a dentist
  • 2000
  • In: Swedish Dental Journal. - : Swedish Dental Association. - 0347-9994. ; 24:3, s. 105-116
  • Journal article (peer-reviewed)abstract
    • The aim of this study was to compare the estimation ability of a dental hygienist to that of a dentist when, independently, recording the oral health status and treatment need in a population of elderly, receiving home nursing. Seventy-three persons, enrolled in a home nursing long-time care programme, were recruited. For the oral examination a newly developed protocol with comparatively blunt measurement variables was used. The oral examination protocol was tested for construct validity and for internal consistency reliability. Statistical analyses were performed using Wilcoxon matched pairs signed rank sum test for testing differences, while inter-examiner agreement was estimated by calculating the kappa-values. Comparing the two examiners, good agreement was demonstrated for all mucosal recordings, colour, form, wounds, blisters, mucosal index, and for the palatal but not the lingual mucosa. For the latter, the dental hygienist recorded significantly more changes. The dental hygienist also recorded significantly higher plaque index values. Also regarding treatment intention and treatment need, the dental hygienist's estimation was somewhat higher. In conclusion, when comparing the dental hygienist's and the dentist's ability to estimate oral health status, treatment intention, and treatment need, some differences were observed, the dental hygienist tending to register "on the safe side", calling attention to the importance of inter-examiner calibration. However, for practical purpose the inter-examiner agreement was acceptable, constituting a promising basis for future out-reach activities.
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