The oral cavity is a common site of complications related to the cytotoxic effect of high-dose chemotherapy and radiation therapy. Considering our limited understanding of the burden of illness in ...the oral cavity from various cytotoxic therapies, it is difficult to produce evidence-based, preventive and management protocols. A prospective multicenter study is necessary to collect data on the burden of illness from various cytotoxic regimens.
The objectives of this prospective international observational multicenter study in hematopoietic stem cell transplant (HSCT) patients are to establish the nature, incidence and temporal relationship of oral complications related to conditioning regimens (chemotherapy with or without total body irradiation), stem cell transplantation and the immunologic reactions (mainly graft-vs-host-disease) that may follow, and to determine what subjective and objective oral complications related to treatment can predict negative clinical and economic outcomes and reduced quality of life.
Adult patients at six study sites receiving full intensity conditioning, reduced intensity conditioning or nonmyeloablative conditioning, followed by autologous or allogeneic hematopoietic stem cell infusion, are included. A pre-treatment assessment includes medical conditions, planned chemo- and radiation therapy regimen, medications, allergies, social history, patient report of oral problems, dental history, subjective oral complaints, objective measures of oral conditions, current laboratory values, dental treatment recommended and untreated dental disease. Starting 1-3 days after hematopoietic stem cell infusion, a bedside assessment is completed 3 days per week until resolution of neutropenia. A patient questionnaire is also completed during hospitalization. Beyond this time, patients with continued oral mucositis or other oral problems are followed 1 day per week in an inpatient or outpatient setting. Additional visits for urgent care for acute oral problems after hospitalization are documented. Autologous transplant patients are being followed up at 100 days (SD 30 days) and at 1 year (SD 30 days) post-transplantation to identify any long-term side effects. Patients treated with allogeneic transplantation are being followed at 100 days (SD 30 days), 6 months (SD 30 days), and 12 months (SD 30 days). The follow-up assessments include cancer response to therapy, current medical conditions, medications, subjective and objective oral findings, quality of life measures and laboratory values. The targeted enrollment is 254 patients who have received HSCT.
A total of 260 participants have been enrolled, with 233 (91%) who have received HSCT. We anticipate enrollment of 20-30 additional participants to obtain the sample size of 254 enrolled participants who have received HSCT.
The results of the ongoing prospective study will provide a unique dataset to understand the impact of oral complications on patients undergoing HSCT and provide needed evidence for guidelines regarding the management of this patient cohort.
Oral mucositis (OM) is a common side effect of conditioning therapy implemented before hematopoietic stem cell transplantation (HSCT). The role of oral microbiome in OM is not fully elucidated.
To ...determine oral microbiome profile changes post-conditioning in HSCT patients who developed moderate OM, or mild to no OM.
Patient groups were: Muc0-1 with OM-score = 0-1 (43 paired samples) and Muc2 with WHO OM-score = 2 (36 paired samples). Bacterial DNA was isolated from oral samples (saliva, swabs of buccal mucosa, tongue, and supragingival plaque) at pre-conditioning (T
0
), post-conditioning mucositis onset (T
Muc
), and one-year post-conditioning (T
Year
). 16S-rRNA gene next-generation sequencing was used to determine the relative abundance (RA) of >700 oral species. Alpha-diversity, beta-diversity and linear discriminant analyses (LDA) were performed Muc2 versus Muc0-1.
Muc2 oral microbiome alpha- and beta-diversity differed between T
0
and T
Muc
. Muc2 alpha-diversity and Muc0-1 beta-diversity did not differ between T
0
and T
Year
. T
0
to T
Muc
LDA scores were significant in Muc2 for Gammaproteobacteria. For Muc2 patients, the average RA decreased for Haemophilus parainfluenza, a species known as mucosal surfaces protector, but increased for Escherichia-Shigella genera.
Post-conditioning OM might contribute to long-term oral microbiome changes affecting Gammaproteobacteria, in HSCT patients.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
To examine how hospital-affiliated dentists assess risk and evaluate oral foci of infection in patients facing certain medical treatments, and whether the nature of upcoming medical treatment affects ...the choice of dental intervention.
A survey comprising six clinical cases (50 teeth) was sent to hospital-affiliated dentists in Sweden. A treatment option for the affected tooth/teeth in each case was selected whether the patient was facing heart valve surgery, chemotherapy, radiation therapy, intravenous bisphosphonate treatment, solid organ transplantation or was diagnosed with endocarditis.
Consensus in choice of dental treatment was high in 62%, moderate in 32% and low in 6% of the assessments. High variability of choice of treatment was seen for eight teeth whereas the remaining 42 teeth often received the same therapy regardless of medical issue. Chemotherapy and radiotherapy were thought to entail the highest risk for oral infectious sequelae with a risk ranging from 1% to 100%.
Pre-medical dental evaluations and recommended treatments are often uniform with the exception of the management of asymptomatic root canal treated teeth with persisting apical radiolucency and heavily decayed molars. In many instances, dental diagnosis has a greater impact on choice of treatment than the underlying medical issue and associated implications thereof.
Objectives
There is a need for monitoring dental health and healthcare, as support for quality development, allocation of resources and long‐term planning of dental care. The aim of this paper is to ...describe the concept and implementation of the Swedish Quality Registry for Caries and Periodontal Diseases (SKaPa). Materials and methods: The SKaPa receives information by automatic transfer of data daily from electronic patient dental records via secure connections from affiliated dental care organisations (DCOs). The registry stores information about DCOs, dental professionals and patients. Information on a patient level includes personal identifier, gender, age, living area, dental status, risk assessments for caries and periodontitis, and dental care provided. In addition, data generated from a global question on patient‐perceived oral health are uploaded. In total, more than 400 variables are transferred to the registry and updated daily. Results: In 2018, all of the 21 public DCOs and the largest private DCO in Sweden were affiliated to SKaPa, representing a total of 1,089 public and 234 private dental clinics. The accumulated amount of information on dental healthcare covers 6.9 million individuals out of the total Swedish population of 10 million. SKaPa produces reports on de‐identified data, both cross‐sectional and longitudinal. Conclusion: As a nationwide registry based on automatic retrieval of data directly from patient records, SKaPa offers the basis for a new era of systematic evaluation of oral health and quality of dental care. The registry supports clinical and epidemiological research, data mining and external validation of results from randomised controlled trials
Full text
Available for:
BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Growth factors and cytokines may be useful in preventing chemotherapy (CT)- and radiotherapy (RT)-induced oral and gastrointestinal mucositis. Two systematic reviews of the medical literature on ...growth factors and cytokines for the amelioration of CT- and RT-induced mucositis throughout the alimentary tract were performed by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology. The aim of these evidence-based scientific reviews was to critically evaluate the literature and create evidence-based guidelines for the use of growth factors and cytokines in the prevention or treatment of CT- and RT-induced mucositis.
The two reviews covered articles on clinical trials from January 1966 through May 2002 and preclinical studies from June 2002 through May 2005, respectively. The systematic review process was based on a well-established method for evaluating scientific literature.
The number of articles in the first review was 29. In the second review, 23 articles were evaluated, 14 preclinical and 9 clinical studies. It was concluded from the first review that there was no sufficient evidence to provide any recommendations for clinical practice guidelines regarding growth factors and cytokines. From the second review, a guideline could be presented recommending the use of recombinant human keratinocyte growth factor-1 (palifermin) to prevent oral mucositis in patients receiving high-dose CT and total body irradiation followed by stem cell transplantation for haematological malignancies. A guideline could also be provided suggesting that granulocyte macrophage colony-stimulating factor mouthwash not be used for the prevention of oral mucositis in the transplant setting with high-dose CT and autologous or allogeneic stem cell transplantation.
These systematic reviews have provided clarity and shown exciting new results. Further studies will provide new options for this debilitating side-effect of cancer therapy.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, ODKLJ, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Objectives The objective of this study was to identify systemic diseases associated with hyposalivation and xerostomia and develop evidence-based management recommendations for ...hyposalivation/xerostomia. Study design Literature searches covered the English language medical literature from 1966 to 2005. An evidence-based review process was applied to management studies published from 2002 to 2005. Results Several systemic diseases were identified. From studies published 2002 to 2005, 15 were identified as high-quality studies and were used to support management recommendations: pilocarpine and cevimeline are recommended for treating hyposalivation and xerostomia in primary and secondary Sjögren’s syndrome (SS). IFN-α lozenges may enhance saliva flow in primary SS patients. Anti-TNF-α agents, such as infliximab or etanercept, are not recommended to treat hyposalivation in SS. Dehydroepiandrosterone is not recommended to relieve hyposalivation or xerostomia in primary SS. There was not enough evidence to support any recommendations for the use of local stimulants, lubricants, and protectants for hyposalivation/xerostomia. However, professional judgment and patient preferences may support the use of a specific product for an individual patient. Conclusions These evidence-based management recommendations should guide the clinician’s management decisions for patients with salivary dysfunction related to systemic disease. Future treatment strategies may include new formulations of existing drugs, e.g., local application of pilocarpine. Recent discoveries on gene expression and a better understanding of the etiopathogenesis of SS may open new treatment options in the future.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Importance of the field:
Topical immunomodulators have been used for the management of oral mucosal diseases. Topical immunomodulating preparations may have utility in local management of oral ...disease which is resistant to topical steroids and oral findings of an immunologic-mediated systemic disease with primary or persisting, oral mucosal involvement.
Areas covered in this review:
This paper is the first part of a systematic review of topical immunomodulators for the management of various oral indications focused on calcineurin inhibitors. The literature search revealed that data are available for cyclosporine, tacrolimus and pimecrolimus. In addition to the review of scientific evidence, this paper presents the potential market, the mechanism of action, the competitive environment and future development options.
What the reader will gain:
The reader will find weighted conclusions for the topical use of the calcineurin inhibitors in the management of oral diseases.
Take home message:
Topical calcineurin inhibitors may be useful as a second-line treatment in several oral diseases, particularly oral lichen planus.
Purpose
The aim of this project was to review the literature and define clinical practice guidelines for the use of cytokines and growth factor agents for the prevention or treatment of oral ...mucositis induced by cancer chemotherapy or radiotherapy.
Methods
A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: Recommendation, Suggestion, No guideline possible.
Results
Sixty-four clinical studies across 11 interventions were evaluated. A recommendation was made for the use of recombinant human KGF-1 (palifermin) at a dose of 60 μg/kg per day for 3 days prior to conditioning treatment and for 3 days post-transplant for prevention of oral mucositis in patients receiving high-dose chemotherapy and total body irradiation followed by autologous stem cell transplantation for hematological malignancies. A suggestion was made against using granulocyte macrophage colony-stimulating factor mouthwash for the prevention of oral mucositis in the setting of high-dose chemotherapy followed by autologous or allogeneic stem cell transplantation. No guideline was possible for any other cytokine or growth factor agents due to inconclusive evidence.
Conclusions
Of the cytokine and growth factor agents studied for oral mucositis, the evidence only supports use of palifermin in the specific population listed above. Additional well-designed research is needed on other cytokine and growth factor interventions and in other cancer treatment settings.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Aim
The aims of this study were to determine the incidence of injuries to permanent incisors in 2011–2013 in children aged 8–10 years living in the county of Värmland, Sweden, and to compare it with ...the incidence rates in 1989/1990 in the county of Västmanland, as well as to determine the cause of dental trauma in relation to time and place.
Method
The study analysed the patient records from dental visits (2011–2013) of trauma to the permanent incisors in children aged 8–10 years. The incidence rates were the incidence per 1000 children at risk. Standardized incidence rates were calculated for the comparison between different years. Information about month, location where the trauma occurred as well as cause of trauma was recorded.
Results
A total of 2.2% of 21 721 children aged 8–10 years had experienced at least one trauma. The incidence rate in Värmland increased from 18.9 in 2011 to 21.3 in 2012 to 28.5 in 2013. The standardized incidence rate in Värmland in 2011 and 2012 was not significantly different than in Västmanland in 1989/1990 (P > 0.05), but the standardized rates in 2013 were significantly higher than in 1989/90 (P < 0.001). Dental trauma occurred most often outdoors, followed by sports arenas/sports fields, and more often at school than at home. Falling and slipping was the most common cause of trauma, followed by accidents during leisure activities, playing and sports.
Conclusion
The incidence rate for dental trauma has not decreased in the past 20 years, and there is an indication that parents and teachers should be more aware of the risks of dental trauma at leisure times and at school as well as during sports and exercise.
Full text
Available for:
BFBNIB, CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Introduction
Chronic graft-versus-host disease (cGVHD) is a debilitating side effect of allogeneic hematopoietic cell transplantation (HCT), affecting the quality of life of patients. We used whole ...exome sequencing to identify candidate SNPs and complete a multi-marker gene-level analysis using a cohort of cGVHD( +) (
N
= 16) and cGVHD( −) (
N
= 66) HCT patients.
Methods
Saliva samples were collected from HCT patients (
N
= 82) pre-conditioning in a multi-center study from March 2011 to May 2018. Exome sequencing was performed and FASTQ files were processed for sequence alignments. Significant SNPs were identified by logistic regression using PLINK2
v3.7
and Fisher’s exact test. One cGVHD( −) patient sample was excluded from further analysis since no SNP was present in at least 10% of the sample population. The FUMA platform’s SNP2GENE was utilized to annotate SNPs and generate a MAGMA output. Chromatin state visualization of lead SNPs was completed using Epilogos tool. FUMA’s GENE2FUNC was used to obtain gene function and tissue expression from lead genomic loci.
Results
Logistic regression classified 986 SNPs associated with cGVHD( +). SNP2GENE returned three genomic risk loci, four lead SNPs, 48 candidate SNPs, seven candidate GWAS tagged SNPs, and four mapped genes. Fisher’s exact test identified significant homozygous genotypes of four lead SNPs (
p
< 0.05). GENE2FUNC analysis of multi-marker SNP sets identified one positional gene set including lead SNPs for
KANK1
and
KDM4C
and two curated gene sets including lead SNPs for
PTPRD
,
KDM4C
, and/or
KANK1
.
Conclusions
Our data suggest that SNPs in three genes located on chromosome 9 confer genetic susceptibility to cGVHD in HCT patients. These genes modulate
STAT3
expression and phosphorylation in cancer pathogenesis. The findings may have implications in the modulation of pathways currently targeted by JAK inhibitors in cGVHD clinical trials.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
PDF
