Continuous Multidisciplinary Care for Patients With Orofacial Clefts—Should the Follow-up Interval Depend on the Cleft Entity?

Objective: The multidisciplinary follow-up of patients with cleft lip with or without palate (CL/P) is organized differently in specialized centers worldwide. The aim of this study was to evaluate the different treatment needs of patients with different manifestations of CL/P and to potentially adapt the frequency and timing of checkup examinations accordingly. Design:We retrospectively analyzed the data of all patients attending the CL/P consultation hour at a tertiary care center between June 2005 and August 2020 (n=1126). We defined 3 groups of cleft entities: (1) isolated clefts of lip or lip and alveolus (CL/A), (2) isolated clefts of the hard and/or soft palate, and (3) complete clefts of lip, alveolus and palate (CLP). Timing and type of therapy recommendations given by the specialists of different disciplines were analyzed for statistical differences. Results: Patients with CLP made up the largest group (n=537), followed by patients with cleft of the soft palate (n=371) and CL ±A (n=218). There were significant differences between the groups with regard to type and frequency of treatment recommendations. A therapy was recommended in a high proportion of examinations in all groups at all ages. Conclusion: Although there are differences between cleft entities, the treatment need of patients with orofacial clefts is generally high during the growth period. Patients with CL/A showed a similarly high treatment demand and should be monitored closely. A close follow-up for patients with diagnosis of CL/P is crucial and measures should be taken to increase participation in followup appointments

Clinical Follow-Up in Orofacial Clefts—Why Multidisciplinary Care Is the Key

(1) Background: Although most clinicians involved in the treatment of cleft patients agree upon the major importance of interdisciplinary cooperation and many protocols and concepts have been discussed in the literature, there is little evidence of the relevance of continuous interdisciplinary care. We aimed to objectify the type and number of therapeutic decisions resulting from an annual multidisciplinary follow-up. (2) Methods: We retrospectively analyzed the data of all 1126 patients followed up in the weekly consultation hours for cleft patients at university clinics in Leipzig for the years 2005–2020. We assessed the clinical data of every patient and specifically evaluated the treatment decisions taken at different points in time by the participating experts of different specialties. (3) Results: In total, 3470 consultations were included in the evaluation, and in 70% of those, a therapeutic recommendation was given. Each specialty showed certain time frames with intense treatment demand, which partially overlapped. Nearly all therapy recommendations were statistically attached to a certain age (p < 0.001). (4) Conclusions: There is an exceptionally high need for the interdisciplinary assessment of patients with cleft formation. Some developmental phases are of particular importance with regard to regular follow-up and initiation of different treatment protocols. The therapy and checkup of cleft patients should be concentrated in specialized centers

CONAN: copy number variation analysis software for genome-wide association studies

<p>Abstract</p> <p>Background</p> <p>Genome-wide association studies (GWAS) based on single nucleotide polymorphisms (SNPs) revolutionized our perception of the genetic regulation of complex traits and diseases. Copy number variations (CNVs) promise to shed additional light on the genetic basis of monogenic as well as complex diseases and phenotypes. Indeed, the number of detected associations between CNVs and certain phenotypes are constantly increasing. However, while several software packages support the determination of CNVs from SNP chip data, the downstream statistical inference of CNV-phenotype associations is still subject to complicated and inefficient in-house solutions, thus strongly limiting the performance of GWAS based on CNVs.</p> <p>Results</p> <p>CONAN is a freely available client-server software solution which provides an intuitive graphical user interface for categorizing, analyzing and associating CNVs with phenotypes. Moreover, CONAN assists the evaluation process by visualizing detected associations via Manhattan plots in order to enable a rapid identification of genome-wide significant CNV regions. Various file formats including the information on CNVs in population samples are supported as input data.</p> <p>Conclusions</p> <p>CONAN facilitates the performance of GWAS based on CNVs and the visual analysis of calculated results. CONAN provides a rapid, valid and straightforward software solution to identify genetic variation underlying the 'missing' heritability for complex traits that remains unexplained by recent GWAS. The freely available software can be downloaded at <url>http://genepi-conan.i-med.ac.at</url>.</p

Candidate Gene Sequencing of SLC11A2 and TMPRSS6 in a Family with Severe Anaemia: Common SNPs, Rare Haplotypes, No Causative Mutation

Contains fulltext : 110476.pdf (publisher's version ) (Open Access)BACKGROUND: Iron-refractory iron deficiency anaemia (IRIDA) is a rare disorder which was linked to mutations in two genes (SLC11A2 and TMPRSS6). Common polymorphisms within these genes were associated with serum iron levels. We identified a family of Serbian origin with asymptomatic non-consanguineous parents with three of four children presenting with IRIDA not responding to oral but to intravenous iron supplementation. After excluding all known causes responsible for iron deficiency anaemia we searched for mutations in SLC11A2 and TMPRSS6 that could explain the severe anaemia in these children. METHODOLOGY/RESULTS: We sequenced the exons and exon-intron boundaries of SLC11A2 and TMPRSS6 in all six family members. Thereby, we found seven known and fairly common SNPs, but no new mutation. We then genotyped these seven SNPs in the population-based SAPHIR study (n = 1,726) and performed genetic association analysis on iron and ferritin levels. Only two SNPs, which were top-hits from recent GWAS on iron and ferritin, exhibited an effect on iron and ferritin levels in SAPHIR. Six SAPHIR participants carrying the same TMPRSS6 genotypes and haplotype-pairs as one anaemic son showed lower ferritin and iron levels than the average. One individual exhibiting the joint SLC11A2/TMPRSS6 profile of the anaemic son had iron and ferritin levels lying below the 5(th) percentile of the population's iron and ferritin level distribution. We then checked the genotype constellations in the Nijmegen Biomedical Study (n = 1,832), but the profile of the anaemic son did not occur in this population. CONCLUSIONS: We cannot exclude a gene-gene interaction between SLC11A2 and TMPRSS6, but we can also not confirm it. As in this case candidate gene sequencing did not reveal causative rare mutations, the samples will be subjected to whole exome sequencing

Large-scale mitochondrial DNA analysis in Southeast Asia reveals evolutionary effects of cultural isolation in the multi-ethnic population of Myanmar

Background: Myanmar is the largest country in mainland Southeast Asia with a population of 55 million people subdivided into more than 100 ethnic groups. Ruled by changing kingdoms and dynasties and lying on the trade route between India and China, Myanmar was influenced by numerous cultures. Since its independence from British occupation, tensions between the ruling Bamar and ethnic minorities increased. Results: Our aim was to search for genetic footprints of Myanmar’s geographic, historic and sociocultural characteristics and to contribute to the picture of human colonization by describing and dating of new mitochondrial DNA (mtDNA) haplogroups. Therefore, we sequenced the mtDNA control region of 327 unrelated donors and the complete mitochondrial genome of 44 selected individuals according to highest quality standards. Conclusion: Phylogenetic analyses of the entire mtDNA genomes uncovered eight new haplogroups and three unclassified basal M-lineages. The multi-ethnic population and the complex history of Myanmar were reflected in its mtDNA heterogeneity. Population genetic analyses of Burmese control region sequences combined with population data from neighboring countries revealed that the Myanmar haplogroup distribution showed a typical Southeast Asian pattern, but also Northeast Asian and Indian influences. The population structure of the extraordinarily diverse Bamar differed from that of the Karen people who displayed signs of genetic isolation. Migration analyses indicated a considerable genetic exchange with an overall positive migration balance from Myanmar to neighboring countries. Age estimates of the newly described haplogroups point to the existence of evolutionary windows where climatic and cultural changes gave rise to mitochondrial haplogroup diversification in Asia

Southeast Asian diversity: first insights into the complex mtDNA structure of Laos

<p>Abstract</p> <p>Background</p> <p>Vast migrations and subsequent assimilation processes have shaped the genetic composition of Southeast Asia, an area of close contact between several major ethnic groups. To better characterize the genetic variation of this region, we analyzed the entire mtDNA control region of 214 unrelated donors from Laos according to highest forensic quality standards. To detail the phylogeny, we inspected selected SNPs from the mtDNA coding region. For <it>a posteriori </it>data quality control, quasi-median network constructions and autosomal STR typing were performed. In order to describe the mtDNA setup of Laos more thoroughly, the data were subjected to population genetic comparisons with 16 East Asian groups.</p> <p>Results</p> <p>The Laos sample exhibited ample mtDNA diversity, reflecting the huge number of ethnic groups listed. We found several new, so far undescribed mtDNA lineages in this dataset and surrounding populations. The Laos population was characteristic in terms of haplotype composition and genetic structure, however, genetic comparisons with other Southeast Asian populations revealed limited, but significant genetic differentiation. Notable differences in the maternal relationship to the major indigenous Southeast Asian ethnolinguistic groups were detected.</p> <p>Conclusions</p> <p>In this study, we portray the great mtDNA variety of Laos for the first time. Our findings will contribute to clarify the migration history of the region. They encourage setting up regional and subpopulation databases, especially for forensic applications. The Laotian sequences will be incorporated into the collaborative EMPOP mtDNA database <url>http://www.empop.org</url> upon publication and will be available as the first mtDNA reference data for this country.</p

Do Gene Variants Influencing Adult Adiposity Affect Birth Weight? A Population-Based Study of 24 Loci in 4,744 Danish Individuals

Several obesity risk alleles affecting adult adiposity have been identified by the recent wave of genome wide association studies. We aimed to examine the potential effect of these variants on fetal body composition by investigating the variants in relation to birth weight and ponderal index of the newborn.Midwife records from the Danish State Archives provided information on mother's age, parity, as well as birth weight, birth length and prematurity of the newborn in 4,744 individuals of the population-based Inter99 study. Twenty-four risk alleles showing genome-wide associations with adult BMI and/or waist circumference were genotyped. None of the 24 risk variants tested showed an association with birth weight or ponderal index after correction for multiple testing. Birth weight was divided into three categories low (≤10(th) percentile), normal (10(th)-90(th) percentile) and high birth weight (≥90th percentile) to allow for non-linear associations. There was no difference in the number of risk alleles between the groups (p = 0.57). No interactions between each risk allele and birth weight in the prediction of adult BMI were observed. An obesity risk score was created by summing up risk alleles. The risk score did not associate with fetal body composition. Moreover there was no interaction between the risk score and birth weight/ponderal index in the prediction of adult BMI.24 common variants associated with adult adiposity did not affect or interact with birth weight among Danes suggesting that the effects of these variants predominantly arise in the post-natal life

Risk Factors for Complications Following Staged Alveolar Ridge Augmentation and Dental Implantation: A Retrospective Evaluation of 151 Cases with Allogeneic and 70 Cases with Autogenous Bone Blocks

Purpose: the aim of this study was to identify potential risk factors favoring complications by assessing the number and types of complications associated with allogeneic or autogenous bone blocks applied as onlay grafts for alveolar ridge augmentation prior to implantation. Methods: A retrospective chart review on the success of 151 allogeneic and 70 autogenous bone blocks in a cohort of 164 consecutive patients, who were treated over a period of 6 years by the same surgeon, was conducted. Statistical conclusions were based on ROC curves and multiple logistic regression models. Results: Complications were observed more frequently with autogenous bone blocks (14 out of 70 cases; 20%) compared to allogeneic bone blocks (12 out of 151 cases; 7.9%; p = 0.013). However, these complications were minor and did not impact the successful dental rehabilitation. In a multiple logistic regression model, the risk of a complication was increased by the use of an autogenous bone block (OR = 3.2; p = 0.027), smoking (OR = 4.8; p = 0.007), vertical augmentation above a threshold of 2.55 mm (OR = 5.0; p = 0.002), and over-contouring (OR = 15.3; p < 0.001). Conclusions: Overall, the complication rate of ridge augmentations carried out with autogenous or allogeneic bone blocks was low. Despite previous recommendations, over-contouring and a vertical augmentation above a threshold of 2.55 mm should be avoided

Survival Rates of Dental Implants in Autogenous and Allogeneic Bone Blocks: A Systematic Review

Background and Objectives: Preliminary studies emphasize the similar performance of autogenous bone blocks (AUBBs) and allogeneic bone blocks (ALBBs) in pre-implant surgery; however, most of these studies include limited subjects or hold a low level of evidence. The purpose of this review is to test the hypothesis of indifferent implant survival rates (ISRs) in AUBB and ALBB and determine the impact of various material-, surgery- and patient-related confounders and predictors. Materials and Methods: The national library of medicine (MEDLINE), Excerpta Medica database (EMBASE) and Cochrane Central Register of Controlled Trials (CENTRAL) were screened for studies reporting the ISRs of implants placed in AUBB and ALBB with &ge;10 participants followed for &ge;12 months from January 1995 to November 2021. The review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The risk of bias was assessed via several scoring tools, dependent on the study design. Means of sub-entities were presented as violin plots. Results: An electronic data search resulted in the identification of 9233 articles, of which 100 were included in the quantitative analysis. No significant difference (p = 0.54) was found between the ISR of AUBB (96.23 &plusmn; 5.27%; range: 75% to 100%; 2195 subjects, 6861 implants) and that of ALBB (97.66 &plusmn; 2.68%; range: 90.1% to 100%; 1202 subjects, 3434 implants). The ISR in AUBB was increased in blocks from intraoral as compared to extraoral donor sites (p = 0.0003), partially edentulous as compared to totally edentulous (p = 0.0002), as well as in patients younger than 45 as compared to those older (p = 0.044), cortical as compared to cortico-cancellous blocks (p = 0.005) and in delayed implantations within three months as compared to immediate implantations (p = 0.018). The ISR of ALBB was significantly increased in processed as compared to fresh-frozen ALBB (p = 0.004), but also in horizontal as compared to vertical augmentations (p = 0.009). Conclusions: The present findings widely emphasize the feasibility of achieving similar ISRs with AUBB and ALBB applied for pre-implant bone grafting. ISRs were negatively affected in sub-entities linked to more extensive augmentation procedures such as bone donor site and dentition status. The inclusion and pooling of literature with a low level of evidence, the absence of randomized controlled clinical trials (RCTs) comparing AUBB and ALBB and the limited count of comparative studies with short follow-ups increases the risk of bias and complicates data interpretation. Consequently, further long-term comparative studies are needed

Patients referred to a German TMD-specialized consultation hour—a retrospective on patients without a diagnosis according to RDC/TMD decision trees

Objectives!#!The objective was to describe the physical and psychosocial features of patients attending a specialized consultation hour for temporomandibular disorders (TMD). This investigation focused on those patients who did not receive a diagnosis according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD).!##!Materials and methods!#!From 2004 to 2017, patients seeking care during a TMD-specialized consultation hour were consecutively recruited. Each patient completed a TMD-related questionnaire, psychosocial questionnaires (Graded Chronic Pain Scale, Hospital Anxiety and Depression Scale, Beschwerden-Liste), and the Oral Health Impact Profile-49. The clinical examination was performed according to the RDC/TMD.!##!Results!#!The mean age of the 1020 patients was 43.3 years (75.3% female). According to the RDC/TMD decision trees, 351 patients were categorized without a TMD diagnosis (NoTMDdx). The most frequent reasons for seeking care were orofacial pain/TMJ pain or headaches revealing an OR of 1.89 (for TMDdx group). A relevant proportion of patients was categorized as positive for anxiety (NoTMDdx/TMDdx 30.8/41.2%; p = 0.072), depression (20.8/23.9%; p = 0.433), non-specific physical symptoms (31.4/44.1%; p &amp;lt; 0.001), or dysfunctional chronic pain (11.5/18.2%; p &amp;lt; 0.001). In both patient groups, the oral health-related quality of life was impaired (42.9/52.7 points; p &amp;lt; 0.001), and the frequency of therapy measures prior to the consultation hour was high.!##!Conclusions!#!Patients seeking care from TMD specialists were usually referred with TMD-associated symptoms. Of those, a relevant proportion did not receive a diagnosis according to RDC/TMD decision trees.!##!Clinical relevance!#!Psychosocial screening and the avoidance of overtreatment are recommended for patients with TMD-related symptoms