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Objectives To characterize the phenotypic presentation at diagnosis of childhood-onset primary SS. Methods The Big Data Sjögren Project Consortium is an international, multicentre registry using worldwide data-sharing cooperative merging of pre-existing clinical SS databases from the five continents. For this study, we selected those patients in whom the disease was diagnosed below the age of 19 years according to the fulfilment of the 2002/2016 classification criteria. Results Among the 12 083 patients included in the Sjögren Big Data Registry, 158 (1.3%) patients had a childhood-onset diagnosis (136 girls, mean age of 14.2 years): 126 (80%) reported dry mouth, 111 (70%) dry eyes, 52 (33%) parotid enlargement, 118/122 (97%) positive minor salivary gland biopsy and 60/64 (94%) abnormal salivary US study, 140/155 (90%) positive ANA, 138/156 (89%) anti-Ro/La antibodies and 86/142 (68%) positive RF. The systemic EULAR Sjögren’s syndrome disease activity index (ESSDAI) domains containing the highest frequencies of active patients included the glandular (47%), articular (26%) and lymphadenopathy (25%) domains. Patients with childhood-onset primary SS showed the highest mean ESSDAI score and the highest frequencies of systemic disease in 5 (constitutional, lymphadenopathy, glandular, cutaneous and haematological) of the 12 ESSDAI domains, and the lowest frequencies in 4 (articular, pulmonary, peripheral nerve and CNS) in comparison with patients with adult-onset disease. Conclusions Childhood-onset primary SS involves around 1% of patients with primary SS, with a clinical phenotype dominated by sicca features, parotid enlargement and systemic disease. Age at diagnosis plays a key role in modulating the phenotypic expression of the disease.

For many decades, the clinical unmet needs of primary Sjögren's Syndrome (pSS) have been left unresolved due to the rareness of the disease and the complexity of the underlying pathogenic mechanisms, including the pSS-associated lymphomagenesis process. Here, we present the HarmonicSS cloud-computing exemplar which offers beyond the state-of-the-art data analytics services to address the pSS clinical unmet needs, including the development of lymphoma classification models and the identification of biomarkers for lymphomagenesis. The users of the platform have been able to successfully interlink, curate, and harmonize 21 regional, national, and international European cohorts of 7,551 pSS patients with respect to the ethical and legal issues for data sharing. Federated AI algorithms were trained across the harmonized databases, with reduced execution time complexity, yielding robust lymphoma classification models with 85% accuracy, 81.25% sensitivity, 85.4% specificity along with 5 biomarkers for lymphoma development. To our knowledge, this is the first GDPR compliant platform that provides federated AI services to address the pSS clinical unmet needs. © 2022 The Author(s)

The aim of this study is to explore the role of labial minor salivary gland (LMSG) focus score (FS) in stratifying Sjögren's Syndrome (SS) patients, lymphoma development prediction and to facilitate early lymphoma diagnosis. Ιn an integrated cohort of 1997 patients, 618 patients with FS ≥ 1 and at least one-year elapsing time interval from SS diagnosis to lymphoma diagnosis or last follow up were identified. Clinical, laboratory and serological features were recorded. A data driven logistic regression model was applied to identify independent lymphoma associated risk factors. Furthermore, a FS threshold maximizing the difference of time interval from SS until lymphoma diagnosis between high and low FS lymphoma subgroups was investigated, to develop a follow up strategy for early lymphoma diagnosis. Of the 618 patients, 560 were non-lymphoma SS patients while the other 58 had SS and lymphoma. FS, cryoglobulinemia and salivary gland enlargement (SGE) were proven to be independent lymphoma associated risk factors. Lymphoma patients with FS ≥ 4 had a statistically significant shorter time interval from SS to lymphoma diagnosis, compared to those with FS < 4 (4 vs 9 years, respectively, p = 0,008). SS patients with FS ≥ 4 had more frequently B cell originated manifestations and lymphoma, while in patients with FS < 4, autoimmune thyroiditis was more prevalent. In the latter group SGE was the only lymphoma independent risk factor. A second LMSG biopsy is patients with a FS ≥ 4, 4 years after SS diagnosis and in those with FS < 4 and a history of SGE, at 9-years, may contribute to an early lymphoma diagnosis. Based on our results we conclude that LMSG FS, evaluated at the time of SS diagnosis, is an independent lymphoma associated risk factor and may serve as a predictive biomarker for the early diagnosis of SS-associated lymphomas. © 2021 Elsevier Ltd

Objective To analyse the prognosis and outcomes of SARS-CoV-2 infection in patients with primary SS. Methods We searched for patients with primary SS presenting with SARS-CoV-2 infection (defined following and according to the European Centre for Disease Prevention and Control guidelines) among those included in the Big Data Sjögren Registry, an international, multicentre registry of patients diagnosed according to the 2002/2016 classification criteria. Results A total of 51 patients were included in the study (46 women, mean age at diagnosis of infection of 60 years). According to the number of patients with primary SS evaluated in the Registry (n = 8211), the estimated frequency of SARS-CoV-2 infection was 0.62% (95% CI 0.44, 0.80). All but two presented with symptoms suggestive of COVID-19, including fever (82%), cough (57%), dyspnoea (39%), fatigue/myalgias (27%) and diarrhoea (24%), and the most frequent abnormalities included raised lactate dehydrogenase (LDH) (88%), CRP (81%) and D-dimer (82%) values, and lymphopenia (70%). Infection was managed at home in 26 (51%) cases and 25 (49%) required hospitalization (five required admission to ICU, four died). Compared with patients managed at home, those requiring hospitalization had higher odds of having lymphopenia as laboratory abnormality (adjusted OR 21.22, 95% CI 2.39, 524.09). Patients with comorbidities had an older age (adjusted OR 1.05, 95% CI 1.00, 1.11) and showed a risk for hospital admission six times higher than those without (adjusted OR 6.01, 95% CI 1.72, 23.51) in the multivariate analysis. Conclusion Baseline comorbidities were a key risk factor for a more complicated COVID-19 in patients with primary SS, with higher rates of hospitalization and poor outcomes in comparison with patients without comorbidities.

This thesis is about the order of knowledge in the Siku Quanshu, the Complete Writings of the Four Repositories, the largest ‘encyclopaedic’ compilation of texts in pre-modern China. While contemporary scholarship has concentrated on what was included in the compilation, the question of how it was organised remains largely unexplored. Divided in five chapters, this thesis explores the understanding of knowledge and its organisation in the Qianlong era (1736–1796 CE). In the Introduction, I interrogate the methodological viability of a cross-cultural investigation and argue for a new conceptual framework to undertake such line of inquiry in the Chinese context. In Chapter 1, I show how the antecedent poetic understanding of knowledge as water determined the order of the Complete Writings. I provide an account of its impact on classification and briefly sketch its historical origins and development. By way of comparison to the western notion of knowledge as tree, I tease out the properties and cultural specificity of each system. In Chapter 2, I explore the intellectual, non-political purposes behind the collection. I provide a short overview of past bibliographic classifications and their impact on the editors’ scholarly objectives and show how the order of the Complete Writings was envisioned as an advising guide to scholarship. In Chapter 3, I identify the ascribed socio-scholarly function of texts as the fundamental principle of order and investigate the different ways in which it was expressed. I also show how the Qianlong-era conception of order differs from Aristotelian and Wittgensteinian notions of classification. In the Conclusion, I summarise the main findings of this thesis and offer some reflections on the nature of bibliographic divisions, imperial scholarship, and the Complete Writings.

Objective: To describe the clinical spectrum of cryoglobulinemic vasculitis (CV) in primary Sjögren's syndrome (pSS), investigate its relation to lymphoma and identify the differences with hepatitis C virus (HCV) related CV. Methods: From a multicentre study population of consecutive pSS patients, those who had been evaluated for cryoglobulins and fulfilled the 2011 classification criteria for CV were identified retrospectively. pSS-CV patients were matched with pSS patients without cryoglobulins (1:2) and HCV-CV patients (1:1). Clinical, laboratory and outcome features were analyzed. A data driven logistic regression model was applied for pSS-CV patients and their pSS cryoglobulin negative controls to identify independent features associated with lymphoma. Results: 1083 pSS patients were tested for cryoglobulins. 115 (10.6%) had cryoglobulinemia and 71 (6.5%) fulfilled the classification criteria for CV. pSS-CV patients had higher frequency of extraglandular manifestations and lymphoma (OR=9.87, 95% CI: 4.7–20.9) compared to pSS patients without cryoglobulins. Purpura was the commonest vasculitic manifestation (90%), presenting at disease onset in 39% of patients. One third of pSS-CV patients developed B-cell lymphoma within the first 5 years of CV course, with cryoglobulinemia being the strongest independent lymphoma associated feature. Compared to HCV-CV patients, pSS-CV individuals displayed more frequently lymphadenopathy, type II IgMk cryoglobulins and lymphoma (OR = 6.12, 95% CI: 2.7–14.4) and less frequently C4 hypocomplementemia and peripheral neuropathy. Conclusion: pSS-CV has a severe clinical course, overshadowing the typical clinical manifestations of pSS and higher risk for early lymphoma development compared to HCV related CV. Though infrequent, pSS-CV constitutes a distinct severe clinical phenotype of pSS. © 2020 The Authors

Background: To compare the clinical, serological and histologic features between male and female patients with Sjögren’s syndrome (SS) and explore the potential effect of gender on lymphoma development. Methods: From a multicenter population (Universities of Udine, Pisa and Athens, Harokopion and Ioannina (UPAHI)) consisting of consecutive SS patients fulfilling the 2016 ACR/EULAR criteria, male patients were identified, matched and compared with female controls. Data-driven multivariable logistic regression analysis was applied to identify independent lymphoma-associated factors. Results: From 1987 consecutive SS patients, 96 males and 192 matched female controls were identified and compared. Males had a higher frequency of lymphoma compared to females (18% vs. 5.2%, OR = 3.89, 95% CI: 1.66 to 8.67; p = 0.0014) and an increased prevalence of serum anti-La/SSB antibodies (50% vs. 34%, OR = 1.953, 95% CI: 1.19 to 3.25; p = 0.0128). No differences were observed in the frequencies of lymphoma predictors between the two genders. Data-driven multivariable logistic regression analysis revealed negative association of the female gender with lymphoma and positive association with lymphadenopathy. Conclusion: Male SS patients carry an increased risk of lymphoma development. Although statistics showed no difference in classical lymphoma predictors compared to females, data-driven analysis revealed gender and lymphadenopathy as independent lymphoma-associated features. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Goal: To present a framework for data sharing, curation, harmonization and federated data analytics to solve open issues in healthcare, such as, the development of robust disease prediction models. Methods: Data curation is applied to remove data inconsistencies. Lexical and semantic matching methods are used to align the structure of the heterogeneous, curated cohort data along with incremental learning algorithms including class imbalance handling and hyperparameter optimization to enable the development of disease prediction models. Results: The applicability of the framework is demonstrated in a case study of primary Sjögren's Syndrome, yielding harmonized data with increased quality and more than 85% agreement, along with lymphoma prediction models with more than 80% sensitivity and specificity. Conclusions: The framework provides data quality, harmonization and analytics workflows that can enhance the statistical power of heterogeneous clinical data and enables the development of robust models for disease prediction. © 2020 Lippincott Williams and Wilkins. All rights reserved.

Objectives: To study the clinical, serological and histologic features of primary Sjögren’s syndrome (pSS) patients with early (young ≤35 years) or late (old ≥65 years) onset and to explore the differential effect on lymphoma development. Methods: From a multicentre study population of 1997 consecutive pSS patients, those with early or late disease onset, were matched and compared with pSS control patients of middle age onset. Data driven analysis was applied to identify the independent variables associated with lymphoma in both age groups. Results: Young pSS patients (19%, n = 379) had higher frequency of salivary gland enlargement (SGE, lymphadenopathy, Raynaud’s phenomenon, autoantibodies, C4 hypocomplementemia, hypergammaglobulinemia, leukopenia, and lymphoma (10.3% vs. 5.7%, p = 0.030, OR = 1.91, 95% CI: 1.11–3.27), while old pSS patients (15%, n = 293) had more frequently dry mouth, interstitial lung disease, and lymphoma (6.8% vs. 2.1%, p = 0.011, OR = 3.40, 95% CI: 1.34–8.17) compared to their middle-aged pSS controls, respectively. In young pSS patients, cryoglobulinemia, C4 hypocomplementemia, lymphadenopathy, and SGE were identified as independent lymphoma associated factors, as opposed to old pSS patients in whom SGE, C4 hypocomplementemia and male gender were the independent lymphoma associated factors. Early onset pSS patients displayed two incidence peaks of lymphoma within 3 years of onset and after 10 years, while in late onset pSS patients, lymphoma occurred within the first 6 years. Conclusion: Patients with early and late disease onset constitute a significant proportion of pSS population with distinct clinical phenotypes. They possess a higher prevalence of lymphoma, with different predisposing factors and lymphoma distribution across time. © Copyright © 2020 Goules, Argyropoulou, Pezoulas, Chatzis, Critselis, Gandolfo, Ferro, Binutti, Donati, Zandonella Callegher, Venetsanopoulou, Zampeli, Mavrommati, Voulgari, Exarchos, Mavragani, Baldini, Skopouli, Fotiadis, De Vita, Moutsopoulos and Tzioufas.

Genetic variants of the three-prime repair exonuclease 1 (TREX1) -an exonuclease involved in DNA repair and degradation- have been previously found to increase susceptibility to Aicardi Goutieres syndrome, familial chilblain lupus and systemic lupus erythematosus. We aimed to explore whether TREX1 common variants could influence the risk of primary Sjogren's syndrome (SS) and SS-related lymphoma. Three single nucleotide polymorphisms (SNPs) of the TREX1 gene (rs11797, rs3135941 and rs3135945) were evaluated in 229 SS, 89 SS-lymphoma (70 SS-MALT and 19 SS non-MALT) and 240 healthy controls by PCR-based assays. In available 52 peripheral blood and 26 minor salivary gland tissues from our SS cohort, mRNA expression of type I interferon (IFN) related genes and TREX1 was determined by real-time PCR. Significantly decreased prevalence of rs11797 A minor allele was detected in SS patients complicated by non-MALT lymphoma compared to controls (ΟR [95% CI]: 0.4 [0.2–0.9], p-value: 0.02). SS patients carrying the rs11797 AA genotype had increased type I IFN related gene mRNA expression in minor salivary gland tissues. These data support genetically related dampened type I IFN production as an additional mechanism for SS-related lymphomagenesis. © 2019

Data quality assessment has gained attention in the recent years since more and more companies and medical centers are highlighting the importance of an automated framework to effectively manage the quality of their big data. Data cleaning, also known as data curation, lies in the heart of the data quality assessment and is a key aspect prior to the development of any data analytics services. In this work, we present the objectives, functionalities and methodological advances of an automated framework for data curation from a medical perspective. The steps towards the development of a system for data quality assessment are first described along with multidisciplinary data quality measures. A three-layer architecture which realizes these steps is then presented. Emphasis is given on the detection and tracking of inconsistencies, missing values, outliers, and similarities, as well as, on data standardization to finally enable data harmonization. A case study is conducted in order to demonstrate the applicability and reliability of the proposed framework on two well-established cohorts with clinical data related to the primary Sjögren's Syndrome (pSS). Our results confirm the validity of the proposed framework towards the automated and fast identification of outliers, inconsistencies, and highly-correlated and duplicated terms, as well as, the successful matching of more than 85% of the pSS-related medical terms in both cohorts, yielding more accurate, relevant, and consistent clinical data. © 2019

Autoimmune diseases are a complex set of diseases characterized by immune system activation and, although many progresses have been done in the last 15 years, several unmet needs in the management of these patients may be still identified. Recently, a panel of international Experts, divided in different working groups according to their clinical and scientific expertise, were asked to identify, debate and formulate a list of key unmet needs within the field of rheumatology, serving as a roadmap for research as well as support for clinicians. After a systematic review of the literature, the results and the discussions from each working group were summarised in different statements. Due to the differences among the diseases and their heterogeneity, a large number of statements was produced and voted by the Experts to reach a consensus in a plenary session. At all the steps of this process, including the initial discussions by the steering committee, the identification of the unmet needs, the expansion of the working group and finally the development of statements, a large agreement was attained. This work confirmed that several unmet needs may be identified and despite the development of new therapeutic strategies as well as a better understanding of the effects of existing therapies, many open questions still remain in this field, suggesting a research agenda for the future and specific clinical suggestions which may allow physicians to better manage those clinical conditions still lacking of scientific clarity. © 2017

Verrucous carcinoma of the oral cavity (OVC) is considered a subtype of classical oral squamous cell carcinoma (OSCC). Diagnosis is problematic, and additional biomarkers are needed to better stratify patients. To investigate their molecular signature, we performed low coverage copy number sequencing on 57 OVC and exome and RNA sequencing on a subset of these and compared the data to the same OSCC parameters. Copy number results showed that OVC lacked any of the classical OSCC patterns such as gain of 3q and loss of 3p and demonstrated considerably fewer genomic rearrangements compared to the OSCC cohort. OVC and OSCC samples could be clearly differentiated. Exome sequencing showed that OVC samples lacked mutations in genes commonly associated with OSCC (TP53, NOTCH1, NOTCH2, CDKN2A and FAT1). RNA sequencing identified genes that were differentially expressed between the groups. In silico functional analysis showed that the mutated and differentially expressed genes in OVC samples were involved in cell adhesion and keratinocyte proliferation, while those in the OSCC cohort were enriched for cell death and apoptosis pathways. This is the largest and most detailed genomic and transcriptomic analysis yet performed on this tumour type, which, as an example of non-metastatic cancer, may shed light on the nature of metastases. These three independent investigations consistently show substantial differences between the cohorts. Taken together they lead to the conclusion that OVC is not a subtype of OSCC, but should be classified as a distinct entity.

The aim of this study was to analyze protein and gene expression of HER2 in 224 head and neck precancerous and malignant lesions by immunohistochemistry and FISH analysis. In parallel, expression of pStat3, Sox2, IFI16 and p16, Ki67 was evaluated. Immunohistochemical analysis was assessed on formalin-fixed paraffin-embedded (FFPE) tissue specimens. A combined method for HPV detection consisting of p16 immunostaining and two PCR probes was applied. HER2 gene status was evaluated by FISH analysis. HPV DNA was detected in 24% of cases with predominant HPV16 genotype. HPV-positive lesions had higher HER2, pStat3 and within carcinoma group, and higher IFI16 expression compared to the HPV-negative group (Fig. 1A-B-C). A strong positive correlation between Sox2 and proliferative activity was observed, whereas IFI16 expression displayed a negative relationship with Sox2 and Ki67 activity. The most striking result was higher pStat3 expression in HPV-positive lesions and its strong positive correlation with IFI16 expression. The presence of HPV may induce upregulation of HER2/neu, pStat3 and IFI16. High levels and a strong positive correlation between pStat3 and IFI16 suggest their synergistic pro-apoptotic effects in HPV-positive lesions.

'Field cancerization' is an accepted model for oral carcinogenesis. So far, genetically altered fields have been just reported in the presence of carcinomas. This study assessed the distant mirror fields (MFs) of oral precancer by DNA high-resolution flow cytometry (hr DNA-FCM) and array-Comparative Genomic Hybridization (a-CGH).Five leukoplakias without dysplasia (OLs), seven dysplastic leukoplakias (DOLs), and 12 corresponding visually normal and non-dysplastic MFs were analyzed. DNA aneuploidy (DNA Index, DI ≠ 1) was detected by hr DNA-FCM on DAPI stained nuclei suspensions. The epithelial DNA aneuploid subclones were FCM-sorted to obtain genomic DNA for a-CGH.Mirror fields, OLs, and DOLs showed increasing prevalence of DNA aneuploidy of, respectively, 8%, 20%, and 57%. The average number of chromosome aberrations (Ch-Abs) was 2.8 in MFs, 3 in OLs, and 10.6 in DOLs. MFs relative to OLs and DOLs had average numbers of Ch-Abs, respectively, of 1.8 and 3.6. Ch-Abs were also observed in DNA diploid sublines, and often the same aberrations were observed in both MFs and corresponding OLs/DOLs.DNA aneuploidy and Ch-Abs in MFs, the last ones being mainly gains, indicate an early onset of field effect in oral carcinogenesis.

Oral squamous cell carcinoma (OSCC) is an extremely invasive tumour of stratified squamous epithelium that spreads throughout degradation of the basement membrane (BM) and extracellular matrix (ECM). Oral verrucous carcinoma (VC) is a rare low-grade variant of OSCC. VC has a different clinical behaviour from classical OSCC and the optimal treatment is controversial. This report analyses the clinical features and outcomes in patients undergoing treatment for oral VC.A group of 74 Northern Italian patients were studied; for each patient, agreement of histological diagnosis, age and gender, risk factors, tumor site, T classification, treatment, outcome and survival rate were examined and analysed statistically.The survival rate was 93.65% at 5 years and 83.44% at 10 years. Retrospective analysis showed no risk of cervical lymph node metastasis and surgical treatment results were good.Our survival rates showed a good prognosis, with no risk of cervical lymph node metastases, suggesting that most cases can be controlled by surgery alone.

It is well known that diagnostic oral exfoliative cytology, even if a useful, economical and practical tool in the diagnosis of oral dysplasia and carcinoma, is not yet used so extensively as is cervico-vaginal cytology.Exfoliative cytology was used for the diagnosis of oral dysplasia and carcinoma, and the results compared to the histological examination. Cytological smears were taken from 89 patients with oral lesions suspicious for neoplasia (in particular erythro- and leukoplakia and lichen). All patients were also subjected to oral biopsy and histological examination.Out of 89 cases studied, histology showed the presence of an invasive squamous carcinoma in 32, dysplasia in 17, phlogosis in 15 and other types of lesions (2 of which malignant non-epithelial tumours) in 25. The cytological smear was inadequate for diagnosis in 11/89 cases (12.4%). In cytologically adequate and histologically positive cases, cytology confirmed the histological diagnosis of dysplasia and/or carcinoma in 38/45 cases (sensitivity 86.5%, accuracy 89.6%). Moreover, 1 case which was histologically negative at the onset, proved positive at cytology. There were 2 false-positive cytology results (specificity 94.3%, predictive positive value 95.7%).Despite the small number of cases in the cohort, oral cytology can improve the accuracy of histology, and may be a useful screening tool for the diagnosis of oral neoplasia/dysplasia.

This study was aimed at evaluating the efficacy of beta-carotene in improving survival (S) and in disease-free survival (DFS) and reducing the incidence of second primary tumors (SPT) in patients with a radically treated stage I-II squamous head and neck tumors. Eligible patients were randomly allocated to receive beta-carotene (n=104) or no treatment (n=110). beta-carotene was administered at the dose of 75 mg/day for 3-month cycles within one month intercycle intervals for a 3-year period. The 3-year compliance to the beta-carotene was 68.7%. Only eight patients reported drug-related toxicity (7.8%). The median follow-up of all patients was 59 months. The median follow-up was 61 months (range 1-116 months) in the beta-carotene and 58 months (1-123 months) in the control group. The 10-year DFS was 75.7% for the patients in the beta-carotene and 74.3% for those in the control group (P=0.56). The 10-year S was 85.9% in the beta-carotene group and 80.9% in the control group (P=0.20). beta-carotene supplementation had no significant effect on the incidence of second primary tumors (RR=0.99; 95% C.I. 0.28-3.44). A statistically non-significant 40% reduction in the risk of death among subjects assigned to the beta-carotene compared to the controls was observed (RR=0.60; 95% C.I. 0.26-1.38). No increase in the death from cardiovascular diseases was observed among patients treated with beta-carotene. Our results might support the hypothesis that an adequate beta-carotene treatment could be potentially associated with a decreased risk of death in these patients.

Our aim is to present a singular case of malacoplakia of the tongue and a review of the literature. Malacoplakia (from the Greek "malacos", soft, and "placos", plaque) is a granulomatosis initially described in 1902. It has the clinical aspect of a yellow-brown, soft plaque of variable size, characterized by a central navel or ulcer and an intense peripheral hyperaemia, usually located in the urogenital and gastrointestinal tract. The mortality rate is higher than 50% if vital organs are involved. In the world literature there are 16 cases of the head and neck region and particularly only 2 of them are located on the tongue. In these 2 cases the lesion caused some distress to the patients who referred to a medical observation for this motive. Conversely we report a case of asymptomatic lingual malacoplakia occurring in a 57-year-old woman, diagnosed by chance during a stomatological examination in the Department of Oral Medicine and Periodontology of Turin University. In this case the outcome was quite plain and our patient did not need any supporting medical therapy. Nevertheless the potential danger of malacoplakia should underline the importance of a more careful histological assessment of submucosal nodules of the oro-pharyngeal region. Moreover the histopathological characteristic, the present etiopathogenetic hypothesis and the therapeutic pattern of malacoplakia suggested in the literature are discussed.

Oral malignancy is often treated with a combination of surgery and radiation therapy (RT). The aim of this systematic review was to examine the effects of pre- and postimplantation RT on dental implant failure.The literature published from 1990 through 2006 was reviewed for studies assessing pre- and postimplantation RT. Potential studies were identified by searches of PubMed, SCIRUS, and the Cochrane Central Register of Controlled Trials (CENTRAL). The incidence of implant failure has been linked to the following variables: post- versus preimplantation RT, site of implant placement, RT dose, delay from RT to implant placement, and timing of implant failure after placement.Similar failure rates were found for implants placed post-RT compared to those placed pre-RT (3.2% and 5.4%). In preimplantation RT, the implant failure rate was lower for the mandible (4.4%) in comparison to the maxilla (17.5%; OR = 4.63; 95% CI: 2.25 to 9.49). Other results did not reach statistical significance. No failures were observed in association with an RT dose lower than 45 Gy. All implant failures observed occurred within 36 months after RT, and most occurred between 1 and 12 months after placement.Notwithstanding the low number of implants evaluated, this review showed similar failure rate for implants placed post-RT and those placed pre-RT (3.2% and 5.4%, respectively).