Prognosis of oral epithelial dysplasia in individuals with and without oral lichen planus.

OBJECTIVES: To investigate the role of oral lichen planus (OLP) on the long-term prognosis of oral epithelial dysplasia (OED). METHODS: Retrospective single-centre cohort study using the 2007-2019 database of the Head and Neck Cancer and Oral Medicine units of University College London Hospital. The exposure of interest was the presence of OLP, and the prognostic outcomes included the development of new primary episodes of OED, progression to malignancy and mortality. Cox proportional hazard and Poisson regression models were performed. RESULTS: A total of 299 patients, of whom 144 had OED arising on the background of OLP (OLP/OED) and 155 had OED without underlying OLP (non-OLP/OED), were included. A pre-existing diagnosis of OLP was significantly associated with a twofold increased risk of subsequent primary OED events (HR = 2.02, p = 0.04), which also developed faster (1.46 vs. 2.96 years, p = 0.04) and with more involvement of non-cancer-prone sites (p = 0.001) than in the non-OLP/OED group. There was no difference between groups in the progression to malignancy or mortality. CONCLUSIONS: Oral lichen planus/OED patients are at higher risk of multiple episodes of primary OED, which can develop faster and at non-cancer-prone sites as compared to non-OLP/OED individuals. Further research is needed to clarify the effects of OLP upon progression to OSCC and mortality.

Long-term effectiveness of a novel intra-oral electro-stimulator for the treatment of dry mouth in patients with Sjogren's syndrome: A randomised sham-controlled feasibility study (LEONIDAS-1).

BACKGROUND: Effective treatments for dry mouth of Sjogren's syndrome are limited and hampered by adverse effects. The aim of LEONIDAS-1 was to explore the feasibility of salivary electrostimulation in individuals with primary Sjogren's syndrome, as well as parameters required to inform the design of a future phase III trial. METHODS: Multicentre, parallel-group, double-blind, randomised sham-controlled trial in two UK centres. Participants were randomised (1:1, computer-generated) to active or sham electrostimulation. The feasibility outcomes included screening/eligibility ratio, consent, and recruitment and drop-out rates. Preliminary efficacy outcome included dry mouth visual analogue scale, Xerostomia Inventory, the EULAR Sjögren's syndrome patient reported index-Q1, and unstimulated sialometry. RESULTS: Forty-two individuals were screened, of whom 30 (71.4%) met the eligibility criteria. All eligible individuals consented to recruitment. Out of the 30 randomised participants (active n = 15, sham n = 15), 4 dropped out and 26 (13 vs. 13) completed all study visits as per protocol. Recruitment rate was 2.73 participants/month. At 6-month post-randomisation the difference in mean reduction in visual analogue scale, xerostomia inventory and EULAR Sjögren's syndrome patient reported index-Q1 scores between groups were 0.36 (95% CI: -0.84, 1.56), 3.31 (0.43, 6.18), and 0.23 (-1.17, 1.63), respectively; unstimulated salivary flow increased by a mean of 0.98 mL/15 min, all in favour of the active group. No adverse events were reported. CONCLUSION: LEONIDAS-1 results support progression to a phase III definitive randomised controlled trial of salivary electrostimulation in individuals with Sjogren's syndrome. Xerostomia inventory could be considered the primary patient-centred outcome measure and the corresponding observed treatment effect could inform the sample size of a future trial.

Point-of-care Analysis for Non-invasive Diagnosis of Oral cancer (PANDORA): A technology-development proof of concept diagnostic accuracy study of dielectrophoresis in patients with oral squamous cell carcinoma and dysplasia.

BACKGROUND: Delays in the identification and referral of oral cancer remain frequent. An accurate and non-invasive diagnostic test to be performed in primary care may help identifying oral cancer at an early stage and reduce mortality. Point-of-care Analysis for Non-invasive Diagnosis of Oral cancer (PANDORA) was a proof-of-concept prospective diagnostic accuracy study aimed at advancing the development of a dielectrophoresis-based diagnostic platform for oral squamous cell carcinoma (OSCC) and epithelial dysplasia (OED) using a novel automated DEPtech 3DEP analyser. METHODS: The aim of PANDORA was to identify the set-up of the DEPtech 3DEP analyser associated with the highest diagnostic accuracy in identifying OSCC and OED from non-invasive brush biopsy samples, as compared to the gold standard test (histopathology). Measures of accuracy included sensitivity, specificity, positive and negative predictive value. Brush biopsies were collected from individuals with histologically proven OSCC and OED, histologically proven benign mucosal disease, and healthy mucosa (standard test), and analysed via dielectrophoresis (index test). RESULTS: 40 individuals with OSCC/OED and 79 with benign oral mucosal disease/healthy mucosa were recruited. Sensitivity and specificity of the index test was 86.8% (95% confidence interval [CI], 71.9%-95.6%) and 83.6% (95% CI, 73.0%-91.2%). Analysing OSCC samples separately led to higher diagnostic accuracy, with 92.0% (95% CI, 74.0%-99.0%) sensitivity and 94.5% (95% CI, 86.6%-98.5%) specificity. CONCLUSION: The DEPtech 3DEP analyser has the potential to identify OSCC and OED with notable diagnostic accuracy and warrants further investigation as a potential triage test in the primary care setting for patients who may need to progress along the diagnostic pathway and be offered a surgical biopsy.

Patient and clinician perspectives of information needs concerning oral epithelial dysplasia.

OBJECTIVES: Individuals diagnosed with a chronic oral disease that increase the risk of mouth cancer, such as oral epithelial dysplasia (OED), require appropriate knowledge to make informed decisions. The present study aimed to assess whether patient information needs of a group of patients concerning dysplasia were met and to what degree clinicians agree with patients on 'important' topics. SUBJECTS AND METHODS: This represented secondary analyses of a cross-sectional study to assess the information needs of 86 patients diagnosed with dysplasia compared with those of 77 clinicians using the validated OED Information Needs Questionnaire. Descriptive, concordance and regression analyses were performed for the collected data. RESULTS: The mean and median total scores for all items in the amount of information received subscale were 2.33 and 2.44, indicating overall unmet needs concerning dysplasia. Clinicians were generally able to predict topics of greatest importance to patients, although their scores were mainly lower than those of patients (k = 0.06). There was a higher agreement between patients (k = 0.25) than clinicians (k = 0.09). CONCLUSION: Clinicians are encouraged to assess a patient's information needs to ensure tailored and patient-centred communication concerning OED during all clinical consultations.

Audiovisual information of oral epithelial dysplasia: Quality, understandability and actionability.

OBJECTIVES: Online information on oral epithelial dysplasia (OED) is insufficient and of low quality. While only written information has been previously assessed, this study aims to evaluate the content and quality of audiovisual (AV) online information about OED. METHODS: One hundred and twenty-seven materials were initially considered using six key words across two search engines (YouTube and Google). Ultimately, 29 materials remained for the final assessment. These materials were then analysed for content, quality (DISCERN instrument, JAMA benchmarks), understandability and actionability. RESULTS: Most contents were scientific (n = 25), while three videos were educational, and one video was a personal experience with OED. On a scale of 1-5, the overall DISCERN score was (mean ± SD = 2.26 ± 0.79), suggesting poor quality of information. Regarding JAMA benchmarks, there was no single material that fulfilled or lacked all four benchmarks. The overall mean understandability score was 82% and the actionability mean score was significantly low at 29%. CONCLUSION: Although the vast majority of AV materials on OED were primarily produced for scientific purposes, these materials could be helpful as resources for patient education. Keeping in mind, however, that the desired quality and essential patient information about OED available online remains largely poor and missing.

Inhibition of Mitochondrial Antioxidant Defense and CDK4/6 in Mesothelioma.

Advanced mesothelioma is considered an incurable disease and new treatment strategies are needed. Previous studies have demonstrated that mitochondrial antioxidant defense proteins and the cell cycle may contribute to mesothelioma growth, and that the inhibition of these pathways may be effective against this cancer. We demonstrated that the antioxidant defense inhibitor auranofin and the cyclin-dependent kinase 4/6 inhibitor palbociclib could decrease mesothelioma cell proliferation alone or in combination. In addition, we determined the effects of these compounds on colony growth, cell cycle progression, and the expression of key antioxidant defense and cell cycle proteins. Auranofin and palbociclib were effective in decreasing cell growth and inhibiting the above-described activity across all assays. Further study of this drug combination will elucidate the contribution of these pathways to mesothelioma activity and may reveal a new treatment strategy.

Intestinal Persistence of Colonizing Escherichia coli Strains, Especially ST131-H30, in Relation to Bacterial and Host Factors.

BACKGROUND: Superior gut colonization may underlie the pandemic emergence of the resistance-associated H30 subclone of Escherichia coli sequence type 131 (ST131-H30). Little is known about the associated host and bacterial characteristics, or the comparative persistence of non-ST131 intestinal E. coli. METHODS: Generic and fluoroquinolone-resistant E. coli isolates from volunteers' serial fecal samples underwent clonal analysis and extensive polymerase chain reaction (PCR)-based characterization (phylogroup, selected sequence types, virulence genes). Kaplan-Meier survival analysis and Cox proportional hazards survival analysis using penalized regression (a machine-learning method) were used to identify correlates of strain persistence. RESULTS: Screening of 2005 subjects at the Minneapolis VA Medical Center identified 222 subjects (117 veterans, 105 human and animal household members) for longitudinal fecal surveillance. Analysis of their 585 unique-by-subject fecal E. coli strains identified multiple epidemiological, ecological, and bacterial correlates of strain persistence. ST131-H30, a strong univariable correlate of persistence, was superseded in multivariable analysis by outpatient status, fluoroquinolone resistance, and diverse (predominantly iron uptake-related) virulence genes. CONCLUSIONS: ST131-H30 exhibits exceptional intestinal persistence, possibly due to a combination of fluoroquinolone resistance and virulence factors, which may be primarily colonization factors. This identifies both likely contributors to the ST131-H30 pandemic and potential targets for interventions against it.

Information needs and oral epithelial dysplasia: Development and psychometric evaluation of a novel instrument.

OBJECTIVES: Oral epithelial dysplasia (OED) can lead to significant information needs (IN) related to the risk of cancer development, the need for long-term monitoring and potential intervention. The present study aimed to develop and perform preliminary psychometric testing for a novel IN instrument specific to OED. SUBJECTS AND METHODS: Patients diagnosed with OED were invited to complete the Oral Epithelial Dysplasia Informational Needs Questionnaire (ODIN-Q), which was developed based on a known theoretical framework and with items generated via expert input and the literature. Face validity and content validity were initially assessed prior to finalisation of the tool. ODIN-Q was tested for internal consistency and test-retest reliability along with construct validity. RESULTS: ODIN-Q consists of 35 items, categorised under six domains, and rated by dual 4-point Likert scales (amount of information received and degree of importance). Internal consistency (Cronbach's alpha) was rated "excellent" for the scale (0.93) and both subscales (0.92/0.94). For test-retest reliability, moderate agreement was found (κ = 0.49-0.53). Regarding construct validity, a significant but limited relationship was found between ODIN-Q and the Krantz Health Opinion Survey. CONCLUSION: ODIN-Q showed adequate psychometric properties of reliability and validity. Further validation is, however, needed to assess its structural validity and responsiveness.

Validity and responsiveness of pain rating scales in patients with chronic oral mucosal diseases.

OBJECTIVES: To validate the Visual Analog Scale (VAS) and Numerical Rating Scale (NRS) for measuring pain intensity in chronic oral mucosal diseases. METHODS: Secondary analyses of data including the VAS, NRS, demographic, clinical and quality-of-life outcomes at baseline and 4-month follow-up were retrieved from a clinical study of chronic oral mucosal diseases. Construct and criterion validity and responsiveness of the VAS and NRS were assessed through testing hypotheses based upon strength of Spearman's correlation coefficients. RESULTS: Data of 500 and 290 patients with chronic oral mucosal diseases were used for the assessment of validity and responsiveness, respectively. Moderate-to-high correlations between both pain scores and scores of clinical and quality-of-life outcomes were observed, supporting construct validity of the VAS and NRS. Their criterion validity was confirmed by significantly strong association between scores of both scales. Responsiveness of both scales was adequate based on moderate association between their change scores and global rating of change scale. CONCLUSION: The present results provide evidence supporting validity and responsiveness of the VAS and NRS for pain intensity assessment in patients with chronic oral mucosal diseases. Future research examining other pain intensity domains and standardizing composite scores for pain intensity in this population is required.

A proof of concept pilot trial of probiotics in symptomatic oral lichen planus (CABRIO).

OBJECTIVE: To preliminary evaluate the clinical effects of probiotics in individuals with symptomatic oral lichen planus and the possible mechanisms of action. SUBJECTS AND METHODS: A group of 30 individuals with symptomatic oral lichen planus were recruited in a randomised double-blind parallel group controlled (1:1) proof-of-concept pilot trial of probiotic VSL#3 vs placebo. Efficacy outcomes included changes in pain numeric rating scale, oral disease severity score and the chronic oral mucosal disease questionnaire. Adverse effects, home diary and withdrawals were assessed as feasibility outcomes. Mechanistic outcomes included changes in salivary and serum levels of CXCL10 and IFN-γ and in oral microbial composition. RESULTS: The probiotic VSL#3 was safe and well tolerated. We observed no statistically significant change in pain, disease activity, quality of life, serum/salivary CXCL10 or oral microbial composition with respect to placebo. Salivary IFN-γ levels demonstrate a trend for a reduced level in the active group (p = 0.082) after 30 days of probiotic consumption. CONCLUSIONS: The present proof-of-concept study provides some weak not convincing indication of biological and clinical effects of probiotic VSL#3 in individuals with painful oral lichen planus. Further research in this field is needed, with the current study providing useful information to the design of future clinical trials.

Coronaviridae-Old friends, new enemy!

Coronaviridae is a family of single-stranded positive enveloped RNA viruses. This article aimed to review the history of these viruses in the last 60 years since their discovery to understand what lessons can be learned from the past. A review of the PubMed database was carried out, describing taxonomy, classification, virology, genetic recombination, host adaptation, and main symptoms related to each type of virus. SARS-CoV-2 is responsible for the ongoing global pandemic, and SARS-CoV and MERS-CoV were responsible for causing severe respiratory illness and regional epidemics in the past while the four other strains of CoVs (229-E OC43, NL63, and HKU1) circulate worldwide and normally only cause mild upper respiratory tract infections. Given the enormous diversity of coronavirus viruses in wildlife and their continuous evolution and adaptation to humans, future outbreaks would undoubtedly occur. Restricting or banning all trade in wild animals in wet markets would be a necessary measure to reduce future zoonotic infections.

Activity of plazomicin against carbapenem-intermediate or -resistant Escherichia coli isolates from the United States and international sites in relation to clonal background, resistance genes, co-resistance, and region.

BACKGROUND: Emerging carbapenem resistance in Escherichia coli, including sequence type 131 (ST131), threatens therapeutic efficacy. Plazomicin (PLZ), a semisynthetic aminoglycoside approved by the FDA in 2018, overcomes the most common aminoglycoside resistance mechanisms and maintains activity against many carbapenem-intermediate or -resistant (CIR) E. coli strains. OBJECTIVES: To assess plazomicin susceptibility among CIR E. coli in relation to region and multiple bacterial characteristics. METHODS: We determined broth microdilution MICs for plazomicin and 11 comparators against 343 CIR clinical E. coli isolates, then compared susceptibility results by bacterial characteristics and region. The collection comprised 203 US isolates (2002-17) and 141 isolates from 17 countries in Europe, Latin America, and the Asia-West Pacific region (2003-17). Isolates were characterized for phylogenetic group, resistance-associated sequence types (STs) and subsets thereof, and relevant ß-lactamase-encoding genes. RESULTS: Plazomicin exhibited the highest percentage susceptible (89%) after tigecycline (99%). The percentage susceptible to plazomicin varied significantly by phylogroup (63%, group B1; versus >93%, others) and ST131 subclone (92%, H30Rx; versus 87%-89%, H30R1 and non-H30), but not ST. It also varied by resistance genotype [higher with Klebsiella pneumoniae carbapenemase (KPC), lower with metallo-ß-lactamases], global region [highest for Latin America (94%), lowest for Asia-West Pacific (69%)], and US region (80%, South, versus 96%-100%, others). Although reduced susceptibility to comparators often predicted reduced susceptibility to plazomicin, even among comparator-intermediate or -resistant isolates the plazomicin-susceptible fraction was ≥77%, except for amikacin (53%). CONCLUSIONS: The likely utility of plazomicin against CIR E. coli is high overall, but varies with region and multiple bacterial characteristics.

Molecular Characteristics, Ecology, and Zoonotic Potential of Escherichia coli Strains That Cause Hemorrhagic Pneumonia in Animals.

Hemorrhagic pneumonia (HP) is a rare but highly lethal disease, mainly of dogs and cats, caused by hemolytic Escherichia coli strains that contain cnf1 (encoding cytotoxic necrotizing factor 1). After encountering fatal HP in two dogs, we used contemporary molecular methods, including multilocus sequence typing and whole-genome sequencing, to compare the corresponding case isolates with published HP clinical isolates and newly obtained fecal E. coli isolates from 20 humans and animals in the index HP case household. We also compared the aggregated HP clinical isolates, which represented 13 discrete strains, by pulsotype with a large, private pulsotype library of diverse-source E. coli. The HP clinical isolates represented a narrow range of phylogenetic group B2 lineages (mainly sequence types 12 and 127), O types (mainly O4 and O6), and H types (mainly H5 and H31), but diverse fimH alleles (type-1 fimbriae adhesin). Their extensive, highly conserved virulence genotypes, which qualified as extraintestinal pathogenic E. coli (ExPEC), encoded diverse adhesins, toxins, iron uptake systems, and protectins. Household surveillance identified multiple HP-like fecal strains, plus abundant between-host strain sharing, including of the household's index HP strain. The pulsotype library search identified, for five HP clinical strains, same-pulsotype human and animal fecal and clinical (predominantly urine) isolates, from diverse locales and time periods. Thus, E. coli strains that cause HP derive from a narrow range of ExPEC lineages within phylogroup B2, contain multiple virulence genes other than cnf1, are shared extensively between hosts, and likely function in nature mainly as intestinal colonizers and uropathogens. IMPORTANCE This study clarifies the clonal background and extensive virulence genotypes of the E. coli strains that cause hemorrhagic pneumonia in domestic animals (mainly dogs and cats), shows that such strains circulate among animals and humans, identifies a substantial intestinal colonization component to their lifestyle, and extends their known clinical manifestations to include bacteremia and urinary tract infection. The findings place these strains better into context vis-à-vis current understandings of E. coli phylogeny, ecology, and pathogenesis; identify questions for future research; and may prove relevant for surveillance and prevention efforts.

Comparative activity of plazomicin against extended-spectrum cephalosporin-resistant Escherichia coli clinical isolates (2012-2017) in relation to phylogenetic background, sequence type 131 subclones, blaCTX-M genotype, and resistance to comparator agents.

Extended-spectrum cephalosporin-resistant Escherichia coli (ESCREC) are a growing threat. Leading ESCREC lineages include sequence type ST131, especially its (blaCTX-M-15-associated) H30Rx subclone and (blaCTX-M-27-associated) C1-M27 subset within the H30R1 subclone. The comparative activity against such strains of alternative antimicrobial agents, including the recently developed aminoglycoside plazomicin, is undefined, so was investigated here. We assessed plazomicin and 11 comparators for activity against 216 well-characterized ESCREC isolates (Minnesota, 2012-2017) and then compared broth microdilution MICs with phylogenetic and clonal background, beta-lactamase genotype (blaCTX-M; group 1 and 9 variants), and co-resistance. Percent susceptible was > 99% for plazomicin, meropenem, imipenem, and tigecycline; 96-98% for amikacin and ertapenem; and ≤ 75% for the remaining comparators. For most comparators, MICs varied significantly in relation to multiple bacterial characteristics, in agent-specific patterns. By contrast, for plazomicin, the only bacterial characteristic significantly associated with MICs was ST131 subclone: plazomicin MICs were lowest among O16 ST131 isolates and highest among ST131-H30R1 C1-M27 subclone isolates. Additionally, plazomicin MICs varied significantly in relation to resistance vs. susceptibility to comparator agents only for amikacin and levofloxacin. For most study agents, antimicrobial activity against ESCREC varied extensively in relation to multiple bacterial characteristics, including clonal background, whereas for plazomicin, it varied only by ST131 subclone (C1-M27 isolates least susceptible, O16 isolates most susceptible). These findings support plazomicin as a reliable alternative for treating ESCREC infections and urge continued attention to the C1-M27 ST131 subclone.

Global molecular epidemiology of carbapenem-resistant Escherichia coli (2002-2017).

The emergence of carbapenem-resistant (CR) Escherichia coli obliges an assessment of such strains' molecular epidemiology. Accordingly, we characterized in detail a globally distributed collection of CR E. coli isolates, then explored for associations between geographical origin and bacterial traits, and between different bacterial traits. We used established PCR-based assays and broth microdilution MIC determinations to characterize 343 global CR (i.e., non-susceptible to ≥ 1 carbapenem) extraintestinal E. coli isolates (2002-2017) for diverse molecular traits-including phylogroups, sequence types (STs), beta-lactamase genes, and 51 virulence genes-and susceptibility to 12 relevant antimicrobial agents. The study population was tremendously diverse according to all assessed variables. Nonetheless, certain geographically aligned, unifying themes emerged. These included an association of an Asia/West Pacific origin with non-B2/D/F phylogroups and STs, lower molecularly inferred virulence, more extensive resistance, and specific resistance genes (notably, metallo-beta-lactamases). Likewise, U.S. isolates from the central region, vs. other regions, were more virulent-appearing and more often from phylogroup B2 and ST131, but less extensively resistant and more often carbapenemase-gene negative. The global CR E. coli population is highly diverse according to multiple characteristics and varies significantly by geographical region. This predictably will pose challenges for prevention and management, and obliges ongoing surveillance.

Psychosocial impacts of oral epithelial dysplasia.

BACKGROUND: The psychosocial impact of receiving the diagnosis of oral epithelial dysplasia, which presents up to 3.5% increased annual risk of mouth cancer, remains unknown. Using validated instruments, the present study aimed to investigate the prevalence and existing correlations between anxiety, depression and dental anxiety symptoms and burden on oral health-related quality of life. METHODS: A clinical cohort of 82 patients with oral dysplasia was asked to complete the Hospital Anxiety and Depression Scale, the Modified Dental Anxiety Scale and the shortened version of the Oral Health Impact Profile. Spearman's correlation coefficient and regression analyses were performed. RESULTS: The participants' scores were in keeping with the presence of anxiety, depression and emotional distress symptoms in 30%, 16% and 26%, respectively. However, 69% experienced anxiety related to procedures that may be required as part of long-term management of oral dysplasia (e.g. local anaesthetic injection). The oral health-related quality of life scores showed 41.5% reporting a recent daily problem due to their oral or dental health. Significant correlations [p >0.05] were found among and between all of the used instruments. Being a female with oral dysplasia also predicted increased odds of indicating higher anxiety and dental anxiety scores than males [p >0.05]. CONCLUSION: Oral dysplasia can adversely impact on the psychosocial well-being of affected persons. Establishing a causal relationship between the measured variables may, however, be challenging and would need further longitudinal studies.

Measuring the impact of systemic sclerosis on oral health-related quality of life in a UK population.

BACKGROUND: The objective of the present study was to identify the impact of systemic sclerosis (SSc) upon oral health-related quality of life (OHRQoL) of affected individuals resident in the UK. METHODS: A total of 100 patients and their partners or carers were invited to complete questionnaires regarding the impact of SSc on quality of life and psychological well-being using valid and reliable patient-reported outcome measures (OHIP-14, MHISS, OIDP, MDAS and HADS). A total of 50 patients with SSc and 18 partners or carers who acted as controls returned the completed questionnaires. Statistical analyses were performed for comparisons of different variables. RESULTS: All the mean scores of OHIP-14 (SSc [16.5 ± 12.4] Vs controls [6.06 ± 7.6, p = 0.001]) and MHISS components were significantly higher in patients than those of control group (SSc [21.26 ± 12] Vs controls [4.8 ± 7.3, p < 0.0001]). Majority of OIDP mean scores were significantly worse in patients compared with controls [SSc (10 ± 8.7) Vs controls (1.72 ± 3.4, p < 0.0001)]. The mean of total MDAS [SSc (11.7 ± 5.3) Vs controls (9.5 ± 4.4)] and HADS scores were higher in patients compared to controls (SSc depression [4.8 ± 3.3] and anxiety [6 ± 4.6] Vs controls [3.7 ± 3.1] [4.7 ± 3.9]). CONCLUSIONS: Although the present study is limited by the low response rate and its cross-sectional design, present results highlighted that systemic sclerosis has a negative impact on OHRQoL of the affected individuals; hence, the evaluation of associated psychological impact including anxiety and depression symptoms is needed to better understand, monitor and evaluate the disease comorbidity in patients with SSc.

Pentoxifylline, tocopherol, and sequestrectomy are effective for the management of advanced osteoradionecrosis of the jaws-a case series.

BACKGROUND: The aim of the present study was to evaluate the efficacy of pentoxifylline and tocopherol for the management of osteoradionecrosis of the jaws. METHODS: Twenty-five patients diagnosed with osteoradionecrosis of the jaws treated with pentoxifylline 400 mg + tocopherol 400 mg three times daily (tid) were evaluated. Clinical records and image tests were reviewed. All patients were previously submitted to head and neck radiation therapy and presented with a clinical and radiographic diagnosis of osteoradionecrosis of the jaws. RESULTS: Following therapy with pentoxifylline and tocopherol, 76% (19/25) of the patients showed complete mucosal healing, in which 47.3% (9/19) did not undergo sequestrectomy. From this particular group, 77.7% (7/9) were in stage I and 33.3% (3/9) used the protocol for up to 3 months. Among those who underwent to sequestrectomy, complete mucosal healing was observed in 52.7% (10/19). Among these, 60% (6/10) were in stage I and 100% of the patients were using the protocol for more than 3 months. In all other patients, partial healing of the mucosa was observed since they presented advanced disease. These represented 24% of the sample (6/25), 66.6% (4/6) were in stage III, and 60% (4/6) used the protocol for over 6 months. CONCLUSION: Pentoxifylline and tocopherol may provide effective management of osteoradionecrosis of the jaws, and the association with sequestrectomy may avoid major surgical procedures.

Evaluating the measurement properties of patient-reported outcome measures in radiotherapy-induced xerostomia.

OBJECTIVE: Radiotherapy-induced xerostomia (RIX) is one of the most common adverse effects of radiotherapy to the head and neck, and a major determinant of survivors' quality of life. A number of patient-reported outcome measures (PROMs) have been used in clinical trials of therapeutic interventions for RIX; however, little is known regarding their measurement properties and methodological quality. METHODS: We conducted a systematic literature search in Embase, MEDLINE and PsycINFO for articles published up to May 2019 and evaluating at least one measurement property of PROMs relevant to RIX. The COSMIN guidelines were used to assess relevant measurement properties and methodological quality. RESULTS: Nine validations studies were identified reporting on four PROMs relevant to RIX. The Xerostomia Questionnaire (XQ) showed overall high-quality evidence for structural validity and internal consistency, but low-quality evidence supporting reliability. The methodological quality of the Groningen Radiotherapy-Induced Xerostomia scale (GRIX), Xerostomia Inventory (XI) and the Xerostomia Quality of Life Scale (XeQoLS) was relatively low for all measurement properties. CONCLUSIONS: The XQ was found to have the highest potential to capture changes in RIX according to COSMIN guidelines. Additional validation studies are required to further understand the methodological quality of the XI, GRIX and XeQoLS.

The patient acceptable symptom state in oral lichen planus: identification of cut-off threshold scores in measures of pain and quality of life.

OBJECTIVES: To establish thresholds of pain and quality of life scores corresponding to patient acceptable symptom state (PASS) in patients with oral lichen planus (OLP) and to assess demographic and clinical factors associated with achieving the PASS. METHODS: Prospective data from baseline and 4-month follow-up including Visual Analogue Scale (VAS), Numerical Rating Scale (NRS), 14-item Oral Health Impact Profile (OHIP-14) and 15-item and 26-item Chronic Oral Mucosal Disease Questionnaire (COMDQ-15; COMDQ-26) were collected from 281 patients with OLP. An anchoring approach based upon the patient's opinion on acceptability of OLP status was applied. Associated factors for achieving the PASS were analysed using multivariate logistic regression. RESULTS: About two-thirds (68.7%) of participants rated their OLP status as acceptable. Cut-off thresholds for PASS were as follows: ≤ 28 mm for VAS, ≤ 3 for NRS, ≤ 18 for total OHIP-14, ≤ 26 for total COMDQ-15 and ≤ 48 for total COMDQ-26. Based upon results of multivariate logistic analysis, factors associated with being in PASS were lower pain intensity, lower depressive symptoms and lower disease activity of OLP. CONCLUSION: The present study established PASS cut-off thresholds as a tool facilitating interpretation of pain and quality of life outcomes relevant to individuals with OLP. CLINICAL RELEVANCE: Identified PASS estimates could be utilised as clinically important endpoints in clinical practice of OLP as well as eligibility criteria for recruiting participants in clinical trials assessing effectiveness of symptomatic intervention of OLP.