Conservative non-surgical treatment of medication-related osteonecrosis of the jaws: a long-term prognostic evaluation

BACKGROUND: The conservative non-surgical treatment of medication-related osteonecrosis of the jaws (MRONJ) is generally advisable in patients with poor general health and/or a concomitant malignant disease as the priority is to control signs of infection and symptoms and to prevent a further bone disease progression. AIMS: the aim of this study is to conduct an exploratory analysis on the long-term outcomes of the exclusive conservative non-surgical treatment on a big sample of MRONJ patients, all having a minimum follow-up of at least 12 months. METHODS: A retrospective medical record review of patients diagnosed with MRONJ was carried out in three Oral Medicine /Oral Maxillofacial outpatients' departments. The conservative non-surgical treatment consisted of the use of local antiseptics with or without the use of antibiotics cycles. Regardless of stage, mobile fragments of bone were managed with non-surgical sequestrectomy. MRONJ lesions were staged according to both the American Association of Oral/Maxillofacial Surgeons staging system and the SICMF- SIPMO staging system. The primary outcome was the pain remission. Secondary outcomes were remission of signs of infection and complete clinical remission of MRONJ lesion. RESULTS: One hundred and twenty-six patients were included in the study and observed for a mean time of 39.73 ± 27.38 months. About seventy-one percent of the sample was composed of oncologic patients. 51.1% of the MRONJ lesions had never experienced pain or relapses after the first pain remission, while in 46.8% relapses were successfully treated with medical therapy. Only in the 2.1% pain was persistent. 93% of the patients achieved either complete clinical healing of the lesions (32%), or a clinical stable disease (61%) experiencing pain and signs of infection remission. Only 7% of the patients were refractory to the non-surgical treatment and needed surgical interventions in order to achieve a better pain/infection control. CONCLUSIONS: Although one third of the patients achieve complete clinical remission of MRONJ lesions, the non-surgical treatment had demonstrated to be effective in controlling pain and signs of infection in almost all the patients. Prospective multicenter, controlled trials are necessary to better determine the relative effectiveness of the non-surgical treatment for a more evidence-based approach to management of MRONJ

Sleep Disorders and Psychological Profile in Oral Cancer Survivors: A Case-Control Clinical Study

Quality of sleep (QoS) and mood may impair oral cancer survivors’ wellbeing, however few evidences are currently available. Therefore, we aimed to assess the prevalence of sleep disorders, anxiety and depression among five-year oral cancer survivors (OC survivors). 50 OC survivors were compared with 50 healthy subjects matched for age and sex. The Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Hamilton Rating Scales for Depression and Anxiety (HAM-D, HAM-A), the Numeric Rating Scale (NRS), the Total Pain Rating Index (T-PRI) were administered. The global score of the PSQI, ESS, HAM-A, HAM-D, NRS, T-PRI, was statistically higher in the OC survivors than the controls (p-value: <0.001). QoS of OC survivors was significantly impaired, especially with regard to some PSQI sub-items as the subjective sleep quality, sleep latency and daytime dysfunction (p-value: 0.001, 0.029, 0.004). Moreover, poor QoS was negatively correlated with years of education (p-value: 0.042 *) and positively correlated with alcohol consumption (p-value: 0.049 *) and with the use of systemic medications (p-value: 0.044 *). Sleep disorders and mood disorders are common comorbidities in OC survivors; therefore, early assessment and management before, during and after treatment should be performed in order to improve the quality of life of OC survivors

Immunocytometric analysis of oral pemphigus vulgaris patients after treatment with rituximab as adjuvant

Background: B-cell depletion therapy was demonstrated to be a valid and safe alternative as an adjuvant in oral-pharyngeal pemphigus vulgaris (OPV) patients. We aimed to assess its effects on anti-desmoglein (Dsg) 1 and 3 and leukocytes subsets profile in these patients’ population. Methods and Materials: We evaluated the immunologic profile of 10 OPV patients treated with RTX as adjuvant by using the ELISA testing for anti-Dsg-1 and -3 titers and the immunophenotyping for B and T-cell lymphocyte subpopulations and compared them with the PDAI score for clinical remission. Results: A significant difference in medians between baseline, end of RTX therapy, and 6 months after RTX therapy was observed in Dsg-3 titer (p 0.001), in the CD8 (p = 0.009), and CD20 counts (p 0.001). Multiple comparisons after Bonferroni adjustment confirmed such significant differences mainly between baseline and the end of RTX therapy and baseline and 6 months after RTX therapy. Only the anti-Dsg-3 titer at the end of RTX therapy demonstrated a slight positive correlation with the PDAI score at baseline (p = 0.046, r = 0.652). Conclusions: B-cell depletion adjuvant therapy in OPV patients demonstrated a significant impact on anti-Dsg-3 titer and B and T-cell lymphocyte subpopulations profile

Burning Mouth Syndrome and Hypertension: Prevalence, Gender Differences and Association with Pain and Psycho-Social Characteristics—A Case Control Study

Background: To assess the prevalence of hypertension (HTN) in burning mouth syndrome (BMS) patients and to investigate its relationship with sociodemographic factors, pain and the psychological profile. Methods: A case-control study was conducted by enrolling 242 BMS patients and 242 controls matched for age and gender. Sociodemographic and clinical characteristics were recorded, and all participants completed numeric rating scale (NRS), the short-form of the McGill pain questionnaire (SF-MPQ), the Hamilton rating scale for anxiety and depression (HAM-A, HAM-D), the Pittsburgh sleep quality index (PSQI) and the Epworth sleepiness scale (ESS). Results: The BMS patients presented with a statistically significant higher prevalence of HTN compared to that in the controls (55% versus 33.5%; p-value: <0.001) and higher median scores of the NRS, SF-MPQ, HAM-A, HAM-D, PSQI and ESS (p < 0.001). Multivariate regression analysis in the BMS patients indicated positive correlations between HTN and age, systemic diseases, drug consumption and anxiety (p-value: <0.001) and these predictors were responsible for 11.3% of the HTN variance in the BMS patients, when considered together. Conclusions: The prevalence of HTN was significantly higher in the BMS patients, since ageing, the presence of comorbidities, drug consumption and anxiety were potential predictors. Further studies are needed to better investigate the relationship between BMS and HTN

Burning Fog: Cognitive Impairment in Burning Mouth Syndrome

Background: Due to its common association with chronic pain experience, cognitive impairment (CI) has never been evaluated in patients with burning mouth syndrome (BMS). The purpose of this study is to assess the prevalence of CI in patients with BMS and to evaluate its relationship with potential predictors such as pain, mood disorders, blood biomarkers, and white matter changes (WMCs). Methods: A case-control study was conducted by enrolling 40 patients with BMS and an equal number of healthy controls matched for age, gender, and education. Neurocognitive assessment [Mini Mental State Examination (MMSE), Digit Cancellation Test (DCT), the Forward and Backward Digit Span task (FDS and BDS), Corsi Block-Tapping Test (CB-TT), Rey Auditory Verbal Learning Test (RAVLT), Copying Geometric Drawings (CGD), Frontal Assessment Battery (FAB), and Trail Making A and B (TMT-A and TMT-B)], psychological assessment [Hamilton Rating Scale for Depression and Anxiety (HAM-D and HAM-A), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and 36-Item Short Form Health Survey (SF-36)], and pain assessment [Visual Analogic Scale (VAS), Total Pain Rating index (T-PRI), Brief Pain Inventory (BPI), and Pain DETECT Questionnaire (PD-Q)] were performed. In addition, blood biomarkers and MRI of the brain were recorded for the detection of Age-Related WMCs (ARWMCs). Descriptive statistics, the Mann-Whitney U-test, the Pearson Chi-Squared test and Spearman's correlation analysis were used. Results: Patients with BMS had impairments in most cognitive domains compared with controls (p < 0.001**) except in RAVLT and CGD. The HAM-D, HAM-A, PSQI, ESS, SF-36, VAS, T-PRI, BPI and PD-Q scores were statistically different between BMS patients and controls (p < 0.001**) the WMCs frequency and ARWMC scores in the right temporal (RT) and left temporal (LT) lobe were higher in patients with BMS (p = 0.023*). Conclusions: Meanwhile, BMS is associated with a higher decline in cognitive functions, particularly attention, working memory, and executive functions, but other functions such as praxis-constructive skills and verbal memory are preserved. The early identification of CI and associated factors may help clinicians to identify patients at risk of developing time-based neurodegenerative disorders, such as Alzheimer's disease (AD) and vascular dementia (VD), for planning the early, comprehensive, and multidisciplinary assessment and treatment

Hematopoietic reconstitution dynamics of mobilized- and bone marrow-derived human hematopoietic stem cells after gene therapy

Mobilized peripheral blood is increasingly used instead of bone marrow as a source of autologous hematopoietic stem/progenitor cells for ex vivo gene therapy. Here, we present an unplanned exploratory analysis evaluating the hematopoietic reconstitution kinetics, engraftment and clonality in 13 pediatric Wiskott-Aldrich syndrome patients treated with autologous lentiviral-vector transduced hematopoietic stem/progenitor cells derived from mobilized peripheral blood (n = 7), bone marrow (n = 5) or the combination of the two sources (n = 1). 8 out of 13 gene therapy patients were enrolled in an open-label, non-randomized, phase 1/2 clinical study (NCT01515462) and the remaining 5 patients were treated under expanded access programs. Although mobilized peripheral blood- and bone marrow- hematopoietic stem/progenitor cells display similar capability of being gene-corrected, maintaining the engineered grafts up to 3 years after gene therapy, mobilized peripheral blood-gene therapy group shows faster neutrophil and platelet recovery, higher number of engrafted clones and increased gene correction in the myeloid lineage which correlate with higher amount of primitive and myeloid progenitors contained in hematopoietic stem/progenitor cells derived from mobilized peripheral blood. In vitro differentiation and transplantation studies in mice confirm that primitive hematopoietic stem/progenitor cells from both sources have comparable engraftment and multilineage differentiation potential. Altogether, our analyses reveal that the differential behavior after gene therapy of hematopoietic stem/progenitor cells derived from either bone marrow or mobilized peripheral blood is mainly due to the distinct cell composition rather than functional differences of the infused cell products, providing new frames of references for clinical interpretation of hematopoietic stem/progenitor cell transplantation outcome.</p

Prevalence of hypertension and correlation with mental health in women with burning mouth syndrome: A case-control study

BackgroundThe relationship between hypertension (HTN) and chronic pain is still a matter of debate, and its prevalence in patients with burning mouth syndrome (BMS) has never been evaluated. This study aimed to assess the prevalence of HTN in women with BMS and to evaluate its relationship with potential predictors such as risk factors for cardiovascular diseases, pain, and mental health status analyzing differences with healthy women.MethodsIn total, 250 women with BMS (WBMS) were prospectively recruited and compared with an equal number of healthy women (HW) matched for age. Education, body mass index, smoke and alcohol consumption, intensity and quality of pain, and psychological profile were further investigated to identify the potential predictors of HTN. Specifically, pain assessment [the Numeric Rating Scale (NRS) and Short-Form McGill Pain Questionnaire (SF-MPQ)] and psychological assessment [Hamilton Rating Scale for Depression and Anxiety (HAM-D and HAM-A), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS)] was carried out for the participants.ResultsHTN was found in 128 (51.2%) WBMS and 76 (30.4%) HW (p &lt; 0.001**). The scores of the NRS, SF-MPQ, HAM-D, HAM-A, and PSQI were statistically significantly higher in the WBMS than in the HW (p &lt; 0.001**). A strongly linear correlation between HTN and employment status, systemic diseases, and education level (p &lt; 0.001**) was found in WBMS, while a strong correlation between HTN and employment status, hypercholesterolemia, systemic diseases, and drug consumption was found in HW (p &lt; 0.001**). No statistically significant correlation was found between HTN and pain, anxiety, depression, and sleep disturbances.ConclusionThese results suggest that WBMS showed a higher prevalence of HTN compared with controls. Unemployed WBMS with lower education and other systemic comorbidities are at an increased risk of developing HTN. HTN is associated with alteration in the vascular structure and function of the brain, and these processes accelerate brain aging, which contributes to a reduction in intracortical connectivity, thus affecting the modulatory system of control of pain in patients with BMS, independently of their mental health assessment. Predictors that may underlie this association remain unclear, taking into account the differences found in HW, and should be further elucidated

Anxiety and depression in keratotic oral lichen planus: a multicentric study from the SIPMO

Objectives: Oral lichen planus with exclusive keratotic reticular, papular, and/or plaque-like lesions (K-OLP) is a clinical pattern of OLP that may be associated with a complex symptomatology and psychological alteration. The aim of the study was to evaluate the prevalence of anxiety (A) and depression (D) in patients with K-OLP, analyzing the potential predictors which can affect mental health status. Methods: Three hundred K-OLP patients versus 300 healthy controls (HC) were recruited in 15 Italian universities. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), and Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A) were administered. Results: The K-OLP patients showed statistically higher scores in the NRS, T-PRI, HAM-D, and HAM-A compared with the HC (p-value < 0.001**). A and D were found in 158 (52.7%) and 148 (49.3%) K-OLP patients. Strong linear correlations were identified between HAM-A, HAM-D, NRS, T-PRI, and employment status and between HAM-D, HAM-A, NRS, T-PRI, employment status, and female gender. Multivariate logistic regression revealed that HAM-D and HAM-A showed the greatest increase in the R2 value for A and D in the K-OLP patients, respectively (DR2 = 55.5% p-value < 0.001**; DR2 = 56.5% p-value < 0.001**). Conclusions: The prevalence of A and D is higher in the K-OLP patients compared with the HC, also found in K-OLP subjects without pain, suggesting that the processing of pain may be in a certain way independent of the processing of mood. Clinical relevance: Mood disorders and pain assessment should be carefully performed in relation to K-OLP to obtain a complete analysis of the patients

Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound-detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross-sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, -0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40-ligand (P = 0.0238), soluble Nox2-derived peptide (sNox2-dp; P &lt; 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD4OL (Spearman's rank correlation coefficient [r(s)], -0.33; P &lt; 0.001), sNox2-dp (r(s), -0.57; P &lt; 0.0001), and urinary excretion of isoprostanes (r(s), -0.48; P &lt; 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2-dp, and urinary 8-iso prostaglandin F2 alpha-III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2-dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015

Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defi ned criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specifi c DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI).Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defi ned criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specifi c DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI)