Enhancing the Anti-Erosive Properties of Fluoride and Stannous with the Polymer Carbopol.

This in vitro study investigated whether Carbopol 980 polymer could potentiate the anti-erosive effect of solutions containing sodium fluoride (F) and sodium fluoride associated with stannous chloride (FS). The dissolution of hydroxyapatite treated with the experimental solutions (F [500 ppm F-], F + Carbopol [0.1%], FS [500 ppm F- + 800 ppm Sn2+], FS + Carbopol) was evaluated. Deionized water was the negative control, and a commercial mouth rinse (AmF/NaF/SnCl2; 500 ppm F + 800 ppm Sn2+; Elmex® Erosion Protection) was the positive control. The solutions were also evaluated in an erosion-rehardening protocol, with two treatments per day, using bovine enamel specimens (n = 15) and human saliva. The acid challenge was performed using 0.3% citric acid (pH 2.6) for 2 min. Microhardness was measured at different times: baseline, after the first erosive challenge, after treatment, and after the second erosive challenge. Based on microhardness values, the demineralization, rehardening, and protective potentials were calculated. The alkali-soluble fluoride on enamel surfaces was also measured. Data were analyzed using ANOVA and Tukey tests (α = 0.05). Groups treated with FS + Carbopol showed the lowest hydroxyapatite dissolution and the highest rehardening and protective potentials. The measurement of alkali-soluble fluoride on enamel surfaces was also higher in the FS + Carbopol group. Carbopol was able to significantly increase the protective effect of the fluoridated solutions in addition to optimizing the adsorption of fluoride on the enamel surface.

A 2-year clinical evaluation of direct and semi-direct resin composite restorations in non-carious cervical lesions: a randomized clinical study.

OBJECTIVES: The purpose of this study was to evaluate the 2-year success of resin composite restorations in non-carious cervical lesions (NCCLs) using the direct or semi-direct techniques. MATERIALS AND METHODS: Thirty volunteers presenting with at least two NCCLs were included. Each participant received one restoration using the direct technique and the other using the semi-direct technique, totaling 60 restorations. Time for completing the treatment was computed. Assessments at baseline, 7 days, and 6, 12, and 24 months were performed using the modified United States Public Health Service criteria. Descriptive analysis was reported as a percentage of successful treatments. For inferential analysis, the Student t test was used to evaluate the differences between extension, depth, and time. The chi-square/Fisher tests were used to compare treatment success after each period (α = 0.05). The results were evaluated by using the Kaplan-Meier survival analysis. RESULTS: Differences were detected regarding mean ± standard deviation time, in which direct and semi-direct procedures were accomplished in 21.8 (± 14.5) and 35.3 (± 19.9) min, respectively. Of the 60 restorations placed, 7 failed in the direct group while 8 failed in the semi-direct group up to 2 years. No differences were detected between restorative protocols. The cumulative survival was 88.5% and 88.4% for the direct technique and semi-direct techniques after 24 months, respectively. CONCLUSION: The tested restorative protocols present similar results for NCCLs within the studied periods. CLINICAL RELEVANCE: The semi-direct technique exhibited clinical performance similar to direct technique for NCCL, demonstrating an alternative for restorations of these lesions.

Influence of Surfactants and Fluoride against Enamel Erosion.

This study investigated the effect of surfactants associated with sodium fluoride (NaF) on enamel erosion prevention, using an erosion-remineralization in vitro model. Sodium lauryl sulfate (SLS), polysorbate 20 (P20), and cocoamidopropyl betaine (CAPB) were tested, at concentrations of 1.0 and 1.5%, and associated or not with NaF (275 ppm). The control groups were distilled water and the NaF solution. Bovine enamel samples (n = 12) were prepared and submitted to a 5-day cycling model: acid challenge (0.3% citric acid, pH 2.6, 4×/day), human saliva (2 h, 4×/day), and the treatment solutions (2 min, 2×/day). The protective potential of the agents against initial erosion was assessed by microhardness and the surface loss by profilometry. Enamel surface wettability was determined by goniometry, protein adsorption was measured by spectroscopy (FTIR), and the KOH-soluble fluoride was quantified. Goniometry showed that SLS and CAPB increased enamel wettability. No differences were found among the surfactants regarding protein adsorption. Microhardness showed that SLS reduced NaF protection. P20 (1 and 1.5%) and CAPB 1.5% presented a protective effect, but lower than the NaF solution. Profilometry showed that CAPB protected enamel, but no agent associated with NaF promoted a higher protection than the NaF solution alone. KOH-soluble fluoride analysis showed that all surfactants reduced the fluoride adsorption on the enamel surface. Therefore, the surfactants tested (except for P20) changed the enamel surface energy. The SLS decreased the protective potential of NaF on initial erosion, but no tested agent interfered with the protective effect of NaF on enamel erosive wear.

Predictors for Permanent Discontinuation of Systemic Immunosuppression in Severely Affected Chronic Graft-Versus-Host Disease Patients.

Predicting the duration of systemic therapy in patients with chronic graft-versus-host disease (cGVHD) is of critical clinical importance when counseling patients and for treatment planning. cGVHD characteristics associated with this outcome have not been studied in severely affected patients. The National Institutes of Health (NIH) cGVHD scoring provides a standardized set of organ severity measures that could represent clinically useful and reproducible predictive characteristics. We analyzed 227 previously treated patients most with moderate (n = 54) or severe (n = 170) cGVHD defined by NIH criteria who were prospectively enrolled in a natural history protocol (NCT00092235). Patients received a median of 4 prior systemic therapy regimens and were seen at the NIH for a single time-point visit and were then monitored for survival and ability to discontinue cGVHD systemic therapy. With a median follow-up of 71.1 months, the cumulative incidence of systemic therapy discontinuation was 9.5% (95% confidence interval, 6.0% to 13.9%) at 2 years and 27.7% (95% confidence interval, 20.9% to 34.8%) by 5 years after the initial visit. Factors associated with a higher incidence of immunosuppression discontinuation included lower NIH global severity (P = .019) and lung (P = .030) scores and less extensive deep sclerosis (<37% body surface area, P = .024). Lower patient- and clinician-reported 0 to 10 severity NIH scores and noncyclosporine prophylaxis regimens were also associated with higher incidence of immunosuppression discontinuation (P <.05). In conclusion, we found low success rates for immune suppression discontinuation in previously treated patients who were severely affected with cGVHD. NIH scoring and clinical measures provide new standardized disease-specific tools to predict discontinuation of systemic therapy.

Adhesive Systems as an Alternative Material for Color Masking of White Spot Lesions: Do They Work?

PURPOSE: To evaluate the color masking effect of infiltration treatment of artificial white spot lesions (AWSL) using a dedicated resin in comparison to different adhesive systems. MATERIALS AND METHODS: Enamel/dentin specimens were obtained from bovine incisors and baseline color was assessed using a reflectance spectrophotometer, according to the CIE L*a*b* system. AWSL were produced using a buffered acid solution and a new color evaluation was performed. The specimens were divided into 8 groups: control: artificial saliva changed daily for 7 days; IC: infiltrating resin Icon; EC: EquiaCoat; FU: Futurabond U; SBU: Single Bond U; SBMP: Scotchbond MP; OB: OptibondFL; BF: Bioforty. After the treatments, the color was evaluated again and the values for the parameters ΔL (change in lightness), Δa (change in chroma), Δb (change in hue), and ΔE (general color difference) were calculated in relation to baseline. Data were analyzed by one-way ANOVA and Tukey's tests. RESULTS: After treatment, ANOVA showed significant differences for all parameters (p = 0.001). Tukey's test showed the greatest lightness reduction (ΔL) for the IC group, followed by EC, FU, and SBU. The SBMP, OB, and BF groups were similar to the control. For Δb values, all groups showed differences in relation to the control, with no differences between them. In relation to ΔE, all groups showed differences in relation to the control (ΔE = 5.24), with no significant differences between them. ΔE values after application of all resinous materials were lower than the threshold of 3.7, indicating effective color masking. CONCLUSIONS: The Icon infiltrant produced a greater lightness reduction of white lesions (ΔL). For general color difference (ΔE), all the resinous materials tested were able to color mask artificial AWSL.

Clinical significance of autoantibodies in a large cohort of patients with chronic graft-versus-host disease defined by NIH criteria.

There is an unmet need for identifying new clinical biomarkers in chronic Graft-versus-Host-disease (cGVHD) suitable for diagnosis and disease monitoring. Circulating autoantibodies represent an ongoing immune response and suggest a pathogenic role for B cells in cGVHD. Autoantibodies could be useful markers of cGVHD disease activity, severity, or organ specificity; however, their clinical utility is not established. The focus of this study was to determine the incidence and associations of a broad array of clinical autoantibodies with cGVHD manifestations in a large patient cohort characterized by NIH criteria. A panel of 21 circulating antibodies commonly used in clinical medicine was tested in 280 cGVHD patients (70% severe) enrolled in a cross-sectional prospective natural history study. Median cGVHD duration was two years. Patients with circulating autoantibodies (62%) had significantly higher levels of IgM (P < 0.0001), IgG (P < 0.0001), and IgA (P = 0.001), elevated uric acid (P = 0.008) and total protein (P = 0.0004), and higher numbers of CD3+ (P = 0.002), CD4+ (P = 0.001), CD8+ (P = 0.023) T cells, and CD19+ B cells (P < 0.0001). Multiple antibodies were detected in 35% of patients. Prior rituximab therapy (n = 66) was associated with reduced presence of autoantibodies (48 vs. 66% P = 0.01). Only oral cGVHD was significantly associated with presence of autoantibodies in this study (P = 0.028). No significant associations were found between cGVHD activity and severity, and presence of autoantibodies. Circulating autoantibodies are common in patients with advanced cGVHD. Their presence is associated with better quantitative immunologic reconstitution but does not have utility as a clinical biomarker of cGVHD.

Costimulated tumor-infiltrating lymphocytes are a feasible and safe alternative donor cell therapy for relapse after allogeneic stem cell transplantation.

Donor lymphocyte infusion (DLI), a standard relapse treatment after allogeneic stem cell transplantation (AlloSCT), has limited efficacy and often triggers GVHD. We hypothesized that after AlloSCT tumor-infiltrating donor lymphocytes could be costimulated ex vivo to preferentially activate/expand antitumor effectors. We tested the feasibility and safety of costimulated, tumor-derived donor lymphocyte (TDL) infusion in a phase 1 trial. Tumor was resected from 8 patients with B-cell malignancy progression post-AlloSCT; tumor cell suspensions were costimulated with anti-CD3/anti-CD28 Ab-coated magnetic beads and cultured to generate TDL products for each patient. Costimulation yielded increased proportions of T-bet(+)FoxP3(-) type 1 effector donor T cells. A median of 2.04 × 10(7) TDL/kg was infused; TDLs were well tolerated, notably without GVHD. Two transient positron emission tomography (PET) responses and 2 mixed responses were observed in these refractory tumors. TDL are a feasible, tolerable, and novel donor cell therapy alternative for relapse after AlloSCT.

Influence of Light-Curing Time and Increment Thickness on the Properties of Bulk Fill Composite Resins With Distinct Application Systems.

The objective of this study was to evaluate the influence of light-curing time and increment thickness on the microhardness and degree of conversion (DC) of bulk fill composite resins with different application systems. Translucency parameter (TP) was also measured. Specimens of resin composites were prepared in a circular matrix using a single increment with different thicknesses (2, 4, and 6 mm) and light-cured with distinct times (10, 20, and 40 s). The materials tested (n = 5 pergroup) were Filtek One (FO) bulk fill, Tetric N-Ceram (TC) bulk fill, SonicFill 3 (SF), VisCalor (VC) bulk. After 24 h, Knoop microhardness (KN) was measured, and the bottom/top ratio (B/Tratio) was calculated. The DC was measured using Fourier transformed infrared (FTIR) spectroscopy. The TP was assessed in additional specimens with 1 mm thick (n = 5). The data were statistically analyzed with analysis of variance (ANOVA) and Tukey's tests (5%). Significant differences were observed for all factors, for both B/Tratio and DC (p < 0.05). The higher increment thickness and the lower curing times resulted in lower B/Tratio and DC means. The VC and TC resins exhibited the overall higher B/Tratio, and the highest TP. SF presented the lowest values of B/Tratio and DC, with compromised polymerization at 6 mm depth. TP (means ± SD) were FO (12.85 ± 1.0)1, SF (15.62 ± 0.73)2, TC (20.32 ± 0.49)3, and VC (20.53 ± 0.73)3. We concluded that the greater the thickness of the increment, the lower the DC. Higher light curing times resulted on increased DC of the tested composites. The higher translucent materials VC and TC showed the greater B/Tratio; and FO resin exhibited the higher DC values.

Flowable bulk-fill versus layering restorative material on Class II restorations: A randomized clinical trial.

OBJECTIVE: This study evaluated the clinical performance of Class II restorations made with flowable bulk-fill base versus conventional layering ORMOCER-based restorative material in a split-mouth randomized clinical trial. METHODS: Thirty patients received two class II restorations (n = 60) performed with different strategies. All preparations received the application of the universal self-etching adhesive system according to the manufacturer's recommendation, followed by the placement of a sectional matrix, wooden wedge, and separation ring. The first restoration was performed using 4 mm of flowable bulk-fill material covered by 2 mm of conventional viscosity restorative material (Bulk-fill technique). The second restoration was performed only with the conventional viscosity material, with a maximum of 2 mm thick increments, up to fill the cavity (Layering technique). After occlusal adjustment, the same polishing system was used for all restorations. Evaluations using the FDI criteria were conducted after 7 days, 12, and 24 months. Data were analyzed with the Fisher's Exact test (α=0.05). RESULTS: From 30 participants, 24 attended the 24-month recall, and 48 restorations were evaluated. All restorations received acceptable overall scores for esthetic and biological properties after this period, while only 6.66 % of the restorations exhibited unacceptable overall scores for the functional properties in both groups. No significant differences between the tested restorative materials and techniques were found for each FDI criterion assessed. The success rate after 2 years was 93.33 % for both groups. CONCLUSION: Both restorative materials exhibited good clinical performance for the parameters analyzed with no differences between them after 24-month follow-up. CLINICAL RELEVANCE: Flowable bulk-fill ORMOCER-based material is a suitable alternative for direct Class II restorations, providing good clinical outcomes and simplifying the restorative procedure. CLINICAL TRIAL REGISTRATION NUMBER: RBR-6mvp9w.

National Institutes of Health chronic graft-versus-host disease staging in severely affected patients: organ and global scoring correlate with established indicators of disease severity and prognosis.

Between 2004 and 2010, 189 adult patients were enrolled on the National Cancer Institute's cross-sectional chronic graft-versus-host disease (cGVHD) natural history study. Patients were evaluated by multiple disease scales and outcome measures, including the 2005 National Institutes of Health (NIH) Consensus Project cGVHD severity scores. The purpose of this study was to assess the validity of the NIH scoring variables as determinants of disease severity in severely affected patients in efforts to standardize clinician evaluation and staging of cGVHD. Out of 189 patients enrolled, 125 met the criteria for severe cGVHD on the NIH global score, 62 of whom had moderate disease, with a median of 4 (range, 1-8) involved organs. Clinician-assigned average NIH organ score and the corresponding organ scores assigned by subspecialists were highly correlated (r = 0.64). NIH global severity scores showed significant associations with nearly all functional and quality of life outcome measures, including the Lee Symptom Scale, Short Form-36 Physical Component Scale, 2-minute walk, grip strength, range of motion, and Human Activity Profile. Joint/fascia, skin, and lung involvement affected function and quality of life most significantly and showed the greatest correlation with outcome measures. The final Cox model with factors jointly predictive for survival included the time from cGVHD diagnosis (>49 versus ≤49 months, hazard ratio [HR] = 0.23; P = .0011), absolute eosinophil count at the time of NIH evaluation (0-0.5 versus >0.5 cells/µL, HR = 3.95; P = .0006), and NIH lung score (3 versus 0-2, HR = 11.02; P < .0001). These results demonstrate that NIH organs and global severity scores are reliable measures of cGVHD disease burden. The strong association with subspecialist evaluation suggests that NIH organ and global severity scores are appropriate for clinical and research assessments, and may serve as a surrogate for more complex subspecialist examinations. In this population of severely affected patients, NIH lung score is the strongest predictor of poor overall survival, both alone and after adjustment for other important factors.

Prospective Phase II Trial of Montelukast to Treat Bronchiolitis Obliterans Syndrome after Hematopoietic Cell Transplantation and Investigation into Bronchiolitis Obliterans Syndrome Pathogenesis.

Bronchiolitis obliterans syndrome (BOS) is a severe manifestation of chronic graft-versus-host disease (cGVHD) following hematopoietic cell transplantation (HCT). Montelukast interrupts cysteinyl leukotriene (CysLT) activity and may diminish the activation and homing of cells to bronchioles and subsequent fibrosis. We performed a prospective phase II trial to test whether montelukast altered lung decline for patients with BOS after HCT. In this single-arm, open-label, multi-institutional study, the primary endpoints were stability or improvement (<15% decline) in forced expiratory volume in 1 second (FEV1) and a <1-point decline in the slope of FEV1 after 6 months of treatment. Secondary endpoints included symptom and functional responses and immune correlates investigating the role of leukotrienes in BOS progression. The study enrolled 25 patients with moderate to severe lung disease after 3 months of stable cGVHD therapy. Montelukast was well tolerated, and no patient required escalation of BOS-directed therapy. At the primary endpoint, all 23 evaluable patients met the criteria for treatment success using FEV1% predicted, and all but 1 patient had stable or improved FEV1 slope. In those with a >5% improvement in FEV1, clinically meaningful improvements were seen in the Lee scores of breathing, energy, and mood. Improvements in the Human Activity Profile and 6-minute-walk test were observed in those with a <5% decline in FEV1. Overall survival was 87% at 2 years. Immune correlates showed elevated leukotriene receptor levels on blood eosinophils and monocytes versus healthy controls, elevated urine leukotrienes in 45% of the cohort, and CysLT receptors in bronchoalveolar lavage subsets and a predominance of Th2 cells, all pretreatment. These data suggest that montelukast may safely halt the progression of BOS after HCT, and that leukotrienes may play a role in the biology of BOS.

Protection of calcium silicate/sodium phosphate/fluoride toothpaste with serum on enamel and dentin erosive wear.

OBJECTIVE: To evaluate the effect of a toothpaste containing calcium silicate/sodium phosphate/fluoride associated or not to the boost serum (BS) against erosive tooth wear (ETW) on enamel and dentin. METHODOLOGY: Bovine enamel and dentin specimens were subjected to an erosion-abrasion cycling model (1% citric acid - pH 3.6 -2 min / artificial saliva - 60 min, 4×/day, 5 days). Toothbrushing was performed for 15 s (2 min exposed to slurry), 2×/day, with the toothpastes (n=10): control without fluoride (Weleda), Arg/Ca/MFP (Colgate Pro-Relief), Si/PO4/MFP (Regenerate-Unilever), and Si/PO4/MFP/BS (Si/PO4/MFP with dual BS - Advanced Enamel Serum-Unilever). The effect of treatments on the eroded tissues was assessed by surface microhardness in the first day, and surface loss (SL) resulting from ETW was evaluated by profilometry (µm) after three and five days. Additional dentin specimens (n=5/group) were subjected to 20,000 brushing cycles to verify the abrasivity of the toothpastes. Data were subjected to ANOVA and correlation tests (5%). RESULTS: For enamel, no difference in microhardness was observed among the treated groups, and similar SL was obtained after 5 days. For dentin, Si/PO4/MFP/BS resulted in higher microhardness values, but none of the groups presented significantly lower SL than the control. There was no significant correlation between SL and abrasiveness. CONCLUSION: The calcium silicate/sodium phosphate toothpaste and serum increased microhardness of eroded dentin, but they did not significantly reduce enamel and dentin loss compared to the non-fluoride control toothpaste. The abrasiveness of the toothpastes could not predict their effect on ETW.

Hematopoietic Cell Transplantation and Outcomes Related to Human Papillomavirus Disease in GATA2 Deficiency.

GATA2 deficiency is a bone marrow failure syndrome effectively treated with hematopoietic cell transplantation (HCT), which also addresses the predisposition to many infections (prominently mycobacterial). However, many GATA2-deficient persons who come to HCT also have prevalent and refractory human papilloma virus disease (HPVD), which can be a precursor to cancer. We analyzed 75 HCT recipients for the presence of HPVD to identify patient characteristics and transplantation results that influence HPVD outcomes. We assessed the impact of cellular recovery and iatrogenic post-transplantation immunosuppression, as per protocol (PP) or intensified/prolonged (IP) graft-versus-host disease (GVHD) prophylaxis or treatment, on the persistence or resolution of HPVD. Our experience with 75 HCT recipients showed a prevalence of 49% with anogenital HPVD, which was either a contributing or primary factor in the decision to proceed to HCT. Of 24 recipients with sufficient follow-up, 13 had resolution of HPVD, including 8 with IP and 5 with PP. Eleven recipients had persistent HPVD, including 5 with IP and 6 with PP immunosuppression. No plausible cellular recovery group (natural killer cells or T cells) showed a significant difference in HPV outcomes. One recipient died of metastatic squamous cell carcinoma, presumably of anogenital origin, at 33 months post-transplantation after prolonged immunosuppression for chronic GVHD. Individual cases demonstrate the need for continued aggressive monitoring, especially in the context of disease prevalent at transplantation or prior malignancy. HCT proved curative in many cases in which HPVD was refractory and recurrent prior to transplantation, supporting a recommendation that HPVD should be considered an indication rather than contraindication to HCT, but post-transplantation monitoring should be prolonged with a high level of vigilance for new or recurrent HPVD.

Salivary gland involvement in chronic graft-versus-host disease: prevalence, clinical significance, and recommendations for evaluation.

Although xerostomia is a commonly reported complaint in patients with chronic graft-versus-host disease (cGVHD), criteria for evaluating the prevalence and characteristics of salivary gland involvement have not been well defined in this patient population. Previous studies also have made no distinction between salivary and mucosal oral cGVHD. We systematically evaluated signs and symptoms of sicca in a large cohort of patients with cGVHD (n = 101) using instruments widely used to study Sjogren's syndrome. Xerostomia was reported in 60 (77%) patients reporting ocular and 52 (67%) patients reporting oral complaints [corrected]. The salivary flow rate was < or =0.2 mL/min in 27%, and < or =0.1 mL/min in 16%. Histopathological changes, consisting of mononuclear infiltration and/or fibrosis/atrophy, were present in all patients with salivary dysfunction. Importantly, there was no correlation of salivary and oral mucosal involvement in cGVHD. Patients with cGVHD-associated salivary gland involvement had diminished oral cavity-specific quality of life and lower body mass index. Salivary gland involvement is a common and clinically distinct manifestation of cGVHD. Formal evaluation of salivary function using standardized criteria is needed, and this could be incorporated as an outcome measure in clinical trials of cGVHD.

Spiritual well-being in long-term survivors with chronic graft-versus-host disease after hematopoietic stem cell transplantation.

Spiritual well-being (Sp-WB) is a resource that supports adaptation and resilience, strengthening quality of life (QOL) in patients with cancer or other chronic illnesses. However, the relationship between Sp-WB and QOL in patients with chronic graft-versus-host disease (cGVHD) remains unexamined. Fifty-two participants completed the Functional Assessment of Chronic Illness Therapy-Spiritual WellBeing (FACIT-Sp) questionnaire as part of a multidisciplinary study of cGVHD. Sp-WB was generally high. Those with the lowest Sp-WB had a significantly longer time since diagnosis of cGVHD (P = 0.05) than those with higher Sp-WB. There were no associations between Sp-WB and demographics, cGVHD severity, or intensity of immunosuppression. Participants with the lowest Sp-WB reported inferior physical (P = 0.0009), emotional (P = 0.003), social (P = 0.027), and functional well-being (P < 0.0001) as well as lower overall QOL (P < 0.0001) compared with those with higher Sp-WB. They also had inferior QOL relative to population norms. Differences between the group reporting the lowest Sp-WB and those groups who reported the highest Sp-WB scores consistently demonstrated a significant difference for all QOL subscales and for overall QOL. Controlling for physical, emotional, and social well-being, Sp-WB was a significant independent predictor of contentment with QOL. Our results suggest that Sp-WB is an important factor contributing to the QOL of patients with cGVHD. Research is needed to identify factors that diminish Sp-WB and to test interventions designed to strengthen this coping resource in patients experiencing the late effects of treatment.

Randomized in situ trial on the efficacy of Carbopol in enhancing fluoride / stannous anti-erosive properties.

OBJECTIVE: To evaluate if the bioadhesive polymer (Carbopol 980) could potentiate the protective effect of sodium fluoride with stannous chloride (FS) solution on the control of enamel erosive wear. METHODS: Cylindrical bovine enamel specimens were polished and randomly allocated into three groups (n = 60): FS (500 ppm F- +800 ppm Sn2+ - positive control), FS + Carbopol (0.1% Carbopol), and ultrapure water (negative control). A randomized double-blind cross-over in situ model with three phases was used. In each phase, volunteers (n = 15) used a palatal appliance containing 4 specimens: two were submitted to an erosion model (2 h of pellicle formation; immersion in 1% citric acid, pH 2.3, for 5 min, 4x/day; 1 h intervals of saliva exposure; and treatment with the test solutions for 1 min, 2x/day). Besides erosion, the other two specimens were also subjected to abrasion (2x/day, 15 s) with active electric toothbrush, before the treatment with the solutions. After 5 days, enamel surface loss (µm) was evaluated by profilometry. Data were analyzed by two-way RM-ANOVA and Tukey tests (5%). RESULTS: There were significant differences for both challenge and treatment factors. Erosion/abrasion challenge resulted in significantly higher enamel loss than erosion only (p < 0.05). The surface loss values for the erosion/remineralization model were (means ±â€¯SL): C = 14.7 ±â€¯5.8b; FS = 9.0 ±â€¯7.5ab; FS + Carbopol = 5.9 ±â€¯3.8a; and for erosion/abrasion: C = 26.6 ±â€¯10.1c; FS = 15.0 ±â€¯8.8b; FS + Carbopol = 12.3 ±â€¯7.9ab. CONCLUSION: The association of Carbopol to the FS solution significantly protected the enamel against erosive wear, but it was not significantly superior to FS only. CLINICAL SIGNIFICANCE: Under highly erosive and abrasive conditions, rinsing with solutions containing sodium fluoride plus stannous chloride, associated or not with the Carbopol polymer, is an effective approach to control enamel erosive wear.

A Panoply of Rheumatological Manifestations in Patients with GATA2 Deficiency.

PURPOSE: To characterize rheumatological manifestations of GATA2 deficiency. METHODS: Single-center, retrospective review of 157 patients with GATA2 deficiency. Disease course, laboratory results, and imaging findings were extracted. In-person rheumatological assessments were performed on selected, available patients. A literature search of four databases was conducted to identify additional cases. RESULTS: Rheumatological findings were identified in 28 patients, out of 157 cases reviewed (17.8%). Twenty-two of those patients (78.6%) reported symptom onset prior to or in conjunction with the molecular diagnosis of GATA2 deficiency. Notable rheumatological manifestations included: piezogenic pedal papules (PPP), joint hyperextensibility, early onset osteoarthritis, ankylosing spondylitis, and seronegative erosive rheumatoid arthritis. In peripheral blood of patients with rheumatological manifestations and GATA2 deficiency, CD4+ CD3+ helper T cells and naïve CD3+ CD4+ CD62L+ CD45RA+ helper T cell subpopulation fractions were significantly lower, while CD8+ cytotoxic T cell fractions were significantly higher, compared to those without rheumatological manifestations and with GATA2 deficiency. No changes in CD19, CD3, or NK populations were observed. CONCLUSION: GATA2 deficiency is associated with a broad spectrum of rheumatological disease manifestations. Low total helper T lymphocyte proportions and low naïve helper T cell proportions are associated with those most at risk of overt rheumatological manifestations. Further, PPP and joint hyperextensibility may explain some of the nonimmunologically-mediated joint problems encountered in patients with GATA2 deficiency. This catalogue suggests that rheumatological manifestations and immune dysregulation are relatively common in GATA2 deficiency.

Strategies to improve long-term outcome in stage IIIB inflammatory breast cancer: multimodality treatment including dose-intensive induction and high-dose chemotherapy.

Inflammatory breast cancer (IBC) is a rare clinicopathologic entity with a poor prognosis, lagging far behind any other form of nonmetastatic breast cancer. Since the advent of systemic chemotherapy over 35 years ago, only minimal progress has been made in long-term outcome. Although multiple randomized trials of high-dose chemotherapy and autologous progenitor cell transplantation (ASCT) for the treatment of breast cancer have yielded disappointing results, these data are not necessarily relevant to IBC, a distinct clinical and pathologic entity. Therefore, the optimal multimodality therapy for IBC is not well established, and remains unsatisfactory. We treated 21 women with nonmetastatic IBC with a multimodality strategy including high-dose melphalan (Mel)/etoposide and ASCT. The treatment was overall tolerated with acceptable morbidity, and no post-ASCT 100-day mortality. With a median potential follow-up of approximately 8 years, the estimated progression-free survival (PFS), event-free survival (EFS), and overall survival (OS) at 6 years from on-study date are: 67%, 55%, and 69%, respectively. These results from a small phase II study are among the most promising of mature outcome data for IBC. They strongly suggest, along with results of several already published phase II trials, that ASCT could play a significant role in the first line treatment of IBC.

GATA2 Deficiency: Early Identification for Improved Clinical Outcomes.

BACKGROUND: Patients with GATA2 deficiency present with nontuberculous mycobacterial infections, severe viral infections (particularly refractory human papillomavirus disease), lymphedema, myelodysplastic syndrome (MDS), and acute myeloid leukemia. Patients with GATA2 deficiency who undergo allogeneic hematopoietic stem cell transplantation prior to the development of life-threatening infections or cytogenetic abnormalities may have optimal clinical outcomes. OBJECTIVES: The aim of this article is to determine ways in which oncology nurses can identify GATA2 deficiency in patients early and optimize treatment decisions. METHODS: A case study is presented of a 33-year-old man with recurrent infections and MDS and his two sons, all of whom were found to have the same GATA2 mutation. FINDINGS: Oncology nurses play an important role in early detection and identification by interviewing patients and obtaining a complete and thorough family history.