Optimization and validation of in vivo flow cytometry chimeric antigen receptor T cell detection method using CD19his indirect staining.

CD19-targeted chimeric antigen receptor T (CAR-T) cell therapy has shown unprecedented results in patients with B cell relapsed/refractory acute lymphoblastic leukemia (R/R-ALL) and B cell non-Hodgkin lymphomas where no other curative options are available. In vivo monitoring of CAR-T cell kinetics is fundamental to understand the correlation between CAR-T cells expansion and persistence with treatment response and toxicity development. The aim of this study was to define a robust, sensitive, and universal method for CAR-T cell detection using flow cytometry. We set up and compared with each other three assays for CD19 CAR-T cell detection, all based on commercially available reagents. All methods used a recombinant human CD19 protein fragment recognized by the single-chain variable fragment of the CAR construct. The two indirect staining assays (CD19his + APC-conjugated antihistidine antibody and CD19bio + APC-conjugated antibiotin antibody) showed better sensitivity and specificity compared with the direct staining with CD19-FITC, and CD19his had a better cost-effective profile. We validated CAR detection with CD19his with parallel quantitative real-time polymerase chain reaction data and we could demonstrate a strong positive correlation. We also showed that CD19his staining can be easily included in a multicolor flow cytometry panel to achieve additional information about the cell phenotype of CAR-T cell positive subpopulations. Finally, this method can be used for different anti-CD19 CAR-T cell products and for different sample sources. These data demonstrate that detection of CAR-T cells by CD19his flow cytometry staining is a reliable, robust, and broadly applicable tool for in vivo monitoring of CAR-T cells.

Long-term effects produced by early treatment of Class III malocclusion with rapid maxillary expansion and facemask followed by fixed appliances: A multicentre retro-prospective controlled study.

OBJECTIVE: To assess the short- and long-term dentoskeletal effects of early Class III treatment with rapid maxillary expansion and facemask (RME/FM) followed by fixed appliances. MATERIALS AND METHODS: A total of 44 patients (27 females, 17 males) treated consecutively with RME/FM were included from the archives of 3 centres. Three lateral cephalograms were available: T0 (before the start of RME/FM therapy, mean age 8.1 ± 1.8 years), T1 (immediately after RME/FM, mean age 9.8 ± 1.6 years), and T2 (long-term observation, mean age 19.5 ± 1.6 years). A control group of 17 untreated Class III subjects (12 females and 5 males) also was selected. Between-group statistical comparisons were performed with ANCOVA. RESULTS: No statistically significant differences for any of the cephalometric variables were found at T0. In the short term, the treated group showed significant improvements in ANB (+2.9°), Wits appraisal (+2.7 mm), SNA (+1.8°) and SNB (-1.1°). A significant closure of CoGoMe angle (-1.3°) associated with smaller increments along Co-Gn (-2.4 mm) also was found together with a significant increase in intermaxillary divergence (+1.3°). In the long-term, significant improvements in ANB (+2.6°), Wits appraisal (+2.7 mm) and SNB (-1.7°) were recorded together with a significant closure of the CoGoMe angle (-2.9°). No significant long-term changes in vertical skeletal relationships were found. CONCLUSIONS: RME/FM therapy was effective in improving Class III dentoskeletal relationships in the short term. These changes remained stable in the long-term due mainly to favourable mandibular changes.

Predictability of expansion movements performed by clear aligners in mixed dentition in both arches: a retrospective study on digital casts.

BACKGROUND: to evaluate the predictability of expansion achieved in patients in early mixed dentition treated with Clear Aligners (CA), analyzing the efficiency of the expansion at the end of the first set of aligners and at the end of the therapy in the upper and lower arch. METHODS: 36 patients (20 F, 16 M; mean age 8.3 ± 1.5 years) were selected retrospectively from the Department of Orthodontics of the Hospital of Rome "Tor Vergata". All subjects were treated with CA with no other auxiliaries than attachments. For each patient a standardized sequential expansion protocol was planned for both arches. Digital dental casts were created at three observation periods from an intraoral scanner: prior to treatment (T0), at the end of the first set of aligners (T1), at the end of treatment (T2). The 3D models in planned position determined by the first Clincheck (CC) were obtained for comparison with T1 and T2. Six linear transversal measurements were used to evaluate the dimensional changes and the predictability of expansion movements, comparing T1-CC and T2-CC. RESULTS: a statistically significant increase within the pre-treatment and the final outcomes for all the variables examined was found. In the upper arch, the greatest level of predictability was detected at the level of the first (46.44%) and second deciduous molar width (44.95%) at T1. The analysis of T2-CC changes showed a significant increase in the percentage of predictability of expansion at the level of the first permanent molars, at mesial (54.86%) and distal (58.92%) width. In the lower arch, a higher percentage of predictability than the upper arch was reported at T1-CC and T2-CC, with the greatest values at the level of second (T1-CC: 48.70%; T2-CC: 75.32%) and first deciduous molar width (T1-CC: 45.71%; T2-CC: 72.75%). CONCLUSIONS: CA can induce significant transversal increments. The predictability of expansion is variable, but it did not exceed the 50% during the first set of aligners. It was necessary to apply refinement set to achieve a good predictability for expansion of about 70%. The expansion in the lower arch was observed to be more predictable than in the upper arch.

Predictive value on advance hodgkin lymphoma treatment outcome of end-of treatment FDG PET/CT in the HD0607 clinical trial.

The Lugano classification for response assessment in lymphoma recommends the use of the 5-point-scale Deauville Score (DS) to assess response evaluation of end-of-treatment FDG-PET/CT (eotPET) in Hodgkin Lymphoma (HL); nevertheless, there is a paucity of data on its accuracy and reproducibility. We focus here on the cohort of advanced stage IIb-IV HL patients enrolled in the HD0607 clinical trial (NCT identifier 00795613) that having had a negative interim PET performed 6 cycles of ABVD (Doxorubicin, Vinblastine, Vincristine and Dacarbazine) and then performed an eotPET. Negative patients were randomized to radiotherapy and no further treatment while positive patients were treated based on local policies. eotPET was re-evaluated independently by two readers evaluated and progression free survival was analysed (PFS). eotPET of 254 patients were analysed. The median follow-up was 43 months. The best receiver operator characteristics cut-off values to distinguish positive and negative patients was 4. The area-under-the-curve was 0.81 (95%CI, 0.70-0.91). Three-years PFS was 0.95 (95% CI 0.90-0.97) in eotPET negative and 0.22 (95% CI 0.11-0.43) in eotPET positive. DS demonstrated a good reproducibility of positivity/negativity between the readers consensus and local site evaluation where the agreement occurred on 95.0% of patients. The present study demonstrates that eotPET is an accurate tool to predict treatment outcome in HL and confirms the appropriateness of the Lugano classification for eotPET evaluation.

Soft tissue evaluation of functional therapy in growing patients with Class II malocclusion: a long-term study.

OBJECTIVE: The objective of this study was to analyse the soft tissue changes produced by the functional treatment of mandibular advancement in growing Class II patients. MATERIALS: The treated group consisted of 25 Caucasian patients (12 females and 13 males) with dento-skeletal Class II malocclusion treated with functional therapy (Activator). All patients were evaluated before treatment (T1; mean age, 9.9 years), at the end of functional treatment phase (T2; mean age, 11.9 years), and at a post-pubertal follow-up observation (T3; mean age, 18.5 years). The treated group was compared with a matched control group of 25 untreated subjects (13 females, 12 males) with untreated Class II division 1 malocclusion. Statistical comparisons between the two groups were performed with independent samples t-tests (P < 0.05). RESULTS: Significant improvements were found during the long-term interval for mandibular sulcus (9.9°) and the profile facial angle (9.8°) in the treated group. No significant effects were found in terms of lower face percentage between the two groups. CONCLUSION: Removable functional appliances induced positive effects on the soft tissue profile in Class II growing subjects with good stability in the long-term.

Effects of pendulum appliance versus clear aligners in the vertical dimension during Class II malocclusion treatment: a randomized prospective clinical trial.

BACKGROUND: The aim of the present study was to compare the effects on vertical dentoskeletal dimension produced by Pendulum appliance and Clear Aligners in patients with Class II malocclusion. TRIAL DESIGN: This is a prospective two-arm parallel group randomized clinical trial with 1:1 allocation ratio. METHODS: The Pendulum Group (PG) consisted of 20 patients (15F, 5 M) with a mean age of 17.2 ± 4.3 years. The Clear Aligners Group (CAG) comprised 20 patients (13F, 7 M) with a mean age of 17.2 ± 3.2 years. Distalization's protocol in PG involved the activation of TMA wires till the achievement of Class I molar relationship. A protocol of sequential distalization was applied in the CAG. For each subject lateral cephalograms have been analyzed before treatment (T1) and at the end of the therapy (T2). Descriptive statistics and statistical between-group comparisons (PG vs CAG) were calculated for the craniofacial starting forms at T1 and for the T2-T1 changes. Statistical between-group comparisons for the T2-T1 changes were performed with independent samples t-tests (P < 0.05). RESULTS: The PG showed significantly greater increases in SN^GoGn° when compared with CAG (+ 2.1 and - 0.3 degrees, respectively). Clockwise rotation of the occlusal plane with significantly greater increase of SN^POccl angle was observed in PG (+ 2.8 degrees) when compared with CAG (- 4.2 degrees). The PG revealed a significant increase in the N-Me variable with a mean change of + 4.4 mm compared to the CAG with mean values of - 1.2 mm. The PG showed an increase in the ArGo^GoMe angle (+ 0.7° degrees) compared to the CAG (- 3.4° degrees). The PG showed significantly greater increases in both maxillary and mandibular first molar to palatal plane (+ 1.3 and + 2.1 mm, respectively) when compared with CAG (- 0.9 and - 0.2 mm, respectively). CONCLUSIONS: Upper molar distalization with clear aligners represents a valid alternative to non-extraction treatment of Class II malocclusion, reducing the extrusion of maxillary first molars and improving the management of the occlusal plane and vertical dimension. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05298280. Registered 28 March 2022-Retrospectively registered, https://clinicaltrials.gov .

Light-curing process for clear aligners' attachment reproduction: comparison between two nanocomposites cured by the auxiliary of a new tool.

BACKGROUND: Attachments' configuration play an important role during Clear Aligner Treatment (CAT) for aligner retention and control of movements planned. The aims were to compare the macroscopic morphology of attachments reproduced with flowable (FNC) and conventional (CNC) composites and the effects on them of two light-guide tips with different dimensions. METHODS: 4 resin casts derived from the initial scan of the same patient were obtained. 10 vestibular attachments were replaced on both upper and lower arches of each model with CNC (Models A, B) and FNC (Models C, D). Each composite was cured by means of the same LED lamp with both regular light-guide (Models A, B) and push and light tool® (Models C, D). The 80 attachments were qualitative analyzed by means of a digital stereo microscope. Surface roughness and waviness measurements were assessed by contact probe surface profiler (TalySurf CLI 2000; Taylor Hobson, Leicester, United Kingdom). Statistical analysis was performed with independent samples t-tests. Significance was established at the P < 0.05 level. RESULTS: Model A showed lower values of surface roughness (Ra - 1.41 µm, Rt - 3.46 µm) and waviness (Wa - 2.36 µm, Wt - 10.95 µm) when compared with Model C. Significant reduction of waviness (Wa - 3.85 µm, Wt - 4.90 µm) was observed on Model B when compared with Model D. Significant increase of roughness and waviness parameters (Ra 3.88 µm, Rt 21.07, Wa 2.89 µm, Wt 14.74 µm) was found when CNC sample (Model A) was cured with regular light-guide tip. Higher values (Ra 2.33 µm, Rt 24.07 µm, Wa 1.67 µm, Wt 20.79 µm) were observed after regular light-guide tips curing on FNC sample (Model C). CONCLUSIONS: CNC resins determine more regular surfaces of attachments profiles. The additional use of a smaller light- guide of the LED push and light tool® allows to improve the macroscopic morphology of the attachments and to maximize light irradiance delivering by enhancing the polymerization process and the integrity of the features during the treatment.

Clinical significance of chromatin-spliceosome acute myeloid leukemia: a report from the Northern Italy Leukemia Group (NILG) randomized trial 02/06.

Secondary acute myeloid leukemia (sAML) after myelodysplastic or myeloproliferative disorders is a high-risk category currently identified by clinical history or specific morphological and cytogenetic abnormalities. However, in the absence of these features, uncertainties remain to identify the secondary nature of some cases otherwise defined as de novo AML. To test whether a chromatin-spliceosome (CS) mutational signature might better inform the definition of the de novo AML group, we analyzed a prospective cohort of 413 newly diagnosed AML patients enrolled into a randomized clinical trial (NILG AML 02/06) and provided with accurate cytogenetic and molecular characterization. Among clinically defined de novo AML, 17.6% carried CS mutations (CS-AML) and showed clinical characteristics closer to sAML (older age, lower white blood cell counts and higher rate of multilineage dysplasia). Outcomes in this group were adverse, more similar to those of sAML as compared to de novo AML (overall survival, 30% in CS-AML and 17% in sAML vs 61% in de novo AML, P<0.0001; disease free survival, 26% in CS-AML and 22% in sAML vs 54% of de novo AML, P<0.001) and independently confirmed by multivariable analysis. Allogeneic transplant in first complete remission improved survival in both sAML and CS-AML patients. In conclusion, these findings highlight the clinical significance of identifying CS-AML for improved prognostic prediction and potential therapeutic implications. (NILG AML 02/06: ClinicalTrials.gov Identifier: NCT00495287).

Early serum TARC reduction predicts prognosis in advanced-stage Hodgkin lymphoma patients treated with a PET-adapted strategy.

Among patients with advanced-stage classical Hodgkin lymphoma (cHL) receiving ABVD chemotherapy, PET performed after the first two treatment cycles (PET-2) has prognostic value. However, 15% of patients with a negative PET-2 will experience treatment failure. Here we prospectively evaluated serum thymus and activation-regulated chemokine (TARC) levels, to improve risk assessment in patients treated according to HD0607 PET-driven trial (#NCT00795613). In 266 patients with available serum samples, who have agreed to participate in a sub-study for assessment of the role of TARC monitoring, serum TARC levels were measured at baseline and at time of PET-2 by commercially available ELISA test kits. The primary end-point was to evaluate the association between TARC after 2 ABVD cycles and PFS. Median TARC-2 values were significantly higher in PET-2-positive patients compared to PET-2-negative patients (P = .001), and in patients with treatment failure compared to those in continuous CR (P = .01). The 4-year PFS significantly differed between patients with TARC-2 >800 pg/mL vs ≤800 pg/mL (64% vs 86%, P = .0001). Moreover, among PET-2-negative patients, elevated TARC-2 identified those with a worse prognosis (74% vs 89%; P = .01). In multivariable analysis, TARC-2 >800 pg/mL was a significant independent predictor of PFS in the whole study population (HR 2.39, P = .004) and among the PET-2-negative patients (HR 2.49, P = .02). In conclusion, our results indicate that TARC-2 serum levels above 800 pg/mL suggest the need for a stringent follow-up in PET-2-negative patients, and the evaluation of new drugs in PET-2-positive, who will likely fail to respond to intensification with escalated BEACOPP.

Changes in mandibular shape after early treatment in subjects with open bite: a geometric morphometric analysis.

OBJECTIVES: To evaluate the mandibular modifications in anterior open bite (OB) growing subjects treated with Rapid Maxillary Expansion and bite block (RME/BB) or Quad Helix with crib (QH/C) when compared with a Control Group (CG) by using Geometric Morphometric Method (GMM) and conventional cephalometric. MATERIALS: The OB group comprised 34 subjects (26 girls, 8 boys) with dentoskeletal OB and a mean age of 8.0 ± 1.0 years. OB group was divided in two subgroups: RME/BB group comprised 17 subjects (13 girls, 4 boys), while QH/C group included 17 subjects (13 girls, 4 boys). The two subgroups were compared with a CG of 17 subjects (13 girls, 4 boys) matched for sex, age, vertical pattern, and observation periods. Two consecutives lateral cephalograms were available: the first one was taken before treatment (T1), and the second one was acquired at a follow-up observation at least 4 years after the completion of treatment (T2). Landmarks and semilandmarks were digitized on lateral cephalograms and GMM was applied. Procrustes analysis and principal component analysis were performed. Analysis of variance (ANOVA) with Tukey post hoc tests was used to compare the T2-T1 cephalometric changes between the RME/BB, QH/C, and CG. RESULTS: In the long term, RME/BB showed a significantly greater decrease of the Condylar axis to mandibular plane angle when compared to CG and QH/C. GMM showed an increased in height of the mandibular ramus in RME/BB group with tendency to counterclockwise rotation of the mandible when compared with QH/C and CG groups. CONCLUSIONS: RME/BB subjects showed significant changes in the shape of the mandibular ramus with a counterclockwise rotation tendency when compared with QH/C and CG subjects.

Conventional versus laser gingivectomy in the management of gingival enlargement during orthodontic treatment: a randomized controlled trial.

OBJECTIVES: To compare the use of diode laser with conventional surgery evaluating the effectiveness of gingivectomy as an adjunct to non-surgical periodontal treatment in the management of gingival enlargement (GE) during orthodontic treatment. TRIAL DESIGN: Prospective three-arm parallel group randomized clinical trial with 1:1:1 allocation ratio. METHODS: Sixty subjects (33 males and 27 females), with a mean age of 14.4 ± 1.9 years, were selected according to inclusion criteria: overgrown gingivae on the labial side of the anterior teeth secondary to fixed appliance therapy, six maxillary anterior teeth present, and healthy non-smokers patients. Patients were enrolled in the study and randomly assigned to three groups by a computer-generated randomization list and by a block size of 4. The allocation information was concealed in opaque and sealed envelopes by the statistician. In the first group, all subjects underwent a conventional scalpel gingivectomy of the maxillary anterior sextant. In the second group, all subjects were treated using laser-assisted gingivectomy; while subjects assigned to the third group underwent only non-surgical periodontal treatment and served as control group (CG). The observer who performed all the measurements was blinded to the group assignment. Blinding was obtained by eliminating from the elaboration file every reference to patient group assignment. Intergroup comparisons of changes in the periodontal parameters were conducted at 1, 3, and 6 months using ANOVA with repeated measures and Tukey's post hoc tests. The significance level was set at P <0.05. RESULTS: After 1 month, the TGs showed a significant improvement of all periodontal parameters when compared with the CG. No statistically significant differences were observed between the two TGs. At the 3-month observation, a relapse occurred in the TGs, while the CG showed the greater improvement of soft tissue health. In the 6-month versus 3-month evaluation, no significant differences between the three groups were found for any periodontal measurements. In the long-term evaluation (6 months versus baseline), a significant greater reduction of pockets were found in the TGs when compared with the CG. CONCLUSIONS: The adjunct use of both scalpel gingivectomy and laser gingivectomy was more effective in controlling gingival inflammation than non-surgical periodontal treatment alone at 1, 3 and 6 months. In the control group, greater improvement in the periodontal parameters were observed within 3 months, depending on a self-care approach for the management of GE. LIMITATIONS: This study was a short-term study (6-month follow-up). TRIAL REGISTRATION: ClinicalTrials.gov (registration number: NCT03514316).

Development and validation of a prediction model for long-term unsuccess of early treatment of Class III malocclusion.

AIM: To develop and validate a prediction model to forecast long-term stability of early treatment with rapid maxillary expansion (RME) and facemask (FM) in a large sample of Class III growing patients. METHODS: The Brazilian Group (BG) consisted of 73 consecutively treated Caucasian Class III patients (41 females and 32 males). Mean age at T0 (before treatment) was 7.1 ± 1.6 years, while mean age at T1 (long-term follow-up) was 21.8 ± 3.2 years. The Italian Group (IG, validation cohort) comprised 28 consecutively treated Caucasian Class III patients (14 females and 14 males, mean age at T0 9.0 ± 1.3 years and mean age at T1 18.2 ± 1.4 years). Cephalometric analysis was performed on lateral cephalograms at T0. Gender and cephalometric variables, chronologic age, and dentition phase at T0 were used as predictors for long-term unsuccessful treatment at T1. All predictors for unsuccessful treatment in the BG were subjected to bivariate logistic regression. Only those statistically significant predictors in the bivariate logistic regression entered mixed stepwise logistic regression with P = 0.05 to enter and to leave. The validity of the prediction model derived from the BG was then tested on the IG. RESULTS: The prediction model consisted of only one cephalometric variable: the angle between the Condylar Axis and the Mandibular Plane (CondAx-MP) (odds ratio: 1.52, 95% confidence interval: 1.25-1.85, P < 0.0001). Unsuccessful treatment at T1 was predicted for values of CondAx-MP at T0 greater than the cut-off value of 147.8 degrees. BG patients predicted incorrectly were 3 out of 22 for the unsuccessful cases and 1 out of 51 for the successful cases. Therefore, accuracy was 0.95, sensitivity 0.86, specificity 0.98, and positive and negative predictive values were 0.95 and 0.94. When the predictive model was applied on IG, all five unsuccessful cases were predicted correctly, while only 1 out of 23 successful patients was predicted incorrectly. CONCLUSION: CondAx-ML was identified as a reliable predictor for long-term stability of early Class III treatment with RME and FM.

Busulfan- or Thiotepa-Based Conditioning in Myelofibrosis: A Phase II Multicenter Randomized Study from the GITMO Group.

We report a randomized study comparing fludarabine in combination with busulfan (FB) or thiotepa (FT), as conditioning regimen for hematopoietic stem cell transplantation (HSCT) in patients with myelofibrosis. The primary study endpoint was progression-free survival (PFS). Sixty patients were enrolled with a median age of 56 years and an intermediate-2 or high-risk score in 65%, according to the Dynamic International Prognostic Staging System (DIPSS). Donors were HLA-identical sibling (n = 25), matched unrelated (n = 25) or single allele mismatched unrelated (n = 10). With a median follow-up of 22 months (range, 1 to 68 months), outcomes at 2 years after HSCT in the FB arm versus the FT arm were as follows: PFS, 43% versus 55% (P = .28); overall survival (OS), 54% versus 70% (P = .17); relapse/progression, 36% versus 24% (P = .24); nonrelapse mortality (NRM), 21% in both arms (P = .99); and graft failure, 14% versus 10% (P = .96). A better PFS was observed in patients with intermediate-1 DIPSS score (P = .03). Both neutrophil engraftment and platelet engraftment were significantly influenced by previous splenectomy (hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.16 to 4.51; P = .02) and splenomegaly at transplantation (HR, 0.51; 95% CI, 0.27 to 0.94; P = .03). In conclusion, the clinical outcome after HSCT was comparable when using either a busulfan or thiotepa based conditioning regimen.

Soft tissue facial profile in Class III malocclusion: long-term post-pubertal effects produced by the Face Mask Protocol.

OBJECTIVES: The objective of this study was to analyze soft tissue changes produced by rapid maxillary expansion and facial mask therapy in growing Class III patients. MATERIALS: The treated group consisted of 32 Caucasian patients (15 females and 17 males) with dentoskeletal Class III malocclusion treated with the Face Mask Protocol (FMP, rapid maxillary expander, facial mask, and removable lower bite-block). All patients were evaluated before treatment (T1; mean age, 8.4 years), at the end of active treatment (T2; mean age, 10.7 years), and at a post-pubertal follow-up observation (T3; mean age, 15.8 years). The treated group was compared with a matched control group of 20 untreated subjects (10 females and 10 males) with dentoskeletal Class III malocclusion. Statistical comparisons between two groups were performed with the independent samples t-test (P < 0.05). RESULTS: Significant improvements were found during the long-term T1-T3 interval for profile facial angle (-5.8°), nasolabial angle (-4.4°), mandibular sulcus (-10.3°), upper lip protrusion (+0.7 mm), and lower lip protrusion (-1.1 mm) in the treated group. No significant post-pubertal effects were found in terms of lower face percentage between two groups. LIMITATIONS: This study has a retrospective design and it used a historical control sample. CONCLUSION: The FMP induced positive effects on soft tissue facial profile with a good long-term post-pubertal stability.

Comparison of the abrasive properties of two different systems for interproximal enamel reduction: oscillating versus manual strips.

BACKGROUND: The aim of the present investigation was to evaluate enamel reduction efficiency, abrasive property decay, and enamel effects between oscillating mechanical and manual systems for interproximal enamel reduction (IPR). METHODS: Three oscillating strips and three manual strips were tested on twelve freshly extracted premolars blocked in an acrylic cylinder pot by means of a material testing machine. Each strip underwent one test of 8 cycles (30 s each). Both abrasive tracks and teeth surfaces were qualitative evaluated before and after IPR by means of SEM analysis. Efficiency and abrasive property decay of both IPR systems were investigated by the amount of enamel reduction within the eight-cycle testing. Independent t-test was used to evaluate differences in variables between the two systems. RESULTS: Mechanical IPR system showed higher efficiency in terms of enamel reduction (p < 0.005) when compared with manual IPR system (0.16 mm and 0.09 mm, respectively). Quantity of removed enamel decreased throughout the 8 cycles for both systems. Less presence of enamel debris and detachment of abrasive grains were observed on mechanical strips rather than manual strips. SEM analysis revealed more regular surface of teeth undergone mechanical IPR procedures. CONCLUSION: Oscillating diamond strips showed more controlled efficiency when compared with the manual IPR system leading to a more regular enamel surface.

Stress on facial skin of class III subjects during maxillary protraction: a finite element analysis.

BACKGROUND: Maxillary protraction with facemask (FM) is an orthopedic approach for treatment of Class III growing patients. Aim of the present investigation was to analyze tension loads produced by two different facial mask (FM) designs on facial skin of subject with skeletal Class III. METHODS: A three-dimensional (3D) geometry of Delaire and Petit FM models were reconstructed from the original Computer Aided Design (CAD) 3D prototype using software package (ANSYS 5.7). A traction load of 9.8 N inclined of 30° to the occlusal plane was applied combining analytical FM models with a 3D facial model. Resulting stresses and deformations on the skin layer were tested through the von Mises yield criterion. RESULTS: Overall tensions were mostly developed on the chin area, while lower stresses were observed on forehead area for both FM designs. When Delaire FM model was tested, maximum stresses were observed on the upper border of the chin cup corresponding to the inferior lip and to marginal gingiva of lower incisors. After Petit FM application, maximum stresses were more extensively localized at the level of both upper border and central area of the chin. Stresses measured on the chin area were significantly higher with Petit FM when compared with Delaire FM (44 KPa versus 29 KPa, respectively). CONCLUSIONS: Delaire FM determined lower stresses and tensile tensions than Petit FM model. Highest tensions were observed at the level of chin cup area for both Delaire and Petit FM. Stresses following Delaire FM application were mostly observed on the upper border of the chin cup, while Petit FM determined stresses more extensively distributed to the central area of the chin.

Treatment timing for functional jaw orthopaedics followed by fixed appliances: a controlled long-term study.

Objective: To evaluate the role of treatment timing on long-term dentoskeletal effects of Class II treatment with removable functional appliances followed by full-fixed appliance therapy. Materials and methods: A group of 46 patients (23 females and 23 males) with Class II malocclusion treated consecutively with either Bionator or Activator, followed by fixed appliances was compared with a matched control group of 31 subjects (16 females and 15 males) with untreated Class II malocclusion. The treated sample was evaluated at T1, start of treatment (mean age: 9.9 ± 1.3 years); T2, end of functional treatment and prior to fixed appliances (mean age: 11.9 ± 1.3 years); and T3, long-term observation (mean age: 18.3 ± 2.1 years). The treated and the control samples were divided into pre-pubertal and pubertal groups according to skeletal maturity observed at the start of treatment. Statistical comparisons were performed with independent sample t-tests. Results: When treatment was initiated before puberty, Class II correction was mostly confined to the dentoalveolar changes, with significant improvements of both overjet and molar relationships. On the other hand, treatment with the outset at puberty produced significant long-term improvement of sagittal skeletal relationships, which were mainly sustained by mandibular changes. Conclusions: Treatment with removable functional appliances (Bionator or Activator) followed by full-fixed appliances produced significant skeletal long-term changes when it begins at puberty. Prepubertal Class II treatment results primarily in dentoalveolar changes.

Phase II Study of Sequential Infusion of Donor Lymphocyte Infusion and Cytokine-Induced Killer Cells for Patients Relapsed after Allogeneic Hematopoietic Stem Cell Transplantation.

Seventy-four patients who relapsed after allogeneic stem cell transplantation were enrolled in a phase IIA study and treated with the sequential infusion of donor lymphocyte infusion (DLI) followed by cytokine-induced killer (CIK) cells. Seventy-three patients were available for the intention to treat analysis. At least 1 infusion of CIK cells was given to 59 patients, whereas 43 patients received the complete cell therapy planned (58%). Overall, 12 patients (16%) developed acute graft-versus-host disease (aGVHD) of grades I to II in 7 cases and grades III to IV in 5). In 8 of 12 cases, aGVHD developed during DLI treatment, leading to interruption of the cellular program in 3 patients, whereas in the remaining 5 cases aGVHD was controlled by steroids treatment, thus allowing the subsequent planned administration of CIK cells. Chronic GVHD (cGVHD) was observed in 11 patients (15%). A complete response was observed in 19 (26%), partial response in 3 (4%), stable disease in 8 (11%), early death in 2 (3%), and disease progression in 41 (56%). At 1 and 3 years, rates of progression-free survival were 31% and 29%, whereas rates of overall survival were 51% and 40%, respectively. By multivariate analysis, the type of relapse, the presence of cGVHD, and a short (<6 months) time from allogeneic hematopoietic stem cell transplantation to relapse were the significant predictors of survival. In conclusion, a low incidence of GVHD is observed after the sequential administration of DLI and CIK cells, and disease control can be achieved mostly after a cytogenetic or molecular relapse.