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.     

Incidence and Risk Factors for Hepatitis C Virus Infection among Illicit Drug Users in Italy

So far, only three small outdated studies have investigated hepatitis C virus (HCV) incidence and risk factors among illicit drug users (DUs) in Italy. Thus, during 2007–2010, we conducted a prospective cohort study among DUs attending 17 Italian rehabilitation centers serving urban areas. Two hundred eighty-four HCV-uninfected DUs were prospectively followed by interview and anti-HCV antibody and RNA testing every 6 months. Incidence was calculated using the person-years method. Infection predictors were assessed by time-dependent Cox analysis. Participants were mostly male (83.4%), under opioid substitution therapy (OST) (78.9%), non-injecting DUs (67.9%), and with a mean age of 30.8. Ninety-one of 224 DUs initially under OST interrupted treatment during the follow-up. Overall HCV incidence was 5.83/100 person-years at risk (PYAR) [95% confidence intervals (CI), 3.63–9.38]. The incidence did not significantly differ according the participants’ sociodemographic characteristics or the degree of urbanization of the towns involved in the study. The incidence was higher for DUs under than for those not under OST (6.23 vs 4.50/100 PYAR; p = 0.681). Incidence was also higher for those with than for those without OST interruption (7.17 vs 5.04/100 PYAR; p = 0.55). However, all these differences were non-significant. At last follow-up visit, a significant decrease in frequency of sharing equipment for preparation/using drugs (by injection or not) was observed by analyzing either the whole cohort or DUs under OST only. Anti-HCV seroconversion resulted independently associated with sharing drug preparation/use equipment, backloading, having a HCV-positive sexual partner, or household and (marginally) intravenous injection. In this study, HCV incidence was non-negligible and OST seemed to lack effectiveness in reducing it. In Italy, implementation of combined harm reduction interventions and antiviral treatment of chronically infected DUs would be needed.     

Alcohol,alcoholic beverages,and melanoma risk: a systematic literature review and dose–response meta-analysis

Purpose

Several studies in recent years have investigated the relationship between alcohol intake and melanoma risk, with conflicting results. To help clarify this issue, we conducted a literature review and dose–response meta-analysis of studies published until June 30th, 2017, that examined the association between alcohol intake (overall and by beverage type) and melanoma risk.

Methods

We used random effect models with maximum likelihood estimation to calculate summary relative risk (SRR) and 95% confidence intervals (95%CI).

Results

We included 20 independent studies (encompassing 10,555 melanoma cases and over 1.6 million non-cases/controls) published during 1986–2016, of which six had a prospective cohort study design. Adjustment for phenotypic characteristics and sunlight exposure was performed in 11 and nine studies, respectively. Alcohol intake was moderately associated with melanoma risk: the SRR were 1.29 (95% CI 1.14–1.45) for those in the highest vs. lowest category of current alcohol intake, and 1.96 (95% CI 1.02–3.76, I²?=?0%) for cumulative intake. In the dose–response analysis, the increase in risk associated with a 10 g increment in daily alcohol intake was 1.07 (95% CI 1.03–1.11). Risk estimates did not differ by gender, study design and adjustment for confounders; between-studies heterogeneity was acceptable, and there was no evidence of publication bias.

Conclusions

Our findings suggest that alcohol drinking may be moderately associated with increased melanoma risk, although residual confounding and bias cannot be ruled out. Further research is needed to confirm these findings, clarify the role of the different alcohol sources, and investigate the interaction with known melanoma risk factors.

     

Sarcopenia in Parkinson Disease: Comparison of Different Criteria and Association With Disease Severity

Objectives

In Parkinson disease (PD), sarcopenia may represent the common downstream pathway that from motor and nonmotor symptoms leads to the progressive loss of resilience, frailty, and disability. Here we (1) assessed the prevalence of sarcopenia in older adults with PD using 3 different criteria, testing their agreement, and (2) evaluated the association between PD severity and sarcopenia.

Capacity of coronal dentin to increase fiberglass post retention: a pull-out test

PURPOSE: To evaluate the capacity of residual dentin in the coronal part of the root canal to increase the retention of serrated fiberglass posts (Extra-glass P-6%). METHODS: 40 freshly-extracted maxillary central incisors were randomly and evenly divided into four test groups (TGs) with no (TG0), one (TG1), two (TG2) and three (TG3) coronal walls, respectively. After shaping, the canals were filled with gutta-percha and prepared to receive fiberglass posts. Coronal wall dentin was etched with 38% phosphoric acid for 60 seconds, rinsed, and dried. Dentin bonding agent (Prime & Bond NT) was applied, and fiberglass posts were luted for 8 mm into the post space using a self-cure composite (ResiLute). All samples were then subjected to tensile forces in a universal testing machine. Data were analyzed with ANOVA and Student t-tests (P< 0.01). RESULTS: The samples with residual coronal dentin showed higher bond strength than the samples without residual crown walls (TG0=100.30N; TG1=201.83N; TG2=263.54N; TG3=278.86N). The differences between the groups were all statistically significant at P< 0.01, except for the difference in tensile strength between TG2 and TG3, which was not statistically significant. Residual crown walls significantly increased the tensile load required to displace the posts.     

Clinical and microbiological effects of different restorative materials on the periodontal tissues adjacent to subgingival class V restorations

OBJECTIVES: The relationship between subgingival dental restorations and periodontal health has been thoroughly investigated for many years. However, longitudinal data on the subgingival microflora features after the placement of well-finished subgingival restorations are still lacking. Therefore, this study compares the short-term clinical and microbiological features occurring in the gingiva after the completion of different subgingival restorations. MATERIAL AND METHODS: Sixteen systemically healthy subjects, 10 males and six females (ages: 31.7-45.8 years; mean age 39.3+/-5.1 years), who were non-smokers and were positive for the presence of three cervical abrasion/erosion defects to be restored in three different adjacent teeth were enrolled in this study. The cervical abrasion/erosion defects were each restored by using one of three different materials: amalgam, glass ionomer cement, or composite resin. Immediately before class V cavity preparations and restorations (baseline), clinical monitoring and subgingival plaque sampling were performed in the mid-buccal aspect of each experimental restored tooth and in one adjacent sound, non-treated, control tooth. These procedures were repeated every 4 months over the following 1 year. RESULTS: Throughout the study, the clinical parameters recorded did not change significantly in any of the experimental groups, and no differences were detected among them at each clinical session. Over this time, no significant changes in the composition of the subgingival microflora were observed in amalgam, glass ionomer cement, and control groups. Conversely, in the composite resin group, there was a significant increase in the total bacterial counts, and a significant (p<0.05) decrease in Gram-positive, aerobic bacteria, which was associated with a significant (p<0.05) increase in the Gram-negative, anaerobic microbiota. CONCLUSIONS: Over a 1-year observation period, amalgam, glass ionomer cement, and composite resin subgingival restorations do not significantly affect the clinical parameters recorded. However, composite resin restorations may have some negative effects on the quantity and quality of subgingival plaque.     

Clinical and microbiologic effects of subgingival controlled-release delivery of chlorhexidine chip in the treatment of periodontitis: a multicenter study

BACKGROUND: The main therapeutic approach for periodontal diseases is mechanical treatment of root surfaces via scaling and root planing (SRP). Multicenter clinical trials have demonstrated that the adjunctive use of a chlorhexidine (CHX) chip is effective in improving clinical results compared to SRP alone. However, some recent studies failed to confirm these clinical results, and conflicting results were reported regarding the effects of the CHX chip on subgingival microflora. The aim of this study was to provide further data on the clinical and microbiologic effects of CHX chips when used as an adjunct to SRP. METHODS: A total of 116 systemically healthy individuals with moderate to advanced periodontitis, aged 33 to 65 years, were recruited from the Departments of Periodontology of four Italian universities. For each subject, two experimental sites were chosen that had probing depths (PD) > or =5 mm and bleeding on probing (BOP) and were located in two symmetric quadrants. These two sites were randomized at the split-mouth level, with one receiving SRP treatment alone and the other receiving treatment with SRP plus one CHX chip (SRP + CHX). PD, relative attachment level (RAL), and BOP were evaluated at baseline, prior to any treatment, and after 3 and 6 months. Supragingival plaque and the modified gingival index were evaluated at baseline and after 15 days and 1, 3, and 6 months. Subgingival microbiologic samples were harvested at baseline and after 15 days and 1, 3, and 6 months, cultured for total bacterial counts (TBCs), and investigated by polymerase chain reaction analysis for the identification of eight putative periodontopathogens. RESULTS: When all of the pockets were considered, the PD and RAL were significantly less at 3 and 6 months compared to the baseline scores (P <0.01) for both treatments. Moreover, the PD was reduced in the SRP + CHX treatment group compared to the SRP treatment group at 3 and 6 months, whereas the RAL was similar for both treatments at 3 months and was reduced in the SRP + CHX treatment group at 6 months. The differences in PD reductions between the treatments were 0.30 and 0.55 mm at 3 and 6 months, respectively (P <0.01); for the RAL gain, the differences were 0.28 and 0.64 mm, respectively (P <0.001). The TBCs decreased significantly with both treatments. A similar, although less evident, pattern was noted when only the pockets with an initial PD > or =7 mm were considered. The percentage of sites positive for BOP was similar between the treatments at each time point. At 15 days and 1 month, the TBC for the SRP + CHX treatment group was significantly lower than for the SRP treatment group (P <0.01 and P <0.05, respectively). Over time, both treatments generally reduced the percentages of sites positive for the eight putative periodontopathic bacteria, although greater reductions were seen often for the SRP + CHX treatment group. CONCLUSIONS: The adjunctive use of the CHX chip resulted in a significant PD reduction and a clinical attachment gain compared to SRP alone. These results were concomitant with a significant benefit of SRP + CHX treatment on the subgingival microbiota.     

Oral breathing and head posture

OBJECTIVE: To determine the head posture and cephalometric characteristics in oral breathing children. MATERIALS AND METHODS: Lateral cephalograms taken in natural head posture of 35 oral breathing patients (OB) (mean age 8.8 +/- 2.2 years SD; range 5-13 years) and of 35 patients with varied malocclusions and physiological breathing (PB) (mean age 9.7 +/- 1.6 years SD; range 7-13 years) were examined. RESULTS: A Student's t-test showed that an increase in angles NSL/OPT (P = .000), NSL/CVT (P = .001), FH/OPT (P = .000), FH/CVT (P = .005), and NSL/VER (P = .000); a decrease in the distance MGP-CV1p (P = .0001); and a decrease in the angles MGP/OP (P = .000) and OPT/ CVT (P = .036) were found in the OB group. A low position of the hyoid bone (H-MP, P = .009), a major skeletal divergence (ANS-PNS/Go-Me, P = .000), and an increased value of the ANB angle (P = .023) were present in OB patients. To ascertain if the changes in posture were connected with posterior obstruction of the upper respiratory airways, the OB group was divided into two subgroups based on the distance Ad2-PNS being greater than or less than 15 mm. No significant differences were found between these two groups. CONCLUSIONS: Our data suggest that OB children show greater extension of the head related to the cervical spine, reduced cervical lordosis, and more skeletal divergence, compared with PB subjects.     

Substantia nigra in Parkinson’s disease: a multimodal MRI comparison between early and advanced stages of the disease

This study focused on the substantia nigra (SN) in Parkinson’s disease (PD). We measured its area and volume, mean diffusivity (MD), fractional anisotropy (FA) and iron concentration in early and late PD and correlated the values with clinical scores. Twenty-two early PD (EPD), 20 late PD (LPD) and 20 healthy subjects (age 64.7 ± 4.9, 60.5 ± 6.1, and 61 ± 7.2 years, respectively) underwent 1.5 T MR imaging with double-TI-IR T1-weighted, T2*-weighted and diffusion tensor imaging scans. Relative SN area, MD, FA and R2* were measured in ROIs traced on SN. Correlation with Unified Parkinson Disease Rating Scale (UPDRS) scores was assessed. In LPD, the SN area was significantly reduced with respect to EPD (p = 0.04) and control subjects (p < 0.001). In EPD, the SN area was also significantly smaller than in controls (p = 0.006). Similarly, the SN volume significantly differed between LPD and controls (p = 0.001) and between EPD and LPD (p = 0.049), while no significant differences were found between controls and EPD. Both SN area (r = 0.47, p = 0.004) and volume (r = 0.46, p = 0.005) correlated with UPDRS scores. At 1.5 T, SN morphological measurements were sensitive to early PD changes and able to track the disease progression, while MD and FA measures and relaxometry did not provide significant results.