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.     

Pigmented skin lesions displaying regression features: Dermoscopy and reflectance confocal microscopy criteria for diagnosis

Melanomas and nevi displaying regression features can be difficult to differentiate. To describe reflectance confocal microscopy features in benign and malignant pigmented skin lesions characterized by regression features in dermoscopy. Observational retrospective study. Inclusion criteria were presence of dermoscopic features of regression; availability of clinical, dermoscopic and RCM imaging; definite histopathologic diagnosis. The study sample comprised 217 lesions; 108 (49.8%) melanomas and 109 were benign lesions, of which 102 (47.0%) nevi and 7 (3.2%) lichen planus‐like keratosis (lplk). Patients with melanoma were significantly older than those with benign lesions (61.9 ± 15.4 vs 46.1 ± 14.8; P < 0.001) and a higher proportion of melanomas displayed dermoscopic regression structures in more than 50% of lesion surface (n = 83/108; 76.9%; P < 0.001). On RCM examination, pagetoid cells were significantly more reported in melanoma group, than in benign lesions (86.1% vs 59.6%; P < 0.001) and were more frequently widespread distributed (65.6% vs 20.0%; P < 0.001) and both dendritic and roundish (36.6% vs 15.4%; P < 0.001) in shape. Aspecific architecture at the dermo‐epidermal junction (DEJ) was more commonly seen among melanomas than benign lesions (23.1% vs 11.9%; P = 0.002) with higher presence of dendritic and both dendritic and roundish atypical cells at the DEJ (28.7% vs 18.3% and 19.4% vs 3.7%; P < 0.001, respectively). Focal pagetoid infiltration and ringed or clod patterns were more commonly seen in benign lesion. In conclusion, the correct interpretation of regressing lesions remains a challenge, assessing carefully the extent and characteristics of architectural and cytologic atypia on RCM is an additional piece of the complex puzzle of melanoma diagnosis.     

Paradigmatic cases of pigmented lesions: How to not miss melanoma

A large number of cases of melanoma exhibit clinical and dermoscopic clues leading to the correct diagnosis; however, sometimes melanoma can mimic benign melanocytic and non‐melanocytic lesions. We present a small series of melanomas in which additional clues provided by confocal microscopy increased the index of suspicion and prompted us to perform an excisional biopsy. Practical rules that are useful in difficult‐to‐diagnose melanomas are discussed.     

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.     

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.     

Evaluation of contrast‐enhanced digital mammography (CEDM) in the preoperative staging of breast cancer: Large‐scale single‐center experience

One of the most important indications for contrast‐enhanced breast imaging is the presurgical breast cancer (BC) staging. This is a large‐scale single‐center experience which evaluates the role of CEDM in presurgical staging and its impact on surgical planning. The aims of this retrospective study were to define the diagnostic performance of CEDM in the presurgical setting and to identify which types of patients could benefit from having CEDM. We selected 326 patients with BC who underwent CEDM as preoperative staging and had breast cancer‐related surgery at our institution. We analyzed those cases in which CEDM led to additional imaging or biopsy and those in which it changed the type of surgery that was planned according to conventional breast imaging (CI) techniques (digital mammography, tomosynthesis and bilateral handheld ultrasound). CEDM sensitivity in identifying the index lesion and sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and accuracy in the correct preoperative staging of BC of the whole population and in various subgroups were calculated. CEDM sensitivity for the index lesion was 98.8% (322/326), which led to additional breast imaging in 23.6% (77/326) of patients and additional biopsies in 17.5% (57/326). CEDM changed the type of surgery in 18.4% (60/326). In the preoperative breast cancer staging, CEDM sensitivity, specificity, PPV, NPV, and accuracy produced results of 93%, 98%, 90%, 98%, and 97%, respectively. CEDM performance was better in patients with palpable lesions. CEDM has an excellent diagnostic performance in the presurgical staging of BC. Symptomatic patients with palpable lesions benefitted most from preoperative CEDM, with a statistically significant difference compared with nonpalpable.     

Low-Dose Anti-T Lymphoglobulin as Prophylaxis for Graft-versus-Host Disease in Unrelated Donor Transplantations for Acute Leukemias and Myelodysplastic Syndromes

Chronic graft-versus-host disease (cGVHD) is a major complication after stem cell transplantation (HSCT). Several randomized studies already demonstrated that anti-T lymphoglobulin (ATLG) is effective in preventing GVHD after myeloablative unrelated and HLA-identical sibling transplants. However, the issue of doses and the potential increase of relapses still remain unsolved. Here we report data on 190 patients with acute leukemia and myelodysplastic syndrome who underwent an unrelated HSCT with low-dose ATLG (15 to 30 mg/kg) given at an earlier timing (days –6 to –2). HSCT was performed from HLA 10/10 (n?=?62, 33%), 9/10 (n?=?91, 48%), 8/10 (n?=?30, 16%), and <8/10 (n?=?7, 4%) identical unrelated donor. Peripheral blood was the stem cell source in 42% (n?=?80). Median follow-up was 51 months. Grades II to IV and III to IV acute GVHD were 26% and 9%, respectively, and 2-year overall and moderate to severe cGVHD were 23% and 14%, respectively. The 3-year incidences of relapse and nonrelapse mortality were 26% and 18%, respectively. The rates of 3-year overall survival (OS), disease-free survival (DFS), and GVHD-free and relapse-free survival (GRFS) were 60%, 56% and 44%, respectively. Factors such as younger donor, good performance status, and early disease were associated with better outcome in terms of OS, DFS, and GRFS. Our data indicate that doses of ATLG lower that those used in randomized clinical trials can be used for GVHD prevention, even in the adult setting, without clear increases in relapse and infections; these findings need to be further validated by a prospective randomized study.