Fasting glucose and body mass index as predictors of activity in breast cancer patients treated with everolimus-exemestane: the EverExt study

Evidence on everolimus in breast cancer has placed hyperglycemia among the most common high grade adverse events. Anthropometrics and biomarkers of glucose metabolism were investigated in a observational study of 102 postmenopausal, HR + HER2- metastatic breast cancer patients treated with everolimus-exemestane in first and subsequent lines. Best overall response (BR) and clinical benefit rate (CBR) were assessed across subgroups defined upon fasting glucose (FG) and body mass index (BMI). Survival was estimated by Kaplan-Meier method and log-rank test. Survival predictors were tested in Cox models. Median follow up was 12.4 months (1.0-41.0). The overall cohort showed increasing levels of FG and decreasing BMI (p < 0.001). Lower FG fasting glucose at BR was more commonly associated with C/PR or SD compared with PD (p < 0.001). We also observed a somewhat higher BMI associated with better response (p = 0.052). More patients in the lowest FG category achieved clinical benefit compared to the highest (p < 0.001), while no relevant differences emerged for BMI. Fasting glucose at re-assessment was also predictive of PFS (p = 0.037), as confirmed in models including BMI and line of therapy (p = 0.049). Treatment discontinuation was significantly associated with changes in FG (p = 0.014). Further research is warranted to corroborate these findings and clarify the underlying mechanisms

Agnostic evaluation of ipilimumab and nivolumab association : a metanalysis

Background: Ipilimumab and Nivolumab, targeting the molecules CTLA-4, PD-1, respectively,have shown efficacy against several types of cancer. Despite these results, only a small percentage of patients maintains a long-lasting effect. Even Ipilimumab, in combination with nivolumab, has demonstrated a significant clinical benefit in multiple tumor types. However, no trial has been designed with the primary endpoint to compare the efficacy of nivolumab plus ipilimumab combined, compared to nivolumab alone. Hence, the added value of ipilimumab in the combination has not clearly been established yet. The aim of this study was to demonstrate the superiority of the combination strategy compared to the single agent therapy. Materials and methods: We performed a meta-analysis of Phase I-II-III Clinical Trials, published from 2010 up to 2020, in which the combination of ipilimumab plus nivolumab was compared to nivolumab alone. We extracted ORR, OS and PFS HR on the basis of treatment from the subgroup analysis of each trial. Results: A total of 7 trials were included in the present meta-analysis. Overall, 1313 patients were treated with the nivolumab plus ipilimumab combination compared to 1110 patients treated with nivolumabalone. All trials reported the Objective response rate(ORR), no heterogeneity was found among studies and the pooled Odds Ratio was highly in favor of the nivolumab plus ipilimumab combination with respect to nivolumab alone (1.683; 95% CI: 1.407–2.012; P < 0.0001). Three studies were considered for Progression free survival (PFS) analysis, and the pooled Hazard Ratio favored the combination of nivolumab plus ipilimumab with respect to nivolumab alone (0.807; 95% CI: 0.719–0.907; P < 0.0001). The Overall survival(OS) endpoint was considered only in 2 trials, and the pooled HR favored, also in this case, the combination of nivolumab plus ipilimumab with respect to nivolumab alone (0.87; 95% CI: 0.763–0.997; P = 0.045). Conclusions: The combination of ipilimumab plus nivolumab seems to be superior to nivolumab alone in cancer patients, regardless of histology

The use of ESEM-EDX as an innovative tool to analyze the mineral structure of peri-implant human bone

This study aimed to investigate the mineralization and chemical composition of the bone-implant interface and peri-implant tissues on human histological samples using an environmental scanning electron microscope as well as energy-dispersive x-ray spectroscopy (ESEM-EDX) as an innovative method. Eight unloaded implants with marginal bone tissue were retrieved after four months from eight patients and were histologically processed and analyzed. Histological samples were observed under optical microscopy (OM) to identify the microarchitecture of the sample and bone morphology. Then, all samples were observed under ESEM-EDX from the coronal to the most apical portion of the implant at 500x magnification. A region of interest with bone tissue of size 750 7 500 microns was selected to correspond to the first coronal and the last apical thread (ROI). EDX microanalysis was used to assess the elemental composition of the bone tissue along the thread interface and the ROI. Atomic percentages of Ca, P, N, and Ti, and the Ca/N, P/N and Ca/P ratios were measured in the ROI. Four major bone mineralization areas were identified based on the different chemical composition and ratios of the ROI. Area 1: A well-defined area with low Ca/N, P/N, and Ca/P was identified as low-density bone. Area 2: A defined area with higher Ca/N, P/N, and Ca/P, identified as new bone tissue, or bone remodeling areas. Area 3: A well-defined area with high Ca/N, /P/N, and Ca/P ratios, identified as bone tissue or bone chips. Area 4: An area with high Ca/N, P/N, and Ca/P ratios, which was identified as mature old cortical bone. Bone Area 2 was the most represented area along the bone-implant interface, while Bone Area 4 was identified only at sites approximately 1.5 mm from the interface. All areas were identified around implant biopsies, creating a mosaic-shaped distribution with well-defined borders. ESEM-EDX in combination with OM allowed to perform a microchemical analysis and offered new important information on the organic and inorganic content of the bone tissue around implants

Ultrashort Implants, Alternative Prosthetic Rehabilitation in Mandibular Atrophies in Fragile Subjects: A Retrospective Study

This study aimed to evaluate the effectiveness of using ultrashort implants in the rehabilitation of jaws of fragile patients. The aim of the study was to retrospectively evaluate the survival rate of full-arch prosthetic rehabilitation on ultrashort implants, length 4 mm, 4 mm in diameter in the premolar and canine area and 4.5 mm in diameter in the molar area, with the insertion torque of 60 Nw and immediate loading. Nineteen patients were evaluated for 3 years clinically and radiographically. The significant majority of the patients at the 3 year follow-up (T4) presented a stable and functional implant-supported prothesis, and the survival rate of the implants was 85%, with a loss of 16 implants on 114 implants. The combination of the innovative implant surfaces and the correct project of the prostheses, with the related implant connection, determined a different timing in the therapy, allowing to obtain an immediate loading, which is currently demanded by patients. This and recent reports on short and ultrashort implant usage in atrophic jaws offer a good solution in critical cases. In conclusion, within the limits of the study, the full-arch rehabilitation with immediate loading on ultrashort implants showed good results with few postoperative complications and related low biological cost

ESEM-EDX Mineralization and Morphological Analysis of Human Retrieved Maxillary Sinus Bone Graft Biopsies before Loading

This study aimed to analyze the morphology of bone graft granules, the presence of granule demineralization, and bone morphology in retrieved human maxillary sinus bone graft biopsies. Healthy patients underwent sinus bone augmentation using lateral access. Two different dimensions of the antrostomy were performed, a 4 mm or 8 mm height. After 6 months, all sites received one implant using a flap technique, crestal positioning, and submerged healing. Implant biopsies were retrieved after 3 months and were histologically processed. The ESEM analysis was performed on the entire portion of the peri-implant bone (up to 750 μm from the implant thread). Three different regions of interest (ROIs) were selected: the coronal, middle, and apical portions of the implant. In these areas, EDX was performed, and calcium (Ca), phosphate (P), nitrogen (N), and their atomic ratios (Ca/P, Ca/N, and P/N) were calculated. Different bone tissue electron-dense areas were detected through grayscale intensity quantification of ESEM images with different organic (N) or inorganic (Ca,P) compositions. A total of 16 biopsies from 16 healthy patients were analyzed. Bone graft granules were mostly detected in the apical ROI. New bone tissue bridges were detected in the apical and middle ROI. These structures, with lower Ca/N and P/N ratios, were connected and enveloped the bone graft granules. Cortical ROI revealed the most mineralized bone tissue. Conclusions: After 9 months, bone graft resorption was only partially completed and new bone tissue appeared less mineralized in the middle and apical ROI than in the coronal ROI

Ultrasonographic evaluation of three approaches for botulinum toxin injection into tibialis posterior muscle in chronic stroke patients with equinovarus foot: An observational study

Spastic equinovarus (SEV) foot deformity is commonly observed in patients with post-stroke spasticity. Tibialis posterior (TP) is a common target for botulinum toxin type-A (BoNT-A) injection, as a first-line treatment in non-fixed SEV deformity. For this deep muscle, ultrasonographic guidance is crucial to achieving maximum accuracy for the BoNT-A injection. In current clinical practice, there are three approaches to target the TP: an anterior, a posteromedial, and a posterior. To date, previous studies have failed to identify the best approach for needle insertion into TP. To explore the ultrasonographic characteristics of these approaches, we investigated affected and unaffected legs of 25 stroke patients with SEV treated with BoNT-A. We evaluated the qualitative (echo intensity) and quantitative (muscle depth, muscle thickness, overlying muscle, subcutaneous tissue, cross-sectional area) ultrasound characteristics of the three approaches for TP injection. In our sample, we observed significant differences among almost all the parameters of the three approaches, except for the safety window. Moreover, our analysis showed significant differences in cross-sectional area between treated and untreated. Advantages and disadvantages of each approach were investigated. Our findings can thus provide a suitable reference for clinical settings, especially for novice operators

Immunotherapy in the Treatment of Metastatic Melanoma: Current Knowledge and Future Directions

Melanoma is one of the most immunologic malignancies based on its higher prevalence in immune-compromised patients, the evidence of brisk lymphocytic infiltrates in both primary tumors and metastases, the documented recognition of melanoma antigens by tumor-infiltrating T lymphocytes and, most important, evidence that melanoma responds to immunotherapy. The use of immunotherapy in the treatment of metastatic melanoma is a relatively late discovery for this malignancy. Recent studies have shown a significantly higher success rate with combination of immunotherapy and chemotherapy, radiotherapy, or targeted molecular therapy. Immunotherapy is associated to a panel of dysimmune toxicities called immune-related adverse events that can affect one or more organs and may limit its use. Future directions in the treatment of metastatic melanoma include immunotherapy with anti-PD1 antibodies or targeted therapy with BRAF and MEK inhibitors