Multi-Layer Technique (MLT) with Porcine Collagenated Cortical Bone Lamina for Bone Regeneration Procedures and Immediate Post-Extraction Implantation in the Esthetic Area: A Retrospective Case Series with a Mean Follow-Up of 5 Years

Background: Augmentation of the edentulous atrophic anterior region is a challenging situation. The purpose of this article was to evaluate the effectiveness of a collagenated cortical bone lamina of porcine origin for horizontal ridge augmentation in patients with inadequate alveolar ridge width undergoing immediate post-extraction implantation in the anterior sites, and to report on implant survival rates/complications. Materials and methods: The cases were extracted electronically from a large database according to these specific inclusion criteria: patients with inadequate alveolar ridge width in the anterior maxilla or mandible, who underwent immediate post-extraction implant placement and simultaneous alveolar bone reconstruction using xenogeneic cortical bone lamina. An additional layer of palatal connective tissue graft was inserted between lamina and the vestibular mucosa, for improving soft tissue healing. A collagenated bone substitute was additionally placed in the gap between the lamina and implant surface in all patients. The main outcomes were implant survival and complications. Results: Forty-nine patients with 65 implants were included. Patients’ mean age at the time of implant surgery was 60.0 ± 13.6 years. The mean follow-up was 60.5 ± 26.6 months after implant placement. The implant survival was 100%. Four postoperative complications occurred in four patients. No specific factor was found to be associated with complication occurrence. Conclusion: The use of collagenated cortical bone lamina can be considered as a successful option for alveolar reconstruction in immediate post-extraction implant insertion procedures in anterior regions with inadequate alveolar ridge width.     

Energy cost of walking measurements in subjects with lower limb amputations: a comparison study between floor and treadmill test

Measuring the energy cost of walking (ECW) is a valid way of assessing the walking efficiency of subjects who were prosthetic users following lower limb amputation. The aim of this study was to determine whether, in these subjects, treadmill and floor ECW measurements are comparable. We tested 24 subjects who had undergone unilateral lower limb amputations for vascular diseases as they walked at a self-selected comfortable speed on the floor and on a treadmill. The tests were conducted at the end of rehabilitative treatment to fit prosthesis. Eight subjects underwent transtibial and 16 transfemoral amputation. The measurements were taken with a portable gas analyzer. The self-selected comfortable speed on the treadmill was significantly lower than that on the floor, where the patients adopted the aid they normally used for walking; oxygen consumption was the same in the two tests. Therefore, for both transtibial and transfemoral patients, ECW was greater during walking on the treadmill. Steady-state heart rate did not differ in the two tests. The data show that the ECW values of the amputated subjects obtained on the treadmill at the end of rehabilitation did not correspond with those they obtained on the floor. The floor test is the one that may better reflect walking with prostheses and aids in everyday life, in subjects with dysvascular lower limb amputation, using the prosthesis for a short time.     

Epidemiology and clinical relevance of mutations in postpolycythemia vera and postessential thrombocythemia myelofibrosis: A study on 359 patients of the AGIMM group

Transformation to secondary myelofibrosis (MF) occurs as part of the natural history of polycythemia vera (PPV‐MF) and essential thrombocythemia (PET‐MF). Although primary (PMF) and secondary MF are considered similar diseases and managed similarly, there are few studies specifically focused on the latter. The aim of this study was to characterize the mutation landscape, and describe the main clinical correlates and prognostic implications of mutations, in a series of 359 patients with PPV‐MF and PET‐MF. Compared with PV and ET, the JAK2V617F and CALR mutated allele burden was significantly higher in PPV‐MF and/or PET‐MF, indicating a role for accumulation of mutated alleles in the process of transformation to MF. However, neither the allele burden nor the type of driver mutation influenced overall survival (OS), while absence of any driver mutation (triple negativity) was associated with significant reduction of OS in PET‐MF, similar to PMF. Of the five interrogated subclonal mutations (ASXL1, EZH2, SRSF2, IDH1, and IDH2), that comprise a prognostically detrimental high molecular risk (HMR) category in PMF, only SRSF2 mutations were associated with reduced survival in PET‐MF, and no additional mutation profile with prognostic relevance was highlighted. Overall, these data indicate that the molecular landscape of secondary forms of MF is different from PMF, suggesting that unknown mutational events might contribute to the progression from chronic phase disease to myelofibrosis. These findings also support more extended genotyping approaches aimed at identifying novel molecular abnormalities with prognostic relevance for patients with PPV‐MF and PET‐MF. Am. J. Hematol. 91:681–686, 2016. © 2016 Wiley Periodicals, Inc.     

Freestyle perforator flaps: an innovative approach to soft tissue reconstruction

Resurfacing of soft tissue defects consequent to skin cancer, melanoma, or sarcoma excision in different anatomical districts represents a difficult challenge for the plastic surgeon. Classic reconstructive procedures are frequently charged by unsatisfactory results. The introduction of perforator flaps in the clinical practice represented a revolution in the field of reconstructive plastic surgery. The technique further evolved with the introduction of the freestyle concept, allowing one to harvest a skin flap from any region of the body where an appropriate and detectable Doppler signal is present and to resurface soft tissue defects mobilizing the surrounding tissues, which present similar features compared with the recipient site in terms of color and texture, on a consistent vascular source and in a tension‐free manner. The authors present their personal approach to the reconstruction of soft tissue defects after excision for a basal cell carcinoma involving the medial tibial region.     

Discovery of Dimeric Arylsulfonamides as Potent ADAM8 Inhibitors

The metalloproteinase ADAM8 is upregulated in several cancers but has a dispensable function under physiological conditions. In tumor cells, ADAM8 is involved in invasion, migration, and angiogenesis. The use of bivalent inhibitors could impair migration and invasion through the double binding to a homodimeric form of ADAM8 located on the cell surface of tumor cells. Herein we report the rational design and synthesis of the first dimeric ADAM8 inhibitors selective over ADAM10 and matrix metalloproteinases. Bivalent derivatives have been obtained by dimerizing the structure of a previously described ADAM17 inhibitor, JG26. In particular, derivative 2 was shown to inhibit ADAM8 proteolytic activity in vitro and in cell-based assays at nanomolar concentration. Moreover, it was more effective than the parent monomeric compound in blocking invasiveness in the breast cancer MDA-MB-231 cell line, thus supporting our hypothesis about the importance of inhibiting the active homodimer of ADAM8.     

Influence of the anatomical features of different brain regions on the spatial localization of fiber photometry signals

Fiber photometry is widely used in neuroscience labs for in vivo detection of functional fluorescence from optical indicators of neuronal activity with a simple optical fiber. The fiber is commonly placed next to the region of interest to both excite and collect the fluorescence signal. However, the path of both excitation and fluorescence photons is altered by the uneven optical properties of the brain, due to local variation of the refractive index, different cellular types, densities and shapes. Nonetheless, the effect of the local anatomy on the actual shape and extent of the volume of tissue that interfaces with the fiber has received little attention so far. To fill this gap, we measured the size and shape of fiber photometry efficiency field in the primary motor and somatosensory cortex, in the hippocampus and in the striatum of the mouse brain, highlighting how their substructures determine the detected signal and the depth at which photons can be mined. Importantly, we show that the information on the spatial expression of the fluorescent probes alone is not sufficient to account for the contribution of local subregions to the overall collected signal, and it must be combined with the optical properties of the tissue adjacent to the fiber tip.     

The role of <Superscript>18</Superscript>F-FDG PET/CT in the detection of osteosarcoma recurrence

Aim

The aim of this study was to investigate the diagnostic accuracy of ¹⁸F-FDG-PET/CT in osteosarcoma patients suspicious for disease recurrence after adequate surgical therapy.

Methods

Inclusion criteria were: a) adequate surgical treatment for proven osteosarcoma and documented complete remission after therapy; b) ¹⁸F-FDG-PET/CT performed during follow-up for clinical/diagnostic suspicion of relapse; c) new surgical treatment with excision of the suspected lesions; d) histological validation of ¹⁸F-FDG-PET/CT findings. Thirty-seven patients matching all inclusion criteria were retrospectively enrolled (20 men and 17 female). Primary surgical treatment consists of resection (31 cases) or amputation (six cases). ¹⁸F-FDG-PET/CT performance was assessed with a per-patient and per-site evaluation of sensitivity, specificity, accuracy, positive predicting value (PPV), and negative predicting value (NPV). The sites of relapse were classified as local, lung, lymphnodes (LNs), and distant (other skeletal segments and/or distant soft tissue). The disease-free survival (DFS) and the overall survival (OS) after 18F-FDG PET/CT were evaluated.

Results

¹⁸F-FDG-PET/CT was positive in 89.2% (33/37) of patients. Local uptake only was observed in 35.1% patients (13/37); lung uptake only in 18.9% (7/37); distant uptake only in 2.7% (1/37) case; multiple sites of uptake in 32.4% (12/37). Histology resulted positive in 92% (34/37) of patients. A total of 51 pathologic lesions were evaluated (22 local relapse, 11 lung metastasis, 10 metastatic LNs, eight distant metastatic lesions). On a per-patient analysis ¹⁸F-FDG-PET/CT showed a sensitivity, specificity, accuracy, PPV, and NPV of 91%, 75%, 89%, 97%, 50%. On a per-site analysis the performance for local relapse was 96%, 100%, 97%, 100%, 93%, while for lung relapse detection was 80%, 100%, 92%, 100%, 88%. The mean follow-up after ¹⁸F-FDG-PET/CT was 21.5 months. At the last follow-up, 19% (7/37) of patients were death with disease, 38% (14/37) were alive with disease, and 43% (16/37) had no evidence of disease. Overall survival was 90% and 75% at 24 and 60 months, respectively.

Conclusion

¹⁸F-FDG-PET/CT showed valuable results for detecting recurrence(s) in osteosarcoma patients with suspicious of relapse after treatment, particularly in the detection of local relapse and lung metastasis.

     

Safety and efficacy of ruxolitinib in splanchnic vein thrombosis associated with myeloproliferative neoplasms

Splanchnic vein thrombosis (SVT) is one of the vascular complications of myeloproliferative neoplasms (MPN). We designed a phase 2 clinical trial to evaluate safety and efficacy of ruxolitinib in reducing splenomegaly and improving disease‐related symptoms in patients with MPN‐associated SVT. Patients diagnosed with myelofibrosis (12 cases), polycythemia vera (5 cases) and essential thrombocythemia (4 cases) received ruxolitinib for 24 weeks in the core study period. Spleen volume was assessed by magnetic resonance imaging (MRI) and splanchnic vein circulation by echo‐Doppler analysis. Nineteen patients carried JAK2V617F, one had MPLW515L, and one CALRL367fs*46 mutation. Eighteen patients had spleno‐portal‐mesenteric thrombosis, two had Budd–Chiari syndrome, and one had both sites involved; 16 patients had esophageal varices. Ruxolitinib was well tolerated with hematological toxicities consistent with those of patients without SVT and no hemorrhagic adverse events were recorded. After 24 weeks of treatment, spleen volume reduction ≥35% by MRI was achieved by 6/21 (29%) patients, and a ≥50% spleen length reduction by palpation at any time up to week 24 was obtained by 13/21 (62%) patients. At week 72, 8 of the 13 (62%) patients maintained the spleen response by palpation. No significant effect of treatment on esophageal varices or in splanchnic circulation was observed. MPN‐related symptoms, evaluated by MPN‐symptom assessment form (SAF) TSS questionnaire, improved significantly during the first 4 weeks and remained stable up to week 24. In conclusion, this trial shows that ruxolitinib is safe in patients with MPN‐associated SVT, and effective in reducing spleen size and disease‐related symptoms.