Behçet’s syndrome as a tool to dissect the mechanisms of thrombo-inflammation: clinical and pathogenetic aspects

Behçet’s syndrome (BS) is a complex disease with different organ involvement. The vascular one is the most intriguing, considering the existence of a specific group of patients suffering from recurrent vascular events involving the venous and, more rarely, the arterial vessels. Several clinical clues suggest the inflammatory nature of thrombosis in BS, especially of the venous involvement, thus BS is considered a model of inflammation-induced thrombosis. Unique among other inflammatory conditions, venous involvement (together with the arterial one) is currently treated with immunosuppressants, rather than with anti-coagulants. Although many in-vitro studies have suggested the different roles of the multiple players involved in clot formation, in-vivo models are crucial to study this process in a physiological context. At present, no clear mechanisms describing the pathophysiology of thrombo-inflammation in BS exist. Recently, we focused our attention on BS patients as a human in-vivo model of inflammation-induced thrombosis to investigate a new mechanism of clot formation. Indeed, fibrinogen displays a critical role not only in inflammatory processes, but also in clot formation, both in the fibrin network and in platelet aggregation. Reactive oxygen species (ROS)-derived modifications represent the main post-translational fibrinogen alterations responsible for structural and functional changes. Recent data have revealed that neutrophils (pivotal in the pathogenetic mechanisms leading to BS damage) promote fibrinogen oxidation and thrombus formation in BS. Altogether, these new findings may help understand the pathogenetic bases of inflammation-induced thrombosis and, more importantly, may suggest potential targets for innovative therapeutic approaches.     

Use of bar-clip attachments to enhance the retention of a maxillofacial prosthetic obturator: a clinical report

Precision attachments are commonly used in prosthetic dentistry but are still questioned in maxillofacial prosthetics. The aesthetic enhancement and functional rigidity provided by attachments are favourable features to many challenging clinical situations such as class-III defect (Aramany's maxillectomy classification). Surgical reconstruction is the standard treatment for this type of defect repair. However, owing to the need for dental rehabilitation and patient reserve, prosthetic rehabilitation was the modality chosen in this clinical case. The use of bar attachments is described in this paper as providing increased stability and retention of the prosthesis, and improved obturator water and airtightness.     

Relocation of a malpositioned maxillary implant with piezoelectric osteotomies: a case report

Implant relocation is a new surgical technique for correcting the alignment of malpositioned implants by mobilizing them with the surrounding bone until the desired position is achieved. In this case report, a 25-year-old woman was treated for the malposition of an implant in the maxillary left canine site. The use of a piezoelectric scalpel permits narrow, precise, and safe osteotomies, thus preventing involvement of the soft tissue and producing better healing potential compared to burs or saws. The results suggest that inadequately axially inclined implants can be successfully reconfigured using segmental piezoelectric osteotomies.     

Muscle mass and functional recovery in women with hip fracture

OBJECTIVE: To investigate the association between muscle mass and functional recovery in women with hip fracture. DESIGN: A total of 200 of 230 women with hip fracture admitted consecutively to a rehabilitation hospital were investigated in this survey study. Lean mass (LM) was assessed by dual-energy x-ray absorptiometry, 23.1 +/- 7.9 (mean +/- SD) days after fracture occurrence. Appendicular LM (aLM) was calculated as the sum of LM in arms and legs. Because metal implants (prostheses and nails) affect the regional assessment of body composition, aLM was corrected by substituting LM in the unfractured leg for LM in the fractured leg: corrected aLM = (LM in unfractured leg x 2) + LM in arms. We used two approaches to adjust corrected aLM for body size: corrected aLM divided by height squared (aLM/ht), and corrected aLM adjusted for height and fat mass (residuals). Functional recovery was assessed by using Barthel index scores. RESULTS: After adjustment for body size, corrected aLM was neither significantly correlated with Barthel index scores nor with the change in Barthel index scores after rehabilitation. Also, after stratification for quintiles of aLM/ht and residuals, no significant differences in functional recovery were found among the five groups. CONCLUSIONS: LM assessed after hip fracture is not associated with functional outcome in women.     

Norepinephrine promotes tumor microenvironment reactivity through β3-adrenoreceptors during melanoma progression

Stress has an emerging role in cancer and targeting stress-related β-adrenergic receptors (AR) has been proposed as a potential therapeutic approach in melanoma. Here we report that β3-AR expression correlates with melanoma aggressiveness. In addition, we highlight that β3-AR expression is not only restricted to cancer cells, but it is also expressed in vivo in stromal, inflammatory and vascular cells of the melanoma microenvironment. Particularly, we demonstrated that β3-AR can (i) instruct melanoma cells to respond to environmental stimuli, (ii) enhance melanoma cells response to stromal fibroblasts and macrophages, (iii) increase melanoma cell motility and (iv) induce stem-like traits. Noteworthy, β3-AR activation in melanoma accessory cells drives stromal reactivity by inducing pro-inflammatory cytokines secretion and de novo angiogenesis, sustaining tumor growth and melanoma aggressiveness. β3-ARs also play a mandatory role in the recruitment to tumor sites of circulating stromal cells precursors, in the differentiation of these cells towards different lineages, further favoring tumor inflammation, angiogenesis and ultimately melanoma malignancy. Our findings validate selective β3-AR antagonists as potential promising anti-metastatic agents. These could be used to complement current therapeutic approaches for melanoma patients (e.g. propranolol) by targeting non-neoplastic stromal cells, hence reducing therapy resistance of melanoma.     

Microenvironment and tumor cell plasticity: An easy way out

Cancer cells undergo genetic changes allowing their adaptation to environmental changes, thereby obtaining an advantage during the long metastatic route, disseminated of several changes in the surrounding environment. In particular, plasticity in cell motility, mainly due to epigenetic regulation of cancer cells by environmental insults, engage adaptive strategies aimed essentially to survive in hostile milieu, thereby escaping adverse sites. This review is focused on tumor microenvironment as a collection of structural and cellular elements promoting plasticity and adaptive programs. We analyze the role of extracellular matrix stiffness, hypoxia, nutrient deprivation, acidity, as well as different cell populations of tumor microenvironment.     

Should we fear direct oral anticoagulants more than vitamin K antagonists in simple single tooth extraction? A prospective comparative study

Objectives

The aim of this prospective comparative clinical study was to evaluate the effect of oral anticoagulants on peri- and post-operative bleeding during simple single tooth extractions, comparing patients in treatment with vitamin K antagonists (VKAs) and patients assuming direct oral anticoagulants (DOACs).

Materials and methods

Patients under oral anticoagulant therapy needing dental extraction were eligible for entering the study; patients were enrolled following inclusion and exclusion criteria and divided into VKAs and DOAC group according to the anticoagulation therapy. Included patients underwent a simple single dental extraction with elevators and forceps with a maximum surgical time of 15 minutes, without anticoagulation therapy discontinuation. All participants were assessed pre-operatively, during surgery, 30 min minutes and 7 days after surgery. Biological complications were registered and post-extraction bleeding was clinically defined according to Iwabuchi classification. Parametric and non-parametric tests were used to evaluate the variables between the groups.

Results

Sixty-five patients per group were enrolled and 130 teeth were extracted. The two groups were comparable for pre-, peri-, and post-operative variables. Only 1 patient of DOAC group and 2 patients for VKA group needed medical evaluation for post-extractive bleeding. No statistically significant difference resulted in post-operative bleeding events between the groups (p = 0.425).

Conclusions

DOAC and VKA patients showed the same incidence of bleeding complications after simple single tooth extraction. Bleeding events were not statistically significant and not clinically relevant.

Clinical relevance

Patients assuming DOACs can be treated similarly to patients in VKAs therapy with INR index between 2 and 3. Non-ceasing of DOAC therapy seems to be appropriate for simple single dental extractions.

     

Genetic factors are major determinants of phenotypic variability in a mouse model of the DiGeorge/del22q11 syndromes

The del22q11 syndrome is associated with a highly variable phenotype despite the uniformity of the chromosomal deletion that causes the disease in most patients. Df1/+ mice, which model del22q11, present with reduced penetrance of cardiovascular defects similar to those seen in deleted patients but not with other del22q11-like findings. The reduced penetrance of cardiovascular defects is caused by the ability of mutant embryos to recover from a fourth pharyngeal arch artery growth abnormality that is fully penetrant in early embryos. Here we show that genetic background has a major effect on penetrance of cardiovascular defects by affecting this embryonic recovery process. This effect could not be explained by allelic variation at the haploid locus, and it is likely to be caused by genetic modifiers elsewhere in the genome. We also show that genetic factors control extension of the Df1/+ phenotype to include thymic and parathyroid anomalies, establishing the Df1 mouse as a model for the genetic analysis of three major features of human del22q11 syndrome. We found that in Df1/+ mice, as in human patients, expression of the heart and thymic phenotypes are essentially independent from each other, suggesting that they may be controlled by different genetic modifiers. These data provide a framework for our understanding of phenotypic variability in patients with del22q11 syndrome and the tools for its genetic dissection.