Franco Bassetto

Infections and autoimmunity: the multifaceted relationship

Multiple factors are thought to contribute to the development of immune response to self, including differences in genotypes, hormonal milieu, and environmental factors. This review focuses on the pivotal role of infection in the induction of autoimmune disorders. Although the development of autoimmune phenomena linked to infections is a common finding, the onset of autoimmune diseases is a rare event, arising from a combination of genetic susceptibility and environmental factors. There are several mechanisms through which pathogens can initiate or perpetuate autoimmunity. Some of them are antigen‐specific, including molecular mimicry, expression of modified, cryptic, or new antigenic determinants, and superantigens. Others are nonspecific and collectively known as “bystander activation.” They include enhanced processing and presentation of self‐antigens, immune cell activation, cytokine release, and cell apoptosis/necrosis. Infections may also trigger organ‐specific autoimmune diseases, but studies carried out until now have provided conflicting and inconclusive results regarding the role of viral and bacterial agents. Infections and autoimmune diseases have multifaceted and multidirectional relationships. It has been suggested recently that infections cannot only induce or precipitate autoimmune diseases, but they may also protect from autoimmunity or even abrogate an ongoing autoimmune process depending on the interaction between microorganisms and host. Therefore, we should look at microorganisms, not only as causes of infections but also as potential agents able to modulate the immune system. On the other hand, numerous evidences have emerged regarding the higher susceptibility of autoimmune patients to infections, possibly as a result of immunosuppressive therapy and treatment with biologic agents.

Electromyography data for non-invasive naturally-controlled robotic hand prostheses

Recent advances in rehabilitation robotics suggest that it may be possible for hand-amputated subjects to recover at least a significant part of the lost hand functionality. The control of robotic prosthetic hands using non-invasive techniques is still a challenge in real life: myoelectric prostheses give limited control capabilities, the control is often unnatural and must be learned through long training times. Meanwhile, scientific literature results are promising but they are still far from fulfilling real-life needs. This work aims to close this gap by allowing worldwide research groups to develop and test movement recognition and force control algorithms on a benchmark scientific database. The database is targeted at studying the relationship between surface electromyography, hand kinematics and hand forces, with the final goal of developing non-invasive, naturally controlled, robotic hand prostheses. The validation section verifies that the data are similar to data acquired in real-life conditions, and that recognition of different hand tasks by applying state-of-the-art signal features and machine-learning algorithms is possible.

Polymyositis, dermatomyositis and malignancy: A further intriguing link

The association between malignancy and autoimmune myositis has been largely described and confirmed by numerous epidemiological studies. The temporal relationship between the two pathologic conditions can vary: malignancy may occur before, at the same time or following the diagnosis of myositis. Beside these observations, the molecular mechanisms underlying this association are still unknown, even though it has been demonstrated a possible antigenic similarity between regenerating myoblasts and some cancer cell populations. To better identify peculiar histopathologic features common to cancer and myositis, we screened muscle biopsies from patients affected with polymyositis, dermatomyositis, myositis in association to cancer, and from patients affected with newly diagnosed cancer, but without myositis. Similarly to the histopatologic features that were observed in the muscle from myositis patients, especially in those with cancer associated myositis, in patients affected with malignancy at the clinical onset of disease we observed early sign of myopathy, characterized by internally nucleated and regenerating myofibers, most of them expressing the neural cell adhesion molecule. The hypothesis that in a particular subset of individuals genetically predisposed to autoimmunity, an initial subclinical tumor-induced myopathy may result in an autoimmune myositis, represents a further intriguing link behind the association of these two conditions.

Updated Scar Management Practical Guidelines: Non-invasive and invasive measures

Hypertrophic scars and keloids can be aesthetically displeasing and lead to severe psychosocial impairment. Many invasive and non-invasive options are available for the plastic (and any other) surgeon both to prevent and to treat abnormal scar formation. Recently, an updated set of practical evidence-based guidelines for the management of hypertrophic scars and keloids was developed by an international group of 24 experts from a wide range of specialities. An initial set of strategies to minimize the risk of scar formation is applicable to all types of scars and is indicated before, during and immediately after surgery. In addition to optimal surgical management, this includes measures to reduce skin tension, and to provide taping, hydration and ultraviolet (UV) protection of the early scar tissue. Silicone sheeting or gel is universally considered as the first-line prophylactic and treatment option for hypertrophic scars and keloids. The efficacy and safety of this gold-standard, non-invasive therapy has been demonstrated in many clinical studies. Other (more specialized) scar treatment options are available for high-risk patients and/or scars. Pressure garments may be indicated for more widespread scarring, especially after burns. At a later stage, more invasive or surgical procedures may be necessary for the correction of permanent unaesthetic scars and can be combined with adjuvant measures to achieve optimal outcomes. The choice of scar management measures for a particular patient should be based on the newly updated evidence-based recommendations taking individual patient and wound characteristics into consideration.

Necrotizing fasciitis: classification, diagnosis, and management.

Necrotizing fasciitis (NF), a life-threatening rare infection of the soft tissues, is a medical and surgical emergency. It is characterized by subtle, rapid onset of spreading inflammation and necrosis starting from the fascia, muscles, and subcutaneous fat, with subsequent necrosis of the overlying skin. Once suspected, immediate and extensive radical debridement of necrotic tissues is mandatory. Appropriate antibiotics and intensive general support avoid massive systemic diffusion of the infective process and are the key for successful treatment. However, early diagnosis is missed or delayed in 85% to 100% of cases in large published series: because of the lack of specific clinical features in the initial stage of the disease, it is often underestimated or confused with cellulitis or abscess. Mortality rates are still high and have shown no tendency to decrease in the last 100 years. Unfortunately, the prevalence of the disease is such that physicians rarely become sufficiently confident with NF to be able to proceed with rapid diagnosis and management. This review covers the literature published in MEDLINE in the period 1970 to December 31, 2010. Particular attention is given to the clinical and laboratory elements to be considered for diagnosis. A wide variety of diagnostic tools have been described to facilitate and hasten the diagnosis of NF, but the most important tool for early diagnosis still remains a high index of clinical suspicion.

Nanotechnology-based therapies for skin wound regeneration

The cutting-edge combination of nanotechnology with medicine offers the unprecedented opportunity to create materials and devices at a nanoscale level, holding the potential to revolutionize currently available macroscale therapeutics. Nanotechnology already provides a plethora of advantages to medical care, and the success of nanoparticulate systems suggests that a progressive increase in the exploration of their potential will take place in the near future. An overview on the current applications of nanotechnology to wound healing and wound care is presented.

Successful recellularization of human tendon scaffolds using adipose-derived mesenchymal stem cells and collagen gel.

The major goal of regenerative medicine is to determine experimental techniques that take maximal advantage of reparative processes that occur naturally in the animal body. Injection of mesenchymal stem cells into the core of a damaged tendon represents such an approach. Decellularization of native tendons as potential targets and seeding protocols are currently under investigation. The aim of our study was to manufacture a recellularized biocompatible scaffold from cadaveric tissue for use in total or partial tendon injuries. Results showed that it was possible to introduce proliferating cells into the core of a decellularized tendon to treat the scaffold with a collagen gel. The method was effective in maintaining scaffold extracellular matrix and for expressing collagen type I and cartilage oligomeric matrix protein by injecting mesenchymal stem cells. Copyright

The importance of recognizing body dysmorphic disorder in cosmetic surgery patients: do our patients need a preoperative psychiatric evaluation?

Abstract. Body dysmorphic disorder (BDD) is classified in DSM IV as a somatoform disorder. The main features of this condition are a persistent preoccupation with a supposed physical defect or the presence of a slight imperfection in appearance. If a real defect should exist, the importance given to this in determining self-appreciation causes an important impairment in social, affective, or other functioning areas. This affection causes the patient to ask for multiple esthetic treatments. In most cases such interventions do not produce positive results in improving symptoms and may induce a chronic situation. The aim of this report is to aid in recognition of BDD in patients requesting esthetic improvements and to study psychopathological comorbidities. A counseling service was established, and 56 patients (11 men, 45 women) were seen. There were two specific interviews, one for personality, psychotic, and mood disorders and the other for the diagnosis of BDD (SCID II 2.0 and MINIPLUS 5.0). The findings in this study confirm those reported previously: BDD is more frequent in this selected population than in the general population (53.6%). There is a high prevalence of mood and anxiety disorders. Among personality disorders the most frequent are borderline and obsessive-compulsive types. We emphasize the importance of increasing the collaboration between the esthetic surgeon and the psychiatrist to determine the true motivation for surgical improvement and to avoid esthetic surgery on patients with psychiatrist disorders.

Decellularized human skeletal muscle as biologic scaffold for reconstructive surgery

Engineered skeletal muscle tissues have been proposed as potential solutions for volumetric muscle losses, and biologic scaffolds have been obtained by decellularization of animal skeletal muscles. The aim of the present work was to analyse the characteristics of a biologic scaffold obtained by decellularization of human skeletal muscles (also through comparison with rats and rabbits) and to evaluate its integration capability in a rabbit model with an abdominal wall defect. Rat, rabbit and human muscle samples were alternatively decellularized with two protocols: n.1, involving sodium deoxycholate and DNase I; n.2, trypsin-EDTA and Triton X-NH4OH. Protocol 2 proved more effective, removing all cellular material and maintaining the three-dimensional networks of collagen and elastic fibers. Ultrastructural analyses with transmission and scanning electron microscopy confirmed the preservation of collagen, elastic fibres, glycosaminoglycans and proteoglycans. Implantation of human scaffolds in rabbits gave good results in terms of integration, although recellularization by muscle cells was not completely achieved. In conclusion, human skeletal muscles may be effectively decellularized to obtain scaffolds preserving the architecture of the extracellular matrix and showing mechanical properties suitable for implantation/integration. Further analyses will be necessary to verify the suitability of these scaffolds for in vitro recolonization by autologous cells before in vivo implantation.

The gracilis muscle and its use in clinical reconstruction: an anatomical, embryological, and radiological study.

The gracilis muscle is used widely in reconstructive surgery, as a pedicled or as a free microsurgical flap, for soft tissue coverage or as a functioning muscle transfer. Many studies, based on cadaver dissections, have focused on the vascular anatomy of the gracilis muscle and provided different data about the number, origin, and caliber of its vascular pedicles. Computed tomographic (CT) angiography of both thighs of 40 patients (35 males and 5 females, mean age: 63 years) have been analyzed to provide a detailed anatomical description of the arterial supply of the gracilis muscle. The gracilis muscle had a mean length of 41 ± 2.1 cm. The principal pedicle enters the gracilis muscle at a mean distance (±SD) of 10 ± 1 cm from the ischiopubic attachment of the muscle. Its caliber shows a mean value of 2.5 ± 0.5 mm, and it is statistically larger when originating directly from the deep femoral artery (45%) than from its muscular branch supplying the adductors, i.e., the “artery to the adductors” (46%) (P < 0.01). A significant correlation between the caliber of the artery of the main pedicle and the volume of the gracilis muscle was found (P < 0.01). The mean number of distal accessory pedicles is 1.8 (range, 1–4,) and the artery of the first of these pedicles shows a mean caliber of 2.0 mm. There is no correlation between either the number or the caliber of the artery of the accessory pedicles and the volume of the gracilis muscle. CT angiography, providing detailed images of the muscular and vascular structures of the thigh of each patient, could be a useful preoperative study for the reconstructive surgeon. It would allow a personalized planning of a gracilis flap, reducing the risk of iatrogenic damage. Clin. Anat. 21:696–704, 2008.