The applications of Wearable Cardioverter Defibrillators in Heart Failure and beyond.

Abstract: Wearable cardioverter defibrillator has revealed a crucial device both in patients with a clear indication of ICD implantation but with temporary contraindications or in expectation of a diagnosis, considering that its use should be individualized.

Funneling Spontaneous Emission into Waveguides via Epsilon-Near-Zero Metamaterials.

In this work, we discuss the use of epsilon-near-zero (ENZ) metamaterials to efficiently couple light radiated by a dipolar source to an in-plane waveguide. We exploit both enhanced and directional emission provided by ENZ metamaterials to optimize the injection of light into the waveguide by tuning the metal fill factor. We show that a net increase in intensity injected into the waveguide with respect to the total power radiated by the isolated dipole can be achieved in experimentally feasible conditions. We think the proposed system may open up new opportunities for several optical applications and integrated technologies, especially for those limited by outcoupling efficiency and emission rate.

Actinomyces and MRONJ: A retrospective study and a literature review.

The AAOMS in 2014 changed from BRONJ to the term Medication-Related Osteonecrosis of the Jaw (MRONJ), because of the growing number of osteonecrosis cases associated with other antiresorptive and antiangiogenic therapies. Even if the drugs involved are different, the histopathological findings are the same. Colonies of Actinomyces are encountered in most cases. The aim of the present study is to report on Actinomyces prevalence among the cases of MRONJ, taking into consideration also antiresorptive and antiangiogenic therapies in the literature and in our sample between 2005 and 2020. The review was performed using the database Medline the linkage between Actinomyces infection and MRONJ. The retrospective study was conducted on patients between with clinical and radiological manifestations of MRONJ May 2005 and February 2020. A total of 42 articles were found, 30 publications have been taken into consideration for the review. A total of 114 patients have been examined at the Padua Hospital. A total of 101 oncological patients presented the histological confirmation of MRONJ. 83 specimens revealed the presence of Actinomyces infection (82.18%). Actinomyces-associated lesions are frequent and present a wide spectrum of clinical manifestation.

Multi-dorsal metacarpal artery perforator adipofascial turnover flap for index to little finger reconstruction: Anatomical study and clinical application.

Reconstruction of the dorsum of the hand and fingers is one of the main challenges in hand surgery. Regional flaps from the forearm, free flaps, or pocket procedures are options when multiple digits are injured with tendon damage and bone exposure. These procedures can be technically demanding and are often plagued by a texture mismatch. We conducted an anatomical study of 20 fresh frozen hands. The second, third and fourth intermetacarpal spaces were analyzed with the aim of defining the vascular foundation of dorsal hand adipofascial-turnover flaps based on dorsal metacarpal artery (DMA) perforators, analyzing their potential for reconstruction procedures on the dorsum of the hand. In three cases, the 4th intermetacarpal space lacked the DMA. A mean of 3.5 arterial communications were found between the DMA and palmar arterial system. Each hand had 11 ± 2 dorsal skin perforators, which were equally distributed among different intermetacarpal spaces. At least one perforator was present in each one-third of the space. The most distal perforators were the largest in all spaces but missing in two hands. A clinical case of multiple index finger to little finger reconstruction with this new multi-dorsal metacarpal artery perforator (mDMAP) adipofascial turnover flap is presented. Our anatomical study confirmed previous descriptions of the anatomy of the dorsum of the hand. It supports the safety of the mDMAP adipofascial turnover flap based on all distal arterial perforator for the simultaneous reconstruction of index to little finger injuries. Similarly, adipofascial turnover flaps can be raised from more proximal perforators arising from DMAs if more than one intermetacarpal space is included.

COVID-19 strategy in organizing and planning orthopedic surgery in a major orthopedic referral center in an area of Italy severely affected by the pandemic: experience of the Department of Orthopedics, University of Padova.

BACKGROUND: According to the required reorganization of all hospital activities, the recent COVID-19 pandemic had dramatic consequences on the orthopedic world. We think that informing the orthopedic community about the strategy that we adopted both in our hospital and in our Department of Orthopedics could be useful, particularly for those who are facing the pandemic later than Italy. METHODS: Changes were done in our hospital by medical direction to reallocate resources to COVID-19 patients. In the Orthopedic Department, a decrease in the number of beds and surgical activity was stabilized. Since March 13, it has been avoided to perform elective surgery, and since March 16, non-urgent outpatient consultations were abolished. This activity reduction was associated with careful evaluation of staff and patients: extensive periodical swab testing of all healthcare staff and swab testing of all surgical patients were applied. RESULTS: These restrictions determined an overall reduction of all our surgical activities of 30% compared to 2019. We also had a reduction in outpatient clinic activities and admissions to the orthopedic emergency unit. Extensive swab testing has proven successful: of more than 160 people tested in our building, only three COVID-19 positives were found, and of over more than 200 surgical procedures, only two positive patients were found. CONCLUSIONS: Extensive swab test of all people (even if asymptomatic) and proactive tracing and quarantining of potential COVID-19 positive patients may diminish the virus spread.

Thiol-to-amine cyclization reaction enables screening of large libraries of macrocyclic compounds and the generation of sub-kilodalton ligands.

Macrocyclic compounds are an attractive modality for drug development, but the limited availability of large, structurally diverse macrocyclic libraries hampers the discovery of leads. Here, we describe the discovery of efficient macrocyclization reactions based on thiol-to-amine ligations using bis-electrophiles, their application to synthesize and screen large libraries of macrocyclic compounds, and the identification of potent small macrocyclic ligands. The thiol-to-amine cyclization reactions showed unexpectedly high yields for a wide substrate range, which obviated product purification and enabled the generation and screening of an 8988 macrocycle library with a comparatively small effort. X-ray structure analysis of an identified thrombin inhibitor (K i = 42 ± 5 nM) revealed a snug fit with the target, validating the strategy of screening large libraries with a high skeletal diversity. The approach provides a route for screening large sub-kilodalton macrocyclic libraries and may be applied to many challenging drug targets.

Infection in orthopaedic oncology: crucial problem in modern reconstructive techniques.

OBJECTIVE: Infection after orthopaedic oncology surgery is a relatively frequent complication. Infection rate ranges in the literature between 3.7% and 19.9%, increasing up to 47% after pelvic resection and reconstruction. It represents a challenging topic when occurring in oncologic patients because of the delay of systemic and local treatments, influencing prognosis. Infection is a major concern in terms of both prevention and treatment. The aim of our review was to analyze data reported in the literature about strategies and new materials for infection prevention in musculoskeletal oncology surgery. MATERIALS AND METHODS: We reviewed the literature focusing on the use of new materials that can reduce the risk of infection, avoiding biofilm formation on the implant surface. RESULTS AND DISCUSSION: New materials are available to try to reduce the risk of infection. Iodine-coating, DAC-coating or silver-coating, are the more promising technologies available at today. Initial results with DAC-coating in non-oncological patients are interesting; however, studies about its efficacy in preventing infection in orthopaedic oncology are not present in literature. On the other side, iodine-coating implants or silver-coating prostheses demonstrated efficacy against early infections, associated with lower risk of implant removal and amputation as final surgery. CONCLUSIONS: Post-operative infections in orthopaedic oncology surgery are still frequent, and their diagnosis and treatment are demanding. According to the literature, silver-coated prostheses should be considered as the best option in case of revision surgery due to infection. However, there is no evidence that these new materials are effective to decrease the risk of infection drastically. Further studies with numerous series and long-term follow up are required.

Quantification of hyaluronan in human fasciae: variations with function and anatomical site.

Recently, alterations in fascial gliding-like movement have been invoked as critical in the etiology of myofascial pain. Various methods have been attempted for the relief of this major and debilitating clinical problem. Paramount have been attempts to restore correct gliding between fascial layers and the movement over bone, joint, and muscular structures. One of the key elements that underlies such fascial movement is hyaluronan. However, until now, the precise content of hyaluronan within fasciae has been unknown. This study quantifies for the first time the hyaluronan content of human fascial samples obtained from a variety of anatomic sites. Here, we demonstrate that the average amount varies according to anatomic site, and according to the different kinds of sliding properties of the particular fascia. For example, the fascia lata has 35 µg of hyaluronan per gram of tissue, similar to that of the rectus sheath (29 µg g-1 ). However, the types of fascia adherent to muscle contain far less hyaluronan: 6 µg g-1 in the fascia overlying the trapezius and deltoid muscles. In the fascia that surrounds joints, the hyaluronan increases to 90 µg g-1 , such as in the retinacula of the ankle, where greater degrees of movement occur. Surprisingly, no significant differences were detected at any site as a function of age or sex (P-value > 0.05, t-test) with the sole exception of the plantar fascia. This work can provide a better understanding of the role of hyaluronan in fascia. It will facilitate a better comprehension of the modulation of the hyaluronan-rich layer that occurs in relation to the various conditions that affect fascia, and the diverse factors that underlie the attendant pathologies.

Megaprosthesis of the knee in tumor and revision surgery.

The introduction of multidisciplinary approach with chemo and radiotherapy, the advances in surgical and the improvements of diagnostic techniques allowed limb salvage surgery in most cases of bone sarcomas instead of amputation. Modular megaprostheses are the most common method of reconstruction after segmental resection of the long bones in the extremities for their availability, immediate fixation, early weight bearing, good function. Despite the advances in materials and implant designs, these systems have an high incidence of complications. Aim of this study was to report the experience on mega-prostheses implanted around the knee in tumor and revision surgery to analyze: the most frequent used current systems, the problems of stems fixation, extensor mechanism reconstructions in proximal tibia resections and the preservation of growth of the lower extremity in children.

The XIIIth Banff Conference on Allograft Pathology: The Banff 2015 Heart Meeting Report: Improving Antibody-Mediated Rejection Diagnostics: Strengths, Unmet Needs, and Future Directions.

The 13th Banff Conference on Allograft Pathology was held in Vancouver, British Columbia, Canada from October 5 to 10, 2015. The cardiac session was devoted to current diagnostic issues in heart transplantation with a focus on antibody-mediated rejection (AMR) and small vessel arteriopathy. Specific topics included the strengths and limitations of the current rejection grading system, the central role of microvascular injury in AMR and approaches to semiquantitative assessment of histopathologic and immunophenotypic indicators, the role of AMR in the development of cardiac allograft vasculopathy, the important role of serologic antibody detection in the management of transplant recipients, and the potential application of new molecular approaches to the elucidation of the pathophysiology of AMR and potential for improving the current diagnostic system. Herein we summarize the key points from the presentations, the comprehensive, open and wide-ranging multidisciplinary discussion that was generated, and considerations for future endeavors.

Past and present of interposition arthroplasties for joint repair with special tribute to the contribution by Vittorio Putti.

Several techniques have been proposed to restore the compromised function of a joint. These include the arthroplasty by placing various tissues or materials between the articular surfaces. An important contribution to the diffusion of arthroplasty techniques was made by Vittorio Putti, head of the Rizzoli Orthopedic Institute in Bologna from 1912 to 1940. Interposition arthroplasty is still used for some non-weight-bearing joints, such as wrist and elbow, and gives good results. This type of surgery has been further developed by the improvement in biomaterials, biomechanical studies and the regenerative medicine. This paper describes the development starting from a historical survey particularly focused on Putti's contribution and ending with the state of the art of regenerative medicine in the treatment of joint diseases. Level of evidence V.

Post-transplant Lymphoproliferative Disorders: A Rare Case of Primary Pericardial Involvement Epstein-Barr Virus-Correlated in Heart Transplantation.

Post-transplant lymphoproliferative disorders (PTLDs) are considered a fatal consequence of immunosuppression. We report a case of a 52-year-old patient, who underwent a cardiac transplantation and presented undefined recurrent episodes of pleuropericardial effusions without lymphoadenomegaly at chest radiographs and computed tomography. Histopathological analysis of the bioptic pericardium showed a specific chronic inflammation. Monitoring endomyocardial biopsies (EMBs) showed only 1 episodes of greater than grade 2R acute cellular rejection requiring immunosuppressive treatment, mild vasculitis in 2 subsequently EMBs while constantly negative for antibody-mediated rejection or infection. Only a post-mortem examination demonstrated the presence of an aggressive acute non-Epstein-Barr virus (EBV)-related proliferative disorder with unusual primitive localization into the pericardium and with coronary epicardial and intramyocardial necrotizing vasculitis and superimposed occlusive and subocclusive thrombosis. Recurrence of unexplained early pleuropericardial effusion and mild intramyocardial vasculitis should raise the suspicion of PTLD requiring reduction of immunosuppression, even in the setting of negative intramyocardial cellular infiltrate and tissue EBV-negative molecular assessment.

Climbing experience in glass eels: A cognitive task or a matter of physical capacities?

The European eel is a panmictic species, whose decline has been recorded since the last 30 years. Among human-induced environmental factors of decline, the impact of water dams during species migration is questioned. Indeed, water impoundments can be a severe obstacle for young eels trying to reach the upstream freshwater zones, even if they are equipped with fish-friendly passes. The passage by such devices could be an important event shaping the outcome of the future life and life history traits of eels. We studied what phenotypic traits were associated with the event of experience of passage by water obstacles. We analyzed specific enzyme activities and/or gene transcription levels in the muscle and brain to test whether the obstacle passage is rather a physical or cognitive task. We found that after a long period of maintenance under homogenous conditions, transcription levels of several genes linked to synaptic plasticity, neurogenesis and thyroid activity differed among the field-experience groups. In contrast, muscle gene transcription levels or enzymatic activities did not show any differences among fish groups. We suggest that cognitive processes such as learning and memory acquisition rather than swimming-related metabolic capacities are involved in passage of water obstacles by young eels.

ANTIPSYCHOTICS REVERSE P-GLYCOPROTEIN-MEDIATED DOXORUBICIN RESISTANCE IN HUMAN UTERINE SARCOMA MES-SA/Dx5 CELLS: A NOVEL APPROACH TO CANCER CHEMOTHERAPY.

Multidrug resistance (MDR) mediated by P-glycoprotein (Pgp) remains one of the major obstacles to effective cancer chemotherapy. Several chemosensitizers have been used in vivo and in vitro to reverse MDR but have exhibited several unwanted side effects. Antipsychotics are often administered to treat psychiatric disorders such as delirium, anxiety and sleep disorders in cancer patients during chemotherapy. The present in vitro study, examined the effects of two common antipsychotic compounds, haloperidol and risperidone, and a natural compound such as theobromine on reversing MDR Pgp-mediated, to evaluate their potential use as chemosensitizing agents. The human doxorubicin (doxo) resistant uterine sarcoma cells (MES-SA/Dx5) that overexpress Pgp (100-fold), were treated with the antipsychotic alone (1, 10 and 20 µM) or in combination with different concentrations of doxo (2, 4 and 8 µM). The accumulation and cytotoxicity of doxo (MTT assay) and cellular GSH content (GSH assay) in comparison with verapamil, a well-known Pgp inhibitor, used as reference molecule were examined. It was found that the three compounds significantly enhanced the intracellular accumulation of doxo in resistant cancer cells, when compared with cells receiving doxo alone (p<0.05). Furthermore, compounds showed strong potency to increase doxo cytotoxicity toward resistant MES-SA/Dx5 cells, when compared with untreated control cells. The antipsychotic compounds also significantly increased GSH content at all concentrations (> 30%) in resistant cells, when compared to untreated control cells (p<0.05). These findings suggest that the antipsychotics or their derivatives might represent a novel class of reversal agents for overcoming MDR in cancer therapy, in particular theobromine showed to be an effective Pgp inhibitor with the lowest toxicity.

Enhanced fluorescence detection of miRNA-16 on a photonic crystal.

We report a novel sensing method for fluorescence-labelled microRNAs (miRNAs) spotted on an all-dielectric photonic structure. Such a photonic structure provides an enhanced excitation and a directional beaming of the emitted fluorescence, resulting in a significant improvement of the overall signal collected. As a result, the Limit of Detection (LoD) is demonstrated to decrease by a factor of about 50. A compact read-out system allows a wide-field imaging-based detection, with little or no optical alignment issues, which makes this approach particularly interesting for further development for example in microarray-type bioassays.

Tumor Necrosis Factor Related Apoptosis Inducing Ligand (Trail) in endothelial response to biomechanical and biochemical stresses in arteries.

Shear stress is determined by three physical components described in a famous triad: blood flow, blood viscosity and vessel geometry. Through the direct action on endothelium, shear stress is able to radically interfere with endothelial properties and the physiology of the vascular wall. Endothelial cells (ECs) have also to sustain biochemical stresses represented by chemokines, growth factors, cytokines, complement, hormones, nitric oxide (NO), oxygen and reactive oxygen species (ROS). Many growth factors, cytokines, chemokines, hormones, and chemical substances, like NO, act and regulate endothelium functions and homeostasis. Among these cytokines Tumor Necrosis Factor Related Apoptosis Inducing Ligand (TRAIL) has been assigned a regulatory role in ECs physiology and physiopathology. Thus, the aim of this review is to provide a general overview of the endothelial response pathways after different types of biomechanical and biochemical stress in in vitro models and to analyze the crucial role of TRAIL under pathological conditions of the cardiocirculatory system like atherosclerosis, coronary artery disease, and diabetes.

Leiomyosarcoma of the hand.

Soft-tissue sarcomas of the hand are rare and the devastating effect of an undiagnosed sarcoma warrants clinical vigilance. We present the case of an unsuspected leiomyosarcoma localised in the hand in order to underline (i) the rarity of the disease in this site, (ii) the role of adequate surgical treatment in the first step, (iii) the relationship with adjuvant treatments, lymph node metastasis and the poor prognosis of this tumour.