A modified Frosch approach for posterior tibial plateau fractures: Technical note and case series.

Achieving the best possible articular congruity following a tibial plateau (TP) fracture is associated with better long-term functional outcomes; TP has an essential role in the movements of the knee joint and is well established that a not optimal reduction leads to articular instability and early osteoarthritis. In recent times, 3D reconstruction from CT scan has greatly contributed to improve the surgical treatment of these fractures since an accurate preoperative plan gives the possibility to decide the best interventional strategy before the surgical incision. Reduction of the posterior part of tibial plateau is not easily achievable with standard surgical access. Several posterolateral approaches, proposed by authors such as Frosch and Lobenhoffer, have been described over the years; these approaches can be divided into 2 groups: with or without osteotomy of the fibula. Main disadvantages of these techniques are the large skin incision, the difficulty of exposing the lateral part of the tibia, the high frequency of damages of the posterolateral TP corner, and in some cases the necessity of performing fibular head osteotomy. The surgical approach presented in this paper is a simple innovation of the well-known Frosch approach: skin incision is about 12 centimeters in length and runs in a "S" shape with the center positioned over the head of the fibula. It starts 2 centimeters laterally to the tibial crest 6 centimeters below the tibial tuberosity and is directed proximally, curving posteriorly at the level of fibular head and returning straight in the most proximal part; it terminates 4 centimeters posteriorly the lateral femoral condyle. This innovative approach allows the trauma surgeon to achieve an optimal exposure and control of posterior tibial plateau fractures, with the great advantage of being able to treat the lateral tibial plateau with the same surgical incision.

SARS-CoV-2 detection in primary thyroid sarcoma: coincidence or interaction?

INTRODUCTION: Thyroid dysfunctions associated with SARS-CoV-2 are emerging in scientific literature. During the second COVID-19 epidemic spread, we evaluated a patient with the suspect of subacute thyroiditis. METHODS AND RESULTS: Specimen from fine-needle aspiration of a hypoechoic undefined area was analyzed for cytology and for SARS-CoV-2 detection. SARS-CoV-2 was retrieved by real-time polymerase chain reaction on the cytologic sample, which was then cultured on Vero E6 cells and demonstrated to be cytopathic. Whole-genome sequence was deposited. Histological exam diagnosed a rare case of primary thyroid sarcoma with diffuse and strong expression of mouse double minute 2 homolog (MDM2) oncoprotein. Ultrastructural examination confirmed, in several neoplastic cells, the presence of viral particles in cytoplasmic vacuoles. CONCLUSIONS: In our hypothesis, SARS-CoV-2 and sarcoma coexistence could represent a synergistic interplay, ultimately favoring both viral persistence and tumor proliferation: the overexpression of MDM2 in tumor cells might have generated a favorable immunological niche for SARS-CoV-2 localization and, in turn, SARS-CoV-2 could have favored tumor growth by inducing MDM2-mediated p53 downregulation. Functional studies are needed to confirm this suggestive pathway.

The efficacy of ultraviolet light-emitting technology against coronaviruses: a systematic review.

The ongoing pandemic of COVID-19 has underlined the importance of adopting effective infection prevention and control (IPC) measures in hospital and community settings. Ultraviolet (UV)-based technologies represent promising IPC tools: their effective application for sanitation has been extensively evaluated in the past but scant, heterogeneous and inconclusive evidence is available on their effect on SARS-CoV-2 transmission. With the aim of pooling the available evidence on the efficacy of UV technologies against coronaviruses, we conducted a systematic review following PRISMA guidelines, searching Medline, Embase and the Cochrane Library, and the main clinical trials' registries (WHO ICTRP, ClinicalTrials.gov, Cochrane and EU Clinical Trial Register). Quantitative data on studies' interventions were summarized in tables, pooled by different coronavirus species and strain, UV source, characteristics of UV light exposure and outcomes. Eighteen papers met our inclusion criteria, published between 1972 and 2020. Six focused on SARS-CoV-2, four on SARS-CoV-1, one on MERS-CoV, three on seasonal coronaviruses, and four on animal coronaviruses. All were experimental studies. Overall, despite wide heterogenicity within included studies, complete inactivation of coronaviruses on surfaces or aerosolized, including SARS-CoV-2, was reported to take a maximum exposure time of 15 min and to need a maximum distance from the UV emitter of up to 1 m. Advances in UV-based technologies in the field of sanitation and their proved high virucidal potential against SARS-CoV-2 support their use for IPC in hospital and community settings and their contribution towards ending the COVID-19 pandemic. National and international guidelines are to be updated and parameters and conditions of use need to be identified to ensure both efficacy and safety of UV technology application for effective infection prevention and control in both healthcare and non-healthcare settings.

Role of circulating endothelial progenitor cells in the reparative mechanisms of stable ischemic myocardium.

BACKGROUND: Mobilization of endothelial progenitor cells (EPCs) into circulation from bone marrow in patients with acute myocardial infarction has strong scientific evidence; less is known about EPC mobilization in patients with stable coronary artery disease (CAD). The aim of this study was to investigate the association of stable ischemic heart disease with EPC levels in tissue and blood. METHODS: Fifty-five consecutive patients admitted to a single treatment center for valve or coronary artery bypass grafting (CABG) surgeries were included in the study. Blood samples were collected in the morning before surgery and analyzed by flow-cytometry to determine peripheral EPC levels (EPC/ml). Tissue EPC (CD34+VEGFR2+) levels were assessed on a right atrial appendage segment. RESULTS: Mean age was 76±5years, 48% were men, and 53% had CAD The number of CD34+ VEGFR2+ cells in the tissue of patients with CAD was significantly higher (p<0.005) and circulating EPC showed a tendency to be reduced by approximately 20% in peripheral blood of patients with CAD when compared to those without CAD. CONCLUSION: Patients with stable CAD had higher EPC density values (EPC/mm2) and were more likely to have lower EPC blood levels when compare with normal controls.

Role and potential therapeutic use of antibodies against herpetic infections.

BACKGROUND: The cellular adaptive response directed against herpesviruses is widely described in the scientific literature as a pivotal component of the immune system able to control virus replication. The role of humoral immunity remains unclear and controversial. AIMS: Discussing the role of adaptive immunity in herpesvirus infection control, highlighting the potential role of the humoral branch of immunity through the description of human monoclonal antibodies directed against herpesviruses. SOURCES: PubMed search for relevant publications related to protective immunity against Herpesviridae. CONTENT: This review describes the role of adaptive immunity directed against Herpesviridae, focusing on the human humoral response naturally elicited during their infections. Given the ever-increasing interest in monoclonal antibodies as novel therapeutics, the contribution of humoral immunity in controlling productive infection, during both primary infection and reactivations, is discussed. IMPLICATIONS: Human monoclonal antibodies directed against the different Herpesviridae species may represent novel molecular probes to further characterize the molecular machinery involved in herpesvirus infection; and allow the development of novel therapeutics and effective vaccine strategies.

Control of infectious mortality due to carbapenemase-producing Klebsiella pneumoniae in hematopoietic stem cell transplantation.

Carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) infections are an emerging cause of death after hematopoietic stem cell transplantation (HSCT). In allogeneic transplants, mortality rate may rise up to 60%. We retrospectively evaluated 540 patients receiving a transplant from an auto- or an allogeneic source between January 2011 and October 2015. After an Institutional increase in the prevalence of KPC-Kp bloodstream infections (BSI) in June 2012, from July 2012, 366 consecutive patients received the following preventive measures: (i) weekly rectal swabs for surveillance; (ii) contact precautions in carriers (iii) early-targeted therapy in neutropenic febrile carriers. Molecular typing identified KPC-Kp clone ST512 as the main clone responsible for colonization, BSI and outbreaks. After the introduction of these preventive measures, the cumulative incidence of KPC-Kp BSI (P=0.01) and septic shocks (P=0.01) at 1 year after HSCT was significantly reduced. KPC-Kp infection-mortality dropped from 62.5% (pre-intervention) to 16.6% (post-intervention). Day 100 transplant-related mortality and KPC-Kp infection-related mortality after allogeneic HSCT were reduced from 22% to 10% (P=0.001) and from 4% to 1% (P=0.04), respectively. None of the pre-HSCT carriers was excluded from transplant. These results suggest that active surveillance, contact precautions and early-targeted therapies, may efficiently control KPC-Kp spread and related mortality even after allogeneic HSCT.

Early molecular diagnosis of aspergillosis in a patient with acute myeloid leukaemia.

Diagnosis of invasive fungal infection remains challenging. Here we report a case of early diagnosis of invasive aspergillosis in a neutropenic patient affected by acute myeloid leukaemia, achieved through the detection of Aspergillus fumigatus species-specific ribonucleic acid sequences by a sensitive multiplex real-time polymerase chain reaction-based molecular assay. Thanks to the early diagnosis, targeted therapy was promptly established and the severe fungal infection controlled, allowing the patient to subsequently receive allogeneic hematopoietic stem cell transplantation from a haploidentical donor, her only curative option. Also in this instance, targeted secondary antifungal prophylaxis with voriconazole avoided any other fungal infection afterwards. This report suggests how the implementation of molecular assays in combination with routine diagnostic procedures, can improve microbiological diagnosis in sepsis, particularly in case of fungal infection, difficult to detect with standard microbiological culture methods.

Conceptual design and analysis of ITM oxy-combustion power cycles.

Ion transport membrane (ITM)-based oxy-combustion systems could potentially provide zero-emissions power generation with a significantly reduced thermodynamic penalty compared to conventional carbon capture applications. This article investigates ITM-based oxy-combustion power cycles using an intermediate-fidelity model that captures the complex physical coupling between the two systems and accurately accounts for operational constraints. Coupled ITM-cycle simulation reveals hidden design challenges, facilitates the development of novel cycle concepts, and enables accurate assessment of new and existing power cycles. Simulations of various ITM-based zero and partial-emissions power cycles are performed using an intermediate-fidelity ITM model coupled to power cycle models created in ASPEN Plus®. The objectives herein are to analyze the prevalent ITM-based power cycle designs, develop novel design modifications, and evaluate the implementation of reactive ITMs. An assessment of the potential for these ITM power cycles to reduce both the thermodynamic penalty and reactor size associated with ITM air separation technology is conducted. The power cycle simulation and analysis demonstrate the various challenges associated with implementing reactive ITMs; hybridization (the use of both reactive and separation-only ITMs) is necessary in order to effectively utilize the advantages of reactive ITMs. The novel hybrid cycle developed herein displays the potential to reduce the size of the ITM compared to the best separation-only concept while maintaining a comparable First Law efficiency. Next, the merit of implementing partial-emissions cycles is explored based on a proposed linear-combination metric. The results indicate that the tradeoff between the main thermodynamic performance metrics efficiency and CO(2) emissions does not appear to justify the use of partial-emissions cycles.

Phage display for the production of human monoclonal antibodies against human pathogens.

In the last decade an increasing number of antibodies have made their way from the research benchtops into the clinics and many more are currently under clinical trial. Among monoclonal antibody-producing techniques, phage-display is undoubtedly the most effective and versatile. Cloning of the entire humoral repertoire derived from an infected patients into a phage display vector allows not only the simple generation of monoclonal antibodies of desired specificity, but also the molecular dissection of the antibody response itself. Generation of large panels of human monoclonal antibodies against human pathogens could open new perspectives in understanding the interplay between the infectious agent and the infected host providing tools for the prevention and the therapy of human communicable diseases. In this paper the basic principles of the phage-display approach as well as its most recent applications are reviewed.

Humoral immune response against hepatitis C virus.

Antibodies are in several instances a reliable marker indicating vigorous immune response against infectious agents and in several viral diseases presence in the blood of specific anti-viral antibodies indicates an effective protection. However, this is not always true. For example, in the case of hepatitis C virus (HCV) an important human pathogen considered the causative agent of the nonA- nonB hepatitis, in spite of an intense antibody response there is no protection against a new infection and in the majority of infected individuals the virus overcomes host defences establishing a persistent infection. Here we describe how the dissection of the humoral immune response against HCV glycoprotein E2 of infected patients was useful for a better comprehension of the virus-host interplay. Cross-reactive antibodies directed against E2 are produced by the HCV-infected patient, but not all of them are protective, and some could even result to be detrimental for the patient. The cross-reactive anti-HCV/E2 humoral antibody response is complex and not necessarily completely beneficial to the host.

Heterogeneity of the humoral anti-HCV/E2 response in persistently infected patients as demonstrated by divergent patterns of inhibition of the binding of anti-HCV/E2 human monoclonal antibodies.

A complete understanding of the molecular features of humoral immune response could be of pivotal importance in the management of persistent viruses as HCV. In this study, 24 HCV-positive samples, characterized by classical virological parameters, are evaluated using a new assay for the quantitation of antibody subpopulations directed against discrete epitopes on surface glycoprotein E2, a key viral protein. The results, besides confirming the usefulness of this new approach, highlight the extreme heterogeneity of anti-HCV/E2 response as far as single epitopes are concerned. The specific epitopes under study are also demonstrated to be widely shared among different genotypes.

Mapping B-cell epitopes of hepatitis C virus E2 glycoprotein using human monoclonal antibodies from phage display libraries.

Clinical and experimental evidence indicates that the hepatitis C virus (HCV) E2 glycoprotein (HCV/E2) is the most promising candidate for the development of an effective anti-HCV vaccine. Identification of the human epitopes that are conserved among isolates and are able to elicit protective antibodies would constitute a significant step forward. This work describes the mapping of the B-cell epitopes present on the surface of HCV/E2, as recognized by the immune system during infection, by the analysis of the reciprocal interactions of a panel of human recombinant Fabs derived from an HCV-infected patient. Three unrelated epitopes recognized by antibodies with no neutralization-of-binding (NOB) activity were identified; a fourth, major epitope was defined as a clustering of minor epitopes recognized by Fabs endowed with strong NOB activity.