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Background B-cell proliferative disorders, such as post-transplant lymphoproliferative disease (PTLD), are increased among persons afflicted by T-cell compromise. Most are Epstein–Barr virus (EBV) + and can first present with a focal lesion. Direct introduction of oncolytic viruses into localized tumors provides theoretical advantages over chemotherapy, immunotherapy and radiation therapy by reducing systemic toxicity. Despite extensive study as a vehicle for gene therapy, adeno-associated viruses (AAV) have rarely been applied to human cancer research due to technical and theoretical obstacles. Moreover, human B-cells have historically been described as resistant to AAV infection. Nonetheless, advances using different recombinant (r)AAV serotypes with unique tropisms to deliver cytotoxic therapy suggested a localized anti-tumor approach was feasible. Methods As a prelude to the development of a therapeutic vehicle, the ability of fifteen distinct EGFP-bearing rAAV serotypes to transduce human B-cells, including primary, immortalized, and B-cell tumor lines ± EBV was assessed by confocal microscopy, flow cytometry and subsequently cell viability assay. Results Rank order analysis revealed augmented transduction by rAAV6.2 and closely related virions. EBV infection of EBV-negative B-cell tumor lines and EBV immortalization of primary B-cells increased susceptibility to rAAV6.2 transduction. As a proof of concept, transduction by rAAV6.2 encoding herpes simplex virus type 1 (HSV1)-thymidine kinase (TK) eliminated TK-negative rhabdomyosarcoma cells and diminished viability of transduced B-cell lines upon incubation with ganciclovir. Conclusions rAAV serotypes differentially transduce human B-cell lines reversing the dogma that human B-cells are refractory to AAV infection. EBV + B-cells display increased susceptibility to rAAV6.2 infection, uncovering a new method for improved nucleic acid transfer into transfection-resistant B-cell lines. The introduction of a functional suicide gene into the rAAV6.2 genome identifies a candidate vector for the development of rAAV-based oncolytic therapy targeting focal EBV-bearing B-lymphoproliferative disorders.

Cutaneous B-cell lymphomas (CBCL) are rare heterogeneous neoplastic diseases composing about 22.5% of all cutaneous lymphomas. These diseases can be divided into primary and secondary cutaneous variants with primary cutaneous B-cell lymphoma (PCBCL) divided into three distinct entities including primary cutaneous marginal zone lymphoma, primary cutaneous follicle center lymphoma, and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT). Secondary cutaneous diffuse large B-cell lymphoma (CDLBCL) and PCDLBCL, LT are more aggressive neoplasms compared to the aforementioned CBCL with survival rates of 37% and 50% after 5 years, respectively. CDLBCL can present as cutaneous or subcutaneous nodules, papular lesions, or indurated plaques. Here, we present a case of CDLBCL of an 88-year-old female that was mistaken for lower extremity cellulitis with phlegmon. Our patient failed two courses of antibiotic therapy as an outpatient and received a third as an inpatient before a cutaneous biopsy clinched the diagnosis.

Abstract Background: Avenues of treatment currently implemented for Covid-19 pandemic are largely supportive in nature. Non -availability of an effective antiviral treatment makes supportive care for acute hypoxic respiratory failure is the most crucial intervention. Highly contagious nature of Covid-19 had created stress and confusion among front line Health Care Workers (HCWs) regarding infectious risk of supportive interventions and best preventive strategies. Purpose: To analyze and summarize key evidence from published literature exploring the risk of transmission of Covid-19 related to common supportive care interventions in hospitalized patients and effectiveness of currently used preventive measures in hospital setting. Data Sources: Curated Covid-19 literature from NCBI Computational Biology Branch ,Embase and Ovid till May 20,2020.Longitudinal and reference search till June 28,2020 Study Selection: Studies pertaining to risk of infection to HCWs providing standard supportive care of hospitalized Covid-19 mainly focusing on respiratory support interventions.Indirect studies from SARS,MERS or other ARDS pathology caused by infectious agents based on reference tracking and snow ball search . Clinical, Healthy volunteer and mechanistic studies were included. Two authors independently screened studies for traditional respiratory supportive-care (Hypoxia management, ventilatory support and pulmonary toileting) related transmission of viral or bacterial pneumonia to HCWs. Data Extraction: Two authors (TK and SP) independently screened articles and verified for consensus. Quality of studies and level of evidence was assessed using Oxford Center for Evidence Based Medicine (OCEBM) , Newcastle - Ottawa quality assessment Scale for observational studies and Grading of Recommendations Assessment, Development and Evaluation (GRADE) system for grading evidence. Data Synthesis: 21 studies were eligible for inclusion. In 11 mechanistic studies, 7 were manikin based,1 was in the setting of GNB pneumonia ,2 were healthy volunteer study and 1 was heterogenous setting.Out of 10 clinical studies ,5 were case controlled and 6 were cohort studies. Risk of corona virus transmission was significantly high in HCWs performing or assisting endotracheal intubation or contact with respiratory secretion.(Moderate certainty evidence, GRADE B) Safety of nebulization treatment in corona virus pneumonia patients are questionable(Low certainty evidence, GRADE C).Very low certainty evidence exist for risk of transmission with conventional HFNC (GRADE D) and NIV (GRADE D),CPR (GRADE D),Bag and mask ventilation(GRADE D).Moderate certainty evidence exist for protective effect of wearing a multilayered mask, gown , eye protection and formal training for PPE use (GRADE B).Low certainty evidence exist for transmission risk with bag and mask ventilation, suctioning before and after intubation and prolonged exposure (GRADE C).Certainty of evidence for wearing gloves,post exposure hand washing and wearing N 95 mask is low(GRADE C). Limitations: This study was limited to articles with English abstract. Highly dynamic nature of body of literature related to Covid-19, frequent updates were necessary even during preparation of manuscript and longitudinal search was continued even after finalizing initial search. Due to the heterogeneity and broad nature of the search protocol, quantitative comparisons regarding the effectiveness of included management strategies could not be performed. Direct evidence was limited due to poor quality and non-comparative nature of available Covid-19 reporting. Conclusions: Major risk factors for transmission of corona virus infection were, performing or assisting endotracheal intubation and contact with respiratory secretion. Risk of transmission with HFNC or NIV can be significantly decreased by helmet interface, modified exhalation circuit or placing a properly fitting face mask over patient interface of HFNC. Evidence for risk of transmission with CPR, suctioning before or after intubation or bag and mask ventilation of very low certainty. Significant protective factors are Formal training for PPE use, consistently wearing mask, gown and eye protection. Primary Funding Source: None Disclosure: None of the authors have any conflict of interest to disclose.

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