Treatment of osteosarcoma patients in the Philippine General Hospital during the COVID-19 outbreak

@#Objectives. The ongoing Coronavirus disease 2019 (COVID-19) pandemic has disrupted healthcare systems worldwide. This study aimed to document the effect of COVID-19 on osteosarcoma treatment pathways in the Philippine General Hospital (PGH) and determine if there were any delays. Method. A retrospective review of osteosarcoma patients treated at the PGH from January 1, 2019 – January 1, 2020 (pre-COVID-19) was compared to those treated during the COVID-19 pandemic from March 1, 2020 – September 1, 2020. Rates of diagnosed osteosarcoma, admission for chemotherapy, admission for surgery, treatment abandonment, metastatic disease on presentation, 1-year mortality, and amputation were calculated and compared between the two groups. Results. From March to September 2020, 11 newly diagnosed osteosarcoma patients sought consult at the PGH. Only one patient sought consult during the initial 3-4 months of the study, suggesting that patients delayed seeking healthcare during the period of enhanced community quarantine. Patients seen during the pandemic had a higher rate of metastatic disease on presentation, reflecting the delay in diagnosis. Due to COVID-19 restrictions early in the pandemic, osteosarcoma patients were coordinated and referred to outside hospitals for intravenous chemotherapy and surgery. Normalization of services (hospital admissions, limb salvage surgeries) were seen at the later stages of the study, corresponding to the loosening of the quarantine. Conclusions. Osteosarcoma patients experienced delays in seeking consult, diagnosis, and treatment at the PGH due to the COVID-19 pandemic. Early indicators suggest worse outcomes for these patients due to the delays. Strategies employed during the pandemic, such as networking of care and telemedicine, may help in future outbreaks.

Human Acellular Dermis versus Submuscular Tissue Expander Breast Reconstruction: A Multivariate Analysis of Short-Term Complications

BACKGROUND: Acellular dermal matrix (ADM) allografts and their putative benefits have been increasingly described in prosthesis based breast reconstruction. There have been a myriad of analyses outlining ADM complication profiles, but few large-scale, multi-institutional studies exploring these outcomes. In this study, complication rates of acellular dermis-assisted tissue expander breast reconstruction were compared with traditional submuscular methods by evaluation of the American College of Surgeon's National Surgical Quality Improvement Program (NSQIP) registry. METHODS: Patients who underwent immediate tissue expander breast reconstruction from 2006-2010 were identified using surgical procedure codes. Two hundred forty tracked variables from over 250 participating sites were extracted for patients undergoing acellular dermis-assisted versus submuscular tissue expander reconstruction. Thirty-day postoperative outcomes and captured risk factors for complications were compared between the two groups. RESULTS: A total of 9,159 patients underwent tissue expander breast reconstruction; 1,717 using acellular dermis and 7,442 with submuscular expander placement. Total complications and reconstruction related complications were similar in both cohorts (5.5% vs. 5.3%, P=0.68 and 4.7% vs. 4.3%, P=0.39, respectively). Multivariate logistic regression revealed body mass index and smoking as independent risk factors for reconstructive complications in both cohorts (P<0.01). CONCLUSIONS: The NSQIP database provides large-scale, multi-institutional, independent outcomes for acellular dermis and submuscular breast reconstruction. Both thirty-day complication profiles and risk factors for post operative morbidity are similar between these two reconstructive approaches.

ADNKA overcomes SARS-CoV2-mediated NK cell inhibition through non-spike antibodies

The outcome of infection is dependent on the ability of viruses to manipulate the infected cell to evade immunity, and the ability of the immune response to overcome this evasion. Understanding this process is key to understanding pathogenesis, genetic risk factors, and both natural and vaccine-induced immunity. SARS-CoV-2 antagonises the innate interferon response, but whether it manipulates innate cellular immunity is unclear. An unbiased proteomic analysis determined how cell surface protein expression is altered on SARS-CoV-2-infected lung epithelial cells, showing downregulation of activating NK ligands B7-H6, MICA, ULBP2, and Nectin1, with minimal effects on MHC-I. This correlated with a reduction in NK cell activation, identifying a novel mechanism by which SARS-CoV2 antagonises innate immunity. Later in the disease process, strong antibody-dependent NK cell activation (ADNKA) developed. These responses were sustained for at least 6 months in most patients, and led to high levels of pro-inflammatory cytokine production. Depletion of spike-specific antibodies confirmed their dominant role in neutralisation, but these antibodies played only a minor role in ADNKA compared to antibodies to other proteins, including ORF3a, Membrane, and Nucleocapsid. In contrast, ADNKA induced following vaccination was focussed solely on spike, was weaker than ADNKA following natural infection, and was not boosted by the second dose. These insights have important implications for understanding disease progression, vaccine efficacy, and vaccine design.