Pigs as Clinically Relevant Models for Synergizing Interventional Oncology and Immunotherapy.

Traditionally, rodent cancer models have driven preclinical oncology research. However, they do not fully recapitulate characteristics of human cancers, and their size poses challenges when evaluating tools in the interventional oncologists' armamentarium. Pig models, however, have been the gold standard for validating surgical procedures. Their size enables the study of image-guided interventions using human ultrasound (US), computed tomography (CT), and magnetic resonance (MR) imaging platforms. Furthermore, pigs have immunologic features that are similar to those of humans, which can potentially be leveraged for studying immunotherapy. Novel pig models of cancer are being developed, but additional research is required to better understand both the pig immune system and malignancy to enhance the potential for pig models in interventional oncology research. This review aims to address the main advantages and disadvantages of using a pig model for interventional oncology and outline the specific characteristics of pig models that make them more suitable for investigation of locoregional therapies.

Evaluation of Myeloid-derived Suppressor Cells in the Blood of Iranian COVID-19 Patients.

The cytokine storm and lymphopenia are reported in coronavirus disease 2019 (COVID-19). Myeloid-derived suppressive cells (MDSCs) exist in two different forms, granulocyte (G-MDSCs) and monocytic (M-MDSCs), that both suppress T-cell function. In COVID-19, the role of chemokines such as interleukin (IL)-8 in recruiting MDSCs is unclear. A recent report has correlated IL-8 and MDSCs with poor clinical outcomes in melanoma patients. In the current study, we evaluated the frequency of MDSCs and their correlation with serum IL-8 levels in severe COVID-19 patients from Iran. Thirty-seven severe patients (8 on ventilation, 29 without ventilation), thirteen moderate COVID-19 patients, and eight healthy subjects participated in this study between 10th April 2020 and 9th March 2021. Clinical and biochemical features, serum, and whole blood were obtained. CD14, CD15, CD11b, and HLA-DR expression on MDSCs was measured by flow cytometry. COVID-19 patients compared to healthy subjects had a greater frequency of M-MDSCs (12.7±13.3% vs 0.19±0.20%,), G-MDSCs (15.8±12.6% vs 0.35±0.40%,) and total-MDSCs (27.5±17.3% vs 0.55±0.41%,). M-MDSC (16.8±15.8% vs 5.4±4.8%,) and total-MDSC (33.3±18.5% vs 17.3±13.3%) frequency was higher in non- ventilated compared to moderate COVID-19 subjects. Serum IL-8 levels were higher in patients with COVID-19 than in normal healthy subjects (6.4±7.8 vs. 0.10±00 pg/mL). Ventilated patients (15.7±6.7 pg/mL), non-ventilated patients (5.7±2.7 pg/mL) and moderate patients (2.8±3.0 pg/mL) had significantly different levels of IL-8.  A negative correlation was found between the frequency of G-MDSCs and the international normalized ratio (INR) test (r=-0.39), and between the frequency of total-MDSCs and oxygen saturation (%) (r=-0.39). COVID-19 patients with severe non-ventilated disease had the highest levels of M-MDSCs. In addition to systemic MDSCs, lung, serum IL-8, and other inflammatory biomarkers should be measured.

Surgical resection, radiotherapy and percutaneous thermal ablation for treatment of stage 1 non-small cell lung cancer: protocol for a systematic review and network meta-analysis.

INTRODUCTION: Non-small cell lung cancer (NSCLC) makes up the majority of lung cancer cases. Currently, surgical resection is the gold standard of treatment. However, as patients are becoming medically more complex presenting with advanced disease, minimally invasive image-guided percutaneous ablations are gaining popularity. Therefore, comparison of surgical, ablative and second-line external beam therapies will help clinicians, as management of NSCLC changes. We will conduct a meta-analysis, reviewing literature investigating these therapies in adult patients diagnosed with stage 1 NSCLC, with neither hilar nor mediastinal nodal involvement, confirmed either through cytology or histology regardless of type. METHODS AND ANALYSIS: We will search electronic databases (MEDLINE, Embase, Web of Science, Scopus, ClinicalTrials.gov, Cochrane) from their inception to January 2021 to identify randomised controlled trials (RCTs), cluster RCTs and cohort studies comparing survival and clinical outcomes between any two interventions (lobectomy, wedge resection, video-assisted thoracoscopic surgery/robot-assisted thoracoscopic surgery, radiofrequency ablation, microwave ablation, cryoablation and consolidated radiation therapies (external beam radiation therapy, stereotactic body radiation therapy, and 3D conformal radiation therapy). The primary outcomes will include cancer-specific survival, lung disease-free survival, locoregional recurrence, death, toxicity and non-target organ injury. We will also search published and unpublished studies in trial registries and will review references of included studies for possible inclusion. Risk of bias will be assessed using tools developed by the Cochrane collaboration. Two reviewers will independently assess the eligibility of studies and conduct the corresponding risk of bias assessments. For each outcome, given enough studies, we will conduct a network meta-analysis. Finally, we will use the Confidence in Network Meta-Analysis tool to assess quality of the evidence for each of the primary outcomes. ETHICS AND DISSEMINATION: We aim to share our findings through high-impact peer review. As interventional techniques become more popular, it will be important for providers in multidisciplinary teams caring for these patients to receive continuing medical education related to these interventions. Data will be made available to readers. PROSPERO REGISTRATION NUMBER: CRD42021276629.

Serum cytokine levels of COVID-19 patients after 7 days of treatment with Favipiravir or Kaletra.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has infected 86,4 M patients and resulted in 1,86 M deaths worldwide. Severe COVID-19 patients have elevated blood levels of interleukin-6 (IL-6), IL-1ß, tumor necrosis factor (TNF)α, IL-8 and interferon (IFN)γ. OBJECTIVE: To investigate the effect of antiviral treatment serum cytokines in severe COVID-19 patients. METHODS: Blood was obtained from 29 patients (aged 32-79 yr) with laboratory-confirmed COVID-19 upon admission and 7 days after antiviral (Favipiravir or Lopinavir/Ritonavir) treatment. Patients also received standard supportive treatment in this retrospective observational study. Chest computed tomography (CT) scans were evaluated to investigate lung manifestations of COVID-19. Serum was also obtained and cytokines levels were evaluated. 19 age- and gender-matched healthy controls were studied. RESULTS: Anti-viral therapy significantly reduced CT scan scores and the elevated serum levels of C-reactive protein (CRP) and lactate dehydrogenase (LDH). In contrast, serum levels of IL-6, IL-8 and IFNγ were elevated at baseline in COVID-19 subjects compared to healthy subjects with IL-6 (p = 0.006) and IL-8 (p = 0.011) levels being further elevated after antiviral therapy. IL-1ß (p = 0.01) and TNFα (p = 0.069) levels were also enhanced after treatment but baseline levels were similar to those of healthy controls. These changes occurred irrespective of whether patients were admitted to the intensive care unit. CONCLUSION: Antiviral treatments did not suppress the inflammatory phase of COVID-19 after 7 days treatment although CT, CRP and LDH suggest a decline in lung inflammation. There was limited evidence for a viral-mediated cytokine storm in these COVID-19 subjects.