Respiratory viral infection promotes the awakening and outgrowth of dormant metastatic breast cancer cells in lungs (preprint)

Breast cancer is the second most common cancer globally. Most deaths from breast cancer are due to metastatic disease which often follows long periods of clinical dormancy1. Understanding the mechanisms that disrupt the quiescence of dormant disseminated cancer cells (DCC) is crucial for addressing metastatic progression. Infection with respiratory viruses (e.g. influenza or SARS-CoV-2) is common and triggers an inflammatory response locally and systemically2,3. Here we show that influenza virus infection leads to loss of the pro-dormancy mesenchymal phenotype in breast DCC in the lung, causing DCC proliferation within days of infection, and a greater than 100-fold expansion of carcinoma cells into metastatic lesions within two weeks. Such DCC phenotypic change and expansion is interleukin-6 (IL-6)-dependent. We further show that CD4 T cells are required for the maintenance of pulmonary metastatic burden post-influenza virus infection, in part through attenuation of CD8 cell responses in the lungs. Single-cell RNA-seq analyses reveal DCC-dependent impairment of T-cell activation in the lungs of infected mice. SARS-CoV-2 infected mice also showed increased breast DCC expansion in lungs post-infection. Expanding our findings to human observational data, we observed that cancer survivors contracting a SARS-CoV-2 infection have substantially increased risks of lung metastatic progression and cancer-related death compared to cancer survivors who did not. These discoveries underscore the significant impact of respiratory viral infections on the resurgence of metastatic cancer, offering novel insights into the interconnection between infectious diseases and cancer metastasis.

Malignant Pseudothyroiditis after COVID-19 Infection Revealing a Poor-Cellular Variant of a Thyroid Anaplastic Carcinoma (preprint)

ATC is a rare cancer with a slightly growing incidence and a poor prognosis determined by the delay of treatment, usually revealed by an enlarging goiter with compressive symptoms and, more rarely, by inflammatory and thyrotoxic symptoms, a clinic entity called malignant pseudothyroiditis (MPT) mimicking subacute thyroiditis (SAT). With the advent of COVID-19 pandemic, many cases of COVID-19 related SAT were described with the usual clinical presentation enriched by the COVID-19 symptoms, leading to the emergence of atypic clinical pictures. We present the case of a 60-year-old patient who developed, one month after a COVID 19 acute infection, a clinical presentation of SAT with atypical ultrasound features leading to the diagnosis of MPT; histological atypia was misleading, finally making precise diagnosis was difficult. To our best knowledge, this is the first ever reported case of MPT mimicking COVID-19 SAT. We reviewed thirty five cases published to date and discuss the mechanisms underlying MPT physiopathogenesis and the ultrasound and histological features. We point out the similarities between MPT and SAT and the role of ultrasound at clinical presentation workup. Finally there are two key points to remind: First, to perform neck ultrasound in any painful goiter and, in case of atypia, perform a US guided core-needle biopsy, a complementary CT-scan and quickly refer the patient to an expert center. Second, always think that COVID-19 infection is a recent entity and be aware that it can influence the clinical presentation of any disease.

COVID-19 Diagnosis Like an Avalanche Triggers a Series of Adverse Events However Saves a Life in the End (preprint)

Patients diagnosed with cancer are less frequently covered by preventive measures for cardiovascular diseases. The frequent co-occurrence of these diseases makes it necessary to apply parallel diagnostics and cardiological treatment with anti-cancer therapy. Case report: We present a case of a 73-year-old former smoker with hyperlipidemia, type 2 diabetes, and arterial hypertension, after a partial right nephrectomy in 2005 due to kidney cancer, diagnosed with SARS-COV-2 infection in April 2022. Follow-up chest imaging showed a 20 mm focal lesion in the left lung further classified as a small cell neuroendocrine carcinoma. Unexpectedly the patient was hospitalized for ST-segment elevation inferior left ventricular (LV) myocardial infarction treated successfully with coronary angioplasty, however heart failure (HF) with reduced left ventricle ejection fraction was diagnosed. One month later patient required another hospitalization due to the HF decompensation and cardiological treatment was optimized with flozin addition to the standard HF therapy. After cardiological approval chemotherapy was initiated with the cisplatinum-etoposide regimen and continued for 6 months without HF decompensation and significant deterioration of renal function. After that, the patient underwent radical radiotherapy. Follow-up chest computed tomography scans showed regression of the neoplastic lesion. Conclusions: Coincidence of newly recognized cancer and infection might contribute and provoke serious cardiological events . To reduce the risk of cardiovascular complications, early periodic cardiological surveillance and optimal pharmacotherapy are required.

Cellular and Humoral Immunity and Infection Responses to SARS-CoV-2:Immune Biomolecular Mechanisms by Case Study within SARS-CoV-2 Pathogenesis and Other Infections (preprint)

The coronavirus 2019 (COVID-19) pandemic was caused by a positive sense single-stranded RNA (ssRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, other human coronaviruses (hCoVs) exist, of which Middle East Respiratory Syndrome (MERS) and SARS-CoV (SARS) showed higher mortality rates without causing a pandemic. As of December 2022, SARS-CoV-2 has resulted in over 6.6 million deaths worldwide through an array of acute to chronic pathologies. Historical pandemics include smallpox and influenza with efficacious therapeutics utilized to reduce overall disease burden. Therefore, immune system process analysis is required to compare innate and adaptive immune system interactions. Lymphatic system organs include bone marrow and thymus using a network of nodes throughout which white blood cells traverse glycolipid membranes utilizing cytokines and chemokine gradients that affect cell development, differentiation, proliferation, and migration processes as well as genetic factors affecting cell receptor expression. Innate processes involve antigen-presenting cells and B lymphocyte cellular responses to pathogens relevant to other viral and bacterial infections but also in oncogenic diseases. Such processes utilize cluster of differentiation (CD) marker expression, major histocompatibility complexes (MHC), pleiotropic interleukins (IL) and chemokines. The adaptive immune system consists of Natural Killer (NK) and T cells. Other viruses are also contributory to cancer including human papillomavirus (cervical carcinoma ), Epstein-Barr virus (EBV) ( lymphoma), hepatitis B and C (hepatocellular carcinoma) and human T cell leukemia virus-1 (adult T-cell leukemia). Bacterial infections also increase the risk of developing cancer( e.g. H. pylori). Therefore, as the above factors can cause both morbidity and mortality along-side being transmitted within clinical and community settings, it is appropriate to now examine advances in single cell sequencing, FACS analysis and many other laboratory techniques that allow insights into discoveries of newer cell types. These developments offer improved clarity and understanding that over-lap with known autoimmune conditions that could be affected by innate B cell or T cell responses to SARS-CoV-2 infection. Thus, this review quantifies and outlines the nature of specific receptors and proteins relevant to clinical laboratories and medical research by documenting both innate and adaptive immune system cells within current coronavirus immunology case study data and other pathologies to date.

Wearing Surgical Masks Coupled With Restricting the Flow of People in Patient Wards Versus Preventive Atomization Inhalation in Preventing Fever After General Anesthesia Surgery: A Retrospective Analysis During COVID-19 (preprint)

Background: The COVID-19 could be transmitted through aerosols, and aerosol can be produced by atomization inhalation. Preventative aerosol inhalation is prohibited in our hospital during COVID-19, however the number of cases of fever after surgery has not increased significantly. We want to know whether wearing surgical masks coupled with restricting the flow of people in patient wards has same effect with preventive atomization inhalation in preventing fever after surgery, and we wonder whether preventive atomization inhalation is unnecessary during COVID-19, as long as strictly wearing surgical masks and restricting the flow of people in patient wards have been met.Methods: Eight kinds of common surgery were covered in this retrospective analysis, including total thyroidectomy (for the treatment of thyroid carcinoma), total adrenalectomy (adrenal tumor), radical gastrectomy (gastric cancer), radical nephrectomy (renal cell carcinoma), radical prostatectomy (prostate cancer), radical resection for sigmoid colon cancer, radical resection for rectal cancer and appendectomy (appendicitis). Cases in Group A underwent preventive atomization inhalation whilst cases in group B wore surgical masks and restricted the flow of people in patient wards. Occurrence of fever, occurrence of fever recurrence and the maximum temperature in the first week after surgery were analyzed in this study.Results: No significant differences can be seen between group A and group B in terms of occurrence of fever, occurrence of fever recurrence and the maximum temperature after surgery in the first week.Conclusion: Wearing surgical masks combined with restricting the flow of people in patient wards has same effect with preventive atomization inhalation in preventing fever after general anesthesia surgery, which means, during COVID-19, preventive atomization inhalation might not be necessary as long as strictly wearing surgical masks and restricting the flow of people in patient wards have been met.

Minimizing Population Health Loss in Times of Scarce Surgical Capacity (preprint)

Background COVID-19 has put unprecedented pressure on healthcare systems worldwide, leading to a reduction of the available healthcare capacity. Our objective was to develop a decision model that supports prioritization of care from a utilitarian perspective, which is to minimize population health loss. Methods A cohort state-transition model was developed and applied to 43 semi-elective non-paediatric surgeries commonly performed in academic hospitals. Scenarios of delaying surgery from two weeks were compared with delaying up to one year, and no surgery at all. Model parameters were based on registries, scientific literature, and the World Health Organization global burden of disease study. For each surgery, the urgency was estimated as the average expected loss of Quality-Adjusted Life-Years (QALYs) per month. Results Given the best available evidence, the two most urgent surgeries were bypass surgery for Fontaine III/IV peripheral arterial disease (0.23 QALY loss/month, 95%-CI: 0.09-0.24) and transaortic valve implantation (0.15 QALY loss/month, 95%-CI: 0.09-0.24). The two least urgent surgeries were placing a shunt for dialysis (0.01, 95%-CI: 0.005-0.01) and thyroid carcinoma resection (0.01, 95%-CI: 0.01-0.02): these surgeries were associated with a limited amount of health lost on the waiting list. Conclusion Expected health loss due to surgical delay can be objectively calculated with our decision model based on best available evidence, which can guide prioritization of surgeries to minimize population health loss in times of scarcity. This tool should yet be placed in the context of different ethical perspectives and combined with capacity management tools to facilitate large-scale implementation.

Prognostic Significance of COVID-19 Receptor ACE2 and Recommendation For Anti-Hypertensive Drug in Renal Cell Carcinoma (preprint)

Background: Owing to its worldwide spread, the coronavirus disease (COVID-19) epidemic was declared a pandemic by the World Health Organization on March 11, 2020. Angiotensin-converting enzyme 2 (ACE2) is the outer surface protein of the cell membrane that is abundantly distributed in the heart, lungs, and kidneys, and plays an important role in molecular docking of the severe acute respiratory syndrome coronavirus 2. In this study, we aimed to analyze the difference in the survival rate according to ACE2 expressions in pan-cancer. Methods: The clinical and genomic data of pan-cancer patients were accessed from The cancer Genome Atlas. To identify the prognostic significance of ACE2, we used Kaplan-Meier with log-rank test, and the Cox proportional hazards regression to analyze prognostic significance. Results: In the Kaplan-Meier curve, clear cell renal cell carcinoma (ccRCC), uveal melanoma, and prostate adenocarcinoma showed statistically significant. In the Cox regression, thyroid carcinoma and glioblastoma multiforme, and ccRCC showed significant results. Only ccRCC had statistically significant, and high ACE2 expression is related to good prognosis. Conclusions: It is known that ACE inhibitor, a primary antihypertensive agent, increases ACE2 expression. Based on these results, we believe that the ACE inhibitor will be important to increase the lifespan of ccRCC patients. This study is the first research to offer a recommendation on the use of anti-hypertensive drugs to ccRCC patients.

18F-FDG PET/CT uptake in COVID-19: case report of a patient with lung metastases after treatment of nasal cavity malignancy (preprint)

Background: In high COVID-19 prevalence region, COVID-19 disease may be incidental found in non-specific symptoms or asymptomatic patient with history of tumor who underwent 18F-FDG-PET/CT for standard oncologic indications.Case presentation: A 51-year-old woman with a 4-year history of adenoid cystic carcinoma of nasal cavity underwent 18F-FDG PET/CT for restaging during COVID-19 outbreak in Wuhan. Pneumonia lesions were characterized by 18F-FDG uptake ground-glass opacities (GGOs) and multifocal high 18F-FDG-avid patchy consolidation, and without lymph node involvement and pleural effusion. Furthermore, multiple 18F-FDG-positive lung and lumbar metastases were observed. Finally, a diagnosis of COVID-19 was made based on a positive real-time fluorescent polymerase chain reaction (RT-PCR) test of SARS-CoV-2 nucleic acid. Conclusion: The non-specific symptoms or asymptomatic cancer patients presenting 18F-FDG-positive GGOs and patchy consolidation lesions in lung may favor COVID-19, who should be quickly SARS-CoV-2 nucleic acid tested and monitored.

Early histologic findings of pulmonary SARS-CoV-2 infection detected in a surgical specimen. (preprint)

Despite the current pandemic season, reports on pathologic features of Coronavirus disease 19 (COVID-19) are exceedingly rare at the present time. Here we describe the pathologic features of early lung involvement by COVID-19 in a surgical sample resected for carcinoma from a patient who developed SARS-CoV-2 infection soon after surgery. The main histologic findings observed were pneumocyte damage, alveolar hemorrhages with clustering of macrophages, prominent and diffuse neutrophilic margination within septal vessels and interstitial inflammatory infiltrates, mainly represented by CD8+ T lymphocytes. These features are similar to those previously described in SARS-CoV infection. Subtle histologic changes suggestive pulmonary involvement by Covid-19 may be accidentally encountered in routine pathology practice, especially when extensive sampling is performed for histology. These findings should be carefully interpreted in light of the clinical context of the patient and could prompt a pharyngeal swab PCR test to rule out the possibility of SARS-CoV-2 infection in asymptomatic patients.