Coronavirus infection and organizational changes in the clinical process in patients with non-muscle-invasive bladder carcinoma.

The spread of the aggressive disease caused by the novel respiratory syndrome coronavirus-2 (SARS-CoV-2) has had an impact not only on the health and psyche of people, but also on the state of health systems in different countries, by complicating the treatment and diagnostic process. These changes have affected patients with cancers to a greater extent. The diagnosis, treatment, and follow-up of patients are of particular scientific and practical interest when working in conditions of special anti-epidemic control. Objective. To assess the possibility of reducing the frequency of hospitalization of patients with non-muscle-invasive bladder carcinoma (NMIBC) during the Covid-19 period. Subjects and methods. Sixty-four patients with urinary tract malignancy, including 19 (29.7%) patients with low-and high-risk re-current NMIBC, were followed up in two clinics (Saint Petersburg, Russia) in March to October 2020. All the patients were oper-ated on;the patients at high risk for recurrence received a cycle of adjuvant BCG therapy. Methods for cytological examination of urine sediment and the biomarkers UBC and Cyfra 21-1 were used for special laboratory diagnosis;the server stations of both clinics were applied for telehealth consultations (TCs). Results. TCs were used to reduce hospitalization rates: after TCs, all the patients reported a reduction in transport costs and recovery time after hospitalization. TCs could protect the followed-up patients against COVID-19 infection, by observing the rules of clinical examination, and achieve maximum individualization of treatment. The authors refused to perform diagnostic operations for low-risk NMIBC and to use laboratory tests using urinary biomarkers. At the place of their residence, outpatients underwent urinalysis for several indicators, transmitting the result to the clinic's servers or through a monitoring system. Inpatient treatment was used only in cases of gross hematuria or after recording abnormal laboratory test results. Control cystoscopy detected no re-current tumor. Conclusion. During the spread of COVID-19, the periods of endoscopic examinations and control diagnostic operations can be post-poned, by replacing face-to-face consultations with TC monitoring. Outpatient laboratory and radiation examinations are indicat-ed in patients with new-onset gross hematuria or after combination treatment. Repeated operations, including diagnostic ones, should be performed in the case of multiple NMIBCs or after incomplete excision of the primary tumor.Copyright © 2021.

Plasma markers of Covid-19 severity: A pilot study

SARS-CoV-2 infected patients show heterogeneous clinical presentations ranging from mild symptoms to severe respiratory failure and death. Consequently, various markers reflect certain disease presentations. Our cohort included moderate (n = 10) and severe (n = 10) COVID-19 patients, and 10 healthy controls. We determined plasma levels of nine acute phase proteins by nephelometry, full-length (M65), caspase-cleaved (M30) cytokeratin 18, and ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type-1 motif 13) by ELISA. In addition, we examined whole plasma N-glycosylation by capillary gel electrophoresis coupled to laser-induced fluorescence detection. When compared to healthy controls, COVID-19 patients had significantly lower concentrations of ADAMTS13 and albumin (ALB) but higher M30, M65, alpha-1-acid glycoprotein, alpha1-antitrypsin (AAT), ceruloplasmin, haptoglobin, and highsensitivity C-reactive protein. The concentrations of alpha1-antichymotrypsin, alpha2-macroglobulin and serum amyloid A proteins did not differ. We found significantly higher levels of AAT and M65 but lower ALB in severe compared to moderate COVID-19 patients. N-glycan analysis of the serum proteome revealed increased levels of oligomannose and sialylated di-antennary glycans, while the non-sialylated di-antennary glycan A2G2 significantly decreased in COVID-19 patients compared to controls. COVID-19-associated changes in levels and N-glycosylation of specific plasma proteins highlight involvement of different pathophysiological mechanisms and grant further investigations.

Sarcomatoid urothelial carcinoma accompanied by elevated serum beta-HCG: Two case reports

Sarcomatoid urothelial carcinoma is a rare and aggressive variant. Serum beta-hCG levels are used as a tumor marker in gestational trophoblastic diseases and germ cell tumors, but may also be elevated in high-grade bladder cancers. Here, we report two urothelial carcinoma cases with sarcomatoid differentiation that relapsed early after surgery with elevated serum beta-hCG levels. The first case was a 65-year-old female and the second case was a 67-year-old man with sarcomatoid urothelial carcinoma located in the ureter and renal pelvicalyceal system, both of them relapsed with elevated beta-hCG serum level to 146.8 mIU/ mL and 242 mIU/mL, respectively. They died a few months after initial diagnosis;4.9 and 2.5 months respectively. Both sarcomatoid variant and beta-hCG expression were associated with poor prognosis and advanced stage. However, beta-hCG is not used as a tumor marker in urinary tract cancers yet, and its relationship with variant pathologies has not been clarified. We need multi-centered studies to reveal this relationship.Copyright © 2023, Derman Medical Publishing. All rights reserved.

PLEOMORPHIC CARCINOMA IN THE MIDST OF COVID

SESSION TITLE: Pathology Identifying Chest Infections Case Report Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Pleomorphic carcinoma is a subtype of sarcomatoid carcinomas that represents <1 % of all primary lung neoplasms. This case highlights a recent diagnosis of a patient with pleomorphic carcinoma in the midst of COVID-19 pneumonia. CASE PRESENTATION: A 75 year old female with a 180-pack year smoking history presented to the emergency department with dyspnea and chest discomfort. Vital signs significant for oxygen saturation at 93% on room air. The patient had been admitted to the hospital 7 months prior for acute hypoxemic respiratory failure due to COVID-19 pneumonia. At that point, computed tomography (CT) of the chest showed a right lower lobe 5.5 cm juxtapleural lesion measuring fluid attenuation by Hounsfield units without intralesional enhancement. The lesion was initially thought to be secondary to the patient's COVID-19 pneumonia and was not investigated further. The patient was subsequently lost to follow up. Seven months later the patient presented with worsening shortness of breath. Chest CT revealed large right complex pleural effusion with near complete lung collapse. The patient underwent pigtail catheter placement with partial re-expansion of the lung. Pleural fluid analysis showed an exudative effusion with no malignant cells on cytology. Follow-up CT imaging showed a large mass-like area in the right mid and lower hemithorax. Video assisted thorascopic surgery (VATS) decortication and thoracotomy revealed a right lower lobe abscess and empyema. Pathology samples collected during procedure showed malignant cells of sarcamatoid features found in right lung and intraparenchymal lymph nodes. Histology and immunostaining showed a tumor composed of a component of poorly differentiated adenocarcinoma and more than 10% spindle/pleomorphic cells. Immunostaining showed the poorly differentiated adenocarcinoma component was positive for moc 31, Ber-EP4, cytokeratin AE1/AE3, CAM 5.2, lack TTF-1 and p40. The spindle/pleomorphic component was negative for cytokeratins. DISCUSSION: Pulmonary pleomorphic carcinoma (PC) is a rare, poorly differentiated non-small cell lung cancer (NSCLC) that contains at least 10% spindle and/or giant cells or a carcinoma consisting only of spindle and giant cells. PC has poor response to conventional treatments for NSCLC and subsequently poor 5 year survival. It more common in men and smokers. COVID-19 causes a variety of pulmonary radiographic manifestations, including nodules and mass-like consolidations. Superimposed bacterial infections are also common. Our case, however, highlights the importance of serial radiographic monitoring and, when indicated, tissue sampling to rule out alternative explanations for abnormal CT findings. CONCLUSIONS: Appropriate screening and careful follow up of suspicious lung lesions is vital to ensure prompt diagnosis and treatment of lung malignancy. Reference #1: WHO Classification of Tumours Editorial Board. Thoracic Tumours. In: WHO Classification of Tumours,Earke 5th ed, IARC Publications, 2021. Vol 5. Reference #2: Ito K, Oizumi S, Fukumoto S, Harada M, Ishida T, Fujita Y, Harada T, Kojima T, Yokouchi H, Nishimura M;Hokkaido Lung Cancer Clinical Study Group. Clinical characteristics of pleomorphic carcinoma of the lung. Lung Cancer. 2010 May;68(2):204-10. doi: 10.1016/j.lungcan.2009.06.002. Epub 2009 Jul 3. PMID: 19577320. Reference #3: Maneenil K, Xue Z, Liu M, Boland J, Wu F, Stoddard SM, Molina J, Yang P. Sarcomatoid Carcinoma of the Lung: The Mayo Clinic Experience in 127 Patients. Clin Lung Cancer. 2018 May;19(3):e323-e333. doi: 10.1016/j.cllc.2017.12.008. Epub 2017 Dec 21. PMID: 29454534. DISCLOSURES: No relevant relationships by Rachel Earle No relevant relationships by Samantha Gillenwater No relevant relationships by Miquel Gonzalez No relevant relationships by Sikandar Khan No relevant relationships by Christopher Lau no disclosure submitted for Jinesh Mehta;

Validated method for assessing the effects of blue light on human skin

The COVID pandemic caused an increase in virtual meetings & work from home scenarios that resulted in people spending increased time in front of computer screens & electronic devices. Studies have shown that blue light can produce cytotoxic effects, primarily through the production of reactive oxygen species & increased inflammation. However, the topic has been controversial with some studies claiming no adverse effects of blue light on the skin. Methods for testing the effects of blue light using in vitro testing models are lacking. Our work was conducted in order to develop a reproducible, validated testing method for assessing the effects of blue light on the skin. We designed a custom blue-light box that can be used to generate blue light at 460 nm wavelength. We performed a series of studies to optimize the dose and timing of the exposure & skin-culture conditions. Our work demonstrates that 6 hours of daily blue light for 5 consecutive days (total 30 J/cm2) produced a dose-and-time dependent decrease in skin health in 3D full thickness in vitro skin tissues. In addition, gene expression data showed an increase in the expression of genes that regulate inflammation and oxidative stress pathways (IL1A, IL6, CXCL8, COX2, CYP1B1, & NQO1) & a decrease in the expression of genes that maintain skin barrier and integrity (KRT1, KRT10, LOR, DSC and Collagen). Genes regulating skin aging & hydration including MMP1 & FLG were also regulated by exposure to blue light. Enzyme-linked immunoassays were performed to confirm changes in specific proteins. Exposure to blue light significantly increased 8-hydroxy-2' -deoxyguanosine, a marker for oxidative stress, & MMP1, markers for photoaging. Immunohistochemistry staining was performed to confirm changes in Collagen, Filaggrin & NQO1 protein expression in skin tissue. Our results showed that consistent blue light exposure produced skin damage via alterations in key biological pathways. This work provides a new, reproducible in vitro testing method for assessing the effects of blue light on human skin using gene expression, protein ELISA and IHC staining.

Biomarker Identification in Fatal Covid-19 and Post-Acute Sequalae of SARS-CoV-2 (PASC) Lungs

Rationale: SARS-CoV-2 has affected millions worldwide. Among those individuals infected with this coronavirus, most recover without hospitalization. However, COVID-19 is characterized by chronic lung failure and death in a significant number of hospitalized patients. Indeed, there is growing evidence that SARS-CoV-2 causes ARDS leading to lung fibrosis that shares similarities with interstitial lung diseases (ILDs) including idiopathic pulmonary fibrosis (IPF). Herein, we addressed the hypothesis that fatal COVID-19, PASC, and ILDs share key biomarkers of interest in lung fibrosis. Methods: This study included 9 fatal COVID-19 and 13 PASC cases, who received lung transplants due COVID-19 associated lung failure. Clinical characteristics such as duration of mechanical ventilation, length of hospitalization, age, sex, and BMI were evaluated in each patient. Autopsy and explanted lung samples were subjected to histopathological and/or immunohistochemical (IHC) analysis for key biomarkers of interest in lung fibrosis including bromodomain-containing protein-4(BRD4), interferon alpha 2(IFNα2), interleukin-1(IL-11), growth differentiation factor 15(GDF15), and keratin 8(KRT8). COVID-19 and PASC lung samples were also compared with lung samples from fatal ARDS due to other causes (i.e., non-COVID-19 ARDS).Results: In the fatal COVID-19 patient group, the mean age was 60.6(50-71) years-old and included 6 males and 3 females. In the transplanted-PASC patient group, the mean age was 46(31-71) years-old and included 12 males and 2 females. The average BMI was 28.3(21-35.5) for fatal COVID-19 and 25.2(19-29.5) for PASC. In fatal COVID-19, comorbidities included hypertension(22%), diabetes(44%), immunocompromised status(11%). The mean duration of mechanical ventilation was 23(8-65) days while hospitalization was 25(8-67) days. Conversely, PASC patients averaged 168(71-539) days from diagnosis to transplant date. The SARS-CoV-2 ARDS survivors that developed chronic lung failure had diffuse interstitial fibrosis frequently with organization into a non-specific interstitial fibrosis (NSIP) pattern. Key IHC findings in fatal COVID-19 and in PASC lung samples included BRD4, IFNalpha2, and IL-11 receptor alpha (IL-11RA) protein expression, which were markedly increased in several cell types most notably macrophages or myeloid cells localized in the alveolar space in COVID-19 lung samples. Although these markers were detected in non-COVID-19 ARDS the levels of each were markedly lower than that detected in the COVID-19 lung samples.Conclusions: These data suggest that key profibrotic pathways in the lung are shared among COVID-19 and chronic fibrotic ILDs. The identification of these pathways provides the impetus to further explore treatment strategies which might survival benefit to chronically ventilated COVID-19 patients and mitigate the need from lung transplantation in PASC patients.

Serum gasdermin D levels are associated with the chest computed tomography findings and severity of COVID-19.

BACKGROUND: The role of programmed cell death, especially pyroptosis and apoptosis, in unfavorable immune responses in COVID-19 remains to be elucidated. METHODS: We conducted a cross-sectional analysis to investigate the association between the serum gasdermin D (GSDMD) levels, a pyroptotic marker, and caspase-cleaved cytokeratin 18 fragment (M30), an apoptotic marker, and the clinical status and abnormal chest computed tomography (CT) findings in patients with COVID-19. RESULTS: In this study, 46 patients diagnosed with COVID-19 were divided into the following three groups according to the disease severity: mild to moderate group (n = 10), severe group (n = 14), and critical group (n = 22). The serum GSDMD levels were higher in the critical group than in the mild to moderate group (P = 0.016). In contrast, serum M30 levels were lower in the critical group than in the severe group (P = 0.048). Patients who required mechanical ventilation or died had higher serum GSDMD levels than those who did not (P = 0.007). Area of consolidation only and of ground glass opacity plus consolidation positively correlated with serum GSDMD levels (r = 0.56, P < 0.001 and r = 0.53, P < 0.001, respectively). CONCLUSION: Higher serum GSDMD levels are associated with critical respiratory status and the consolidation area on chest CT in patients with COVID-19, suggesting that excessive activation of pyroptosis may affect the clinical manifestations in patients with COVID-19.

Neuroendocrine cancer of the prostate. Two case reports

Background: Neuroendocrine cancer of the prostate can present in diverse clinical pictures, potentially hampering the diagnosis and probably leading to underdiagnosis. Methods: Two cases are presented corresponding respectively to two forms of the disease: de novo neuroendocrine cancer and dedifferenciation of an adenocarcinoma of the prostate to neuroendocrine cancer under long term luteinising hormone releasing hormone (LHRH) agonist treatment. Results: Suspicion of neuroendocrine cancer may be raised in prostate cancer patients presenting either clinical or radiological metastatic progression without prostate specific antigen (PSA) rise, or relatively extended metastatic disease right at diagnosis associated to relatively low PSA, yet any non-pulmonary visceral metastases. Neuroendocrine cancer of the prostate can also turn out to be the origin of an adenocarcinoma of unknown primary. Conclusion: In case these considerations are respected the risk of missing the correct diagnosis of a neuroendocrine cancer of the prostate may be minimised.

Sars-Cov-2 Infection Promotes Endothelial Dysfunction and Thrombosis in a Mouse Model of COVID-19

Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Most infected individuals are asymptomatic or show only mild symptoms, but 20% of infected individuals become severely ill resulting in a 2-5% mortality rate for severe infections. Men, the elderly and patients with comorbidities (such as cardiovascular disease, hypertension, diabetes, and obesity) are more likely to develop severe disease. Clinical features characterizing severe COVID-19 cases include inflammation and thrombosis, but the molecular mechanisms underlying these processes remain elusive. K18 hACE2 transgenic mice express the SARSCoV-2 receptor human angiotensin-converting enzyme 2 (hACE2) under the control of the human cytokeratin 18 (K18) promoter. K18 hACE2 mice express hACE2 in airway epithelial cells and are susceptible to SARS-CoV-1 and SARS-CoV-2 infections. At the dose of 10 5 PFU/mouse, all SARS-CoV-2-infected K18 hACE2 mice rapidly lose weight and succumb to viral infection by 5-6 days post infection. Morbidity and mortality correlated with SARS-CoV-2 replication in the nasal turbinates and lungs. Notably, susceptibility was highly associated with a local and systemic cytokine/chemokine storm. SARS-CoV-2 infection in K18 hACE2 mice recapitulates many of the pathological findings observed in human patients offering a reliable animal model for the study of SARS-CoV-2 pathogenesis. Infection with a lower viral dose (10 4 and 2.5x10 3 PFU/mouse) prolongs the symptomatic phase of the infection, postponing time of death up to 16 days post infection (mortality rate at 10 4 PFU: ~40% in females, 100% in males;mortality rate at 2.5x10 3 PFU: ~30% in females, ~55% in males). At these lower viral doses, K18 hACE2 mouse males exhibited both increased susceptibility to the SARS-CoV-2 infection and more severe disease. Male mice showed increased mortality associated with an increase in weight loss and decrease in body temperature. Disease characteristics showed striking similarities with reported human COVID-19 cases, including severely reduced O 2 saturation. The pathogenesis of severe COVID-19 cases involves both virus-induced cell damage and secondary tissue damage due to a vicious cycle of dysregulated - hyperactive coagulation and inflammatory pathways that present as “a cytokine storm”, endothelial dysfunction, and “immunothrombosis”. Analysis of murine plasma analytes from infected mice revealed additional pathogenetic features resembling SARS-CoV-2 infection in humans. High circulating D-dimer levels are now considered a main predictor of poor outcome of SARS-CoV-2 infection. Notably, we also observed a progressive increase of circulating D-dimer levels in the plasma of K18 hACE2 infected mice peaking at day 7 post infection, suggestive of a hypercoagulable state. Moreover, similar to humans, the increase in soluble thrombomodulin plasma concentration and its correlation with disease severity was indicative of endothelial activation and dysfunction in K18 hACE2 infected mice. SARS-CoV-2 infection-induced changes of coagulation and endothelial activation in mice resulted in a biphasic alteration of endothelial permeability where an initial increase in vascular permeability, peaking at day 5 post infection, was followed by a sudden decrease in Evan's blue dye extravasation in the lung parenchyma and characterized by the appearance of areas of hemorrhagic infarction indicative of thrombotic events. Altogether, our results identify the K18 hACE2 transgenic mouse as an important small animal model to study the molecular mechanisms involved in the derangement of the finely tuned interaction between the immune and coagulation systems associated with severe cases of SARS-CoV-2 infections. Disclosures: Mosnier: Hematherix: Membership on an entity's Board of Directors or advisory committees;Coagulant Therapeutics: Research Funding.

Elevations of serum cancer biomarkers correlate with severity of COVID-19.

In this retrospective study, we evaluated the levels of a series of serum biomarkers in coronavirus disease 2019 (COVID-19) patients (mild: 131; severe: 98; critical: 23). We found that there were significant increases in levels of human epididymis protein 4 (HE4) (73.6 ± 38.3 vs 46.5 ± 14.7 pmol/L; P < .001), cytokeratin-19 fragment (CYFRA21-1) (2.2 ± 0.9 vs 1.9 ± 0.8 µg/L; P < .001), carcinoembryonic antigen (CEA) (3.4 ± 2.2 vs 2.1 ± 1.2 µg/L; P < .001), carbohydrate antigens (CA) 125 (18.1 ± 13.5 vs 10.5 ± 4.6 µg/L; P < .001), and 153 (14.4 ± 8.9 vs 10.1 ± 4.4 µg/L; P < .001) in COVID-19 mild cases as compared to normal control subjects; their levels showed continuous and significant increases in severe and critical cases (HE4, CYFRA21-1, and CA125: P < .001; CEA and CA153: P < .01). Squamous cell carcinoma antigen (SCC) and CA199 increased significantly only in critical cases of COVID-19 as compared with mild and severe cases and normal controls (P < .01). There were positive associations between levels of C-reactive protein and levels of HE4 (R = .631; P < .001), CYFRA21-1 (R = .431; P < .001), CEA (R = .316; P < .001), SCC (R = .351; P < .001), CA153 (R = .359; P < .001) and CA125 (R = .223; P = .031). We concluded that elevations of serum cancer biomarkers positively correlated with the pathological progressions of COVID-19, demonstrating diffuse and acute pathophysiological injuries in COVID-19.