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Introduction: SARS-CoV-2 is responsible for the current global pandemic. SARS-CoV-2 infection underlies the novel viral condition coronavirus disease 2019 (COVID-19). COVID-19 causes significant pulmonary sequelae contributing to serious morbidities. The pathogenesis of COVID-19 is complex with a multitude of factors leading to varying levels of injury numerous extrapulmonary organs. This review of 124 published articles documenting COVID- 19 autopsies included 1,142 patients. Method(s): A PubMed search was conducted for COVID-19 autopsy reports published before March 2021 utilizing the query COVID-19 Autopsy. There was no restriction regarding age, sex, or ethnicity of the patients. Duplicate cases were excluded. Findings were listed by organ system from articles that met selection criteria. Result(s): Pulmonary pathology (72% of articles;866/1142 patients): diffuse alveolar damage (563/866), alveolar edema (251/866), hyaline membrane formation (234/866), type II pneumocyte hyperplasia (165/866), alveolar hemorrhage (164/866), and lymphocytic infiltrate (87/866). Vascular pathology (41% of articles;771/1142 patients): vascular thrombi (439/771)-microvascular predominance (294/439)-and inflammatory cell infiltrates (116/771). Cardiac pathology (41% of articles;502/1142 patients): cardiac inflammation (186/502), fibrosis (131/502), cardiomegaly (100/502), hypertrophy (100/502), and dilation (35/502). Hepatic pathology (33% of articles;407/1142 patients): steatosis (106/402) and congestion (102/402). Renal pathology (30% of articles;427/1142 patients): renal arteries arteriosclerosis (111/427), sepsis-associated acute kidney injury (81/427) and acute tubular necrosis (77/427). Conclusion(s): This review revealed anticipated pulmonary pathology, along with significant extrapulmonary involvement secondary to COVID-19, indicating widespread viral tropism throughout the human body. These diverse effects require additional comprehensive longitudinal studies to characterize short-term and long-term COVID-19 sequelae and inform COVID-19 treatment.
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Introduction: Syphilis is a multi-systemic disease caused by spirochete Treponema pallidum. Very rarely, it can affect the liver and cause hepatitis. Since most cases of hepatitis are caused by viral illnesses, syphilitic hepatitis can be missed. Here, we present a case of syphilitic hepatitis in a 35-year-old male. Case Description/Methods: Patient was a 35-year-old male who presented to the hospital for jaundice and mild intermittent right upper quadrant abdominal pain. His medical history was only significant for alcohol abuse. His last drink was 4 weeks ago. He was sexually active with men. On exam, hepatomegaly, mild tenderness in the right upper quadrant, jaundice, and fine macular rash on both hands and feet were noted. Lab tests revealed an ALT of 965 U/L, AST of 404 U/L, ALP of 1056 U/L, total bilirubin of 9.5 mg/dL, direct bilirubin of 6.5 mg/dL, INR of 0.96, and albumin of 2.0 g/dL. Right upper quadrant ultrasound showed an enlarged liver but was negative for gallstones and hepatic vein thrombosis. MRI of the abdomen showed periportal edema consistent with hepatitis without any gallstones, masses, or common bile duct dilation. HIV viral load and Hepatitis C viral RNA were undetectable. Hepatitis A & B serologies were indicative of prior immunization. Hepatitis E serology and SARS-CoV-2 PCR were negative. Ferritin level was 177 ng/mL. Alpha-1-antitrypsin levels and ceruloplasmin levels were normal. Anti-Smooth muscle antibody titers were slightly elevated at 1:80 (Normal < 1:20). Anti-Mitochondrial antibody levels were also slightly elevated at 47.9 units (Normal < 25 units). RPR titer was 1:32 and fluorescent treponemal antibody test was reactive which confirmed the diagnosis of syphilis. Liver biopsy was then performed which showed presence of mixed inflammatory cells without any granulomas which is consistent with other cases of syphilitic hepatitis. Immunohistochemical stain was negative for treponemes. Patient was treated with penicillin and did have Jarisch-Herxheimer reaction. ALT, AST, ALP, and total bilirubin down trended after treatment. Repeat tests drawn exactly 1 month post treatment showed normal levels of ALT, AST, ALP, and total bilirubin (Figure). Discussion(s): Liver damage can occur in syphilis and can easily be missed because of the non-specific nature of presenting symptoms. In our patient, the fine macular rash on both hands and feet along with history of sexual activity with men prompted us to test for syphilis which ultimately led to diagnosis and treatment in a timely manner. (Figure Presented).
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Purpose of Study: The spread of SARS-CoV-2 and the resulting Coronavirus Disease 2019 (COVID-19) continues to manifest in individuals in varying severity with limited treatment options available. Despite research efforts put forth in developing therapeutic options for treatment of COVID-19 disease, effective and well understood mechanisms remain limited. Corticosteroid treatment with dexamethasone was shown to be beneficial for those with severe illness early in the pandemic with little understanding of its beneficial mechanism. This narrative review describes the current findings regarding the mechanism of action of dexamethasone treatment in the setting of SARS-CoV-2 infection. Methods Used: A comprehensive search of Embase and PubMed was conducted in consultation with a health sciences librarian. Search terms included (1) COVID-19 (2) dexamethasone (3) animal model and (4) immune response. No limits were used on the search and other reviews were excluded. Search results were screened based on titles and s before being selected for full text review. Outcomes recorded included characterization of the microenvironment of lung tissue following SARS-CoV-2 through cytokine measurement, histopathological staining and analysis of lung tissue, and clinical outcomes such as survival time. Summary of Results: The search resulted in 100 articles. Of these, 8 articles were identified that met the inclusion criteria. Three conducted experiments with Syrian hamsters, two with mice, two with alveolar macrophages, and one study was conducted with human subjects. Dexamethasone treatment was found to diminish inflammatory cytokine levels and preserve the integrity of lung tissue in several animal models and in vitro experiments in the setting of SARS-CoV-2 infection. Dexamethasone treatment was also found to reduce inflammatory cell infiltration of lung tissue infected with SARS-CoV-2. In humans, combination therapy of low dose dexamethasone with spironolactone proved more effective at lowering inflammatory markers than high dose dexamethasone alone. Conclusion(s): Collectively, the articles included in this review support the use of dexamethasone treatment in SARS-CoV-2 infection. Protective effects exhibited with dexamethasone treatment suggest that its action may be linked to the inflammatory nature of COVID-19 disease. Macrophage regulation and diminished inflammatory cytokine levels were hypothesized as possible mechanistic features of dexamethasone action but lacked exact characterization. Further exploration of combination treatment with dexamethasone and its mechanism of action is needed to identify specific and effective therapeutic strategies in the future.
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Introduction/Aim: Coronavirus disease 2019 (COVID-19) is a novel viral infection that can cause severe pneumonia and acute respiratory failure;however, the mechanism of disease progression is still unclear. The aim of this study is to evaluate inflammatory cells in the lung by analysing cell populations of bronchial aspirates of COVID-19 pneumonia. Method(s): Eligible cases were diagnosed as COVID-19, confirmed by SARS-CoV-2 PCR. All cases had developed severe COVID-19 pneumonia and undergone invasive positive pressure ventilation for the treatment of respiratory failure. Bronchial aspirates were collected during endotracheal intubation, and SARS-CoV-2 PCR was done. The populations of obtained cells from bronchial aspirates were examined by Giemsa staining and immunohistochemical staining of CD3, CD4, CD8, CD20 and CD68 antigens. Bronchial aspirates were cultured to confirm respiratory bacterial co-infections. Result(s): A total of 14 cases (median age 70;eleven male and three female) were enrolled in this study. Their bronchial aspirates were all positive for SARS-CoV-2 PCR. Bacterial co-infections were developed in 10 cases, including 6 cases of pneumonia/respiratory tract infection, 2 cases of sepsis, and 2 cases of urinary tract infection. Cell populations of bronchial aspirates with or without bacterial co-infections were as follows: neutrophils 33.0% vs. 21.5%;CD3+ mononuclear cells (MNCs) 2.5% vs. 5.8%;CD4+ MNCs 4.6% vs. 3.4%;CD8+ MNCs 3.5% vs. 5.2%;CD20+ MNCs 0.2% vs. 0.1%;CD68+ MNCs 39.7% vs. 38.8%, respectively. Conclusion(s): CD68 antigen is mainly expressed in monocytes/macrophages. CD68+ MNCs were dominant in bronchial aspirates of the cases with severe COVID-19 pneumonia. Our data suggests that CD68+ MNCs, presumably macrophages, would play an essential role during the innate immune response to acute SARS-CoV-2 infection in the lung.
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"COVID-toes" are chilblains that occurred in patients who may have been exposed to SARS-CoV-2, but without COVID-19 symptoms and/or with negative PCR or serology. The literature suggests that chilblains are an unexpected consequence of a strong interferon-mediated antiviral response, but the underlying molecular mechanisms remain poorly understood. We thus sought to explore the physiopathology of COVID-related chilblains by using spatially and temporally resolved transcriptomics. We included 19 patients with COVID-toes, and performed a complete virological assessment to exclude SARS-CoV-2 infection including skin viral metagenomics. Some patients had clinical symptoms evoking viral infection, but none had COVID-19. Apart from low levels of non-conventional antiphospholipid antibodies, biological tests were unremarkable. We performed spatially resolved transcriptomics (Visium, 10X Genomics) in 3 patients at different timepoints and compared them with 1 vaccination-related chilblain. We observed a different transcriptional profile in COVID-toes compared with COVID-19 vaccine-related chilblains. IRF1, CXCL10, ISG15 and STAT1 were highly expressed in COVID-toes and their expression decreased over time, confirming an activation of interferon and JAK/STAT pathways that was absent in vaccine-related chilblains. The proportion of inflammatory cell types obtained by spatial deconvolution varied over time in COVID-toes. Migratory dendritic cells were present at early stages, while T lymphocytes populations increased later. Overall, this work explores the mechanisms of COVID-19-related chilblains using spatially and temporally resolved transcriptomics.Copyright © 2023
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Background: SARS-CoV-2 infection is a risk factor for the development of depressive symptoms such as lack of energy, loss of interest, and depressed mood. Inflammatory processes might underline this association. The aim of this study was to investigate the association between inflammatory markers and the severity of depression after SARS-CoV-2 infection and the predictive effect of inflammatory markers on the severity of depressive symptoms. Lifestyle factors and lifestyle-related diseases can influence inflammation and depressive symptoms. As these lifestyle factors and lifestyle-related diseases are less common in physically active individuals, they are a suitable population for investigating this research question. Methods: We investigated 61 at least moderate physically active individuals on average â¼6 months (SD = 4.22, range = 0.5-19 months) after SARS-CoV-2 infection (t0) and performed a follow-up after 3 months (t1). Depressive symptoms and biomarkers of inflammation (interleukin [IL]-1ß, IL-8, IL-10, Ferritin, Lipopolysaccharide-binding-protein [LBP], neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], lymphocyte-to-monocyte ratio [LMR]) and kynurenine [KYN] were measured at both time points. Concentrations of inflammatory markers at t0 were used to predict the severity of depressive symptoms at t0 and t1. Results: Concentrations of KYN were negatively related to the severity of depressive symptoms at t0. Concentrations of LMR predicted higher depressive symptoms at t0 as well as at t1. Furthermore, individuals with lower concentrations of LBP at t0 showed a higher severity of depressive symptoms at t1. No correlation was found between severity of depressive symptoms and IL-1ß, IL-8, IL-10, ferritin, NLR, and PLR at both time points. Conclusions: KYN, LBP and LMR might be useful as a predictive factor of depressive symptoms in physically active individuals after SARS-CoV-2 infection. While the results for KYN confirm the current scientific evidence, our results highlight the importance of the innovative inflammatory markers LMR and LBP. LMR and LBP might be interesting targets for predicting the development of depressive symptoms in SARS-CoV-2 infected populations and should be further investigated in future studies.
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Introduction: Varicella zoster virus is a highly infectious alpha-herpesvirus, pathogenic only to humans. The primary infection of varicella zoster virus causes chickenpox, which is contagious and primarily infects children and adolescents in India. Following the primary infection, the virus remains dormant in sensory root ganglia. Activation of the dormant virus in later stages of life causes herpes zoster infection which may vary from subclinical infection to typical zoster, scattered vesicles, zoster sine herpete or disseminated zoster, which depends on the individual's immune status. Case report: In this case series, we present two patients with herpes zoster involving the mandibular branch of the trigeminal nerve. Cytology revealed characteristic features of the infection including nuclear moulding, multinucleated giant cells and ballooning degeneration. Conclusion(s): More recently, patients presenting with herpes zoster have been reported to have sub-clinical Covid-19 infection, suggesting a possibility that herpes zoster might be an indicator for latent Covid-19. Timely detection and treatment of this infection can reduce the risk of post herpetic neuralgia.Copyright © 2022 Sciendo. All rights reserved.
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Psoriasis is a chronic inflammatory disease associated with a de-fective epidermal barrier, in which the immune system is already activated in lesional sites of the skin, and it is thus possible that affected individuals can have different immunologic rates of viral response. This is especially impor-tant in the era of the novel coronavirus disease (COVID-19) that is affecting the entire world. Patients with psoriasis are often receiving systemic therapy which includes immunosuppressive and biologic therapy, so this new infec-tious disease has raised concerns among dermatologists regarding psoriasis treatment. Some of the risk factors of psoriasis are obesity, diabetes mellitus, and hypertension - all of which are diseases linked with negative outcomes and higher severity of COVID-19. Psoriasis is mediated by inflammatory cells and proinflammatory cytokines such as IL-17, IL-23, IFN-gamma, and TNF-alpha, and patients with skin diseases have been shown to be more susceptible to CO-VID-19 infection, but with a less severe disease course. As an anti-inflamma-tory agent, vitamin D could play a significant role in the future as a possible treatment for reducing the risk and severity of psoriasis and COVID-19. It has been suggested that patients treated with biologic therapy should continue treatment, as it has not been shown to cause severe complications of the CO-VID-19 disease. Preventive measures, including vaccination, should be taken to minimize the risk of infection and severity of the clinical outcome.Copyright © 2022, Croatian Dermatovenerological Society. All rights reserved.
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SARS-CoV2 infection induces a complex interaction between virus and host immune system, activating multiple inflammatory pathways and leading to hyperinflammation, diffuse alveolar damage (DAD), ARDS, and multiorgan failure. We aimed to correlate the quantification of viral load, inflammatory cells and cytokines in lung tissue of fatal COVID-19. We assessed inflammatory cells by multiplex immunohistochemistry, cytokines by Luminex xMAP Assay and viral load by real time PCR in autopsy lung tissue of 18 COVID-19 patients. Correlations were considered statistically significant if p<0.05. Macrophages correlated with IL-1beta (r=0.54), IL-10 (r=0.5), IFN-alpha2 (r=0.72), IFN-gamma (r=0.6), CCL20 (r=0.5), TGF-beta1 (r=0.6), TGF-beta2 (r=0.6). CD4+T cells correlated with CCL20 (r=0.6), MDC/CCL2 (r=0.53), CCL17 (r=0.5), IP-10 (r=0.6), CXCL9 (r=0.6). CD8+T cells correlated with IL-1beta (r=0.54), IL-4 (r=0.63), IL-6 (r=0.7), IL-8 (r=0.63), IL-10 (r=0.6), TNF-alpha (r=0.6), IFN-gamma (r=0.74), CCL20 (r=0.7), TGF-beta1 (r=0.7), TGF-beta2 (r=0.56), TGF-beta3 (r=0.54), MDC/CCL2 (r=0.7), CCL17 (r=0.64). Langerin dendritic cells (DC) correlated with symptom onset to death interval (r=0.6), hospitalization length (r=0.65), mechanical ventilation (MV) length (r=0.6), ICU stay (r=0.6), exudative DAD (r=-0.5), viral load (r=-0.6). Myeloid DC correlated with symptom onset to death interval (r=0.8), hospitalization length (r=0.8), MV length (r=0.8), ICU stay (r=0.8), exudative DAD (r=-0.5), viral load (r=-0.7). Viral load correlated with symptom onset to death interval (r=-0.7), hospitalization length (r=-0.8), MV length (r=-0.7), ICU stay (r=-0.8), exudative DAD (r=0.6). There is a complex temporal inflammatory modulation in severe COVID-19.
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A 59-year-old white female who was previously fit and well, developed gradual tightening and thickening of the skin on her forearms progressing to the abdomen, chest and lower legs associated with restricted movement. She also noticed bruise-like patches on her trunk. There were no systemic symptoms and no history of Raynaud syndrome. Since the beginning of the COVID-19 lockdown, the patient had engaged in increasing amounts of exercise compared with normal;this included yoga once weekly for 75 min, high-intensity interval training for 20 min on alternate days, running three times weekly for 45 min, lifting 2.5 kg weights for the arms every day and regular long walks. Examination showed a 'groove' sign on her forearms and a peau d'orange appearance of the skin with a woody induration and hardness on palpation. Symmetrical and circumferential involvement on the forearms and lower legs and bruise-like indurated patches on the abdomen were noted. Differential diagnoses included eosinophilic fasciitis (EF), morphoea, EF/morphoea overlap, scleroderma, scleromyxoedema and nephrogenic systemic fibrosis. Blood investigations showed an eosinophilia of 1.2 x 109 cells L-1, erythrocyte sedimentation rate of 31 mm h-1, a C-reactive protein of 20 mg L-1 and negative autoimmune and viral serology. She underwent two incisional biopsies down to fascia. The first was taken from the back, which showed an interstitial inflammatory cell infiltrate composed of lymphocytes, plasma cells and very occasional eosinophils. The subcutaneous septa were minimally thickened. The second biopsy taken from the left forearm showed striking thickening of the subcutaneous septa, with an associated inflammatory cell infiltrate, composed predominantly of lymphocytes and plasma cells. This process was deeper and more established than that seen in the biopsy from the trunk. The appearances were clearly those of a sclerosing process of the dermis and subcutis and consistent with eosinophilic fasciitis. Our diagnosis was EF with morphoea overlap and she was treated with oral methotrexate 15 mg weekly and oral prednisolone 50 mg once daily (weight 60 kg), reducing the dose by 5 mg every 2 weeks. An 80% improvement was seen in functionality within 3 months, but the skin remained tight and thickened and therefore the patient was referred for phototherapy [ultraviolet A 1 (UVA1)] as combination therapy. We present a rare case of EF, which appears to have been triggered by intensive exercise. Other causes include insect bites, radiation, infections (Mycoplasma and Borrelia) and paraneoplastic. Haematological associations have been seen, including aplastic anaemia and lymphoma. Treatment options for EF include prednisolone, UVA1/psoralen + UVA, immunosuppressive systemic agents (including ciclosporin and methotrexate), biological agents (including infliximab and rituximab) and physiotherapy.
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Microparticles (MPs) are vesicles of less than 1 mum in diameter (submicron vesicles) shed from plasma membranes to cell activation, injury, and apoptosis response. They consisted of membrane proteins and cytosolic material from the cell they originated. These vesicles are vital mediators of pathological and physiological cellular processes. Polycystic ovary syndrome (PCOS) is a regular endocrine, menstrual and metabolic condition that affects 10-15% of females in their reproductive period. Numerous researches have described the association between low-grade chronic inflammation and PCOS;however, the relation is not well understood. Chronic low-grade inflammation is reflected as a risk factor for cardiovascular disease, atherosclerosis, and endothelial dysfunction, and it is linked to abdominal obesity and insulin resistance (IR). MPs may be useful biomarkers for the early detection of cardiovascular disease and thrombosis in PCOS patients. In March 2020, the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) became pandemic, wreaking havoc on healthcare systems worldwide and the global economy. Obesity, diabetes, and cardiovascular disease have all been linked to COVID-19 increased risk of infection. PCOS patients have recently been identified as an underserved and potentially high-risk demographic for COVID-19 problems. This article tried to review and present recent studies that explored the role of microparticles in polycystic ovarian syndrome.Copyright © 2022 International Journal of Pharmaceutical Research and Allied Sciences. All rights reserved.
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Introduction/Background: Eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss Syndrome, is a rare, small to medium vessel ANCA associated vasculitis. Hallmarks of EGPA include asthma, chronic rhinosinusitis, and peripheral neuropathy. EGPA is characterized by a prodrome of asthma and allergic rhinitis, followed by peripheral blood hyper-eosinophilia and accumulation of extravascular eosinophils, and finally systemic vasculitis. Extrapulmonary involvement is common, sometimes with fatal outcomes. The onset of EPGA is typically between 25-50 years;however, EGPA also occurs during childhood and has a significant morbidity and mortality. Description/Method: Our patient presented to the emergency department with a 2-week history of lethargy, wheeze and left sided neck swelling. After testing COVID-19 positive eight months prior to this, she developed wheezy episodes and was subsequently diagnosed with asthma which was managed with bronchodilators as required. She was reviewed by an allergist who confirmed a dust mite allergy and prescribed Montelukast. She remained well during the summer months however during winter she had 3 distinctive episodes of wheeze and cough which were managed by antibiotics and prednisolone. In the emergency department, an echocardiogram was performed which showed a cardiac tamponade. She was transferred to CICU where she had a pericardial drain inserted. The fluid was abundant with inflammatory cells. Multiple investigations were performed as follows: Hb: 135g/L, wbc: 20.30 x 10 9/L, Eosinophils: 12.77 x 10 9/L, CRP: 51 mg/L, ESR: 75 mm/hr, LDH: 1188 IU/L, IgE: 8000 UI/ml, ANA, ANCA: negative. CT chest showed mediastinal lymphadenopathy and patchy bilateral infiltrate and cardiac MRI showed myopericarditis and LV fibrosis. BMA showed no malignant cells and sinusitis was confirmed by CT. On examination, she was underweight. Her nasal mucosa looked inflamed. Otherwise systemic examination was unremarkable. In the context of poor ejection fraction (20%) with LV fibrosis, urgent MDT was arranged and concluded that our working diagnosis was EGPA. The decision was made to start IV methylprednisolone 10mg/kg/day for 3 days and Ivermectin. That night our patient had a VF arrest which required a single shock conversion 4J/kg. There was 7-minute downtime. Treatment was escalated to include cyclophosphamide, rituximab and plasmapheresis. The patient made a remarkable recovery, extubated and transferred to a normal ward. Her eosinophils count and inflammatory markers improved dramatically following treatment. However, she developed severe neuropathic left leg pain and NCS confirmed peripheral neuropathy Discussion/Results: EGPA is a very rare disease and diagnosis can be challenging especially with the absence of histopathology diagnosis. Early empirical treatment especially in a very ill child in intensive care unit can save lives and divert the progress of the disease. This patient has fulfilled the American College of Rheumatology criteria to diagnose EGPA including asthma, eosinophil count > 10% of upper normal, peripheral neuropathy, pulmonary infiltrates on CT thorax and paranasal sinuses abnormalities. Cardiac biopsy of the fibrotic mass may be a useful tool for diagnosis;however, this invasive procedure may expose this patient with high risk of fatal arrhythmias. Since other causes of eosinophilia were ruled out including parasitic infections, lymphoproliferative disorders, and rare primary immunodeficiency syndromes (hyper-IgE syndrome due to STAT3 or DOCK8 deficiency and Omenn syndrome) and the patient responded well to treatment, the diagnosis of EGPA was supported. Key learning points/Conclusion: Asthma not responding to bronchodilator could be another diagnosis Eosinophilia should be interpreted with caution. Defer the need for histopathology diagnosis in critically ill children Cardiac involvement is a life-threatening marker Early diagnosis prevents life threatening complications.
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Case Report: Most common causes of shortness of breath are asthma, COPD, CHF, pulmonary embolism, diffuse lung parenchymal diseases and obesity hypoventilation syndrome. Rare conditions can be bronchiectasis, constrictive pericarditis, kyphoscoliosis, tracheomalacia, cardiomyopathies and so on. We present a rare case of tracheal stenosis presenting with repeated hospital admissions followed by intubations and resolution after spontaneous expectoration. A 52-year-old female with a history of end stage renal disease on hemodialysis, resistant hypertension, and COVID pneumonia on supplemental oxygen, presented with dyspnea associated with yellowish productive sputum for one day. She was admitted one week prior due to the same complaint associated with encephalopathy due to hypercapnia, required endotracheal intubation, got extubated four days later, was provisionally diagnosed with asthma and volume overload, and discharged home. During the admission of interest, the patient's examwas normal except severe hypertension with BP of 192/101, bilateral crackles and rhonchi. Arterial blood gasses (ABGs) again showed hypercapnia. CT thorax showed evidence of left lower lobe pulmonary infiltrate and ground-glass opacities. Due to repeated admissions for hypercapnic respiratory failure, suspicion for persistent anatomic or pathologic abnormality was high. Reexamination of CT thorax suggested subglottic stenosis and she underwent fiberoptic laryngoscopy which revealed grade 3 subglottic stenosis. On day three, she became hypoxic and unresponsive, ABGs revealed PCO2 of 150, and got intubated again. Soon after intubation, the patient had spontaneous expectoration of a large piece of firm, fleshy, blood-tinged, thick, luminal tissue. On the histologic examination, the material was found to be a plug of fibrin with small to moderate numbers of inflammatory cells embedded in the matrix. Follow-up CT neck and chest revealed resolution of previously visualized tracheal stenosis. She underwent repeat direct laryngoscopy and flexible bronchoscopy which did not show any tracheal stenosis. The patient remained hemodynamically stable and was discharged home. Tracheal stenosis is challenging to diagnose. Examples of tracheal stenosis due to pseudomembrane formation are rare in medical literature, and the expectoration of fibrin material after intubation in a person with this condition is even rarer. A similar case has been described before with an identical situation of coughing up soft tissue and comparable histopathology report. Our case highlights the importance of critical analysis for broad differentials, adding up pieces of the puzzle to explain the missing link. This patient came with recurrent episodes of dyspnea that were misdiagnosed as volume overload, pneumonia, and asthma exacerbations. CT chest findings of possible subglottic stenosis were the missing link in this case which steered further work-up and led to the final diagnosis. Copyright © 2023 Southern Society for Clinical Investigation.
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Purpose/Objectives: Bioprinted models of lung tissue are in high demand but in short supply, particularly for addressing the research needs in response to COVID-19 pandemic. The lung is arguably one of the most complex organs in the body, with a multiscale cytoarchitectural organization serving its multiple functions. In particular, the cellular structure of the alveolar sacs poses a big challenge to extrusion bioprinting, which is more adept at capturing the external shape of biological objects than their cell-level details.Methodology: Recently, we proposed a constructive compromise, attainable by bioprinting of equivalent 3D constructs derived from individual (such as 'precision cut lung slices') or stackable (serial histological sections) anatomic images. The advantage of this approach is that in these images, which can be obtained either from regular histology, or confocal fluorescence or electron microscopy (EM), is already incorporated a wealth of structural information. This can be first transferred to '2.5 dimensional' models (by giving them a finite thickness), and then these can be printed layer-by-layer and stacked as tissue-equivalent 3D volumes. Here we illustrate this proposed workflow with 3D printed human lung sections, and with a lung fragment reconstituted from serial sections, while also simulating the infection with SARS-CoV-2 virus in the same constructs by an agent-based modeling approach.Results: As proof of concept, we processed a human lung histological section in CAD, converted it as .stl file and then 3D printed it using as materials both polycaprolactone (by fused filament fabrication), and by the FRESH method using alginate as hydrogel bioink. Similarly, we extracted from a serial EM stack an image selection which was imported in CAD as well and printed as a self-standing object by photolithography. Here we also report the re-purposing of a simulation program of SARS-CoV-2 infection created on the CompuCell 3D (CC3D) platform, to analyze the propagation of infection in cellular patterns derived from the same histological and ultrastructural sections of human lungs. Using it, we explored the spatial distribution and kinetics of several cell classes (infected, virus shedding, apoptotic), the associated viral and cytokine fields, as well as the impact of the presence of generic inflammatory cells, in comparison with the comparable situations when the cell distribution was a uniform epithelial monolayer. We noted a good reproducibility of these simulations, in spite of the section-characteristic cell distribution patterns, and of the initial locations ('seeding') of the viral infection. In addition, we reconstructed thicker virtual tissue slices from multiple single-cell layers for the study of their viral infection as well.Conclusion/Significance: In conclusion, while more sophisticated methods to capture the tissue structure in 3D constructs certainly exist, the extrusion bioprinting is shown here to be capable to offer a simpler, more practical, and more affordable alternative. We also demonstrated how computational simulations on the same images as used in bioprinting, can be used as a useful heuristic instrument to anticipate the results of the interaction of viruses with bioprinted structures that are more complex than cellular monolayers.
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SESSION TITLE: Occupational and Environmental Lung Disease Cases SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Chlorine gas is a pulmonary irritant with pungent odor that damages the respiratory tract. Chlorine gas exposure occurs in industrial or household exposures,Chlorine gas has two forms either a liquid or gas, toxicity of chlorine gas depends on the dose and duration of exposure. Chlorine gas used in manufacturing products like paper, insecticides, Chlorine is used to treat bottled and swiming pool water. CASE PRESENTATION: A 37 Y.O Male, no PMH presents with progressive dyspnea for three days worse with activity,decreases with rest, denied cough fever or chest pain he is vaccinated for COVID,no smoking history. The patient worked at a chlorine gas factory in the Dominican Republic for 15 years. Exam: Vitals: BP 124/72 mmHg. HR 100 BPM. RR 21 BPM. SpO2 84%. General: acute distress. Heart: normal S1, S2. RRR. Lung: wheeze bilaterally. Abdomen: Soft. Musculoskeletal: no pitting edema. he was placed on 6 LPM NC saturation improved to 90%. CBC and Chemistry were unremarkable, he was started on steroid, breathing treatment with antibiotics. ABG showed hypoxemia. he was placed on Venturi mask and his saturation improved to 95%.CTA was negative for PE. EKG, troponin were unremarkable. A proBNP normal. The antibiotics were discontinued because of a negative workup. A TTE study was normal. HRCT scan of the chest, showed atelectasis and infiltrates of lower lobes. No interstitial fibrosis.A PFT showed obstructive airway disease. He was discharged on oral and inhaled steroids.Hi new onset obstructive airway could be due to chlorine gas exposure. DISCUSSION: Chlorine gas causes cellular injury through oxidative damage but further damage results from activation and recruitment of inflammatory cells with subsequent release of oxidants and proteolytic enzymes. Humans can detect chlorine gas odor at a concentration between 0.1-0.3 ppm. At 1-3 ppm,it causes irritation of oral,eye mucosal membranes. At 30-40 ppm causes cough, chest pain, and SOB. At 40-60 ppm, toxic pneumonitis and pulmonary edema and can be fatal at 430 ppm concentration or higher within thirty minutes. Chronic exposure to chlorine gas lead to chest pain, cough, sore throat, hemoptysis, recurrent asthma. Physical exam findings include tachypnea cyanosis, wheezing, intercostal retractions, decreased breath sounds. Pulmonary function tests may reveal obstructive lung function disease. Chronic exposure to a low level was found to be associated with an increased risk of asthma in swimmers. CONCLUSIONS: Chlorine exposure results in direct chemical toxicity to the airways with acute airways obstruction or airways hyperreactivity, presentation varies from acute overwhelming intoxication with acute lung injury and or death, occupational exposure increase the likelihood of chronic bronchitis or isolated wheezing attacks. Treatment for chlorine exposure is largely supportive. Reference #1: 1- Center of disease control and prevention website/emergency preparedness and response/ https://emergency.cdc.gov/agent/chlorine/basics/facts.asp Reference #2: 2- C- Morim A, Guldner GT. Chlorine Gas Toxicity. [Updated 2021 Jul 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing;2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537213/. Reference #3: A- Gummin DD, Mowry JB, Beuhler MC, et al. 2020 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 38th Annual Report. Clin Toxicol (Phila). 2021;59(12):1282-1501. doi:10.1080/15563650.2021.1989785 DISCLOSURES: No relevant relationships by Abdallah Khashan No relevant relationships by Samer Talib no disclosure on file for Matthew Yotsuya;
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SESSION TITLE: Autoimmune Diffuse Lung Disease Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Nonspecific interstitial pneumonia (NSIP) is an interstitial lung disease (ILD) that can be idiopathic or associated with connective tissue disorders (CTDs). The two subtypes of NSIP are cellular interstitial pneumonitis (CIP) and fibrotic, with CIP being less common. Subtypes can be distinguished through pathology and imaging. NSIP constitutes 14-36% of cases of idiopathic interstitial pneumonias. ILD-associated DM has a higher mortality, making diagnosis crucial. In specific, fibrotic NSIP has a high 10-year mortality rate, making differentiation relevant. CASE PRESENTATION: A 36-year-old female presented with fatigue and erythematous papular lesions on her face, palms, shoulder, and neck for one month. She also developed a fever and dry cough a week before. She denied recent travel or sick contacts. COVID-19 was negative. On exam, she was tachypneic and tachycardic with a maculopapular rash. A pulmonary exam revealed bilateral fine crackles. CXR showed dense left and mild right-sided patchy consolidations. Labs revealed elevated inflammatory markers (ESR-63, CRP-1.9, LDH-982). CPK was high - 517. CBC and procalcitonin were normal. CT showed extensive patchy and confluent areas of opacification of the left lower lobe, including a mass-like area measuring 3.3cm. Infectious workup was negative. Autoimmune testing ( Anti-Jo 1 Ab, ANA, etc) was negative. Bronchoscopic left lower lobe biopsy showed cellular interstitial inflammation composed of lymphocytes, plasma cells, rare eosinophils, and foci of intra-alveolar fibrinous exudates, suggestive of CIP and OP. She was treated successfully with corticosteroids and was discharged on prednisone. Repeat autoimmune antibody workup was negative. Skin biopsy showed a lichenoid lymphocytic infiltrate and necrotic keratinocytes consistent with dermatomyositis. Mycophenolate and rituximab were initiated;prednisone was tapered off. Follow-up chest CT showed cleared infiltrates with symptomatic improvement. DISCUSSION: CIP is an uncommon form of NSIP. On CT, bilateral ground-glass opacities are the most common feature. CIP is characterized histologically by interstitial thickening due to the presence of inflammatory cells and type-II pneumocyte hyperplasia with preserved lung architecture. Treatment is corticosteroids. The prognosis is excellent. ILD associated with DM is strongly associated with a positive Anti-Jo Ab, which was negative here making diagnosis challenging. She was diagnosed with dermatomyositis using histological findings from a skin biopsy. She responded to steroids at acute presentation and treatment was tailored once DM was diagnosed leading to complete recovery. CONCLUSIONS: ILD is not uncommon in CTD, however it is usually associated with a positive Anti-Jo 1 antibody. Our case is unique as the patient had negative Anti- Jo 1 Ab, however was found to have cellular NSIP with DM responding well to treatment following diagnosis. Reference #1: https://ard.bmj.com/content/63/3/297 Reference #2: https://www.ncbi.nlm.nih.gov/books/NBK518974/ Reference #3: https://pubmed.ncbi.nlm.nih.gov/33916864/ DISCLOSURES: No relevant relationships by Nawal Ahmed No relevant relationships by TAIKCHAN LILDAR No relevant relationships by Namratha Shripad No relevant relationships by David Wisa
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SESSION TITLE: Infections In and Around the Heart Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Due to the novelty of COVID-19 virus, complications of this severe respiratory infection are continually emerging. The inflammatory response to the virus carries a high mortality rate and can lead to a variety of cardiothoracic complications such as acute coronary syndrome, thromboembolism, and heart failure [1]. Here, we present a case of a young female who suffered cardiac tamponade (CT) from a pericardial effusion (PEEF) attributed to COVID-19 infection, which has only been described a handful of times in the literature. CASE PRESENTATION: A 33-year-old female with a history of Down syndrome and morbid obesity presented with worsening dyspnea and fever for one week. Her initial oxygen saturation was 50% on room air, and bilevel noninvasive ventilatory support was initiated. Her viral PCR was positive for COVID-19. A computed tomography angiogram of the chest revealed small bilateral pulmonary emboli, diffuse ground-glass consolidations, and small bilateral pleural effusions. Her respiratory status continued to decompensate and she was placed on mechanical ventilation. She became hypotensive requiring vasopressor support. The following morning, an echocardiogram (TTE) revealed an ejection fraction of 40-45% and a new PEEF with early right ventricular diastolic collapse consistent with CT physiology. She underwent emergent pericardiocentesis, and 220 mL of bloody fluid was drained. PEEF studies revealed a glucose level of 186 mg/dL, LDH of 1380 U/L, and protein of 3.0 g/dL. Total nucleated count was 16,545/uL with 68% neutrophils. Gram stain showed a few white blood cells without organisms, and final bacterial, fungal, and acid-fast cultures were negative. A pericardial drain was left in place, but the procedure was complicated by a pneumothorax and a chest tube was placed. A follow-up TTE the next day revealed improvement of the PEEF without signs of CT. A repeat chest x-ray showed resolution of the pneumothorax. Unfortunately, the patient’s oxygenation and hemodynamic status continued to worsen. She eventually suffered cardiac arrest with pulseless electrical activity and succumbed to her illness. DISCUSSION: New knowledge regarding complications of COVID-19 infection is continually emerging. According to a February 2022 systematic review, only 30 cases of severe PEEFs with CT secondary to COVID-19 have been recorded. The mechanism by which PEEFs form is unclear. It is proposed that the entry of the virus into inflammatory cells causes a release of cytokines such as TNF-alpha, IL-1, IL-6, and IL-8. This resulting cytokine storm allows rapid inflammation and infiltration of fluid into the pericardial sac [1]. CONCLUSIONS: In a decompensated patient with COVID-19, a stat TTE should be obtained to rule out PEEF. Physicians must be cognizant of this uncommon yet highly fatal complication in unstable COVID-19 patients, as cardiac tamponade is a potentially reversible cause of cardiac arrest. Reference #1: Kermani-Alghoraishi, M., Pouramini, A., Kafi, F., & Khosravi, A. (2022). Coronavirus Disease 2019 (COVID-19) and Severe Pericardial Effusion: From Pathogenesis to Management: A Case Report Based Systematic Review. Current problems in cardiology, 47(2), 100933. https://doi.org/10.1016/j.cpcardiol.2021.100933 DISCLOSURES: No relevant relationships by Amanda Cecchini No relevant relationships by Arthur Cecchini No relevant relationships by Kevin Cornwell No relevant relationships by Krupa Solanki
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Background & Aim: COVID-19 suggested to be treated with pleiotropic agents rather than single-target agents due to its complicated pathophysiology. There are currently no approved effective therapy that can stop the progression of COVID-19. Mesenchymal stem cells and its secretome have been studied in several in vivo lung disease models. The therapeutic application of Secretome therapy has been shown to be efficient in influenza infection, resulting in decreased alveolar fluid clearance and lung injury. This has been linked to attenuation of pro-inflammatory cytokine release, inflammatory cell recruitment, and increased alveolar macrophage content. In this article, we report case series of three COVID-19 patients received an experimental treatment with secretome from umbilical cord-derived mesenchymal stem cells (UC-MSCs) therapy in conjunction with recommended treatment protocols. Methods, Results & Conclusion: Three male patients who were tested positive for COVID-19 are initially presented with mild case of COVID-19 symptoms. The patients were treated with recommended treatment protocols of COVID-19 and add-on secretome from umbilical cord-derived mesenchymal stem cells (UC-MSCs) therapy. In this cases we report the administration of 1 cc and 0,5 cc secretome from UC-MSCs through nasal drop, with 0,5 cc and 0,25 cc for each nostril. Ground Glass Opacity (GGO) were checked by chest CT and the observation stop when patients were symptom-free and tested negative for (Figure Presented)Figs 1 and 2 COVID-19. Significant improvement showed in patients’s respiratory symptoms include GGO profiles, proven by chest CT and no side effects reported. Our report showed that nasal drop of secretome from UC-MSC therapy in patients with mild COVID-19 is safe and well tolerated. No serious therapy-associated adverse event was observed. Further study with more patients and comprehensive biomarker testing is needed to evaluate the efficacy of secretome from UC-MSC therapy to improve long-term treatment outcomes in COVID-19 patients
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As of November 2021, there were 21 million confirmed active cases of COVID-19, including 77,016 patients in serious or critical condition (virusncov.com). However, there are no effective oral drugs for the treatment of severe COVID 19 patients. We here discuss the mechanism of action for Proxalutaminde to treat mild, moderate and severe COVID-19 Patients. Cellular entry and infection of SARS-CoV-2 virus are mediated by two key proteins in host cells, angiotensin converting enzyme 2 (ACE2), a host transmembrane protein, providing the binding sites for SARS-CoV-2 on the host cell surface, and transmembrane protease serine 2 protein (TMPRSS2), priming the S protein of SARS-Cov-2 to facilitate the viral entry into the host cells. Both ACE2 and TMPRSS2 proteins are regulated by androgen receptor (AR) signaling. Previously, Proxalutamide has been reported to downregulate the expression of ACE2 and TMPRSS2 in cells derived from prostate, lung cancer and normal lung epithelial cells. In this study, we demonstrate that Proxalutamide inhibited the infection of SARS-COV-2 wild type, alpha and delta variants, with IC50s of 69, 48 and 39 nM, respectively. Moreover, Proxalutamide reduced SARS-COV-2 viral load in outpatients with COVID-19 (82% viral RT-PCR negative rate in active group vs. 31% in placebo group after treatment for 7 days (p-value<0.0001). Severe COVID-19 disease leads to cytokine storm resulting in pulmonary inflammation and extensive damage in lung and other organs. Anti-inflammatory drugs, including Baricitinib and dexamethasone, have shown limited clinical benefit for hospitalized COVID-19 patients. Therefore, more effective drugs are in urgent need for patients suffering from severe COVID-19. Recently, Proxalutamide has been reported to reduce the mortality rate (HR=0.16) and lung injury (by 57%, active drug vs placebo groups) in hospitalized patients with COVID-19 in an IIT phase III study. We presented here the mechanism of action of Proxalutamide for targeting cytokine storm in severe COVID-19 patients. Proxalutamide was demonstrated to activate nuclear factor erythroid 2-related factor 2 (Nrf2) in macrophages, which stimulates the antioxidant response element (ARE) for reducing cytokine storm-induced organ damage in COVID-19. In addition, Proxalutamide inhibited TNF alpha and IL-6 expression and blocked INF gamma signaling by downregulating STAT1 expression in immune cells. Importantly, Proxalutamide reduced inflammatory cells in lungs in a Poly (I:C), pseudoviral induced-lung injury animal models. Further, Proxalutamide decreased C-reactive protein, D-Dimer and improved lymphocyte count, biomarkers for COVID-19 progression in clinical studies. Together, these results provide a strong rationale for the treatment of severe COVID-19 patients with Proxalutamide.
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Background: A meta-analysis of COVID-19 shows that the pooled prevalence of cancer is 1.4%. Febrile illness during COVID-19 is caused by cytokine release syndrome energized by innate inflammatory immune cells, neutrophils, monocytes, and macrophages. Cancer has a worse clinical outcome with COVID-19 due to a potential contribution of the disordered inflammatory microenvironment and immune system. This study aimed to determine the impact of peripheral inflammatory responses on clinical outcome and severity of COVID-19 patients with and without cancer and compare their clinical spectra. Methodology: This IRB-approved, retrospective chart review performed at PNOC included patients 18 years or older with PCR-confirmed COVID-19 from April 2020 to April 2021. Histopathology-confirmed cases identified excluded cranial metastases, pregnancy, or ICU-ineligible due to advanced malignancy or missing data. We collected the first clinical encounter data following a positive COVID-19 test, including CDC-defined COVID-19 symptoms, co-morbidities, cancer status, and treatment' clinical outcomes and death from any cause within30 days of COVID-19 diagnosis. We determined peripheral blood inflammatory cells of neutrophils, lymphocytes, monocytes, platelets and the ratios between lymphocytes and the other three. According to INH guidelines, we ranked clinical severity as presymptomatic, mild, moderate, severe, or critical. Results: Of 3745 people with PCR-confirmed COVID-19, 65 (1.7%) had cancer. We randomly selected 130 non-cancer subjects, homogeneously distributed across each month. The median age was 59 years. Of all, 52.3% were women, 43% were diabetic, 45% were hypertensive, and 35% had the cardiopulmonary disease. Dyspnea occurs in 30.8% of those with cancer but in 59.2% of those without cancer (P < .001). High neutrophil was significantly associated with severity (P = .038), but there was no significant difference between cancer and non-cancer groups. High lymphocytes, MPV, and Neutrophil/Lymphocyte ratio were associated with symptoms but not outcome or severity. Death from any cause was more in the group with cancer 23.1% vs. 6.9%, P= .001. Only 2% of study participants with cancer continued chemotherapy after the diagnosis of COVID-19 was confirmed. Conclusion: Mortality significantly remains higher when cancer is comorbid with COVID-19, as seen in international groups. Further studies are needed to confirm whether cancer immunomodulation is a factor. Peripheral inflammatory response modestly predicts a worse outcome, particularly with elevated neutrophils, known for its proinflammatory rule by polarization and neutrophil extracellular trap (NET) formation with platelet activation. There was a modest increase in symptoms severity in non-cancer COVID19 but more mortality in cancer comorbid COVID-19.