Upper deep vein thrombosis in a patient with COVID-19 infection and a giant goiter (preprint)

A 74-year-old female presented with COVID-19 pneumonia and multinodular goiter with right lobe enlargement, occupying medium mediastinum with trachea compression is presented. COVID-19 pro-thrombotic status combined with low dynamic flow due to the large goiter resulted in deep vein thrombosis of subclavian and jugular veins in this case.

Improving Fairness of Automated Chest X-ray Diagnosis by Contrastive Learning (preprint)

Purpose: Limited studies exploring concrete methods or approaches to tackle and enhance model fairness in the radiology domain. Our proposed AI model utilizes supervised contrastive learning to minimize bias in CXR diagnosis. Materials and Methods: In this retrospective study, we evaluated our proposed method on two datasets: the Medical Imaging and Data Resource Center (MIDRC) dataset with 77,887 CXR images from 27,796 patients collected as of April 20, 2023 for COVID-19 diagnosis, and the NIH Chest X-ray (NIH-CXR) dataset with 112,120 CXR images from 30,805 patients collected between 1992 and 2015. In the NIH-CXR dataset, thoracic abnormalities include atelectasis, cardiomegaly, effusion, infiltration, mass, nodule, pneumonia, pneumothorax, consolidation, edema, emphysema, fibrosis, pleural thickening, or hernia. Our proposed method utilizes supervised contrastive learning with carefully selected positive and negative samples to generate fair image embeddings, which are fine-tuned for subsequent tasks to reduce bias in chest X-ray (CXR) diagnosis. We evaluated the methods using the marginal AUC difference ($\delta$ mAUC). Results: The proposed model showed a significant decrease in bias across all subgroups when compared to the baseline models, as evidenced by a paired T-test (p<0.0001). The $\delta$ mAUC obtained by our method were 0.0116 (95\% CI, 0.0110-0.0123), 0.2102 (95% CI, 0.2087-0.2118), and 0.1000 (95\% CI, 0.0988-0.1011) for sex, race, and age on MIDRC, and 0.0090 (95\% CI, 0.0082-0.0097) for sex and 0.0512 (95% CI, 0.0512-0.0532) for age on NIH-CXR, respectively. Conclusion: Employing supervised contrastive learning can mitigate bias in CXR diagnosis, addressing concerns of fairness and reliability in deep learning-based diagnostic methods.

The association between COVID-19 infection and cardiac involvement in hospitalized patients at a tertiary care center (preprint)

Objective The effect of COVID-19 infection on the cardiovascular system is well established. However, knowledge gaps in the clinical implications of cardiac involvement in COVID-19 patients are yet to be addressed. This study aimed to investigate acute cardiac injury (ACI) risk factors and the outcomes associated with COVID-19 infection with cardiac involvement.Method In this study, we included hospitalized patients between March 2020 and May 2022 with confirmed COVID-19 infection and evidence of cardiac involvement.Results In total, 501 patients were included, of whom 396 (79%) had evidence of ACI. The median troponin level was 25.8 (interquartile range [IQR]: 10.8–71). The patients with evidence of ACI were significantly more likely to have diabetes mellitus (75% vs. 60%; p = 0.003), cardiovascular disease (48% Vs. 37%; p = 0.042), chronic lung disease (22.2% vs. 12.4%; p = 0.02), and chronic kidney disease (32.3% vs. 16.2%; p = < 0.001). Additionally, the patients with ACI were significantly more likely to have cardiomegaly (60.6% vs. 44.8%; p = 0.004) and bilateral lobe infiltrates (77.8% vs. 60%; p < 0.001) on X-ray. The patients with ACI were significantly more likely to suffer from complications such as cardiogenic shock (5.3% vs. 0%; p = 0.001), arrhythmias (42% vs. 30.5%; p = 0.002), pneumonia (80.1% vs. 65.7%; p = 0.003), sepsis (24.2% vs. 9.5%; p < 0.001), and acute respiratory distress syndrome (ARDS) (33.1% vs. 8.6%; p < 0.001). Patients with ACI were also significantly more likely to be admitted to the intensive care unit (ICU) (57% vs. 26.7%; p < 0.001) and significantly more likely to die (38.1% vs. 11.4%; p < 0.001). The results of the multivariate regression analysis indicated that mortality was significantly higher in patients with elevated troponin levels (adjusted odds ratio [OR]: 4.73; 95% confidence interval [CI]: 2.49–8.98).Conclusion In COVID-19 patients who exhibited evidence of ACI, age, diabetes mellitus, chronic lung disease, and chronic kidney disease were associated with increased risk of ACI. Patients with these risk factors are at risk of severe complications, such as ICU admission, sepsis, and death.

Clinical Manifestations of Perinatal Pregnant Women with Pulmonary Embolism (preprint)

Purpose： To analyze the clinical manifestations of perinatal pregnant women with pulmonary embolism(PE) and improve the understanding of maternal PE disease.  Methods：We retrospectively reviewed maternities diagnosed with PE in a maternity and infant hospital between July 2018 and June 2020. Patients were divided into different groups according to risk stratification. Clinical data were collected and statistically analyzed by SPSS.  Results: A total of 49 patients, with an average age of (32.31±4.17) years at delivery were clarified into low-risk group (28 patients, 57.1%) and medium-risk group (21 patients, 42.9%). The medium-risk group had a significant higher serum level of TnI (0.0052±0.0073 ng/ml) compared with low-risk group (0.0009±0.0013 ng/ml). Although d-dimer level (5.1±3.6 mg/l) of selected patients were higher than normal range at the time of admitting, a significant increasing trend was still observed when diagnosed with PE (p=0.012 in low-risk group, p=0.005 in medium-risk group). The location of thrombosis distributed mainly in right lung (28(57.1%)) and lower field of lung (32(65.3%)) according to CTA image, while 5 cases of right ventricular enlargement were limited in medium-risk group. While 87.8% of patients were asymptomatic. The frequencies of PE in Febraury 2020 and March 2020 were higher compared to any other month, which was in accordance with the first episode period of COVID-19 in China.  Conclusion: Perinatal PE is frequently found in elderly pregnant women, with a more benign clinical presentation compared with reported data. Dynamic monitoring of d-dimer may have more clinical value for early identification of perinatal PE.

Sigma-1 Receptor Signaling: In Search of New Therapeutic Alternatives for Cardiovascular and Renal Diseases.

Cardiovascular and renal diseases are among the leading causes of death worldwide, and regardless of current efforts, there is a demanding need for therapeutic alternatives to reduce their progression to advanced stages. The stress caused by diseases leads to the activation of protective mechanisms in the cell, including chaperone proteins. The Sigma-1 receptor (Sig-1R) is a ligand-operated chaperone protein that modulates signal transduction during cellular stress processes. Sig-1R interacts with various ligands and proteins to elicit distinct cellular responses, thus, making it a potential target for pharmacological modulation. Furthermore, Sig-1R ligands activate signaling pathways that promote cardioprotection, ameliorate ischemic injury, and drive myofibroblast activation and fibrosis. The role of Sig-1R in diseases has also made it a point of interest in developing clinical trials for pain, neurodegeneration, ischemic stroke, depression in patients with heart failure, and COVID-19. Sig-1R ligands in preclinical models have significantly beneficial effects associated with improved cardiac function, ventricular remodeling, hypertrophy reduction, and, in the kidney, reduced ischemic damage. These basic discoveries could inform clinical trials for heart failure (HF), myocardial hypertrophy, acute kidney injury (AKI), and chronic kidney disease (CKD). Here, we review Sig-1R signaling pathways and the evidence of Sig-1R modulation in preclinical cardiac and renal injury models to support the potential therapeutic use of Sig-1R agonists and antagonists in these diseases.

Association of severe COVID-19 outcomes with radiological scoring and cardiomegaly: findings from the COVID-19 inpatients database, Japan.

PURPOSE: We aimed to characterize novel coronavirus infections based on imaging [chest X-ray and chest computed tomography (CT)] at the time of admission. MATERIALS AND METHODS: We extracted data from 396 patients with laboratory-confirmed COVID-19 who were managed at 68 hospitals in Japan from January 25 to September 2, 2020. Case patients were categorized as severe (death or treatment with invasive ventilation during hospitalization) and non-severe groups. The imaging findings of the groups were compared by calculating odds ratios (ORs) and 95% confidence intervals (95% CIs), adjusted for sex, age, and hospital size (and radiographic patient positioning for cardiomegaly). Chest X-ray and CT scores ranged from 0 to 72 and 0 to 20, respectively. Optimal cut-off values for these scores were determined by a receiver-operating characteristic (ROC) curve analysis. RESULTS: The median age of the 396 patients was 48 years (interquartile range 28-65) and 211 (53.3%) patients were male. Thirty-two severe cases were compared to 364 non-severe cases. At the time of admission, abnormal lesions on chest X-ray and CT were mainly observed in the lower zone/lobe. Among severe cases, abnormal lesions were also seen in the upper zone/lobe. After adjustment, the total chest X-ray and CT score values showed a dose-dependent association with severe disease. For chest X-ray scores, the area under the ROC curve (AUC) was 0.91 (95% CI = 0.86-0.97) and an optimal cut-off value of 9 points predicted severe disease with 83.3% sensitivity and 84.7% specificity. For chest CT scores, the AUC was 0.94 (95% CI = 0.89-0.98) and an optimal cut-off value of 11 points predicted severe disease with 90.9% sensitivity and 82.2% specificity. Cardiomegaly was strongly associated with severe disease [adjusted OR = 24.6 (95% CI = 3.7-166.0)]. CONCLUSION: Chest CT and X-ray scores and the identification of cardiomegaly could be useful for classifying severe COVID-19 on admission.

Radiological Imaging of Viral Pneumonia Cases Identified Before the COVID-19 Pandemic Period and COVID-19 Pneumonia Cases Comparison of Characteristics (preprint)

Background: Thoracic CT imaging is widely used as a diagnostic method in the diagnosis of COVID-19 pneumonia. Radiological differential diagnosis and isolation of other viral agents causing pneumonia in patients gained importance, especially during the pandemic period. Aims: We aimed to investigate whether there is a difference between the CT imaging findings characteristically defined in COVID-19 pneumonia and the findings detected in pneumonia due to other viral agents, and which finding may be more effective in the diagnosis. Study Design: The study included 249 adult patients with pneumonia found in thorax CT examination and positive COVID-19 RT-PCR test and 94 patients diagnosed with non-COVID pneumonia (viral PCR positive, no bacterial/fungal agents were detected in other cultures) from the last 5 years before the pandemic. It was retrospectively analyzed using the PACS System. CT findings were evaluated by two radiologists with 5 and 20 years of experience who did not know to which group the patient belonged, and it was decided by consensus. Methods: Demographic data (age, gender, known chronic disease) and CT imaging findings (percentage of involvement, number of lesions, distribution preference, dominant pattern, ground-glass opacity distribution pattern, nodule, tree in bud sign, interstitial changes, crazy paving sign, reversed halo sign, vacuolar sign, halo sign, vascular enlargement, linear opacities, traction bronchiectasis, peribronchial wall thickness, air trapping, pleural retraction, pleural effusion, pericardial effusion, cavitation, mediastinal/hilar lymphadenopathy, dominant lesion size, consolidation, subpleural curvilinear opacities, air bronchogram, pleural thickening) of the patients were evaluated. CT findings were also evaluated with the RSNA consensus guideline and the CORADS scoring system. Data were divided into two main groups as non-COVID-19 and COVID-19 pneumonia and compared statistically with chi-square tests and multiple regression analysis of independent variables. Results: Two main groups; RSNA and CORADS classification, percentage of involvement, number of lesions, distribution preference, dominant pattern, nodule, tree in bud, interstitial changes, crazy paving, reverse halo vascular enlargement, peribronchial wall thickness, air trapping, pleural retraction, pleural/pericardial effusion, cavitation and mediastinal/hilar lymphadenopathy were compared, significant differences were found between the groups (p < 0.01). Multiple linear regression analysis of independent variables found a significant effect of reverse halo sign ({beta} = 0.097, p <0.05) and pleural effusion ({beta} = 10.631, p <0.05) on COVID-19 pneumonia. Conclusion: Presence of reverse halo and absence of pleural effusion was found to be efficient in the diagnosis of COVID-19 pneumonia.

Mechanism of Blood-Heart-Barrier Leakage: Implications for COVID-19 Induced Cardiovascular Injury.

Although blood-heart-barrier (BHB) leakage is the hallmark of congestive (cardio-pulmonary) heart failure (CHF), the primary cause of death in elderly, and during viral myocarditis resulting from the novel coronavirus variants such as the severe acute respiratory syndrome novel corona virus 2 (SARS-CoV-2) known as COVID-19, the mechanism is unclear. The goal of this project is to determine the mechanism of the BHB in CHF. Endocardial endothelium (EE) is the BHB against leakage of blood from endocardium to the interstitium; however, this BHB is broken during CHF. Previous studies from our laboratory, and others have shown a robust activation of matrix metalloproteinase-9 (MMP-9) during CHF. MMP-9 degrades the connexins leading to EE dysfunction. We demonstrated juxtacrine coupling of EE with myocyte and mitochondria (Mito) but how it works still remains at large. To test whether activation of MMP-9 causes EE barrier dysfunction, we hypothesized that if that were the case then treatment with hydroxychloroquine (HCQ) could, in fact, inhibit MMP-9, and thus preserve the EE barrier/juxtacrine signaling, and synchronous endothelial-myocyte coupling. To determine this, CHF was created by aorta-vena cava fistula (AVF) employing the mouse as a model system. The sham, and AVF mice were treated with HCQ. Cardiac hypertrophy, tissue remodeling-induced mitochondrial-myocyte, and endothelial-myocyte contractions were measured. Microvascular leakage was measured using FITC-albumin conjugate. The cardiac function was measured by echocardiography (Echo). Results suggest that MMP-9 activation, endocardial endothelial leakage, endothelial-myocyte (E-M) uncoupling, dyssynchronous mitochondrial fusion-fission (Mfn2/Drp1 ratio), and mito-myocyte uncoupling in the AVF heart failure were found to be rampant; however, treatment with HCQ successfully mitigated some of the deleterious cardiac alterations during CHF. The findings have direct relevance to the gamut of cardiac manifestations, and the resultant phenotypes arising from the ongoing complications of COVID-19 in human subjects.

Severe COVID-19 acute respiratory distress syndrome in an adult with single-ventricle physiology: a case report.

BACKGROUND: COVID-19 can induce acute respiratory distress syndrome (ARDS). In patients with congenital heart disease, established treatment strategies are often limited due to their unique cardiovascular anatomy and passive pulmonary perfusion. CASE PRESENTATION: We report the first case of an adult with single-ventricle physiology and bidirectional cavopulmonary shunt who suffered from severe COVID-19 ARDS. Treatment strategies were successfully adopted, and pulmonary vascular resistance was reduced, both medically and through prone positioning, leading to a favorable outcome. CONCLUSION: ARDS treatment strategies including ventilatory settings, prone positioning therapy and cannulation techniques for extracorporeal oxygenation must be adopted carefully considering the passive venous return in patients with single-ventricle physiology.

Clinical and radiological findings for the new multisystem inflammatory syndrome in children associated with COVID-19.

The World Health Organization defines the multisystem inflammatory syndrome in children (MIS-C) as a new syndrome reported in patients aged <19 years old who have a history of exposure to SARS-CoV-2. The onset of this syndrome is characterized by persistent fever that is associated with lethargy, abdominal pain, vomiting and/or diarrhea, and, less frequently, rash and conjunctivitis. The course and severity of the signs and symptoms vary; in some children, MIS-C worsens rapidly and can lead to hypotension, cariogenic shock, or even damage to multiple organs. The characteristic laboratory findings are elevated markers of inflammation and heart dysfunction. The most common radiological findings are cardiomegaly, pleural effusion, signs of heart failure, ascites, and inflammatory changes in the right iliac fossa. In the context of the current COVID-19 pandemic, radiologists need to know the clinical, laboratory, and radiological characteristics of this syndrome to ensure the correct diagnosis.

Selectively expressing SARS-CoV-2 Spike protein S1 subunit in cardiomyocytes induces cardiac hypertrophy in mice. (preprint)

Cardiac injury is common in hospitalized COVID-19 patients and portends poorer prognosis and higher mortality. To better understand how SARS-CoV-2 (CoV-2) damages the heart, it is critical to elucidate the biology of CoV-2 encoded proteins, each of which may play multiple pathological roles. For example, CoV-2 Spike glycoprotein (CoV-2-S) not only engages ACE2 to mediate virus infection, but also directly impairs endothelial function and can trigger innate immune responses in cultured murine macrophages. Here we tested the hypothesis that CoV-2-S damages the heart by activating cardiomyocyte (CM) innate immune responses. HCoV-NL63 is another human coronavirus with a Spike protein (NL63-S) that also engages ACE2 for virus entry but is known to only cause moderate respiratory symptoms. We found that CoV-2-S and not NL63-S interacted with Toll-like receptor 4 (TLR4), a crucial pattern recognition receptor that responsible for detecting pathogen and initiating innate immune responses. Our data show that the S1 subunit of CoV-2-S (CoV-2-S1) interacts with the extracellular leucine rich repeats-containing domain of TLR4 and activates NF-kB. To investigate the possible pathological role of CoV-2-S1 in the heart, we generated a construct that expresses membrane-localized CoV-2-S1 (S1-TM). AAV9-mediated, selective expression of the S1-TM in CMs caused heart dysfunction, induced hypertrophic remodeling, and elicited cardiac inflammation. Since CoV-2-S does not interact with murine ACE2, our study presents a novel ACE2-independent pathological role of CoV-2-S, and suggests that the circulating CoV-2-S1 is a TLR4-recognizable alarmin that may harm the CMs by triggering their innate immune responses.

Evaluation of High Resolution Computed Tomography Findings and its Relationship with the Clinical Course of Patients with Covid-19 (preprint)

Background: Due to the Covid 19 pandemic and the lack of useful information, in this study, we evaluated the hrct of patients with Covid 19 Method: 92 patients confirmed by RT_PCR in Razi Hospital in Rasht were included in the study. In addition to their demographic and clinical information, their hrct findings were collected for evaluation. Among 92 patients (47 men, 45 women), the earliest symptoms included cough (81.5%), fever (67.4%), and muscle pain (58.7%) And Six patients required intubation and mechanical ventilation at some point during their hospital stay. Results: The most common hrct findings in our study were grade 4, peripheral lesion 87%, bilateral 95.7%, mixed 76.08%, ggos 75%, left lower lobe 94.56%. Among 92 patients, we had some inconsistent findings including two patients with cardiomegaly, three patients with pleural effusion, and bilateral pleural effusion in only one patient Conclusion: Compared to other studies, it can be concluded that peripheral, bilateral, mixed, ggos, left lower lobe involvement are important findings in most patients with covid 19. We suspect that the disease has more severe lung involvement in men and less involvement in women, which needs further investigation.

First reported case of unrepaired tetralogy of Fallot complicated with coronavirus disease-19 (COVID-19).

The incidence of novel coronavirus disease-19 (nCoV-19) and its associated complications is higher in high-risk groups. In this article, we explain the symptoms and course of the disease and the treatment for an adult patient with CHD who has been infected with novel nCoV-19.

New Mexico's COVID-19 Experience.

ABSTRACT: The 2019 novel coronavirus disease (COVID-19) has spread worldwide, infiltrating, infecting, and devastating communities in all locations of varying demographics. An overwhelming majority of published literature on the pathologic findings associated with COVID-19 is either from living clinical cohorts or from autopsy findings of those who died in a medical care setting, which can confound pure disease pathology. A relatively low initial infection rate paired with a high biosafety level enabled the New Mexico Office of the Medical Investigator to conduct full autopsy examinations on suspected COVID-19-related deaths. Full autopsy examination on the first 20 severe acute respiratory syndrome coronavirus 2-positive decedents revealed that some extent of diffuse alveolar damage in every death due to COVID-19 played some role. The average decedent was middle-aged, male, American Indian, and overweight with comorbidities that included diabetes, ethanolism, and atherosclerotic and/or hypertensive cardiovascular disease. Macroscopic thrombotic events were seen in 35% of cases consisting of pulmonary thromboemboli and coronary artery thrombi. In 2 cases, severe bacterial coinfections were seen in the lungs. Those determined to die with but not of severe acute respiratory syndrome coronavirus 2 infection had unremarkable lung findings.

Chest X-ray lung and heart segmentation based on minimal training sets (preprint)

As the COVID-19 pandemic aggravated the excessive workload of doctors globally, the demand for computer aided methods in medical imaging analysis increased even further. Such tools can result in more robust diagnostic pipelines which are less prone to human errors. In our paper, we present a deep neural network to which we refer to as Attention BCDU-Net, and apply it to the task of lung and heart segmentation from chest X-ray (CXR) images, a basic but ardous step in the diagnostic pipeline, for instance for the detection of cardiomegaly. We show that the fine-tuned model exceeds previous state-of-the-art results, reaching $98.1\pm 0.1\%$ Dice score and $95.2\pm 0.1\%$ IoU score on the dataset of Japanese Society of Radiological Technology (JSRT). Besides that, we demonstrate the relative simplicity of the task by attaining surprisingly strong results with training sets of size 10 and 20: in terms of Dice score, $97.0\pm 0.8\%$ and $97.3\pm 0.5$, respectively, while in terms of IoU score, $92.2\pm 1.2\%$ and $93.3\pm 0.4\%$, respectively. To achieve these scores, we capitalize on the mixup augmentation technique, which yields a remarkable gain above $4\%$ IoU score in the size 10 setup.

A Case Report: Unexpectedly Earlier Recurrence of COVID-19 Infection with Severe Cardiac Involvement (preprint)

ABSTRACT Background COVİD 19 is a relapsing and reccurrent infectious disease caused by SARS-CoV-2. It can be associated with cardiac pathologies . we present a case of COVİD 19 reinfection leading to cardiac involvement . Case Summary A 22 year old men who had a history of COVID-19 pneumonia one and a half month ago arrived at the emergency department with progressive dyspnea. He was . under treatment for chronic idiopathic urticaria with levocetirizine dihydrochloride .He was hypoxic, tachycardic and hypotensive. Thorax computed tomography images demonstrated bilateral ground-glass opacity ,right-sided pleural effusion and cardiomegaly, Bedside transthoracic echocardiography revealed global Left Ventricul (LV)systolic dysfunction with ejection fraction of%28, dilation of the LV cavity and anteriorly directed eccentric jet of severe mitral. regurgitation .The COVID-19 RT-PCR test was re-positive. whereas the blood cultures remain negative. Coronary angiogram performed was normal.The patient improved clinically within one week by furosemid, dopamin favipravir methylprednisolone and antibiotic treatments. C-reactive protein (CRP) levels returned to normal.. The follow-up echocardiography showed normal. ejection fraction and mild mitral. regurgitation. Conclusion This case highlights characteristics of

Quantifying and reporting cardiac findings in imaging of COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to be a public health emergency and a pandemic of international concern. As of April 31st,  the reported cases of COVID-19 are three million in 186 countries. Reported case fatality has crossed 200 thousand among which more than fifty thousand has been in the USA. Most patients present with symptoms of fever, cough, and shortness of breath following exposure to other COVID-19 patients. Respiratory manifestations predominate in patients with mild, moderate, severe illness. Imaging of patients with COVID-19 consistently reports various pulmonary parenchymal involvement. In this article we wanted to reinforce and review the various reported imaging patterns of cardiac and mediastinal involvement in COVID-19 patients. Among patients with COVID 19 who underwent various imaging of chest various cardiac findings including pericardial effusion, myocarditis, cardiomegaly has been reported. Most of these findings have been consistently reported in patients with significant acute myocardial injury, and fulminant myocarditis. Acute biventricular dysfunction has also been reported with subsequent improvement of the same following clinical improvement. Details of cardiac MRI is rather limited. In a patient with clinical presentation of acute myocarditis, biventricular myocardial interstitial edema, diffuse biventricular hypokinesia, increased ventricular wall thickness, and severe LV dysfunction has been reported. Among patients with significant clinical improvement in LV structure and function has also been documented. With increasing number of clinical cases, future imaging studies will be instrumental in identifying the various cardiac manifestations, and their relation to clinical outcome.