ABSTRACT
Case Diagnosis: A 59-year-old, previously healthy female. Case Description or Program Description: The patient presented with sudden-onset, severe left posterior shoulder pain. After two days, the pain resolved and she noticed numbness and tingling throughout the left upper extremity and weakness in her left hand. Three weeks prior to symptom onset, the patient experienced COVID-like symptoms but had a negative rapid antigen test. Two weeks prior, the patient received a third COVID-19 vaccination. Cervical spine MRI revealed severe foraminal stenosis at C4-5 and C6-7 and significant central canal stenosis at C6-7, measuring 8.3 mm. MRI imaging of the brain and brachial plexus, as well as upper extremity sonography, were noncontributory. EMG findings suggested a left C5-C6 radiculopathy and a left brachial plexopathy involving the lower trunk. A diagnosis of both cervical radiculopathy and Parsonage Turner Syndrome (PTS) was made, with viral infection followed by vaccination as the suspected etiology. Setting(s): Outpatient PMR Clinic Assessment/Results: A methylprednisone dose-pack, pregabalin 150 mg twice daily, and outpatient physical therapy were prescribed. She was referred to neurosurgery for further evaluation. The patient's symptoms have continued to slowly improve with steroids. Discussion (relevance): The patient's presentation includes a variety of overlying pathology. Posterior shoulder pain, upper extremity numbness and tingling, and hand weakness are common symptoms of radiculopathy and PTS. MRI and EMG confirmed C5-C6 cervical radiculopathy. Clinically, concurrent PTS was diagnosed due to the resolution of shoulder pain, occurring after a viral illness and COVID vaccination, and the improvement of strength without therapy. As COVID-19 vaccination efforts increase, PTS must be considered to maintain a comprehensive differential. Conclusion(s): PTS is a rare neurological condition that is underrecognized. Physiatrists play a critical role in identifying PTS through performing a detailed history, physical exam, and diagnostic studies. As COVIDrelated illness and vaccination rates increase, future studies are needed to explore the frequency of PTS in conjunction with other diagnoses.
ABSTRACT
La prise en charge des tumeurs hépatiques est multidisciplinaire parce qu’elle fait appel à l’oncologie, les exérèses chirurgicales et les destructions locales (radiofréquence, micro-ondes). Chez les patients cirrhotiques et pour les petites tumeurs (≤3cm), les destructions locales sont considérées comme aussi efficaces que l’exérèse chirurgicale. But du travail : vérifier si la destruction percutanée des tumeurs hépatiques est faisable en ambulatoire. Étude monocentrique, rétrospective et observationnelle qui incluait tous les patients ayant eu au sein de l’unité de chirurgie ambulatoire une destruction percutanée de tumeurs hépatiques, entre septembre 2019 et décembre 2020. Le critère de jugement principal est la destruction complète sur l’imagerie après 1 mois. Dix-neuf destructions percutanées ont été réalisées sans échec du processus ambulatoire, chez 19 patients (H/F=16/3), âgés de 66±12 ans. Les tumeurs étaient réparties : 14 carcinomes hépatocellulaires (86 % de cirrhose, 11 Child A, 1 Child B) et 5 métastases. Le taux de destruction complète sur l’imagerie à 1 mois était de 100 %. Durant la même période, 30 patients ont eu une destruction percutanée et n’ont pas été pris en charge en ambulatoire pour les raisons suivantes : geste chirurgical associé (hépatectomie : 2, cœlioscopie : 14, cure d’éventration : 2), comorbidités (âge : 6, anticoagulant : 1, Child B : 3, autre : 18) et organisationnelle (COVID : 1, fermeture annuelle : 2, absence d’entourage : 2). Les destructions locales de tumeurs hépatiques sont faisables en ambulatoire, avec des résultats immédiats très satisfaisants, y compris chez les patients cirrhotiques.
ABSTRACT
In this paper we present a deterministic discrete-time networked SEIR model that includes a number of transportation networks, and present assumptions under which it is well defined. We analyze the limiting behavior of the model and present necessary and sufficient conditions for estimating the spreading parameters from data. We illustrate these results via simulation and with real COVID-19 data from the Northeast United States, integrating transportation data into the results.
ABSTRACT
Rationale: Neutrophils are an important component of the immune system and are crucial for the inflammatory response during infection from a foreign pathogen. Phagocytosis is a vital cellular mechanism in which pathogens are engulfed in a phagosome to be eliminated. Once taken inside the cell, the pathogen is subject to a cytotoxic environment inside the phagolysosome. While neutrophils are critical in suppressing the spread of infection, too much activity has been linked to tissue damage. Inflammatory lung conditions such as acute respiratory distress syndrome (ARDS) can occur, often leading to death. Our aim is to determine whether the rate of phagocytosis is associated with disease severity among patients with COVID-19. Methods: Neutrophils were isolated from the peripheral blood of 20 COVID-19 human subjects. Neutrophils were isolated with Polymorphoprep and mixed in a 1:1 ratio with pHrodo TM Red Staphylococcus aureus Bioparticles TM (Invitrogen) in a 96-well plate and centrifuged at 1200 rpm for 6 min. Fluorescence was quantified via plate reader (Infinite M200, TECAN) every 15min for 2 hours to define the rate of phagocytosis, with excitation at 560nm and emission at 585nm. Cells were incubated at 37°C with 5% CO2 in-between reads. Statistical analysis was performed via simple linear regression with detection of significant differences in slopes. Paired two-tailed non-parametric t-tests (Wilcoxon) were conducted for each time point. Results: Rates of phagocytosis were significantly higher in neutrophils from critically ill COVID-19 patients relative to neutrophils from healthy controls (487.5 versus 374.5 at 120min;p<0.05 at 75, 90, 105 and 120 min). Conclusion: Despite the functional role of neutrophils in suppression of foreign pathogens, increased activity of neutrophils can lead to collateral damage and thus exacerbated lung injury. We found that neutrophils from COVID-19 patients have higher rates of phagocytosis than those from healthy subjects. These findings suggest that neutrophils circulating in COVID-19 patients have an elevated activation state and may contribute to increased severity of disease. However, the elevation in phagocytosis may also suggest that neutrophils in critically ill COVID patients are well able to phagocytose and kill pathogens which cause secondary infections in this at-risk cohort. Figure: .
ABSTRACT
Background: Neutrophils are an important part of the innate immune system and play a vital role in host defense. Neutrophils target invading pathogens through both intracellular and extracellular mechanisms. One of their primary antimicrobial mechanisms is the production of reactive oxygen species (ROS) within phagolysosomes during oxidative burst. ROS production is a marker of the inflammatory/activity state of neutrophils. Although neutrophils are crucial in the defense against microorganisms, recruitment and hyperactivation of neutrophils can also cause collateral damage to the host. Recent studies have shown that neutrophils may be playing a role in acute respiratory distress syndrome (ARDS) in COVID-19. We hypothesized that ROS production would be increased secondary to elevated activation of circulating neutrophils in COVID-19 patients and may be playing a role in immunopathology.Methods: Circulating neutrophils were isolated from the blood of 20 human subjects with COVID-19 and 12 healthy controls. Neutrophils at 2x106 cells/ml were incubated with 10μM 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) for 20min at 37°C. Neutrophils were centrifuged at 500g, resuspended in HBSS-/-, plated at 2x105 in 96-well plates and exposed to 0, 2.5, 25 and 250nM phorbol myristate acetate (PMA;in triplicate). Fluorescence was measured (Infinite M200, TECAN) at 495nm:520nm every 15min for 2hr. ROS production was analyzed using mixed-effects models with Geisser- Greenhouse correction and Sidak's multiple comparisons test.Results: ROS production was increased in neutrophils isolated from the circulation of critically ill COVID-19 patients as compared to healthy controls (2581nm versus 3790nm, respectively, at 120min, p<0.05). Upon stimulation with PMA, ROS production was also increased in COVID-19 patients relative to controls (2.5 PMA: 16597 versus 10549, respectively, <0.001;25 PMA: 20633 versus 11312, respectively, p<0.0001). At the final timepoint, 1.57, 1.82 and 1.85-fold difference in ROS production was noted at 2.5, 25 and 250nM respectively between patient populations. Conclusion: Increased ROS production at baseline and upon stimulation demonstrates that neutrophils in the circulation of critically ill COVID-19 patients with ARDS have an elevated activation state. These patients are known to have recruitment of neutrophils to the lung parenchyma, where the production and release of ROS may cause collateral damage. Further, neutrophils have been implicated in the vascular and systemic immunopathology of COVID-19, which may be driven by release of these damaging and toxic molecules. Neutrophil-associated pathways may serve as therapeutic targets and quantitative markers of disease in COVID-19 patients.
ABSTRACT
Background: Neutrophils are key players in the immune and aid in the defense against microorganisms. Neutrophil extracellular traps (NETs) are extracellular DNA complexes, which are released during NETosis, a programmed form of cell death. Although NETs are crucial in the fight against infectious agents, an overabundance of neutrophils has been implicated in many inflammatory lung conditions. Our aim is to determine whether an overabundance of NETosis is associated with clinical deterioration of patients with COVID-19. Methods: Circulating polymorphonuclear cells (neutrophils) were isolated from human peripheral blood of 20 human subjects with COVID-19. Neutrophils were seeded in 96-well plates and treated with 0, 2.5 nM, 25 nM, and 250 nM of phorbol 12-myrisate 13-acetate (PMA) or 12 uM nigericin for 2 hours to stimulate NET production via canonical and noncanonical pathways, respectively. Following incubation, wells were treated with micrococcal nuclease, supernatants were collected from each well, and extracellular DNA content to quantify NETosis was detected by fluorescent plate reader. We calculated acute physiology and chronic health evaluation (APACHE-II) scores for every human subject. These were calculated at the same time point at which the neutrophils were collected. They were then compared to the degree of NETosis and absolute neutrophil count (ANC). These were analyzed using a simple linear regression model. We also categorized participants based on APACHE-II scores (APACHE-II <15, APACHE-II>15) and compared them to rates of NETosis using a bar graph. Results: APACHE II is a widely used ICU mortality prediction score that is used to risk-stratify patients. We found that participants with higher APACHE-II scores had higher rates of NETosis, both at 0 nM PMA and when stimulated with nigericin (figure 1a-b). This suggests that higher rates of NETosis correlate with increased disease severity. Additionally, we found a positive correlation between ANC and NETosis (Figure 1c-1d), suggesting that ANC itself is a reliable marker of NETosis and disease severity. Conclusion: NETosis is an important player in immune system defense but has also been implicated in various inflammatory lung conditions. We found that in patients with COVID-19, there was a positive correlation between worsening disease state, measure by APACHE II scores, and increased NETosis. This suggests that over-activation of neutrophils may play a role in disease progression. We also found a positive correlation between NETosis and ANC, indicating that the degree of circulating neutrophils is a reliable marker of the functional state of neutrophils, as well as disease severity.
ABSTRACT
Introduction. The pathophysiology of infection with SARS-CoV-2 involves the lower airways and host-launched aggressive inflammatory responses leading to exacerbated lung damage in these vital tissues. Early clinical studies found that COVID-19 patients have higher levels of neutrophils in the circulation. Neutrophils are the most abundant leukocyte in circulation and are known to be highly proinflammatory due to production of neutrophil extracellular traps (NETosis). NETs are web-like chromatin structures coated with histones and proteases that both capture and kill invading pathogens. However, while being an effective countermeasure towards foreign microbes, this process also causes undesirable damage in host tissues. Therefore, we sought to characterize NETosis in circulating neutrophils from COVID-19 patients to determine whether this immunological response might be exacerbating or driving the disease state in COVID-19, rather than mitigating the virus. Methods.Blood was drawn daily from critically ill COVID-19 patients (n=16) after consent was obtained. Healthy controls (n=13) were screened for COVID-19 and gave blood once a week. Blood was drawn into lithium heparin tubes (BD Vacutainer). Neutrophils were isolated using PolymorphprepTM(PROGEN) per manufacturer's instructions. Cells were resuspended at 2x106 cells/ml for functional assays. Neutrophils were stimulated with increasing concentrations of PMA (Phorbol 12-myristate 13-acetate) of 2.5nM, 25nM and 250nM to stimulate NETosis via the canonical pathway, and nigericin at 15uM for the non-canonical pathway. NETosis was quantified using the Quant-iT™ PicoGreen™ dsDNA Assay Kit (Invitrogen) and by NET visualization via myeloperoxidase and nuclear staining (using Polyclonal Rabbit Anti-Human Myeloperoxidase by Dako and Hoescht stain by Invitrogen). Results.Functional NETosis assays of circulating neutrophils from COVID-19 patients demonstrate overall increased NETosis determined by increased release of dsDNA. This enhanced NETosis occurred at baseline and after stimulation with PMA when compared to healthy controls (Figure 1A, p <0.0001). Fluorescent microscopy also demonstrated increased NETosis in neutrophils from COVID-19 patients (Figure 1B;MPO-green and nucleus-blue). NETosis via the non-canonical pathway (induction with nigericin) was also increased in COVID-19 patients versus controls (p=0.02). Conclusions.Circulating neutrophils from critically ill COVID-19 patients are more prone to produce NETs than circulating neutrophils from healthy individuals. This is likely to lead to NETmediated tissue injury once neutrophils enter inflamed tissue, where they can potentially drive acute lung injury and acute respiratory distress syndrome, common causes of mortality in COVID-19. The finding of increased production of NETs by both canonical and non-canonical pathways is consistent with an overall hyper-activated state in COVID-19.
ABSTRACT
SESSION TITLE: Medical Student/Resident Disorders of the Mediastinum Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: In March, 2020 the World Health Organization (“WHO”) declared SARS-CoV-2 as a global pandemic. SARS-CoV-2 viral infection has been noted to present a variety of symptoms including anosmia (loss of sense of smell), dyspnea, cough, fever, diarrhea and acute respiratory failure. Spontaneous pneumomediastinum is a rare complication with viral pneumonia. We here present one of the two cases with this finding. CASE PRESENTATION: 63-years-old male presented with fever, chills, and progressive shortness of breath over the past week. Patient was previously diagnosed with corona virus disease with reverse transcriptase RNA PCR test. Past medical history was significant for diabetes, hypertension and hyperlipidemia. On presentation, patient was hypoxic (SaO2 84%). Physical examination revealed reduced breath sounds bilaterally and soft-tissue crepitus in bilateral clavicle area. Laboratory test results showed elevated C-reactive protein concentration, leukocytosis, and lymphopenia. Chest Computed Tomography (CT) showed diffuse lower neck/chest wall subcutaneous emphysema with associated diffuse pneumomediastinum and bilateral ground-glass airspace infiltrates (Figure 1,2,3). Patient was started on anti-infective therapy with vancomycin, piperacillin/tazobactam, and azithromycin, and placed on nasal cannula at 4 liter/minute. On day four of admission, patient developed multi-organ failure requiring mechanical ventilation and vasopressor support. Later on day twelve, patient expired due to cardiopulmonary arrest. DISCUSSION: Pneumomediastinum is defined as the presence of free air in the mediastinum with an incidence of 1 in every 25,000 cases in ages between 5-34 years, predominantly found in males. It may be spontaneous from a predisposing factor or due to secondary causes. SARS-CoV-2 is a new addition to secondary pulmonary causes, being reported recently in literature. The pathophysiology of spontaneous pneumomediastinum is explained due to pressure gradient difference between alveoli and lung interstitial tissue. SARS-CoV-2 infects type I and II pneumocytes, disrupting alveolar membrane integrity leading to alveolar rupture and leakage of air into interstitial tissue, as well as severe hypoxemia increasing respiratory effort. Associated clinical symptoms of pneumomediastinum are varying, including dyspnea, although a portion of patient are asymptomatic. Pneumomediastinum is typically identified through chest x-ray with management being primary conservative. CONCLUSIONS: Spontaneous pneumomediastinum in association with SARS-CoV-2 is a serious condition and merits early recognition. Despite early diagnosis and optimal management, the mortality was 100% in our two patients of Covid-19 associated mediastinum. Reference #1: Wang J, Su X, Zhang T, Zheng C. Spontaneous Pneumomediastinum: A Probable Unusual Complication of Coronavirus Disease 2019 (COVID-19) Pneumonia. Korean J Radiol. 2020;21(5):627-628. doi:10.3348/kjr.2020.0281 Reference #2: Dionísio P, Martins L, Moreira S, et al. Spontaneous pneumomediastinum: experience in 18 patients during the last 12 years. J Bras Pneumol. 2017;43(2):101-105. doi:10.1590/S1806-37562016000000052 Reference #3: Kolani S, Nawfal H, Haloua M, et al. Spontaneous pneumomediastinum occurring in the SARS-COV-2 infection [published online ahead of print, 2020 May 11]. IDCases. 2020;21:e00806. doi:10.1016/j.idcr.2020.e00806 DISCLOSURES: No relevant relationships by Darakhshan Ahmad, source=Web Response No relevant relationships by Marium Ghani, source=Web Response No relevant relationships by Parvez Mir, source=Web Response No relevant relationships by Judy Pham, source=Web Response No relevant relationships by Yariana Rodriguez-Ortiz, source=Web Response No relevant relationships by Phanthira Tamsukhin, source=Web Response