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1.
Blood Purification ; 51(Supplement 3):21, 2022.
Article in English | EMBASE | ID: covidwho-20239415

ABSTRACT

Background/aims: Controlled DCD organ donation (cDCD) is a strategic target for the Italian transplantation network. Italian peculiarities in cDCD donation make published results questionable and raise concern over organ ischemic damage. Consequently, normothermic regional perfusion (NRP) has been strongly recommended in potential cDCD donors. In 2019 the randomized multicenter DONARE study was designed to describe ischemic-reperfusion and inflammatory biomarkers during NRP and to test the potential benefit of apheresis by an adsorbent filter (CytoSorb) included in the NRP circuit. The aim of this report is to describe the modulation of the clinical characteristics and of the NRP in the DONARE study enrolled cases. Method(s): The study protocol was defined by the DCD national working group and proposed to all the Italian DCD donation centers. The coordinating center (CNT) has monitored the evolving cDCD activity to preserve the study capacity of representing the Italian scenario. Samples have been blindly centralized to an independent laboratory for cytokines profiling. The outcomes of transplanted organs have been recorded in the national quality database. Result(s): From September 2020 to June 2022, 27 out of the 40 planned cases have been enrolled in six centers: 4 in 2020, 12 in 2021 and 11 within June 2022. Approval is still pending in other centers. Main causes of exclusion among potential cDCD donors were: age above 65 (in 2020), e-CPR prior- to-death, shortage in personnel and COVID-19 restrictions. The age limit for enrolment (<65yrs) was abolished by amendment due to the national trend: mean age of enrolled cases increased from 57+/-6 in 2020 to 67+/-6 years in 2022. Mean NRP duration decreased from 223,3+/-39,2 in 2020 to 168,9+/-42,6 minutes in 2022;serial samples (4/2 with/without Cytosorb, from T0 to T4) from different points of the NRP circuit have been completed throughout the procedure in all the cases. All the enrolled cases became utilized donors. No study-related adverse event has been reported. Conclusion(s): Coordination of multicenter studies in the rapidly evolving scenario of controlled DCD donation should take advantage of continuous monitoring of real-life procedures and auditing of adherence to operational recommendations. The interim evaluation confirms the feasibility and safety of the study.

2.
Progress in Biomedical Optics and Imaging - Proceedings of SPIE ; 12465, 2023.
Article in English | Scopus | ID: covidwho-20235527

ABSTRACT

COVID-19 still affects a large population worldwide with possible post-traumatic sequelae requiring long-term patient follow-up for the most severe cases. The lung is the primary target of severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) infection. In particular, the virus affects the entire pulmonary vascular tree from large vessels to capillaries probably leading to an abnormal vascular remodeling. In this study we investigated two modalities for assessing this remodeling, SPECT perfusion scintigraphy and computed tomography, the latter enabling the computation of vascular remodeling patterns. We analyzed on a cohort of 30 patients the relationship between vascular remodeling and perfusion defects in the peripheral lung area, which is a predominant focus of the COVID-19 infectious patterns. We found that such relationship exists, demonstrated by moderate significant correlations between SPECT and CT measures. In addition, a vascular remodeling index derived from the z-score normalized peripheral CT images showed a moderate significant correlation with the diffusing capacity of the lung for carbon monoxide (DLCO) measures. Altogether these results point CT scan as a good tool for a standardized, quantitative, and easy-to-use routine characterization and follow-up of COVID-19-induced vascular remodeling. An extensive validation of these results will be carried out in the near future on a larger cohort. © 2023 SPIE.

3.
Nevrologiya, Neiropsikhiatriya, Psikhosomatika ; 15(2):83-90, 2023.
Article in Russian | EMBASE | ID: covidwho-20233359

ABSTRACT

Cerebral microangiopathy (CMA) is one of the significant causes of depression in the elderly. Close associations of the risk of developing depression with white matter hyperintensity, the presence of lacunar infarcts, and other markers of vascular disease are shown. The available data suggest that various vascular mechanisms, in particular, involvement of small vessels of the brain, generalized microvascular and endothelial dysfunction, metabolic risk factors, - are risk factors for the development of depression. Pathogenetic mechanisms include cerebral hypoperfusion and immune dysregulation. Depression is also a common complication of coronavirus infection, occurring both in the acute and post-COVID periods. The same mechanisms as in vascular depression are involved in the pathogenesis of the development of post-COVID depressive disorders. Given the complexity of the mechanisms of development of depressive disorders in patients with CMA, the presence of severe comorbid vascular pathology, antidepressants with an optimal ratio of efficacy and safety should be preferred. Agomelatine (Valdoxan) is one of such drugs.Copyright © 2023 Ima-Press Publishing House. All rights reserved.

4.
Australas J Ultrasound Med ; 26(2): 100-114, 2023 May.
Article in English | MEDLINE | ID: covidwho-20242274

ABSTRACT

Due to their often peripheral pleural-based location, pneumonias can be visualised by B-mode ultrasound. Therefore, sonography can be used as an alternative imaging modality to chest X-ray in suspected cases of pneumonia. Depending on the clinical background of the patient, and various underlying pathological mechanisms, a heterogeneous pattern of pneumonia is seen in both B-mode lung ultrasound and contrast-enhanced ultrasound. Here, we describe the spectrum of sonographic manifestations of pneumonic/inflammatory consolidation on B-mode lung ultrasound and contrast-enhanced ultrasound.

5.
Asia Ocean J Nucl Med Biol ; 11(2): 128-134, 2023.
Article in English | MEDLINE | ID: covidwho-20240304

ABSTRACT

Objectives: We evaluated the impact of the COVID-19 pandemic on the number of referrals for SPECT myocardial perfusion imaging (SPECT-MPI) as well as changes in the clinical and imaging characteristics. Methods: We respectively reviewed 1042 SPECT-MPI cases performed in a 4-month period during the COVID-19 pandemic (PAN; n=423) and compared their findings with those acquired in the same months before the pandemic (PRE; n=619). Results: The number of stress SPECT-MPI studies performed during the PAN period significantly dropped compared to the number of studies carried out in the PRE period (p = 0.014). In the PRE period, the rates of patients presenting with non-anginal, atypical and typical chest pain were 31%, 25% and 19%, respectively. The figures significantly changed in the PAN period to 19%, 42%, and 11%, respectively (all p-values <0.001). Regarding the pretest probability of coronary artery disease (CAD), a significant decrease and increase were noticed in patients with high and intermediate pretest probability, respectively (PRE: 18% and 55%, PAN: 6% and 65%, p <0.001 and 0.008, respectively). Neither the rates of myocardial ischemia nor infarction differed significantly in the PRE vs. PAN study periods. Conclusion: The number of referrals dropped significantly in the PAN era. While the proportion of patients with intermediate risk for CAD being referred for SPECT-MPI increased, those with high pretest probability were less frequently referred. Image parameters were mostly comparable between the study groups in the PRE and PAN periods.

6.
Indian J Anaesth ; 67(1): 102-109, 2023 Jan.
Article in English | MEDLINE | ID: covidwho-20236166

ABSTRACT

Medical colleges are now developing or refurbishing their anaesthesia intensive care units. In most teaching colleges, the residency post includes working in the critical care unit (CCU). Critical care is a rapidly evolving and popular super-speciality for postgraduate students. In some hospitals, anaesthesiologists play a key role in the management of the CCU. As perioperative physicians, all anaesthesiologists should be aware of the recent advancements in diagnostic and monitoring gadgets and investigations in critical care so that they may manage perioperative events effectively. Haemodynamic monitoring gives us warning signs about the change in the internal milieu of the patient. Point-of-care ultrasonography helps in rapid differential diagnosis. Point-of-care diagnostics give us instant bed-side information on the condition of a patient. Biomarkers help in confirming diagnosis, in monitoring, treatment, and providing prognosis. Molecular diagnostics guide anaesthesiologists in providing specific treatment to a causative agent. This article touches upon all of these management strategies in critical care and attempts to put forth the recent advancements in this speciality.

7.
Organ Transplantation ; 13(4):417-424, 2022.
Article in Chinese | EMBASE | ID: covidwho-2323874

ABSTRACT

During the novel coronavirus pneumonia (COVID-19) pandemic from 2020 to 2021, lung transplantation entered a new stage of development worldwide. Globally, more than 70 000 cases of lung transplantation have been reported to the International Society for Heart and Lung Transplantation (ISHLT). With the development of medical techniques over time, the characteristics of lung transplant donors and recipients and the indications of pediatric lung transplantation recipients have undergone significant changes. Application of lung transplantation in the treatment of COVID-19-related acute respiratory distress syndrome (ARDS) has also captivated worldwide attention. Along with persistent development of lung transplantation, it will be integrated with more novel techniques to make breakthroughs in the fields of artificial lung and xenotransplantation. In this article, research progresses on the characteristics of lung transplant donors and recipients around the world were reviewed and the development trend was predicted, enabling patients with end-stage lung disease to obtain more benefits from the development of lung transplantation technique.Copyright © 2022 Organ Transplantation. All rights reserved.

8.
Organ Transplantation ; 12(5):506-511, 2021.
Article in Chinese | EMBASE | ID: covidwho-2323425

ABSTRACT

Lung transplantation has been advanced for nearly half a century around the globe, and it has been developed rapidly for over 20 years in China. The field of lung transplantation in China has been gradually integrated into the international community. The outbreak of novel coronavirus pneumonia (COVID-19) in 2020 brought big challenges, as well as diverted the worldwide attention to the development of lung transplantation in China, accelerating international communication and cooperation. With the steadily deepening of clinical and basic research on lung transplantation for severe cases of COVID-19, organ transplant physicians have deepened the understanding and thinking of the maintenance of donors, selection of elderly and pediatric candidates, and perioperative management of recipients, as the future perspective of lung transplantation in China. For interdisciplinary research related to lung transplantation, it is necessary to carry out multi-center clinical trials with qualified study design and constantly promote the theoretic and practical innovation.Copyright © 2021 The authors.

9.
ERS Monograph ; 2022(97):173-185, 2022.
Article in English | EMBASE | ID: covidwho-2323150

ABSTRACT

Breathlessness can occur in a number of autonomic conditions, often in the form of dysfunctional breathing. The exact mechanism remains uncertain, but reduced perfusion of blood pressure receptors and chemoreceptors in the carotid sinus and carotid body, leading to hyperventilation, is postulated. This is recognised to occur in vasovagal syncope and in cases of significant autonomic dysfunction. It also occurs in PoTS, a condition predominantly affecting young women and often precipitated by another illness and increasingly by coronavirus disease 2019. It is characterised by cardiovascular and respiratory symptoms when upright, is relieved by recumbency and is associated with a significant heart rate increase. Other autonomic symptoms of organ dysfunction can occur, in the gastrointestinal and genitourinary system for example. There are guidelines and therapies that can produce significant symptomatic improvements, but maintaining a high level of suspicion for the diagnosis is important, as it can easily be overlooked.Copyright © ERS 2021.

10.
Clinical Nuclear Medicine ; 48(5):e273, 2023.
Article in English | EMBASE | ID: covidwho-2321746

ABSTRACT

Objectives: The aim of this study is to evaluate the effect of the COVID-19 pandemic on myocardial perfusion scans (MPS) during the COVID-19 pandemic period. Method(s): We respectively reviewed single photon emission computed tomography myocardial perfusion scans (SPECT-MPS) performed between June and September 2020 during the COVID-19 pandemic at the Nuclear Medicine Research Center at Mashhad University of Medical Sciences. The findings of stress SPECT-MPS studies acquired in the corresponding months of 2019 were also evaluated for direct comparison. Result(s): In COVID-19 pandemic compared to period prior to the pandemic, no difference was observed in terms of age range of patients under study or their cardiovascular risk factors, except smoking which underwent a significant increase during the COVID-19 pandemic ( 19% vs. 13% , p = 0.009). While the number of patients with non-angina (19% vs. 31%, p = 0.000) or typical (11% vs. 19%, p = 0.000) chest pain significantly decreased during the COVID-19 pandemic, atypical (42% vs. 25%, p = 0.000) chest pain cases showed an increasing number. By considering pretest probability of the patients (high, intermediate and low/very low), during the COVID-19 period, cases of high pretest probability decreased (6% vs. 18%, p = 0.000) and intermediate pretest probability patients also increased (64% vs. 55%, p = 0.005) while low/very low pretest probability cases showed no changes between the two periods. All types of MPS stress tests in the COVID-19 period were pharmacological compared to exercise stress test. No statistically significant difference on the myocardial ischemia or cardiomyopathy between patients between the two periods was observed. Summed stress score (SSS) and summed rest score (SRS) was similar over the two periods,while summed difference score (SDS) significantly increased over the course of COVID-19, confirming a non- increasing pattern of myocardial ischemia. Conclusion(s): Previous research underscores the fact that the number of stress SPECT-MPS studies was significantly reduced during the COVID-19 pandemic compared to the corresponding months prior to the pandemic [1, 2]. Our study concluded that all types of MPS stress tests in the COVID-19 period were pharmacological. This is due to the fact that all related recommendations published in the literature [3] highlighted the avoidance of exercise stress tests during the COVID-19 pandemic to reduce the risk of droplet exposure. During the COVID-19 pandemic, patients in two ends of the spectrum (e.g., non-angina & typical chest pain) were referred less for MPS. However, patients in the middle of the spectrum (e.g., atypical chest pain) underwentMPS less frequently. Myocardial ischemia and cardiomyopathy were not decreased or increased in patients over the COVID-19 period.

11.
Clinical Nuclear Medicine. Conference: Annual Meeting of the American College of Nuclear Medicine, ACNM ; 48(5), 2022.
Article in English | EMBASE | ID: covidwho-2321637

ABSTRACT

The proceedings contain 91 papers. The topics discussed include: the new approach of COVID-19 patients with deteriorating respiratory functions using perfusion SPECT/CT imaging;increasing interest in nuclear medicine: evaluation of an educational workshop;cost-benefit analysis recommends further utilization of cardiac PET/MR for sarcoidosis evaluation;development of a nomogram model for predicting the recurrence of differentiated thyroid carcinoma patients based on a thyroid cancer database from a tertiary hospital in China;multi-center validation of radiomic models in new data using ComBat-based harmonization of features;bone scan with Tc99m-MDP, the missing link in the initial staging of muscle-invasive bladder carcinoma;and comparison of absorbed doses to kidneys calculated employing three time points and employing two time points in neuroendocrine patients undergoing Lu-177 DOTATATE therapy using planar images.

12.
Hepatology International ; 17(Supplement 1):S75, 2023.
Article in English | EMBASE | ID: covidwho-2327218

ABSTRACT

Globally, hepatitis C (26%), alcohol (24%), and hepatitis B (23%) contribute almost equally to the global burden of cirrhosis. The contribution from nonalcoholic fatty liver disease (8%) is small but increasing. Patients with acutely decompensated cirrhosis have a dismal prognosis and frequently progress to acuteon-chronic liver failure, which is characterised by hepatic and extrahepatic organ failure, Cardiovascular alterations including portal hypertension trigger the formation of portocaval shunts and varices. Systemic under filling and arterial hypotension is compensated by vasoconstriction but might decline into a state of aggravated portal hypertension and cirrhotic cardiomyopathy, leading to a hyperdynamic state, microvascular dysfunction and reduced organ perfusion culminating in decompensation. The immune system is dysfunctional showing a contrary co-existence of immune paralysis and immune overstimulation leading to secondary infections and inflammatory response syndrome aggravating cardiovascular alterations but also initiating tissue injury and metabolic alteration. This transition from compensated to decompensated cirrhosis is characterised by the occurrence of ascites, variceal bleeding and/or hepatic encephalopathy or organ failures (in the case of ACLF. Precipitating events for ACLF vary between Western countries (bacterial infection, alcohol intake) and Eastern countries (flare of HBV, superimposed HAV or HEV). In the majority of patients, systemic inflammation is a major driver of progression from compensated to decompensated cirrhosis. Once the first episode of AD develops, systemic inflammation follows a chronic course, with transient periods of aggravation due to proinflammatory precipitants or bursts of bacterial translocation resulting in repeated episodes of AD. The multistate model describing the clinical outcomes of decompensated cirrhosis has been well validated. State 3 is defined by the occurrence of variceal bleeding alone, state 4 by any single non-bleeding event, state 5 by any 2 or more events and the late decompensate state by any event with organ failures either with or without ACLF. 5-year mortality across states from 3 to 5 is in the order of, respectively: 20%, 30%, 88%. With late decompensation mortality ranges between 60 and 80% at 1 year. Cirrhosis is increasingly common and morbid. Optimal utilisation of therapeutic strategies to prevent and control the complications of cirrhosis are central to improving clinical and patient-reported outcomes. Aetiology-focused therapies that can prevent cirrhosis and its complications. These include anti-viral therapies, psychopharmacological therapy for alcohol-use disorder, management of hepatic encephalopathy (HE), ascites, hepatorenal syndrome, non-pain symptoms of cirrhosis including pruritis, muscle cramps, sexual dysfunction and fatigue, and reduce the risk of hepatocellular carcinoma. New disease-modifying agents are expected to be identified in the next few years by systematic drug repurposing and the development of novel molecules currently undergoing pre-clinical or early clinical testing. COVID-19 continues to pose a significant healthcare challenge throughout the world. Comorbidities including diabetes and hypertension are associated with a significantly higher mortality risk. Cirrhosis is associated with an increased risk of all-cause mortality in COVID-19 infection compared to non-cirrhotic patients. Patients with cirrhosis should be considered for targeted public health interventions to prevent COVID-19 infection, such as shielding and prioritisation of vaccination.

13.
Heart Rhythm ; 20(5 Supplement):S509, 2023.
Article in English | EMBASE | ID: covidwho-2326582

ABSTRACT

Background: Ictal-induced cardiac bradyarrhythmia and asystole is a rare phenomenon. The exact mechanism of ictal-induced cardiac bradyarrhythmia and asystole remains unclear. It was postulated that stimulation of central autonomic network during ictal episode may trigger an abrupt burst of hypervagotonia. Prolonged episode of cardiac bradyarrhythmia and asystole may result in syncope or death due to impairment of cerebral perfusion. The role of cardioneuroablation (CNA) in this condition has not been well-described in the literature. Objective(s): To describe a case of successful CNA in a patient with ictal-induced bradyarrhythmia and asystole. Method(s): n/a Results: A 47-year-old female has a 1.5-year history of intractable focal epilepsy and COVID-19 infection. She started having multiple episodes of seizures following a mild COVID-19 infection. Electroencephalogram (EEG) and brain MRI revealed right temporal onset seizures without structural lesions. Due to ongoing uncontrolled seizures with multiple semiologies despite multiple anti-epileptic drugs, she was admitted to Epilepsy Monitoring Unit for seizure classification. Her ictal EEGs (Figure 1) showed onset of ictal rhythm in the right temporal region with episodes of severe sinus bradycardia (15-30 bpm) and sinus pauses (15-16 seconds). Telemetry tracings demonstrated PP interval slowing with PR interval prolongation prior to the pauses consistent with a vagally-mediated mechanism. Cardiac electrophysiology team recommended CNA for treating the episodes of ictal-induced bradyarrhythmia and asystole. 3D anatomic maps of the right atrium (RA) and left atrium (LA) were created using CARTO system (Biosense Webster). Right superior ganglionated plexus (RSGP) was localized with fractionation mapping and intracardiac echocardiography guidance. RSGP was targeted from the RA using an irrigated radiofrequency catheter with power limit of 25 W. Post-ablations of RSGP, her heart rate increased from 60 - 99 bpm. Additional lesions were delivered from the LA site but no additional heart rate increase was not seen. An implantable loop recorder was implanted post-ablation procedure. During follow-up of 8 months, she had recurrent focal epilepsy, but no bradyarrhythmias or asystole was noted on her loop recorder. Resting heart rates at long-term follow up were between 70 - 100 bpm. Conclusion(s): This case highlights the utility of CNA in patient with ictal-induced cardiac bradyarrhythmia and asystole. CNA may be an approach to avoid permanent pacemakers in this population. [Formula presented]Copyright © 2023

14.
Cardiopulmonary Bypass: Advances in Extracorporeal Life Support ; : 9-23, 2022.
Article in English | Scopus | ID: covidwho-2320220

ABSTRACT

The importance of developing an artificial means to oxygenate blood and perfuse the body, and their potential benefits to mankind were postulated as early as the 17th century. The modern artificial circulatory devices which are capable of tackling life-threatening conditions are powerful tools in the medical armamentarium. The painstaking research which paved the way for these technologies spanned over a century. The introduction of cardiopulmonary bypass heralded the development and worldwide adoption of open-heart surgery in the last 70 years. The ability to support the failing heart and lungs has averted early deaths for tens of thousands of patients. The recent severe acute respiratory distress syndrome coronavirus 2 pandemic is the latest example of how the use of respiratory extracorporeal membrane oxygenation has been catapulted to unprecedented levels. This chapter takes the reader on a brief journey through some of the key historical developments that underpinned the successes of these medical innovations. © 2023 Elsevier Inc. All rights reserved.

15.
Critical Care Conference: 42nd International Symposium on Intensive Care and Emergency Medicine Brussels Belgium ; 27(Supplement 1), 2023.
Article in English | EMBASE | ID: covidwho-2316769

ABSTRACT

Introduction: We have previously described decreased renal perfusion in acute kidney injury (AKI) due to critical COVID-19 [1]. The objective of this study was to compare the effects of plasma expansion with a standardized fluid bolus on renal perfusion in patients with AKI compared to similar patients without AKI. Method(s): A case control study design was used to investigate group differences before and after a standardized intervention. ICU-treated COVID-19 patients without underlying kidney disease were assigned to two groups based on KDIGO Creatinine criteria for AKI. Renal perfusion was assessed by magnetic resonance imaging using phase contrast and arterial spin labeling before and directly after plasma expansion with 7.5 ml/kg Ringer's Acetate (Baxter). Mean arterial pressure (MAP) was recorded before plasma infusion and compared with maximum value after. Data was analyzed with a mixed model repeated measures ANOVA for all kidneys using a random effect to account for research subjects. Result(s): Nine patients with AKI and eight without were included in the study. Patients in both groups were of similar mean age and weight, 66 (SD 8) years and 94 (SD 22) kg in AKI group and 64 (SD 15) years and 93 (SD 20) kg in patients without AKI. The response to plasma expansion was similar with increased MAP by 18 (CI 8-28) mmHg and 20 (CI 10-31) mmHg respectively (Table 1). Total renal perfusion and cortical perfusion was not significantly changed by plasma expansion, however there was a reduction of medullary perfusion in patients without AKI (Table 1). Conclusion(s): Plasma expansion with a standardized fluid bolus did not increase renal perfusion in critically ill patients with ARDS due to COVID-19.

16.
Circulation Conference: American Heart Association's ; 144(Supplement 2), 2021.
Article in English | EMBASE | ID: covidwho-2316022

ABSTRACT

Asymmetric cerebral perfusion can occur when extracorporeal membrane oxygenation (ECMO) flow competes with native cardiac circulation. It is unclear whether this phenomenon associates with brain injury. Diffuse correlation spectroscopy (DCS) provides continuous, laser-based, non-invasive, bedside monitoring of relative cerebral blood flow (rCBF). This study measured rCBF in ECMO patients via DCS to determine whether comatose patients experience asymmetric cerebral perfusion. Adults receiving ECMO for any indication were prospectively recruited from 12/2019-3/2021. Patients with prior neurologic injury, scalp/facial lacerations, and SARS-CoV-2 infection were excluded. DCS monitoring was performed daily during ECMO support with sensors placed on bilateral foreheads. Mean arterial pressure (MAP) was continuously recorded from the bedside monitor. The Glasgow Coma Scale (GCS) was assessed by clinical staff multiple times daily with sedation pauses, if possible, per standard of care. rCBF was calculated by comparing continuous cerebral blood flow (CBF) measurements to the daily median CBF, then averaged at each MAP value. Daily rCBF asymmetry was calculated by summing the absolute difference of rCBF between the two hemispheres at each MAP value, normalized for the total MAP range experienced by the patient that day. Twelve subjects were enrolled in this study (ages 21-78, 6 with cardiac arrest, 4 with acute heart failure, 2 with ARDS) and grouped by maximum GCS motor (GCS-M) score during ECMO, with 3 "comatose" subjects (GCS-M <= 4), and 9 "awake" subjects (GCS-M > 4). DCS was performed over 66 sessions with a mean duration of 131.83 +/- 1.13 minutes. Comatose subjects exhibited more rCBF asymmetry than awake subjects (0.28 +/- 0.06 mmHg-1 vs. 0.10 +/- 0.001 mmHg-1, p=0.045). No difference in asymmetry was noted between patients with or without cardiac arrest. We found that comatose ECMO subjects exhibited higher inter-hemispheric rCBF asymmetry over a range of blood pressures than awake subjects. Though our comatose sample is small, further validation of this finding and its causes, such as cerebrovascular dysregulation, is warranted.

17.
Topics in Antiviral Medicine ; 31(2):132, 2023.
Article in English | EMBASE | ID: covidwho-2315714

ABSTRACT

Background: Secondary lymphoid organs provide the adequate microenvironment for the development of antigen (Ag)-specific immune responses. The tight collaboration between CD4+ T cells and B cells in germinal centers is crucial to shape B cell fate and optimize antibody maturation. Dissecting these immune interactions remains challenging in humans, and animal models do not always recapitulate human physiology. To address this issue, we developed an in vitro 3D model of a human lymphoid organ. The model relies on a microfluidic device, enabling primary human cells to self-organize in an extracellular matrix (ECM) under continuous fluid perfusion. We applied this Lymphoid Organ-Chip (LO chip) system to the analysis of B cell recall responses to SARS-CoV-2 antigens. Method(s): We used a two-channel microfluidic Chip S1 from Emulate, where the top channel is perfused with antigen (spike protein or SARS-CoV-2 mRNA vaccine), while the bottom channel contains PBMC (n = 14 independent donors) seeded at high-density in a collagen-based ECM. Immune cell division and cluster formation were monitored by confocal imaging, plasmablast differentiation and spike-specific B cell amplification by flow cytometry, antibody secretion by a cell-based binding assay (S-flow). Result(s): Chip perfusion with the SARS-CoV-2 spike protein for 6 days resulted in the induction CD38hiCD27hi plasmablast maturation compared to an irrelevant BSA protein (P< 0.0001). Using fluorescent spike as a probe, we observed a strong amplification of spike-specific B cell (from 3.7 to 140-fold increase). In line with this rapid memory B cell response, spike-specific antibodies production could be detected as early as day 6 of culture. Spike perfusion also induced CD4+ T cell activation (CD38+ ICOS+), which correlated with the level of B cell maturation. The magnitude of specific B cell amplification in the LO chip was higher than in 2D and 3D static cultures at day 6, showing the added value of 3D perfused culture for the induction of recall responses. Interestingly, the perfusion of mRNA-based SARS-CoV-2 vaccines also led to strong B cell maturation and specific B cell amplification, indicating that mRNA-derived spike could be expressed and efficiently presented in the LO chip. Conclusion(s): We developed a versatile Lymphoid Organ-Chip model suitable for the rapid evaluation of B cell recall responses. The model is responsive to protein and mRNA-encoded antigens, highlighting its potential in the evaluation of SARS-CoV-2 vaccine boosting strategies.

18.
Topics in Antiviral Medicine ; 31(2):193, 2023.
Article in English | EMBASE | ID: covidwho-2313499

ABSTRACT

Background: Post-acute sequelae of SARS-COV-2 infection (PASC) is associated with cognitive impairment (CI) with unclear pathogenesis though blood brain barrier (BBB) impairment and excitotoxic injury appear significant. Post-acute sequelae of SARS-COV-2 infection (PASC) is associated with cognitive impairment (CI) with unclear pathogenesis though blood brain barrier (BBB) impairment and excitotoxic injury appear significant. We hypothesized that PASC CI patients would have brain inflammation and BBB disruption using advanced MR imaging. Method(s): In this prospective longitudinal study, 14 patients with PASC CI (mild and non-hospitalised) were enrolled (mean age of 45;10 F and 4 M) and 10 sex and age matched healthy controls. 13 had a follow up MR at 9-12 months (mean 10 months). All participants underwent DCE perfusion (an index of BBB integrity with Ktrans as the measurement), Diffusion Tensor Imaging (DTI) and single voxel MR spectroscopy (MRS) of the frontal cortex/white matter and the brainstem in addition to brain anatomical MRI. Between group analyses were used to determine which MRI outcomes were significantly different from controls in patients with PASC CI. Result(s): The PASCI CI group showed significantly increased (ie BBB impairment) Ktrans, and increased region (Frontal white matter and Brain Stem)-specific areas in the brain (p=< 0.005), reduction in NAA (ie neuronal injury) and mild reduction of Glx (ie excitotoxicity) in the frontal white matter and brain stem (p=0.004), and reduction in white matter integrity (increased diffusivity -greater radial and mean diffusivity). Increased Ktrans was correlated with increased both radial and mean diffusivity (r=0.9) in all tested brain regions. Ktrans significantly improved in the follow up MR (p= 002596 Z=-2.794872) with no difference between subjects and controls indicating BBB normalisation (p= 0.442418, z= -0.144841). White matter integrity also improved especially in the fractional anisotropy values in the executive networks (p=< 0.00045). MRS showed significant improvement in the NAA in the frontal white matter but Glx remain high as compared to the controls (p=0.0006). Conclusion(s): PASC CI was characterised by reversible diffuse BBB impairment, neuronal/axonal and excitotoxic injury. BBB impairment was associated with white matter disruption. These are suggestive biomarkers for the presence, severity and prognosis of PASC CI. Such biomarkers could underpin appropriate trial design and timing of intervention.

19.
Thromb J ; 21(1): 51, 2023 May 02.
Article in English | MEDLINE | ID: covidwho-2320178

ABSTRACT

BACKGROUND: Pulmonary embolism (PE) is an important complication of Coronavirus disease 2019 (COVID-19). COVID-19 is associated with respiratory impairment and a pro-coagulative state, rendering PE more likely and difficult to recognize. Several decision algorithms relying on clinical features and D-dimer have been established. High prevalence of PE and elevated Ddimer in patients with COVID-19 might impair the performance of common decision algorithms. Here, we aimed to validate and compare five common decision algorithms implementing age adjusted Ddimer, the GENEVA, and Wells scores as well as the PEGeD- and YEARS-algorithms in patients hospitalized with COVID-19. METHODS: In this single center study, we included patients who were admitted to our tertiary care hospital in the COVID-19 Registry of the LMU Munich. We retrospectively selected patients who received a computed tomography pulmonary angiogram (CTPA) or pulmonary ventilation/perfusion scintigraphy (V/Q) for suspected PE. The performances of five commonly used diagnostic algorithms (age-adjusted D-dimer, GENEVA score, PEGeD-algorithm, Wells score, and YEARS-algorithm) were compared. RESULTS: We identified 413 patients with suspected PE who received a CTPA or V/Q confirming 62 PEs (15%). Among them, 358 patients with 48 PEs (13%) could be evaluated for performance of all algorithms. Patients with PE were older and their overall outcome was worse compared to patients without PE. Of the above five diagnostic algorithms, the PEGeD- and YEARS-algorithms performed best, reducing diagnostic imaging by 14% and 15% respectively with a sensitivity of 95.7% and 95.6%. The GENEVA score was able to reduce CTPA or V/Q by 32.2% but suffered from a low sensitivity (78.6%). Age-adjusted D-dimer and Wells score could not significantly reduce diagnostic imaging. CONCLUSION: The PEGeD- and YEARS-algorithms outperformed other tested decision algorithms and worked well in patients admitted with COVID-19. These findings need independent validation in a prospective study.

20.
Curr Atheroscler Rep ; 25(7): 351-357, 2023 07.
Article in English | MEDLINE | ID: covidwho-2317609

ABSTRACT

PURPOSE OF REVIEW: Despite single-photon emission computerized tomography (SPECT) being the most used nuclear imaging technique for diagnosis of coronary artery disease (CAD), many now consider positron emission tomography (PET) as a superior modality. This review will focus on the advances of cardiac PET in recent years and its advantages compared to SPECT in diagnosis and prognosis of CAD. RECENT FINDINGS: PET's higher resolution and enhanced diagnostic accuracy, as well as lower radiation exposure, all help explain the rationale for its wider spread and use. PET also allows for measurement of myocardial blood flow (MBF) and myocardial flow reserve (MFR), which aids in several different clinical scenarios, such as diagnosing multivessel disease or identifying non-responders. PET has also been shown to be useful in diagnosing CAD in various specific populations, such as patients with prior COVID-19 infection, cardiac transplant, and other comorbidities.


Subject(s)
COVID-19 , Coronary Artery Disease , Fractional Flow Reserve, Myocardial , Myocardial Ischemia , Myocardial Perfusion Imaging , Humans , Myocardial Ischemia/diagnostic imaging , Positron-Emission Tomography/methods , Coronary Artery Disease/diagnostic imaging , Coronary Angiography/methods , Prognosis , Myocardial Perfusion Imaging/methods , Fractional Flow Reserve, Myocardial/physiology , COVID-19 Testing
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