Severe Respiratory Failure Developing in the Course of High-Altitude Pulmonary Edema in an Alpinist with COVID-19 Pneumonia: A Case Report.

Pigon, Katarzyna, Ryszard Grzanka, Ewa Nowalany-Kozielska, and Andrzej Tomasik. Severe respiratory failure developing in the course of high-altitude pulmonary edema in an alpinist with COVID-19 pneumonia: a case report. High Alt Med Biol. 23:372-376, 2022.-The case of a 38-year-old Polish alpinist, evacuated from base camp (4,200 m) under Lenin's Peak due to severe high-altitude pulmonary edema (HAPE) and symptoms of acute mountain sickness/high-altitude cerebral edema (HACE), is presented. Starting the expedition, the man was asymptomatic and had a negative COVID-19 molecular test. After a few days of trekking, he developed typical HAPE and HACE. After evacuation to the hospital in Bishkek, a diagnosis of acute bronchopneumonia was made by computed tomography (CT) imaging. A COVID-19 test was not performed at that time. After returning to Poland, a complete noninvasive cardiac and pulmonary assessment disclosed no pathology. The initial chest CT reassessment was read as demonstrating the densities typical for COVID-19 pneumonia, and a SARS-CoV-2 antibody test corroborated the diagnosis. Pre-existing lung disease increases the risk of developing HAPE. In the era of the COVID-19 pandemic, people traveling at a high altitude and unaware of the infection are at particular risk.

[The case of the development of ischemic stroke and cerebral edema after SARS-COV-2 infection in a patient with discirculatory encephalopathy and concomitant schizophrenia]. / Sluchai razvitiya ishemicheskogo insul'ta i oteka golovnogo mozga posle infitsirovaniya SARS-CoV-2 na fone distsirkulyatornoi entsefalopatii i soputstvuyushchei shizofrenii.

The article presents a case of ischemic stroke after SARS-CoV-2 infection in a patient with dyscirculatory encephalopathy and schizophrenia. Patient 44 years old, was hospitalized due to a confirmed diagnosis of a new coronavirus infection (COVID-19) and diagnosed bilateral pneumonia with a damage to 65% of the lung parenchyma. The patient has a history of dyscirculatory encephalopathy and paranoid schizophrenia, a continuous type of course. A fatal outcome occurs on the 2nd day of inpatient treatment. A brain autopsy revealed pericellular and perivascular edema, looseness of neuroglia with necrobiotic changes in the brain substance. Neuronal damage, small-focal gliosis, basophilic balls, destructive-productive vasculitis, ischemic small-focus necrosis were revealed. In the lungs, areas of atelectasis, disatelectasis, hyaline membranes, and edematous fluid were found. Epithelium of the convoluted tubules showed dystrophic and necrotic changes. The cause of death of the patient was a new coronavirus infection COVID-19, which caused bilateral viral pneumonia, complicated by the development of acute respiratory failure and COVID-associated ischemic cerebral infarction complicated by neuromorphological changes in the brain.

Outcome of post-traumatic acute respiratory distress syndrome in young patients requiring extracorporeal membrane oxygenation (ECMO).

We aimed to evaluate the outcomes of post-traumatic acute respiratory distress syndrome (ARDS) in young patients with and without Extracorporeal membrane oxygenation (ECMO) support. A retrospective analysis was conducted for trauma patients who developed ARDS at a level I trauma facility between 2014 and 2020. Data were analyzed and compared between ECMO and non-ECMO group. We identified 85 patients with ARDS (22 patients had ECMO support and 63 matched patients managed by the conventional mechanical ventilation; 1:3 matching ratio). The two groups were comparable for age, sex, injury severity score, abbreviated injury score, shock index, SOFA score, and head injury. Kaplan Meier survival analysis showed that the survival in the ECMO group was initially close to that of the non-ECMO, however, during follow-up, the survival rate was better in the ECMO group, but did not reach statistical significance (Log-rank, p = 0.43 and Tarone-Ware, p = 0.37). Multivariable logistic regression analysis showed that acute kidney injury (AKI) (Odds ratio 13.03; 95% CI 3.17-53.54) and brain edema (Odds ratio 4.80; 95% CI 1.10-21.03) were independent predictors of mortality. Sub-analysis showed that in patients with severe Murray Lung Injury (MLI) scores, non-ECMO group had higher mortality than the ECMO group (100% vs 36.8%, p = 0.004). Although ARDS is uncommon in young trauma patients, it has a high mortality. ECMO therapy was used in a quarter of ARDS cases. AKI and brain edema were the predictors of mortality among ARDS patients. ECMO use did not worsen the outcome in trauma patients; however, the survival was better in those who had severe MLI and ECMO support. Further prospective study is needed to define the appropriate selection criteria for the use of ECMO to optimize the outcomes in trauma patients.

Neurological Complications of Malaria.

PURPOSE OF REVIEW: To discuss the neurological complications and pathophysiology of organ damage following malaria infection. RECENT FINDINGS: The principal advancement made in malaria research has been a better understanding of the pathogenesis of cerebral malaria (CM), the most dreaded neurological complication generally caused by Plasmodium falciparum infection. However, no definitive treatment has yet been evolved other than the use of antimalarial drugs and supportive care. The development of severe cerebral edema in CM results from two distinct pathophysiologic mechanisms. First, the development of "sticky" red blood cells (RBCs) leads to cytoadherence, where red blood cells (RBCs) get stuck to the endothelial walls and between themselves, resulting in clogging of the brain microvasculature with resultant hypoxemia and cerebral edema. In addition, the P. falciparum-infected erythrocyte membrane protein 1 (PfEMP1) molecules protrude from the raised knob structures on the RBCs walls and are in themselves made of a combination of human and parasite proteins in a tight complex. Antibodies to surfins, rifins, and stevors from the parasite are also located in the RBC membrane. On the human microvascular side, a range of molecules involved in host-parasite interactions, including CD36 and intracellular adhesion molecule 1, is activated during interaction with other molecules such as endothelial protein C receptor and thrombospondin. As a result, an inflammatory response occurs with the dysregulated release of cytokines (TNF, interleukins 1 and 10) which damage the blood-brain barrier (BBB), causing plasma leakage and brain edema. This second mechanism of CNS injury often involves multiple organs in adult patients in endemic areas but remains localized only to the central nervous system (CNS) among African children. Neurological sequelae may follow both P. falciparum and P. vivax infections. The major brain pathology of CM is brain edema with diffuse brain swelling resulting from the combined effects of reduced perfusion and hypoxemia of cerebral neurons due to blockage of the microvasculature by parasitized RBCs as well as the neurotoxic effect of released cytokines from a hyper-acute immune host reaction. A plethora of additional neurological manifestations have been associated with malaria, including posterior reversible encephalopathy syndrome (PRES), reversible cerebral vasoconstriction syndrome (RCVS), malarial retinopathy, post-malarial neurological syndrome (PMNS), acute disseminated encephalomyelitis (ADEM), Guillain-Barré syndrome (GBS), and cerebellar ataxia. Lastly, the impact of the COVID-19 pandemic on worldwide malaria control programs and the possible threat from co-infections is briefly discussed.

Cortical unihemispheric brain edema (CUBE) due to a multi-system inflammatory syndrome in adults (MIS-A).

Unilateral hemispheric edema may occur with or without seizures. It is a rare entity, found more often in children, than in adults. As many of these patients develop pronounced unilateral complete cortical hemispheric (uni-hemispheric) edema on MRI, we have used the term "cortical unihemispheric brain edema" (CUBE) to describe this entity. We describe a case of CUBE occurring along with a post COVID multi-system inflammatory syndrome in adults (MIS-A). A 30-year-old man was admitted with status epilepticus. He was found to have CUBE and features of MIS-A. He had a history of mild COVID-19 illness one month earlier. He was noted to have persistently elevated inflammatory markers and multiorgan dysfunction compatible with MIS-A. We review the cases of CUBE in the literature and describe the features and etiology of this uncommon syndrome. Furthermore, we discuss the differences between two types of CUBE;cytotoxic CUBE (CUBE-C) and vasogenic CUBE (CUBE-V).

Epidemiologic Characteristics of Children with Diabetic Ketoacidosis Treated in a Pediatric Intensive Care Unit in a 10-Year-Period: Single Centre Experience in Croatia.

Background and Objectives: The incidence of severe and moderate forms of DKA as the initial presentation of type 1 diabetes mellitus (T1D) is increasing, especially during the COVID-19 pandemic. This poses a higher risk of developing cerebral edema as a complication of diabetic ketoacidosis (DKA), as well as morbidity and mortality rates. The aim of this study was to determine the trend and clinical features of children treated in the last 10 years in the Pediatric Intensive Care Unit (PICU) due to the development of DKA. Materials and Methods: This retrospective study was performed in the PICU, Clinical Hospital Centre Rijeka, in Croatia. All children diagnosed with DKA from 2011-2020 were included in this study. Data were received from hospital medical documentation and patient paper history. The number of new cases and severity of DKA were identified and classified using recent International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines. Results: In this investigation period, 194 children with newly diagnosed T1D were admitted to our hospital: 58 of them were treated in the PICU due to DKA; 48 had newly diagnosed T1D (48/58); and ten previously diagnosed T1D (10/58). DKA as the initial presentation of T1D was diagnosed in 24.7% (48/194). Moderate or severe dehydration was present in 76% of the children at hospital admission. Polyuria, polydipsia, and Kussmaul breathing were the most common signs. Three patients (5.2%) developed cerebral edema, of whom one died. Conclusions: During the investigation period a rising trend in T1D was noted, especially in 2020. About one quarter of children with T1D presented with DKA at initial diagnosis in western Croatia, most of them with a severe form. Good education of the general population, along with the patients and families of children with diabetes, is crucial to prevent the development of DKA and thus reduce severe complications.

Diabetic ketoacidosis, cerebral venous sinus thrombosis and fulminant cerebral oedema in COVID-19 infection complicated by Klebsiella pneumoniae infection.

We present an unusual case of a woman in her 30s who was admitted for diabetic ketoacidosis (DKA) in the setting of newly diagnosed but late COVID-19 infection with associated Klebsiella pneumoniae infection. Her altered mental status, out of proportion with her metabolic decompensation, revealed a superimposed cerebral venous sinus thrombosis (CVST) with fulminant cerebral oedema and ultimately brain death. This unusual and fulminant case of cerebral oedema in the setting of COVID-19 infection with bacterial infection, DKA and CVST was the perfect storm with multiple interwoven factors. It offered diagnostic and treatment challenges with an unfortunate outcome. This unique case is a reminder that it is important to consider a broad neurological differential in patients with COVID-19 with unexplained neurological manifestations, which may require specific neurointensive care management.

Brain death in a vaccinated patient with COVID-19 infection.

We present a case of brain death in a vaccinated, immunocompromised patient who presented with COVID-19 pneumonia. Imaging was characterized by diffuse cerebral edema, pseudo-subarachnoid hemorrhage, and no antegrade flow above the terminal internal carotid arteries. To our knowledge, this is the first case report with such findings in a vaccinated patient.

Severe diabetic ketoacidosis precipitated by COVID-19 in pediatric patients: Two case reports. / Cetoacidosis diabética severa precipitada por COVID-19 en pacientes pediátricos: reporte de dos casos.

INTRODUCTION: The association of COVID-19 with diabetes mellitus is bidirectional. In one direction, diabetes mellitus is associated with an increased risk of severe COVID-19. In the opposite direction, in patients with COVID-19 new-onset diabetes mellitus, severe diabetic ketoacidosis and severe metabolic complications have been described. CLINICAL CASE: This report describes two patients with diabetes mellitus who came to our hospital with ketoacidosis resulting from new-onset diabetes mellitus. We describe the clinical course and the management approach during the COVID-19 pandemic. CONCLUSION: COVID-19 is associated with metabolic complications such as severe diabetic ketoacidosis.

INTRODUCCIÓN: La relación entre la enfermedad por el coronavirus de 2019 (COVID-19) secundaria a SARS-CoV-2 y la diabetes mellitus es bidireccional. Por un lado, la diabetes mellitus se asocia con un mayor riesgo de COVID-19 grave. Por otro lado, en pacientes con COVID-19 se han observado diabetes mellitus de nueva aparición con presentaciones de cetoacidosis diabética y complicaciones metabólicas graves de dicha presentación. CASOS CLÍNICOS: En este informe, describimos a dos pacientes pediátricos con diabetes mellitus que acudieron a nuestro hospital con cetoacidosis diabética, de debut inicial. Describimos la evolución y el manejo clínico y terapéutico durante la pandemia de COVID-19. CONCLUSIÓN: La infección por COVID-19 puede precipitar complicaciones como cetoacidosis diabética severa.

COVID-19 as a Cause of Acute Neonatal Encephalitis and Cerebral Cytotoxic Edema.

The majority of coronavirus disease 2019 (COVID-19) have been confirmed in adults, with only a few reported cases in children. In the pediatric population, COVID-19 infection appears to be often unremarkable or associated with mild respiratory symptoms. Little is known about neurologic complications related to COVID-19 in newborns. We present a case of severe encephalitis with cytotoxic brain edema in a newborn with COVID-19.

Early postmortem brain MRI findings in COVID-19 non-survivors.

OBJECTIVES: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered to have potential neuroinvasiveness that might lead to acute brain disorders or contribute to respiratory distress in patients with coronavirus disease 2019 (COVID-19). This study investigates the occurrence of structural brain abnormalities in non-survivors of COVID-19 in a virtopsy framework. METHODS: In this prospective, monocentric, case series study, consecutive patients who fulfilled the following inclusion criteria benefited from an early postmortem structural brain MRI: death <24 hours, SARS-CoV-2 detection on nasopharyngeal swab specimen, chest CT scan suggestive of COVID-19, absence of known focal brain lesion, and MRI compatibility. RESULTS: Among the 62 patients who died of COVID-19 from March 31, 2020, to April 24, 2020, at our institution, 19 decedents fulfilled the inclusion criteria. Parenchymal brain abnormalities were observed in 4 decedents: subcortical microbleeds and macrobleeds (2 decedents), cortico-subcortical edematous changes evocative of posterior reversible encephalopathy syndrome (PRES; 1 decedent), and nonspecific deep white matter changes (1 decedent). Asymmetric olfactory bulbs were found in 4 other decedents without downstream olfactory tract abnormalities. No brainstem MRI signal abnormality was observed. CONCLUSIONS: Postmortem brain MRI demonstrates hemorrhagic and PRES-related brain lesions in non-survivors of COVID-19. SARS-CoV-2-related olfactory impairment seems to be limited to olfactory bulbs. Brainstem MRI findings do not support a brain-related contribution to respiratory distress in COVID-19.

Posterior Reversible Encephalopathy Syndrome.

PURPOSE OF REVIEW: This review provides an updated discussion on the clinical presentation, diagnosis and radiographic features, mechanisms, associations and epidemiology, treatment, and prognosis of posterior reversible encephalopathy syndrome (PRES). Headache is common in PRES, though headache associated with PRES was not identified as a separate entity in the 2018 International Classification of Headache Disorders. Here, we review the relevant literature and suggest criteria for consideration of its inclusion. RECENT FINDINGS: COVID-19 has been identified as a potential risk factor for PRES, with a prevalence of 1-4% in patients with SARS-CoV-2 infection undergoing neuroimaging, thus making a discussion of its identification and treatment particularly timely given the ongoing global pandemic at the time of this writing. PRES is a neuro-clinical syndrome with specific imaging findings. The clinical manifestations of PRES include headache, seizures, encephalopathy, visual disturbances, and focal neurologic deficits. Associations with PRES include renal failure, preeclampsia and eclampsia, autoimmune conditions, and immunosuppression. PRES is theorized to be a syndrome of disordered autoregulation and endothelial dysfunction resulting in preferential hyperperfusion of the posterior circulation. Treatment typically focuses on treating the underlying cause and removal of the offending agents.

Janus Kinase Inhibition Ameliorates Cerebral Ischemic Injury and Neuroinflammation through Reducing NLRP3 Inflammasome Activation via JAK2/STAT3 Pathway Inhibition (preprint)

BackgroundEvidence shows that inflammatory responses play multiphasic roles in stroke pathogenesis. Ruxolitinib (Rux), a selective oral JAK 1/2 inhibitor, is efficacious in COVID-19 by reducing inflammation via the JAK2/STAT3 pathway. MethodsHere, we investigated whether JAK2 inhibition has neuroprotective effects against ischemic stroke (IS) in MCAO mice in vivo and in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) model, and explored the potential molecular mechanisms. Rux was applied to MCAO mice. Immunofluorescence staining, RT-qPCR, and western blots were used to measure the expression of NLRP3 inflammation components and proinflammatory cytokines as well as JAK2/STAT3 pathway. Local STAT3 deficiency in brain tissue was established to investigate the interplay between NLRP3 and STAT3 signaling.ResultsRux treatment obviously improved neurological scores, decreased the infarct size and ameliorated cerebral edema 3 days after stroke. In addition, immunofluorescence staining and western blots showed that Rux application inhibited the expression of NLRP3 inflammasome components, proteins related to the NLRP3 inflammasome and phosphorylated STAT3 (p-STAT3) in neurons. Furthermore, Rux administration inhibited the expression of proinflammatory cytokines, including TNF-α, IFN-γ, HMBG1, IL-1β, IL-2, and IL-6 in middle cerebral artery occlusion (MCAO) model mice, suggesting that Rux may alleviate IS injury by inhibiting proinflammatory reactions via JAK2/STAT3 signaling pathway regulation. Local STAT3 deficiency decreased histone H3 and H4 acetylation on the NLRP3 promoter and the NLRP3 inflammasome component expression, indicating that the NLRP3 inflammasome may be directly regulated by STAT3 signaling. Finally, the effect of Rux on the NLRP3 inflammasome was further assessed in a HT22 cell OGD/R model in vitro. Rux application markedly suppressed lipopolysaccharide (LPS)-induced NLRP3 inflammasome secretion and JAK2/STAT3 pathway activation in vitro the in OGD/R HT22 cell model.ConclusionJAK2 inhibition by Rux in MCAO mice decreased STAT3 phosphorylation, thus inhibiting downstream proinflammatory cytokines and H3 and H4 acetylation on the NLRP3 promoter, resulting in downregulation of NLRP3 inflammasome component expression.

Acute Ischemic Stroke and COVID-19: An Analysis of 27 676 Patients.

BACKGROUND AND PURPOSE: Acute ischemic stroke may occur in patients with coronavirus disease 2019 (COVID-19), but risk factors, in-hospital events, and outcomes are not well studied in large cohorts. We identified risk factors, comorbidities, and outcomes in patients with COVID-19 with or without acute ischemic stroke and compared with patients without COVID-19 and acute ischemic stroke. METHODS: We analyzed the data from 54 health care facilities using the Cerner deidentified COVID-19 dataset. The dataset included patients with an emergency department or inpatient encounter with discharge diagnoses codes that could be associated to suspicion of or exposure to COVID-19 or confirmed COVID-19. RESULTS: A total of 103 (1.3%) patients developed acute ischemic stroke among 8163 patients with COVID-19. Among all patients with COVID-19, the proportion of patients with hypertension, diabetes, hyperlipidemia, atrial fibrillation, and congestive heart failure was significantly higher among those with acute ischemic stroke. Acute ischemic stroke was associated with discharge to destination other than home or death (relative risk, 2.1 [95% CI, 1.6-2.4]; P<0.0001) after adjusting for potential confounders. A total of 199 (1.0%) patients developed acute ischemic stroke among 19 513 patients without COVID-19. Among all ischemic stroke patients, COVID-19 was associated with discharge to destination other than home or death (relative risk, 1.2 [95% CI, 1.0-1.3]; P=0.03) after adjusting for potential confounders. CONCLUSIONS: Acute ischemic stroke was infrequent in patients with COVID-19 and usually occurs in the presence of other cardiovascular risk factors. The risk of discharge to destination other than home or death increased 2-fold with occurrence of acute ischemic stroke in patients with COVID-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.

Severe cortical damage associated with COVID-19 case report.

Symptoms of COVID-19, as reported during the SARS-CoV-2 pandemic in 2019-2020, are primarily respiratory and gastrointestinal, with sparse reports on neurological manifestations. We describe the case of a 17-year old female with Cornelia de Lange syndrome and well controlled epilepsy, who sustained significant cortical injury during a COVID-19 associated multi-inflammatory syndrome.