Angiotensin-converting enzyme 2 (ACE2) in COVID-19 and other diseases.

The coronavirus SARS-CoV-2 was detected in isolates of pneumonia patients in January 2020. The virus cannot multiply extracellularly but requires access to the cells of a host organism. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as a receptor, to which it docks with its spikes. ACE2 belongs to the renin angiotensin system (RAS), whose inhibitors have been used for years against high blood pressure. Renin is an endopeptidase that is predominantly formed in the juxtaglomerular apparatus of the kidney and cleaves the decapeptide angiotensin I (Ang I) from angiotensinogen. Through the angiotensin-converting enzyme (ACE), another 2 C-terminal amino acids are removed from Ang I, so that finally the active octapeptide angiotensin II (Ang II) is formed. The biological effect of Ang II via the angiotensin II receptor subtype 1 (AT1-R) consists of vasoconstriction, fibrosis, proliferation, inflammation, and thrombosis formation. ACE2 is a peptidase that is a homolog of ACE. ACE2 is predominantly expressed by pulmonary alveolar epithelial cells in humans and has been detected in arterial and venous endothelial cells. In contrast to the dicarboxy-peptidase ACE, ACE2 is a monocarboxypeptidase that cleaves only one amino acid from the C-terminal end of the peptides. ACE2 can hydrolyze the nonapeptide Ang-(1-9) from the decapeptide Ang I and the heptapeptide Ang-(1-7) from the octapeptide Ang II. Ang-(1-7) acts predominantly antagonistically (vasodilatory, anti-fibrotic, anti-proliferative, anti-inflammatory, anti-thrombogenetically) via the G protein-coupled Mas receptor to the AT1-R-mediated effects of Ang II. In the pathogenesis of COVID-19 infection, it is therefore assumed that there is an imbalance due to overstimulation of the AT1 receptor in conjunction with a weakening of the biological effects of the Mas receptor.Copyright © 2022 Dustri-Verlag Dr. K. Feistle.

Advances in Management of the Stroke Etiology One-Percenters.

PURPOSE OF REVIEW: Uncommon causes of stroke merit specific attention; when clinicians have less common etiologies of stoke in mind, the diagnosis may come more easily. This is key, as optimal management will in many cases differs significantly from "standard" care. RECENT FINDINGS: Randomized controlled trials (RCT) on the best medical therapy in the treatment of cervical artery dissection (CeAD) have demonstrated low rates of ischemia with both antiplatelet and vitamin K antagonism. RCT evidence supports the use of anticoagulation with vitamin K antagonism in "high-risk" patients with antiphospholipid antibody syndrome (APLAS), and there is new evidence supporting the utilization of direct oral anticoagulation in malignancy-associated thrombosis. Migraine with aura has been more conclusively linked not only with increased risk of ischemic and hemorrhagic stroke, but also with cardiovascular mortality. Recent literature has surprisingly not provided support the utilization of L-arginine in the treatment of patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS); however, there is evidence at this time that support use of enzyme replacement in patients with Fabry disease. Additional triggers for reversible cerebral vasoconstriction syndrome (RCVS) have been identified, such as capsaicin. Imaging of cerebral blood vessel walls utilizing contrast-enhanced MRA is an emerging modality that may ultimately prove to be very useful in the evaluation of patients with uncommon causes of stroke. A plethora of associations between cerebrovascular disease and COVID-19 have been described. Where pertinent, authors provide additional tips and guidance. Less commonly encountered conditions with updates in diagnosis, and management along with clinical tips are reviewed.

Scientific debrief: cirrhosis

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.

Microvascular injuries, secondary edema, and inconsistencies in lung vascularization between affected and nonaffected pulmonary segments of non-critically ill hospitalized COVID-19 patients presenting with clinical deterioration.

PURPOSE: We aimed to better understand the pathophysiology of SARS-CoV-2 pneumonia in non-critically ill hospitalized patients secondarily presenting with clinical deterioration and increase in oxygen requirement without any identified worsening factors. METHODS: We consecutively enrolled patients without clinical or biological evidence for superinfection, without left ventricular dysfunction and for whom a pulmonary embolism was discarded by computed tomography (CT) pulmonary angiography. We investigated lung ventilation and perfusion (LVP) by LVP scintigraphy, and, 24 h later, left and right ventricular function by Tc-99m-labeled albumin-gated blood-pool scintigraphy with late (60 mn) tomographic albumin images on the lungs to evaluate lung albumin retention that could indicate microvascular injuries with secondary edema. RESULTS: We included 20 patients with confirmed SARS-CoV-2 pneumonia. All had CT evidence of organizing pneumonia and normal left ventricular ejection fraction. No patient demonstrated preserved ventilation with perfusion defect (mismatch), which may discard a distal lung thrombosis. Patterns of ventilation and perfusion were heterogeneous in seven patients (35%) with healthy lung segments presenting a relative paradoxical hypoperfusion and hypoventilation compared with segments with organizing pneumonia presenting a relative enhancement in perfusion and preserved ventilation. Lung albumin retention in area of organizing pneumonia was observed in 12 patients (60%), indicating microvascular injuries, increase in vessel permeability, and secondary edema. CONCLUSION: In hospitalized non-critically ill patients without evidence of superinfection, pulmonary embolism, or cardiac dysfunction, various types of damage may contribute to clinical deterioration including microvascular injuries and secondary edema, inconsistencies in lung segments vascularization suggesting a dysregulation of the balance in perfusion between segments affected by COVID-19 and others. SUMMARY STATEMENT: Microvascular injuries and dysregulation of the balance in perfusion between segments affected by COVID-19 and others are present in non-critically ill patients without other known aggravating factors. KEY RESULTS: In non-critically ill patients without evidence of superinfection, pulmonary embolism, macroscopic distal thrombosis or cardiac dysfunction, various types of damage may contribute to clinical deterioration including 1/ microvascular injuries and secondary edema, 2/ inconsistencies in lung segments vascularization with hypervascularization of consolidated segments contrasting with hypoperfusion of not affected segments, suggesting a dysregulation of the balance in perfusion between segments affected by COVID-19 and others.

Superior Cerebellar Artery Dissection in a Patient Diagnosed with Reversible Cerebral Vasoconstriction Syndrome: A Case Report

Arterial dissection is an uncommon complication of reversible cerebral vasocon-striction syndrome (RCVS). We describe the case of a 35-year-old woman with a migraine history who presented with recurrent thunderclap headache and focal neurological signs, including right hemiataxia. She had been diagnosed with COVID-19 disease two weeks earlier. Neuroimaging revealed multifocal stenosis of the posterior circulation arteries and dissection of the right superior cerebellar artery. She improved significantly throughout her one-week hospitalization and maintained only mild ataxia. The interplay between COVID-19 disease, RCVS, and arterial dissection requires further investigation.Copyright © Author(s) (or their employer(s)) and Sinapse 2022.

Ventilatory support in Covid-19 pneumonia.

The Covid-19 pandemic led to a major influx of patients suffering from acute hypoxemic respiratory failure, which conducted intensivists to adapt ICU structures and question respiratory support strategies. Available data suggest that pathophysiology of Covid-19 associated - acute respiratory distress syndrome (ARDS) is substantially similar to the pathophysiology of ARDS unrelated to Covid-19. Specific vascular injuries may however be more frequent during Covid-19 and some patients may present a major alteration in hypoxic pulmonary vasoconstriction. To date, ventilatory support strategies of patients with Covid-19 should be in line with guidelines for ARDS unrelated to Covid-19, including in particular a cautious evaluation of positive end-expiratory pressure effects.Copyright © SRLF 2021.

Eclampsia with hypothyroidism complicated with posterior reversible encephalopathy syndrome-a case report.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a rare neurological disorder with complex physiopathological mechanisms that have not been fully understood. Early identification is of great prognostic significance, of which the symptoms and radiological abnormalities can be completely reversed. If the diagnosis and treatment are delayed, ischemia and massive infarction may be developed in some patients. Posterior reversible encephalopathy syndrome (PRES) has been reported mainly in association with postpartum eclampsia, which have been rarely reported, while the association with hypothyroidism has not been reported at home or abroad. CASE PRESENTATION: Here we report on a pregnant 29-year-old with multipara and a chief complication of hypothyroidism. She presented in the emergency department with frequent attacks of severe headache symptoms resulting from reversible cerebral vasoconstriction syndrome (RCVS), accompanied with prenatal eclampsia. PRES was determined by radiological examination. CONCLUSION: To the best of our knowledge, this is the first case of PRES complicated by hypothyroidism and prepartum eclampsia.Clinicians should be alert for the co-occurence of eclampsia, PRES, and RCVS when patients have convulsions after a typical throbbing headache. Moreover, regular monitoring of thyroid function during pregnancy should also occupy certain special attention.

RCVS: by clinicians for clinicians-a narrative review.

BACKGROUND/OBJECTIVE: Reversible cerebral vasoconstriction syndrome may be underdiagnosed. It can be accompanied by various complications, mainly intracerebral hemorrhage and ischemic stroke. The clinical presentation of this condition varies according to its localization. The aims of this review are to raise awareness of the disease, especially in the presence of corresponding risk factors; to connect its precipitating factors, pathophysiology, and complications; and to compare various differential diagnoses of vasoconstriction. METHODS: A review of the literature in PubMed/MEDLINE and Google Scholar was conducted from May 1997 until May 2022. RESULTS: Reversible cerebral vasoconstriction syndrome, which is a clinical-radiological syndrome, is mainly characterized by the occurrence of thunderclap headache and widespread vasoconstriction. The most common precipitating factors are the use of vasoactive substances and postpartum status. The pathophysiology is currently assumed to include two mechanisms: sympathetic overactivity and endothelial dysfunction. From these mechanisms, it is possible to derive potential complications as well as the most important differential diagnoses: posterior reversible encephalopathy syndrome, convexity subarachnoid hemorrhage, ischemic and hemorrhagic stroke, and primary angiitis of the central nervous system. CONCLUSION: In general, the outcome of reversible cerebral vasoconstriction syndrome is very good. Vasospasm as well as thunderclap headache attacks can be fully reversible, and > 90% of patients are functionally independent at discharge.

Chest dual-energy CT to assess the effects of steroids on lung function in severe COVID-19 patients.

BACKGROUND: Steroids have been shown to reduce inflammation, hypoxic pulmonary vasoconstriction (HPV) and lung edema. Based on evidence from clinical trials, steroids are widely used in severe COVID-19. However, the effects of steroids on pulmonary gas volume and blood volume in this group of patients are unexplored. OBJECTIVE: Profiting by dual-energy computed tomography (DECT), we investigated the relationship between the use of steroids in COVID-19 and distribution of blood volume as an index of impaired HPV. We also investigated whether the use of steroids influences lung weight, as index of lung edema, and how it affects gas distribution. METHODS: Severe COVID-19 patients included in a single-center prospective observational study at the intensive care unit at Uppsala University Hospital who had undergone DECT were enrolled in the current study. Patients' cohort was divided into two groups depending on the administration of steroids. From each patient's DECT, 20 gas volume maps and the corresponding 20 blood volume maps, evenly distributed along the cranial-caudal axis, were analyzed. As a proxy for HPV, pulmonary blood volume distribution was analyzed in both the whole lung and the hypoinflated areas. Total lung weight, index of lung edema, was estimated. RESULTS: Sixty patients were analyzed, whereof 43 received steroids. Patients not exposed to steroids showed a more extensive non-perfused area (19% vs 13%, p < 0.01) and less homogeneous pulmonary blood volume of hypoinflated areas (kurtosis: 1.91 vs 2.69, p < 0.01), suggesting a preserved HPV compared to patients treated with steroids. Moreover, patients exposed to steroids showed a significantly lower lung weight (953 gr vs 1140 gr, p = 0.01). A reduction in alveolar-arterial difference of oxygen followed the treatment with steroids (322 ± 106 mmHg at admission vs 267 ± 99 mmHg at DECT, p = 0.04). CONCLUSIONS: The use of steroids might cause impaired HPV and might reduce lung edema in severe COVID-19. This is consistent with previous findings in other diseases. Moreover, a reduced lung weight, as index of decreased lung edema, and a more homogeneous distribution of gas within the lung were shown in patients treated with steroids. TRIAL REGISTRATION: Clinical Trials ID: NCT04316884, Registered March 13, 2020.

SARS-CoV-2 mitochondriopathy in COVID-19 pneumonia exacerbates hypoxemia.

RATIONALE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 pneumonia. We hypothesize that SARS-CoV-2 causes alveolar injury and hypoxemia by damaging mitochondria in airway epithelial cells (AEC) and pulmonary artery smooth muscle cells (PASMC), triggering apoptosis and bioenergetic impairment, and impairing hypoxic pulmonary vasoconstriction (HPV), respectively. OBJECTIVES: We examined the effects of: A) human betacoronaviruses, SARS-CoV-2 and HCoV-OC43, and individual SARS-CoV-2 proteins on apoptosis, mitochondrial fission, and bioenergetics in AEC; and B) SARS-CoV-2 proteins and mouse hepatitis virus (MHV-1) infection on HPV. METHODS: We used transcriptomic data to identify temporal changes in mitochondrial-relevant gene ontology (GO) pathways post-SARS-CoV-2 infection. We also transduced AECs with SARS-CoV-2 proteins (M, Nsp7 or Nsp9) and determined effects on mitochondrial permeability transition pore (mPTP) activity, relative membrane potential, apoptosis, mitochondrial fission, and oxygen consumption rates (OCR). In human PASMC, we assessed the effects of SARS-CoV-2 proteins on hypoxic increases in cytosolic calcium, an HPV proxy. In MHV-1 pneumonia, we assessed HPV via cardiac catheterization and apoptosis using the TUNEL assay. RESULTS: SARS-CoV-2 regulated mitochondrial apoptosis, mitochondrial membrane permeabilization and electron transport chain (ETC) GO pathways within 2 hours of infection. SARS-CoV-2 downregulated ETC Complex I and ATP synthase genes, and upregulated apoptosis-inducing genes. SARS-CoV-2 and HCoV-OC43 upregulated and activated dynamin-related protein 1 (Drp1) and increased mitochondrial fission. SARS-CoV-2 and transduced SARS-CoV-2 proteins increased apoptosis inducing factor (AIF) expression and activated caspase 7, resulting in apoptosis. Coronaviruses also reduced OCR, decreased ETC Complex I activity and lowered ATP levels in AEC. M protein transduction also increased mPTP opening. In human PASMC, M and Nsp9 proteins inhibited HPV. In MHV-1 pneumonia, infected AEC displayed apoptosis and HPV was suppressed. BAY K8644, a calcium channel agonist, increased HPV and improved SpO2. CONCLUSIONS: Coronaviruses, including SARS-CoV-2, cause AEC apoptosis, mitochondrial fission, and bioenergetic impairment. SARS-CoV-2 also suppresses HPV by targeting mitochondria. This mitochondriopathy is replicated by transduction with SARS-CoV-2 proteins, indicating a mechanistic role for viral-host mitochondrial protein interactions. Mitochondriopathy is a conserved feature of coronaviral pneumonia that may exacerbate hypoxemia and constitutes a therapeutic target.

COVID 19 Effects on Patients with Compensated Cirrhosis

Background: The coronavirus disease 19 (COVID-19) is a highly transmittable and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in Wuhan, China and spread around the world. Genomic analysis revealed that SARS-CoV-2 is phylogenetically related to severe acute respiratory syndrome-like (SARS-like) bat viruses, therefore bats could be the possible primary reservoir.The intermediate source of origin and transfer to humans is not known, however, the rapid human to human transfer has been confirmed widely. There is no clinically approved antiviral drug or vaccine available to be used against COVID-19. However, few broad-spectrum antiviral drugs have been evaluated against COVID-19 in clinical trials, resulted in clinical recovery.The liver, the largest internal organ in the body, is essential in keeping the body functioning properly. It removes or neutralizes poisons from the blood, produces immune agents to control infection, and removes germs and bacteria from the blood. It makes proteins that regulate blood clotting and produces bile to help absorb fats and fat-soluble vitamins. Several studies have shown a significant risk of mortality in patients with cirrhosis and in liver transplantation recipients.2, 3, 4 The severity of presentation and risk of mortality is more in patients with decompensated cirrhosis.5,6 COVID-19 had lead to a significant decrease in number of liver transplant surgeries being performed, which would lead to an increased wait list mortality in these patients.

The Successful Use of De Novo Belatacept with Reduced Dose Tacrolimus to Mitigate the Risks of Delayed Graft Function in Kidney Transplantation

Purpose: The new kidney allocation system has caused increased organ travel times and therefore increased cold ischemia time. Furthermore, the change in the priority to larger transplant centers has caused deprioritized centers to accept higher risk extended criteria donors. These factors lead to increased risk of delayed graft function (DGF). Method(s): To mitigate these risk factors of delayed graft function we have adopted an immunosuppression regimen of de novo belatacept with reduced dose tacrolimus with trough goal level of 5. We hypothesize that the use of belatacept will allow protection against rejection while allowing the renal allogaft to recover from ischemia reperfusion injury without concomitant calcineurin toxicity or vasoconstriction. The delayed addition of low dose tacrolimus can then aid in rejection prevention in addition to belatacept. Result(s): In a cohort of 83 patients we observed one graft loss, two episodes of rejection and three deaths. Of the 130 standard dose tacrolimus with no belatacept we observed no graft losses, seven rejections and one death. Two patients were converted from tacrolimus alone therapy to belatacept plus tacrolimus therapy after the diagnosis of rejection with concomitant tacrolimus toxicity. The belatacept group had a lower rate of rejection, but a higher rate of patient death with a P value <0.001 as calculated with the Z score test. The death in the tacrolimus group was due to covid. Two of the deaths in the belatacept group were cardiovascular, one was a cerebrovascular accident possible related to skull based osteomyelitis. The graft loss in the belatacept group was related to non-compliance. Conclusion(s): Despite initial reports of increased rates of rejection;we report decreased rejection with our belatacept for DGF regimen. We believe this regimen can be a useful tool to utilize more extended criteria donor kidneys in the new kidney allocation system.

Pathophysiology of reversible cerebral vasoconstriction syndrome.

Reversible cerebral vasoconstriction syndrome (RCVS) is a complex neurovascular disorder being recognized during the past two decades. It is characterized by multiple abrupt severe headaches and widespread cerebral vasoconstrictions, with potential complications such as ischemic stroke, convexity subarachnoid hemorrhage, intracerebral hemorrhage and posterior reversible encephalopathy syndrome. The clinical features, imaging findings, and dynamic disease course have been delineated. However, the pathophysiology of RCVS remains elusive. Recent studies have had substantial progress in elucidating its pathogenesis. It is now believed that dysfunction of cerebral vascular tone and impairment of blood-brain barrier may play key roles in the pathophysiology of RCVS, which explains some of the clinical and radiological manifestations of RCVS. Some other potentially important elements include genetic predisposition, sympathetic overactivity, endothelial dysfunction, and oxidative stress, although the detailed molecular mechanisms are yet to be identified. In this review, we will summarize what have been revealed in the literature and elaborate how these factors could contribute to the pathophysiology of RCVS.

Management of Hypoxia in Pediatric Population Affected with COVID-19

Pediatric acute respiratory distress syndrome (PARDS) is a life-threatening condition characterized by hypoxemia and is the most important cause of respiratory failure .It has been proposed that adult COVID-19 respiratory illness has two phenotypes: a low compliance ARDS- like phenotype and a normal compliance phenotype with low ventilation to perfusion ratio. The normal compliance phenotype is theorized to be due to a loss of hypoxic pulmonary vasoconstriction although the pediatric presentation in critical care has not been reported yet;the adult phenotype could be considered when managing pediatric patients with severe COVID-19. PARDS characterized by hypoxemia, radiographic haziness and decreased lung ,compliance per the criteria purposed by the pediatric acute lung injury consensus conference group (PALICC). High frequency nasal cannula or NIV by CPAP or BIPAP has been used successfully in pediatric patient with COVID-19 hypoxemia but increases risk of aerosolization and air born transmission that obligate strict airborne precautions. Management in ICU aims to maintain oxygenation while minimizing ventilation induced lung injury (VILI). For mechanical ventilation oxygen supplementation to maintain SPO2 > 92% and OI < 4 or OSI < 5 is recommended. Prone position and HFO ventilation (HFOV) are mostly utilized as rescue oxygenation. Prone position has been used as an adjunct therapy in adult patients with COVID 19 as chest computed tomography shows ground-glass appearance and depended lung injury. Pediatric evidence supp onorting prone position is scarce;however, there have been promising results with improved ventilation in dependent lung regions If HFOV is considered in patients with COVID-19, it should be used cautiously due to the high risk of aerosolization.

Recent Status of Development of Hb-based Blood Substitute With Pharmacologic Properties of ATP, Adenosine and Reduced Glutathione

Background: SARS-CoV-2 pandemic brought new attention to blood substitutes as a potential remedy for treatment of COVID-19 associated hypoxemia and more importantly to provide relief for sagging blood banks. In fact the American Red Cross declared a national blood crisis, the worst in decades. Although commercialization attempts of 1st generation blood substitutes have been unsuccessful due to toxicity and/or poor efficacy problems, the artificial oxygen carriers' field is rapidly expanding again creating more innovative products. To attenuate the adverse effects of blood substitutes caused by intrinsic toxicity of Hb we implemented a novel concept of 'pharmacologic cross-linking' and formulated a safe and effective blood substitute - HemoTech. Methods: HemoTech consists of pure bovine Hb cross-linked intramolecularly with o-ATP and intermolecularly with oadenosine and conjugated with reduced glutathione (GSH). HemoTech cGMP manufacturing includes a novel, validated orthogonal technology platform for effective clearance of endotoxin, prions and non-enveloped and enveloped viruses. Regulatory mandated requirements have been met including CMC and GLP non-clinical pharmacology, toxicology, genotoxicity and efficacy studies. HemoTech's clinical 'proof-of-concept' was performed in children with sickle cell anemia. Results: HemoTech is formulated as a 6.5 g/dL modified Hb solution in oxy- or carbon monoxy-form, enriched with electrolytes and mannitol. The 'pharmacologic cross-linking' does not interfere with Hb respiratory function, but eradicates Hb's intrinsic toxicity and provides Hb molecules with new medicinal properties of ATP, adenosine and GSH. The results of preclinical and clinical studies indicate that HemoTech is non-toxic and works as a physiological oxygen carrier with prolonged intravascular persistence, is vasodilatory and can reduce vasoconstriction that follows hemorrhage, has antioxidant and anti-inflammatory activities, and erythropoietic properties. Conclusion: HemoTech promises to be an effective blood substitute for various clinical indications.

Covid19 Vaccines and the Misinterpretation of Perceived Side Effects

In the era of Covid 19 and mass vaccination programs, the anti-vaccination movement across the world is currently at an all-time high. Much of this anti-vaccination sentiment could be attributed to the alleged side effects that are perpetuated across social media from anti-vaccination groups. Fear mongering and misinformation being peddled by people with no scientific training to terrorise people into staying unvaccinated is not just causing people to remain susceptible to viral outbreaks, but could also be causing more side effects seen in the vaccination process. This brief review will offer data that may demonstrate that misinformation perpetuated by the anti-vaccination movement may be causing more deaths and side effects from any vaccine. A mini review of published literature has been conducted and found that mental stress clearly causes vasoconstriction and arterial constriction of the blood vessels. Therefore, if subjects are panicked, concerned, stressed or scared of the vaccination, their arteries will constrict and become smaller in and around the time of receiving the vaccine. This biological mechanism (the constriction of veins, arteries and vessels under mental stress) is the most likely cause for where there has been blood clots, strokes, heart attacks, dizziness, fainting, blurred vision, loss of smell and taste that may have been experienced shortly after vaccine administration. The extreme mental stress of the patient could most likely be attributed to the fear mongering and scare tactics used by various anti-vaccination groups. This paper does not aim to rule in or out every side effect seen, but it is highly likely that many apparent side effects seen shortly after a subject has received a vaccine could be the result of restricted or congested blood flow from blood vessel or arterial constriction caused by emotional distress or placebo based on fear around vaccines.

Atypical Presentation of Cocaine-Induced Thrombotic Microangiopathy

Cocaine is one of the most used illicit drugs. Cocaine induced toxicity can result in hepatotoxicity, pulmonary toxicity, and renal dysfunction. Acute kidney injury (AKI) is an emergent complication in cocaine abusers. Rhabdomyolysis and vasoconstrictions mechanism are well known cause of AKI, cocaine induce thrombotic microangiopathy (TMA) is rarely reported. Cocaine is widely used in the United States, we report a case of Cocaine induced TMA in a cocaine abuser. We chronicle a case of a 42-Year-old male cocaine abuser, who presented to ED with complaints of Dyspnea, cough, anorexia and chest tightness for two days. He attributed to inhaling ammonia from cat urine along with cocaine abuse. No prior history of kidney disease or any other chronic illness. On examination, the patient appeared malnourished and cachectic. He was normotensive, lethargic and oriented. There were crackles at the lung bases. Blood tests revealed serum creatinine 18.0 mg/dL, blood urea nitrogen 150 mg/dL, hemoglobin 8.2 g/dL, platelets 173000/mm3, Retics count 8 %, LDH 1120 (84–246 IU/L) and haptoglobin < 8 (30–200mg/dL). A blood film revealed occasional schistocytes. Urinalysis showed proteinuria and microscopic hematuria. Urine toxicology revealed cocaine. Routine blood and urine cultures showed no growth. Serologic tests showed reduced complement C3 level of 40 (82-185 mg/dL) and normal C4 level of 32 (10–53mg/dL). There were no antibodies against HIV 1/2 and Covid 19. His ADAMTS-13 results showed 0.61 and 0.63 (0.68 to 1.63). Renal Ultrasound was unremarkable. Patient was intubated and ventilated in ICU;he was initiated on hemodialysis. He was provided four sessions of plasma exchanges till his ADAMTS-13 result came back near normal that was indicative of Cocaine induce TMA. Cocaine abuse is a global issue with increasing number of cases in the USA. It can cause AKI due to well-known etiologies like Rhabdomyolysis, Vasculitis, Acute interstitial Nephritis and Renal Infarction. However, Clinicians and nephrologists should also consider rare causes like TMA as a possible differential cause of AKI in the setting of cocaine abuse.

TELEMEDICAL EVALUATION OF ACUTE HEADACHE IN SETTING OF ONGOING COVID PANDEMIC

CASE: 50 yo generally healthy female with two sudden “throbbing” frontal headaches (HA) over the 7 days. First episode (rated 9 out of 10) was preceded by abd pain and emesis. The HA worsened in the laying down, which decreased after 5 hrs of “pacing around the house." Second HA preceded by neck pain and nausea. HA persist (2 out of 10) after the episodes with 'persistent brain fog.' Positive for recent life stressors. Has Mirena. During the video visit, she appears alert, not in distress, speech and mentation at baseline. Face symmetrical. However, no traditional intake such as vital signs were not available and the physical exam was limited. Due to the red flags symptoms, imaging was indicated. CT is the first pass work up for intracranial hemorrhage. Differential diagnoses include migraines, benign HA, hemorrhage, thrombosis, dissection, and neoplasms. There were logistical limitations as this occurred over the holiday with reduced clinic hours, no urgent care and the ED on diversion. An urgent head CT ordered with the plan for follow up in person visit after the holiday for further assessment, and likely consultation with neuro. Findings concerning for acute SAH. Radiology sends patient to ED. Repeat CT angio, again, shows “multifocal beaded and narrowing in circulation. Suggestive of cerebral vasoconstriction syndrome (RCVS).” After admission, pt is evaluated by neuro and undergoes angio, which finds mild diffused artery luminal stenosis consistent with RVCS. Intra-arterial verapamil administered into 3 cerebral arteries had marked improvement. Discharged on 90 days of oral verapamil with close PCP follow up. IMPACT/DISCUSSION: RVCS is evolving neurological condition. Given the low incidence of 3 in 1million patients, the understanding of RVCS continues to grow. RVCS commonly presents as severe thunderclap HA. Triggered by use of vasoconstricting medication, illicit drug, postpartum and grief. However, acute HA have a relatively large differential. Primarily diagnosed through imaging. As in this case, RVCS requires urgent interventions. To differentiate from benign etiologies of HA particularly as health services are limited or overwhelmed by COVID health epidemic, telehealth can play a pivotal role in increasing accessibility to reduce pt harm and potentially negative outcomes. Impact on practice: Red flag symptoms associated with thunderclap HA, even after improvement necessitate urgent evaluation of address the risk of RCVS. Thorough limited neuro examinations through video can assist in diagnostic differential development. As the COVID continues and impacts burden of healthcare, post pandemic incorporation of telehealth can play in acute settings with limited resources that can significantly reduce poor pt outcomes. CONCLUSION: Thorough investigations of presenting illness and medical history supply critical details in distinguishing atypical HA In the setting of limited resources and time constraints, virtual assessments provide sufficient information to support expedited workup.