Paradoxical Immune Reconstitution Inflammatory Syndrome in SARS-CoV-2 Infection After Improvement of Chemotherapy-Induced Aplasia.

Severe coronavirus disease 2019 (COVID-19) is known to manifest in two phases, with a potential worsening in the second week. The pathophysiology of the first phase is expected to be heavily influenced by viral replication while the second phase is thought to be primarily characterized by systemic inflammation. We present the case of a 42-year-old man hospitalized for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with a history of Philadelphia-positive chronic myeloid leukemia, diagnosed seven months earlier, proposed to bone marrow allotransplantation after refractory imatinib and dasatinib treatment. After an initial clinical and laboratory improvement, the patient got worse. A pulmonary CT scan showed worsening ground-glass opacities and multiple bilateral consolidations. Neutropenia was resolved, and on the same day, the patient developed progressive respiratory failure with rapidly increasing oxygen demand and distributive shock, requiring mechanical ventilation. Acute respiratory distress syndrome (ARDS) induced by paradoxical COVID-19 immune reconstitution inflammatory syndrome (IRIS) following chemotherapy-induced aplasia was equated. High-dose corticosteroid therapy was rapidly effective. IRIS occurs in patients with severe immunosuppression in response to rapid immune reconstitution and results in an uncontrolled inflammatory response to infectious agents that cause tissue damage. The inflammation associated with both IRIS and COVID-19 shares a common path in terms of immunological response. We hypothesize that in our patient, a hyperinflammation overlap exerted a synergistic effect, leading to the worsening of the disease.

COVID-19-Related Acalculous Groove Pancreatitis.

Introduction: Groove pancreatitis is a rare form of chronic pancreatitis. Its radiological diagnosis is challenging and it can be difficult to distinguish from pancreaticoduodenal malignancy. Case description: A 64-year-old woman was admitted to our internal medicine ward after she contracted severe COVID-19 pneumonia requiring mechanical ventilation. She presented with right upper abdominal pain, and a CT scan showed pancreaticoduodenal inflammatory tissue; malignancy was ruled out. Conclusion: Diagnosing groove pancreatitis is challenging and malignancy must be quickly excluded. No cases of COVID-19-associated groove pancreatitis have been previously described. LEARNING POINTS: Groove or paraduodenal pancreatitis is a rare form of chronic pancreatitis, and usually associated with alcohol use.The differential diagnosis includes pancreaticobiliary and duodenal malignancies.Radiological diagnosis is challenging and treatment is usually supportive.

Hepatic Coma Secondary to Fontan Conduit Thrombosis.

Introduction: The Fontan procedure is used to treat congenital heart defects and has improved long-term survival. Long-term complications include liver disease due to congestive hepatopathy. Fontan-related cirrhosis can manifest with ascites, gastrointestinal bleeding and encephalopathy. Case description: A 43-year-old man with history of Fontan surgery was admitted with COVID-19 pneumonia. There was rapid clinical and neurological deterioration, with coma and shock. CT imaging showed thrombosis of the Fontan conduit. The patient was successfully subjected to recanalization of the Fontan circulation, with progressive improvement of coma. Discussion: Fontan-associated liver disease is a major complication following the Fontan procedure. Clinicians must be aware of this pathology during patient follow-up. LEARNING POINTS: The Fontan procedure has improved the long-term survival of patients with single ventricle pathology.Fontan-associated liver disease is a result of haemodynamic changes associated with Fontan circulation; complications include hepatic encephalopathy and coma.Patients with Fontan circulation should be evaluated over time in order prevent and treat systemic complications.

SPONTANEOUS RENAL HAEMORRHAGE.

Introduction: Spontaneous renal haemorrhage is a rare condition with potentially serious complications. Case description: We describe a 76-year-old woman with a 3-day history of fever and malaise, with no associated trauma. She was admitted to our emergency room with signs of shock. A contrast-enhanced computed tomography scan revealed an extensive right kidney haematoma. Despite fast surgical management, the patient died less than 24 h after admission. Conclusion: Spontaneous renal haemorrhage should be quickly identified due to its fatal complications. Early diagnosis leads to a better prognosis. LEARNING POINTS: Spontaneous renal haemorrhage is a severe and rare condition in the absence of trauma and antithrombotic therapy.Contrast-enhanced abdominal CT scan is the gold standard for diagnosis.Surgical nephrectomy should be considered in haemodynamically unstable patients.Conservative therapy with intravenous resuscitation and blood products should be considered in stable patients.

ANTERIOR THALAMIC ISCHAEMIC STROKE SECONDARY TO CARDIOPULMONARY ARREST.

Introduction: Ischaemic anterior thalamic lesions are rare and can present with disturbances of behaviour and memory. We describe a patient with post-cardiac arrest thalamic stroke. Case description: A 63-year-old man presented with cardiac arrest, was resuscitated after receiving life support, and showed no lesions on computed tomography. Three days later, he presented with short-term memory disturbance and disorientation, with a de novo anterior thalamic lesion. Conclusion: The anterior thalamic nucleus, supplied by the posterior communicating artery, is part of the Papez circuit and has a role in modulating behaviour and memory. An anterior thalamic syndrome presents with no sensory-motor deficits. LEARNING POINTS: Anterior thalamic stroke is a rare condition and can present with disturbances of short-term memory and behaviour; it usually does not include any motor or sensory deficits.Thalamic stroke can occur due to global hypoxia, such as during cardiopulmonary arrest.

COVID-19 Myopericarditis in a Young Healthy Male.

SARS-CoV-2 infection can present in different clinical forms, most commonly as bilateral pneumonia, but also with pericardial/myocardial involvement. Cardiac involvement in COVID-19 is associated with worse outcomes. The authors report a case of myopericarditis as the primary manifestation of SARS-CoV-2 infection in a 20-year-old male patient with no known cardiovascular (CV) disorders or risk factors. The patient presented with pleuritic chest pain and high fever, with no respiratory symptoms. Electrocardiogram (ECG) and echocardiogram changes were consistent with pericarditis; concomitant elevation of cardiac enzymes revealed myocardial involvement. The patient had a slow but favourable evolution with no apparent impact on cardiac function. Other causes of myopericarditis were excluded and SARS-CoV-2 admitted as the most likely aetiological agent. This case highlights possible cardiac involvement in SARS-CoV-2 infection with little or no pulmonary disease in a young healthy patient. Such systemic and potentially troublesome manifestations of COVID-19 are increasingly being described. LEARNING POINTS: Acute myopericarditis is a possible manifestation of SARS-CoV-2 infection.SARS-CoV-2 cardiac involvement may occur both in older and in younger previously healthy subjects, and could be more frequent than expected.Further investigation should address the prevalence of myocardium and pericardium involvement in COVID-19 patients, as well as its complications, sequelae and prognostic value for both older and young patients.

Humoral Immune Response of SARS-CoV-2-Infected Patients with Cancer: Influencing Factors and Mechanisms.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients with cancer show worse outcomes compared with patients without cancer. The humoral immune response (HIR) of patients with cancer against SARS-CoV-2 is not well characterized. To better understand it, we conducted a serological study of hospitalized patients with cancer infected with SARS-CoV-2. MATERIALS AND METHODS: This was a unicentric, retrospective study enrolling adult patients with SARS-CoV-2 admitted to a central hospital from March 15 to June 17, 2020, whose serum samples were quantified for anti-SARS-CoV-2 receptor-binding domain or spike protein IgM, IgG, and IgA antibodies. The aims of the study were to assess the HIR to SARS-CoV-2; correlate it with different cancer types, stages, and treatments; clarify the interplay between the HIR and clinical outcomes of patients with cancer; and compare the HIR of SARS-CoV-2-infected patients with and without cancer. RESULTS: We included 72 SARS-CoV-2-positive subjects (19 with cancer, 53 controls). About 90% of controls revealed a robust serological response. Among patients with cancer, a strong response was verified in 57.9%, with 42.1% showing a persistently weak response. Treatment with chemotherapy within 14 days before positivity was the only factor statistically shown to be associated with persistently weak serological responses among patients with cancer. No significant differences in outcomes were observed between patients with strong and weak responses. All IgG, IgM, IgA, and total Ig antibody titers were significantly lower in patients with cancer compared with those without. CONCLUSION: A significant portion of patients with cancer develop a proper HIR. Recent chemotherapy treatment may be associated with weak serological responses among patients with cancer. Patients with cancer have a weaker SARS-CoV-2 antibody response compared with those without cancer. IMPLICATIONS FOR PRACTICE: These results place the spotlight on patients with cancer, particularly those actively treated with chemotherapy. These patients may potentially be more vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, so it is important to provide oncologists further theoretical support (with concrete examples and respective mechanistic correlations) for the decision of starting, maintaining, or stopping antineoplastic treatments (particularly chemotherapy) not only on noninfected but also on infected patients with cancer in accordance with cancer type, stage and prognosis, treatment agents, treatment setting, and SARS-CoV-2 infection risks.

The Effect of Chronic and Inhospital Exposure to Renin-Angiotensin System Inhibitors on the Outcome and Inflammatory State of Coronavirus Disease 2019 Adult Inpatients.

BACKGROUND: Controversies exist about the effect of renin-angiotensin system inhibitors (RASi) on coronavirus disease 2019 (COVID-19) outcome. The inhospital use of RASi and its effect on inflammatory sate are still poorly studied during the COVID-19 pandemic. OBJECTIVES: We aimed to compare the impact of previous and inhospital RASi exposure on the outcome and inflammatory response of COVID-19 patients. METHODS: Single-centre, ambispective analysis of hospitalized adult COVID-19 patients at Hospital de Santa Maria, Lisbon, between March and August 2020 was performed. We excluded asymptomatic patients and those admitted due to another disease. The primary outcome was inhospital all-cause mortality. Illness severity was assessed based on the development of acute respiratory distress syndrome/acute lung injury (ARDS/ALI), intensive care unit (ICU) admission, and need for invasive mechanical ventilation (IMV). We used C-reactive protein (CRP), ferritin, and interleukin 6 (IL-6) as surrogate markers of the inflammatory response. RESULTS: From a total of 432 patients, 279 were selected, among whom 133 (47.7%) were receiving a RASi. Chronic treatment with RASi was not associated with the risk of death (OR 1.24, 95% CI 0.66-2.31, p=0.500), ARDS/ALI development (OR 1.12, 95% CI 0.67-1.86, p=0.676), ICU admission (OR 1.11, 95% CI 0.67-1.84, p = 0.686), and IMV need (OR 1.03, 95% CI 0.58-1.84, p=0.917) in a univariable and multivariable analysis. Inhospital RASi withdrawing was associated with the risk of death (OR 4.38, 95% CI 1.11-17.21, p=0.035) and ARDS/ALI development (OR 4.33, 95% CI 1.49-12.6, p=0.007), the latter remaining significant after adjustment. Previous exposure to RASi was associated with lower CRP levels at admission (p=0.018). IL-6 levels were significantly higher in those patients whose RASi were stopped (p=0.024). CONCLUSION: Previous and inhospital exposure to RASi was not associated with mortality nor severity of COVID-19. This study supports current guidance on RASi management during the COVID-19 pandemic.

Organizing pneumonia and COVID-19: A report of two cases.

Organizing pneumonia (OP) is a sub-acute process of pulmonary tissue repair secondary to lung injury, defined histopathologically by intra-alveolar buds of granulation tissue within the lumen of distal pulmonary airspaces. It can be either cryptogenic or secondary (SOP) to different clinical conditions, namely infections. Despite being nonspecific, its diagnosis can be made by the association of clinical and imaging criteria. We report two cases of OP associated to SARS-CoV-2 pneumonia, admitted at a Portuguese tertiary hospital unit dedicated to COVID-19. Both patients presented with severe respiratory failure with need of invasive mechanical ventilation. After initial recovery, there was worsening of dyspnea and hypoxemic respiratory failure with increase in inflammatory markers. Chest CT revealed an OP pattern. Other conditions such as superinfection, auto-immune disease and iatrogenic etiology, were excluded and corticotherapy at a dose of 1 mg/kg/day was administered. Chest CT follow up of both our patients showed complete resolution of OP pattern, with mild to moderate residual pulmonary fibrosis without honeycombing. There is no OP to SARS-CoV-2 case series yet published describing the progress of patients after corticotherapy, although the association between systemic corticosteroids and lower all-cause mortality in patients with COVID-19 has been recently established. It is possible that, as has been described with other viruses, OP secondary to SARS-CoV-2 represents an immunological process after initial infection, presenting with elevation of inflammatory markers and cytokines storm in the bloodstream and lung tissue, which may explain the favorable response to corticosteroids.

Bird Fancier's Lung diagnosis in times of COVID-19 / Diagnóstico de la neumonitis de los avicultores en tiempos de la covid-19

No disponible

Immunosuppression Therapy in Acquired Hemophilia A: Pursuing an Optimal Regimen.

Acquired hemophilia A (AHA) is a rare bleeding disorder occurring mostly in elderly persons, caused by inhibition of factor VIII (FVIII). It is generally detected prior to surgery by an isolated prolonged activated partial thromboplastin time (aPTT) not correcting on mixing studies, with subsequent identification of reduced FVIII levels and presence of FVIII inhibitor. It is treated with hemostatics and immunosuppressants, which may increase the risk for life-threatening opportunistic infections. A 79-year-old woman with idiopathic acquired FVIII inhibition and severe bleeding presented with anemia, isolated and prolonged aPTT, low FVIII activity (<1%), and elevated FVIII inhibitor titer (471 Bethesda units per milliliter [BU/mL]). Initially, she was treated with recombinant activated factor VII and steroids. However, several hematomas appeared, one of which caused airway compression that required orotracheal intubation. Cyclophosphamide, rituximab (RTX), and activated prothrombin complex concentrate were initiated, resulting in clinical and laboratory resolution after five weeks. Cyclophosphamide and RTX were maintained for six and four weeks more, respectively. After 12 weeks of oral immunosuppression, the patient was readmitted due to antibiotic-resistant Pseudomonas aeruginosa sepsis, which resulted in death. Infection secondary to immunosuppression is the leading cause of death of patients with AHA. In AHA, combination therapy was shown to be more effective than monotherapy, but it was also identified to increase the risk of infection. Age, FVIII activity <1%, and FVIII inhibitor titers >20 BU are predictors of adverse events and poor prognosis in AHA patients. Additional studies are needed to clarify the ideal drug regimens and the need for prophylactic antibiotics in this population.

Exploring local and global regression models to estimate the spatial variability of Zika and Chikungunya cases in Recife, Brazil.

INTRODUCTION: In this study, we aim to compare spatial statistic models to estimate the spatial distribution of Zika and Chikungunya infections in the city of Recife, Brazil. We also aim to establish the relationship between the diseases and the analyzed geographical conditions. METHODS: The models were defined by combining three categories: type of spatial unit, calculation of the dependent variable format, and estimation methods (Geographical Weighted Regression [GWR] and Ordinary Least Square [OLS]). We identified the most accurate model to estimate the spatial distribution of the diseases. After selecting the model that provided best results, the relationship between the geographical conditions and the incidence of the diseases was analyzed. RESULTS: It was observed that the matrix of 100 meters (as the spatial unit) showed the highest efficiency to estimate the diseases. The best results were observed in the models that utilized the kernel density estimation (as the calculation of the dependent variable). In all models, the GWR method showed the best results. By considering the OLS coefficient values, it was observed that all geographical conditions are related to the incidence of Zika and Chikungunya, while the GWR coefficient values showed where this relationship was more noticeable. CONCLUSIONS: The model that utilized the combination of the matrix of 100 meters, kernel density estimation (as the calculation of the dependent variable) and GWR method showed the highest efficiency in estimating the spatial distribution of the diseases. The coefficient values showed that all analyzed geographical conditions are related to the illnesses' incidence.

Exploring local and global regression models to estimate the spatial variability of Zika and Chikungunya cases in Recife, Brazil

Abstract INTRODUCTION: In this study, we aim to compare spatial statistic models to estimate the spatial distribution of Zika and Chikungunya infections in the city of Recife, Brazil. We also aim to establish the relationship between the diseases and the analyzed geographical conditions. METHODS: The models were defined by combining three categories: type of spatial unit, calculation of the dependent variable format, and estimation methods (Geographical Weighted Regression [GWR] and Ordinary Least Square [OLS]). We identified the most accurate model to estimate the spatial distribution of the diseases. After selecting the model that provided best results, the relationship between the geographical conditions and the incidence of the diseases was analyzed. RESULTS: It was observed that the matrix of 100 meters (as the spatial unit) showed the highest efficiency to estimate the diseases. The best results were observed in the models that utilized the kernel density estimation (as the calculation of the dependent variable). In all models, the GWR method showed the best results. By considering the OLS coefficient values, it was observed that all geographical conditions are related to the incidence of Zika and Chikungunya, while the GWR coefficient values showed where this relationship was more noticeable. CONCLUSIONS: The model that utilized the combination of the matrix of 100 meters, kernel density estimation (as the calculation of the dependent variable) and GWR method showed the highest efficiency in estimating the spatial distribution of the diseases. The coefficient values showed that all analyzed geographical conditions are related to the illnesses' incidence.

Felty's syndrome - a rare case of febrile neutropenia.

Felty's syndrome (rheumatoid arthritis with neutropenia and splenomegaly) is a rare condition with poor long-term prognosis, mainly as a result of severe infection risk. An effective treatment strategy has not been developed so far and current treatment options are based upon case reports, small series and clinical experience since no randomized clinical trials are available. The authors describe the case of a 53-year-old female patient with a 14-year history of rheumatoid arthritis presenting with fever, neutropenia and splenomegaly. Broad-spectrum antibiotics and granulocyte colony-stimulating factor were administered with good clinical outcome and low dose methotrexate for disease control was successfully initiated after discharge. We would like to highlight the importance of being aware of this syndrome in the differential diagnosis of long term rheumatoid arthritis patients presenting with febrile neutropenia.

Correlação entre fragilidade e força de preensão manual em idosos / Correlation between fragility and manual pressing force in elderly

Objetivo: verificar a relação entre IMC e força de preensão com os critérios de classificação da fragilidade. Método: trata-se de um estudo quantitativo, de campo, exploratório e descritivo, por meio de um questionário com 300 idosos. Os dados foram registrados no programa SPSS, versão 20, e analisados por estatística descritiva e inferencial. Resultados: observaram-se associações do sexo com a fragilidade em tempo de caminhada, força de preensão e nível de atividade como, também, na correlação da estrutura com a força de preensão e da massa corporal com a força de preensão para os idosos e as idosas. Por fim, identificaram-se diferenças estatísticas entre a fragilidade em força de preensão, massa corporal e estatura dos homens. Conclusão: com relação aos componentes de fragilidade, houve diferença entre os sexos. As mulheres apresentaram fragilidade para a variável tempo de caminhada e os idosos foram mais frágeis para a força de preensão e o nível de atividade física.(AU)

Fatty Acid Cysteamine Conjugates as Novel and Potent Autophagy Activators That Enhance the Correction of Misfolded F508del-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR).

A depressed autophagy has previously been reported in cystic fibrosis patients with the common F508del-CFTR mutation. This report describes the synthesis and preliminary biological characterization of a novel series of autophagy activators involving fatty acid cysteamine conjugates. These molecular entities were synthesized by first covalently linking cysteamine to docosahexaenoic acid. The resulting conjugate 1 synergistically activated autophagy in primary homozygous F508del-CFTR human bronchial epithelial (hBE) cells at submicromolar concentrations. When conjugate 1 was used in combination with the corrector lumacaftor and the potentiator ivacaftor, it showed an additive effect, as measured by the increase in the chloride current in a functional assay. In order to obtain a more stable form for oral dosing, the sulfhydryl group in conjugate 1 was converted into a functionalized disulfide moiety. The resulting conjugate 5 is orally bioavailable in the mouse, rat, and dog and allows a sustained delivery of the biologically active conjugate 1.

[High-sensitivity C-reactive protein as a biomarker of risk in coronary artery disease]. / Proteína C reativa de alta sensibilidade como biomarcador de risco na doença coronária.

Vascular inflammation plays a crucial role in the pathogenesis of atherosclerosis and mediates various stages of atherosclerotic plaque development, from lipid streak formation to the plaque rupture and destabilization that precedes the clinical syndromes of cardiovascular disease. Inflammatory biomarkers constitute valuable tools to study this process, enabling the effects of different therapeutic interventions to be assessed. Currently, C-reactive protein (CRP) determined by high-sensitivity methods (hs-CRP) is the most extensively studied biomarker. Data regarding hs-CRP and cardiovascular risk, though largely consistent, are of unclear clinical relevance. This article provides a comprehensive review of current knowledge concerning cardiovascular risk and hs-CRP, and concludes with an evidence-based analysis of the current role of hs-CRP in cardiovascular risk assessment.

Oral vanoxerine prevents reinduction of atrial tachyarrhythmias: preliminary results.

BACKGROUND: Vanoxerine is a promising, new, investigational antiarrhythmic drug. The purpose of this study was to test the hypothesis that oral dosing of vanoxerine would first terminate induced atrial flutter (AFL) and atrial fibrillation (AF), and then prevent their reinduction. METHODS: In 5 dogs with sterile pericarditis, on the fourth day after creating the pericarditis, we performed electrophysiologic (EP) studies at baseline, measuring atrial excitability, refractoriness (AERP), and conduction time (CT) when pacing from the right atrial appendage, Bachmann's bundle (BB), and the posteroinferior left atrium at cycle lengths (CLs) of 400, 300, and 200 ms. Then, after induction of AFL or AF, all dogs received hourly oral doses of vanoxerine: 90 mg, followed by 180 mg and 270 mg. Blood was obtained to determine plasma vanoxerine concentrations at baseline, every 30 minutes, when neither AFL nor AF were inducible, and, finally, 1 hour after the 270 mg dose. Then we repeated the baseline EP studies. RESULTS: Four dogs had inducible, sustained AFL, and 1 dog only had induced, nonsustained AF. In 4 AFL episodes, oral vanoxerine terminated the AFL and then rendered it noninducible after an average of 111 minutes (range 75-180 minutes) after the first dose was administered. The mean vanoxerine plasma level at the point of noninducibility was 84 ng/mL, with a narrow range of 76-99 ng/mL. In the dog with induced, nonsustained AF, it was no longer inducible at a drug level of 75 ng/mL. Vanoxerine did not significantly (1) prolong the AERP except at BB, and then only at the faster pacing CLs; (2) change atrial excitability thresholds; (3) prolong atrial conduction time, the PR interval, the QRS complex or the QT interval. CONCLUSIONS: Orally administered vanoxerine effectively terminated AFL and rendered it noninducible. It also suppressed inducibility of nonsustained AF. These effects occurred at consistent plasma drug levels. Vanoxerine's insignificant or minimal effects on measured electrophysiologic parameters are consistent with little proarrhythmic risk.