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Petitjeans, Fabrice, and Luc Quintin. "Noninvasive Failure in De Novo Acute Hypoxemic Respiratory Failure." Critical Care Medicine 44, no. 11 (November 2016): e1153-e1154. http://dx.doi.org/10.1097/ccm.0000000000001967.
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Carteaux, Guillaume, Teresa Millán-Guilarte, Nicolas De Prost, Keyvan Razazi, Shariq Abid, Arnaud W. Thille, Frédérique Schortgen, Laurent Brochard, Christian Brun-Buisson, and Armand Mekontso Dessap. "Failure of Noninvasive Ventilation for De Novo Acute Hypoxemic Respiratory Failure." Critical Care Medicine 44, no. 2 (February 2016): 282–90. http://dx.doi.org/10.1097/ccm.0000000000001379.
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García-de-Acilu, Marina, Bhakti K. Patel, and Oriol Roca. "Noninvasive approach for de novo acute hypoxemic respiratory failure." Current Opinion in Critical Care 25, no. 1 (February 2019): 54–62. http://dx.doi.org/10.1097/mcc.0000000000000570.
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Costa, Bárbara. "Ventilação Não-Invasiva na Falência Respiratória Aguda." Medicina Interna 28, no. 2 (June 18, 2021): 133–39. http://dx.doi.org/10.24950/o/320/20/2/2021.
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Introdução: A ventilação não invasiva (VNI) é uma opção válida, ainda que não consensual, no tratamento de doentes com falência respiratória aguda. O presente artigo tem o objetivo de identificar fatores preditores de resposta à VNI neste grupo de doentes. Métodos: Estudo retrospectivo longitudinal que incluiu todos os doentes admitidos numa unidade de cuidados intensivos nos anos 2016 e 2017, nos quais a VNI foi utilizada no decurso de falência respiratória aguda de novo (PaO2/ FiO2 < 200). Foram incluídos doentes com pneumonia adquirida na comunidade (PAC) e síndrome da dificuldade respiratória aguda (SDRA) e comparados doentes com resposta à VNI com os não respondedores. Resultados: Entre 2016 e 2017, 83 doentes com falência respiratória aguda de novo foram tratados com VNI. Destes, 50 (60%) foram tratados com sucesso. A causa mais comum de falência respiratória foi a PAC, que registou valores de resposta à VNI de 70%. Doentes respondedores à terapêutica de ventilação não invasiva apresentaram scores de gravidade (APACHE 2; SAPS 2; SOFA) inferiores à admissão (17,5; 37,5; 6 vs 22; 48; 9, p=0,014, p<0,01 e p<0,01, respetivamente). Os não respondedores apresentaram valores significativamente inferiores de pH arterial (7,35 vs 7,42, p<0,01), rácio PaO2/FiO2 (118 vs 145, p=0,03), e valores significativamente superiores de lactato sérico (2,2 vs 1,46, p<0,01) assim como maior necessidade de suporte vasopressor (51,5% vs 30%, p=0,04). No que diz respeito a dados gasimétricos após início de VNI, o rácio PaO2/FiO2 registou um aumento superior e estatisticamente significativo no grupo de doentes com resposta à VNI (+53, p<0,01 vs +14, p=0,09). Conclusão: A VNI foi eficaz como estratégia ventilatória em 60% dos doentes com falência respiratória aguda. Os doentes que aparentam ter maior probabilidade de resposta à introdução da VNI são: doentes com PAC, com ou sem SDRA moderado (em detrimento do SDRA severo), doentes sem acidemia respiratória e doentes sem hiperlactacidemia e/ou necessidade de suporte vasopressor. A melhoria do ratio PaO2/FiO2 após as primeiras duas horas de VNI parece ser um bom preditor de sucesso.
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Park, Sunghoon. "Treatment of acute respiratory failure: noninvasive mechanical ventilation." Journal of the Korean Medical Association 65, no. 3 (March 10, 2022): 144–50. http://dx.doi.org/10.5124/jkma.2022.65.3.144.
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Background: Noninvasive ventilation (NIV) has been an important strategy to support patients with respiratory failure, while preventing complications assorted with invasive mechanical ventilation. Physicians need to be aware of the various roles of NIV and the challenges encountered in clinical practice.Current Concepts: Traditionally, the application of NIV has been well-known to be associated with reduced mortality in patients with chronic obstructive pulmonary disease (COPD) or acute pulmonary edema and those suffering from acute respiratory failure. However, despite some positive results of NIV treatment in patients with de novo hypoxemic respiratory failure such as acute pneumonia or acute respiratory distress syndrome, NIV failure (or delayed intubation) can have deleterious effects on patients outcomes. Besides, the aggravation of lung injury should also be taken into consideration when applied to patients exhibiting high respiratory drive. Nonetheless, NIV has potential for wide applications in various clinical situations such as facilitation of ventilator weaning, post-operative respiratory failure, or palliative treatment.Discussion and Conclusion: In addition to the strong evidence in patients with acute respiratory failure due to COPD or acute pulmonary edema, the NIV treatment can be potentially used for various clinical conditions. However, compared to European countries, the prevalence of NIV use continues to remain lower in South Korea. Nevertheless, when applied in appropriately selected patients in a timely manner, NIV treatment can be associated with improved patient outcomes.
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Zayed, Yazan, Mahmoud Barbarawi, Babikir Kheiri, Tarek Haykal, Adam Chahine, Laith Rashdan, Harsukh Dhillon, Sina Khaneki, Ghassan Bachuwa, and Elfateh Seedahmed. "Initial Noninvasive Oxygenation Strategies in Subjects With De Novo Acute Hypoxemic Respiratory Failure." Respiratory Care 64, no. 11 (October 25, 2019): 1433–44. http://dx.doi.org/10.4187/respcare.06981.
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Spicuzza, Lucia, and Matteo Schisano. "High-flow nasal cannula oxygen therapy as an emerging option for respiratory failure: the present and the future." Therapeutic Advances in Chronic Disease 11 (January 2020): 204062232092010. http://dx.doi.org/10.1177/2040622320920106.
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Conventional oxygen therapy (COT) and noninvasive ventilation (NIV) have been considered for decades as frontline treatment for acute or chronic respiratory failure. However, COT can be insufficient in severe hypoxaemia whereas NIV, although highly effective, is poorly tolerated by patients and its use requires a specific expertise. High-flow nasal cannula (HFNC) is an emerging technique, designed to provide oxygen at high flows with an optimal degree of heat and humidification, which is well tolerated and easy to use in all clinical settings. Physiologically, HFNC reduces the anatomical dead space and improves carbon dioxide wash-out, reduces the work of breathing, and generates a positive end-expiratory pressure and a constant fraction of inspired oxygen. Clinically, HFNC effectively reduces dyspnoea and improves oxygenation in respiratory failure from a variety of aetiologies, thus avoiding escalation to more invasive supports. In recent years it has been adopted to treat de novo hypoxaemic respiratory failure, exacerbation of chronic obstructive pulmonary disease (COPD), postintubation hypoxaemia and used for palliative respiratory care. While the use of HFNC in acute respiratory failure is now routine as an alternative to COT and sometimes NIV, new potential applications in patients with chronic respiratory diseases (e.g. domiciliary treatment of patients with stable COPD), are currently under evaluation and will become a topic of great interest in the coming years.
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Lindstedt, Sandra, Edgar Grins, Hillevi Larsson, Johan Nilsson, Hamid Akbarshahi, Iran Silva, Snejana Hyllen, et al. "Lung transplant after 6 months on ECMO support for SARS-CoV-2-induced ARDS complicated by severe antibody-mediated rejection." BMJ Open Respiratory Research 8, no. 1 (September 2021): e001036. http://dx.doi.org/10.1136/bmjresp-2021-001036.
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There have been a few reports of successful lung transplantation (LTx) in patients with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS); however, all reports were with rather short follow-up. Here we present a 62-year-old man without prior lung diseases. Following SARS-CoV-2-induced ARDS and 6 months of extracorporeal membrane oxygenation, he underwent LTx. 3 months post-transplantation he developed acute hypoxia requiring emergency intubation. Chest imaging showed acute rejection, and de novo DQ8-DSA was discovered. He was treated with a high dose of corticosteroids and plasmapheresis and was extubated 4 days later, yet the de novo DQ8-DSA remained. After sessions of plasmapheresis and rituximab, the levels of de novo DQ8-DSA remained unchanged. Nine months post-transplantation the patient died of respiratory failure. We herein discuss the decision to transplant, the transplantation itself and the postoperative course with severe antibody-mediated rejection. In addition, we evaluated the histological changes of the explanted lungs and compared these with end-stage idiopathic pulmonary fibrosis tissue, where both similarities and differences are seen. With the current case experience, one might consider close monitoring regarding DSA, and gives further support that LTx should only be considered for very carefully selected patients.
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Coudroy, Rémi, Jean-Pierre Frat, Stephan Ehrmann, Frédéric Pène, Nicolas Terzi, Maxens Decavèle, Gwenaël Prat, et al. "High-flow nasal oxygen therapy alone or with non-invasive ventilation in immunocompromised patients admitted to ICU for acute hypoxemic respiratory failure: the randomised multicentre controlled FLORALI-IM protocol." BMJ Open 9, no. 8 (August 2019): e029798. http://dx.doi.org/10.1136/bmjopen-2019-029798.
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IntroductionNon-invasive ventilation (NIV) is recommended as first-line therapy in respiratory failure of critically ill immunocompromised patients as it can decrease intubation and mortality rates as compared with standard oxygen. However, its recommendation is only conditional. Indeed, the use of NIV in this setting has been challenged recently based on results of trials finding similar outcomes with or without NIV or even deleterious effects of NIV. To date, NIV has been compared with standard oxygen but not to high-flow nasal oxygen therapy (HFOT) in immunocompromised patients. Several studies have found lower mortality rates using HFOT alone than when using HFOT with NIV sessions in patients with de novo respiratory failure, and even in immunocompromised patients. We are hypothesising that HFOT alone is more effective than HFOT with NIV sessions and reduces mortality of immunocompromised patients with acute hypoxemic respiratory failure.Methods and analysisThis study is an investigator-initiated, multicentre randomised controlled trial comparing HFOT alone or with NIV in immunocompromised patients admitted to intensive care unit (ICU) for severe acute hypoxemic respiratory failure. Around 280 patients will be randomised with a 1:1 ratio in two groups. The primary outcome is the mortality rate at day 28 after inclusion. Secondary outcomes include the rate of intubation in each group, length of ICU and hospital stay and mortality up to day 180.Ethics and disseminationThe study has been approved by the ethics committee and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT02978300
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Boulos, Peter K., Scott V. Freeman, Timothy D. Henry, Ehtisham Mahmud, and John C. Messenger. "Interaction of COVID-19 With Common Cardiovascular Disorders." Circulation Research 132, no. 10 (May 12, 2023): 1259–71. http://dx.doi.org/10.1161/circresaha.122.321952.
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The onset and widespread dissemination of the severe acute respiratory syndrome coronavirus-2 in late 2019 impacted the world in a way not seen since the 1918 H1N1 pandemic, colloquially known as the Spanish Flu. Much like the Spanish Flu, which was observed to disproportionately impact young adults, it became clear in the early days of the coronavirus disease 2019 (COVID-19) pandemic that certain groups appeared to be at higher risk for severe illness once infected. One such group that immediately came to the forefront and garnered international attention was patients with preexisting cardiovascular disease. Here, we examine the available literature describing the interaction of COVID-19 with a myriad of cardiovascular conditions and diseases, paying particular attention to patients diagnosed with arrythmias, heart failure, and coronary artery disease. We further discuss the association of acute COVID-19 with de novo cardiovascular disease, including myocardial infarction due to coronary thrombosis, myocarditis, and new onset arrhythmias. We will evaluate various biochemical theories to explain these findings, including possible mechanisms of direct myocardial injury caused by the severe acute respiratory syndrome coronavirus-2 virus at the cellular level. Finally, we will discuss the strategies employed by numerous groups and governing bodies within the cardiovascular disease community to address the unprecedented challenges posed to the care of our most vulnerable patients, including heart transplant recipients, end-stage heart failure patients, and patients suffering from acute coronary syndromes, during the early days and height of the COVID-19 pandemic.
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Maquet, Emilie, Sabine Costagliola, Jasmine Parma, Christiane Christophe-Hobertus, Luc L. Oligny, Jean-Christophe Fournet, Yves Robitaille, et al. "Lethal Respiratory Failure and Mild Primary Hypothyroidism in a Term Girl with a de Novo Heterozygous Mutation in the TITF1/NKX2.1 Gene." Journal of Clinical Endocrinology & Metabolism 94, no. 1 (January 1, 2009): 197–203. http://dx.doi.org/10.1210/jc.2008-1402.
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Abstract Context: Thyroid transcription factor 1 (TITF1/NKX2.1) is expressed in the thyroid, lung, ventral forebrain, and pituitary. In the lung, TITF1/NKX2.1 activates the expression of genes critical for lung development and function. Titf/Nkx2.1−/− mice have pituitary and thyroid aplasia but also impairment of pulmonary branching. Humans with heterozygous TITF1/NKX2.1 mutations present with various combinations of primary hypothyroidism, respiratory distress, and neurological disorders. Objective: The objective of the study was to report clinical and molecular studies of the first patient with lethal neonatal respiratory distress from a novel heterozygous TITF1/NKX2.1 mutation. Participant: This girl, the first child of healthy nonconsanguineous French-Canadian parents, was born at 41 wk. Birth weight was 3460 g and Apgar scores were normal. Soon after birth, she developed acute respiratory failure with pulmonary hypertension. At neonatal screening on the second day of life, TSH was 31 mU/liter (N <15) and total T4 245 nmol/liter (N = 120–350). Despite mechanical ventilation, thyroxine, surfactant, and pulmonary vasodilators, the patient died on the 40th day. Results: Histopathology revealed pulmonary tissue with low alveolar counts. The thyroid was normal. Sequencing of the patient’s lymphocyte DNA revealed a novel heterozygous TITF1/NKX2.1 mutation (I207F). This mutation was not found in either parent. In vitro, the mutant TITF-1 had reduced DNA binding and transactivation capacity. Conclusion: This is the first reported case of a heterozygous TITF1/NKX2.1 mutation leading to neonatal death from respiratory failure. The association of severe unexplained respiratory distress in a term neonate with mild primary hypothyroidism is the clue that led to the diagnosis.
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Peigh, Graham, Marysa V. Leya, Jayson R. Baman, Eric P. Cantey, Bradley P. Knight, and James D. Flaherty. "Novel coronavirus 19 (COVID-19) associated sinus node dysfunction: a case series." European Heart Journal - Case Reports 4, FI1 (May 8, 2020): 1–6. http://dx.doi.org/10.1093/ehjcr/ytaa132.
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Abstract Background Novel coronavirus-19 disease (COVID-19) is associated with significant cardiovascular morbidity and mortality. To date, there have not been reports of sinus node dysfunction (SND) associated with COVID-19. This case series describes clinical characteristics, potential mechanisms, and short-term outcomes of COVID-19 patients who experience de novo SND. Case summary We present two cases of new-onset SND in patients recently diagnosed with COVID-19. Patient 1 is a 70-year-old female with no major past medical history who was intubated for acute hypoxic respiratory failure secondary to COVID-19 pneumonia and developed new-onset sinus bradycardia without a compensatory increase in heart rate in response to relative hypotension. Patient 2 is an 81-year-old male with a past medical history of an ascending aortic aneurysm, hypertension, and obstructive sleep apnoea who required intubation for COVID-19-induced acute hypoxic respiratory failure and exhibited new-onset sinus bradycardia followed by numerous episodes of haemodynamically significant accelerated idioventricular rhythm. Two weeks following the onset of SND, both patients remain in sinus bradycardia. Discussion COVID-19-associated SND has not previously been described. The potential mechanisms for SND in patients with COVID-19 include myocardial inflammation or direct viral infiltration. Patients diagnosed with COVID-19 should be monitored closely for the development of bradyarrhythmia and haemodynamic instability.
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Novikova, A. A., G. A. Klyasova, E. O. Gribanova, V. A. Okhmat, V. V. Ryzhko, and V. G. Savchenko. "Infectious complications in patients with multiple myeloma on first chemotherapy cycle." Oncohematology 13, no. 3 (October 27, 2018): 63–75. http://dx.doi.org/10.17650/1818-8346-2018-13-3-63-75.
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The aim of the study was to evaluate the profile and risk factors for acquisition of infections in patients with de novo multiple myeloma (MM) on the 1st chemotherapy cycle (CC).Materials and methods. Study included patients with de novo MM undergoing chemotherapy from January 2013 till November 2017 in National Research Center for Hematology, Russia.Results. A total of 156 patients with de novo MM (median age 61 years) were included in the study. Follow-up period was 21–82 days (median 26 days), first CC contained bоrtezomib. Infections occurred in 77 (49.4 %) of patients with MM, from them 29 (37.7 %) – on admission, 48 (62.3 %) – throughout treatment. Solitary infections were in 47 (61%) of patients, multiple infections – in 30 (39 %) of patients. The most prevalent type of infection was pneumonia (62.3 %), followed by urinary tract infections (27.3 %) and herpesvirus infections (24.7 %). 30% of patients with infections were afebrile. Significant risk factors associated with infections at admission and during CC were ECOG score 4, anemia, hypercalcemia, humoral immunodeficiency, admission from other hospital, use of antibiotics prior to first CC. Additional risk factors for infections at admission were Durie–Salmon stage III MM, paresis, lower extremity paraplegia and dysfunction of the pelvic organs, whereas during treatment – ISS stage III MM and renal failure. Infections were uncommon in patients with ISS stage I MM (7.8 %). Mortality after 1st CC was 1.9 % caused by pneumonia and acute respiratory failure.Conclusions. Patients with de novo MM undergoing 1st CC had high incidence of infections with a prevalence of pneumonia. Factors associated with infections were stage III MM, serious illness, admission from other hospital, humoral immunodeficiency, and renal failure.
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Ilieva, V., T. Mihalova, Yo Yamakova, R. Petkov, and B. Velev. "Cost-Minimization Analysis of Non-Invasive and Invasive Mechanical Ventilation for De Novo Acute Hypoxemic Respiratory Failure in an Eastern European Setting." Acta Medica Bulgarica 46, no. 1 (February 1, 2019): 17–20. http://dx.doi.org/10.2478/amb-2019-0003.
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Abstract Introduction: In the light of constant pressure for minimizing healthcare costs we made a cost-minimization analysis comparing invasive mechanical ventilation (IMV) and non-invasive ventilation (NIV) as treatment for hypoxemic acute respiratory failure (ARF). Aim: The primary objective was to estimate the direct medical costs generated by a patient on IMV and NIV. A secondary objective was to identify which aspect of the treatment was most expensive. Material and Methods: This is a single center retrospective study including 36 patients on mechanical ventilation due to hypoxemic ARF, separated in two groups – NIV (n = 18) and IMV (n = 18). We calculated all direct medical costs in Euro and compared them statistically. Results: On admission the PaO2/FiO2 and SAPS II score were comparable in both groups. We observed a significant difference in the costs per patient for drug treatment (NIV: 616.07; IQR: 236.68, IMV:1456.18; IQR:1741.95, p = 0.005), consumables (NIV: 16.47; IQR: 21.44, IMV: 98.79; IQR: 81.52, p < 0.001) and diagnostic tests (NIV: 351; IQR: 183.88, IMV: 765.69; IQR: 851.43, p < 0.001). We also computed the costs per patient per day and there was a significant difference in the costs in all above listed categories. In both groups the highest costs were for drug treatment – around 61%. Conclusions: In the setting of hypoxemic ARF NIV reduces significantly the direct medical costs of treatment in comparison to IMV. The decreased costs in NIV are not associated with severity of disease according to the respiratory quotient and SAPS II score.
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Schellongowski, Peter, Thomas Staudinger, Klaus Laczika, Gottfried Locker, Andja Bojic, Ulrich Jaeger, Peter Valent, and Wolfgang R. Sperr. "Prognostic Factors Predicting Survival in De Novo AML Patients Requiring Intensive Care." Blood 110, no. 11 (November 16, 2007): 2860. http://dx.doi.org/10.1182/blood.v110.11.2860.2860.
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Abstract Acute myeloid leukemia (AML) is an acute life-threatening disease with variable clinical presentation. In this study, the percentage of patients (pts) with de novo AML requiring intensive care prior or during induction chemotherapy (ICT), as well as prognostic factors predicting survival in these pts were analyzed. A total of 471 consecutive pts (median age 62 years; range: 16–92) seen at the Vienna University Hospital between 1994–2006 were enrolled. In pts requiring critical care, simplified acute physiology score (SAPS) II as well as the need for invasive mechanical ventilation (IMV), vasopressor support (VP), and disease related markers were recorded at the intensive care unit (ICU). Eighty six percent (n=404) of all patients were eligible for ICT. Fifty four of these 404 patients (13.4%) required critical care prior or during ICT (median SAPS II 64, range 30–107), primarily due to respiratory failure (26 pts=48%) or life-threatening bleeding (12 pts=22%). Comparing ICU and non-ICU-pts with regard to disease-related markers, differences were found in white blood cell counts, WBC (ICU: 16.8 G/L; non-ICU: 11.9 G/L; p=0.084), whereas no differences were found regarding age, plt, and LDH. Forty pts received IMV (63%), and 32 VP (59%). The ICU survival rate was 41%. Significant prognostic factors with respect to ICU-survival were higher SAPS II scores (p<0.05), the need of IMV (p<0.05), and need of VP (p<0.05), whereas CRP, WBC, age, karyotype, or the time of admission to ICU (prior or during ICT) were not of prognostic significance. Survival was favourable in non-ICU-pts (median: 4.14 months; 22% at 8 years) compared to ICU-pts (median: 1.2 months; 9% at 8 years; p<0.05). Similar results were obtained when analyzing the overall survival, OS (non-ICU-pts: median: 4.1 months; 22% at 8 years; ICU-pts: median: 1.6 months; 12% at 8 years; p<0.05). Interestingly, the continuous complete remission, CCR (non-ICU-pts: 37% at 6 years; ICU-pts: 31% at 6 years; p>0.5) as well as OS of patients who had survived the first 28 days of therapy (non-ICU-pts: 29% at 6 years; ICU-pts: 20% at 6 years; p>0.5) did not differ significantly between ICU-pts and non-ICU-pts. With regard to OS, multivariate analysis revealed that ICU admission was an independent adverse prognostic parameter, as was a higher WBC, advanced age, higher LDH, or unfavourable karyotype. With regard to CCR, age and karyotype were independent prognostic variables, whereas ICU-admission was not of prognostic significance. In summary, 13% of pts with de novo AML eligible for ICT required critical care, primarily due to respiratory failure or bleeding. The probability of survival and OS of ICU-pts is inferior compared to non-ICU-pts. However, with regard to CCR and OS of pts surviving 28 days, no differences were observed between ICU-pts and non-ICU-pts. These observations favour the assumption that critical care should be considered in all de novo AML pts eligible for ICT.
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Mistrulli, Raffaella, Armando Ferrera, Melwyn Luis Muthukkattil, Massimo Volpe, Emanuele Barbato, and Allegra Battistoni. "SARS-CoV-2 Related Myocarditis: What We Know So Far." Journal of Clinical Medicine 12, no. 14 (July 15, 2023): 4700. http://dx.doi.org/10.3390/jcm12144700.
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A minority of patients with severe acute respiratory syndrome coronavirus 2 (COVID-19) develop cardiovascular complications, such as acute cardiac lesions with elevated troponins, de novo systolic heart failure, pericardial effusion and, rarely, acute myocarditis. The prevalence of COVID-19-related myocarditis ranges from 10 to 105 cases per 100,000 COVID-19-infected individuals, with a male predominance (58%) and a median age of 50 years. The etiopathogenetic mechanism is currently unclear, but may involve direct virus-mediated damage or an exaggerated immune response to the virus. Mortality is high, as fulminant myocarditis (FM) develops very often in the form of cardiogenic shock and ventricular arrhythmias. Hence, medical therapy with ACE inhibitors and beta-blockers may not always be sufficient, in which case inotropic and immunosuppressive drugs, most commonly corticosteroids, may be necessary. In this review we analyze the current data on COVID-19 myocarditis, management strategies and therapy, with a brief description of COVID-19 vaccine-associated myocarditis to help clinicians dealing with this peculiar form of myocarditis.
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Lodhi, F. A. K., T. Akcan, J. N. Mojarrab, S. Sajjad, and R. Blonsky. "A Case of De Novo Antiglomerular Basement Membrane Disease Presenting during Pregnancy." Case Reports in Nephrology 2021 (March 17, 2021): 1–5. http://dx.doi.org/10.1155/2021/5539205.
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Background. Acute kidney injury (AKI) requiring dialysis during pregnancy is uncommon. We present a case of a young female diagnosed with antiglomerular basement membrane (anti-GBM) disease during pregnancy. Case Presentation. A 23-year-old woman approximately 15 weeks pregnant experienced weakness, nausea, vomiting, and anorexia for one week and anuria for 48 hours. No known drug allergies and no significant social or family history for kidney or genitourinary disease were reported. Laboratory analysis revealed anemia, life-threatening hyperkalemia, AKI, and elevated antiglomerular basement membrane (GBM) antibodies. Renal biopsy revealed 100% cellular crescents, confirming the diagnosis. The patient was treated using plasmapheresis and methylprednisolone followed by oral steroids, azathioprine, and tacrolimus. At 24 weeks and 4 days of gestation, the patient had hypoxic respiratory failure as well as preterm premature rupture of membranes. Due to the development of infection and lack of renal recovery, immunosuppression was discontinued. At 28 weeks and 0 days of gestation, the patient developed uncontrollable hypertension requiring emergent delivery. Postpartum, her hypertension improved without signs of preeclampsia though still requires dialysis. Discussion. Pregnancy presents a unique challenge for providers treating patients with anti-GBM disease. Fetal safety should be considered and risks thoroughly discussed with the patient when choosing an immunosuppressive regimen for this condition.
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Pandor, Abdullah, Praveen Thokala, Steve Goodacre, Edith Poku, John W. Stevens, Shijie Ren, Anna Cantrell, Gavin D. Perkins, Matt Ward, and Jerry Penn-Ashman. "Pre-hospital non-invasive ventilation for acute respiratory failure: a systematic review and cost-effectiveness evaluation." Health Technology Assessment 19, no. 42 (June 2015): 1–102. http://dx.doi.org/10.3310/hta19420.
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BackgroundNon-invasive ventilation (NIV), in the form of continuous positive airway pressure (CPAP) or bilevel inspiratory positive airway pressure (BiPAP), is used in hospital to treat patients with acute respiratory failure. Pre-hospital NIV may be more effective than in-hospital NIV but requires additional ambulance service resources.ObjectivesWe aimed to determine the clinical effectiveness and cost-effectiveness of pre-hospital NIV compared with usual care for adults presenting to the emergency services with acute respiratory failure and to identify priorities for future research.Data sourcesFourteen electronic databases and research registers (including MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, and Cumulative Index to Nursing and Allied Health Literature) were searched from inception to August 2013, supplemented by hand-searching reference lists and contacting experts in the field.Review methodsWe included all randomised or quasi-randomised controlled trials of pre-hospital NIV in patients with acute respiratory failure. Methodological quality was assessed according to established criteria. An aggregate data network meta-analysis (NMA) of mortality and intubation was used to jointly estimate intervention effects relative to usual care. A NMA, using individual patient-level data (IPD) and aggregate data where IPD were not available, was carried out to assess whether or not covariates were treatment effect modifiers. A de novo economic model was developed to explore the costs and health outcomes when pre-hospital NIV (specifically CPAP provided by paramedics) and standard care (in-hospital NIV) were applied to a hypothetical cohort of patients with acute respiratory failure.ResultsThe literature searches identified 2284 citations. Of the 10 studies that met the inclusion criteria, eight were randomised controlled trials and two were quasi-randomised trials (six CPAP; four BiPAP; sample sizes 23–207 participants). IPD were available from seven trials (650 patients). The aggregate data NMA suggested that CPAP was the most effective treatment in terms of mortality (probability = 0.989) and intubation rate (probability = 0.639), and reduced both mortality [odds ratio (OR) 0.41, 95% credible interval (CrI) 0.20 to 0.77] and intubation rate (OR 0.32, 95% CrI 0.17 to 0.62) compared with standard care. The effect of BiPAP on mortality (OR 1.94, 95% CrI 0.65 to 6.14) and intubation rate (OR 0.40, 95% CrI 0.14 to 1.16) compared with standard care was uncertain. The combined IPD and aggregate data NMA suggested that sex was a statistically significant treatment effect modifier for mortality. The economic analysis showed that pre-hospital CPAP was more effective and more expensive than standard care, with an incremental cost-effectiveness ratio of £20,514 per quality-adjusted life-year (QALY) and a 49.5% probability of being cost-effective at the £20,000-per-QALY threshold. Variation in the incidence of eligible patients had a marked impact on cost-effectiveness and the expected value of sample information for a future randomised trial.LimitationsThe meta-analysis lacked power to detect potentially important differences in outcome (particularly for BiPAP), the intervention was not always compared with the best alternative care (in-hospital NIV) in the primary studies and findings may not be generalisable.ConclusionsPre-hospital CPAP can reduce mortality and intubation rates, but cost-effectiveness is uncertain and the value of further randomised evaluation depends on the incidence of suitable patients. A feasibility study is required to determine if a large pragmatic trial of clinical effectiveness and cost-effectiveness is appropriate.Study registrationThe study is registered as PROSPERO CRD42012002933.FundingThe National Institute for Health Research Health Technology Assessment programme.
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Ghosh, Samit, Frances Weidert, Bethany Flage, Prithu Sundd, and Solomon F. Ofori-Acquah. "A Novel Role for P-Selectin in the Pathogenesis of Acute Chest Syndrome." Blood 128, no. 22 (December 2, 2016): 157. http://dx.doi.org/10.1182/blood.v128.22.157.157.
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Abstract Acute chest syndrome (ACS) is a potentially fatal lung complication of sickle cell disease (SCD). There are currently no mechanistic based therapies for ACS and it continues to be a leading cause of death in SCD. Recent studies have identified independent links between extracellular heme with ACS, and with vaso-occlusive crisis (VOC) a common prodrome of ACS. Our experimental ACS model involves intravenous injection of purified hemin typically 35 µmoles/kg, which raises total plasma heme to a clinically relevant pathophysiologic level equivalent to ~0.5g/dl of hemoglobin, and causes respiratory failure exclusively in transgenic SCD mice of both the Townes and Berkeley strains (Ghosh et al., J Clin Invest, 2013). We have determined using time-lapse video microscopy and electrical cell impedance that hemin rapidly disrupts the pulmonary endothelial barrier in vitro. Hemopexin blocks hemin-induced pulmonary endothelial barrier disruption in vitro and respiratory failure in hemin-challenged SS mice. Importantly, genetic polymorphisms in the gene encoding heme oxygenase-1 the rate-limiting heme degradation enzyme are associated with ACS risk in the Cooperative Study of Sickle Cell Disease and the Silent Infarct Transfusion cohorts. These human data and our mechanistic results in SS mice support the heme hypothesis for ACS pathogenesis. P-selectin is a cell adhesion molecule involved in vascular inflammation. It is normally sequestered inside quiescent endothelium. However, recent evidence indicates extracellular heme activates the release of P-selectin unto the endothelial surface wall. Thus, in this study, we tested the hypothesis that P-selectin promotes ACS development. Infusion of a function blocking anti-P-selectin antibody protected SS mice (n=3) from hemin-induced ACS while all control SS mice (n=3) pretreated with IgG before the hemin challenge died (p=0.03) with severe hypoxemia and postmortem evidence of alveolar flooding. The apparent requirement for P-selectin in heme-induced lethal acute lung injury was confirmed by a 100% survival of P-selectin-/- (n=5) and 100% lethality of congenic P-selectin+/+ (n=5) mice challenged with hemin infusions (p=0.005). To identify the cell population involved in this disease process we generated bone marrow chimeric C57BL/6 mice lacking P-selectin in hematopoietic (P-selectinPLT-/-) and non-hematopoietic (P-selectinEC-/-) compartments. Seventy-five percent of P-selectinEC-/- mice were protected while all P-selectinPLT-/- congenic controls succumbed to hemin (n=3-4). The severity of lung injury in the P-selectinPLT-/- C57BL/6 mice was reflected by severe hypoxemia (SpO2: 82.75±2.14%) and a significantly higher lung wet/dry weight ratio compared to the ratio of the P-selectinEC-/- mouse lungs (p<0.05). Next, we transplanted congenic P-selectin-/- and P-selectin+/+ mice with SS mouse bone marrow to generate chimeric SS mice lacking endothelial P-selectin or expressing endothelial P-selectin respectively. Induction of ACS resulted in 40% lethality in the SS/P-selectinEC-/- mice (n=7) and 100% lethality in SS/P-selectinEC+/+ mice (n=7; p<0.01). The development of respiratory failure in the hemin modelinvolves de novo heme release from acute intravascular hemolysis. In this study, we found that SS/P-selectinEC-/- mice cleared ~70% of the hemin bolus within 30 min, which attenuated intravascular hemolysis and damped de novo heme release, while total plasma heme increased over 2-fold in the SS/P-selectinEC+/+ mice during the same time interval. Together these results demonstrate a critical intermediary role for P-selectin in the ACS triggered by acute intravascular hemolysis and elevated extracellular heme. In addition, we provide proof-of-principle in mice that antagonists of P-selectin can prevent and potentially treat ACS. Disclosures No relevant conflicts of interest to declare.
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Bzdęga, Katarzyna, Anna Kutkowska-Kaźmierczak, Gail H. Deutsch, Izabela Plaskota, Marta Smyk, Magdalena Niemiec, Artur Barczyk, et al. "Prenatal Detection of a FOXF1 Deletion in a Fetus with ACDMPV and Hydronephrosis." Genes 14, no. 3 (February 23, 2023): 563. http://dx.doi.org/10.3390/genes14030563.
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Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by the arrest of fetal lung formation, resulting in neonatal death due to acute respiratory failure and pulmonary arterial hypertension. Heterozygous single-nucleotide variants or copy-number variant (CNV) deletions involving the FOXF1 gene and/or its lung-specific enhancer are found in the vast majority of ACDMPV patients. ACDMPV is often accompanied by extrapulmonary malformations, including the gastrointestinal, cardiac, or genitourinary systems. Thus far, most of the described ACDMPV patients have been diagnosed post mortem, based on histologic evaluation of the lung tissue and/or genetic testing. Here, we report a case of a prenatally detected de novo CNV deletion (~0.74 Mb) involving the FOXF1 gene in a fetus with ACDMPV and hydronephrosis. Since ACDMPV is challenging to detect by ultrasound examination, the more widespread implementation of prenatal genetic testing can facilitate early diagnosis, improve appropriate genetic counselling, and further management.
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Bazhenov, Aleksei, Elena N. Parovichnikova, Gennadiy M. Galstyan, Vera V. Troitskaya, Elena O. Gribanova, and Valery G. Savchenko. "Long-Term Outcomes of De Novo Acute Myeloid Leukemia (AML) Patients (pts) with Life Threating Complications." Blood 132, Supplement 1 (November 29, 2018): 5898. http://dx.doi.org/10.1182/blood-2018-99-116114.
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Abstract Background. Induction of remission in pts with AML is often associated with the life-threating complication and ICU admission. The long-term outcomes of these AML pts discharged from ICU are unknown. The aim was to estimate the long-term outcomes of de novo AML pts required ICU admission due to life-threating complications during induction of remission. Methods. All de novo AML pts, younger than 60 y.o, median age 34 (17-60 yo), from 2013 to 2016 were enrolled in the study. All pts were divided into 2 groups: pts who required ICU admission during induction chemotherapy due to life-threating complications and pts who didn't require ICU admission during induction chemotherapy. Overall survival (OS) and disease free survival (DSF) were assessed by the Kaplan - Meier method, log rank value p<0.05 consider as significant. Univariate analysis was performed with χ 2 tests or Fisher's exact tests for categorical variables to find an independent ICU mortality predictor. Results In total, 73 AML pts included in study, 26 (36%) of them were admitted in ICU during induction of remission (tab. 1). ICU pts had more advanced AML. Reasons for ICU admissions were acute respiratory failure (ARF) (62%); neurological events (16%); septic shock (SS) (16%); cardiac arrhythmia (7%). ICU survival rate was 69%. 8 pts died in ICU (5 SS and 3 ARF). Needs for mechanical ventilation, vasopressors and ≥2 organ dysfunctions were independent predictors (p<0.05) of ICU mortality. 18 of 26 (69%) pts received chemotherapy during their stay in ICU. Modifications of chemotherapy were required in 46% of ICU pts and in 36% in non-ICU pts (p>0.05). There were differences in 30-day OS between ICU and non-ICU pts (69% vs. 0%, p=0.001). However, a landmark analysis for long term OS for patients who survived the first 30 days of treatment were the similar in ICU and non-ICU groups (p=0.946)( picture1, A). DSF also were the similar in ICU and non-ICU groups (p=0.946) (picture 1,B) Conclusion. During remission induction 36% of AML pts needed ICU admission due to life-threating complications. Mortality rate in ICU is high (31%). However, after discharging from ICU AML patents had the similar long-term outcomes as well as non-ICU AML pts. Figure. Figure. Disclosures No relevant conflicts of interest to declare.
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Koga, Yasutaka, Kotaro Kaneda, Nao Fujii, Ryo Tanaka, Takashi Miyauchi, Motoki Fujita, Kouko Hidaka, and Ryosuke Tsuruta. "Association between increased nonaerated lung weight and treatment failure in patients with de novo acute respiratory failure: Difference between high-flow nasal oxygen therapy and noninvasive ventilation in a multicentre retrospective study." Journal of Critical Care 65 (October 2021): 221–25. http://dx.doi.org/10.1016/j.jcrc.2021.06.025.
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Ocaña-Macchi, Manuela, Michael Bel, Laurence Guzylack-Piriou, Nicolas Ruggli, Matthias Liniger, Kenneth C. McCullough, Yoshihiro Sakoda, Norikazu Isoda, Mikhail Matrosovich, and Artur Summerfield. "Hemagglutinin-Dependent Tropism of H5N1 Avian Influenza Virus for Human Endothelial Cells." Journal of Virology 83, no. 24 (October 7, 2009): 12947–55. http://dx.doi.org/10.1128/jvi.00468-09.
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ABSTRACT Although current H5N1 highly pathogenic avian influenza viruses (HPAIV) are inefficiently transmitted to humans, infected individuals can suffer from severe disease, often progressing rapidly to acute respiratory distress syndrome and multiorgan failure. This is in contrast with the situation with human influenza viruses, which in immunocompetent individuals usually cause only a respiratory disease which is less aggressive than that observed with avian H5N1 viruses. While the biological basis of inefficient transmission is well documented, the mechanisms by which the H5N1 viruses cause fatal disease remain unclear. In the present study, we demonstrate that human pulmonary microvascular endothelial cells (hPMEC) had a clearly higher susceptibility to infection by H5N1 HPAIV than to infection by human influenza viruses. This was measurable by de novo intracellular nucleoprotein production and virus replication. It was also related to a relatively higher binding capacity to cellular receptors. After infection of hPMEC, cell activation markers E-selectin and P-selectin were upregulated, and the proinflammatory cytokines interleukin-6 and beta interferon were secreted. H5N1 virus infection was also associated with an elevated rate of cell death. Reverse genetics analyses demonstrated a major role for the viral hemagglutinin in this cell tropism. Overall, avian H5N1 viruses have a particular receptor specificity targeting endothelial cells that is different from human influenza viruses, and this H5N1 receptor specificity could contribute to disease pathogenesis.
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Schiller, Gary J., Daniel J. DeAngelo, Arnaud Pigneux, Norbert Vey, Jonathan Kell, Scott R. Solomon, Robert K. Stuart, Bonny L. Johnson, Susan O’Brien, and Francis J. Giles. "Phase II Study of VNP40101M (Cloretazine®) in Elderly Patients with De Novo Poor Risk Acute Myelogenous Leukemia (AML)." Blood 110, no. 11 (November 16, 2007): 917. http://dx.doi.org/10.1182/blood.v110.11.917.917.
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Abstract VNP40101M (Cloretazine®) is a novel sulfonylhydrazine alkylating agent which preferentially targets the O6 position of guanine resulting in DNA cross-links. Data from a previously reported phase II multi-center single agent study (CLI-033) in patients ≥60 years old with newly diagnosed AML or high risk MDS showed an overall response rate of 31% after VNP40101M induction (Giles, 2007). Subgroup analysis showed significant activity in 54 elderly patients with de novo AML with 24 patients (45%) achieving a complete response (CR) or CRp (CI: 30.9;58.6). Subsequently a confirmatory phase II study of single agent VNP40101M was conducted in elderly patients with poor risk de novo AML (CLI-043). Patients received induction therapy with 600 mg/m2 VNP40101M as a 60-minute infusion on day 1. A second induction cycle could be administered to patients with a partial response or hematologic improvement. Patients with CR or CRp received consolidation with cytarabine 400mg/m2/day CIV for 5 days. Patients were eligible if they were ≥60 yrs and had one of the following poor risk factors: age ≥70 yrs, ECOG PS 2, unfavorable cytogenetics, or cardiac, pulmonary or hepatic dysfunction. Patients with a prior diagnosis of MDS or favorable cytogenetics were excluded. A 2-stage optimal minimax design was employed with a target response rate of 35%. The study proceeded to the 2nd stage when >8 responses were confirmed. At least 22 responses in 77 patients are required to accept the hypothesis of a 35% target response rate. Eighty-five patients were treated as of August 14, 2007. Median age (range): 73 yrs (61– 86 y); male: 59%. The majority of patients (79%) had 2 or more risk factors. The most common risk factors were age ≥70 (78%), unfavorable cytogenetics (45%, half with complex karyotype), ECOG PS 2 (41%) and cardiac dysfunction (38%). Thirty VNP40101M-related serious adverse events (SAE) have been reported to date in 22 of 85 patients. The most common SAEs are myelosuppression or complications thereof (pancytopenia (10%), infection (47%)). Non-hematologic SAEs consist of the following gr.3 events: left ventricular dysfunction (1), transaminitis (1), confusion (1), seizure (1), rash (1), hypokalemia (1), weakness (1) and hypoxia/pleural effusion (2). Seventy-nine patients are currently evaluable for early death analysis. Of these, 12 patients (15%) and 16 patients (20%) died at ≤30 days and ≤42 days from first induction therapy, respectively. The most common causes of induction death were progression of disease (6) and infection (6). Other causes were tumor lysis syndrome (1), acute renal failure (1), and respiratory failure (2). A confirmatory Phase II single-agent study of VNP40101M shows anti-leukemia activity in elderly patients with de novo AML and multiple poor-risk features. Major toxicities include myelosuppression. Severe drug-related non-hematological toxicity is uncommon. Patients continue in follow up, and additional safety and response data is pending.
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Bereda, Gudisa. "COVID-19 increases a person’s risk of cardiovascular problems: how common is chronic heart failure in SARS-CoV-2 patients? a case report." Annals of Medicine & Surgery 85, no. 5 (April 18, 2023): 2208–11. http://dx.doi.org/10.1097/ms9.0000000000000635.
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Background and importance: The coronavirus disease of 2019 (COVID-19) infection typically affects the lungs but can also cause life-threatening heart issues. Heart failure is a common condition that can occur either with an existing heart condition or de novo as part of the clinical course of COVID-19. Case presentation: On 11 October 2022, a 60-year-old middle-aged black African woman widow was admitted with a history of muscular weakness for 2 days, a lack of appetite, and occasional vomiting for 1 day. She arrived at the emergency room after complaining for 2 days of peeing less than usual, a fast heartbeat, swelling in the feet, pink blood-tinged mucus, fever, headache, dehydration, a nonproductive cough, and shortness of breath. The left ventricular ejection fraction was 43% on the echocardiogram. Routine reverse transcription polymerase chain reaction testing was performed in the emergency room; she tested COVID-19 positive. To treat her proven COVID-19 infection, she received subcutaneous enoxaparin 80 mg every 12 h as prophylaxis for deep venous thromboembolism. Clinical discussion: A COVID-19 infection can induce cardiac failure and arrhythmias, as well as cause direct harm to the heart. This study explains how enoxaparin has dual benefits in this case report: it reduces the risk of venous thromboembolism in the COVID-19 hospitalized case and prevents death and cardiac ischemia in myocardial infarction. Conclusion: Higher mortality and more frequent acute decompensation may be caused by the capacity of severe acute respiratory syndrome associated coronavirus 2 to cause myocardial injury, as well as by patients with chronic heart failure’s lower baseline features, decreased cardiopulmonary reserve, and susceptibility for myocardial injury.
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Ghosh, Samit, and Solomon F. Ofori-Acquah. "Extracellular Hemin Auto-Amplification Intensifies Tissue Injury In Sickle Cell Disease." Blood 122, no. 21 (November 15, 2013): 972. http://dx.doi.org/10.1182/blood.v122.21.972.972.
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Abstract Acute organ failure is a major clinical concern in sickle cell disease (SCD). However, the mechanism responsible for this potentially lethal complication is poorly understood. We tested the hypothesis that extracellular hemin liberates an intracellular danger molecule that promotes acute organ failure in SCD. Transgenic homozygous SCD (SS), sickle-trait (AS) and normal human hemoglobin (Hb) AA mice were infused with purified hemin (35 µmoles/kg), which raised total plasma hemin by ∼0.45 mM (equivalent to 0.72 g/dl Hb) within 5 min in all three groups of mice. In agreement with our previous results, SS but not AA and AS mice (n= 6 for each genotype) developed cardiopulmonary depression at 30 min evident by reductions in oxygen saturation (99.88±0.23% to 92.1±1.3%, p<0.001), breath rate (175.4±20.6 to 77.36±2.25, p<0.001, breath per min), heart rate (574.5±22.7 to 361.9±23.25 beats per min, p<0.001) and pulse distension (512.8±18.7 to 238.8±17.6 µm, p<0.001), and ∼70% of these animals died within 2 hours. Markedly raised lung wet/dry weight ratio in SS mice that succumbed to hemin suggests that the cardiopulmonary depression was secondary to a severe pulmonary edema. To identify biological correlates for the acute adverse effects in the SS mice, cohorts of both sickle and control mice were challenged with the same dose of hemin, blood samples were drawn at baseline (i.e. time=0 min), and 5 and 30 min after the hemin infusion and analyzed for markers of oxidative stress, tissue damage, plasma scavengers and high mobility group box-1 (HMGB-1), a prototypical danger molecule. Plasma hemopexin decreased by ∼80% at 5 min compared to baseline values in all three groups of mice regardless of the Hb genotype. The catabolism of hemopexin was associated with clearance of ∼50% of the hemin infusion from the circulation of AS and AA mice at 30 min. Paradoxically, the plasma concentration of hemin in the SS mice during this same time interval increased by ∼0.2 mM (p<0.001, n=6). The magnitude of this increase was dependent on the dose of hemin administered exogenously. We discovered that the de novo hemin release in the SS mice was preceded by acute intravascular hemolysis (mean decrease in total Hb: ∼1.4 g/dl, p<0.001, n=9, mean increase in cell-free Hb: 1.0 g/dl, p=0.001, n=9), oxidation of oxyHbS to metHbS (mean increase: 12%, p<0.001, n=6) and persistence of metHbS. It is noteworthy that de novo hemin release did not occur in AS mice suggesting that this phenomenon is dominantly influenced by sickle erythrocytes and not by the presence of intracellular HbS per se. Auto-amplification of hemin may help to explain an observation made nearly fifty years ago that SCD patient plasma contains more hemin than the plasma of patients with more severe intravascular hemolysis involving normal adult Hb (e.g. paroxysmal nocturnal hemoglobinuria), who have higher plasma Hb. To determine whether this phenomenon is critical to the cardiopulmonary depression in the SS mice, recombinant human hemopexin was administered 5 min after the infusion to sequester the endogenous hemin release. In hemin challenged SS mice with respiratory distress, intravenous recombinant human hemopexin rapidly halted the decline in oxygen saturation and breath rate and averted inevitable respiratory failure. In conclusion, we have identified a phenomenon of extracellular hemin auto-amplification that appears to be unique to SCD, and may play a critical role in propagating tissue injury in this disorder. Factors that inhibit erythrocyte lysis and accelerate metHb reduction may help to limit extracellular hemin amplification and preserve organ function during episodes of acute exacerbations in SCD. Disclosures: No relevant conflicts of interest to declare.
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Massara, M., L. Zappelli, A. Lanari, M. Pergolini, A. Giovagnoli, G. Refi, and G. Di Noto. "LYME AND DENGUE FEVER: FROM BANGLADESH TO ITALY." European Heart Journal Supplements 26, Supplement_2 (April 2024): ii59. http://dx.doi.org/10.1093/eurheartjsupp/suae036.134.
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Abstract Background Dengue fever (Flavivirus) and Lyme disease (Borrelia burgdorferi) are rare tropical infectious diseases transmitted by hematophagous vectors (Aedes mosquitoes and ticks, respectively), and they are extremely uncommon in Italy. In European countries, both represent a public health concern as they manifest as imported diseases. Case Report A 54–year–old man from Bangladesh was admitted with symptoms of fever, dyspnea, and pericarditic chest pain. Laboratory and imaging examinations revealed severe acute respiratory failure secondary to left lower lobe pneumonia and pleuropericardial effusion. Broad–spectrum antibiotic therapy and anti–inflammatory treatment were initiated, suspecting para–pneumonic pleuropericarditis. During hospitalization, there was a gradual improvement with a reduction in inflammatory indices and resolution of lung consolidation. The patient was discharged after 14 days with anti–inflammatory therapy (ibuprofen and colchicine). Approximately 7 days later, the patient returned to the emergency department complaining of a recurrence of symptoms and fatigue. The EKG showed phases of 2:1 AV block, EAS and EPS, complete de novo left bundle branch block (LBBB), alternating with an escape atrial rhythm, not evident in previous EKG. During hospitalization, complete AV block emerged with prolonged asystolic phases, requiring urgent placement of a temporary pacemaker. Concurrently, blood tests revealed anemia and increased levels of inflammatory markers, troponin, creatinine, transaminases, cholestatic indices, LDH, and lipase, indicative of multiple organ failure (MOF). Acute pathologies or active bleeding were ruled out by total body CT with contrast. Blood cultures and serological tests were performed to exclude infections by Trichinella, Mycoplasma, Borrelia, Dengue, and other rare infectious diseases. Due to progressive deterioration, the patient was transferred to a tertiary care hospital. In the following days, laboratory results showed positive IgG and IgM for Dengue (without serological evidence of viral RNA) and positive IgG and IgM antibodies for Borrelia burgdorferi. Conclusion In Italy, the incidence of these diseases is low, and their coexistence in the same host is even rarer (if not anecdotal). However, coinfection cannot be excluded in patients from areas where these diseases are endemic, such as Bangladesh.
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Su, Jingdong, Hazem E. El-Osta, Reinhold Munker, Glenn M. Mills, and Srinivas S. Devarakonda. "Concomitant Acute Promyelocytic Leukemia and Chronic Lymphocytic Leukemia: Molecularly Two Distinct Diseases." Blood 126, no. 23 (December 3, 2015): 4904. http://dx.doi.org/10.1182/blood.v126.23.4904.4904.
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Abstract Introduction: Acute myeloid leukemia (AML) developing in chronic lymphocytic leukemia (CLL) patients is very uncommon and is usually treatment-related. Acute promyelocytic leukemia (APL) occurring concurrently with CLL is extremely rare and there is only one published case of treatment-related APL. No case of concomitant APL and CLL in patients without history of malignancy has been found in the literature. We report such a case of coexisting CLL and APL. Case report: A 52-years-old Caucasian male with past medical history of hypertension, diabetes mellitus, and coronary artery disease, presented to an outside facility with chest pain and dyspnea for two day duration. He had lymphocytosis (WBC 31,500 /µL and 66 % lymphocytes) one year prior, however, was lost to follow up and no further workup was pursued. On examination, he was pale with no petechiae or ecchymosis. There was no lymphadenopathy or hepatosplenomegaly. Labs showed WBC 17,000/µL with 97% lymphocytes and 2% blasts, Hemoglobin 6.0 g/dL, and platelet 16,000/µL. Serum troponin was 0.30 ng/mL. EKG revealed ST-depression in lateral leads concerning for non-ST elevation MI (NSTEMI). Patient was admitted and received packed red blood cells and platelet transfusion with resolution of chest pain. Upon transfer to our hospital, he was afebrile and hemodynamically stable. Lab work showed WBC of 72,000/µL and platelet count of 9,000/µL. Slides from outside facility were reviewed and immunohistochemistry from bone marrow specimen revealed dense staining of myeloperoxidase (MPO) on sheets of myeloid blasts and strong CD79a staining on clumps of lymphocytes. Peripheral blood, bone marrow aspiration and biopsy showed two distinct morphological abnormalities including immature myeloid blasts with prominent cytoplasmic granules as well as increased number of small lymphocytes. Flow cytometry demonstrated a clonal B-cell population consistent with chronic lymphocytic leukemia. Further evaluation with fluorescent in-situ hybridization (FISH) revealed presence of a t(15;17) (q22;q12), PML-RARA translocation consistent with acute promyelocytic leukemia. Co-existence of CLL and APL was confirmed. Treatment with All-trans-retinoic acid (ATRA) and hydroxyurea was started immediately along with dexamethasone for prevention of differentiation syndrome. Shortly after initiation of ATRA, patient developed acute hypoxic respiratory failure with extensive patchy opacities in bilateral lungs on chest radiography. WBC further increased to 130,000/µL. Respiratory failure worsened despite bi-level positive airway pressure (BiPAP) and diuretics, and he was subsequently transferred to intensive care unit (ICU). Patient's clinical condition deteriorated rapidly, developed disseminated intravascular coagulation (DIC), and eventually died from cardiopulmonary arrest. Discussion: CLL is the most common hematologic malignancy in adults in western countries and the treatment of CLL is associated with increased incidence of secondary malignancies. However, transformation of CLL into AML is uncommon and most reported cases were therapy-related (t-AML). In patients with t-AML, exposure to topoisomerase II inhibitors (mainly Etoposide), alkylating agents and ionizing radiation are among the main causative factors. AML after treatment with DNA-topoisomerase II inhibitors has a short latency period, presents without a prior myelodysplastic syndrome, and is associated with 11q23 translocation. There was only one reported case of APL which developed 2 years after radiotherapy for prostate cancer in a patient with chronic lymphocytic leukemia. Although no treatment was given for CLL, radiotherapy for prostate cancer in that patient might have contributed to the development of APL, which is considered therapy-related. High dose of radiation has also been considered to increase the risk of t-AML. To date, no report in literature has been found on simultaneous occurrence of CLL and APL in patients without any previous treatment, either for CLL or for other co-existing conditions. We report here the first case of CLL co-existing with APL, diagnosed as two separate disease entities based on evidence from molecular testing and immunohistochemistry staining. APL is a hematological emergency. Management of APL, regardless of it being de novo or therapy-related, is the same. Disclosures No relevant conflicts of interest to declare.
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Nakar, Charles, Neelam Thukral, Heather L. McDaniel, Joseph M. Parker, Diane Trybul, and Amy D. Shapiro. "Acute Airway Obstruction in 4 Pediatric Patients with Congenital Plasminogen Deficiency (C-PLGD) Treated with Intravenous Plasminogen (Human) Replacement Therapy Under an Expanded Access Protocol." Blood 136, Supplement 1 (November 5, 2020): 2. http://dx.doi.org/10.1182/blood-2020-137177.
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C-PLGD is a rare autosomal recessive multisystem disorder of the fibrinolytic system. Mutations in the PLG gene result in extravascular fibrinous deposits, termed ligneous for their woody appearance, that accumulate on mucous membranes such as the conjunctiva and airways, with resultant tissue injury or organ dysfunction. Ligneous conjunctivitis (LC) is the most common manifestation (> 80%) of C-PLGD. Ligneous lesions affecting the respiratory system have been reported in 20% of patients in a large case series (Schuster et. al. JTH 2007). We report 3 new cases in addition to a previously reported case of airway obstruction with respiratory distress successfully treated with intravenous Glu-plasminogen concentrate (Human) (IV-PLG). Case 1: A 16-month-old female with C-PLGD, with onset of LC at 3 weeks of age, developed a febrile illness with upper respiratory tract symptoms and exacerbation of LC. Four weeks after the exacerbation presented, she developed wheezing unresponsive to bronchodilator and corticosteroid treatment. She progressed to stridor, tachypnea and hypercapnia and was treated with fresh frozen plasma (FFP) infusions. She underwent a bronchoscopy which revealed friable airways and fibrinous lesions in the right mainstem bronchus (Figure 1). Computed tomography (CT) of the chest revealed airway narrowing (R>L) with distal air trapping. She was admitted to the pediatric intensive care unit (PICU) for monitoring and continued FFP treatment every 12 hours without relief. Compassionate use of IV-PLG was requested and she initiated urgent treatment under an expanded access protocol. Significant improvement in stridor and tachypnea occurred within 48 hours of starting therapy and was discharged from the PICU after 2 weeks without symptom recurrence. 10 days post treatment repeat bronchoscopy showed improvement in obstructing airway lesions (Figure 2), and CT scan revealed improvement in airway narrowing and air trapping. She is currently continuing treatment administered every 5 days. Case 2: A 16-month-old male with C-PLGD and shunted congenital hydrocephalous, presented with worsening LC (onset at 7 months) and hoarseness from suspected ligneous airway disease. He was admitted to the PICU for monitoring, supplemental oxygen therapy for hypoxemia, and FFP infusions every 12 hours with only minimal relief. Chest CT revealed bronchiectasis and possible airway lesions. IV-PLG compassionate use was requested; he initiated urgent treatment under an expanded access protocol. Four days after starting treatment he underwent bronchoscopy confirming airway ligneous involvement, and ophthalmologic membranes were also stripped. He responded to treatment with improvement of both respiratory and eye symptoms without further requirement for supplemental oxygen; he was discharged from PICU after 8 days total, and 6 days after starting IV-PLG. His eyes healed without lesion recurrence. He continues to receive IV plasminogen replacement infusions every 5 days. Case 3: A 3-year-old C-PLGD male, diagnosed at 7 weeks of age with LC, developed an upper respiratory infection with persistent hoarseness over a 3-week period. Due to potential airway involvement concern, he underwent upper airway laryngoscopy; a right vocal cord small polyp and a papillomatous mass noted below vocal cords were observed. Compassionate use of IV-PLG was requested; he initiated urgent treatment under an expanded access protocol. The patient experienced resolution of hoarseness in 4 weeks, with significant improvement in his LC. He has had no further clinical respiratory symptoms or LC exacerbations and is currently continuing treatment administered every 5 days. Plasminogen replacement has previously been reported in a fourth C-PLGD pediatric patient (22-month-old male) who had experienced cardiopulmonary arrest due to airway obstruction (Hassenpflug et. al. Blood 2016). This patient required ongoing ventilator support; treatment with IV-PLG assisted in weaning from ventilator support. These cases demonstrate the potential role for IV-PLG treatment in C-PLGD patients with airway obstruction due to fibrinous lesions, to prevent progression of obstruction resulting in respiratory failure; additional controlled studies would need to be performed to further support these observations. Disclosures Nakar: Prometic Biotherapeutics: Research Funding; Kedrion SpA: Research Funding. McDaniel:Prometic Biotherapeutics: Consultancy, Other: Investigator Clinical Trial. Parker:Liminal BioSciences: Current Employment, Current equity holder in publicly-traded company. Trybul:Liminal BioSciences: Current Employment, Current equity holder in publicly-traded company. Shapiro:Sangamo: Research Funding; ProMetic Bio Therapeutics: Consultancy, Research Funding; Pfizer: Research Funding; Octapharma: Research Funding; OPKO: Research Funding; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Research Funding; Kedrion Biopharma: Research Funding; Glover Blood Therapeutics: Research Funding; Genentech/Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Daiichi Sankyo: Research Funding; Catalyst BioSciences: Membership on an entity's Board of Directors or advisory committees; BioMarin: Research Funding; Bioverativ: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk Hemophilia Foundation: Membership on an entity's Board of Directors or advisory committees; Sigilon: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Research Funding.
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Kavcic, Marko, Brian T. Fisher, Yimei Li, Alix E. Seif, Kari Torp, Yuan-Shung Huang, Grace E. Lee, et al. "Mortality and Resource Utilization in Children with De Novo Acute Myeloid Leukemia Treated with Chemotherapy and Gemtuzumab Ozogamicin in the United States." Blood 120, no. 21 (November 16, 2012): 4283. http://dx.doi.org/10.1182/blood.v120.21.4283.4283.
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Abstract Abstract 4283 Background The role of Gemtuzumab ozogamicin (GO) for acute myeloid leukemia (AML) remains controversial. GO was removed from the U.S. market in 2010 due to concerns of increased induction mortality in adults. Other studies have shown a survival benefit without increased treatment related mortality. Moreover, no data are available on the resources required to deliver GO based chemotherapy. Since pediatric data are limited, we evaluated in-hospital mortality and resource utilization in pediatric AML patients treated with GO and standard chemotherapy. Methods We used the Pediatric Information Health System (PHIS) to establish a cohort of children < 19 years old treated for de novo AML with GO and standard cytarabine, daunorubicin, and etoposide (ADE) induction. Cohort assembly was validated by local chart review and used ICD-9 diagnosis codes and manual review of chemotherapy. Case fatality was determined after induction (defined from the start of therapy to the initiation course 3), at 6 months and at 12 months. Resource utilization was determined for each patient based on daily billing data. Each resource variable was dichotomized (exposure or no exposure) for each inpatient day and then summarized during each study period to determine resource utilization days per 1,000 hospital days. Results In total, 253 children who had billing data for GO during the first course of ADE induction were identified. Median age was 9.6 years; a slight male predominance was observed (54%) and most patients were white (69%). In-hospital case-fatality rates were 2.4% during induction, 6.7% at 6 months, and 13.0% at 12 months from start of therapy. PHIS billing data demonstrated that patients received opioids almost on one in four hospital days, that during induction period 12% of patients received vasopressors on at least two consecutive days, and 12% needed assisted ventilation. Mean inpatient stay and resource utilization rates are presented in Table 1. Discussion In-hospital mortality rates at the three time points were low and concordant with published data on pediatric AML trials using an ADE induction (Gibson, BJH 2011) and ADE Induction + GO (Cooper, Cancer 2012) and lower than trials using intensively timed DCTER regimens (Woods, Blood 2001; Lange, Blood 2008). Resource utilization data demonstrated an extensive use of resources needed to manage infections (blood cultures, imaging, antimicrobials). While infections are the leading cause of non-relapse morbidity and mortality in pediatric AML, such extensive use of resources has not been previously quantified. In addition, PHIS billing data describe toxicities such as pain (opioid use), hypotension (vasopressor support), and respiratory failure (assisted ventilation) at rates higher than those previously reported in clinical trials. In conclusion, the in-hospital mortality of children treated with GO at PHIS centers appears comparable to previously published studies of ADE and ADE + GO. The resource utilization data provide a more comprehensive description of resources needed to treat pediatric AML than previously reported. In addition, the resource utilization data suggest that toxicities reported on clinical trials may underestimate the resources needed to administer AML induction therapy safely. Disclosures: No relevant conflicts of interest to declare.
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Nelson, Blessie Elizabeth, Adrian Gerard Murphy, and Jacquelyn W. Zimmerman. "Expecting the unexpected." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e14066-e14066. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e14066.
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e14066 Background: Myasthenia gravis is an autoimmune neuro-muscular disorder traditionally seen in bi-modal distribution in young women or older men. Discovery of immunotherapy has brought hope in survival outcomes for patients with malignant melanoma, lung, renal and head/neck cancers but it also opens Pandora’s box of immune-related toxicities for which early recognition and appropriate clinical management are paramount. Here we describe a case of immunotherapy induced myasthenia gravis de novo. Methods: A 77-year-old man with HPV+ stage IVA squamous cell carcinoma of the tongue presented with sudden onset orthopnea and dyspnea on exertion for the past day. One week ago, he received his second cycle of nivolumab as part of his neoadjuvant therapy. He was seen at an outside hospital and was found to be acute hypercapnic respiratory failure and placed on BiPAP. He was started on antibiotics for community-acquired pneumonia with levofloxacin and doxycycline and transferred to a tertiary care center for further management. On further evaluation, he endorsed diplopia, blurry vision, fluctuating muscle weakness that is worse at the end of the day, change in voice and proximal muscle weakness. His exam was consistent with bilateral ptosis, weak hip flexion and shoulder abduction, positive sniff test and poor vital capacity and negative inspiratory force values suggestive of impending respiratory and diaphragmatic failure secondary to myasthenic crisis. He was admitted to the ICU and placed on BiPAP and frequent NIF and VC monitoring. He was started on pyridostigmine but showed no clinical improvement on day 1 and hence was initiated on plasmapheresis from day 2 for a total of 10 days. Results: Investigations showed positivity of Ach-R modulating and binding and blocking antibodies with negative voltage gated calcium channel antibodies. EMG revealed decrement of the compound muscle action potential in the repetitive stimulation test indicative of myasthenia gravis. He responded well to the above treatment and underwent successful left partial glossectomy and weaned off mechanical ventilation and has been cancer free so far. He is doing well on maintenance prednisone and pyridostigmine. Conclusions: There is a significant 30.4% MG-specific-related mortality due to immunotherapy alone which this case demonstrates the importance of vigilance and early detection for effective treatment and management. It highlights need for the oncological world and our colleagues in various other disciplines of healthcare to identify and mitigate the effects of immunotherapy which has become our hope in beating cancer.
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Knoebl, Paul, Peter Schellongowski, Thomas Staudinger, Wolfgang R. Sperr, and Christian Scheibenpflug. "Treatment Of Infection-Associated Purpura Fulminans With Protein C Zymogen Is Associated With a High Survival Rate." Blood 122, no. 21 (November 15, 2013): 3606. http://dx.doi.org/10.1182/blood.v122.21.3606.3606.
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Abstract Purpura fulminans (PF) is rapidly progressing, life-threatening disorder, characterized by skin lesions with a typical morphology, disseminated intravascular coagulopathy, multiple organ failure, septic shock, most often, but not exclusively caused by infections (meningococci, pneumococci, and others). It is associated with a breakdown of the protein C system, an important regulator of blood coagulation, leading to consumption coagulopathy, intravascular fibrin deposition, downregulated fibrinolysis, disturbance of microcirculation and finally death from multiple organ failure. Mortality of severe sepsis with coagulopathy is as high as 80-100%, and persistent disabilities (i.e. amputations) are frequent in survivors. Several case series including more than 340 patients, suggest that substitution of protein C zymogen can impressively improve coagulopathy, reduce amputation rate and improve survival compared to historical controls in PF associated with sepsis in neonates, children and adults, encouraging some centers to incorporate it in their local guidelines for treatment of purpura fulminans. We report a series of 9 consecutive patients with purpura fulminans, treated with a plasma-derived protein C zymogen concentrate (Ceprotin®, Baxter, Vienna, Austria) for acute onset PF in 3 Vienna hospitals, in which the treatment guidelines included protein C replacement. Median age was 29 years (range 2 months to 73 years), 5 male, 4 female, 5 adult, 4 pediatric patients were treated, respectively. Six patients had meningococcal sepsis, 2 had overwhelming post-splenectomy infections, and 1 had heat-shock induced coagulopathy. All patients presented with typical skin lesions and acute critical illness and were admitted to intensive care units. Coagulopathy was present in 100%, severe vasopressor-dependent sepsis in 100%, acute renal failure in 89%, respiratory failure in 89%. Median SAPS II score in the adults was 78 (range 45-97), predicting a mortality of 78.3% (range 31-88.5%). All pediatric patients had a Glasgow Meningococcal Septicemia prognostic score >8, indicating a fatal outcome. Renal replacement therapy was necessary in 56%, mechanical ventilation in 89%. Initial protein C levels were markedly decreased in the 8 patients with infections. Standardized sepsis therapy was applied according to the surviving sepsis guidelines. Protein C was given as an initial bolus infusion (100 U/kg) followed by a continuous infusion with 10 U/kg/h, adjusted to obtain plasma protein C activity levels of 1.0 U/mL. In addition, platelet, red blood cell, fibrinogen and antithrombin concentrates were given as needed. In one patient (PF caused by heat shock) protein C infusion was stopped after 2 days, and he died after 10 days from refractory multiple organ failure. All other patients (with infection-induced PF) survived. Coagulopathy resolved within a few days, and all patients could successfully be weaned from intensive care therapy. Organ function was completely restored without residual dysfunction. One patient needed amputation of both forefeet and nose reconstruction, 6 patients had, in part extended, scar formation at the skin. Median follow up was 8 months (range 2-20). At that time all patients were fully active without apparent limitations. In conclusion, standardized, full-code sepsis therapy, together with protein C substitution, resulted in very high survival rate of patients with infection-induced PF (as compared to predicted mortality) and a low rate of disabilities in this otherwise deleterious disease. As Ceprotin® is approved only for congenital protein C deficiency, controlled clinical studies are urgently needed to gain more scientific evidence for this potentially life-saving, but still off-label therapy in patients with PF. Disclosures: Knoebl: Novo Nordisk: Consultancy, Honoraria; Baxter: Consultancy, Honoraria. Off Label Use: plasma derived protein C concentrate (Ceprotin(R)) for acquired protein C deficiency in purpura fulminans.
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Schuettpelz, Laura, Daniel C. Link, Dong Shen, Matthew J. Walter, Daniel C. Koboldt, David J. Dooling, Robert S. Fulton, et al. "DNA Sequence of the Cancer Genome of a Patient with Therapy-Related Acute Myeloid Leukemia." Blood 116, no. 21 (November 19, 2010): 580. http://dx.doi.org/10.1182/blood.v116.21.580.580.
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Abstract Abstract 580 Therapy-related acute myeloid leukemia/myelodysplasia (t-AML/t-MDS) accounts for 10–20% of all cases of AML, and its incidence is rising. Treatment options are limited and the prognosis very poor, highlighting the need for new therapies in t-AML/t-MDS. However, the genetic mutations contributing to transformation in t-AML/t-MDS are largely unknown, limiting the development of novel targeted therapeutics. Our group previously reported the sequence of the first two cancer genomes, both in patients with de novo AML (Nature 456:66, 2008; NEJM 361:1058, 2009). Herein, we report the sequence of the cancer genome of a patient with t-AML. The patient presented with early-onset breast, then ovarian cancer (age <40), and was treated with surgery, radiation and combination chemotherapy (cytoxan, etoposide, adriamycin, carboplatinum and taxol). Clinical sequencing of BRCA1 and BRCA2 revealed no mutations. Four years later, recurrence of her ovarian cancer was detected and she again was treated with chemotherapy. Two months after completing this chemotherapy, she presented with t-AML and respiratory failure, and she died 8 days after presentation. Typical of t-AML, the karyotype of this leukemia was complex, with -7, del(5q), and several marker chromosomes that could not be resolved with standard cytogenetic analysis. Bone marrow and a skin biopsy were obtained after informed consent and analyzed in the following ways: 1) whole genome sequencing of leukemic bone marrow and skin DNA on the Illumina platform using paired end reads with an average read length of 75 bp; 2) SNP genotyping on the Affymetrix 6.0 array (on leukemic and skin DNA) to detect copy number alterations and uniparental disomy; 3) RNA expression profiling using the Affymetrix Exon 1.0 array; 4) spectral karyotyping. For the leukemic sample, a total of 115 Gb of sequence was obtained (28.7X haploid coverage). Based on SNP genotyping, >96% of heterozygous SNPs were detected. Similar data were obtained for the skin sample. A total of 27 validated somatic single nucleotide variants or indels were detected in coding sequences. None of these mutations have been previously reported in de novo AML. Eight novel chromosomal translocations were identified and the breakpoints defined. One translocation, t(3;4)(q27.3;p15.32), resulted in the production of an in frame fusion transcript of DGKG (diacylglycerol kinase gamma) with BST1 (bone marrow cell stromal antigen 1). Studies are underway to characterize the effect of this fusion gene on hematopoietic cell growth and differentiation. In addition to -7 and del(5q), somatic copy number alterations on chromosome 3 and 12 were identified. There is controversy whether haploinsufficiency of genes on chromosomes 7 and 5q is sufficient to contribute to transformation, or whether further mutations lead to loss of heterozygosity of one or more genes in these regions. In the present case, careful review of the sequence and array data revealed no ‘homozygous' somatic single nucleotide variants, indels, or copy number alterations of coding genes on the remaining copy of chromosome 5 or 7. The patient's clinical presentation strongly suggested genetic cancer susceptibility. Analysis of the skin genome of this patient identified a heterozygous deletion of exons 7–9 of TP53, likely contributing to the early onset of her breast cancer; a uniparental disomy event resulted in the deletion being homozygous in the leukemia sample. Interestingly, the mutant TP53 allele is expressed, and it is predicted to produce a truncated p53 protein lacking most of its DNA binding domain. Functional studies of the mutant p53 protein are underway. Of note, based on a detailed family history and genotyping of the patient's mother, we suspect that the TP53 deletion occurred spontaneously. Ongoing whole genome sequencing studies in a large number of t-AML samples should identify novel somatic mutations and germline variants that contribute to t-AML. Disclosures: No relevant conflicts of interest to declare.
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Ma, Jun, Junbin Hu, Li Liu, Yuqing Chen, Aili He, Shifeng Lou, Jian Ge, et al. "Analysis of short-term efficacy and safety of mitoxantrone hydrochloride liposome regimen therapy in adult acute myeloid leukemia." Journal of Clinical Oncology 41, no. 16_suppl (June 1, 2023): 7039. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.7039.
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7039 Background: Acute myeloid leukemia (AML) is highly heterogeneous, and more than half of patients (pts) will experience refractory or relapse, with poor prognosis. Currently, chemotherapy and hematopoietic stem cell transplantation (HSCT) are the main treatments for AML. Mitoxantrone is a synthetic anthracenedione anti-cancer drug that is effective in lymphoma, leukemia, and other solid tumors. Mitoxantrone hydrochloride liposome (PLM60) is the first approved mitoxantrone nano-drug, which has shown favorable pharmacokinetic characteristics and significantly prolong the survival time of animals compared with the same dose of mitoxantrone (Li 2008). However, there is still a lack of systematic reports about the real-world application of PLM60 in AML. Methods: We performed a multicenter retrospective analysis of 82 pts with newly diagnosed AML and relapsed/refractory (R/R) AML, who received at least one cycle of PLM60 regimen between January 2022 and November 2022. Pts aged 18 years and above with confirmed diagnosis of AML according to the 2016-revised WHO criteria were eligible for inclusion, except acute promyelocytic leukemia (APL). The median dose of PLM60 in the regimen was 20.0 (range 10.3–31.6) mg/m2. Efficacy was assessed by composite complete remission (CRc) rate and overall response rate (ORR), and logistic regression analysis was performed to analyze factors affecting the curative effect. Adverse events were assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: 82 pts were enrolled with a median age of 50.5 (range 20-83) years. There were 71 cases of de novo AML and 11 cases of secondary AML. Targeted sequencing was performed on 86.6% of pts (71/82). FLT3 was the most commonly mutated gene found in 22.5% (16/71), followed by ASXL1 mutated in 12.7%, NPM1 in 11.3%, and TP53 in 11.3%. 4.9% (4/82) of pts underwent HSCT. Among the 25 newly diagnosed pts, CRc rate was 72.0% (18/25) and ORR was 92.0% (23/25). Among the 57 R/R pts, CRc rate was 24.6% (14/57) and ORR was 40.4% (23/57). The courses of induction failure ( OR= 16.617, P= 0.026), and the duration of the first complete remission (CR1) ( OR= 20.647, P= 0.007) were independent influencing factors of the efficacy. Common grade 3/4 AEs included decreased neutrophil count (84.1%), thrombocytopenia (76.8%), anemia (73.2%), febrile neutropenia (47.6%), pulmonary infection (11.0%) and upper respiratory tract infection (2.4%). The overall safety was acceptable and controllable. Conclusions: The PLM60 regimen had an encouraging efficacy and showed a manageable safety profile with the most adverse events being hematologic toxicities.
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Zhou, Xiaoqin, David B. Loran, Dongfang Wang, Brannon R. Hyde, Scott D. Lick, and Joseph B. Zwischenberger. "Seventy-two hour gas exchange performance and hemodynamic properties of NOVALUNG®iLA as a gas exchanger for arteriovenous carbon dioxide removal." Perfusion 20, no. 6 (December 2005): 303–8. http://dx.doi.org/10.1191/0267659105pf838oa.
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Objective: Acute respiratory failure is complicated by acidosis and altered end-organ perfusion. NOVA-LUNG®iLA is an interventional lung assist (ILA) device for arteriovenous carbon dioxide removal (AVCO2R). The present study was conducted to evaluate the device for short-term CO2 removal performance and hemodynamic response. Methods: Six adult sheep received cannulation of the jugular vein and carotid artery. The ILA-AVCO2R circuit was placed on the sheep for 72 hours. Hemodynamics and PaCO2 were measured; CO2 removal was calculated while varying sweep gas flow rates (Qg), device blood flow rates (Qb), and PaCO2. Results: Hemo-dynamic variables remained normal throughout the 72 hour study. CO2 removal increased with increases in Qgor Qb. Mean CO2 removal was 119.3 ml/min for Qb 1L/min, Qg 5 L/min, and PaCO2 40 - 50 mmHg.PaCO2 was directly proportional to CO2 clearance (R-0.72, p B/0.001). Conclusion: NOVALUNG®iLA can provide near total CO2 removal with Qb 1 - 2 L/min,Qg 5 L/min, and minimal flow resistance (3.889/0.82 mmHg/L/min). PaCO2 correlates with CO2 removal and is dependent on Qb and Qg.
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Schellongowski, Peter, Philipp Wohlfarth, Kundi Michael, Alexander Hauswirth, Andja Bojic, Werner Rabitsch, Ulrich Jäger, Peter Valent, Thomas Staudinger, and Wolfgang R. Sperr. "Incidence of Intensive Care Unit Admission, Outcome, and Post Intensive Care Survival in Patients with Acute Lymphocytic Leukemia or Burkitt Lymphoma." Blood 124, no. 21 (December 6, 2014): 2633. http://dx.doi.org/10.1182/blood.v124.21.2633.2633.
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Abstract Acute lymphocytic leukemia (ALL) and Burkitt lymphoma (BL) are highly aggressive hematologic neoplasms. We analyzed reasons for and the incidence of admission to the intensive care unit (ICU) in de novo ALL/BL patients (pts) as well as their ICU and long-term outcome. A total of 177 consecutive pts (age 15-88 years, f/m ratio 1:1.3), including 135 with ALL (B-ALL, n=12; c-ALL, n=26; prae-B-ALL, n=33; T-ALL, n=28; bcr/abl+ ALL, n=29; T-LBL, n=3; ALL NOS, n=4) and 42 with BL were analyzed retrospectively. First-line chemotherapy (CHT) was administered between 02/1995 and 01/2013 according to the Hšlzer-protocol. In a subset of patients (n=52) hematopoietic stem cell transplantation (HSCT) was performed in complete remission (CR). Thirty-one pts (17.5%) required intensive care, 21 (11.9%) during induction CHT, 6 (3.4%) during conventional post-remission therapy and 4 (2.3%) within one year after HSCT in first CR. In these 31 pts the reasons for ICU admission were «observation after surgery due to malignancy«, therapy-related complications (n=10, 32%), respiratory failure (n=8, 26%), sepsis (n=4, 13%), neurological deterioration (n=3, 10%), renal failure (n=3; 6%) as well as cardiopulmonary resuscitation, bleeding, III¡ AV-blockage and pancreatitis in one patient each. The percentage of ICU admissions was comparable in BL (23%) and ALL (16%; p=0.26). In BL more pts were admitted to the ICU for observation after surgery (50%) compared to ALL patients (23%; p=0.15). Whereas intensive care was required in pts with BL only during the induction phase of CHT (Block A1), ALL pts were admitted during induction as well as during post-remission treatment (conventional CHT or HSCT; p<0.05). At ICU admission the median SAPS II score in all pts was 45 (range 13-93). Invasive mechanical ventilation was necessary in 28 pts (90%) and vasopressor therapy in 29 pts (94%). The median number of days at the ICU was 6 (range 1-88 days) and 25/31 pts (81%) were ICU survivors. All pts with BL (n=10) survived the ICU, and 71% of our ALL patients (15/21, p=0.06) were ICU survivors. In ICU pts, the medin survival from hospital admission was 18 months and thus shorter compared to non-ICU pts (44 months) with a similar plateau at 60 months of 40% and 43%, respectively (Figure 1). However, these differences were not statistically significant (p=0.32). Moreover, no differences in the median survival were observed with regard to continuous complete remission (CCR). In summary, a substantial number (17.5%) of pts with ALL/BL require intensive care during first line CHT. Importantly, the long-term survival and CCR of the ICU pts did not differ significantly from that of non-ICU pts. These observations have obvious clinical implications and are in favor of ICU admission and intensive care as needed in this group of aggressive malignancies. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
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Carregosa Ribeiro, Keyse Mirelle, Karen Monique Carregosa Ribeiro, Aloisio Santos Neto, Iara Santana Santos Carvalho, Gabriela Rodrigues De Andrade Souza, Leticia Lima Costa, and Mônica Melo. "ACOMETIMENTO E INCIDÊNCIA POR COVID-19 EM PACIENTES PEDIÁTRICOS NOS ESTADOS DE ALAGOAS E DA BAHIA." Diálogos & Ciência 1, no. 42 (December 13, 2021): 113–22. http://dx.doi.org/10.7447/1678-0493.2021v1n42p113-122.
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RESUMO
Introdução: O novo coronavírus, descoberto aproximadamente em 2019, recebeu o nome de SARS-CoV-2 (coronavírus 2 da síndrome respiratória aguda grave), cujo foi denominado pela Organização Mundial da Saúde (OMS) de COVID-19. Surgiu na China, disseminando por todo o mundo e rapidamente se tornou um grande desafio a ser enfrentado pela sociedade. Tal comorbidade está associada a amplo cenário de óbitos mundialmente. Entretanto, na pediatria apresentam menores taxas de incidências e complicações. Material e Métodos: Base de dados do LILACS, SCIELO e PUBMED. Os descritores utilizados: "covid", "pediatria", juntamente ao operador Booleano “AND”, entre os anos de 2016 a 2021. Além dos boletins epidemiológicos do estado de Alagoas e Bahia, entre 2020 e 2021. Resultados e Discussão: Observa-se menor incidência entre as crianças, com menores taxas de complicações e óbitos. Acredita-se que esse público seja menos suscetível às complicações da COVID-19 por apresentar menor expressão da enzima conversora de angiotensina 2 (ECA2). O patógeno possui tropismo tanto pelo sistema respiratório, assim há uma variabilidade na gravidade de insuficiência respiratória e manifestações clínicas, diferindo desde formas assintomáticas até graves. Os sinais e sintomas geralmente são tosse, eritema faríngeo e febre. Conclusão: O cenário pandêmico da COVID-19 embora mostre que as crianças possuem um baixo perfil de morbidade e letalidade, alerta para a necessidade de políticas públicas que visem a contenção do vírus, já que as crianças são também transmissoras.
ABSTRACT
Introduction: The new coronavirus, discovered approximately in 2019, was named SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which was named by the World Health Organization (WHO) as COVID-19. It appeared in China, spread throughout the world and quickly became a great challenge to be faced by society. Such comorbidity is associated with a wide scenario of deaths worldwide. However, in pediatrics they have lower incidence and complication rates. Material and Methods: LILACS, SCIELO and PUBMED database. The descriptors used: "covid", "pediatrics", together with the Boolean operator “AND”, between the years 2016 to 2021. In addition to the epidemiological bulletins of the state of Alagoas and Bahia, between 2020 and 2021.Results and Discussion: There is a lower incidence among children, with lower rates of complications and deaths. It is believed that this public is less susceptible to the complications of COVID-19 due to its lower expression of the angiotensin-2 converting enzyme (ACE2). The pathogen has tropism for both the respiratory system, so there is variability in the severity of respiratory failure and clinical manifestations, differing from asymptomatic to severe forms. Signs and symptoms are usually cough, pharyngeal erythema, and fever. Conclusion: Although the COVID-19 pandemic scenario shows that children have a low morbidity and lethality profile, it alerts to the need for public policies aimed at containing the virus, since children are also transmitters.
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Sun, Jie, Zhen Wang, Yi Luo, Yamin Tan, Jimin Shi, Jingsong He, Wanzhuo Xie, et al. "Imatinib Combined with Chemotherapy and Allogeneic Stem Cell Transplantation Results In Long Time Survival In Patients with De Novo Ph+ AML." Blood 116, no. 21 (November 19, 2010): 4368. http://dx.doi.org/10.1182/blood.v116.21.4368.4368.
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Abstract Abstract 4368 De novo Philadelphia chromosome-positive acute myeloid leukemia is a rare condition with a poor prognosis. Allogeneic stem cell transplantation (allo-SCT) is always recommended to treat this disease although its results are not always satisfactory even in young patients. Imatinib is a protein tyrosine kinase inhibitor that has now been shown to be active in Ph+ chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia, however its role in Ph+ AML has not been extensively investigated. We present two patients with de novo Ph+ AML who received Imatinib combined with chemotherapy and allogeneic stem cell transplantation (allo-SCT), followed by Imatinib maintainance treatment after allo-SCT. These patients achieved long-term disease-free survival for 34 and 44 months respectively. Patient 1: A 19-year-old woman was admitted in October 2007 with fever and fatigue for one week. Physical examination showed pallor and severe sternal tenderness. Blood routine showed WBC 93.7×109/L, Hb 80.7g/L, platelets 42×109/L, 60% blast cells. Flow cytometry analysis of marrow mononuclear cells showed 84.41% blast cells positive for CD34, 80.49% for HLA-DR, 34.63% for CD13, and 5.71% for MPO. Karyotype at diagnosis was 46, XX, t (9; 22) (q34; 11) in 10 analyzed metaphases. Major BCR/ABL rearrangement (M-BCR-ABL, P210) was positive tested by real-time quantitative polymerase chain reaction(RQ-PCR). She was diagnosed with Ph+ AML (FAB M0). The patient was treated with 2 courses of DA chemotherapy then achieved bone marrow remission after the first course and achieved Complete Hemotology Response (CHR) after the second course. Then another 2 courses of high dose cytarabine were given. The status of minimal residual disease (MRD) was monitored by RQ-PCR for BCR-ABL/ABL ratio. After that BCR-ABL/ABL ratio was 68%, and then oral treatment with Imatinib 300mg/d×14d was started 4 months after diagnosis. Then 2 more cycles of Imatinib (300 mg/day for 14 days) following IA consolidation chemotherapy were taken and the patient maintained CHR and achieved statuses Complete Molecular Response (CMR) by her BCR-ABL/ABL ratio reducing to 0.4% 8 months after diagnosis. Then she took another course of Imatinib 400mg×4w therapy before allo-SCT. The patient underwent allo-SCT from a HLA-identical unrelated donor 9 months after diagnosis. STR analysis showed completely donor phenotype 1, 3 and 6 months after SCT. Imatinib (300 mg/day) was continued 74 days after SCT and the patient remains continuous CHR with Complete Cytogenetic Response (CCyR) and CMR till now. Patient 2: A 46-year-old man was admitted in Dec. 2004 with fever, cough and fatigue. Physical examination showed pallor and a small submaxillary lymphnode on the right. Blood Routine showed Hb 59g/L, platelets 115×109/L, WBC 3.1×109/L, and 24% blast cells. Bone barrow immunophenotype was CD34+, CD13+, CD117+, HLA-DR+ and MPO-. Karyotype analysis showed 46, XY, t (9; 22) (q34; 11) in 10 analyzed metaphases. Major BCR-ABL rearrangement was positive. He was diagnosed as Ph+ AML (FAB M0). The patient received induction chemotherapy as MA/VP plus Imatinib (400 mg/day×4w) and achieved CHR. Imatinib combined chemotherapy continued for another 7 more cycles. Imatinib was taken as 400 mg/day×2 w during the intermission period of chemotherapy. He had a bone marrow relapse with 18% blasts 48 days after the last chemotherapy, although CCyR and CMR were still maintained. Imatinib was added in a dose of 600mg/day and CHR achieved again 1 month later. The patient then took continuous Imatinib (400mg/day) until he received allo-SCT 26months after diagnosis. STR analysis showed completely donor phenotype 1, 3 and 6 months after SCT. Imatinib (400 mg/day) administration was continued and the patient maintained CHR and CMR in the following clinical course. However, he developed interstitial pneumonia 11 months after SCT and died from severe respiratory failure 30 months after SCT with CHR and CMR still maintained at that time. Our cases indicate that Imatinib combined with daunorubicin based chemotherapy followed by allo-SCT and Imatinib maintenance treatment appears to be the best way to treat Ph+ de novo AML, especially when Imatinib is used in an early phase of AML and when a complete molecular response is achieved before allo-SCT. Disclosures: No relevant conflicts of interest to declare.
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Villgran, Vipin Das, Caitlan Lyons, Adeel Nasrullah, Charmaine Clarisse Abalos, Eric Bihler, and Ahmad Alhajhusain. "Acute Respiratory Failure." Critical Care Nursing Quarterly 45, no. 3 (July 2022): 233–47. http://dx.doi.org/10.1097/cnq.0000000000000408.
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Birkun, A. A., and O. O. Osunsanya. "Acute Respiratory Failure." EMERGENCY MEDICINE, no. 7.78 (December 20, 2016): 102–8. http://dx.doi.org/10.22141/2224-0586.7.78.2016.86102.
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Hankins, Gary D. V. "Acute Respiratory Failure." Clinical Obstetrics and Gynecology 33, no. 3 (September 1990): 493–501. http://dx.doi.org/10.1097/00003081-199009000-00015.
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Kelly, Maryann. "Acute Respiratory Failure." American Journal of Nursing 96, no. 12 (December 1996): 46. http://dx.doi.org/10.1097/00000446-199612000-00046.
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Frat, Jean-Pierre, Damien Marie, and Arnaud W. Thille. "Acute respiratory failure." Current Opinion in Critical Care 25, no. 6 (December 2019): 591–96. http://dx.doi.org/10.1097/mcc.0000000000000670.
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COX, S. C., S. H. NORWOOD, and C. A. DUNCAN. "Acute Respiratory Failure." Survey of Anesthesiology 30, no. 5 (October 1986): 300. http://dx.doi.org/10.1097/00132586-198610000-00049.
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