Fatal Acute Respiratory Distress Syndrome Research Articles

Fulminant Acute Respiratory Distress Syndrome After Calcineurin Inhibitor-belatacept Conversion in a Lung Transplant Recipient

Belatacept is increasingly used in lung transplant (LTx) recipients intolerant to calcineurin inhibitors (CNIs), with satisfactory outcome.1 We describe a case of fatal acute respiratory distress syndrome (ARDS) that developed in a single LTx recipient after starting a belatacept-based immunosuppres

Fatal Acute Respiratory Distress Syndrome Due to Influenza A (H1N1) Infection in Patients After Kidney Transplantation: A Report of Five Cases

BackgroundIn the general population, swine influenza is a self-limited infection. Patients after kidney transplantation, however, are at increased risk for complications and mortality from influenza A (H1N1). Acute respiratory distress syndrome (ARDS) complicates up to 55% of influenza-related pneumonia in hospitalized patients and carries a mortality of 40–46%. We describe our experience in intensive care of kidney transplant patients with ARDS complicating influenza A (H1N1) pneumonia during a flu outbreak.Case ReportFive adult post kidney transplantation patients with progressive respiratory failure admitted to the ICU between February 2016 and April 2016 were included in this retrospectively analysis.All patients had influenza A (H1N1) viral pneumonia (confirmed with RT-PCR) complicated by ARDS and septic shock with multiple organ dysfunction syndrome. None of the patients received seasonal influenza vaccines. All patients had negative rapid influenza bedside tests, which resulted in delay of administration of antiviral therapy prior to admission to the ICU. All patients were managed with a lung protective ventilation strategy (average days of mechanical ventilation, 17.6±15.3). Three patients required additional therapies for refractory hypoxemia, including high positive end-expiratory pressure and prone positioning. Extracorporeal membrane oxygenation was not implemented. Treatment with oseltamivir was added to a broad-spectrum antibiotic on the first to the fifth day of intensive care. Despite these measures, all patients eventually died.ConclusionsDespite great progress in the management of ARDS, based mostly on advanced mechanical ventilation, early antiviral treatment of pneumonia caused by influenza A (H1N1) and annual vaccinations seem essential in prevention and management of influenza A (H1N1) infection among kidney transplant recipients.

Novelties in the field of autoimmunity - 1st Saint Petersburg congress of autoimmunity, the bridge between east and west.

The novel SARS-CoV-2 has been rattling the world since its outbreak in December 2019, leading to the COVID-19 pandemic. The learning curve of this new virus has been steep, with a global scientific community desperate to learn how the virus is transmitted, how it replicates, why it causes such a wide spectrum of disease manifestations, resulting in none or few symptoms in some. Others are burdened by an intense immune response that resembles the cytokine storm syndrome (CSS), which leads to severe disease manifestations, often complicated by fatal acute respiratory distress syndrome and death. Research efforts have been focusing on finding effective cures and vaccinations for this virus.The presence of SARS-CoV-2 in the gastrointestinal (GI) tract, represented by several GI manifestations, has led to its investigation as a target for the virus and as an indicator of disease severity. The response of the microbiome (which is heavily linked to immunity) to the novel SARS-CoV-2 virus, and its role in igniting the exaggerated immune response has therefore become a focus of interest. The objective of our study was to gather the data connecting between the microbiome, the GI tract and COVID-19 and to investigate whether these reported alterations in the gut microbiome bear any resemblance to those seen in lupus, the prototypical autoimmune disease. Confirming such changes may become the steppingstone to potential therapies that may prevent transmission, progression and immune related manifestations of COVID-19, via manipulation of the gut microbiota.We performed an extensive literature review, utilizing the Pubmed search engine and Google Scholar for studies evaluating the microbiome in COVID-19 patients and compared results with studies evaluating the microbiome in lupus. We searched for the terms: microbiome, dysbiosis, COVID-19, SARS-CoV-2, gastrointestinal as well as lupus and autoimmune. While there were hundreds of articles which referred to gastrointestinal manifestations in COVID-19, to date only 4 studies investigated the gastrointestinal microbiome in this setting. We compared the similarities between microbiome of COVID-19 patients and lupus patients.We found that there are several similar processes of immune dysregulation in patients with COVID-19 and in those with lupus, with several other alterations seen in other pathological states. Some of these similarities include loss of microbiota biodiversity, increased representation of pathobionts, which are microbes associated with inflammation and disease (i.e Proteobacteria) and a relative decrease of symbionts, which are protective microbes, associated with anti-inflammatory properties (i.e Lactobacillus). Compromise to the intestinal barrier has also been reported in both.We conclude that the gastrointestinal tract contributes to the disease manifestations in COVID-19. Whether gastrointestinal dysbiosis is the cause or effect of gastrointestinal manifestations and several severe systemic manifestations, which may be the response to an increased pro-inflammatory environment, is still debatable and warrants further investigation. Given the resemblance of the microbiome in COVID-19 patients to that seen in lupus patients, it becomes clearer why several therapies used in autoimmune conditions are currently under investigation for the treatment of COVID-19 patients. Moreover, these findings should promote further investigating the utility of manipulation of the microbiome, via nutritional supplementation or even fecal transplantations, interventions that may alter the course of the disease, and potentially prevent disease transmission at low cost and low risk.

ANLN truncation causes a familial fatal acute respiratory distress syndrome in Dalmatian dogs.

Acute respiratory distress syndrome (ARDS) is the leading cause of death in critical care medicine. The syndrome is typified by an exaggerated inflammatory response within the lungs. ARDS has been reported in many species, including dogs. We have previously reported a fatal familial juvenile respiratory disease accompanied by occasional unilateral renal aplasia and hydrocephalus, in Dalmatian dogs. The condition with a suggested recessive mode of inheritance resembles acute exacerbation of usual interstitial pneumonia in man. We combined SNP-based homozygosity mapping of two ARDS-affected Dalmatian dogs and whole genome sequencing of one affected dog to identify a case-specific homozygous nonsense variant, c.31C>T; p.R11* in the ANLN gene. Subsequent analysis of the variant in a total cohort of 188 Dalmatians, including seven cases, indicated complete segregation of the variant with the disease and confirmed an autosomal recessive mode of inheritance. Low carrier frequency of 1.7% was observed in a population cohort. The early nonsense variant results in a nearly complete truncation of the ANLN protein and immunohistochemical analysis of the affected lung tissue demonstrated the lack of the membranous and cytoplasmic staining of ANLN protein in the metaplastic bronchial epithelium. The ANLN gene encodes an anillin actin binding protein with a suggested regulatory role in the integrity of intercellular junctions. Our study suggests that defective ANLN results in abnormal cellular organization of the bronchiolar epithelium, which in turn predisposes to acute respiratory distress. ANLN has been previously linked to a dominant focal segmental glomerulosclerosis in human without pulmonary defects. However, the lack of similar renal manifestations in the affected Dalmatians suggest a novel ANLN-related pulmonary function and disease association.

Fatal acute respiratory distress syndrome after stem cell infusion

Fatal acute respiratory distress syndrome after stem cell infusion

Safety of endoscopic retrograde cholangiopancreatography in pregnancy: Fluoroscopy time and fetal exposure, does it matter?

To estimate the fetal radiation exposure using thermoluminescent dosimeters (TLD's) in pregnant patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) and assess its relevance. Data on thirty-five therapeutic ERCPs conducted in pregnant patients from 2001 to 2009 were retrieved from a prospective database. Techniques to minimize fluoroscopy time were implemented and the fluoroscopy times captured. TLD's were placed on the mother to estimate the fetal radiation exposure and the results were compared to the maximum allowed dose of radiation to the fetus [0.005 gray (Gy)]. Obstetrics consultations were obtained and the fetus was monitored before and after the ERCP. Fluoroscopy was performed at 75 kVp. ERCP was performed with the patients supine by dedicated biliary endoscopists performing more than 500 cases a year. A total of 35 pregnant patients underwent ERCP and biliary sphincterotomy (14 in first trimester, 11 in second trimester, and 10 in third trimester). Mean maternal age was 25 years (range 16-37 years) and mean gestational age was 18.9 wk (range 4-35 wk). Mean fluoroscopy time was 0.15 min (range 0-1 min). For 23 women, the estimated fetal radiation exposure was almost negligible (< 0.0001 Gy) while for 8 women, it was within the 0.0001-0.0002 Gy range. Three women had an estimated fetal radiation exposure between 0.0002 and 0.0005 Gy and 1 woman had an estimated fetal radiation exposure greater than 0.0005 Gy. Complications included 2 post-sphincterotomy bleeds, 2 post-ERCP pancreatitis, and 1 fatal acute respiratory distress syndrome. One patient developed cholecystitis 2 d after ERCP. ERCP with modified techniques is safe during pregnancy, and estimating the fetal radiation exposure from the fluoroscopy time or measuring it via TLD's is unnecessary.

A rare case of fatal acute respiratory distress syndrome following diesel oil siphonage

Sir, Diesel oil aspiration is an uncommon mode of hydrocarbon aspiration and can lead to severe chemical pneumonitis either due to direct inhalation of aerosol or aspiration of liquid or indirectly following aspiration of vomitus secondary to diesel oil ingestion during the manual siphoning from fuel tanks. Siphonage of fuel from the motor vehicles fuel tanks is a typical practice seen in third world countries. Data are sparse on outcomes and complications of direct diesel oil aspiration following manual siphoning.[12] We report a case of 21-year-old male industrial worker who was admitted to the emergency room with a history of diesel oil ingestion and aspiration following accidental siphoning of oil. He was febrile, dyspneic with altered sensorium and having feeble pulse (pulse rate-124/min) and falling blood pressure (82/40 mmHg). On auscultation of chest, coarse, basal, inspiratory crepitations were heard. Arterial blood gas (ABG) analysis showed severe hypoxemia with metabolic acidosis. In view of deteriorating clinical condition, his trachea was intubated with endotracheal tube and was supported with intravenous fluids and inotropes. He was then shifted to intensive care unit (ICU) for mechanical ventilatory support and further management. In ICU, chest X-ray Anteroposterior view (AP) showed bilateral, non-segmental, homogeneous opacities in the lower zones. There was a significant increase in leukocyte counts (total leukocyte count-16,200/Ul, neutrophills 92%). Empirical broad spectrum antibiotics (piperacillin/tazobactam 4.5 g IV q8h) were immediately started after sending blood and tracheal aspirate for culture and sensitivity. On day 2 in ICU, the patient's clinical condition deteriorated dramatically. Chest X-ray showed bilateral progression of infiltrates involving nearly all lobes of the lungs. ABG analysis showed severely diminished PF ratio (PaO2/ FIO2 < 100). These findings were suggestive of a severe form of acute respiratory distress syndrome (ARDS).[3] Aggressive supportive therapy and low tidal volume ventilation strategy was immediately initiated.[4] We also started a continuous infusion of low dose methylprednisolone (@ 1 mg/kg/day after giving bolus of 1 mg/kg IV). On day 5, he had an episode of pulseless ventricular tachyarrhythmia, unresponsive to all possible resuscitative measures and eventually expired that day. Direct aspiration of hydrocarbons may cause severe chemical (lipoidal) pneumonitis with perilous outcome.[25] The severity of lung tissue damage depends on physical characteristics of hydrocarbon, which includes viscosity, volatility and side chains of hydrocarbons. The probability of severe lung affliction is extensive with hydrocarbons having high volatility and low viscosity (<60 saybolts seconds universal (SSU)).[6] Diesel fuel (grade 1D and 2D) have a low viscosity (32-45 SSU) and is highly volatile and a potential hydrocarbon to cause severe progressive lung damage and fatal ARDS.[6] In early period of hydrocarbon induced pneumonia, patients may have non-specific symptoms such as cough, breathlessness and rarely chest pain or haemoptysis.[7] Later, these patients may develop cardiomyopathies or fatal cardiac arrhythmias.[7] Although right middle lobes are commonly affected by direct aspiration of diesel, chest radiographic findings may include consolidation, atelectasis, pleural effusion and lower lobe involvement as seen in this patient.[128] The management strategies in these patients are usually symptomatic and supportive. There is limited and controversial role of corticosteroids and antibiotics with sparse data on outcomes.[18] This patient showed accelerated deterioration of lung functions and eventually expired due to fatal cardiac arrhythmias within a period of 4 days despite initiating corticosteroids, broad-spectrum antibiotics and strict adherence to ventilator protocols followed in ARDS patients.[4] This case highlights that chemical pneumonitis triggered by direct diesel oil aspiration following manual siphoning is a pernicious clinical condition in which lung damage is progressive and extensive resulting in ARDS, which seldom respond to standard management strategies. Moreover, death can ensue due to fatal cardiac arrhythmias even in early course of the disease. Critical carers should circumspect this rare and fatal clinical condition early in its course and should intervene with aggressive management strategies to avoid cataclysmic outcomes.

Pulmonary blastomycosis in a professional diver: An occupational risk

In certain parts of the United States and Canada, and northern Ontario in particular, the dimorphic fungus Blastomyces dermatitidis is endemic and can cause infection in exposed individuals. The site of infection is usually pulmonary, causing respiratory and constitutional symptoms, but can also affect other sites in the body. Symptom severity can vary substantially from no symptoms to fatal acute respiratory distress syndrome. The present report describes a 27-year-old professional diver who had recently worked in northern Ontario, who developed symptoms of pneumonia and exhibited atypical findings on chest imaging. He was diagnosed with blastomycosis based on histopathological findings and fungal culture, and was treated with amphotericin B and itraconazole in accordance with treatment guidelines. While outdoor occupations in endemic areas increase the risk of infection, there is no literature specifically identifying professional diving as an occupational risk for blastomycosis.

Human Metapneumovirus Infection as an Emerging Pathogen Causing Acute Respiratory Distress Syndrome

To the Editor—Viral respiratory infections represent a frequent cause of intensive care unit (ICU) admissions in children and impose a considerable burden worldwide [1]. The main pathogens are respiratory syncytial virus (RSV) and seasonal influenza. Human metapneumovirus (hMPV) is an emerging pathogen of the Paramyxoviridae family causing acute bronchiolitis-like respiratory illness in children [2]. Williams et al [2] have recently reported an annual rate of hMPV-associated hospitalizations of 1.2 per 1000 hospitalized children <5 years of age in the United States, confirming that hMPV contributes significantly to respiratory morbidity with a similar impact as influenza. In their study, most hMPV-infected children had a relatively mild course, with only 1 participant (3%) requiring ICU admission. We would like to comment on severe hMPV infections and to present the case of a child with fatal acute respiratory distress syndrome (ARDS) due to infection with hMPV. The 20-month-old boy initially presented with a bronchiolitis-like pattern, with rhinitis, cough, and increasing respiratory distress. The child's history was unremarkable except for moderate neurodevelopmental delay of unknown etiology. Because of impending respiratory failure (capillary pH, 7.17; partial carbon dioxide pressure, 86 mm Hg; saturation 83% with 100% oxygen), he was intubated. The oxygenation index was 0.32 and the PaO2/FiO2 ratio resulted 68 (55 mm Hg/0.8). On the basis of radiological findings of bilateral diffuse pulmonary infiltrates, the diagnosis of ARDS was made. Echocardiography demonstrated good biventricular function and no evidence for pulmonary hypertension. The patient was placed on high-frequency oscillatory ventilation (Sensormedics 3100A), with a mean airway pressure of up to 30 cm water. Tests for RSV and H1N1 influenza virus were negative. Results of repeated bacterial blood and tracheal fluid cultures were negative. Therefore, an expanded panel of respiratory viruses (adenovirus, picornaviruses, influenzavirus A/B, parainfluenzaviruses 1–3, RSV, and hMPV) was assessed using direct immunofluorescence. The patient tested positive for hMPV. Viral testing was repeated several times and confirmed only infection with hMPV. Because of the high risk of bacterial superinfection, empirical treatment with cefuroxime and vancomycin was initiated. The patient subsequently developed multi-organ failure, with catecholamine-dependent arterial hypotension, renal failure requiring continuous renal replacement, coagulopathy, thrombocytopenia, leukopenia, and hepatitis. Because oxygenation further deteriorated (oxygenation index, .45), venoarterial extracorporal membrane oxygenation (ECMO) was initiated. After repeated failed attempts to wean from ECMO, the decision to limit treatment was made on day 18 after admission. The patient died after cessation of ECMO. The parents declined an autopsy. To date, lethal hMPV infections have been primarily described in immunosuppressed adults [3]. hMPV was first reported in the Netherlands in 2001, and several studies have shown that the clinical course of hMPV closely resembles RSV infection with bronchiolitis, pneumonia, and asthma exacerbation as the main manifestations [2]. In contrast, the proportion of children with severe hMPV infection requiring ICU admission or respiratory support is small [2, 4]. However, infants with RSV and hMPV coinfection had a 10-fold increased risk of requiring mechanical ventilation when compared with infants with isolated RSV infection [4]. Although ARDS is known to occur in patients with RSV bronchiolitis [5], hMPV-associated pediatric ARDS is very rare. An extensive literature search resulted in only 4 pediatric patients with isolated hMPV infection who developed severe ARDS: a 17-month-old girl receiving chemotherapy for acute leukemia died after a prolonged period of mechanical ventilation [6]. Two other children, both with underlying diseases (prematurity with chronic lung disease in one, transplant-related immunosuppression in the other), required ECMO but ultimately recovered [7, 8]. The fourth reported case concerns a 2 year-old, previously healthy girl without any known immunodeficiency who died of pulmonary hemorrhage soon after admission [9]. It has been suggested that deficiencies in innate immunity pathways, such as Toll-like receptor 4, lead to an increased risk of severe RSV infection [10], but the role of innate immunity in hMPV infections has not been studied thus far. The underlying neurodevelopmental delay may represent a clinical risk factor for severe respiratory disease in the presented case [2]. In conclusion, the summarized cases illustrate that hMPV infection may cause severe ARDS in susceptible children. Considering that testing for hMPV is not routinely performed, it is likely that hMPV-related ARDS is underreported. The mortality of pediatric ARDS remains high and early identification of the causative agent is crucial. We, therefore, suggest early testing for hMPV in patients with presumptive viral ARDS where no other agent can be identified. Additional studies investigating the role of hMPV in severe respiratory infections are needed to improve early and appropriate treatment of high-risk patients.

Cleaved caspase-3 in lung epithelium of children who died with acute respiratory distress syndrome

To investigate the extent of cleaved caspase-3 immunostaining in lung epithelial cells in children with acute respiratory distress syndrome. Observational study in sixteen children who died with acute respiratory distress syndrome and diffuse alveolar damage. Pediatric intensive care unit. Sixteen children with fatal acute respiratory distress syndrome and diffuse alveolar damage. None. Double immunohistochemistry for cleaved caspase-3 and (pan)cytokeratin in lung tissues obtained at autopsy. Spectral imaging was used for the quantification of immunohistochemistry colocalization of these markers. We found a wide range in the percentage of alveolar epithelial cell surface area with positive cleaved caspase-3 staining in the lungs of children with acute respiratory distress syndrome (from 1% to almost 20%). The degree of caspase-3 immunostaining in epithelial cells positively correlated with age. There is a high variability in the extent of classic apoptosis in lung epithelial cells in pediatric acute respiratory distress syndrome, potentially in part dependent on age.

Fatal acute respiratory distress syndrome in a patient with paracoccidioidomycosis: first case report

Paracoccidioidomycosis is a systemic mycosis that is usually acquired early in life by inhalation of conidia which convert in the lungs into yeast forms; these in turn trigger an inflammatory process. This mycosis may appear as an acute/subacute form or a chronic, adult form. Acute/subacute presentations can be observed in children and young adults, with the reticuloendothelial system frequently involved but the lungs are usually spared or present with mild clinical or radiological alterations. Acute respiratory distress syndrome (ARDS), an extensive dysfunction of the lungs alveolar-capillary barrier has occasionally been observed in other endemic mycoses such as coccidioidomycosis, cryptococcosis, histoplasmosis and blastomycosis. We describe the first patient with acute paracoccidioidomycosis who developed fatal ARDS accompanied by multiple organ injuries. The basis of the rarity of this entity in patients with paracoccidioidomycosis, as well as the reasons that may have lead to the development of ARDS in this patient are discussed.

A fulminant case of acute respiratory distress syndrome associated with Mycoplasma pneumoniae infection

Acute respiratory distress syndrome (ARDS) caused by mycoplasmas is very rare. This report describes a severe case of atypical pneumonia due to M. pneumoniae in a formerly healthy young woman who developed high grade fever and cough leading to severe disseminated lung disease and finally to fatal ARDS. This case came into picture when killer atypical pneumonia, namely, SARS (severe acute respiratory syndrome), spread very fast from South-Asian countries to the rest of the world. Moreover, the clinical presentation and radiologic features of SARS bear resemblance to the syndrome of atypical pneumonia, which lead us to investigate this case into detail. We suggest that M. pneumoniae infections should be included in the differential diagnosis of pathogens causing ARDS, establishing an early diagnosis may have important therapeutic implications.

Syndrome de détresse respiratoire aiguë à la gemcitabine d’évolution favorable

Gemcitabine is a new important drug used to treat solid tumors including non-small cell lung cancer, pancreatic, bladder and breast cancers. Myelosuppression is the most common adverse effect. Pulmonary toxicity is rare and usually mild and self-limiting with acute dyspnea. Severe pneumonitis and potentially fatal acute respiratory distress syndrome (ARDS) have been described in patients treated for a non-small cell lung cancer. We report a case of gemcitabine-induced ARDS in a 72-year old patient treated with gemcitabine and cisplatin for a bladder cancer without lung metastasis. Administration of high doses of corticosteroids led to a prompt symptomatic improvement.

Compounded Colistimethate as Possible Cause of Fatal Acute Respiratory Distress Syndrome

To the Editor: We report a case of pharmacy compounding of the colistin prodrug colistimethate sodium that led to a fatal case of the acute respiratory distress syndrome (ARDS). The patient was a 2...

Thoraxverletzungen

Thorax injuries may be divided etiologically into blunt and penetrating types, depending on the nature of the insult. In European practice, the former predominates by far, and in only about 5% of cases thoracotomy provides the necessary thorax drainage. Morbidity in this type of injury typically involves concomitant lung contusion, sometimes with fatal acute respiratory distress syndrome. In these cases, special ventilation forms, optimal reduction of pain, and organ replacement are the decisive therapeutic methods. In contrast, about 80% of penetrating trauma to the thorax require prompt transpleural or trans-sternal surgery, depending on the type of injury. Emergency first aid must follow the principle of "scoop and run". Each minute elapsed until emergent thoracotomy can be decisive to survival in these cases, and the fastest possible transport from the place of injury takes priority over time-consuming stabilization.

Lethal acute respiratory distress syndrome during anti-TNF-α therapy for rheumatoid arthritis

Tumor necrosis factor alpha (TNF-alpha) blocking drugs improve therapy for rheumatic diseases, but the risk of additional immunosuppression and infection is unclear. We report on a patient with rheumatoid arthritis treated with etanercept for 2 years, in addition to methotrexate and prednyliden, who developed fulminant pneumococcal pneumonia with rapid progression to fatal acute respiratory distress syndrome (ARDS) and septic shock. In patients receiving anti-TNF-alpha therapy, especially in combination with corticosteroids, signs of pulmonary infection should be regarded as very serious, as fulminant pneumonia with ARDS and severe sepsis may develop within 24 h.

Experience of the Gynecologic Oncology Unit at Ain Shams University in the treatment of gestational trophoblastic tumors.

The aim of the study is to evaluate the different treatment modalities in the management of gestational trophoblastic tumors (GTT) in a tertiary care setting. One hundred and twenty patients between 16 and 55 years of age (mean 30.6) diagnosed and treated for GTT at the Gynecologic Oncologic Unit, Ain Shams University, between June 1992 and November 1998 were studied. The mean parity of the group was 2.5 (0-12) with a mean follow-up of 47.4 months (16-96). One hundred cases (83.3%) followed a molar pregnancy, while 17 (14.2%) and three (2.5%) had an antecedent abortion and term pregnancy, respectively. By adopting the National Institutes of Health Classification due to its practicality, 65 (54.1%) were nonmetastatic and 55 (45.9%) were metastatic; 17 (14.2%) low-risk metastatic and 38 (31.7%) high-risk metastatic. Forty-two patients (35%) had a hysterectomy, which was curative in 16 (13.3%). In the high-risk metastatic group, 22 patients were treated with EMA achieving a complete stable remission in 19 (86.3%) with one of the remaining three being salvaged by EMA-EP. One hundred fourteen (95%) patients are alive and well without evidence of disease with all six deaths occurring in the high-risk metastatic group. One of the deaths was due to unrelated disease (repeat variceal hemorrhage from portal hypertension), while the remaining five followed nonmolar pregnancies with four having brain and/or liver metastases and another presenting with resistant fatal acute respiratory distress syndrome (ARDS) despite optimal support. By using multivariate analysis, it was found that only the presence of brain and/or liver metastases, followed by an antecedent nonmolar pregnancy and resistance to multiple agent chemotherapy were significant as regards the prognosis of high-risk metastatic GTT. These tumors are highly curable with death almost limited to those with brain and/or liver metastases, particularly following nonmolar pregnancies. In these extremely high-risk categories, elaboration of more intensive and innovative combination chemotherapy protocols is needed in order to achieve better results than those currently reported. In addition the use of EMA instead of EMA-CO deserves to be tested in properly randomized controlled collaborative studies to reduce treatment toxicity.

Pancreatitis and fatal ARDS following high-dose cytarabine induction for acute myelogenous leukemia

Objective. To describe a case of fatal acute respira tory distress syndrome (ARDS) and pancreatitis aris ing from high-dose cytarabine induction therapy. Case Summary. A 50-year-old male without a history of hepatobiliary disease and with a diagnosis of acute myelogenous leukemia was treated with high-dose cytarabine therapy. Tumor lysis occurred promptly; the white cell count reached a nadir of 100/mm 3 3 days after initiation of therapy. Severe mid-epigastric pain, fever, hypotension, and increased lipase and amylase occurred on the 6th day of cytara bine therapy. Cytarabine was discontinued 6 days after initiation. Serum amylase and lipase were persis tently elevated; respiratory failure due to ARDS ensued, and the patient expired of refractory hypoxemia. Discussion. Cytarabine-associated pancreatitis is a rare occurrence. Literature reports have described pancreatitis after high-dose cytarabine therapy for induction of remission of ALL and acute myelogenous leukemia. Pancreatitis resolved in all reported cases on discontinuation of cytarabine. In our patient, drug-induced pancreatitis likely provoked the onset of ARDS, which concluded with fatal respiratory failure. The absence of positive cultures decreased the likeli hood of sepsis-induced ARDS; the time course of cytarabine administration was temporally associated with the development of pancreatitis. Conclusions. Acute pancreatitis is a rare but potentially fatal event associated with high-dose cy tarabine therapy.