Pulmonary Alveolar Hemorrhage Research Articles

Clinical manifestations and pulmonary histopathological analysis related to different diseases in patients with fatal pulmonary thromboembolism: an autopsy study.

BackgroundTo correlate underlying diseases, in autopsies of patients with pulmonary thromboembolism (PTE) to histological findings and manifestations reviewed in the medical records.MethodsThe autopsy records between 2001 and 2008 of 291 patients whose cause of death was PTE were reviewed. The following data were obtained: age, sex, clinical “in vivo” manifestations, postmortem pathological patterns, and main associated underlying diseases, cancers, and surgeries performed in the last hospitalization. The pulmonary histopathological changes were categorized as diffuse alveolar damage, pulmonary edema, alveolar hemorrhage, and lymphoid interstitial pneumonia. Odds ratios of positive relations were obtained by logistic regression and were considered significant when P<0.05.ResultsThe median age was 64 years old. About 64% of patients presented cardiovascular illness associated with PTE. The most prevalent pulmonary finding was pulmonary edema. Only 13% of cases had clinical suspicion of PTE. Acute respiratory failure was positively related to pulmonary edema, alveolar hemorrhage, and diffuse alveolar damage as well as hemodynamic instability to alveolar hemorrhage and diffuse alveolar damage.ConclusionWe found important relations between clinical data and histological findings of patients with fatal PTE. A greater understanding of the pulmonary physiopathological mechanisms involved with each disease associated to PTE could improve its diagnosis and treatment.

Life-threatening hemorrhagic pneumonia caused by Stenotrophomonas maltophilia in the treatment of hematologic diseases

Since the late 1990s, Stenotrophomonas maltophilia (S. maltophilia) has become one of the most common nonfermenting Gram-negative bacilli that cause opportunistic infection. Patients with hematologic diseases are the most risky candidate for S. maltophilia pneumonia or sepsis because of chemotherapy-induced neutropenia or immunodeficiency. Frequent exposure to broad-spectrum antibiotics and prolonged insertion of central venous catheter further enhance the risk of S. maltophilia infection. One of the most severe S. maltophilia infections is hemorrhagic pneumonia. This type of infection is mostly fatal because of pulmonary alveolar hemorrhage that leads to acute respiratory failure. Furthermore, S. maltophilia exhibits a high-level intrinsic resistance to conventional antibiotics such as β-lactams and aminoglycosides and, more recently, the increasing acquired resistance to co-trimoxazole and quinolones. According to our experienced and previously reported cases, all of the patients with hemorrhagic pneumonia caused by S. maltophilia had a fatal course within a few days after the onset of the pneumonia. In this article, we perform a systematic review on a total 30 cases of hemorrhagic pneumonia induced by S. maltophilia from our institutions and the literature, and we describe its early diagnosis, prophylaxis, and recommended therapeutic strategy for the infection in the treatment of hematologic disease.

High-Resolution Computed Tomographic Findings of Cocaine-Induced Pulmonary Disease: A State of the Art Review

Cocaine is the most commonly used illicit drug among patients presenting at hospital emergency departments and the most frequent cause of drug-related deaths reported by medical examiners. Various respiratory problems temporally associated with cocaine use have been reported. Acute and chronic uses also are responsible for lung complications, such as pulmonary edema, alveolar hemorrhage, pulmonary hypertension, organizing pneumonia, emphysema, barotrauma, infection, cancer, eosinophilic disease, and aspiration pneumonia. Although most imaging findings are nonspecific, they may raise suspicion of a cocaine-related etiology when considered together with patients' profiles and medical histories. This literature review describes cocaine-induced diseases with pulmonary involvement, with an emphasis on high-resolution chest computed tomographic findings and patterns.

Pulmonary alveolar hemorrhage from a pulmonary artery false aneurysm after Swan-Ganz catheterization in a thoracic aortic aneurysm patient: a case report.

Pulmonary artery (PA) rupture caused by a PA Swan-Ganz catheter is a rare complication but remains fatal in almost 50% of cases. False aneurysm of the PA is a rare presentation of PA rupture and should be considered as a possible diagnosis in a patient with a new lung mass after PA catheterization. We present a case of sudden-onset pulmonary alveolar hemorrhage during cardiovascular surgery due to a traumatic PA false aneurysm. The Swan-Ganz catheter might have been displaced by the thoracic aortic aneurysm with displacement of the catheter causing the false aneurysm and bleeding.

Translational toxicological research: investigating and preventing acute lung injury in organophosphorus insecticide poisoning

Poisoning through ingestion of organophosphorus (OP) insecticide is a leading cause of suicide globally. Severe poisoning with OP compounds creates an unconscious, paralysed patient with respiratory failure. These symptoms make...

Mycobacterium abscessus Bacteremia After Receipt of Intravenous Infusate of Cytokine-Induced Killer Cell Therapy for Body Beautification and Health Boosting

We report the first series of Mycobacterium abscessus bacteremia after cytokine-induced killer cell therapy for body beautification and health boosting. The clinical manifestations, laboratory and radiological investigations, cytokine/chemokine profiles, and outcomes were described and analyzed. Four patients were admitted, and 3 patients had septic shock. Chest radiographs showed pulmonary infiltrates in all patients. Three patients developed peripheral gangrene, and 1 patient required lower limb and finger amputations. Patient 1 also developed disseminated infection including meningitis and urinary tract infection. Postmortem examination of patient 1 showed focal areas of pulmonary hemorrhage and diffuse alveolar damage, splenic infarct, adrenal necrosis, and hemorrhage, and acid-fast bacilli (AFB) were seen in the lung, liver, kidney, and adrenal gland. Patient 2 developed inguinal granulomatous lymphadenitis about 40 days after onset of lower limb gangrene. Wedge-shaped pulmonary infarcts were found in patient 3, and retinitis and subcutaneous lesions developed in patient 4. Patients in septic shock had dysregulated cytokine/chemokine profiles. Patient 4 with relatively milder presentation had increasing levels of interleukin 17 and cytokines in the interferon-γ/interleukin 12 pathway. All survivors required prolonged intravenous antibiotics. Blood cultures grew M. abscessus for all patients, and admission peripheral blood smear revealed AFB for 3 patients. Mycobacterium abscessus was also isolated from respiratory specimens (2 patients), urine (1 patient), and cerebrospinal fluid (1 patient). Time to initial blood culture positivity (patients 1, 2, and 3: ≤52 hours; patient 4: 83 hours) appeared to correlate with disease severity. Empirical coverage for rapidly growing mycobacteria should be considered in patients with sepsis following cosmetic procedures.

Phillyrin attenuates LPS-induced pulmonary inflammation via suppression of MAPK and NF-κB activation in acute lung injury mice

Phillyrin (Phil) is one of the main chemical constituents of Forsythia suspensa (Thunb.), which has shown to be an important traditional Chinese medicine. We tested the hypothesis that Phil modulates pulmonary inflammation in an ALI model induced by LPS. Male BALB/c mice were pretreated with or without Phil before respiratory administration with LPS, and pretreated with dexamethasone as a control. Cytokine release (TNF-α, IL-1β, and IL-6) and amounts of inflammatory cell in bronchoalveolar lavage fluid (BALF) were detected by ELISA and cell counting separately. Pathologic changes, including neutrophil infiltration, interstitial edema, hemorrhage, hyaline membrane formation, necrosis, and congestion during acute lung injury in mice were evaluated via pathological section with HE staining. To further investigate the mechanism of Phil anti-inflammatory effects, activation of MAPK and NF-κB pathways was tested by western blot assay. Phil pretreatment significantly attenuated LPS-induced pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration. The lung wet-to-dry weight ratios, as the index of pulmonary edema, were markedly decreased by Phil pretreatment. In addition, Phil decreased the production of the proinflammatory cytokines including (TNF-α, IL-1β, and IL-6) and the concentration of myeloperoxidase (MPO) in lung tissues. Phil pretreatment also significantly suppressed LPS-induced activation of MAPK and NF-κB pathways in lung tissues. Taken together, the results suggest that Phil may have a protective effect on LPS-induced ALI, and it potentially contributes to the suppression of the activation of MAPK and NF-κB pathways. Phil may be a new preventive agent of ALI in the clinical setting.

Methyl palmitate attenuates lipopolysaccharide-induced acute lung injury in mice.

The study is aimed to determine the beneficial effects of methyl palmitate (MP) which has antioxidant and anti-inflammatory effects demonstrated on murine model of acute lung injury induced by lipopolysaccharide (LPS). Forty male BALB/C mice were randomly allocated into four groups (n=10, each): control group, methyl palmitate group (300 mg/kg), LPS group, and methyl palmitate -treated groups. Methyl palmitate or vehicle was given with an intraperitoneal administration 1 h before an intratracheal instillation of LPS (5 mg/kg). The severity of pulmonary injury was evaluated 6 h after LPS challenge. All experimental procedures complied with the requirements of the Animal Care and Ethics Committee of the Adnan Menderes University. Methyl palmitate pretreatment significantly attenuated LPS-induced pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration. Methyl palmitate pretreatment also reduced the concentrations of malondialdehyde in lung tissues. This study indicates that methyl palmitate may have a protective effect against LPS-induced acute lung injury, and the potential mechanism of this action may involve the inhibition of NF-κB. activation.

Rapid Progression of Metastatic Pulmonary Calcification and Alveolar Hemorrhage in a Patient with Chronic Renal Failure and Primary Hyperparathyroidism

Rapid Progression of Metastatic Pulmonary Calcification and Alveolar Hemorrhage in a Patient with Chronic Renal Failure and Primary Hyperparathyroidism

Rituximab: rescue therapy in life-threatening complications or refractory autoimmune diseases: a single center experience

Rituximab (RTX) is a chimeric anti-CD20 antibody, approved for rheumatoid arthritis (RA) patients who failed anti-Tumor Necrosis Factor therapy. It has been used occasionally for life-threatening autoimmune diseases (AID). We report our center experience in the use of RTX in life-threatening complications or refractory AID. Clinical charts of patients treated with RTX at our center were reviewed, cases treated for life-threatening complications or refractory AID were analyzed. Acute damage to vital organs such as lung, heart, kidney, nervous system with severe functional impairment were defined as life-threatening complications; treatment failure with high-dose corticosteroids, cyclophosphamide, IVIG, plasmapheresis was defined as refractory autoimmune disease. During the years 2003-2009, 117 patients were treated with RTX, most of them for RA. Nine patients (6 females, mean age 51.5 years, mean disease duration 6.3 years) answered the criteria. The indications were as follows: pulmonary hemorrhage (1 patient with cryoglobulinemic vasculitis, 1 with systemic sclerosis, 1 with ANCA-associated vasculitis), catastrophic anti-phospholipid syndrome (2 SLE patients), non-bacterial endocarditis and pulmonary hypertension (1 patient with mixed connective tissue disease), vasculitis and feet necrosis (1 patient with systemic lupus erythematosus), severe lupus demyelinative neuropathy and acute renal failure (1 patient), and severe rheumatoid lung disease with recurrent empyema and pneumothorax (1 patient). B cell depletion was achieved in all patients. The median time since starting of complications to RTX administration was 3 weeks (range 2-15 weeks). Complete remission (suppression of the hazardous situation and return to previous stable state) was seen in 7 out of 9 patients. Partial remission (significant improvement) was achieved in the remained. The median time to response was 3 weeks (range 1-8 weeks), mean follow-up 47.2 months (range 6-60 months). A rapid tapering off of steroids was achieved in all patients. Two patients relapsed and were successfully retreated with RTX: the patient with severe RA lung relapsed after 3 years, one of the patients with ANCA-associated pulmonary alveolar hemorrhage relapsed after 10 months. There were no side effects during RTX infusion. Two episodes of serious infections were registered: fatal Gram-negative sepsis 6 months after RTX treatment, and septic discitis 4 months after receiving RTX. RTX serves as a safe, efficient, and prompt rescue therapy in certain life-threatening conditions and resistant to aggressive immunosuppression AID. RTX when administrated at an earlier stage, prevented irreversible vital organ damage, and allowed rapid steroid tapering off in already severe immunodepressed patients.

Multicenter Phase 2 Trial of G-CSF Priming, Clofarabine, and High Dose Cytarabine (GCLAC) for Newly Diagnosed Acute Myeloid Leukemia, Advanced Myelodysplastic Syndrome or Advanced Myeloproliferative Neoplasm

AbstractAbstract 3594 Background:Several regimens composed of clofarabine and cytarabine have exhibited efficacy for both newly diagnosed and relapsed/refractory acute myeloid leukemia (AML) (Faderl et al Blood 2005, 2006, 2008). Clofarabine's ability to increase araCTP formation and inhibit ribonucleotide reductase confer potent anti-leukemic effect. We previously reported the results of an induction regimen consisting of G-CSF priming, clofarabine, and high dose cytarabine for relapsed/refractory AML (GCLAC) (Becker et al Br J Haematol 2011), which resulted in a complete remission (CR) rate of 46% overall, and a CR rate of 50% in patients with poor risk cytogenetics. Furthermore, we demonstrated that GCLAC is superior to fludarabine/cytarabine combinations in the relapsed/refractory setting (retrospective comparison; Becker et al Haematologica Epub ahead of print, 2012). Because of its activity as a salvage regimen, we examined the response rate and toxicity of GCLAC in the upfront setting. Methods:A multicenter clinical trial (NCT01101880) of G-CSF priming, clofarabine, and high dose cytarabine enrolled newly diagnosed patients < 65 years old with acute myeloid leukemia (AML), advanced myelodysplastic syndrome (MDS) or advanced myeloproliferative neoplasm (MPN) from September 2010 through May 2012. The GCLAC regimen consists of G-CSF 5 mcg/kg/day by subcutaneous injection beginning the day prior to chemotherapy until neutrophil recovery, clofarabine 30 mg/m2/day × 5, and cytarabine 2 gm/m2/day × 5. A second induction with the same regimen was permissible if marrow blasts over 5% persisted on day 21 or thereafter. Consolidation courses were administered for up to 3 cycles, with clofarabine 25 mg/m2/day days 1–4, cytarabine 2 gm/m2/day days 1–4, and G-CSF days 0–4. Results:Fifty patients with non-APL AML, RAEB2, or myelofibrosis with >10% blasts were treated. The median age was 53, range 22–64. Twenty-one of the patients (42%) had antecedent hematologic disorders or proliferative/dysplastic disorders with ≥10% blasts or secondary leukemia. Twelve patients (24%) had unfavorable, 32 patients (64%) intermediate, and 4 (8%) favorable cytogenetics. Overall, 37 patients (74%) achieved complete remission (CR; 95% CI 62–86%), 40 (80%) CR + CRp (CR with incomplete platelet recovery). Of these remissions, 5CRs and 1 CRp had been attained after a second induction course in 11 patients. Thirty-four patients received one, 20 two, and 11 three cycles of consolidation treatment. The CR rate was 83% for patients without antecedent hematological disorder (AHD), and 57% for those with AHD. The CR rate was 100% for patients with favorable risk, 84% for those with intermediate risk, and 46% for those with unfavorable risk cytogenetics. The median time to neutrophil recovery (>500/μl) was 19 days (13–35 range) and to platelet recovery >100,000/μl 24 days (16–63 range) after induction. The most significant grade 4 toxicity occurring in 3 patients, was a constellation of pulmonary infiltrates, hypoxia, and diffuse alveolar hemorrhage that responded to steroids, and was rarely seen when patients were premedicated with steroids. Out of the 125 cycles of chemotherapy administered, the most frequent grade 3 adverse events (AEs) were pulmonary (11), bacteremia (22), and transaminase elevation (10). There were 11 grade 4 AEs including pulmonary (5), hyperglycemia (2), transaminase elevation (1), acute cholecystits (1), and septic shock (2). The 30 day mortality was 0%. Conclusion:GCLAC is a well tolerated induction regimen and a comparison with 7+3 is in progress, using data from Southwest Oncology Group (SWOG) and the Fred Hutchinson Cancer Research Center (FHCRC). Disclosures:Becker:Sanofi: Research Funding. Off Label Use: Clofarabine is indicated for the treatment of pediatric patients with relapsed or refractory acute lymphoblastic leukemia.

Shikonin attenuates lipopolysaccharide-induced acute lung injury in mice

BackgroundShikonin, a natural naphthoquinone pigment extracted from the root of Lithospermum erythrorhizon, has shown a variety of pharmacologic properties including anti-inflammatory effect. In the present study, we analyzed the role of shikonin in acute lung injury induced by lipopolysaccharide (LPS) in mice. Materials and methodsSixty male BALB/C mice were randomly allocated into six groups (n = 10, each): control group, shikonin group (50 mg/kg), LPS group, and three different doses (12.5, 25, and 50 mg/kg) for shikonin-treated groups. Shikonin or vehicle was given with an intragastric administration 1 h before an intratracheal instillation of LPS (5 mg/kg). The severity of pulmonary injury was evaluated 6 h after LPS challenge. ResultsShikonin pretreatment significantly attenuated LPS-induced pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration. The lung wet-to-dry weight ratios, as the index of pulmonary edema, were markedly decreased by shikonin pretreatment. Moreover, shikonin decreased the productions of the proinflammatory cytokines including tumor necrosis factor alpha and interleukin 1β and the concentration of total proteins in the bronchoalveolar lavage fluid. Shikonin pretreatment also reduced the concentrations of myeloperoxidase and nitric oxide in lung tissues. In addition, shikonin pretreatment significantly suppressed LPS-induced activation of cyclooxygenase 2 and inducible nitric oxide synthase and the nuclear factor κB DNA-binding activity in lung tissues. ConclusionsThis study indicates that shikonin may have a protective effect against LPS-induced acute lung injury, and the potential mechanism of this action may attribute partly to the inhibition of inducible nitric oxide synthase and cyclooxygenase 2 expression by downregulating nuclear factor κB activation.

Pulmonary Capillaritis and Diffuse Alveolar Hemorrhage in a Patient With Moderately Positive Anti-PL-12 Antibodies

Pulmonary Capillaritis and Diffuse Alveolar Hemorrhage in a Patient With Moderately Positive Anti-PL-12 Antibodies

Influenza B Infection Complicated by Patent Foramen Ovale and High Altitude Pulmonary Edema

A 34-year-old man presented to a clinic at a ski resort in the Rocky Mountains at 9000 feet (2743 m) with shortness of breath and fatigue, a few days after arriving to altitude from sea level. He was found to be hypoxic with radiographic findings consistent with high altitude pulmonary edema (HAPE). He was treated with high flow oxygen, steroids, and calcium channel blockers and transferred to a lower altitude tertiary care hospital for intensive care unit monitoring and further treatment. During his diagnostic evaluation, he was found to have both a patent foramen ovale and influenza B infection. While patent foramen ovale is a known risk factor for HAPE, there is also some evidence that upper respiratory tract infections in general and influenza in particular may also be risk factors for HAPE. The 2 diseases may share an underlying pulmonary pathophysiology, as both cause noncardiogenic pulmonary edema and alveolar hemorrhage. We report an unusual case of influenza B virus compounded by previously undiagnosed patent foramen ovale, travel to high altitude, and subsequent development of HAPE.

Leukemic Infiltration of Lung Mimicking Fungal Pneumonia

Leukemic infiltration of lung may be seen in acute leukemia especially in those with high white cell counts. However, it is difficult to diagnose antemortem as it mimics infections or pulmonary hemorrhage which are much more common complications. We present an unusual patient who had a fatal outcome due to leukemic progression in the lung despite blood and marrow response to induction chemotherapy. Twenty-eight year old female presented with fever and lymphadenopathy for 4 weeks. Investigations: Hemoglobin: 6.7 g/dL; Thrombocyte count: 0.92 × 109/L; white blood cell (WBC) count: 4.1 × 109/L with 65 % blasts confirmed as precursor B acute lymphoblastic leukemia on bone marrow studies. At baseline, patient was afebrile with a normal chest radiograph (Fig. 1a). By day 7 of therapy (only Prednisolone 60 mg/m2 for the first 1 week as per BFM 95 protocol) her WBC count had dropped to 0.6 × 109/L and her peripheral blood had cleared blasts. However, she developed high grade fever and her general condition deteriorated; infection was suspected and empiric antibiotics were started. The day 8 chemotherapy was modified (only Vincristine was delivered, Daunorubicin was omitted). After initial stabilization, the patient had recurrent fever spikes and worsening respiratory status. Patient’s chest radiograph showed lung infiltrates and nodular shadows which made us suspect fungal pneumonia (Fig. 1b). A bone marrow exam was done which showed hypocellular marrow hence all leukemic therapy was withheld and we started her on 2nd line antibiotics and antifungal therapy (voriconazole). She continued to remain febrile and had persistent pancytopenia. Bleeding manifestations precluded any attempt at tissue diagnosis from lung lesions. Repeat chest imaging (Fig 1c) showed further worsening of pulmonary infiltrates. On day 22, she developed progressive respiratory failure and expired. Post mortem lung biopsy showed extensive leukemic infiltration of lung (Fig. 1d, e). No fungal pathogen/infection could be found. Fig. 1 Chest X-ray before starting chemotherapy (a). Chest X-ray showing path infiltrates in both lung fields (b).Chest X-ray showing progression of lung infiltrates (c). Low magnification (×20) view showing leukemic infiltrates in lung (d). Higher magnification ... Pulmonary involvement in acute leukemia can manifest as pulmonary leukostasis, leukemic infiltrates, alveolar hemorrhage, pulmonary nodules, or pleural infiltrates [1–3]. Clinical presentation can vary from asymptomatic pulmonary infiltrates on imaging to acute respiratory distress syndrome—like features. Various radiological findings based on computed tomography of lung have been described for pulmonary leukemic infiltrates [4] but we could not do any imaging other than chest X-ray as patient was too sick to be transferred. We suspected fungal pneumonia in our patient as she was profoundly neutropenic and was not responding to antibiotics. However, postmortem lung biopsy proved that it was leukemic pulmonary infiltrates rather than infection which caused death in our patient. Most of the reported literature of involvement of lung in leukemic patients is in cases of acute leukemia in pre-treatment setting. However postmortem series have shown pulmonary infiltrates in 31–66 %. It’s very intriguing that our patient had a dramatic response with clearance of blasts while the disease progressed in the lungs. The tissue diagnosis of pulmonary infiltrates in leukemic patients can bring about significant changes in management. However, the procedure can be risky especially where patients have significant bleeding tendencies, as in our patient. This led to empiric therapy which resulted in a negative outcome in our patient. We report this case to create awareness about the possibility of leukemic infiltrates being an important cause of respiratory failure during acute leukemia induction even when there is apparent response in the bone marrow.

Impact of Breath Holding on Cardiovascular Respiratory and Cerebrovascular Health

Human underwater breath-hold diving is a fascinating example of applied environmental physiology. In combination with swimming, it is one of the most popular forms of summer outdoor physical activities. It is performed by a variety of individuals ranging from elite breath-hold divers, underwater hockey and rugby players, synchronized and sprint swimmers, spear fishermen, sponge harvesters and up to recreational swimmers. Very few data currently exist concerning the influence of regular breath holding on possible health risks such as cerebrovascular, cardiovascular and respiratory diseases. A literature search of the PubMed electronic search engine using keywords 'breath-hold diving' and 'apnoea diving' was performed. This review focuses on recent advances in knowledge regarding possibly harmful physiological changes and/or potential health risks associated with breath-hold diving. Available evidence indicates that deep breath-hold dives can be very dangerous and can cause serious acute health problems such a collapse of the lungs, barotrauma at descent and ascent, pulmonary oedema and alveolar haemorrhage, cardiac arrest, blackouts, nitrogen narcosis, decompression sickness and death. Moreover, even shallow apnoea dives, which are far more frequent, can present a significant health risk. The state of affairs is disturbing as athletes, as well as recreational individuals, practice voluntary apnoea on a regular basis. Long-term health risks of frequent maximal breath holds are at present unknown, but should be addressed in future research. Clearly, further studies are needed to better understand the mechanisms related to the possible development or worsening of different clinical disorders in recreational or competitive breath holding and to determine the potential changes in training/competition regimens in order to prevent these adverse events.

Leptospirosis -A Case Report of a Patient with Unusual Pulmonary Involvement

Leptospirosis is prevalent worldwide and endemic in many areas of South India including Kolar district, Karantaka. It has a broad spectrum of clinical manifestations varying from inapparent Influenza like illness to fulminant fatal disease with hepatorenal dysfunction, myocarditis and pulmonary alveolar hemorrhage with respiratory distress. We report a case presented with high degree fever and puffiness of face of 8 days duration and respiratory distress of 2days duration. Examination revealed hepatosplenomegaly and signs of respiratory failure. Investigation revealed thrombocytopenia, abnormal liver function test and positive for antileptospira antibody (IgM).This patient expired 6 hours after admission. Leptospirosis is a grossly underdiagnosed disease in our country due lack of awareness, protean manifestations and inadequate diagnostic facilities in many areas, Early diagnosis and appropriate treatment can prevent fatal outcome. Keywords: Leptospirosis, pulmonary, manifestation.

High-resolution Computed Tomography Findings in a Case of Severe Leptospira Infection (Weil Disease) Complicated With Jarisch-Herxheimer Reaction

In this report, we describe a case of Weil disease. Chest x-ray and computed tomography (CT) findings showed temporary deterioration 1 day after the initiation of antibiotic treatment, and high-resolution CT findings with the patient's physical findings made us suspect pulmonary alveolar hemorrhage (PAH). We believed that the PAH had been induced by Weil disease and subsequently caused Jarisch-Herxheimer reaction. We confirmed the patient's contact history with mice, and symptoms improved immediately after starting appropriate treatments. Leptospirosis is a relatively rare cause of PAH. Therefore, the possibility of this disease should be included in the differential diagnosis, especially when high-resolution CT findings indicate PAH, and the imaging findings deteriorate rapidly after antibiotic therapy.

A Case of Diffuse Alveolar Hemorrhage with Glomerulonephritis after Propylthiouracil Treatment

Propylthiouracil (PTU) is one of the most common drugs used in the treatment of Graves' disease. There are a number of side effects found with PTU use including fever, rash, arthralgia, and flu-like symptoms. Recently antineutrophil cytoplasmic antibodies (ANCA) positive vasculitis after PTU treatment was reported as a rare side effect, which can cause diffuse alveolar hemorrhage and glomerulonephritis. A 45-year-old woman with Graves' disease had been treated with PTU for five months, complained of hemoptysis due to pulmonary alveolar hemorrhage causing anemia, and also had hematuria. Simple chest X-ray and HRCT showed bilateral consolidation and bronchoalveolar lavage fluid revealed alveolar hemorrhage. A serologic test was positive for ANCA against myeloperoxidase and proteinase-3. Such findings suggested that the presence of PTU induced ANCA positive vasculitis. Cessation of PTU and the administration of high dose steroids improved the clinical manifestation, radiologic and serologic findings. We observed ANCA titer serially for 6 years. During the follow up period, ANCA titer decreased slowly and stayed within the acceptable upper normal limit.

Phase 2 Trial of G-CSF Priming, Clofarabine, and High Dose Cytarabine (GCLAC) for the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML) or Advanced Myelodysplastic Syndrome or Advanced Myeloproliferative Neoplasm,

Abstract 3617Clofarabine and cytarabine combinations have been effective in the treatment of adult acute myeloid leukemia (AML) in both the relapsed/refractory and upfront settings. Based on our results with GCLAC (G-CSF priming, clofarabine, and high dose cytarabine) in a trial for relapsed/refractory AML (Becker et al. Br J Haematol in press), we are currently testing this regimen in newly diagnosed patients age < 65. The G-CSF dose is 5 mcg/kg/day by subcutaneous injection beginning the day prior to chemotherapy, clofarabine 30 mg/m2/day × 5 and cytarabine 2 gm/m2/day × 5. Second induction with the same regimen was permissible if marrow blasts over 5% persisted on day 21 or thereafter. Consolidation courses were administered for up to 3 cycles, with clofarabine at a dose of 25 mg/m2/day × 4 days and cytarabine 2 gm/m2/day × 4 days. The primary objectives of this trial are to estimate rates of CR (complete remission) and EFS (event free survival). A stopping rule would be imposed if there was reasonable evidence that the CR rate was inferior to that obtained with standard induction 7+3, 70% (Fernandez et al. NEJM 2009; 361:1249–59). Absent early stopping, 50 patients will be treated. Twenty-five patients with non-APL AML, RAEB2, CMML2, or myelofibrosis with >10% blasts have been treated thus far; their median age is 52, range 22–63. Eleven patients had antecedent hematologic disorders(AHD). Four patients had poor risk cytogenetics, four patients had normal cytogenetics with Flt3+, and 5 patients had good risk cytogenetics. The most significant grade 3/4 toxicity occurring in 2 patients, was a constellation of pulmonary infiltrates, hypoxia, and diffuse alveolar hemorrhage that responded to steroids. This incidence is not dissimilar to the pulmonary toxicity described with single-agent high-dose cytarabine (Andersson et al. Cancer 1990; 65:1079–84). Pulmonary toxicity has not occurred in 8 subsequent patients given steroid premedication. The other grade 3 adverse events (AEs) included pneumonia (8), viral respiratory infection (6), abscess (4), bacteremia (13), and one additional grade 4 AE was septic shock. There has been no treatment related mortality. Fifteen of 17 currently evaluable patients have achieved CR, all but one with a single course, and 1 additional patient attained CRp (complete remission with incomplete platelet recovery). Using a model that accounts for cytogenetics, age, AHD, and organ function, the observed CR rate of 88% (95% CI 64%to 95%) exceeds the expected rate of 61% had the same patients received other high-dose cytarabine containing regimens but without clofarabine. Given the recent shortage of daunorubicin and the lack of assurance that an idarubicin dose (18mg/m2) that would be the nominal equivalent of 90mg/m2 daunorubicin is safe (Garcia-Manero et al. Haematologica 2002; 87:804–7), GCLAC may be a suitable alternative induction regimen for newly diagnosed AML and advanced myelodysplastic syndrome or myeloproliferative neoplasm. Disclosures:Becker:Sanofi-Oncology: Research Funding. Off Label Use: Clofarabine is FDA approved for treatment of relapsed pediatric acute lymphoblastic leukemia.