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Pulmonary Edema [keywords]
- Acute Lung Injury Complicating Blood Transfusion in Post-Partum Hemorrhage: Incidence and Risk Factors. [JOURNAL ARTICLE]
- Mediterr J Hematol Infect Dis 2014; 6(1):e2014069.
We retrospectively investigated the incidence and risk factors for transfusion-related acute lung injury (TRALI) among patients transfused for post-partum hemorrhage (PPH).We identified a series of 71 consecutive patients with PPH requiring the urgent transfusion of three or more red blood cell (RBC) units, with or without transfusion of fresh frozen plasma (FFP) and/or platelets (PLT). Clinical records were then retrieved and examined for respiratory distress events. According to the 2004 consensus definition, cases of new-onset hypoxemia, within 6 hours after transfusion, with bilateral pulmonary changes, in the absence of cardiogenic pulmonary edema were identified as TRALI. If an alternative risk factor for acute lung injury was present, possible TRALI was diagnosed.Thirteen cases of TRALI and 1 case of possible TRALI were identified (overall incidence 19.7%). At univariate analysis, patients with TRALI received higher number of RBC, PLT and FFP units and had a longer postpartum hospitalization. Among the diseases occurring in pregnancy- and various pre-existing comorbidities, only gestational hypertension and pre-eclampsia, significantly increased the risk to develop TRALI (p = 0.006). At multivariate analysis including both transfusion- and patient-related risk factors, pregnancy-related, hypertensive disorders were confirmed to be the only predictors for TRALI, with an odds ratio of 27.7 ( 95% CI 1.27-604.3, p=0.034).Patients suffering from PPH represent a high-risk population for TRALI. The patients with gestational hypertension and pre-eclampsia, not receiving anti-hypertensive therapy, have the highest risk. Therefore, a careful monitoring of these patients after transfusions is recommended.
- Diagnostic point-of-care ultrasound for hospitalists. [JOURNAL ARTICLE]
- J Hosp Med 2014 Nov 19.
We review the literature on diagnostic point-of-care ultrasound applications most relevant to hospital medicine and highlight gaps in the evidence base. Diagnostic point-of-care applications most relevant to hospitalists include cardiac ultrasound for left ventricular systolic function, pericardial effusion, and severe mitral regurgitation; lung ultrasound for pneumonia, pleural effusion, pneumothorax, and pulmonary edema; abdominal ultrasound for ascites, aortic aneurysm, and hydronephrosis; and venous ultrasound for central venous volume assessment and lower extremity deep venous thrombosis. Hospitalists and other frontline providers, as well as physician trainees at various levels of training, have moderate to excellent diagnostic accuracy after brief training programs for most of these applications. Despite the evidence supporting the diagnostic accuracy of point-of-care ultrasound, experimental evidence supporting its clinical use by hospitalists is limited to cardiac ultrasound. Journal of Hospital Medicine 2014. © 2014 Society of Hospital Medicine.
- p18, a novel adaptor protein, regulates pulmonary endothelial barrier function via enhanced endocytic recycling of VE-cadherin. [JOURNAL ARTICLE]
- FASEB J 2014 Nov 17.
Vascular permeability is a hallmark of several disease states including acute lung injury (ALI). Endocytosis of VE-cadherin, away from the interendothelial junction (IEJ), causes acute endothelial barrier permeability. A novel protein, p18, anchors to the endosome membrane and plays a role in late endosomal signaling via MAPK and mammalian target of rapamycin. However, the fate of the VE-cadherin-positive endosome has yet to be elucidated. We sought to elucidate a role for p18 in VE-cadherin trafficking and thus endothelial barrier function, in settings of ALI. Endothelial cell (EC) resistance, whole-cell ELISA, and filtration coefficient were studied in mice or lung ECs overexpressing wild-type or nonendosomal-binding mutant p18, using green fluorescent protein as a control. We demonstrate a protective role for the endocytic protein p18 in endothelial barrier function in settings of ALI in vitro and in vivo, through enhanced recycling of VE-cadherin-positive early endosomes to the IEJ. In settings of LPS-induced ALI, we show that Src tethered to the endosome tyrosine phosphorylates p18 concomitantly with VE-cadherin internalization and pulmonary edema formation. We conclude that p18 regulates pulmonary endothelial barrier function in vitro and in vivo, by enhancing recycling of VE-cadherin-positive endosomes to the IEJ.-Chichger, H., Duong, H., Braza, J., Harrington, E. O. p18, a novel adaptor protein, regulates pulmonary endothelial barrier function via enhanced endocytic recycling ofVE-cadherin.
- PARP inhibitor, olaparib ameliorates acute lung and kidney injury upon intratracheal administration of LPS in mice. [JOURNAL ARTICLE]
- Mol Cell Biochem 2014 Nov 18.
We have previously shown that PARP-1 inhibition provides protection against lung inflammation in the context of asthma and acute lung injury. Olaparib is a potent new generation PARP inhibitor that has been approved for human testing. The present work was designed to evaluate its beneficial potential against LPS-induced acute lung injury and acute kidney injury upon intratracheal administration of the endotoxin in mice. Administration of olaparib at different doses, 30 min after LPS treatment showed that single intraperitoneal injection of the drug at 5 mg/kg b.wt. reduced the total number of inflammatory cells particularly neutrophils in the lungs. This was associated with reduced pulmonary edema as the total protein content in the bronchoalveolar fluid was found to be decreased substantially. Olaparib provided strong protection against LPS-mediated secondary kidney injury as reflected by restoration of serum levels of urea, creatinine, and uric acid toward normal. The drug restored the LPS-mediated redox imbalance toward normal in lung and kidney tissues as assessed by measuring malondialdehyde and GSH levels. Finally, RT-PCR data revealed that olaparib downregulates the LPS-induced expression of NF-κB-dependent genes namely TNF-α, IL-1β, and VCAM-1 in the lungs without altering the expression of total p65NF-κB. Overall, the data suggest that olaparib has a strong potential to protect against LPS-induced lung injury and associated dysfunctioning of kidney in mice. Given the fact that olaparib is approved by FDA for human testing, our findings can pave the way for testing of the drug on humans inflicted with acute lung injury.
- ATF3 Protects Pulmonary Resident Cells from Acute Lung Injury by Preventing Keap-1-mediated Nrf2 Degradation in a DJ-1-dependent manner. [JOURNAL ARTICLE]
- Antioxid Redox Signal 2014 Nov 17.
Aims: Ventilator-induced lung injury (VILI) contributes to mortality in patients with acute respiratory distress syndrome, the clinical form of acute lung injury (ALI). Absence of activating transcription factor 3 (ATF3) confers susceptibility to ALI/VILI. To identify cell-specific ATF3-dependent mechanisms of susceptibility to ALI/VILI, we generated ATF3 chimera by adoptive bone marrow transfer and randomized to inhaled saline or lipopolysacharide (LPS) in the presence of mechanical ventilation (MV). Adenovirus vectors to silence or overexpress ATF3 were used in primary human bronchial epithelial cells and murine bone marrow derived macrophages from wild type or ATF3 deficient mice. Results: Absence of ATF3 in myeloid cells caused increased pulmonary cellular infiltration. In contrast, absence of ATF3 in parenchymal cells resulted in loss of alveolar-capillary membrane integrity and increased edema. ATF3-deficient macrophages were unable to limit the expression of pro-inflammatory mediators. Knockdown of ATF3 in resident cells resulted in decreased junctional protein expression and increased leak. ATF3 overexpression abrogated LPS induced membrane permeability. Despite release of ATF3-dependent Nrf2 transcriptional inhibition, mice that lacked ATF3 in resident cells had increased Nrf2 protein degradation. Innovation: In our model, in the absence of ATF3 in parenchymal cells increased Nrf2 degradation is the result of increased Keap-1 expression and loss of DJ-1 (Parkinson disease [autosomal recessive, early onset] 7), previously not known to play a role in lung injury. Conclusion: Results suggest ATF3 confers protection to lung injury by preventing inflammatory cell recruitment and barrier disruption in a cell-specific manner opening novel opportunities for cell specific therapy for ALI/VILI.
- The Use of Dexamethasone in Support of High-Altitude Ground Operations and Physical Performance: Review of the Literature. [JOURNAL ARTICLE]
- J Spec Oper Med 2014; 14(4):53-58.
Objective: Military Special Operators (SOs) are exposed environmental conditions that can alter judgment and physical performance: uneven terrain, dryness of ambient air, reduction of air density, and a diminished partial pressure of oxygen. The primary purpose of this review was to determine the medical efficacy of dexamethasone as an intervention for the prevention and treatment of high-altitude illness. The secondary purpose was to determine its ability to maintain physical performance of SOs at high altitudes. Methods: A search of the literature from 1970 to 2014 was performed, locating 61 relevant articles, with 43 addressing the primary and secondary purposes of this literature review. Conclusions: The review indicates that dexamethasone is an effective prevention and treatment intervention for high-altitude illness. Commonly used dosages of either 2mg every 6 hours or 4mg every 12 hours can prevent high-altitude illnesses in adults. Currently in USSOCOM operations, there is an option to use 4mg every 6 hours (concurrently with acetazolamide 125mg bid) if ascending rapidly to or above 11,500 ft without time for acclimatization. Researchers also determined that acute exposure to high altitude, even in asymptomatic subjects, resulted in small cognitive deficits that could be reversed with dexamethasone. Dexamethasone may also help improve cognition and maximal aerobic capacity in SOs who are susceptible to high-altitude pulmonary edema.
- Pulmonary Hilar Lymph Node Metastasis of Breast Cancer Induced Bronchopleural Fistula and Superior Vena Cava Syndrome. [JOURNAL ARTICLE]
- Am J Case Rep 2014.:492-495.
Background It is extremely rare for pulmonary hilar lymph node metastasis (PHLNM) of a cancer to be independently lethal. Here, we report an exceedingly rare case of cavitation in PHLNM from breast cancer triggering broncho-pleural fistula and empyema (BPFE), complicated with superior vena cava syndrome (SVCS). Case Report A 56-year-old woman who had undergone left segmental mastectomy and axillary lymph node dissection due to left breast cancer was then treated for 1 year with postoperative adjuvant chemotherapy. Recurrence of right PHLNM was observed 2 years after the operation, for which 3 courses of bevacizumab (BEV) and paclitaxel combination chemotherapy were administered. The woman had dyspnea and fever during the washout period, and CT examination revealed fistula formation between the right PHLNM cavitation and right main bronchus, so she was admitted for further treatment. This fistula rapidly progressed to BPFE, and contralateral aspiration was observed to cause pneumonia of the left lung. In addition, edema of both upper limbs and head and neck were observed, and CT examination revealed SVCS caused by re-enlargement of PHLNM. Active treatment was performed, but the recommencement of chemotherapy was not possible, and she died on Day 150 of admission. Conclusions We think that PHLNM deteriorated to central necrosis due to chemotherapy with BEV taking effect, leading to formation of BPFE. The case was also made more difficult due to the complication of SVCS caused by the re-enlarged PHLNM.
- Differential Modulation of S1PR(1-5) and Specific Activities of SphK and nSMase in Pulmonary and Cerebral Tissues of Rats Exposed to Hypobaric Hypoxia. [JOURNAL ARTICLE]
- Lipids 2014 Nov 16.
Recent preclinical and clinical studies have unfolded the potential of pharmacological modulation of activities of sphingosine-1-phosphate (S1P) receptors and S1P metabolizing enzymes for the development of therapeutic interventions against a variety of pathologies. An understanding of differential and temporal effects of hypoxia exposure on the key components of S1P signalling would certainly aid in designing improved drug development strategies in this direction. In view of this, the aim of the present study was to assess the effect of progressive hypobaric hypoxia exposure on expression of S1P receptors (S1PR1-5) and specific activities of S1P synthesizing enzymes-neutral sphingomyelinase (nSMase) and sphingosine kinase (Sphk) in pulmonary and cerebral tissues of rats exposed to simulated altitude of 21,000 feet in an animal decompression chamber. Along with this, development of cerebral and pulmonary edema and markers of inflammation were studied at 12, 24, and 48 h to validate our study model of hypobaric hypoxia-induced stress. The protein expression of S1PR1-5 and activities of Sphk and nSMase enzymes were observed to be dramatically affected by simulated hypobaric hypoxia exposure, concurrent with deterioration of pathology, with 12 h of exposure appearing to be the most critical of the various time points studied.
- Initiating Acute Dialysis at earlier Acute Kidney Injury Network stage in critically ill patients without traditional indications does not improve outcome: a prospective cohort study. [JOURNAL ARTICLE]
- Nephrology (Carlton) 2014 Nov 13.
Optimal timing for acute renal replacement therapy (ARRT) initiation in critically ill patients with acute kidney injury (AKI) is unclear. We aimed to evaluate outcomes in patients who initiated ARRT for traditional indications versus those who met Acute Kidney Injury Network (AKIN) criteria without traditional indications.This was a single-centre prospective cohort of medical and surgical intensive care patients with AKI. Traditional indications for ARRT initiation included: serum potassium ≥6.0 mmol/L, serum urea ≥30 mmol/L, arterial pH <7.25, serum bicarbonate <10 mmol/L, acute pulmonary edema, acute uremic encephalopathy or pericarditis. In absence of these indications, ARRT was commenced if patients had (1) AKIN Stage 3 or (2) AKIN Stage 1 or 2 with "compelling" conditions. Primary outcomes were ICU and in-hospital mortality.ARRT was initiated in 140 patients: traditional indications in 56 (40%); AKIN Stage 3 without traditional indications in 38 (27%); AKIN Stages 1 or 2 with "compelling" conditions in 46 (33%) patients. Traditional indications at ARRT initiation was associated with increased in-hospital mortality [adjusted OR (95% CI), 6.48 (1.54, 27.29)]. In absence of traditional indications, earlier ARRT initiation, as defined by those with AKIN Stages 1 or 2, did not decrease ICU deaths (30.0% vs. 18.8%, p=0.30) or in-hospital mortality (50.0% vs. 34.2%, p=0.15) compared to those who were started on ARRT for AKIN Stage 3.Presence of traditional indications at ARRT initiation was associated with greater mortality. Initiating dialysis at earlier AKIN stage did not improve survival in patients without traditional indications.
- Follow-up study of post-infectious glomerulonephritis in adults: Analysis of predictors of poor renal outcome. [Journal Article]
- Saudi J Kidney Dis Transpl 2014 Nov-Dec; 25(6):1210-6.
Post-infectious glomerulonephritis (PIGN) still remains one of the most common glomerulonephritis in the developing world. We studied the epidemiology and clinical spectrum of PIGN in adults to identify the clinical, biochemical and histological factors that would predict renal outcome. Data of 102 adult PIGN patients treated between 2009 and 2011 with a mean fol-low-up of 12 months (6-36 months) were analyzed retrospectively. The mean age of the patients was 32.7 ± 15 years, with a male to female ratio of 1.2:1. At presentation, 99% of the patients had edema and oliguria, 73% had hypertension, 55% had macrohematuria and 60% had nephrotic range proteinuria. About 14% presented with complications (pulmonary edema-6%, seizure-1%, dialysis requiring renal failure-7%) and 9% had comorbid illness. Sixty percent of the patients had serum creatinine >2 mg/dL at presentation, which was persistent in 30% at the end of one week and 68% had hypo-complementemia. Renal biopsy revealed diffuse proliferative glomerulonephritis in 70% of the patients. At 12 months, 2% had persistent hypertension, 10% had persistent proteinuria and hematuria and 11% had serum creatinine >1.5 mg/dL. Univariate analysis with the Fischer Exact test revealed age >40 years, male gender, serum creatinine >2 mg/dL at one week, comorbid illness, requirement of dialysis, crescents in >30% glomeruli and persistent proteinuria and microscopic hematuria at 12 months as significant risk factors for poor renal outcome. Serum creatinine >2 mg/dL at one week and persistent proteinuria at 12 months were the independent risk factors that predicted poor renal outcome at one year.