Portal vein embolization with N-butyl cyanoacrylate before partial hepatectomy in patients with hepatocellular carcinoma and underlying cirrhosis or advanced fibrosis.

PURPOSE: To describe the safety, complications, and liver regeneration associated with the left liver after embolization of the right portal vein (PV) in patients with hepatocellular carcinoma (HCC) developed in the setting of advanced liver fibrosis and cirrhosis. MATERIALS AND METHODS: Forty patients (31 men, nine women; mean age, 62 years) with HCC underwent PV embolization over a 4-year period. Embolization was performed from a left PV percutaneous access with use of n-butyl cyanoacrylate (NBCA) mixed with iodized oil. Computed tomography (CT) volumetry was performed before and 1 month after PV embolization to measure the left lobe volume as well as the functional liver ratio defined by the ratio between the left lobe and the total liver volume minus tumoral volume. PV pressure and liver enzyme levels were compared before and 1 month after the procedure and complications were registered. Factors potentially affecting regeneration (age, sex, diabetes, chemoembolization, functional liver ratio before PV embolization, and Knodell histologic score) were evaluated by one-way and stepwise regression analysis. RESULTS: PV embolization could be achieved successfully in all cases. Two patients had partial PV thrombosis on the 1-month follow-up CT and two patients developed transient ascites after PV embolization. The left lobe volume increase was 41% +/- 32% after PV embolization and the functional liver ratio increased from 28% +/- 10% to 36% +/- 10% (P < .0001). Hypertrophy of the left lobe was greater in patients with a low functional liver ratio before PV embolization and those with an F3 fibrosis score. Other factors had no influence on left lobe regeneration. CONCLUSION: PV embolization with use of NBCA is feasible in patients with advanced fibrosis and cirrhosis. Hypertrophy of the left lobe of the liver after PV embolization has a statistically significant correlation with lower functional liver ratio and lower degrees of fibrosis.

Magnetic resonance cholangiography features of biliary abnormalities due to cavernous transformation of the portal vein.

BACKGROUND: The aim of this retrospective and monocentric study was to describe the magnetic resonance cholangiography (MRC) features of biliary abnormalities related to extrahepatic obstruction of the portal vein (EHOPV). METHODS: From September 2001 to May 2003, MRC was performed in 10 consecutive patients who had a portal thrombosis. RESULTS: Biliary ductal pathology was demonstrated via MRC in nine patients. It consisted of stenoses, ductal narrowing or irregularities involving the common bile duct for three patients with extrahepatic portal vein thrombosis discovered a mean of 1.5 years ago, or involving both right and left intrahepatic bile ducts and common bile duct for six patients with extrahepatic portal vein thrombosis discovered a mean of 16.2 years ago. Dilation of intrahepatic bile ducts was seen for seven patients, four of them having cholestasis. For three patients with symptomatic cholestasis, direct cholangiography (DC) was performed and showed the same findings as MRC which nevertheless overestimated the degree of bile duct stenosis. CONCLUSIONS: MRC seems to constitute an accurate tool to investigate noninvasively patients with portal biliopathy.

First detection of Corynebacterium ulcerans producing a diphtheria-like toxin in a case of human with pulmonary infection in the Rio de Janeiro metropolitan area, Brazil

The frequency and severity of human infections associated with Corynebacterium ulcerans appear to be increasing in different countries. Here, we describe the first C. ulcerans strain producing a diphtheria-like toxin isolated from an elderly woman with a fatal pulmonary infection and a history of leg skin ulcers in the Rio de Janeiro metropolitan area.

Comparison of serological responses in two different populations with pulmonary tuberculosis

Observational studies on the humoural immune responses of the Warao indigenous people from Delta Amacuro, an isolated area, were compared with urban residents of the Venezuelan capital. Mycobacterium tuberculosis-specific reactivities (IgM, IgE, sIgA, IgG and IgG subclasses) were measured by ELISA using PPD and 38-kDa M. tuberculosis antigens. A total of 294 individuals were studied, 162 Warao (indigenous people) and 132 Creole (non-indigenous people). The patient group consisted of 87 Warao patients and 58 Creole patients, while the control group consisted of 75 Warao controls and 74 Creole controls. Combinations among the isotypes studied were performed. The findings showed that for the Warao people, sensitivity to the combination including anti-PPD IgG and IgE was 92.0%, while for the Creole people, sensitivity to the combination including anti-PPD IgG but more so anti-PPD IgG1 and IgG2 was 90.0%. Simple tests were able to show higher specificities, which were population-specific; specificities were anti-PPD IgG3, 100.0% and anti-PPD IgM, 97.4% for the Warao and Creole peoples, respectively. In conclusion, while simple tests reached high specificity, the multi-isotype tests improved sensitivity; the latter shows this approach may be useful in diagnostic testing.

Induction of apoptosis in A549 pulmonary cells by two Paracoccidioides brasiliensis samples

Paracoccidioidomycosis presents a variety of clinical manifestations and Paracoccidioides brasiliensis can reach many tissues, most importantly the lungs. The ability of the pathogen to interact with host surface structures is essential to its virulence. The interaction between P. brasiliensis and epithelial cells has been studied, with particular emphasis on the induction of apoptosis. To investigate the expression of different apoptosis-inducing pathways in human A549 cells, we infected these cells with P. brasiliensis Pb18SP (subcultured) and 18R (recently isolated from cell culture and showing a high adhesion pattern) samples in vitro. The expressions of Bcl-2, Bak and caspase 3 were analysed by flow cytometry and DNA fragmentation using the TUNEL technique. Apoptosis of human A549 cells was induced by P. brasiliensis in a sample and time-dependent manner. Using an in vitro model, our data demonstrates that caspase 3, Bak, Bcl-2 and DNA fragmentation mediate P. brasiliensis-induced apoptosis in A549 cells. The overall mechanism is a complex process, which may involve several signal transduction pathways. These findings could partially explain the efficient behaviour of this fungus in promoting tissue infection and/or blood dissemination.

Intratracheal dopamine attenuates pulmonary edema and improves survival after ventilator-induced lung injury in rats

INTRODUCTION Clearance of alveolar oedema depends on active transport of sodium across the alveolar-epithelial barrier. beta-Adrenergic agonists increase clearance of pulmonary oedema, but it has not been established whether beta-agonist stimulation achieves sufficient oedema clearance to improve survival in animals. The objective of this study was to determine whether the increased pulmonary oedema clearance produced by intratracheal dopamine improves the survival of rats after mechanical ventilation with high tidal volume (HVT). METHODS This was a randomized, controlled, experimental study. One hundred and thirty-two Wistar-Kyoto rats, weighing 250 to 300 g, were anaesthetized and cannulated via endotracheal tube. Pulmonary oedema was induced by endotracheal instillation of saline solution and mechanical ventilation with HVT. Two types of experiment were carried out. The first was an analysis of pulmonary oedema conducted in six groups of 10 rats ventilated with low (8 ml/kg) or high (25 ml/kg) tidal volume for 30 or 60 minutes with or without intratracheally instilled dopamine. At the end of the experiment the animals were exsanguinated and pulmonary oedema analysis performed. The second experiment was a survival analysis, which was conducted in two groups of 36 animals ventilated with HVT for 60 minutes with or without intratracheal dopamine; survival of the animals was monitored for up to 7 days after extubation. RESULTS In animals ventilated at HVT with or without intratracheal dopamine, oxygen saturation deteriorated over time and was significantly higher at 30 minutes than at 60 minutes. After 60 minutes, a lower wet weight/dry weight ratio was observed in rats ventilated with HVT and instilled with dopamine than in rats ventilated with HVT without dopamine (3.9 +/- 0.27 versus 4.9 +/- 0.29; P = 0.014). Survival was significantly (P = 0.013) higher in animals receiving intratracheal dopamine and ventilated with HVT, especially at 15 minutes after extubation, when 11 of the 36 animals in the HVT group had died as compared with only one out of the 36 animals in the HVT plus dopamine group. CONCLUSION Intratracheal dopamine instillation increased pulmonary oedema clearance in rats ventilated with HVT, and this greater clearance was associated with improved survival.

Late pulmonary metastases of renal cell carcinoma immediatelyafter post-transplantation immunosuppressive treatment: a case report

INTRODUCTION We report a case of pulmonary metastatic recurrence of renal adenocarcinoma soon after radical nephrectomy that was followed by renal transplant and immunosuppressive medication. Increased risk of metastatic recurrence of renal cell carcinoma should be considered in the immediate post-transplant period when immunosuppressive medication is administered, even if nephrectomy had been performed many years earlier. CASE PRESENTATION In 1986 the patient demonstrated renal insufficiency secondary to mesangial glomerulonephritis. In 1992 he underwent left side radical nephrectomy with histopathological diagnosis of clear cell adenocarcinoma. Mesangial glomerulonephritis in the remaining right kidney progressed to end-stage renal failure. In October 2000 he received a kidney transplant from a cadaver and commenced immunosuppressive medication. Two months later, several nodules were found in his lungs, which were identified as metastases from the primary renal tumor that had been removed with the diseased kidney 8 years earlier. CONCLUSION Recurrence of renal cell carcinoma metastases points to tumor dormancy and reflects a misbalance between effective tumor immune surveillance and immune escape. This case demonstrates that a state of tumor dormancy can be interrupted soon after administration of immunosuppressant medication.

A prediction rule to identify low-risk patients with pulmonary embolism.

BACKGROUND: A simple prognostic model could help identify patients with pulmonary embolism who are at low risk of death and are candidates for outpatient treatment. METHODS: We randomly allocated 15,531 retrospectively identified inpatients who had a discharge diagnosis of pulmonary embolism from 186 Pennsylvania hospitals to derivation (67%) and internal validation (33%) samples. We derived our rule to predict 30-day mortality using classification tree analysis and patient data routinely available at initial examination as potential predictor variables. We used data from a European prospective study to externally validate the rule among 221 inpatients with pulmonary embolism. We determined mortality and nonfatal adverse medical outcomes across derivation and validation samples. RESULTS: Our final model consisted of 10 patient factors (age > or = 70 years; history of cancer, heart failure, chronic lung disease, chronic renal disease, and cerebrovascular disease; and clinical variables of pulse rate > or = 110 beats/min, systolic blood pressure < 100 mm Hg, altered mental status, and arterial oxygen saturation < 90%). Patients with none of these factors were defined as low risk. The 30-day mortality rates for low-risk patients were 0.6%, 1.5%, and 0% in the derivation, internal validation, and external validation samples, respectively. The rates of nonfatal adverse medical outcomes were less than 1% among low-risk patients across all study samples. CONCLUSIONS: This simple prediction rule accurately identifies patients with pulmonary embolism who are at low risk of short-term mortality and other adverse medical outcomes. Prospective validation of this rule is important before its implementation as a decision aid for outpatient treatment.

Traitement des fibroses pulmonaires idiopathiques [Treatment of idiopathic pulmonary fibrosis]

Idiopathic pulmonary fibrosis still has to be diagnosed by elimination. Neoplasm, toxic treatments, collagen vascular disease, professional exposure or diagnosis such as sarcoidosis have to be ruled out. The repercussions on gas exchange are the most reliable indications of the severity of the disease, the pulmonary function test or chest x-rays alone being often misleading. Transbronchic biopsies, thoracotomy or thoracoscopies provide a precise diagnosis. In many cases only broncho-alveolar lavage and a high resolution CT-scan are performed to rule out infection or tumor and to assess the inflammatory state of the disease. Due to the often poor prognosis of this disease and its often poor response to steroids, the role of cytostatic drugs, cyclosporine and colchicine, and of pulmonary graft is discussed.

Lung function in idiopathic pulmonary fibrosis--extended analyses of the IFIGENIA trial.

BACKGROUND The randomized placebo-controlled IFIGENIA-trial demonstrated that therapy with high-dose N-acetylcysteine (NAC) given for one year, added to prednisone and azathioprine, significantly ameliorates (i.e. slows down) disease progression in terms of vital capacity (VC) (+9%) and diffusing capacity (DLco) (+24%) in idiopathic pulmonary fibrosis (IPF). To better understand the clinical implications of these findings we performed additional, explorative analyses of the IFGENIA data set. METHODS We analysed effects of NAC on VC, DLco, a composite physiologic index (CPI), and mortality in the 155 study-patients. RESULTS In trial completers the functional indices did not change significantly with NAC, whereas most indices deteriorated with placebo; in non-completers the majority of indices worsened but decline was generally less pronounced in most indices with NAC than with placebo. Most categorical analyses of VC, DLco and CPI also showed favourable changes with NAC. The effects of NAC on VC, DLco and CPI were significantly better if the baseline CPI was 50 points or lower. CONCLUSION This descriptive analysis confirms and extends the favourable effects of NAC on lung function in IPF and emphasizes the usefulness of VC, DLco, and the CPI for the evaluation of a therapeutic effect. Most importantly, less progressed disease as indicated by a CPI of 50 points or lower at baseline was more responsive to therapy in this study.

D-dimer levels and 90-day outcome in patients with acute pulmonary embolism with or without cancer.

BACKGROUND: The prognostic value of D-dimer testing in patients with acute pulmonary embolism (PE) has not been thoroughly studied. METHODS: We used the RIETE Registry data to assess the 90-day prognostic value of increased IL Test D-dimer levels at baseline in patients with PE, according to the presence or absence of cancer. RESULTS: As of May 2013, 3,283 patients with acute PE underwent D-dimer testing using IL Test D-dimer. Among 2,588 patients without cancer, those with D-dimer levels in the highest quartile had a higher rate of fatal PE (2.6% vs. 0.9%; p=0.002), fatal bleeding (1.1% vs. 0.3%; p=0.017) and all-cause death (9.1% vs. 4.4%; p<0.001) at 90 days compared with those with levels in the lowest quartiles. Among 695 patients with cancer, those with levels in the highest quartile had a similar rate of fatal PE or fatal bleeding but higher mortality (35% vs. 24%; p<0.01). On multivariate analysis, non-cancer patients with D-dimer levels in the highest quartile had an increased risk for fatal PE (odds ratio [OR]: 3.3; 95% CI: 1.6-6.6), fatal bleeding (OR: 4.3; 95% CI: 1.4-13.7) and all-cause death (OR: 2.1; 95% CI: 1.4-3.1) compared with patients with levels in the lowest quartiles. CONCLUSIONS: Non-cancer patients with acute PE and IL Test D-dimer levels in the highest quartile had an independently higher risk for fatal PE, fatal bleeding and all-cause death at 90 days than those with levels in the lowest quartiles. In patients with cancer, D-dimer levels failed to predict fatal PE or fatal bleeding.

Pulmonary Sarcoid-like Granulomatosis after Multiple Vaccinations of a Long-term Surviving Patient with Metastatic Melanoma.

Autoimmune side effects are frequent in patients with cancer treated with immune checkpoint-targeting antibodies, but are rare with cancer vaccines. Here, we present a case report on a patient with metastatic melanoma who developed pulmonary sarcoid-like granulomatosis following repetitive vaccinations with peptides and CpG. Despite multiple metastases, including one lesion in the brain, the patient is alive and well more than 13 years after the diagnosis of metastatic disease. The strongly activated tumor-specific CD8(+) T cells showed robust long-term memory and effector functions. It is possible that long-term survival and adverse autoimmune events may become more common for vaccines inducing robust anticancer immune responses as were present in this patient. Cancer Immunol Res; 2(12); 1148-53. ©2014 AACR.

Perinatal Hypoxia Enhances Cyclic Adenosine Monophosphate-mediated BKCa Channel Activation in Adult Murine Pulmonary Artery.

Exposure to perinatal hypoxia results in alteration of the adult pulmonary circulation, which is linked among others to alterations in K channels in pulmonary artery (PA) smooth muscle cells. In particular, large conductance Ca-activated K (BKCa) channels protein expression and activity were increased in adult PA from mice born in hypoxia compared with controls. We evaluated long-term effects of perinatal hypoxia on the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway-mediated activation of BKCa channels, using isoproterenol, forskolin, and dibutyryl-cAMP. Whole-cell outward current was higher in pulmonary artery smooth muscle cells from mice born in hypoxia compared with controls. Spontaneous transient outward currents, representative of BKCa activity, were present in a greater proportion in pulmonary artery smooth muscle cells of mice born in hypoxia than in controls. Agonists induced a greater relaxation in PA of mice born in hypoxia compared with controls, and BKCa channels contributed more to the cAMP/PKA-mediated relaxation in case of perinatal hypoxia. In summary, perinatal hypoxia enhanced cAMP-mediated BKCa channels activation in adult murine PA, suggesting that this pathway could be a potential target for modulating adult pulmonary vascular tone after perinatal hypoxia.

Hospital volume and patient outcomes in pulmonary embolism.

BACKGROUND: In numerous high-risk medical and surgical conditions, a greater volume of patients undergoing treatment in a given setting or facility is associated with better survival. For patients with pulmonary embolism, the relation between the number of patients treated in a hospital (volume) and patient outcome is unknown. METHODS: We studied discharge records from 186 acute care hospitals in Pennsylvania for a total of 15 531 patients for whom the primary diagnosis was pulmonary embolism. The study outcomes were all-cause mortality in hospital and within 30 days after presentation for pulmonary embolism and the length of hospital stay. We used logistic models to study the association between hospital volume and 30-day mortality and discrete survival models to study the association between in-hospital mortality and time to hospital discharge. RESULTS: The median annual hospital volume for pulmonary embolism was 20 patients (interquartile range 10-42). Overall in-hospital mortality was 6.0%, whereas 30-day mortality was 9.3%. In multivariable analysis, very-high-volume hospitals (> or = 42 cases per year) had a significantly lower odds of in-hospital death (odds ratio [OR] 0.71, 95% confidence interval [CI] 0.51-0.99) and of 30-day death (OR 0.71, 95% CI 0.54-0.92) than very-low-volume hospitals (< 10 cases per year). Although patients in the very-high-volume hospitals had a slightly longer length of stay than those in the very-low-volume hospitals (mean difference 0.7 days), there was no association between volume and length of stay. INTERPRETATION: In hospitals with a high volume of cases, pulmonary embolism was associated with lower short-term mortality. Further research is required to determine the causes of the relation between volume and outcome for patients with pulmonary embolism.

Sex differences in patients receiving anticoagulant therapy for venous thromboembolism.

In patients with venous thromboembolism (VTE), the outcome during the course of anticoagulant therapy may differ according to the patient's sex. We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to compare the rate of VTE recurrences, major bleeding, and mortality due to these events according to sex.As of August 2013, 47,499 patients were enrolled in RIETE, of whom 24,280 (51%) were women. Women were older, more likely presented with pulmonary embolism (PE), and were more likely to have recent immobilization but less likely to have cancer than men. During the course of anticoagulation (mean duration: 253 d), 659 patients developed recurrent deep vein thrombosis (DVT), 576 recurrent PE, 1368 bled, and 4506 died. Compared with men, women had a lower rate of DVT recurrences (hazard ratio [HR]: 0.78; 95% confidence interval [CI]: 0.67-0.91), a similar rate of PE recurrences (HR: 0.98; 95% CI: 0.83-1.15), a higher rate of major bleeding (HR: 1.21; 95% CI: 1.09-1.35), and higher mortality due to PE (HR: 1.24; 95% CI: 1.04-1.47). On multivariable analysis, any influence of sex on the risk for recurrent DVT (HR: 0.88; 95% CI: 0.75-1.03), major bleeding (HR: 1.10; 95% CI: 0.98-1.24), or fatal PE (HR: 1.01; 95% CI: 0.84-1.22) was no longer statistically significant.In conclusion, women had fewer DVT recurrences and more bleeds than men during the course of anticoagulation. These differences were not due to sex, but very likely to other patient characteristics more common in female patients and differences in treatment choice.