CPAP by helmet for treatment of acute respiratory failure after pediatric liver transplantation.

ARF after pediatric liver transplantation accounts for high rate of morbidity and mortality associated with this procedure. The role of CPAP in postoperative period is still unknown. The aim of the study was to describe current practice and risk factors associated with the application of helmet CPAP. In this retrospective observational cohort study, 119 recipients were divided into two groups based on indication to CPAP after extubation. Perioperative variables were studied, and determinants of CPAP application were analyzed in a multivariate logistic model. Sixty patients (60/114) developed ARF and were included in the CPAP group. No differences were found between the two groups for primary disease, graft type, and blood product transfused. At multivariate analysis, weight <11 kg (OR = 2.9; 95% CI = 1.1-7.3; P = .026), PaO2 /FiO2 <380 before extubation (OR = 5.4; 95% CI = 2.1-13.6; P < .001), need of vasopressors (OR = 2.6; 95% CI = 1.1-6.4; P = .038), and positive fluid balance >148 mL/kg (OR = 4.0; 95% CI = 1.6-10.1; P = .004) were the main determinants of CPAP application. In the CPAP group, five patients (8.4%) needed reintubation. Pediatric liver recipients with lower weight, higher need of inotropes/vasopressors, higher positive fluid balance after surgery, and lower PaO2 /FiO2 before extubation were at higher odds of developing ARF needing CPAP application.

Extracorporeal support for severe acute respiratory failure.

Extracorporeal membrane oxygenation (ECMO) and extracorporeal CO(2) removal (ECCO(2)R) techniques have increasingly been applied in patients with severe acute lung injury refractory to conventional mechanical ventilatory support. The objectives of this article are to review current concepts of extracorporeal life support techniques (ECMO and ECCO(2)R systems) and provide the rationale for their application in patients with acute respiratory distress syndrome, chronic obstruction pulmonary disease, and as adjunctive therapy for bridging patients to lung transplantation.

Heavy holes as a precursor to superconductivity in antiferromagnetic CeIn3.

Numerous phenomenological parallels have been drawn between f- and d-electron systems in an attempt to understand their display of unconventional superconductivity. The microscopics of how electrons evolve from participation in large moment antiferromagnetism to superconductivity in these systems, however, remains a mystery. Knowing the origin of Cooper paired electrons in momentum space is a crucial prerequisite for understanding the pairing mechanism. Of special interest are pressure-induced superconductors CeIn(3) and CeRhIn(5) in which disparate magnetic and superconducting orders apparently coexist-arising from within the same f-electron degrees of freedom. Here, we present ambient pressure quantum oscillation measurements on CeIn(3) that crucially identify the electronic structure-potentially similar to high-temperature superconductors. Heavy hole pockets of f-character are revealed in CeIn(3), undergoing an unexpected effective mass divergence well before the antiferromagnetic critical field. We thus uncover the softening of a branch of quasiparticle excitations located away from the traditional spin fluctuation-dominated antiferromagnetic quantum critical point. The observed Fermi surface of dispersive f-electrons in CeIn(3) could potentially explain the emergence of Cooper pairs from within a strong moment antiferromagnet.

Risk factors for a first thrombotic event in antiphospholipid antibody carriers. A multicentre, retrospective follow-up study.

OBJECTIVES: To asses risk factors for a first thrombotic event in antiphospholipid antibody (aPL) positive carriers and evaluate the efficacy of prophylactic treatments. METHODS: Recruitment criteria were age 18-65 years, no history of thrombosis, positivity for lupus anticoagulant and/or IgG/IgM anticardiolipin antibody (aCL) on > or =2 occasions at least 6 weeks apart. Demographic, laboratory and clinical parameters were collected at enrolment and at the time of the thrombotic event. RESULTS: 370 patients/subjects (mean (SD) age 34 (9.9) years) were analysed retrospectively for a mean (SD) follow-up of 59.3 (45.5) months. Thirty patients (8.1%) developed a first thrombotic event during follow-up. Hypertension and medium/high levels of IgG aCL were identified by multivariate logistic regression analysis as independent risk factors for thrombosis. Thromboprophylaxis during high-risk and long-term periods was significantly protective. CONCLUSIONS: Hypertension or medium/high titres of IgG aCL are risk factors for a first thrombotic event in asymptomatic aPL carriers and primary prophylaxis is protective.

[Primary antiphospholipid syndrome evolving into systemic lupus erythematosus: may antinucleosome antibodies be predictive?]. / L'evoluzione da sindrome da anticorpi antifosfolipidi primaria a lupus eritematoso sistemico: possono gli anticorpi anti-nucleosomi essere predittivi?

OBJECTIVE: It was reported by several groups that patients diagnosed as primary antiphospholipid syndrome (PAPS) had developed a full-blown systemic lupus erythematosus (SLE) even after many years of follow-up. Little is known about clinical and/or serological factors that may help predict such evolution. Antinucleosome antibodies (anti-NCS) were described to appear in early stages of SLE, in particular before anti-dsDNA antibodies. The aim of the study is to evaluate the prevalence of anti-NCS in a large cohort of PAPS patients. METHODS: IgG and IgM anti-NCS antibodies were detected using a home made assay with H1-stripped chromatin as antigen. Sera from 106 PAPS patients were tested; 52 of them were also tested during the follow-up, at least 2 years apart form the basal sample. RESULTS: Medium-high titre anti-NCS were found in nearly half of the patients (49/106, 46%), more frequently in those presenting features of "lupus like disease". Most of patients displayed an unchanged pattern of anti-NCS over time. We describe three cases of PAPS patients that developed SLE after many years of follow-up; high titre and low titre anti-NCS were present in two and one of them respectively several years before evolving into SLE. CONCLUSIONS: A significant proportion of PAPS patients displayed medium-high titre anti-NCS, suggesting that the autoimmune response against chromatin may be a relevant event not only in patients with SLE. Further studies are warranted to explore the predictive value of anti-NCS with respect to the evolution from PAPS to SLE.

[Clinical and therapeutic considerations on hepatic encephalopathy]. / Considerazioni cliniche e terapeutiche sulla encefalopatia epatica.

Impairment of consciousness in liver encephalopathy ranges from slight anomalies to clinically manifest coma. Since the triggering causes are extremely varied and often include dietary errors and/or medication, it is extremely important for the physician to be able to identify the initial signs so as the to start the appropriate treatment. After reviewing the etiopathogenesis and pathology of liver encephalopathy, the authors list the possibilities for medical management which often lead to satisfactory results.

Q-dependence of the spin fluctuations in the intermediate valence compound CePd3.

We report inelastic neutron scattering experiments on a single crystal of the intermediate valence compound CePd3. At 300 K the magnetic scattering is quasielastic, with half-width Γ = 23 meV, and is independent of momentum transfer Q. At low temperature, the Q-averaged magnetic spectrum is inelastic, exhibiting a broad peak centered near Emax = 55 meV. These results, together with the temperature dependence of the susceptibility, 4f occupation number, and specific heat, can be fit by the Kondo/Anderson impurity model. The low temperature scattering near Emax, however, shows significant variations with Q, reflecting the coherence of the 4f lattice. The intensity is maximal at (1/2, 1/2, 0), intermediate at (1/2, 0, 0) and (0, 0, 0), and weak at (1/2, 1/2, 1/2). We discuss this Q-dependence in terms of current ideas about coherence in heavy fermion systems.

Donation after cardiac death: is a "paradigm shift" feasible in Italy?

Donation after cardiac death (DCD) is one of the growing strategies to overcome the problem of organ shortage. Cardiac death is defined as "irreversible cessation of circulatory and respiratory function"; the time interval to define irreversibility of cardiac death, the peculiarity of consent, and the framework of end-of-life decision making are the most compelling ethical issues which have been raised with DCD. National protocols that balance medical, ethical, and social issues are mandatory to guide transplant care professionals. In Italy, the 20 min cardiac arrest demonstrated by continuous electrocardiography recording is the time interval necessary for death diagnosis based on cardiopulmonary criteria. This time negatively affects donation after cardiac death because warm ischemic time (WIT) - the most important predictor of grafts' poor outcome - is prolonged. However, this time seems to be prudential to define the irreversibility of death and to respect the "dead donor rule", as established by the National Committee of Bioethics. National reference protocols regulating DCD practice are therefore a compelling issue.

Brain-lung crosstalk in critical care: how protective mechanical ventilation can affect the brain homeostasis.

The maintenance of brain homeostasis against multiple internal and external challenges occurring during the acute phase of acute brain injury may be influenced by critical care management, especially in its respiratory, hemodynamic and metabolic components. The occurrence of acute lung injury represents the most frequent extracranial complication after brain injury and deserves special attention in daily practice as optimal ventilatory strategy for patients with acute brain and lung injury are potentially in conflict. Protecting the lung while protecting the brain is thus a new target in the modern neurointensive care. This article discusses the essentials of brain-lung crosstalk and focuses on how mechanical ventilation may exert an active role in the process of maintaining or treatening brain homeostasis after acute brain injury, highlighting the following points: 1) the role of inflammation as common pathomechanism of both acute lung and brain injury; 2) the recognition of ventilatory induced lung injury as determinant of systemic inflammation affecting distal organs, included the brain; 3) the possible implication of protective mechanical ventilation strategy on the patient with an acute brain injury as an undiscovered area of research in both experimental and clinical settings.

Extracorporeal membrane oxygenation rescue therapy in a case of portopulmonary hypertension during liver transplantation: a case report.

Portopulmonary hypertension has been reported in 2% to 9% of candidates for liver transplantation (OLT). If it is moderate to severe, it represents a contraindication to the procedure until pulmonary vasodilatative therapy has been optimized. We report the case of a 43-year-old man, scheduled for OLT due to alcoholic cirrhosis with hemosiderosis. His Model for End-Stage Liver Disease was 25 at that time. The preoperative evaluation showed a severe alteration of diffusion (pO2 68 mm Hg), without hepatopulmonary syndrome or portopulmonary hypertension (PPH) upon basal and dobutamine stress echocardiography. At the beginning of the OLT the hemodynamic profile showed mean pulmonary artery pressure (mPAP) 38 mm Hg, wedge pressure (WP) 19 mm Hg, cardiac output (CO) 9.1 L/min, pulmonary vascular resistance (PVR) 166 dyne s/cm(5), transpulmonary gradient (TPG) 19 mm Hg, which lead us to promptly initiate inhaled nitric oxide (iNO) and intravenous epoprostenol 2 to 5 ng/kg/min. Upon graft reperfusion the hemodynamic profile was: mPAP 47 mm Hg, WP 23 mm Hg, CO 14.2 L/min, PVR 135 dyne s/cm(5), TPG 24 mm Hg, and at the end of surgery, mPAP 39 mm Hg, WP 20 mm Hg, CO 10.6 L/min, PVR 123 dyne s/cm(5), TPG 19 mm Hg. On postoperative day (POD) 3, we observed severe worsening of PPH: mPAP 60 mm Hg, WP 10 mm Hg, CO 9.8 L/min, PVR 395 dyne s/cm(5), TPG 50 mm Hg even with maximal pulmonary vasodilatatory therapy (ambrisentan 5 mg, intravenous sildenafil 20 mg × 3 and epoprostenol 22 ng/kg/min, iNO). Severe acute respiratory distress syndrome (ARDS) was presents. Therefore we decided to begin veno-venous extracorporeal membrane oxygenation (v-v ECMO) to correct the hypoxic vasoconstriction. Subsequent weaning from inotropic support with iNO and epoprostenol was possible on POD 7 due to mPAP 42 mm Hg, WP 15 mm Hg, CO 7.9 L/min, PVR 273 dyne s/cm(5), and TPG 27 mm Hg. On POD 11 he was weaned from ECMO due to: mPAP 40 mm Hg, WP 16 mm Hg, CO 6.5 L/min, PVR 295 dyne s/cm(5) and TPG 24 mm Hg. The patient was extubated on POD 17. The cardiac catheterization 1 month after OLT showed: mPAP 28 mm Hg, WP 13 mm Hg, CO 5.4 L/min, PVR 220 dyne s/cm(5) and TPG 15 mm Hg. ECMO rescue therapy in this "extreme" case allowed us to correct hypoxemia responsible for worsening of pulmonary hypertension allowing time to reach the goal of vasodilatatory therapy.

Are guidelines for non-invasive ventilation during weaning still valid?

Noninvasive ventilation (NIV) has gained increasing acceptance over the years to reduce endotracheal intubation, pneumonia and to prevent or treat respiratory failure in patients with different diagnoses. The international consensus conference, and the British society guidelines on NIV ventilation have analyzed its use during the weaning phase concluding that there were still conflicting results of its use. However, recent clinical trials have shown clear clinical benefits on the use of NIV in several patient populations during the weaning period. Acute respiratory failure (ARF) during the weaning process is the main object of recently published studies. The latest published randomized trials on the application of NIV for acute respiratory failure following extubation failed to demonstrate any favorable outcome. Even so, the use of NIV during the process of weaning in patients experiencing multiple weaning failure or as a preventive therapy in patients at higher risk of respiratory deterioration showed improved clinical outcomes only in chronic obstructive pulmonary disease and in particular in hypercapnic patients. Reduced invasive mechanical ventilation, tracheostomy and lower mortality rate at 90 days were the major advantages.

De novo everolimus-based therapy in renal transplant recipients: effect on proteinuria and renal prognosis.

BACKGROUND: In large-scale clinical trials, the proliferation signal inhibitor (PSI) everolimus (EVL) combined with cyclosporine (CsA) and steroids, has been shown to be efficacious among de novo renal transplant recipients. Development of proteinuria has been shown to be an important predictor of renal dysfunction after conversion from CsA to a PSI-based regimen, and a key marker of allograft disease progression. Whether EVL de novo treatment is associated with a similar proteinuric effect is still under investigation. METHODS: We compared the development of proteinuria among a cohort of 24 renal transplant recipients who were prescribed EVL (3 mg/d; n = 12; high-dose group) or 1.5 mg/d (n = 12; standard-dose group), in association with CsA, versus third control cohort of 12 patients who received mycophenolate mofetil (control group). EVL doses were adjusted to achieve trough blood levels of 3-8 ng/mL and 8-12 ng/mL among the standard and high-dose groups, respectively. We assessed renal function and protein excretion over a 2-year observation. RESULTS: The high-dose group showed a trend toward greater proteinuria than the standard-dose on control groups. They showed significantly greater proteinuria from 9 months until 2 years; 0.86 +/- 0.5, 0.5 +/- 0.3, 0.47 +/- 0.2 g/24 h (P = .03 and P = .02, respectively, at 24 months). Mean proteinuria significantly correlated with mean EVL doses (n = .73; P = .0001). Concomitantly, the estimated glomerular filtration rate (eGFR) was significantly lower among patients treated with EVL 3.0 versus 1.5 mg/d (53.7 +/- 24 vs 73.04 +/- 17.6 mL/min; P = .037). Among patients in the standard-dose, the eGFR was consistently higher than the control group (62.6 +/- 29 mL/min). CONCLUSION: EVL/CsA therapy is a safe alternative regimen for de novo renal transplant recipients. Higher EVL doses are correlated with greater increases in proteinuria. The standard EVL dose seems to be useful treatment strategy to prevent acute rejection episodes, with a better renal prognosis in the long term.