The hepato-pulmonary syndrome--where do we stand in the year 2006?

The hepato-pulmonary syndrome (HPS) is characterized by a combination of liver disease and pulmonary gas exchange abnormalities with arterial hypoxemia, intrapulmonary vasodilatation and arteriovenous shunting in the absence of intrinsic cardiopulmonary disease. The course of the disease is typically progressive. The mortality rate correlates with the pulmonary shunt volume and the degree of hypoxemia at room air. While the patho-physiology of HPS is still not fully understood, a multifactorial etiology is favored. Apart from functional intrapulmonary arteriovenous shunts which appear to represent a major factor in the development of HPS, both ventilation-perfusion mismatch and limited oxygen diffusion contribute to the HPS. Regarding its clinical appearance, pulmonary and hepatic symptoms have to be distinguished. Contrast echocardiography is the primary diagnostic tool. Symptomatically, hypoxemia can be treated with oxygen. So far, the only successful treatment approach which has been tested in larger patient groups, is liver transplantation. Given this background, the aim of this review is to critically discuss current concepts of this serious complication of liver diseases.

Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV-infection

BACKGROUND: Pneumocystis jiroveci pneumonia (PCP) remains the most common opportunistic infection in patients infected with the human immunodeficiency virus (HIV). Among patients with HIV infection and PCP the mortality rate is 10 to 20% during the initial infection and increases substantially with the need for mechanical ventilation. It was suggested that in these patients corticosteroids adjunctive to standard treatment for PCP could prevent the need for mechanical ventilation and decrease mortality. OBJECTIVES: To assess the effects of adjunctive corticosteroids on overall mortality and the need for mechanical ventilation in HIV-infected patients with PCP and substantial hypoxemia (arterial oxygen partial pressure <70 mmHg or alveolar-arterial gradient >35 mmHg on room air). SEARCH STRATEGY: We searched Medline (January 1980-December 2004), EMBASE (January 1985-December 2004) and The Cochrane Library (Issue 4, 2004) without language restrictions to identify randomised controlled trials that compared adjunctive corticosteroids to control in HIV-infected patients with PCP. We further reviewed the reference lists from previously published overviews, we searched UptoDate version 2005 and Clinical Evidence Concise (Issue 12, 2004), contacted experts of the field, and searched reference lists of identified publications for citations of additional relevant articles. SELECTION CRITERIA: Trials were considered eligible for this review if they compared corticosteroids to placebo or usual care in HIV-infected patients with PCP in addition to baseline treatment with trimethoprim-sulfamethoxazole, pentamidine or dapsone-trimethoprim, used random allocation, and reported mortality data. We excluded trials in patients with no or mild hypoxemia (arterial oxygen partial pressure >70 mmHg or an alveolar-arterial gradient <35 mmHg on room air) and trials with a follow-up of less than 30 days. DATA COLLECTION AND ANALYSIS: Two teams of reviewers independently evaluated the methodology and extracted data from each primary study. We pooled treatment effects across studies and calculated a weighted average risk ratio of overall mortality in the treatment and control groups by using a random effects model. MAIN RESULTS: Six studies were included in the review and meta-analysis. Risk ratios for overall mortality for adjunctive corticosteroids were 0.56 (95% confidence interval [CI], 0.32-0.98) at 1 month and 0.68 (95% CI, 0.50-0.94) at 3-4 months of follow-up. To prevent 1 death, numbers needed to treat are 9 patients in a setting without highly active antiretroviral therapy (HAART) available, and 23 patients with HAART available. Only the 3 largest trials provided data on the need for mechanical ventilation with a risk ratio of 0.38 (95% CI, 0.20-0.73) in favour of adjunctive corticosteroids. AUTHORS' CONCLUSIONS: The number and size of trials investigating adjunctive corticosteroids for HIV-infected patients with PCP is small, but evidence from this review suggests a beneficial effect for patients with substantial hypoxemia.

Detection of hepatic portal venous gas: its clinical impact and outcome

The clinical impact and outcome of a rare radiographic finding of hepatic portal venous gas (HPVG) as well as the effectiveness of computed tomography (CT), CT scanogram, and conventional radiography in the detection of HPVG were retrospectively analyzed. CT scans, CT scanogram, and plain film radiographs of 11 patients with HPVG were reviewed and compared with their medical records and surgical and pathology reports. Eight of the 11 patients underwent plain film radiographs 1 day before or after the CT scan. HPVG was detected at CT in all 11 patients, on CT scanogram in three (3 of 11, 27.3%), and on plain films in one (one of eight, 12.5%). In nine of 11 patients (81.8%), CT revealed an associated pneumatosis intestinalis. In six of the 11 patients (54.6%), acute mesenteric ischemia was the underlying disease for HPVG. Seven patients (63.6%) underwent emergency exploratory laparotomy. The mortality rate for HPVG alone was 27.3% (3 of 11) and for HPVG related to mesenteric bowel disease 50% (three of six). Acute mesenteric ischemia is the most common cause of HPVG, which continues to have a predictably higher mortality. CT is superior to CT scanograms and radiographs in the detection of HPVG and its underlying diseases and, therefore, should be used as the primary diagnostic tool.

Quality of life of survivors of paediatric intensive care

OBJECTIVE: The mortality rate in paediatric intensive care units (PICU) has fallen over the last two decades. More advanced treatment is offered to children with life-threatening disease and there is substantial interest in knowing whether long term outcome and quality of life after intensive care are acceptable. SETTING: 12-bed paediatric and neonatal intensive care unit. INTERVENTION: Prospective follow-up study with telephone interview 1 and 2 years after discharge. METHODS: Four domains of quality of life (physical function, role function, social-emotional function and health problem) were recorded by calculating the health state classification (HSC) index. Outcome was classified good (HSC 1.0-0.7), moderate (HSC 0.69-0.3), poor (HSC 0.29-0) and very poor (HSC <0). RESULTS: 661 patients were admitted to the PICU in the year 2001 with a mortality within the unit of 3.9%. Over 2 years follow-up there were 21 additional deaths (3.2%). 574 patients could be followed up after 1 year and 464 patients after 2 years. After two years the outcome was good in 77%, moderate in 15% and poor in 8%. Patients with respiratory disease had the best outcome, similar to those admitted for neurological and medical reasons. Patients admitted for postoperative care and for cardiovascular disease had a poorer quality of life. 31% of the children had preexisting health care problems and 21% of all patients had new chronic disease after intensive care. CONCLUSION: The majority of survivors admitted to the PICU have a good outcome. The overall mortality rate doubled if assessed two years after discharge.

Variability in outcome and resource use in intensive care units

OBJECTIVE: To examine variability in outcome and resource use between ICUs. Secondary aims: to assess whether outcome and resource use are related to ICU structure and process, to explore factors associated with efficient resource use. DESIGN AND SETTING: Cohort study, based on the SAPS 3 database in 275 ICUs worldwide. PATIENTS: 16,560 adults. MEASUREMENTS AND RESULTS: Outcome was defined by standardized mortality rate (SMR). Standardized resource use (SRU) was calculated based on length of stay in the ICU, adjusted for severity of acute illness. Each unit was assigned to one of four groups: "most efficient" (SMR and SRU < median); "least efficient" (SMR, SRU > median); "overachieving" (low SMR, high SRU), "underachieving" (high SMR, low SRU). Univariate analysis and stepwise logistic regression were used to test for factors separating "most" from "least efficient" units. Overall median SMR was 1.00 (IQR 0.77-1.28) and SRU 1.07 (0.76-1.58). There were 91 "most efficient", 91 "least efficient", 47 "overachieving", and 46 "underachieving" ICUs. Number of physicians, of full-time specialists, and of nurses per bed, clinical rounds, availability of physicians, presence of emergency department, and geographical region were significant in univariate analysis. In multivariate analysis only interprofessional rounds, emergency department, and geographical region entered the model as significant. CONCLUSIONS: Despite considerable variability in outcome and resource use only few factors of ICU structure and process were associated with efficient use of ICU. This suggests that other confounding factors play an important role.

Streptozotocin-induced diabetes mellitus in pigs

We induced, as a precondition for a pancreas transplant, insulin-dependent diabetes mellitus in 67 Yorkshire Landrace pigs by administering streptozotocin. A dosage of 150 mg/kg body weight gave rise to a long-lasting diabetes mellitus that persisted with time (follow-up period: 26 weeks). Consecutive measurements of serum glucose and plasma insulin, before and up to 30 hours after administering streptozotocin, revealed triphasic behavior: initial hyperglycemia (1st to 3rd hour), pronounced hypoglycemia (12th to 18th hour), then hyperglycemia (22nd hour on). IVGTTs done 1 to 7 days after administering streptozotocin revealed a reduction of the K-value (glucose disappearance rate) from 0.3 (day 2) to 0.07 (day 4). Immunohistochemical studies revealed a complete loss of all beta-cells, concomitantly with a relative increase in glucagon- and somatostatin-positive cells. We also observed a complete loss of pp (pancreatic polypeptide)-positive cells. Diabetes induced by streptozotocin at 150 mg/kg body weight is complete and permanent; our mortality rate was 0%. Given the high morbidity rate after pancreatectomy, streptozotocin should be the method of choice for inducing diabetes mellitus in pigs.

An infant mouse model of brain damage in pneumococcal meningitis

Bacterial meningitis due to Streptococcus pneumoniae is associated with an significant mortality rate and persisting neurologic sequelae including sensory-motor deficits, seizures, and impairments of learning and memory. The histomorphological correlate of these sequelae is a pattern of brain damage characterized by necrotic tissue damage in the cerebral cortex and apoptosis of neurons in the hippocampal dentate gyrus. Different animal models of pneumococcal meningitis have been developed to study the pathogenesis of the disease. To date, the infant rat model is unique in mimicking both forms of brain damage documented in the human disease. In the present study, we established an infant mouse model of pneumococcal meningitis. Eleven-days-old C57BL/6 (n = 299), CD1 (n = 42) and BALB/c (n = 14) mice were infected by intracisternal injection of live Streptococcus pneumoniae. Sixteen hours after infection, all mice developed meningitis as documented by positive bacterial cultures of the cerebrospinal fluid. Sixty percent of infected C57BL/6 mice survived more than 40 h after infection (50% of CD1, 0% of BALB/c). Histological evaluations of brain sections revealed apoptosis in the dentate gyrus of the hippocampus in 27% of infected C57BL/6 and in 5% of infected CD1 mice. Apoptosis was confirmed by immunoassaying for active caspase-3 and by TUNEL staining. Other forms of brain damage were found exclusively in C57BL/6, i.e. caspase-3 independent (pyknotic) cell death in the dentate gyrus in 2% and cortical damage in 11% of infected mice. This model may prove useful for studies on the pathogenesis of brain injury in childhood bacterial meningitis.

Mothers adjust egg size to helper number in a cooperatively breeding cichlid

Mothers should adjust the size of propagules to the selective forces to which these offspring will be exposed. Usually, a larger propagule size is favored when young are exposed to high mortality risk or conspecific competition. Here we test 2 predictions on how egg size should vary with these selective agents. When offspring are cared for by parents and/or alloparents, protection may reduce the predation risk to young, which may allow mothers to invest less per single offspring. In the cooperatively breeding cichlid Neolamprologus pulcher, brood care helpers protect group offspring and reduce the latters' mortality rate. Therefore, females are expected to reduce their investment per egg when more helpers are present. In a first experiment, we tested this prediction by manipulating the helper number. In N. pulcher, helpers compete for dispersal opportunities with similar-sized individuals of neighboring groups. If the expected future competition pressure on young is high, females should increase their investment per offspring to give them a head start. In a second experiment, we tested whether females produce larger eggs when perceived neighbor density is high. Females indeed reduced egg size with increasing helper number. However, we did not detect an effect of local density on egg size, although females took longer to produce the next clutch when local density was high. We argue that females can use the energy saved by adjusting egg size to reduced predation risk to enhance future reproductive output. Adaptive adjustment of offspring size to helper number may be an important, as yet unrecognized, strategy of cooperative breeders.

Pefloxacin therapy for experimental endocarditis caused by methicillin-susceptible or methicillin-resistant strains of Staphylococcus aureus

The therapeutic efficacy of pefloxacin in experimental endocarditis caused by methicillin-susceptible or methicillin-resistant Staphylococcus aureus was evaluated. In rabbits infected with a methicillin-susceptible strain, 4 days of pefloxacin therapy significantly reduced both the number of bacteria per gram of vegetation and the mortality rate compared with untreated controls, and pefloxacin was equivalent to cephalothin. Pefloxacin was also as effective as vancomycin in reducing vegetation titers and mortality rate in animals with endocarditis caused by a methicillin-resistant strain. These results suggest that pefloxacin may be an effective agent in the therapy of serious infections caused by either methicillin-susceptible or -resistant strains of S. aureus.

Takotsubo cardiomyopathy or transient left ventricular apical ballooning syndrome: A systematic review

BACKGROUND: Transient left ventricular apical ballooning syndrome (TLVABS) is an acute cardiac syndrome mimicking ST-segment elevation myocardial infarction characterized by transient wall-motion abnormalities involving apical and mid-portions of the left ventricle in the absence of significant obstructive coronary disease. METHODS: Searching the MEDLINE database 28 case series met the eligibility criteria and were summarized in a narrative synthesis of the demographic characteristics, clinical features and pathophysiological mechanisms. RESULTS: TLVABS is observed in 0.7-2.5% of patients with suspected ACS, affects women in 90.7% (95% CI: 88.2-93.2%) with a mean age ranging from 62 to 76 years and most commonly presents with chest pain (83.4%, 95% CI: 80.0-86.7%) and dyspnea (20.4%, 95% CI: 16.3-24.5%) following an emotionally or physically stressful event. ECG on admission shows ST-segment elevations in 71.1% (95% CI: 67.2-75.1%) and is accompanied by usually mild elevations of Troponins in 85.0% (95% CI: 80.8-89.1%). Despite dramatic clinical presentation and substantial risk of heart failure, cardiogenic shock and arrhythmias, LVEF improved from 20-49.9% to 59-76% within a mean time of 7-37 days with an in-hospital mortality rate of 1.7% (95% CI: 0.5-2.8%), complete recovery in 95.9% (95% CI: 93.8-98.1%) and rare recurrence. The underlying etiology is thought to be based on an exaggerated sympathetic stimulation. CONCLUSION: TLVABS is a considerable differential diagnosis in ACS, especially in postmenopausal women with a preceding stressful event. Data on longterm follow-up is pending and further studies will be necessary to clarify the etiology and reach consensus in acute and longterm management of TLVABS.

Percutaneous aortic valve replacement for severe aortic stenosis in high-risk patients using the second- and current third-generation self-expanding CoreValve prosthesis: device success and 30-day clinical outcome

OBJECTIVES: We sought to determine both the procedural performance and safety of percutaneous implantation of the second (21-French [F])- and third (18-F)-generation CoreValve aortic valve prosthesis (CoreValve Inc., Irvine, California). BACKGROUND: Percutaneous aortic valve replacement represents an emerging alternative therapy for high-risk and inoperable patients with severe symptomatic aortic valve stenosis. METHODS: Patients with: 1) symptomatic, severe aortic valve stenosis (area <1 cm2); 2) age > or =80 years with a logistic EuroSCORE > or =20% (21-F group) or age > or =75 years with a logistic EuroSCORE > or =15% (18-F group); or 3) age > or =65 years plus additional prespecified risk factors were included. Introduction of the 18-F device enabled the transition from a multidisciplinary approach involving general anesthesia, surgical cut-down, and cardiopulmonary bypass to a truly percutaneous approach under local anesthesia without hemodynamic support. RESULTS: A total of 86 patients (21-F, n = 50; 18-F, n = 36) with a mean valve area of 0.66 +/- 0.19 cm2 (21-F) and 0.54 +/- 0.15 cm2 (18-F), a mean age of 81.3 +/- 5.2 years (21-F) and 83.4 +/- 6.7 years (18-F), and a mean logistic EuroSCORE of 23.4 +/- 13.5% (21-F) and 19.1 +/- 11.1% (18-F) were recruited. Acute device success was 88%. Successful device implantation resulted in a marked reduction of aortic transvalvular gradients (mean pre 43.7 mm Hg vs. post 9.0 mm Hg, p < 0.001) with aortic regurgitation grade remaining unchanged. Acute procedural success rate was 74% (21-F: 78%; 18-F: 69%). Procedural mortality was 6%. Overall 30-day mortality rate was 12%; the combined rate of death, stroke, and myocardial infarction was 22%. CONCLUSIONS: Treatment of severe aortic valve stenosis in high-risk patients with percutaneous implantation of the CoreValve prosthesis is feasible and associated with a lower mortality rate than predicted by risk algorithms.

Stent-grafts in the treatment of emergent or urgent carotid artery disease: review of 25 cases

PURPOSE: To report the authors' initial experience with carotid artery stent-grafts in a comparatively large patient series for the treatment of acute bleeding and impending rupture or the prevention of distal embolization. MATERIALS AND METHODS: This retrospective study was approved by the institutional review boards and performed according to HIPPA standards. Twenty-five patients were treated with 27 carotid artery stent-grafts (Gore Viabahn, n = 10; Bard Fluency, n = 9; polytetrafluoroethylene-covered Palmaz, n = 5; and Wallgraft, n = 3). Thirteen stent-grafts were placed in patients with carotid blow-out syndrome (including three patients with carotid-airway fistula), 12 in patients with either pseudoaneurysm (n = 9) or true aneurysm (n = 3), and two in patients with intractable high-grade bare stent restenosis. RESULTS: The technical success rate was 100% (27 of 27 cases). No acute procedural transient ischemic attacks or strokes occurred. Procedural dissections occurred in two of the 27 cases (7.4%). Short-term complications occurred in three of the 27 cases (11%) (repeat hemorrhage, n = 2; common carotid artery occlusion, n = 1). The overall patient mortality rate was 36% (nine of 25 patients, all with carotid blow-out syndrome). Six-month follow-up in 15 of the 16 living patients demonstrated widely patent stent-grafts. Two patients with pseudoaneurysm also demonstrated patent stents at 18- and 33-month follow-up. CONCLUSIONS: Stent-grafts may be useful in the treatment of carotid artery bleeding syndrome, aneurysm, and stenosis, with a high procedural success rate in selected cases. The results of mid-term follow-up are encouraging, but results of long-term follow-up must be evaluated in future studies.

Intravascular US-guided direct intrahepatic portocaval shunt with an expanded polytetrafluoroethylene-covered stent-graft

PURPOSE: To retrospectively evaluate the midterm patency rate of the nitinol (Viatorr, W.L. Gore and Associates, Flagstaff, Ariz) stent-graft for direct intrahepatic portacaval shunt (DIPS) creation. MATERIALS AND METHODS: Institutional Review Board approval for this retrospective HIPAA-compliant study was obtained with waiver of informed consent. DIPS was created in 18 men and one woman (median age, 54 years; range, 45-65 years) by using nitinol polytetrafluoroethylene (PTFE)-covered stent-grafts. The primary indications were intractable ascites (n = 14), acute variceal bleeding (n = 3), and hydrothorax (n = 2). Follow-up included Doppler ultrasonography at 1, 6, and 12 months and venography with manometry at 6-month intervals after the procedure. Shunt patency and cumulative survival were evaluated by using the Kaplan-Meier method and survival curves were plotted. Differences in mean portosystemic gradients (PSGs) were evaluated by using the Student t test. Multiple regression analysis for survival and DIPS patency were performed for the following parameters: Child-Pugh class, model of end-stage liver disease score, pre- and post-DIPS PSGs, pre-DIPS liver function tests, and pre-DIPS creatinine levels. RESULTS: DIPS creation was successful in all patients. Effective portal decompression and free antegrade shunt flow was achieved in all patients. Intraperitoneal bleeding occurred in one patient during the procedure and was controlled during the same procedure by placing a second nitinol stent-graft. The primary patency rate was 100% at all times during the follow-up period (range, 2 days to 30 months; mean, 256 days; median, 160 days). Flow restrictors were deployed in two (11%) of 19 patients. The 1-year mortality rate was 37% (seven of 19). CONCLUSION: Patency after DIPS creation with the nitinol PTFE-covered stent-graft was superior to that after TIPS with the nitinol stent-graft.

Procedural and 30-day outcomes following transcatheter aortic valve implantation using the third generation (18 Fr) corevalve revalving system: results from the multicentre, expanded evaluation registry 1-year following CE mark approval

AIMS: To describe the procedural performance and 30-day outcomes following implantation using the 18 Fr CoreValve Revalving System (CRS) as part of the multicentre, expanded evaluation registry, 1-year after obtaining CE mark approval. METHODS AND RESULTS: Patients with symptomatic severe aortic stenosis and logistic Euroscore > or =15%, or age > or =75 years, or age > or =65 years associated with pre-defined risk factors, and for whom a physician proctor and a clinical specialist were in attendance during the implantation and who collected the clinical data, were included. From April 2007, to April 2008, 646 patients with a mean age of 81 +/- 6.6 years, mean aortic valve area 0.6 +/- 0.2 cm2, and logistic EuroSCORE of 23.1 +/- 13.8% were recruited. After valve implantation, the mean transaortic valve gradient decreased from 49.4 +/- 13.9 to 3 +/- 2 mmHg. All patients had paravalvular aortic regurgitation < or = grade 2. The rate of procedural success was 97%. The procedural mortality rate was 1.5%. At 30 days, the all-cause mortality rate (i.e, including procedural) was 8% and the combined rate of death, stroke and myocardial infarction was 9.3%. CONCLUSIONS: The results of this study demonstrate the high rate of procedural success and a low 30-day mortality in a large cohort of high-risk patients undergoing transcatheter aortic valve implantation (TAVI) with the CRS.

Promoting Biodiversity in Forest Ecosystems Using Ecological Forestry

A subset of forest management techniques, termed ecological forestry, have been developed in order to produce timber and maintain the ecological integrity of forest communities through practices that more closely mirror natural disturbance regimes. Even though alternative methods have been described and tested, these approaches still need to be established and analyzed in a variety of geographic regions in order to calibrate and measure effectiveness across different forest types. The primary objective of this research project was to assess whether group selection combined with legacy-tree retention could enhance mid-tolerant tree recruitment in a late-successional northern hardwood forest. In order to evaluate a novel alternative regeneration technique, 49 group-selection openings in three size classes were created in 2003 with a biological legacy tree retained in the center of each opening. Twenty reference sites, managed using single-tree selection, were also analyzed for comparison. The specific goals of the project were to: 1) determine the fate and persistence of the openings and legacy trees 2) assess the understory response of the group-selection openings versus the single-tree selection reference sites, and 3) evaluate the spatial patterns of yellow birch (Betula alleghaniensis Britt.) and eastern hemlock (Tsuga canadensis (L.) Carr.) in the group-selection openings. The results from 8-9 years post-study implementation and the changes that have occurred between 2004/5 and 2011/12 are discussed. The alternative regeneration technique developed and assessed in this study has the potential to enrich biodiversity in a range of forest types. Projected group-selection opening persistence rates ranged from 41-91 years. Openings from 500-1500 m2 are predicted to persist long enough for mid-tolerant tree recruitment. The legacy trees responded well to release and experienced a low mortality rate. Yellow birch (the primary shade mid-tolerant tree in the study area) densities increased with opening size. Maples surpassed all other species in abundance. In the sapling layer, sugar maple (Acer saccharum Marsh.) was 2 to over 300 times more abundant in the group-selection openings and 2 to 3 times more abundant in the references sites than all other species present. Red maple (Acer rubrum L.) was the second most abundant species present in the openings and reference sites. Spatial patterns of yellow birch and eastern hemlock in the openings were mostly aggregated. The southern edges of the largest openings contained the highest magnitude of yellow birch and eastern hemlock per unit area. Continued monitoring and additional treatments will likely be necessary in order to ensure underrepresented species successfully reach maturity.