Extracorporeal CO2 removal as bridge to lung transplantation in life‐threatening hypercapnia

In patients awaiting lung transplantation (LTX), adequate gas exchange may not be sufficiently achieved by mechanical ventilation alone if acute respiratory decompensation arises. We report on 20 patients with life‐threatening hypercapnia who received extracorporeal CO₂ removal (ECCO2‐R) by means of the interventional lung assist (ILA®, Novalung) as bridge to LTX. The most common underlying diagnoses were bronchiolitis obliterans syndrome, cystic fibrosis, and idiopathic pulmonary fibrosis, respectively. The type of ILA was pumpless arteriovenous or pump‐driven venovenous (ILA activve®, Novalung) in 10 patients each. ILA bridging was initiated in 15 invasively ventilated and five noninvasively ventilated patients, of whom one had to be intubated prior to LTX. Hypercapnia and acidosis were effectively corrected in all patients within the first 12 h of ILA therapy: PaCO₂ declined from 109 (70–146) to 57 (45–64) mmHg, P < 0.0001; pH increased from 7.20 (7.06–7.28) to 7.39 (7.35–7.49), P < 0.0001. Four patients were switched to extracorporeal membrane oxygenation due to progressive hypoxia or circulatory failure. Nineteen patients (95%) were successfully transplanted. Hospital and 1‐year survival was 75 and 72%, respectively. Bridging to LTX with ECCO2‐R delivered by arteriovenous pumpless or venovenous pump‐driven ILA is feasible and associated with high transplantation and survival rates.     

Prognostic Tools for Early Mortality in Hemorrhagic Stroke: Systematic Review and Meta-Analysis

Background and Purpose

Several risk scores have been developed to predict mortality in intracerebral hemorrhage (ICH). We aimed to systematically determine the performance of published prognostic tools.

Methods

We searched MEDLINE and EMBASE for prognostic models (published between 2004 and April 2014) used in predicting early mortality (<6 months) after ICH. We evaluated the discrimination performance of the tools through a random-effects meta-analysis of the area under the receiver operating characteristic curve (AUC) or c-statistic. We evaluated the following components of the study validity: study design, collection of prognostic variables, treatment pathways, and missing data.

Results

We identified 11 articles (involving 41,555 patients) reporting on the accuracy of 12 different tools for predicting mortality in ICH. Most studies were either retrospective or post-hoc analyses of prospectively collected data; all but one produced validation data. The Hemphill-ICH score had the largest number of validation cohorts (9 studies involving 3,819 patients) within our systematic review and showed good performance in 4 countries, with a pooled AUC of 0.80 [95% confidence interval (CI)=0.77-0.85]. We identified several modified versions of the Hemphill-ICH score, with the ICH-Grading Scale (GS) score appearing to be the most promising variant, with a pooled AUC across four studies of 0.87 (95% CI=0.84-0.90). Subgroup testing found statistically significant differences between the AUCs obtained in studies involving Hemphill-ICH and ICH-GS scores (p=0.01).

Conclusions

Our meta-analysis evaluated the performance of 12 ICH prognostic tools and found greater supporting evidence for 2 models (Hemphill-ICH and ICH-GS), with generally good performance overall.     

Linear regression models and k-means clustering for statistical analysis of fNIRS data

We propose a new algorithm, based on a linear regression model, to statistically estimate the hemodynamic activations in fNIRS data sets. The main concern guiding the algorithm development was the minimization of assumptions and approximations made on the data set for the application of statistical tests. Further, we propose a K-means method to cluster fNIRS data (i.e. channels) as activated or not activated. The methods were validated both on simulated and in vivo fNIRS data. A time domain (TD) fNIRS technique was preferred because of its high performances in discriminating cortical activation and superficial physiological changes. However, the proposed method is also applicable to continuous wave or frequency domain fNIRS data sets.OCIS codes: (000.5490) Probability theory, stochastic processes, and statistics; (170.2655) Functional monitoring and imaging; (170.6920) Time-resolved imaging; (170.1470) Blood or tissue constituent monitoring     

Phenotype-Genotype Correlations and Estimated Carrier Frequencies of Primary Hyperoxaluria

Primary hyperoxaluria (PH) is a rare autosomal recessive disease characterized by oxalate accumulation in the kidneys and other organs. Three loci have been identified: AGXT (PH1), GRHPR (PH2), and HOGA1 (PH3). Here, we compared genotype to phenotype in 355 patients in the Rare Kidney Stone Consortium PH registry and calculated prevalence using publicly available whole-exome data. PH1 (68.4% of families) was the most severe PH type, whereas PH3 (11.0% of families) showed the slowest decline in renal function but the earliest symptoms. A group of patients with disease progression similar to that of PH3, but for whom no mutation was detected (11.3% of families), suggested further genetic heterogeneity. We confirmed that the AGXT p.G170R mistargeting allele resulted in a milder PH1 phenotype; however, other potential AGXT mistargeting alleles caused more severe (fully penetrant) disease. We identified the first PH3 patient with ESRD; a homozygote for two linked, novel missense mutations. Population analysis suggested that PH is an order of magnitude more common than determined from clinical cohorts (prevalence, approximately 1:58,000; carrier frequency, approximately 1:70). We estimated PH to be approximately three times less prevalent among African Americans than among European Americans because of a limited number of common European origin alleles. PH3 was predicted to be as prevalent as PH1 and twice as common as PH2, indicating that PH3 (and PH2) cases are underdiagnosed and/or incompletely penetrant. These results highlight a role for molecular analyses in PH diagnostics and prognostics and suggest that wider analysis of the idiopathic stone-forming population may be beneficial.