The latest medical research on Intensive Care Medicine

Clinical variables associated with shortened survival in advanced-stage cystic fibrosis (CF) patients are not included in the lung allocation score (LAS).

Identify variables associated with waitlist and posttransplant mortality for CF lung transplant candidates using a novel database; analyze the impact of including new CF-specific variables in the LAS.

A deterministic matching algorithm identified patients from the Scientific Registry of Transplant Recipients and the Cystic Fibrosis Foundation Patient Registry. LAS waitlist and posttransplant survival models were recalculated using CF-specific variables. This multi-center, retrospective, population-based study of lung transplant waitlist candidates aged ≥ 12 years, January 1, 2011-December 31, 2014, included 9043 patients on the lung transplant waiting list and 6110 lung transplant recipients, 2011-2014, 1020 and 677 with CF, respectively.

Measured outcomes were changes in LAS and lung allocation rank. For CF candidates, any Burkholderia sp. (hazard ratio 2.8, 95% confidence interval 1.2-6.6), 29-42 days hospitalized (2.8, 1.3-5.9), massive hemoptysis (2.1, 1.1-3.9), and relative drop in FEV1 ≥ 30% over 12 months (1.7, 1.0-2.8) increased waitlist mortality risk; pulmonary exacerbation time 15-28 days (1.8, 1.1-2.9) increased posttransplant mortality risk. A relative drop in FEV1 of ≥ 10% in chronic obstructive pulmonary disease (COPD) candidates was associated with increased waitlist mortality risk (2.6, 1.2-5.4). Variability in LAS score and rank increased in CF patients. Priority for transplant increased for COPD candidates. Access did not change for other diagnosis groups.

Adding CF-specific variables improved discrimination among waitlisted CF candidates, and benefitted COPD candidates.

Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACDMPV) is a lethal congenital disorder causing respiratory failure and pulmonary hypertension shortly after birth. There are no effective treatments for ACDMPV other than lung transplant, and new therapeutic approaches are urgently needed. While ACDMPV is linked to mutations in the FOXF1 gene, molecular mechanisms through which FOXF1 mutations cause ACDMPV are unknown.

Identify molecular mechanisms by which S52F FOXF1 mutations cause ACDMPV.

We generated a clinically relevant mouse model of ACDMPV by introducing the S52F FOXF1 mutation into the mouse Foxf1 gene locus using CRISPR/Cas9 technology. Immunohistochemistry, whole lung imaging and biochemical methods were used to examine vasculature in Foxf1WT/S52F lungs and identify molecular mechanisms regulated by FOXF1.

FOXF1 mutations were identified in 28 subjects with ACDMPV. Foxf1WT/S52F knock-in mice recapitulated histopathological findings in ACDMPV infants. The S52F FOXF1 mutation disrupted STAT3-FOXF1 protein-protein interactions and inhibited transcription of Stat3, a critical transcriptional regulator of angiogenesis. STAT3 signaling and endothelial proliferation were reduced in Foxf1WT/S52F mice and human ACDMPV lungs. S52F FOXF1 mutant protein did not bind chromatin and was transcriptionally inactive. Furthermore, we have developed a novel formulation of highly-efficient nanoparticles and demonstrated that nanoparticle delivery of STAT3 cDNA into the neonatal circulation restored endothelial proliferation and stimulated lung angiogenesis in Foxf1WT/S52F mice.

FOXF1 acts through STAT3 to stimulate neonatal lung angiogenesis. Nanoparticle delivery of STAT3 is a promising strategy to treat ACDMPV associated with decreased STAT3 signaling.

Technical factors at the moment of catheter insertion might have a role in peripherally inserted central catheter-related thrombotic risk. We performed a systematic review and meta-analysis to define the actual rate of peripherally inserted central catheter-related symptomatic deep vein thrombosis in patients in whom catheter insertion was performed according to ultrasound guidance, appropriate catheter size choice, and proper verification of tip location.

We searched Medline, Embase, and Cochrane Library. Only prospective observational studies published in peer-reviewed journals after 2010 up to November 2018 reporting peripherally inserted central catheter-related deep vein thrombosis rate were included. All studies were of adult patients who underwent peripherally inserted central catheter insertion. Results were restricted to those studies which included in their methods ultrasound guidance for venipuncture, catheter tip location, and a catheter size selection strategy. Random-effect meta-analyses and arcsine transformation for binomial data were performed to pool deep vein thrombosis weighted frequencies.

Of the 1441 studies identified, 15 studies involving 5420 patients and 5914 peripherally inserted central catheters fulfilled our inclusion criteria. The weighted frequency of peripherally inserted central catheter-related deep vein thrombosis was 2.4% (95% confidence interval = 1.5-3.3) and remained low in oncologic patients (2.2%, 95% confidence interval = 0.6-3.9). Thrombotic rate was higher in onco-hematologic patients (5.9%, 95% confidence interval = 1.2-10). Considerable heterogeneity (I2 = 74.9) was observed and all studies were considered at high risk of attrition bias.

A proper technique is crucial at the moment of peripherally inserted central catheter insertion. Peripherally inserted central catheter-related deep vein thrombosis rate appears to be low when evidence-based technical factors are taken into consideration during the insertion procedure.

The aim of this study was to compare two complex vascular access techniques that utilize the axillary artery as inflow and accesses were created with early cannulation grafts: the axillary-atrial arteriovenous graft versus axillary-iliac arteriovenous graft.

This is a retrospective study of end-stage renal disease patients with occluded intrathoracic central veins that underwent complex hemodialysis access creation in our institution after failed endovascular recanalization attempts. Patients' demographics, comorbidities, number and types of previous accesses, intraoperative variables, and clinical outcomes were collected and compared.

Four patients underwent axillary-atrial arteriovenous graft creation with Flixene™ (Atrium™, Hudson, NH, USA) grafts, through a midline sternotomy to expose the right atrium; all were successfully implanted and used for hemodialysis within the first 72 h; one patient developed a pseudoaneurysm in the mid-graft portion, requiring surgical repair, and it is currently functional. Eight axillary-iliac arteriovenous grafts were created; all grafts were patent and were utilized within 96 h after placement. At 6 months of follow-up period, five (62 %) of our patients underwent graft thrombectomy, one (12 %) balloon angioplasty at the vein anastomosis secondary to stenosis, and two (25 %) grafts were removed due to infectious complications. Axillary-atrial arteriovenous graft and axillary-iliac arteriovenous graft primary patency rates at 6 months were 75% and 48%, respectively; 6-month secondary patency of the axillary-atrial arteriovenous graft compares favorably against that of axillary-iliac arteriovenous graft (100% vs 75%, respectively).

Despite the invasiveness, direct atrial outflow procedures remain a valid alternative in carefully selected patients with adequate cardiopulmonary reserve.

Anemia is one of the most common complications of sepsis. Sepsis-related anemia is associated mainly with inflammation. We aimed to observe the changes in the inflammatory anemia-associated parameters of patients with sepsis in the early stage of intensive care unit (ICU) admission and to evaluate their association with 28-day mortality.

A total of 198 patients with sepsis were divided into survivor (n = 110) and non-survivor (n = 88) groups on the basis of 28-day survival. Healthy volunteers (n = 20) were enrolled as a control group. Plasma levels of iron, ferritin, erythropoietin (EPO), soluble transferrin receptor (sTfR), hepcidin, interleukin-6 (IL-6), hemoglobin and the red blood cell distribution width (RDW) were measured on days 1, 3 and 7 of ICU admission. Clinical data and laboratory findings were collected, and the Sequential Organ Failure Assessment (SOFA) score was calculated.

Patients with sepsis showed significant decreases in hemoglobin, plasma iron and sTfR/log ferritin and significant increases in plasma EPO, sTfR, hepcidin, ferritin and IL-6 on days 1, 3 and 7 of ICU admission compared with healthy volunteers. Hemoglobin was correlated negatively with plasma IL-6 and hepcidin. In patients with sepsis, non-survivors had significantly lower plasma iron, EPO and sTfR/log ferritin, but higher plasma hepcidin, ferritin and IL-6 than survivors on days 1, 3 and 7 of ICU admission. Plasma EPO, hepcidin, ferritin, IL-6, sTfR/log ferritin, the RDW and SOFA score were associated significantly with 28-day mortality but to a varying extent. In particular, in predicting 28-day mortality, plasma hepcidin had an area under the receiver operating curve of 0.808 and 87.3% specificity, which was the highest among the inflammatory anemia-associated parameters tested.

Inflammatory anemia-associated parameters changed significantly in patients with sepsis in the first week of ICU admission. Plasma EPO, hepcidin, ferritin, IL-6, sTfR/log ferritin, the RDW and SOFA score were associated significantly with 28-day mortality. Plasma hepcidin might have a superior predictive value, with high specificity, compared with other inflammatory anemia-associated parameters for 28-day mortality of sepsis patients in the ICU.

Although no specific treatment facilitates renal tubular regeneration in acute kidney injury (AKI), the rapid increase in aging populations with more comorbidities and advances in critical care management are expected to change the epidemiology of AKI. However, few recent studies dissected the current epidemiologic characteristics of critically ill patients with AKI. We investigated recent epidemiologic changes in severe AKI in critically ill patients.

All adult admissions to intensive care units (ICUs) in Korea from 2008 to 2015 were screened using the national health insurance review and assessment database, and 1,744,235 patients were included. Clinical characteristics and changes in AKI incidence and mortality rate were analyzed.

The incidence of AKI increased from 7.4% in 2008 to 8.3% in 2015 (p for trend < 0.001). Age-standardized AKI rate was 7018.6 per 100,000 person-years. In-hospital mortality significantly decreased from 39.1% in 2008 to 37.2% in 2015 (p for trend < 0.001) with 2427.6 deaths per 100,000 person-years. Patients with AKI showed higher in-hospital mortality, prolonged ICU length of stay, and higher total cost. Multivariable analysis showed increased risk of in-hospital mortality (adjusted odds ratio [OR] 3.74), mechanical ventilation (OR 2.87), ECMO (OR 6.99), and vasopressor requirement (OR 2.75) in patients with AKI.

Recent advances in medical management for AKI have improved in-hospital mortality of critically ill patients with AKI despite increases in the elderly population and AKI incidence.