Association Between Body Mass Index and Outcomes in Venoarterial Extracorporeal Membrane Oxygenation.

BACKGROUND: The association between obesity, or elevated body mass index (BMI), and outcomes in patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) has not been well established. Recent studies in patients receiving venovenous ECMO did not detect an association between obesity and increased mortality. The purpose of this retrospective observational study is to evaluate the association between BMI and survival in patients receiving VA-ECMO for cardiogenic shock. METHODS: All patients >18 years of age supported on VA-ECMO for refractory cardiogenic shock in a single academic center between 2009 and 2019 were included. ECMO outcomes, including successful ECMO decannulation and 30-day survival, were analyzed after stratification according to BMI. Multivariable and univariate logistic regression were used to assess the association between BMI and VA-ECMO outcomes. RESULTS: Of the total patients (n = 355) cannulated for VA-ECMO, 61.7% of the patients survived to ECMO recovery/decannulation, 45.5% of the patients survived to 30 days after ECMO decannulation, and 38.9% of the patients survived to hospital discharge with no statistically significant differences among the BMI groups. Multivariable logistic regression did not reveal any associations between obesity as defined by BMI and survival to ECMO decannulation (odds ratio [OR] 1.07 per 5 unit increase in BMI, 95% confidence interval [CI], 0.86-1.33; P = .57), 30-day survival (OR = 0.91, 95% CI, 0.73-1.14; P = .41) or survival to hospital discharge (OR = 0.95, 95% CI, 0.75-1.20; P = .66). CONCLUSIONS: Despite potential challenges to cannulation and maintaining adequate flow during ECMO, this single centered, retrospective observational study did not detect association between BMI and survival to ECMO decannulation, 30-day survival, or survival to hospital discharge for patients requiring VA-ECMO for refractory cardiogenic shock. These data suggest that obesity alone should not exclude candidacy for VA-ECMO.The primary outcome in this retrospective study was survival of the ECMO therapy (survival to ECMO decannulation), defined as surviving >24 hours after decannulation without a withdrawal of care. Secondary outcomes included survival at 30 days and survival to hospital discharge.

Heart valve disease in elderly Chinese population: effect of advanced age and comorbidities on treatment decision-making and outcomes.

BACKGROUND: A considerable proportion of elderly patients with symptomatic severe heart valve disease are treated conservatively despite clear indications for surgical intervention. However, little is known about how advanced age and comorbidities affect treatment decision-making and therapeutic outcomes. METHODS: Patients (n = 234, mean age: 78.5 ± 3.7 years) with symptomatic severe heart valve disease hospitalized in our center were included. One hundred and fifty-one patients (65%) were treated surgically (surgical group) and 83 (35%) were treated conservatively (conservative group). Factors that affected therapeutic decision-making and treatment outcomes were investigated and long-term survival was explored. RESULTS: Isolated aortic valve disease, female sex, chronic renal insufficiency, aged ≥ 80 years, pneumonia, and emergent status were independent factors associated with therapeutic decision-making. In-hospital mortality for the surgical group was 5.3% (8/151). Three patients (3.6%) in the conservative group died during initial hospitalization. Low cardiac output syndrome and chronic renal insufficiency were identified as predictors of in-hospital mortality in the surgical group. Conservative treatment was identified as the single risk factor for late death in the entire study population. The surgical group had better 5-year (77.2% vs. 45.4%, P < 0.0001) and 10-year (34.5% vs. 8.9%, P < 0.0001) survival rates than the conservative group, even when adjusted by propensity score-matched analysis. CONCLUSIONS: Advanced age and geriatric comorbidities profoundly affect treatment decision-making for severe heart valve disease. Valve surgery in the elderly was not only safe but was also associated with good long-term survival while conservative treatment was unfavorable for patients with symptomatic severe valve disease.

Therapeutic Decision-Making for Elderly Patients With Symptomatic Severe Valvular Heart Diseases.

The aim of this study was to determine how older age and co-morbidities affect the treatment decision-making and long-term survival in elderly patients with symptomatic severe valvular heart diseases.A total of 181 elderly patients (mean age, 78.4 ± 3.4 years) hospitalized between January 2003 and June 2012 with symptomatic severe valvular heart diseases were enrolled. Cardiac and geriatric factors associated with treatment decision-making were analyzed. Survival outcomes were investigated.Surgical treatment was performed in 116 (64%) patients (surgical group) and 65 patients (36%) were treated conservatively (conservative group). The most common [62% (40/65)] reason for refusing surgical treatment was high operative risk as assessed by the physicians who initially cared for the patients. Multivariate logistic regression analysis identified female gender, chronic renal insufficiency, older age, pneumonia, and emergent status as independent predictors of the conservative treatment. Patients with isolated aortic valve disease tended to undergo an operation. Overall 5-year survival in the surgical group was 76.8% versus 42.9% in the conservative group (P < 0.0001). After matching using the propensity score, the surgical group still had a better long-term survival than the conservative group (P = 0.001). Cox regression analysis revealed conservative treatment as the single risk factor associated with poor long-term survival in all series.Approximately 40% of the elderly patients with symptomatic severe heart valve disease were treated conservatively despite a definite indication for surgical intervention. Cardiac and geriatric co-morbidities profoundly affect the treatment decision-making. Interdisciplinary discussion should be encouraged to optimize therapeutic options for elderly patients with valvular heart disease.

Noninferiority of Shanghai Cingular biotech's bovine pericardial valve preclinical study in juvenile ovine model.

BACKGROUND: This study introduces a newly Chinese domestic-designed/manufactured bovine pericardial valve, the SCBC valve (Shanghai Cingular Biotech Corporation, Shanghai, China), and evaluates its hemodynamic performance and calcification potential compared with the Carpentier-Edwards (CE) Perimount(TM) valve (Edwards Lifesciences, Irvine, CA, USA) in juvenile sheep for preclinical study. METHODS: Five SCBC valves in study group and three CE Perimount(TM) valves (6900P with TFX) in control group were implanted in the mitral position of juvenile sheep and followed up for five months. Transthoracic echocardiography (TTE) for hemodynamic measurement was performed ten days, three months and five months postoperatively. Valve calcification was assessed by X-ray after euthanasia. Other collected data included macroscopic examination, blood analysis, microorganism culture and histological assessment. RESULTS: All sheep in two groups lived to sacrifice without evidence of valvular dysfunction. The SCBC valve had similar hemodynamic performance and susceptibility of calcification compared with the CE Perimount(TM) valve in juvenile ovine model. In all other parameters, the SCBC valve also exhibited no significant difference compared with the CE Perimount(TM) valve. CONCLUSIONS: Our study demonstrated that the SCBC valve can exhibit similar mid-term satisfactory safety and efficacy compared with the CE Perimount(TM) valve in the mitral position of juvenile sheep model.

Ex vivo evaluation of 4 different viscoelastic assays for detecting moderate to severe coagulopathy during liver transplantation.

Prolonged prothrombin time (PT) and its ratio are routinely used for the assessment of candidates for liver transplantation (LT), but intraoperative coagulation management of transfusion is hindered by its long turnaround time. Abnormal reaction time (R time) on thromboelastography (TEG) or clotting time (CT) of rotational thromboelastometry (ROTEM) are presumably an alternative, but there is a paucity of clinical data on abnormal R time/CT values compared to PT during LT. After receiving institutional review board approval and informed consent, we obtained blood samples from 36 LT patients for international normalized ratio (INR), factor (F) X level, and viscoelastic tests (EXTEM/INTEM and kaolin/rapid TEG) at baseline and 30 minutes after graft reperfusion. Receiver operating characteristic (ROC) curves were calculated for INR > 1.5 and viscoelastic R time/CT thresholds to assess the ability to diagnose FX deficiency at the moderate (<50%) or severe (<35%) level. The FX deficiency data were calculated using cutoff values of INR (>1.5) and abnormal R time/CT for TEG and ROTEM. Tissue factor (TF)-activated INR and EXTEM-CT performed well in diagnosing FX below 50%, but rapid TEG with combined TF and kaolin activators failed. Improved performance of INTEM-CT in diagnosing FX below 35% underlies multifactorial deficiency involving both intrinsic and common pathways. In conclusion, the differences among different viscoelastic tests and clinical situations should be carefully considered when they are used to guide transfusion during LT.

Cognitive impairment in native Chinese with spinocerebellar ataxia type 3.

BACKGROUND: Previous studies have shown cognitive impairment in patients with spinocerebellar ataxia type 3 (SCA3). However, there is a lack of data on Chinese patients with SCA3. METHOD: We investigated 22 native Chinese with SCA3 and 18 controls matched for age, education as well as mental status. Cognitive assessments were carefully carried out to measure verbal fluency, memory, attention, executive function, visuospatial and visuoconstructive functions. RESULTS: The most common impairments of cognition in native Chinese with SCA3 were disruption of phonemic verbal fluency and frontal executive dysfunction. Deficits in semantic fluency were detected in about 31.8% patients. Impaired visuospatial function and verbal memory were also found in native Chinese with SCA3. The degree of ataxia, CAG repeat length and education were found to correlate with cognitive performance. Multivariate binary logistic regression suggested that an oculomotor disorder and depression are predictors of cognitive impairment. CONCLUSION: Native Chinese with SCA3 had cognitive impairment of frontal executive function, temporal and parietal functions. An oculomotor disorder might be an index of cognitive dysfunction.

Stationary versus agitated storage of whole blood during acute normovolemic hemodilution.

BACKGROUND: Acute normovolemic hemodilution is an intraoperative technique to reduce the number of red blood cells lost in shed blood during surgery. Standard guidelines for storage of platelets recommend constant gentle agitation to maintain gas exchange for the metabolically active platelets. The collected whole blood (WB) for acute normovolemic hemodilution remains stationary for as long as 8 hours before reinfusion. We hypothesized that gentle agitation of WB throughout storage would improve the coagulation properties of the WB at the time of reinfusion. METHODS: WB was collected from 10 volunteer donors and control samples taken. The units were split in 2 storage groups: agitated (rocked) and stationary (unrocked). Cell counts and fibrinogen levels, as well as thromboelastography (TEG®) measurements, including TEG® PlateletMapping® assays, were performed on the control sample and the test samples after 8 hours of rocked or unrocked storage at room temperature. RESULTS: Nine units WB from 9 different healthy volunteers were tested. There were no significant differences in hematocrit, hemoglobin, red blood cells counts, platelet counts, or fibrinogen levels between the control samples and the rocked and unrocked WB samples. WB coagulation as measured by TEG® was preserved during the 8-hour storage period in both the rocked and unrocked samples. There were no significant differences between the control, rocked, and unrocked samples in time to initiate clotting, time of clot formation, rate of clot formation, or maximum strength of clot values. There were also no significant differences in the fibrin contribution to clot strength between the control, rocked, and unrocked samples, and no significant difference between the platelet activation from adenosine diphosphate or arachidonic acid among any of the 3 groups. CONCLUSIONS: Given the small sample size, there is no statistical evidence on which to reject the null hypothesis of there being no difference in the changes from the baseline between coagulation function as measured by TEG® between WB that is either agitated or kept stationary for 8 hours. These findings need to be confirmed in a larger study.

High Runx1 levels promote a reversible, more-differentiated cell state in hair-follicle stem cells during quiescence.

Quiescent hair follicle (HF) bulge stem cells (SCs) differentiate to early progenitor (EP) hair germ (HG) cells, which divide to produce transit-amplifying matrix cells. EPs can revert to SCs upon injury, but whether this dedifferentiation occurs in normal HF homeostasis (hair cycle) and the mechanisms regulating both differentiation and dedifferentiation are unclear. Here, we use lineage tracing, gain of function, transcriptional profiling, and functional assays to examine the role of observed endogenous Runx1 level changes in the hair cycle. We find that forced Runx1 expression induces hair degeneration (catagen) and simultaneously promotes changes in the quiescent bulge SC transcriptome toward a cell state resembling the EP HG fate. This cell-state transition is functionally reversible. We propose that SC differentiation and dedifferentiation are likely to occur during normal HF degeneration and niche restructuring in response to changes in endogenous Runx1 levels associated with SC location with respect to the niche.

Runx1 directly promotes proliferation of hair follicle stem cells and epithelial tumor formation in mouse skin.

Runx1/AML1 is a transcription factor implicated in tissue stem cell regulation and belongs to the small Runx family of cancer genes. In the hair follicle (HF), Runx1 epithelial deletion in morphogenesis impairs normal adult hair homeostasis (cycle) and blocks adult hair follicle stem cells (HFSCs) in quiescence. Here, we show that these effects are overcome later in adulthood. By deleting Runx1 after the end of morphogenesis, we demonstrate its direct role in promoting anagen onset and HFSC proliferation. Runx1 deletion resulted in cyclin-dependent kinase inhibitor Cdkn1a (p21) upregulation. Interfering with Runx1 function in cultured HFSCs impaired their proliferation and normal G(0)/G1 and G(1)/S cell cycle progression. The proliferation defect could be rescued by Runx1 readdition or by p21 deletion. Chemically induced skin tumorigenesis in mice turned on broad Runx1 expression in regions of the skin epithelium, papillomas, and squamous cell carcinomas. In addition, it revealed reduced rates of tumor formation in the absence of Runx1 that were accompanied by decreased epithelial levels of phospho-Stat3. Runx1 protein expression was similar in normal human and mouse hair cycles. We propose that Runx1 may act as a skin oncogene by directly promoting proliferation of the epithelial cells.