Novel application of amino-acid buffered solution for neuroprotection against ischemia/reperfusion injury.

Ischemic neuron loss contributes to brain dysfunction in patients with cardiac arrest (CA). Histidine-tryptophan-ketoglutarate (HTK) solution is a preservative used during organ transplantation. We tested the potential of HTK to protect neurons from severe hypoxia (SH) following CA. We isolated rat primary cortical neurons and induced SH with or without HTK. Changes in caspase-3, hypoxia-inducible factor 1-alpha (HIF-1α), and nicotinamide adenine dinucleotide phosphate oxidase-4 (NOX4) expression were evaluated at different time points up to 72 h. Using a rat asphyxia model, we induced CA-mediated brain damage and then completed resuscitation. HTK or sterile saline was administered into the left carotid artery. Neurological deficit scoring and mortality were evaluated for 3 days. Then the rats were sacrificed for evaluation of NOX4 and H2O2 levels in blood and brain. In the in vitro study, HTK attenuated SH- and H2O2-mediated cytotoxicity in a volume- and time-dependent manner, associated with persistent HIF-1α expression and reductions in procaspase-3 activation and NOX4 expression. The inhibition of HIF-1α abrogated HTK's effect on NOX4. In the in vivo study, neurological scores were significantly improved by HTK. H2O2 level, NOX4 activity, and NOX4 gene expression were all decreased in the brain specimens of HTK-treated rats. Our results suggest that HTK acts as an effective neuroprotective solution by maintaining elevated HIF-1α level, which was associated with inhibited procaspase-3 activation and decreased NOX4 expression.

Chronic wound assessment and infection detection method.

BACKGROUND: Numerous patients suffer from chronic wounds and wound infections nowadays. Until now, the care for wounds after surgery still remain a tedious and challenging work for the medical personnel and patients. As a result, with the help of the hand-held mobile devices, there is high demand for the development of a series of algorithms and related methods for wound infection early detection and wound self monitoring. METHODS: This research proposed an automated way to perform (1) wound image segmentation and (2) wound infection assessment after surgical operations. The first part describes an edge-based self-adaptive threshold detection image segmentation method to exclude nonwounded areas from the original images. The second part describes a wound infection assessment method based on machine learning approach. In this method, the extraction of feature points from the suture area and an optimal clustering method based on unimodal Rosin threshold algorithm that divides feature points into clusters are introduced. These clusters are then merged into several regions of interest (ROIs), each of which is regarded as a suture site. Notably, a support vector machine (SVM) can automatically interpret infections on these detected suture site. RESULTS: For (1) wound image segmentation, boundary-based evaluation were applied on 100 images with gold standard set up by three physicians. Overall, it achieves 76.44% true positive rate and 89.04% accuracy value. For (2) wound infection assessment, the results from a retrospective study using confirmed wound pictures from three physicians for the following four symptoms are presented: (1) Swelling, (2) Granulation, (3) Infection, and (4) Tissue Necrosis. Through cross-validation of 134 wound images, for anomaly detection, our classifiers achieved 87.31% accuracy value; for symptom assessment, our classifiers achieved 83.58% accuracy value. CONCLUSIONS: This augmentation mechanism has been demonstrated reliable enough to reduce the need for face-to-face diagnoses. To facilitate the use of this method and analytical framework, an automatic wound interpretation app and an accompanying website were developed. TRIAL REGISTRATION: 201505164RIND , 201803108RSB .

Adipose-Derived Stem Cell Modulation of T-Cell Regulation Correlates with Heme Oxgenase-1 Pathway Changes.

BACKGROUND: The authors' previous proteome study revealed that haptoglobin was involved in adipose-derived stem cell modulation of allotransplant survival and T-cell regulation to induce immune tolerance. This study investigated whether adipose-derived stem cells could modulate T-cell regulation through haptoglobin and the downstream heme oxgenase-1 pathway in vitro. METHODS: Splenocytes were isolated from Lewis rat spleens and then CD3 T cells were purified using anti-CD3 beads. Adipose-derived stem cells were harvested from Lewis rats and co-cultured with the T cells. After Transwell co-culture at different periods, the authors analyzed cell proliferation with a bromodeoxyuridine assay. Cell extractions and culture supernatants were collected for further analysis. Heme oxgenase-1 and related protein expression levels from the adipose-derived stem cells and T cells were detected using Western blotting. The related cytokine expression levels were analyzed with enzyme-linked immunosorbent assay kits. Flow cytometry was used to detect the regulatory T-cell proportion. RESULTS: The adipose-derived stem cells significantly suppressed T-cell proliferation. The regulatory T-cell percentages were significantly increased in the adipose-derived stem cells that were co-cultured with T cells compared with T cells alone without adipose-derived stem cell co-culture. Heme oxgenase-1 expression in concanavalin A-stimulated T cells that were co-cultured with adipose-derived stem cells revealed a significant increase compared with concanavalin A-stimulated T cells alone. Cytokine assays of the culture supernatants revealed that transforming growth factor-ß and interleukin-10 were significantly increased and interferon-γ was statistically decreased in the adipose-derived stem cell-co-cultured T-cell group compared with other groups; however, blockade with a heme oxgenase-1 inhibitor (zinc protoporphyrin IX) protected against these changes. CONCLUSION: Adipose-derived stem cells modulate T-cell proliferation and enhance regulatory T-cell expression, and this correlated with heme oxgenase-1 expression and related cytokine pathway changes.

Sustained low-efficiency dialysis versus continuous veno-venous hemofiltration for postsurgical acute renal failure.

BACKGROUND: In postsurgical acute renal failure patients with moderate unstable hemodynamics or fluid overload, the choice of dialysis modality is difficult. This study was performed to compare the outcomes between the sustained low-efficiency dialysis (SLED) and continuous veno-venous hemofiltration (CVVH) in these patients. METHODS: Sequential postsurgical acute renal failure patients undergoing acute dialysis with CVVH (2002-2003), or SLED (2004-2005) as a result of severe fluid overload or moderately unstable hemodynamics were analyzed. Multivariate analyses of comorbidity, disease severity before initiating dialysis, biochemical measurements, and hemodynamic parameters for 3 days after the first dialysis session were performed by fitting multiple logistic regression models to predict patient's 30-day after hospital discharge (AHD) mortality. RESULTS: Among the 101 recruited patients, 38 received SLED and the rest received CVVH. The 30-day AHD mortality was 62.4%. The independent risk factors of 30-day AHD mortality included older age (P = .008), lower first postdialysis mean arterial pressure (MAP) (P = .021), higher first postdialysis blood urea nitrogen level (P = .009), and absence of a history of hypertension (P = .002). A further linear regression analysis found that dialysis using SLED was associated with higher first postdialysis MAP (P = .003). CONCLUSIONS: Among the postsurgical patients requiring acute dialysis with severe fluid overload or moderately unstable hemodynamics, the patients treated with SLED had a higher first postdialysis MAP than those treated with CVVH, which led to lower mortality. Further multicenter randomized clinical trials of larger sample size are needed to compare the effects of SLED and CVVH on the outcomes of postsurgical acute dialysis patients.

The 90-day mortality and the subsequent renal recovery in critically ill surgical patients requiring acute renal replacement therapy.

BACKGROUND: Particular attention should be paid to postoperative patients that suffer from severe acute kidney injury (AKI) requiring renal replacement therapy (RRT). METHODS: This multicenter prospective observational study included 342 patients with postoperative AKI requiring RRT from January 2002 to December 2006. RESULTS: There were 137 (40%) survivors at 90 days after the commencement of RRT. Independent predictors of 90-day mortality were older age, presence of sepsis, status post-cardiopulmonary resuscitation, necessity of continuous renal replacement therapy (CRRT), requirement of total parenteral nutrition, lower body mass index, higher Sequential Organ Failure Assessment score, and higher serum lactate level at the commencement of RRT. Further analysis among the survivors showed that lower serum creatinine at intensive care unit admission, lower Simplified Acute Physiology Score II and inotropic equivalent score at the commencement of RRT, and using CRRT were independent predictors for subsequent renal recovery. CONCLUSIONS: The development of AKI requiring RRT in postoperative critical patients represents a substantial risk for mortality and morbidity.

A modified sequential organ failure assessment score to predict hospital mortality of postoperative acute renal failure patients requiring renal replacement therapy.

BACKGROUND: A predictive model for hospital mortality in postoperative acute renal failure (ARF) patients requiring renal replacement therapy (RRT) may aid clinicians' therapeutic decision-making and research design. METHODS: A prospective observational study of 398 postoperative ARF patients requiring RRT was conducted in four hospitals. The derivation cohort consisted of 334 patients recruited between January 2002 and December 2005. The validation cohort consisted of 64 patients recruited between January 2006 and December 2006. RESULTS: The hospital mortality rates for the derivation and validation cohorts were 65.6 and 62.5%, respectively. A modified Sequential Organ Failure Assessment (SOFA) score was constructed at the commencement of RRT by a formula of serum lactate level (mM) + 2 x (generic SOFA score) + 3 x (age per decade) + 8 (if mechanical circulatory support required) + 10 (if total parenteral nutrition required) + 11 (if status postcardiopulmonary resuscitation) + 13 (if positive sepsis sign). The area under the receiver operating characteristic curve of the model for the derivation and validation cohorts was 0.804 and 0.839, respectively. CONCLUSION: This validated score at dialysis commencement might assist clinicians in estimating hospital mortality, planning future clinical trials, and providing quantitative guidance for decision making in postoperative ARF patients requiring RRT.

Risk factors of early redialysis after weaning from postoperative acute renal replacement therapy.

OBJECTIVE: The aim of this study was to identify risk factors for redialysis in postoperative patients with acute renal failure (ARF) who had previously been weaned from acute dialysis. Although recovery of renal function is anticipated in patients with ARF, no data have been reported on successful weaning from acute dialysis. DESIGN AND SETTING: Retrospective observational case-control study in a 64-bed surgical ICU. PATIENTS AND METHODS: Success in discontinuing dialysis was defined as cessation from dialysis for at least 30 days. A total of 304 postoperative patients who underwent acute renal replacement therapy in a surgical ICU between July 2002 and April 2005 were included. SOFA score biochemical data and renal function parameters were assessed on the day after the last session of renal replacement therapy, designated as day 0 (D0). RESULTS: We could wean 94 patients (30.9%) from acute dialysis for more than 5 days, and 64 of these (21.1%) were successfully weaned for at least 30days. The independent predictors for resuming dialysis within 30 days were: (a) longer duration of dialysis (OR 1.06), (b) higher SOFA score on D0 (OR 1.44), (c) oliguria (urine output <100cc/8h; OR 4.17) on D1, and (d) age over 65 years (OR 6.35). The area under the ROC curve was 0.880. Two-way analysis of variance with repeated measurements over time showed a larger decline in SOFA score and an increase in urine output in patients with successful cessation of dialysis. Kaplan-Meier analysis showed a significant difference in early resumption of dialysis between patients with or without oliguria at D0. CONCLUSIONS: More than two-thirds of patients weaned from postoperative acute dialysis for more than 5 days were free of dialysis for at least 30 days. Less urine output, longer duration of dialysis, age over 65 years, and higher disease severity score are predictive of a patient's redialysis after initial weaning from acute dialysis.

Early renal replacement therapy in patients with postoperative acute liver failure associated with acute renal failure: effect on postoperative outcomes.

BACKGROUND: Acute liver failure after major surgical procedures is associated with a high risk of multiple organ failure, including acute renal failure. The optimal time to initiate renal replacement therapy for acute renal failure is controversial because of the poor overall clinical outcomes. STUDY DESIGN: From July 2002 to January 2005, all patients who had no history of liver disease, but developed acute liver failure and subsequent renal failure requiring renal replacement therapy after major surgery, at a surgical intensive care unit, were retrospectively analyzed. Patients were divided into early or late dialysis groups based on an arbitrary blood urea nitrogen cut-off level of 80 mg/dL before renal replacement therapy. RESULTS: Eighty consecutive patients (21 women), with a mean age of 57.8+/-17.0 (SD) years, comprised the study group. The late dialysis group (n=26) had a higher ICU mortality rate (p=0.02) and a lower renal function recovery rate (p=0.02) than the early dialysis group (n=54). Fifty-three (66.3%) patients died during their ICU stay. Independent risk factors for ICU mortality were renal replacement therapy modality (intermittent hemodialysis versus continuous venous-venous hemofiltration; odds ratio [OR]=4.32, 95% CI 1.26 to 14.79; p=0.02), predialysis APACHE II score> 20 (OR=6.52, 95% CI 1.61 to 26.36; p < 0.01), and late dialysis (OR=4.01, 95% CI 1.05 to 15.27; p=0.04). CONCLUSIONS: The mortality rate in postoperative patients with acute liver failure-associated acute renal failure was very high. Earlier initiation of renal replacement therapy, based on the predialysis blood urea nitrogen level, with continuous venous-venous hemofiltration might provide a better ICU survival rate.