Author Correction: High expression of MMP14 is associated with progression and poor short-term prognosis in muscle-invasive bladder cancer.

Correction to: Eur Rev Med Pharmacol Sci 2020; 24 (12): 6605-6615-DOI: 10.26355/eurrev_202006_21646-published online on June 25, 2020. After publication, the authors have applied some corrections to the galley proof: -       In Table II, data display in MMP14 expression between Low and high group was inverted. This correction does not involve any statistical data modification and does not affect the conclusion of the article. The correct table display should be as follows: -       In Figure 4F, the cell invasion image of siRNA-2 group in T24 was misplaced. The authors have adjusted the brightness and contrast appropriately as well. The correct Figure 4F display should be as follows: There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/21646.

Vascular contributions to cognitive decline: Beyond amyloid and tau in the Harvard Aging Brain Study.

In addition to amyloid and tau pathology, elevated systemic vascular risk, white matter injury, and reduced cerebral blood flow contribute to late-life cognitive decline. Given the strong collinearity among these parameters, we proposed a framework to extract the independent latent features underlying cognitive decline using the Harvard Aging Brain Study (N = 166 cognitively unimpaired older adults at baseline). We used the following measures from the baseline visit: cortical amyloid, inferior temporal cortex tau, relative cerebral blood flow, white matter hyperintensities, peak width of skeletonized mean diffusivity, and Framingham Heart Study cardiovascular disease risk. We used exploratory factor analysis to extract orthogonal factors from these variables and their interactions. These factors were used in a regression model to explain longitudinal Preclinical Alzheimer Cognitive Composite-5 (PACC) decline (follow-up = 8.5 ±2.7 years). We next examined whether gray matter volume atrophy acts as a mediator of factors and PACC decline. Latent factors of systemic vascular risk, white matter injury, and relative cerebral blood flow independently explain cognitive decline beyond amyloid and tau. Gray matter volume atrophy mediates these associations with the strongest effect on white matter injury. These results suggest that systemic vascular risk contributes to cognitive decline beyond current markers of cerebrovascular injury, amyloid, and tau.

Etiology of White Matter Hyperintensities in Autosomal Dominant and Sporadic Alzheimer Disease.

Importance: Increased white matter hyperintensity (WMH) volume is a common magnetic resonance imaging (MRI) finding in both autosomal dominant Alzheimer disease (ADAD) and late-onset Alzheimer disease (LOAD), but it remains unclear whether increased WMH along the AD continuum is reflective of AD-intrinsic processes or secondary to elevated systemic vascular risk factors. Objective: To estimate the associations of neurodegeneration and parenchymal and vessel amyloidosis with WMH accumulation and investigate whether systemic vascular risk is associated with WMH beyond these AD-intrinsic processes. Design, Setting, and Participants: This cohort study used data from 3 longitudinal cohort studies conducted in tertiary and community-based medical centers-the Dominantly Inherited Alzheimer Network (DIAN; February 2010 to March 2020), the Alzheimer's Disease Neuroimaging Initiative (ADNI; July 2007 to September 2021), and the Harvard Aging Brain Study (HABS; September 2010 to December 2019). Main Outcome and Measures: The main outcomes were the independent associations of neurodegeneration (decreases in gray matter volume), parenchymal amyloidosis (assessed by amyloid positron emission tomography), and vessel amyloidosis (evidenced by cerebral microbleeds [CMBs]) with cross-sectional and longitudinal WMH. Results: Data from 3960 MRI sessions among 1141 participants were included: 252 pathogenic variant carriers from DIAN (mean [SD] age, 38.4 [11.2] years; 137 [54%] female), 571 older adults from ADNI (mean [SD] age, 72.8 [7.3] years; 274 [48%] female), and 318 older adults from HABS (mean [SD] age, 72.4 [7.6] years; 194 [61%] female). Longitudinal increases in WMH volume were greater in individuals with CMBs compared with those without (DIAN: t = 3.2 [P = .001]; ADNI: t = 2.7 [P = .008]), associated with longitudinal decreases in gray matter volume (DIAN: t = -3.1 [P = .002]; ADNI: t = -5.6 [P < .001]; HABS: t = -2.2 [P = .03]), greater in older individuals (DIAN: t = 6.8 [P < .001]; ADNI: t = 9.1 [P < .001]; HABS: t = 5.4 [P < .001]), and not associated with systemic vascular risk (DIAN: t = 0.7 [P = .40]; ADNI: t = 0.6 [P = .50]; HABS: t = 1.8 [P = .06]) in individuals with ADAD and LOAD after accounting for age, gray matter volume, CMB presence, and amyloid burden. In older adults without CMBs at baseline, greater WMH volume was associated with CMB development during longitudinal follow-up (Cox proportional hazards regression model hazard ratio, 2.63; 95% CI, 1.72-4.03; P < .001). Conclusions and Relevance: The findings suggest that increased WMH volume in AD is associated with neurodegeneration and parenchymal and vessel amyloidosis but not with elevated systemic vascular risk. Additionally, increased WMH volume may represent an early sign of vessel amyloidosis preceding the emergence of CMBs.

A facile imine-linked covalent organic framework doped with a carbon dot composite for the detection and removal of Hg2+ in surface water.

Hg2+ is one of the most toxic chemical species in the water environment, and thus developing a new fluorescent covalent organic framework for both the detection and removal of Hg2+ is highly desirable. Herein, a fluorescent composite, termed TpPa-1 COF@CDs, was synthesized by inverse emulsion polymerization method using an imine covalent organic framework as the supporting material and carbon dots as the fluorescent sensor element. The crystallinity, porosity, rich functional receptors (hydroxyl and amino groups), thermal stability and fluorescent properties of TpPa-1 COF@CDs were characterized. The results showed that TpPa-1 COF@CDs exhibited a good detection and removal performance for Hg2+, which was evidenced by its high sensitivity (LOD = 0.75 µg L-1), superior selectivity, large adsorption capacity (235 mg g-1), fast adsorption rate (30 min equilibrium time) and good regeneration (at least five cycles). More importantly, the simple functional monomer, short reaction time and metal-free raw material made TpPa-1 COF@CDs reliable, cost effective and eco-friendly. This research demonstrated the facile construction of a functional covalent organic framework composite for water environmental remediation technologies of metal pollution.

Progressive White Matter Injury in Preclinical Dutch Cerebral Amyloid Angiopathy.

Autosomal-dominant, Dutch-type cerebral amyloid angiopathy (D-CAA) offers a unique opportunity to develop biomarkers for pre-symptomatic cerebral amyloid angiopathy (CAA). We hypothesized that neuroimaging measures of white matter injury would be present and progressive in D-CAA prior to hemorrhagic lesions or symptomatic hemorrhage. In a longitudinal cohort of D-CAA carriers and non-carriers, we observed divergence of white matter injury measures between D-CAA carriers and non-carriers prior to the appearance of cerebral microbleeds and >14 years before the average age of first symptomatic hemorrhage. These results indicate that white matter disruption measures may be valuable cross-sectional and longitudinal biomarkers of D-CAA progression. ANN NEUROL 2022;92:358-363.

Plasma IL-12/IFN-γ axis predicts cognitive trajectories in cognitively unimpaired older adults.

INTRODUCTION: Immune dysregulation is implicated in neurodegeneration and altered cytokine levels are seen in people with dementia. However, whether cytokine levels are predictive of cognitive decline in cognitively unimpaired (CU) elderly, especially in the setting of elevated amyloid beta (Aß), remains unclear. METHODS: We measured nine cytokines in the baseline plasma of 298 longitudinally followed CU elderly and assessed whether these measures were associated with cognitive decline, alone or synergistically with Aß. We next examined associations between cytokine levels and neuroimaging biomarkers of Aß/tau/neurodegeneration. RESULTS: Higher IL-12p70 was associated with slower cognitive decline in the setting of higher Aß (false discovery rate [FDR] = 0.0023), whereas higher IFN-γ was associated with slower cognitive decline independent of Aß (FDR = 0.013). Higher IL-12p70 was associated with less tau and neurodegeneration in participants with higher Aß. DISCUSSION: Immune dysregulation is implicated in early-stage cognitive decline, and greater IL-12/IFN-γ axis activation may be protective against cognitive decline and early-stage AD progression.

Thresholds for Transverse Stimulation: Fiber Bundles in a Uniform Field.

Cable theory is used to model fibers (neural or muscular) subjected to an extracellular stimulus or activating function along the fiber (longitudinal stimulation). There are cases however, in which activation from fields across a fiber (transverse stimulation) is dominant and the activating function is insufficient to predict the relative stimulus thresholds for cells in a bundle. This work proposes a general method of quantifying transverse extracellular stimulation using ideal cases of long fibers oriented perpendicular to a uniform field (circular cells in a 2-D extracellular domain). Several methods are compared against a fully coupled model to compute electrical potentials around each cell of a bundle and predict the magnitude of applied plate potential (Öp) needed to activate a given cell (Öpact). The results show that with transverse stimulation, the effect of cell presence on the external field must be considered to accurately compute Öpact. They also show that approximating cells as holes can accurately predict firing order and Öpact of cells in bundles. Potential profiles from this hole model can also be applied to single cell models to account for time-dependent transmembrane voltage responses and more accurately predict Öpact. The approaches used herein apply to other examples of transverse cell stimulation where cable theory is inapplicable and coupled model simulation is too costly to compute.

Value of three biopsy methods in prostate cancer detection: a meta-analysis and systematic review.

OBJECTIVE: The study aimed at investigating the value of systemic biopsy (sysPbx), magnetic resonance imaging/ultrasound fusion targeted biopsy (fusPbx) and fusPbx combined with sysPbx (comPbx) for prostate cancer (PCa) detection. MATERIALS AND METHODS: Data from the PubMed, Cochrane, and Embase databases were searched from inception until March 23, 2020. Prospective studies comparing the detection rates of sysPbx, fusPbx and comPbx were identified. We pooled the detection rates for all PCa, clinically significant prostate cancer (csPCa), and clinically insignificant prostate cancer (cinsPCa) of fusPbx, sysPbx, and comPbx. Risk ratios (RRs) were calculated for the meta-analysis. Then, analyses were performed to identify the possible sources of heterogeneity. RESULTS: Seventeen studies, including 18 cohorts with 3035 men, were included. No patients had previous evidence of PCa. Each patient had one or more suspicious lesions found on multiparametric magnetic resonance imaging (mpMRI) and received both fusPbx and sysPbx. The results showed that fusPbx and sysPbx did not differ significantly in detecting all PCa (RR=1.00, 95% CI: 0.95-1.05, p>0.05). However, fusPbx provided a higher detection rate for csPCa (RR=1.24, 95% CI: 1.14-1.34, p<0.05) and a lower detection rate for cinsPCa (RR=0.68, 95% CI: 0.61-0.76, p<0.05) than sysPbx. In addition, comPbx detected more PCa (RR=1.22, 95% CI: 1.16-1.29, p<0.05) and csPCa cases (RR=1.13, 95% CI: 1.05-1.21, p<0.05) than fusPbx. CONCLUSIONS: In men with positive mpMRI findings, compared to sysPbx, fusPbx had significantly increased the detection rates for csPCa and decreased those for cinsPCa. The combination of fusPbx with sysPbx outperformed fusPbx in detecting both overall PCa and csPCa.

High expression of MMP14 is associated with progression and poor short-term prognosis in muscle-invasive bladder cancer.

OBJECTIVE: To evaluate the short-term prognostic value of matrix metalloproteinase 14 (MMP14) in muscle-invasive bladder cancer (MIBC). PATIENTS AND METHODS: Expression of MMP14 and clinical information from The Cancer Genome Atlas (TCGA) were mined in MIBC patients to analyse expression differences and conduct survival analyses. The mRNA and protein expression levels of MMP14 in other tumours were analysed using Gene Expression Profiling Interactive Analysis (GEPIA) and The Human Protein Atlas. The expression level of MMP14 in bladder cancer (BC) cell lines and clinical samples and its clinical significance were indicated using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), Western blotting, and immunohistochemistry. The biological functions of MMP14 were investigated by examining cell migration using in vitro wound-healing assays and cell invasion using transwell invasion assays. Survival analyses were conducted with the collected clinical follow-up data. RESULTS: Our study revealed that MMP14 is highly expressed in MIBC based, on both TCGA derived data and our clinical tissues (p<0.05). MMP14 is also highly expressed in head and neck cancer, renal cancer, pancreatic cancer and other cancers, as analysed using GEPIA and The Human Protein Atlas (p<0.05). Survival analyses of the TCGA data and our clinical follow-up data revealed high expression of MMP14 indicates a poor short-term prognosis in MIBC (p<0.05). Furthermore, downregulation of MMP14 suppressed BC cell invasion and migration abilities in vitro. MMP14 expression was closely correlated with tumour metastasis (p<0.05). T stage [hazard ratio (HR)=1.412, 95% confidence interval (CI)=1.121-1.779, p=0.003] and metastasis (HR=2.256, 95% CI=1.242-4.100, p=0.008) were unfavourable prognostic factors in BC patients. CONCLUSIONS: In MIBC, MMP14 expression is upregulated and closely associated with disease progression and poor short-term prognosis.

Race and socioeconomic differences associated with endovascular peripheral vascular interventions for newly diagnosed claudication.

BACKGROUND: Despite guidelines cautioning against the use of endovascular peripheral vascular interventions (PVI) for claudication, more than 1.3 million PVI procedures are performed annually in the United States. We aimed to describe national rates of PVI for claudication, and identify patient and county-level risk factors associated with a high rate of PVI. METHODS: We used the Medicare claims database to identify all Medicare beneficiaries with a new diagnosis of claudication between January 2015 and June 2017. A hierarchical logistic regression model accounting for patient age, sex, comorbidities; county region and setting; and a patient race-county median income interaction was used to assess the associations of race and income with a high PVI rate. RESULTS: We identified 1,201,234 patients with a new diagnosis of claudication for analysis. Of these, 15,227 (1.27%) underwent a PVI. Based on hierarchical logistic regression accounting for patient and county-level factors, black patients residing in low-income counties had a significantly higher odds of undergoing PVI than their white counterparts (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.20-1.40), whereas the odds of PVI for black versus white patients was similar in high-income counties (OR, 1.06; 95% CI, 0.99-1.14). PVI rates were higher for low versus high-income counties in both the black (OR, 1.46; 95% CI, 1.31-1.64) and white (OR, 1.19; 95% CI, 1.12-1.27) groups. There were no significant associations of Hispanic, Asian, North American native, or other races with PVI in either low- or high-income counties after risk adjustment (all P ≥ .09). CONCLUSIONS: In the Medicare population, the mean rate of PVI of 12.7 per 1000 claudication patients varies significantly based on race and income. Our data suggest there are racial and socioeconomic differences in the treatment of claudication across the United States.

Long-term Outcomes of an Endovascular-First Approach for Diabetic Patients With Predominantly Tibial Disease Treated in a Multidisciplinary Setting.

BACKGROUND: Randomized studies suggest that open lower extremity revascularization procedures are associated with improved outcomes compared with endovascular peripheral vascular interventions (PVIs). However, advances in endovascular technologies and treatment by multidisciplinary limb preservation teams have shown improved outcomes. The aim of our study was to compare perioperative and long-term outcomes after open versus PVI procedures in diabetic patients with chronic limb-threatening ischemia (CLTI) treated in a multidisciplinary setting. METHODS: All patients presenting to our multidisciplinary diabetic limb-preservation service from 6/2012 to 07/2018 were enrolled in a prospective database. Patients who underwent either an open lower extremity bypass (LEB) or a PVI for CLTI were included in the analysis. Perioperative (30-day) complications and 4-year patency and limb salvage rates were compared between PVI and LEB using chi-squared tests, Kaplan-Meier curve analyses, and stepwise multivariable Cox proportional hazards models. RESULTS: A total of 195 lower extremity revascularization procedures were performed in 120 patients (mean age: 65.0 ± 1.0 years, 61.7% male, 63.3% black), including 53 (27.2%) open procedures and 142 (72.8%) PVIs. Nearly two-thirds of procedures (65.6%) treated multilevel diseases, while 27.2% treated isolated tibial disease and 7.2% treated isolated femoropopliteal disease. More than half of the procedures (53.3%) were performed for Wound, Ischemia, and foot Infection (WIfI) classification stage 4 limbs, 25.1% for stage 3, and 21.6% for stage 1/2. In the LEB group, 67.9% of targets were infrapopliteal. In the PVI group, 63.4% of procedures were isolated tibial interventions or were multilevel interventions including the tibial segment. Perioperative complications occurred in 52.8% of LEB versus 12.0% of PVI (P < 0.001). At 4 years postoperatively, there was no significant difference in crude (unadjusted) primary patency for PVI versus LEB (34.5 ± 6.6% vs. 49.6 ± 8.1, P = 0.89). Secondary patency was better for the LEB group (50.3 ± 7.4% vs. 55.4 ± 7.5%; P = 0.04), but amputation-free survival was similar (65.1 ± 6.7% vs. 60.9 ± 9.7%; P = 0.79). After adjusting for baseline differences between groups, primary patency (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.34 to 1.10) and amputation-free survival (HR: 1.51; 95% CI: 0.71 to 2.34) remained similar for PVI versus LEB, but secondary patency was persistently lower for PVI (HR: 0.35; 95% CI: 0.14 to 0.90). CONCLUSIONS: In this cohort of diabetic patients with CLTI undergoing predominantly tibial interventions, open revascularization was associated with a higher risk of perioperative complications than PVIs. While secondary patency rates were better after LEBs, our data suggest that an endovascular-first approach results in equivalent long-term amputation-free survival for diabetic patients treated in a multidisciplinary setting.

Assessment of Use of Arteriovenous Graft vs Arteriovenous Fistula for First-time Permanent Hemodialysis Access.

Importance: Initial hemodialysis access with arteriovenous fistula (AVF) is associated with superior clinical outcomes compared with arteriovenous graft (AVG) and should be the procedure of choice whenever possible. To address the national underuse of AVF in the United States, the Centers for Medicare & Medicaid has established an AVF goal of 66% or greater in 2009. Objective: To explore contemporary practice patterns and physician characteristics associated with high AVG use compared with AVF use. Design, Setting, and Participants: This review of 100% Medicare Carrier claims between January 1, 2016, and December 31, 2017, includes both inpatient and outpatient Medicare claims data. All patients undergoing initial permanent hemodialysis access placement with an AVF or AVG were included. All surgeons performing more than 10 hemodialysis access procedures during the study period were analyzed. Exposures: Placement of an AVF or AVG for initial permanent hemodialysis access. Main Outcomes and Measures: A surgeon-level AVG (vs AVF) use rate was calculated for all included surgeons. Hierarchical logistic regression modeling was used to identify patient-level and surgeon-level factors associated with AVG use. Results: A total of 85 320 patients (median age, 70 [range, 18-103] years; 47 370 men [55.5%]) underwent first-time hemodialysis access placement, of whom 66 489 (77.9%) had an AVF and 18 831 (22.1%) had an AVG. Among the 2397 surgeons who performed more than 10 procedures per year, the median surgeon level AVG use rate was 18.2% (range, 0.0%-96.4%). However, 498 surgeons (20.8%) had an AVG use rate greater than 34%. After accounting for patient characteristics, surgeon factors that were independently associated with AVG use included more than 30 years of clinical practice (vs 21-30 years; odds ratio, 0.85 [95% CI, 0.75-0.96]), metropolitan setting (odds ratio, 1.25 [95% CI, 1.02-1.54]), and vascular surgery specialty (vs general surgery; odds ratio, 0.77 [95% CI, 0.69-0.86]). Surgeons in the Northeast region had the lowest rate of AVG use (vs the South; odds ratio, 0.83 [95% CI, 0.73-0.96]). First-time hemodialysis access benchmarking reports for individual surgeons were created for potential distribution. Conclusions and Relevance: In this study, one-fifth of surgeons had an AVG use rate above the recommended best practices guideline of 34%. Although some of these differences may be explained by patient referral practices, sharing benchmarked performance data with surgeons could be an actionable step in achieving more high-value care in hemodialysis access surgery.

Duplex Ultrasound Assessment and Outcomes of Renal Malperfusion Syndromes after Acute Aortic Dissection.

BACKGROUND: We investigated the feasibility of renal duplex ultrasound in the identification of renal malperfusion in acute aortic dissection and evaluated whether intervention for renal malperfusion improved outcomes over best medical management alone. METHODS: All patients with acute aortic dissections involving the renovisceral aorta who underwent a duplex ultrasound were included (2004-2016). We assessed duplex findings among patients who developed acute kidney injury (AKI; 50% increase in serum creatinine) and compared AKI, 30-day mortality, and overall survival among patients who underwent a procedure to treat malperfusion versus those who did not. RESULTS: Of 37 patients with acute dissection involving the renovisceral aorta (73% were male, 59% had type B dissection, mean follow-up 4.6 ± 0.6 years), 70% developed AKI, 11% required dialysis, and 5% developed permanent dialysis dependence. AKI was correlated with higher peak creatinine levels (4.2 vs. 2.2 mg/dL, P < 0.001), although 30-day mortality and overall survival were similar (both, P ≥ 0.24). Progression to AKI was associated with significantly lower end-diastolic velocity (EDV) measurements on renal duplex (17 vs. 27 cm/sec, P = 0.03); an EDV threshold of 23 cm/sec had a positive predictive value of 85% for AKI. Operative intervention (n = 10) was associated with lower follow-up creatinine (0.9 vs. 2.1 mg/dL, P = 0.002), although there was no difference in progression to dialysis dependence, 30-day mortality, or overall survival (all, P ≥ 0.34). CONCLUSIONS: Patients who developed AKI demonstrated characteristic renal duplex ultrasound findings with lower EDV measurements in the distal renal arteries bilaterally. Performing a renal malperfusion procedure was associated with normalization of postoperative creatinine without affecting 30-day mortality or overall survival.

Drug-eluting stents are associated with improved outcomes for the treatment of infrainguinal bypass graft stenoses.

BACKGROUND: Existing endovascular therapies for failing infrainguinal bypass grafts are associated with modest patency rates. The use of everolimus drug-eluting stents (eDESs) for endovascular bypass graft revision has not yet been reported. The objective of this study was to describe and to compare clinical outcomes of eDESs vs percutaneous cutting balloons (PCBs) vs percutaneous transluminal angioplasty (PTA) for the treatment of infrainguinal bypass graft stenoses. METHODS: A multicenter, single-institution retrospective analysis of patients with infrainguinal bypass graft stenoses treated by endovascular intervention (August 2010-December 2017) was conducted. The primary study outcome was primary patency of the treated lesion. The secondary outcome was limb salvage. Outcomes are described overall and stratified by endovascular treatment modality using Kaplan-Meier curves and log-rank tests. RESULTS: During the 7-year study period, 43 patients with 78 infrainguinal bypass stenoses were treated by endovascular intervention (eDES, 15; PCB, 23; PTA, 40). Mean age was 63.3 ± 1.7 years, 53.5% were male, and 55.8% were black. The majority of patients were diabetic (60.5%) with a history of smoking (74.4%), and nearly all (83.7%) had two or more comorbidities. Half (48.7%) of bypasses treated were femoral-popliteal bypasses, followed by popliteal-distal (25.6%) and femoral-tibial (25.6%) configurations. The location of revision was the proximal anastomosis in 37.2%, midbypass in 25.6%, and distal anastomosis in 37.2%. There were no significant differences in baseline characteristics, bypass configuration, or revision location between treatment groups (P ≥ .19). Technical success for endovascular bypass intervention was 100%. At 2 years after intervention, primary patency was significantly better for patients treated with eDES (81.8%) compared with PCB (54.7%) or PTA (33.2%; log-rank, P = .03). Limb salvage was achieved in 93.6% of patients, including 86.7%, 91.3%, and 97.5% for eDES, PCB, and PTA, respectively (P = .30). CONCLUSIONS: This is the first study reporting the results of eDESs for the treatment of infrainguinal bypass graft stenoses. Use of eDESs for endovascular bypass graft revision not only is feasible but may have better primary patency than other endovascular therapies. These data suggest that eDESs may be considered a safe and efficacious endovascular technique in the armamentarium for treatment of infrainguinal bypass graft stenoses.

Effects of Ulinastatin on myocardial oxidative stress and inflammation in severely burned rats.

OBJECTIVE: By constructing the severe burns model in rat, we explored the effects of different doses of Ulinastatin (UTI) on protecting myocardium from oxidative stress and inflammatory reaction. MATERIALS AND METHODS: The severe burns model in rat was first constructed. Burned rats were intervened with different doses of UTI. Contents of cardiac troponin I (cTnI), Interleukin-1 (IL-1), Interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in rat serum and heart homogenate were detected by enzyme-linked immunosorbent assay (ELISA). Activities of SOD (superoxide dismutase), CAT (catalase), GSH-Px (glutathione peroxidase), and MDA (malondialdehyde) were detected by commercial kits. The inflammation and pathological changes in rat heart were observed by HE (Hematoxylin-Eosin) staining. Protein expressions of Cox-2, iNOS, NF-κB, Nrf2, and HO-1 in rat myocardium were detected by Western blot. RESULTS: Higher levels of cTnI, IL-1, IL-6, and TNF-α were found in model group than those of control group (p<0.05). Besides, decreased contents of cTnI, IL-1, IL-6, and TNF-α were observed in both UTI 50 ku/kg group and UTI 100 ku/kg group compared with those of model group (p<0.05). Decreased activities of SOD, CAT, and GSH-Px, as well as increased MDA level were observed in model group than those of control group (p<0.05). However, UTI treatment remarkably elevated SOD, CAT, and GSH-Px activities, whereas downregulated MDA level in burned rats (p<0.05). Abundant infiltration of inflammatory cells was found in the rat's myocardium of model group, which was alleviated in UTI group in a dose-dependent manner. Upregulated Cox-2, iNOS, and NF-κB, as well as downregulated Nrf2 and HO-1 were found in model group compared with those of control group (p<0.05). UTI pretreatment remarkably reversed the above-mentioned trends. CONCLUSIONS: Ulinastatin alleviates myocardial injury induced by severe burns. It exerts a protective role in myocardium via inhibiting oxidative stress and inflammatory response.

Resection of retroperitoneal sarcoma en-bloc with inferior vena cava: 20 year outcomes of a single institution.

BACKGROUND: Margin negative resection offers the best chance of long-term survival in retroperitoneal sarcoma (RPS). En-bloc resection of adjacent structures, including the inferior vena cava (IVC), is often required to achieve negative margins. We review our 20-year experience of en-bloc IVC and RPS resection. METHODS: Retrospective review of patients with RPS resection involving the IVC were matched 1:3 by age and histology to RPS without IVC resection. Prognostic factors for overall survival (OS) and disease free survival (DFS) were assessed. RESULTS: Thirty-two patients underwent RPS resection en-bloc with IVC. They were matched with 96 cases of RPS without IVC resection. Median OS of 59 months and DFS 18 months in IVC resection group was comparable to RPS resection without vascular involvement: median OS 65 months, DFS 18 months (P = 0.519, P = 0.604). On multivariate analyses, R2 margin (OS: HR = 6.52 [95%CI: 1.18-36.09], P = 0.032) was associated with inferior OS. R2 margin and increased number of organs resected (DFS: HR = 5.07, [1.15-22.27], P = 0.031, HR = 1.28 [1.01-1.62], P = 0.014) were associated with inferior DFS. Reconstructions included graft (n = 19, 59%), patch (n = 4, 13%), primary repair (n = 6, 19%), and ligation (n = 4, 13%). CONCLUSIONS: RPS resection en-bloc with IVC can achieve equivalent rates of DFS and OS to patients without vascular involvement.

Obesity-induced changes in lipid mediators persist after weight loss.

BACKGROUND: Obesity induces significant changes in lipid mediators, however, the extent to which these changes persist after weight loss has not been investigated. SUBJECTS/METHODS: We fed C57BL6 mice a high-fat diet to generate obesity and then switched the diet to a lower-fat diet to induce weight loss. We performed a comprehensive metabolic profiling of lipid mediators including oxylipins, endocannabinoids, sphingosines and ceramides in key metabolic tissues (including adipose, liver, muscle and hypothalamus) and plasma. RESULTS: We found that changes induced by obesity were largely reversible in most metabolic tissues but the adipose tissue retained a persistent obese metabolic signature. Prostaglandin signaling was perturbed in the obese state and lasting increases in PGD2, and downstream metabolites 15-deoxy PGJ2 and delta-12-PGJ2 were observed after weight loss. Furthermore expression of the enzyme responsible for PGD2 synthesis (hematopoietic prostaglandin D synthase, HPGDS) was increased in obese adipose tissues and remained high after weight loss. We found that inhibition of HPGDS over the course of 5 days resulted in decreased food intake in mice. Increased HPGDS expression was also observed in human adipose tissues obtained from obese compared with lean individuals. We then measured circulating levels of PGD2 in obese patients before and after weight loss and found that while elevated relative to lean subjects, levels of this metabolite did not decrease after significant weight loss. CONCLUSIONS: These results suggest that lasting changes in lipid mediators induced by obesity, still present after weight loss, may play a role in the biological drive to regain weight.

Peak season plant activity shift towards spring is reflected by increasing carbon uptake by extratropical ecosystems.

Climate change is lengthening the growing season of the Northern Hemisphere extratropical terrestrial ecosystems, but little is known regarding the timing and dynamics of the peak season of plant activity. Here, we use 34-year satellite normalized difference vegetation index (NDVI) observations and atmospheric CO2 concentration and δ13 C isotope measurements at Point Barrow (Alaska, USA, 71°N) to study the dynamics of the peak of season (POS) of plant activity. Averaged across extratropical (>23°N) non-evergreen-dominated pixels, NDVI data show that the POS has advanced by 1.2 ± 0.6 days per decade in response to the spring-ward shifts of the start (1.0 ± 0.8 days per decade) and end (1.5 ± 1.0 days per decade) of peak activity, and the earlier onset of the start of growing season (1.4 ± 0.8 days per decade), while POS maximum NDVI value increased by 7.8 ± 1.8% for 1982-2015. Similarly, the peak day of carbon uptake, based on calculations from atmospheric CO2 concentration and δ13 C data, is advancing by 2.5 ± 2.6 and 4.3 ± 2.9 days per decade, respectively. POS maximum NDVI value shows strong negative relationships (p < .01) with the earlier onset of the start of growing season and POS days. Given that the maximum solar irradiance and day length occur before the average POS day, the earlier occurrence of peak plant activity results in increased plant productivity. Both the advancing POS day and increasing POS vegetation greenness are consistent with the shifting peak productivity towards spring and the increasing annual maximum values of gross and net ecosystem productivity simulated by coupled Earth system models. Our results further indicate that the decline in autumn NDVI is contributing the most to the overall browning of the northern high latitudes (>50°N) since 2011. The spring-ward shift of peak season plant activity is expected to disrupt the synchrony of biotic interaction and exert strong biophysical feedbacks on climate by modifying the surface albedo and energy budget.

The Society for Vascular Surgery Wound, Ischemia, and foot Infection (WIfI) classification system predicts wound healing but not major amputation in patients with diabetic foot ulcers treated in a multidisciplinary setting.

OBJECTIVE: The Society for Vascular Surgery Wound, Ischemia, and foot Infection (WIfI) threatened limb classification has been shown to correlate well with risk of major amputation and time to wound healing in heterogeneous diabetic and nondiabetic populations. Major amputation continues to plague the most severe stage 4 WIfI patients, with 1-year amputation rates of 20% to 64%. Our aim was to determine the association between WIfI stage and wound healing and major amputation among patients with diabetic foot ulcers (DFUs) treated in a multidisciplinary setting. METHODS: All patients presenting to our multidisciplinary DFU clinic from July 2012 to December 2015 were enrolled in a prospective database. Wound healing and major amputation were compared for patients stratified by WIfI classification. RESULTS: There were 217 DFU patients with 439 wounds (mean age, 58.3 ± 0.8 years; 58% male, 63% black) enrolled, including 28% WIfI stage 1, 11% stage 2, 33% stage 3, and 28% stage 4. Peripheral arterial disease and dialysis were more common in patients with advanced (stage 3 or 4) wounds (P ≤ .05). Demographics of the patients, socioeconomic status, and comorbidities were otherwise similar between groups. There was a significant increase in the number of active wounds per limb at presentation with increasing WIfI stage (stage 1, 1.1 ± 0.1; stage 4, 1.4 ± 0.1; P = .03). Mean wound area (stage 1, 2.6 ± 0.6 cm2; stage 4, 15.3 ± 2.8 cm2) and depth (stage 1, 0.2 ± 0.0 cm; stage 4, 0.8 ± 0.1 cm) also increased progressively with increasing wound stage (P < .001). Minor amputations (stage 1, 18%; stage 4, 56%) and revascularizations (stage 1, 6%; stage 4, 55%) were more common with increasing WIfI stage (P < .001). On Kaplan-Meier analysis, WIfI classification was predictive of wound healing (P < .001) but not of major amputation (P = .99). For stage 4 wounds, the mean wound healing time was 190 ± 17 days, and risk of major amputation at 1 year was 5.7% ± 3.2%. CONCLUSIONS: Among patients with DFU, the WIfI classification system correlated well with wound healing but was not associated with risk of major amputation at 1 year. Although further prospective research is warranted, our results suggest that use of a multidisciplinary approach for DFUs may augment healing time and reduce amputation risk compared with previously published historical controls of standard wound care among patients with advanced stage 4 disease.

M30/M65 ratio predicts the outcome of paclitaxel chemotherapy for NSCLC

Purpose. Paclitaxel is an effective treatment for some of the non-small-cell lung cancer (NSCLC) patients. However, prediction of the outcome of paclitaxel treatment at the early stage of the chemotherapy is difficult. M30 and M65 are circulating fragments of cytokeratin 18 released during apoptosis or necrosis, respectively, and have been used as markers to evaluate chemotherapy in some cancers. Here, we aimed to examine M30 and M65 values for predicting the therapeutic outcome of paclitaxel treatment of NSCLC. Methods. The serum levels of M30 and M65 before and after paclitaxel treatment in advance-stage NSCLC patients were analyzed, and compared to those in healthy controls. The importance of the M30 and M65 levels to the outcome of chemotherapy was analyzed. Result. We found that the serum M30 and M65 levels were higher in patients with NSCLC (n = 44) than in control healthy subjects (n = 56) (p < 0.001). Two days after paclitaxel treatment, the serum levels of both M30 and M65 significantly increased in NSCLC patients (p < 0.001). Neither marker alone significantly correlated with overall patient survival, but the ratio of M30 vs M65 appeared to be an important prognostic factor for the overall survival of the patients (p < 0.01). Conclusion. Our results suggest that the serum M30/M65 ratio may be a prognostic factor for the outcome of paclitaxel treatment in NSCLC (AU)

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