Pulmonary embolectomy in high-risk acute pulmonary embolism: The effectiveness of a comprehensive therapeutic algorithm including extracorporeal life support

Objectives

To investigate the effectiveness of a comprehensive therapeutic algorithm including extracorporeal life support (ECLS) in high-risk acute pulmonary embolism (aPE) treated with pulmonary embolectomy.

Materials and methods

This retrospective study included 25 consecutive patients of aPE treated with pulmonary embolectomy in a single institution between June 2005 and July 2012. All patients had high-risk aPE identified by computed tomographic angiography and were not suitable for thrombolytic therapy. High-risk aPE here was defined as aPE with (1) hemodynamic instability, (2) a pulmonary artery obstruction index (PAOI) ≥ 0.5, (3) a diameter ratio of right ventricle-to-left ventricle (RV-to-LV) ≥ 1.0, or (4) right heart thrombi. Once the eligibility was confirmed, a 3-staged therapeutic algorithm was adopted to perform an aggressive preoperative resuscitation, an expeditious pulmonary embolectomy with multidisciplinary postoperative care, and a thorough surveillance for recurrence.

Results

Among the 25 patients, 24 had a PAOI ≥ 0.5 and 23 had a RV-to-LV diameter ratio ≥ 1.0. Four patients had right heart thrombi. Sixteen patients developed preoperative instability requiring inotropic and/or mechanical support. Eight in the 16 had a preoperative cardiac arrest (CA) and six of these were bridged to surgery on ECLS. Three in the 6 patients weaned ECLS after surgery and survived to discharge. The overall in-hospital mortality was 20% (n = 5). A preoperative CA (Odds ratio [OR]: 16, 95% confidence interval [CI]: 1.4–185.4, p = 0.027, c-index: 0.80) and a postoperative requirement of ECLS (OR: 36, 95% CI: 2.1–501.3, p = 0.008, c-index: 0.85) was the pre- and postoperative predictor of in-hospital mortality. No late deaths or re-admission for recurrence were found during a median follow-up of 19 months (interquartile range: 8–29).

Conclusion

Pulmonary embolectomy was an effective intervention of high-risk aPE. However, the occurrence of preoperative CA still carried a high mortality in spite of the assistance of ECLS.     

Mortality in Emergency Department Sepsis score as a prognostic indicator in patients with pyogenic liver abscess

Objectives

The purpose of this study was to explore the predictor index of mortality in patients with pyogenic liver abscess (PLA).

Methods

We performed a retrospective review that enrolled 431 patients 18 years and older hospitalized due to PLA between January 2005 and December 2010. Clinical characteristics, laboratory results, treatments, and outcomes retrieved from medical records were analyzed. Multiple logistic regression and receiver operating characteristic curve analyses were performed.

Results

The mean age of the 431 patients identified with PLA was 56.9 ± 15.0 years. The mean Mortality in Emergency Department Sepsis (MEDS) score on admission was 4.8 ± 4.1 (range, 0-17). During hospitalization, 94 patients (22%) required intensive care. Of the 431 patients, 63 died, yielding a 15% case fatality rate. Multivariate analysis revealed that higher MEDS scores on admission (P < .0001) and the presence of underlying malignancy (P = .006), multiple abscesses (P = .001), anaerobic infections (P < .0001), hyperbilirubinemia (P < .0001), and higher serum creatinine levels (P < .0001) were significantly associated with PLA mortality. The estimated area under the receiver operating characteristic curve for MEDS in predicting PLA mortality was 0.829 (95% confidence interval, 0.791-0.864; P < .0001). The optimal cutoff MEDS value of 7 or higher had a sensitivity of 76% sensitivity and a specificity of 81%, with a 10.7-fold PLA mortality risk (P < .0001) and a 26.2-fold intensive care unit admission risk (P < .0001).

Conclusions

The MEDS scores on admission represent a significant prognostic indicator for patients with PLA.     

Electrostatic immobilization of DNA polyplexes on small intestinal submucosa for tissue substrate-mediated transfection

Naturally occurring extracellular matrices (ECMs) such as small intestinal submucosa (SIS) have received significant attention for their therapeutic applications in tissue repair and regeneration. However, there have been no reports exploring the electrostatic properties of naturally occurring ECMs as a means to control transgene delivery. In the present study, we electrostatically adsorbed DNA polyplexes onto SIS for transfection upon cellular adhesion. To associate polyplexes with SIS, we first used a streaming potential method to characterize the surface charge of SIS and obtained a negative zeta potential at neutral pH, which can be attributed to the abundant glycosaminoglycan (GAG) content in SIS. We next prepared cationic polyethylenimine (PEI)/DNA polyplexes to associate with the negatively charged SIS for conjugation. Using the Cy(TM)3 dye-labeled control DNA as the reporter, we visualized the adsorption of PEI/DNA polyplexes at the SIS surface. Using luciferase, green fluorescent protein and beta-galactosidase as reporter proteins, we showed that the adsorbed PEI/DNA polyplexes were active and capable of carrying out transfection upon cellular adhesion, indicating that the electrostatic binding of polyplexes with SIS was reversible. In addition, the SIS-mediated transfection was contact-dependent: separation of SIS from the target cells via a 0.5 mm porous polyester membrane significantly reduced the efficiency of transfection in comparison to a direct seeding of cells onto SIS. We conclude that electrostatic immobilization of PEI/DNA polyplexes on SIS is capable of initiating efficient transgene delivery, which can be a useful tool in developing localized gene transfer.     

Disparities and survival in newly diagnosed gastric cancer in Hispanic patients in the United States: a propensity score matched analysis

BackgroundThe burden of gastric cancer involving Hispanic patients in the United States is growing as both the population and the incidence of gastric cancer in this group increases. This burden is compounded by presentation with advanced disease and socioeconomic challenges shaping cancer care. We sought to describe the demographics, socioeconomic factors, treatment, and survival experience of Hispanic patients with gastric adenocarcinoma.MethodsPatients with gastric adenocarcinoma diagnosed between 2004 and 2015 (n=90,737) in the National Cancer Database were retrospectively identified. Patients of Hispanic ethnicity were compared against non-Hispanic white patients. Surgical cohort was further analyzed, and 1:1 propensity score matching was used to balance covariates between Hispanic and non-Hispanic white surgical patients. Survival was compared using Kaplan-Meier method. Cox regression was used to determine prognostic factors for survival.ResultsCompared to non-Hispanic white patients, Hispanic patients are more likely to be younger, female, and healthier. They were more likely to be uninsured, reside in poorer neighborhoods and reside in areas with lower rates of education. Hispanic patients were more likely to live in a metropolitan area, travel shorter distances for healthcare, and receive treatment at an academic and high volume centers. Hispanic patients were more likely to have higher stage disease presentation, higher grade tumors, lymphovascular invasion, and poorly cohesive adenocarcinoma. Hispanic patients were more likely to receive surgery, but less likely to receive adjuvant therapy. In Cox regression of all patients, unmatched surgical patients, and matched surgical patients, Hispanic ethnicity was an independent prognostic factor of improved survival.ConclusionsHispanic patients with gastric adenocarcinoma present with several unfavorable clinicopathologic and socioeconomic factors. Paradoxically, these patients demonstrate improved survival. Further study is warranted to characterize disease biology in this population.     

Influences of surgical decompression on the dorsal horn after chronic constriction injury: changes in peptidergic and delta-opioid receptor (+) nerve terminals

To understand plastic changes in the dorsal horn related to neuropathic pain, we developed a model of decompression in rats with chronic constriction injury (CCI) and investigated corresponding changes in the dorsal horn. At postoperative week 4 (POW 4) of CCI, rats were divided into a decompression group, in which ligatures were removed, and a CCI group, in which ligatures remained. Spinal cords were immunostained for substance P (SP), the delta-opioid receptor (DOR), and calcitonin gene-related peptide (CGRP). Areas of immunoreactive nerve terminals in the dorsal horn were quantified and expressed as the dorsal horn index (immunoreactive areas of the operated side compared with those of the contralateral side). At POW 4, dorsal horn indexes of all of these molecules were significantly reduced in both groups to similar degrees (0.36-0.43). At POW 8, neuropathic pain behaviors had completely disappeared in the decompression group with significant reversal of the dorsal horn indexes compared with the CCI group (0.81+/-0.02 vs. 0.58+/-0.09, P < 0.001 for SP and 0.75+/-0.04 vs. 0.55+/-0.03, P < 0.001 for DOR). In the CCI group, neuropathic pain behaviors became normalized at POW 12 with corresponding changes in dorsal horn indexes for both SP and DOR similar to those of the decompression group. In contrast, changes in the dorsal horn indexes of CGRP were similar in both the CCI and decompression groups throughout the experimental period. These findings suggest that CCI and decompression cause different patterns in peptidergic and DOR (+) nerve terminals in the dorsal horn.     

Abeta inhibits the proteasome and enhances amyloid and tau accumulation

The accumulation of misfolded protein aggregates is a common feature of numerous neurodegenerative disorders including Alzheimer disease (AD). Here, we examined the effects of different assembly states of amyloid beta (Abeta) on proteasome function. We find that Abeta oligomers, but not monomers, inhibit the proteasome in vitro. In young 3xTg-AD mice, we observed impaired proteasome activity that correlates with the detection of intraneuronal Abeta oligomers. Blocking proteasome function in pre-pathological 3xTg-AD mice with specific inhibitors causes a marked increase in Abeta and tau accumulation, highlighting the adverse consequences of impaired proteasome activity for AD. Lastly, we show that Abeta immunotherapy in the 3xTg-AD mice reduces Abeta oligomers and reverses the deficits in proteasome activity. Taken together, our results indicate that Abeta oligomers impair proteasome activity, contributing to the age-related pathological accumulation of Abeta and tau. These findings provide further evidence that the proteasome represents a viable target for therapeutic intervention in AD.     

Systematic analysis of stutters to enhance the accuracy of chimerism testing

Post-transplantation chimerism testing is important to monitor the engraftment of donor stem cells and for the diagnosis of relapse. Detecting the presence of donor/recipient-specific short tandem repeats (STRs) is a frequently used method for engraftment study. Unfortunately, the interpretation of the STR-based chimerism tests is often subject to interference by the presence of a stutter peak, which is one 4-base repeat unit smaller than an authentic allele. The aim of this study was to systematically analyze and resolve the effect of stutter peaks on the interpretation of STR-based chimerism tests. The AmpFlSTR Identifiler Amplification kit (Applied Biosystems)was used to amplify 15 STR loci using genomic DNA from 30 randomly selected, healthy donors. We found that the stutter peaks had locus-specific characteristics. The stutter percentage was defined as the percentage of the stutter peak area/main STR peak area. Based on mean values for the 30 DNA samples, the stutter percentage varied from locus to locus and ranged from 3.12% to 10.71% for 15 STR loci. The locus-specific stutter effect can be eliminated through appropriately adjusted equations. The usefulness of these equations in the prediction of relapse was confirmed by the 5% sensitivity test. Hence, this report offers a valuable scheme to enhance the accuracy of chimerism testing.