Parasitic helminths induce fetal-like reversion in the intestinal stem cell niche.

Epithelial surfaces form critical barriers to the outside world and are continuously renewed by adult stem cells1. Whereas dynamics of epithelial stem cells during homeostasis are increasingly well understood, how stem cells are redirected from a tissue-maintenance program to initiate repair after injury remains unclear. Here we examined infection by Heligmosomoides polygyrus, a co-evolved pathosymbiont of mice, to assess the epithelial response to disruption of the mucosal barrier. H. polygyrus disrupts tissue integrity by penetrating the duodenal mucosa, where it develops while surrounded by a multicellular granulomatous infiltrate2. Crypts overlying larvae-associated granulomas did not express intestinal stem cell markers, including Lgr53, in spite of continued epithelial proliferation. Granuloma-associated Lgr5- crypt epithelium activated an interferon-gamma (IFN-γ)-dependent transcriptional program, highlighted by Sca-1 expression, and IFN-γ-producing immune cells were found in granulomas. A similar epithelial response accompanied systemic activation of immune cells, intestinal irradiation, or ablation of Lgr5+ intestinal stem cells. When cultured in vitro, granuloma-associated crypt cells formed spheroids similar to those formed by fetal epithelium, and a sub-population of H. polygyrus-induced cells activated a fetal-like transcriptional program, demonstrating that adult intestinal tissues can repurpose aspects of fetal development. Therefore, re-initiation of the developmental program represents a fundamental mechanism by which the intestinal crypt can remodel itself to sustain function after injury

The financial burden of juvenile idiopathic arthritis: A Nova Scotia experience

Background: Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic illness. There is little published data on the financial burden of this illness. The primary objective of this study was to determine the annual costs borne by families of a child with JIA living in Nova Scotia (NS).Methods: All families in NS with a child followed in the Pediatric Rheumatology Clinic at the Izaak Walton Killam Health Centre (IWK) in 2009 were mailed a self-report questionnaire. The questionnaire evaluated disease related costs, gross household income and perceived financial burden. Dillman\u27s method was used to optimize return rates. Descriptive statistics were used to summarize results. Spearman\u27s correlation coefficient was used to assess the relationship of distance from the IWK and cost. The Mann-Whitney U test was used to compare median costs between groups.Results: Of 172 possible respondents, we received 54 completed questionnaires and 11 blank questionnaires (overall response rate 31.4%). Approximately one third (35.9%) of parents rated the financial burden as moderate or large and 36% rated financial resources available as poor. The median annual total cost per patient was $619.50 CAD (range 0,$5535) which was a median 0.7% (range 0, 37%) of gross household incomes. The largest expense for families was visit related costs. There was not a significant relationship between total annual costs and distance from the IWK (rs = 0.18, P = 0.2). Families of a child with oligoarthritis had significantly lower costs than the families of a child with another subtype of JIA ($359.00 CAD vs.$877.00 CAD, P = 0.02).Conclusions: The costs associated with having a child with JIA in NS are on average modest, but may be considerable for some families. Oligoarticular JIA is associated with smaller costs. Many families perceive the burden to be at least moderate and the availability of financial resources to be poor. Supports should be targeted to those families most in need. © 2013 Ens et al.; licensee BioMed Central Ltd

The financial burden of juvenile idiopathic arthritis: A Nova Scotia experience

Background: Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic illness. There is little published data on the financial burden of this illness. The primary objective of this study was to determine the annual costs borne by families of a child with JIA living in Nova Scotia (NS).Methods: All families in NS with a child followed in the Pediatric Rheumatology Clinic at the Izaak Walton Killam Health Centre (IWK) in 2009 were mailed a self-report questionnaire. The questionnaire evaluated disease related costs, gross household income and perceived financial burden. Dillman\u27s method was used to optimize return rates. Descriptive statistics were used to summarize results. Spearman\u27s correlation coefficient was used to assess the relationship of distance from the IWK and cost. The Mann-Whitney U test was used to compare median costs between groups.Results: Of 172 possible respondents, we received 54 completed questionnaires and 11 blank questionnaires (overall response rate 31.4%). Approximately one third (35.9%) of parents rated the financial burden as moderate or large and 36% rated financial resources available as poor. The median annual total cost per patient was $619.50 CAD (range 0,$5535) which was a median 0.7% (range 0, 37%) of gross household incomes. The largest expense for families was visit related costs. There was not a significant relationship between total annual costs and distance from the IWK (rs = 0.18, P = 0.2). Families of a child with oligoarthritis had significantly lower costs than the families of a child with another subtype of JIA ($359.00 CAD vs.$877.00 CAD, P = 0.02).Conclusions: The costs associated with having a child with JIA in NS are on average modest, but may be considerable for some families. Oligoarticular JIA is associated with smaller costs. Many families perceive the burden to be at least moderate and the availability of financial resources to be poor. Supports should be targeted to those families most in need. © 2013 Ens et al.; licensee BioMed Central Ltd

Fate of patients with spinal cord ischemia complicating thoracic endovascular aortic repair

ObjectiveSpinal cord ischemia (SCI) is a potentially devastating complication of thoracic endovascular aortic repair (TEVAR) that can result in varying degrees of short-term and permanent disability. This study was undertaken to describe the clinical outcomes, long-term functional impact, and influence on survival of SCI after TEVAR.MethodsA retrospective review of all TEVAR patients at the University of Florida from 2000 to 2011 was performed to identify individuals experiencing SCI, defined by any new lower extremity neurologic deficit not attributable to another cause. SCI was dichotomized into immediate or delayed onset, with immediate onset defined as SCI noted upon awakening from anesthesia, and delayed characterized as a period of normal function, followed by development of neurologic injury. Ambulatory status was determined using database query, record review, and phone interviews with patients and/or family. Mortality was estimated using life-table analysis.ResultsA total of 607 TEVARs were performed for various indications, with 57 patients (9.4%) noted to have postoperative SCI (4.3% permanent). SCI patients were more likely to be older (63.9 ± 15.6 vs 70.5 ± 11.2 years; P = .002) and have a number of comorbidities, including chronic obstructive pulmonary disease, hypertension, dyslipidemia, and cerebrovascular disease (P < .0001). At some point in their care, a cerebrospinal fluid drain was placed in 54 patients (95%), with 54% placed postoperatively. In-hospital mortality was 8.8% for the entire cohort (SCI vs no SCI; P = .45). SCI developed immediately in 12 patients, delayed onset in 40, and indeterminate in five patients due to indiscriminate timing from postoperative sedation. Three patients (25%) with immediate SCI had measurable functional improvement (FI), whereas 28 (70%) of the delayed-onset patients experienced some degree of neurologic recovery (P = .04). Of the 34 patients with complete data available, 26 (76%) reported quantifiable FI, but only 13 (38%) experienced return to their preoperative baseline. Estimated mean (± standard error) survival for patients with and without SCI was 37.2 ± 4.5 and 71.6 ± 3.9 months (P < .0006), respectively. Patients with FI had a mean survival of 53.9 ± 5.9 months compared with 9.6 ± 3.6 months for those without improvement (P < .0001). Survival and return of neurologic function were not significantly different when patients with preoperative and postoperative cerebrospinal fluid drains were compared.ConclusionsThe minority of patients experience complete return to baseline function after SCI with TEVAR, and outcomes in patients without early functional recovery are particularly dismal. Patients experiencing delayed SCI are more likely to have FI and may anticipate similar life-expectancy with neurologic recovery compared with patients without SCI. Timing of drain placement does not appear to have an impact on postdischarge FI or long-term mortality

Recent Shifts in the Occurrence, Cause, and Magnitude of Animal Mass Mortality Events

Mass mortality events (MMEs) are rapidly occurring catastrophic demographic events that punctuate background mortality levels. Individual MMEs are staggering in their observed magnitude: re- moving more than 90% of a population, resulting in the death of more than a billion individuals, or producing 700 million tons of dead biomass in a single event. Despite extensive documentation of individual MMEs, we have no understanding of the major features characterizing the occurrence and magnitude of MMEs, their causes, or trends through time. Thus, no framework exists for contextualizing MMEs in the wake of ongoing global and regional perturbations to natural systems. Here we present an analysis of 727 published MMEs from across the globe, affecting 2,407 animal populations. We show that the magnitude of MMEs has been intensifying for birds, fishes, and marine invertebrates; invariant for mammals; and decreasing for reptiles and amphibians. These shifts in magnitude proved robust when we accounted for an increase in the occurrence of MMEs since 1940. However, it remains unclear whether the increase in the occurrence of MMEs represents a true pattern or simply a perceived increase. Regardless, the increase in MMEs appears to be associated with a rise in disease emergence, biotoxicity, and events produced by multiple interacting stressors, yet temporal trends in MME causes varied among taxa and may be associated with increased de- tectability. In addition, MMEs with the largest magnitudes were those that resulted from multiple stressors, starvation, and disease. These results advance our understanding of rare demographic processes and their relationship to global and regional perturba- tions to natural systems

Outcomes after redo aortobifemoral bypass for aortoiliac occlusive disease

ObjectivePatients presenting with occluded aortobifemoral (ABF) bypass grafts are managed with a variety of techniques. Redo ABF (rABF) bypass procedures are infrequently performed because of concerns about procedural complexity and morbidity. The purpose of this analysis was to compare midterm results of rABF bypass with those of primary ABF (pABF) bypass for aortoiliac occlusive disease to determine if there are significant differences in outcomes.MethodsA retrospective review was performed of all patients undergoing ABF bypass for occlusive disease between January 2002 and March 2012. A total of 19 patients underwent rABF bypass and 194 received pABF bypass during that period. Data for an indication- and comorbidity-matched case-control cohort of 19 elective pABF bypass patients were collected for comparison to the rABF bypass group. Primary end points included rate of major complications as well as 30-day and all-cause mortality. Secondary end points were amputation-free survival and freedom from major adverse limb events.ResultsThe rABF bypass patients more frequently underwent prior extra-anatomic or lower extremity bypass operations compared with pABF bypass patients (P = .02); however, no difference was found in the incidence of prior failed endovascular iliac intervention (P = .4). By design, indications for the rABF and pABF bypass groups were the same (claudication, n = 6/6 [31.6%]; P = 1; critical limb ischemia, n = 13/13 [78.4%]; P = 1). Aortic access was more frequently by retroperitoneal exposure in the rABF bypass group (n = 13 vs n = 1; P < .0001), and a significantly higher proportion of the rABF bypass patients required concomitant infrainguinal bypass or intraprocedural adjuncts such as profundaplasty (n = 14 vs n = 5; P = .01). The rABF bypass patients experienced greater blood loss (1097 ± 983 mL vs 580 ± 457 mL; P = .02), received more intraoperative fluids (3400 ± 1422 mL vs 2279 ± 993 mL; P = .01), and had longer overall procedure times (408 ± 102 minutes vs 270 ± 48 minutes; P < .0001). Length of stay (days ± standard deviation) was similar (pABF bypass, 11.2 ± 10.4; rABF bypass, 9.1 ± 4.5; P = .7), and no 30-day or in-hospital deaths occurred in either group. Similar rates of major complications occurred in the two groups (pABF bypass, n = 6 [31.6%]; rABF bypass, n = 4 [21.1%]; observed difference, 9.5%; 95% confidence interval, −17.6% to 36.7%; P = .7). Two-year freedom from major adverse limb events (±standard error mean) was 82% ± 9% vs 78% ± 10% for pABF and rABF bypass patients (log-rank, P = .6). Two-year amputation-free survival was 90 ± 9% vs 89 ± 8% between pABF and rABF bypass patients (P = .5). Two-year survival was 91% ± 9% and 90% ± 9% for pABF and rABF bypass patients (P = .8).ConclusionsPatients undergoing rABF bypass have higher procedural complexity compared with pABF bypass as evidenced by greater operative time, blood loss, and need for adjunctive procedures. However, similar perioperative morbidity, mortality, and midterm survival occurred in comparison to pABF bypass patients. These results support a role for rABF bypass in selected patients

Preoperative prediction of spinal cord ischemia after thoracic endovascular aortic repair

ObjectiveSpinal cord ischemia (SCI) is a devastating but potentially preventable complication of thoracic endovascular aortic repair (TEVAR). The purpose of this analysis was to determine what factors predict SCI after TEVAR.MethodsAll TEVAR procedures at a single institution were reviewed for patient characteristics, prior aortic repair history, aortic centerline of flow analysis, and procedural characteristics. SCI was defined as any lower extremity neurologic deficit that was not attributable to an intracranial process or peripheral neuropathy. Forty-three patient and procedural variables were evaluated individually for association with SCI. Those with the strongest relationships to SCI (P < .1) were included in a multivariable logistic regression model, and a stepwise variable elimination algorithm was bootstrapped to derive a best subset of predictors from this model.ResultsFrom 2002 to 2013, 741 patients underwent TEVAR for various indications, and 68 (9.2%) developed SCI (permanent: n = 38; 5.1%). Because of the lack of adequate imaging for centerline analysis, 586 patients (any SCI, n = 43; 7.4%) were subsequently analyzed. Patients experiencing SCI after TEVAR were older (SCI, 72 ± 11 years; no SCI, 65 ± 15 years; P < .0001) and had significantly higher rates of multiple cardiovascular risk factors. The stepwise selection procedure identified five variables as the most important predictors of SCI: age (odds ratio [OR] multiplies by 1.3 per 10 years; 95% confidence interval [CI], 0.9-1.8, P = .06), aortic coverage length (OR multiplies by 1.3 per 5 cm; CI, 1.1-1.6; P = .002), chronic obstructive pulmonary disease (OR, 1.9; CI, 0.9-4.1; P = .1), chronic renal insufficiency (creatinine concentration ≥ 1.6 mg/dL; OR, 1.9; CI, 0.8-4.2; P = .1), and hypertension (defined as chart history or medication; OR, 6.4; CI, 2.6-18; P < .0001). A logistic regression model with just these five covariates had excellent discrimination (area under the receiver operating characteristic curve = .83) and calibration (χ2 = 9.8; P = .28).ConclusionsThis analysis generated a simple model that reliably predicts SCI after TEVAR. This clinical tool can assist decision-making about when to proceed with TEVAR, guide discussions about intervention risk, and help determine when maneuvers to mitigate SCI risk should be implemented