Current Research and Scholarly Interests
Health systems, services, and management.
Health systems, services, and management.
Blood production is ensured by rare, self-renewing haematopoietic stem cells (HSCs). How HSCs accommodate the diverse cellular stresses associated with their life-long activity remains elusive. Here we identify autophagy as an essential mechanism protecting HSCs from metabolic stress. We show that mouse HSCs, in contrast to their short-lived myeloid progeny, robustly induce autophagy after ex vivo cytokine withdrawal and in vivo calorie restriction. We demonstrate that FOXO3A is critical to maintain a gene expression program that poises HSCs for rapid induction of autophagy upon starvation. Notably, we find that old HSCs retain an intact FOXO3A-driven pro-autophagy gene program, and that ongoing autophagy is needed to mitigate an energy crisis and allow their survival. Our results demonstrate that autophagy is essential for the life-long maintenance of the HSC compartment and for supporting an old, failing blood system.
View details for DOI 10.1038/nature11895
View details for Web of Science ID 000315312900031
View details for PubMedID 23389440
After endovascular aortic aneurysm repair (EVAR), the Society for Vascular Surgery recommends a computed tomography (CT) scan ≤30 days, followed by annual imaging. We sought to describe long-term adherence to surveillance guidelines among United States Medicare beneficiaries and determine patient and hospital factors associated with incomplete surveillance.We analyzed fee-for-service Medicare claims for patients receiving EVAR from 2002 to 2005 and collected all relevant postoperative imaging through 2011. Additional data included patient comorbidities and demographics, yearly hospital volume of abdominal aortic aneurysm repair, and Medicaid eligibility. Allowing a grace period of 3 months, complete surveillance was defined as at least one CT or ultrasound assessment every 15 months after EVAR. Incomplete surveillance was categorized as gaps for intervals >15 months between consecutive images as or lost to follow-up if >15 months elapsed after the last imaging.Our cohort comprised 9695 patients. Median follow-up duration was 6.1 years. A CT scan ≤30 days of EVAR was performed in 3085 (31.8%) patients and ≤60 days in 60.8%. The median time to the postoperative CT was 38 days (interquartile range, 25-98 days). Complete surveillance was observed in 4169 patients (43.0%). For this group, the mean follow-up time was shorter than for those with incomplete surveillance (3.4 ± 2.74 vs 6.5 ± 2.1 years; P < .001). Among those with incomplete surveillance, follow-up became incomplete at 3.3 ± 1.9 years, with 57.6% lost to follow-up, 64.1% with gaps in follow-up (mean gap length, 760 ± 325 days), and 37.6% with both. A multivariable analysis showed incomplete surveillance was independently associated with Medicaid eligibility (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.29-1.55; P < .001), low-volume hospitals (HR, 1.12; 95% CI, 1.05-1.20; P < .001), and ruptured abdominal aortic aneurysm (HR, 1.51; 95% CI, 1.24-1.84; P < .001).Postoperative imaging after EVAR is highly variable, and less than half of patients meet current surveillance guidelines. Additional studies are necessary to determine if variability in postoperative surveillance affects long-term outcomes.
View details for DOI 10.1016/j.jvs.2014.07.003
View details for Web of Science ID 000346637600004
View details for PubMedID 25088738
Checklists may help reduce discharge errors; however, current paper checklists have limited functionality. In 2013 a best-practice discharge checklist using the electronic health record (EHR) was developed and evaluated at Stanford University Medical Center (Stanford, California) in a cluster randomized trial to evaluate its usage, user satisfaction, and impact on physicians' work flow.The study was divided into four phases.In Phase I, on the survey (N = 76), most of the participants (54.0%) reported using memory to remember discharge tasks. On a 0-100 scale, perception of checklists as being useful was strong (mean, 66.4; standard deviation [SD], 21.2), as was interest in EHR checklists (64.5, 26.6). In Phase II, the checklist consisted of 15 tasks categorized by admission, hospitalization, and discharge-planning. In Phase III, the checklist was implemented as an EHR "smart-phrase" allowing for automatic insertion. In Phase IV, in a trial with 60 participating physicians, 23 EHR checklist users reported higher usage than 12 paper users (28.5 versus 7.67, p = .019), as well as higher checklist integration with work flow (22.6 versus 1.67, p = .014), usefulness of checklist (33.7 versus. 8.92, p = .041), discharge confidence (30.8 versus 5.00, p = .029), and discharge efficiency (25.5 versus 6.67, p = .056). Increasing EHR checklist use was correlated with usefulness ( r = .85, p < .001), confidence (r = .81, p < .001), and efficiency (r = .87, p < .001).The EHR checklist reminded physicians to complete discharge tasks, improved confidence, and increased process efficiency. This is the first study to show that medicine residents use "memory" as the most common method for remembering discharge tasks. These data reinforce the need for a formalized tool, such as a checklist, that residents can rely on to complete important discharge tasks.
View details for PubMedID 25977128
To evaluate the impact of hospital accreditation upon bariatric surgery outcomes.Since 2004, the American College of Surgeons and the American Society of Metabolic and Bariatric Surgery have accredited bariatric hospitals. Few studies have evaluated the impact of hospital accreditation on all bariatric surgery outcomes.Bariatric surgery hospitalizations were identified using International Classification of Diseases, Ninth Revision (ICD9) codes in the 2010 Nationwide Inpatient Sample (NIS). Hospital names and American Hospital Association (AHA) codes were used to identify accredited bariatric centers. Relevant ICD9 codes were used for identifying demographics, length of stay (LOS), total charges, mortality, complications, and failure to rescue (FTR) events.There were 117,478 weighted bariatric patient discharges corresponding to 235 unique hospitals in the 2010 NIS data set. A total of 72,615 (61.8%) weighted discharges, corresponding to 145 (61.7%) named or AHA-identifiable hospitals were included. Among the 145 hospitals, 66 (45.5%) were unaccredited and 79 (54.5%) accredited. Compared with accredited centers, unaccredited centers had a higher mean LOS (2.25 vs 1.99 days, P < 0.0001), as well as total charges ($51,189 vs $42,212, P < 0.0001). Incidence of any complication was higher at unaccredited centers than at accredited centers (12.3% vs 11.3%, P = 0.001), as was mortality (0.13% vs 0.07%, P = 0.019) and FTR (0.97% vs 0.55%, P = 0.046). Multivariable logistic regression analysis identified unaccredited status as a positive predictor of incidence of complication [odds ratio (OR) = 1.08, P < 0.0001], as well as mortality (OR = 2.13, P = 0.013).Hospital accreditation status is associated with safer outcomes, shorter LOS, and lower total charges after bariatric surgery.
View details for DOI 10.1097/SLA.0000000000000891
View details for PubMedID 25115426
Internal herniation is a potential complication following laparoscopic Roux-en-Y gastric bypass (LRYGB). Previous studies have shown that closure of mesenteric defects after LRYGB may reduce the incidence of internal herniation. However, controversy remains as to whether mesenteric defect closure is necessary to decrease the incidence of internal hernias after LRYGB. This study aims to determine if jejeunal mesenteric defect closure reduces incidence of internal hernias and other complications in patients undergoing LRYGB.105 patients undergoing laparoscopic antecolic RYGB were randomized into two groups: closed mesenteric defect (n = 50) or open mesenteric defect (n = 55). Complication rates were obtained from the medical record. Patients were followed up to 3 years post-operatively. Patients also completed the gastrointestinal quality of life index (GI QoL) pre-operatively and 12 months post-operatively. Outcome measures included: incidence of internal hernias, complications, readmissions, reoperations, GI QoL scores, and percent excess weight loss (%EWL).Pre-operatively, there were no significant differences between the two groups. The closed group had a longer operative time (closed-153 min, open-138 min, p = 0.073). There was one internal hernia in the open group. There was no significant difference at 12 months for decrease in BMI (closed-15.9, open-16.3 kg/m(2), p = 0.288) or %EWL (closed-75.3 %, open-69.0 %, p = 0.134). There was no significant difference between the groups in incidence of internal hernias and general complications post-operatively. Both groups showed significantly improved GI QoL index scores from baseline to 12 months post-surgery, but there were no significant differences at 12 months between groups in total GI QoL (closed-108, open-112, p = 0.440).In this study, closure or non-closure of the jejeunal mesenteric defect following LRYGB appears to result in equivalent internal hernia and complication rates. High index of suspicion should be maintained whenever internal hernia is expected after LRYGB.
View details for DOI 10.1007/s00464-014-3970-3
View details for PubMedID 25480607
Multipotent stromal cells (MSCs) and their osteoblastic lineage cell (OBC) derivatives are part of the bone marrow (BM) niche and contribute to hematopoietic stem cell (HSC) maintenance. Here, we show that myeloproliferative neoplasia (MPN) progressively remodels the endosteal BM niche into a self-reinforcing leukemic niche that impairs normal hematopoiesis, favors leukemic stem cell (LSC) function, and contributes to BM fibrosis. We show that leukemic myeloid cells stimulate MSCs to overproduce functionally altered OBCs, which accumulate in the BM cavity as inflammatory myelofibrotic cells. We identify roles for thrombopoietin, CCL3, and direct cell-cell interactions in driving OBC expansion, and for changes in TGF-β, Notch, and inflammatory signaling in OBC remodeling. MPN-expanded OBCs, in turn, exhibit decreased expression of many HSC retention factors and severely compromised ability to maintain normal HSCs, but effectively support LSCs. Targeting this pathological interplay could represent a novel avenue for treatment of MPN-affected patients and prevention of myelofibrosis.
View details for DOI 10.1016/j.stem.2013.06.009
View details for PubMedID 23850243
Adult hematopoiesis occurs primarily in the BM space where hematopoietic cells interact with stromal niche cells. Despite this close association, little is known about the specific roles of osteoblastic lineage cells (OBCs) in maintaining hematopoietic stem cells (HSCs), and how conditions affecting bone formation influence HSC function. Here we use a transgenic mouse model with the ColI(2.3) promoter driving a ligand-independent, constitutively active 5HT4 serotonin receptor (Rs1) to address how the massive increase in trabecular bone formation resulting from increased G(s) signaling in OBCs impacts HSC function and blood production. Rs1 mice display fibrous dysplasia, BM aplasia, progressive loss of HSC numbers, and impaired megakaryocyte/erythrocyte development with defective recovery after hematopoietic injury. These hematopoietic defects develop without compensatory extramedullary hematopoiesis, and the loss of HSCs occurs despite a paradoxical expansion of stromal niche cells with putative HSC-supportive activity (ie, endothelial, mesenchymal, and osteoblastic cells). However, Rs1-expressing OBCs show decreased expression of key HSC-supportive factors and impaired ability to maintain HSCs. Our findings indicate that long-term activation of G(s) signaling in OBCs leads to contextual changes in the BM niche that adversely affect HSC maintenance and blood homeostasis.
View details for DOI 10.1182/blood-2011-11-395418
View details for Web of Science ID 000311623800009
View details for PubMedID 22859604
View details for Web of Science ID 000307319600079
View details for Web of Science ID 000293801700062
Because secondhand smoke is a public health concern, many colleges have adopted bans to ensure healthier environments. This study demonstrates how outdoor smoking policy change can be accomplished at a large public university.The participants were 1,537 students housed in residential communities at the University of California, Berkeley, who completed an online survey.A proposal for smoke-free residential communities that included student resident survey data was prepared.The survey data indicated that most students (77%) were bothered by secondhand smoke, and most (66%) favored smoke-free environments. The data were used to advocate for a change in the residential community smoking policy.The survey data and institutional comparisons played a key role in administrators' decision-making about campus smoking policy. Despite administrators' concerns about students' safety and freedom of choice, student-led advocacy was able to influence policy change.
View details for DOI 10.1080/07448481.2010.546464
View details for Web of Science ID 000299478200014
View details for PubMedID 21950261
View details for Web of Science ID 000316555201530