Research Spotlight

Chang, C. A., K. Murphy, R. R. Kane, M. Lawrence and B. Naziruddin (2018). “Early TLR4 blockade attenuates sterile inflammation-mediated stress in islets during isolation and promotes successful transplant outcomes.” Transplantation. May 22. [Epub ahead of print].

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BACKGROUND: During the isolation process, pancreatic islets are exposed to an environment of sterile inflammation resulting in an upregulated inflammatory state prior to transplantation. Toll-like receptor 4 (TLR4) has been identified as a major mediator of sterile inflammation. Therefore, we sought to determine whether early TLR4 blockade would be effective in reducing the inflammatory burden in islets pretransplant. METHODS: Islets from C57BL/6 mice were treated with a TLR4 antagonist during the pancreatic ductal perfusion and digestion steps of the isolation process. Islets were then analyzed for inflammation by RT-PCR and western blot, and for viability and function in vitro. A syngeneic transplant model using a marginal mass of islets transplanted intraportally into mice with streptozotocin-induced diabetes was used to study transplant outcomes after early TLR4 blockade. RESULTS: Diabetic mice receiving 150 islets treated with early TLR4 blockade achieved euglycemia at a higher rate than mice receiving untreated islets (75% vs 29%; p < 0.05) and had improved long-term function (P < 0.05). Serum markers for islet damage and inflammation were significantly reduced posttransplant (P < 0.05). Both the expression of key inflammatory genes and the activation of mitogen-activated protein kinases were reduced by early TLR4 blockade. Islet viability was improved (P < 0.05) while preserving islet insulin secretory capacity postisolation. CONCLUSIONS: Early TLR4 blockade protects islets from sterile inflammation-mediated stress sustained during isolation and promotes positive transplant outcomes. Our findings support the use of early TLR4 blockade during clinical islet isolation procedures to reduce pretransplant inflammation and improve transplant outcomes.

Asrani, S. K., M. Kouznetsova, G. Ogola, T. Taylor, A. Masica, B. Pope, J. Trotter, P. Kamath and F. Kanwal (2018). “Increasing Healthcare Burden of Chronic Liver Disease Compared to Other Chronic Diseases, 2004-2013.” Gastroenterology. May 23. [Epub ahead of print].

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BACKGROUND & AIMS: Chronic liver disease (CLD) is a common and expensive condition, and studies of CLD-related hospitalizations have underestimated the true burden of disease. We analyzed data from a large diverse healthcare system to compare time trends in CLD-related hospitalizations with those of congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD). METHODS: We collected data from a large healthcare system in Texas on hospitalizations related to CLD (n=27,783), CHF (n=60,415), and COPD (n=34,199) from January 1, 2004 through December 31, 2013. We calculated annual hospitalization rates (per 100,000) and compared hospital course, inpatient mortality, ancillary services and re-admissions. RESULTS: Compared to patients with CHF (median age, 71 years) or COPD (median age 69 years), patients with CLD were significantly younger (median age 57 years; P<.01 vs CHF and COPD). Higher proportions of patients with CLD were uninsured (11.7% vs 5.4% for CHF and 5.4% for COPD; P<.01) and Hispanic (17% for CLD vs 9.3% for CHF and 5.0% for COPD; P<.01). A lower proportion of patients with CLD had Medicare (41.5% vs 68.6% with CHF and 70.1% with COPD; P<0.01). From 2004 through 2013, the rate of CLD-related hospitalization increased by 92% (from 1295/100,000 to 2490/100,000), compared to 6.7% for CHF (from 3843/100,000 to 4103/100,000) and 48.8% for COPD (from 1775/100,000 to 2642/100,000). During this time period, CLD-related hospitalizations covered by Medicare increased from 31.8% to 41.5%, whereas hospitalizations covered by Medicare did not change for CHF (remained at 70%) or COPD (remained at 70%). Patients with CLD had longer hospital stays (7.3 days vs 6.2 days for CHF or 5.9 days for COPD; P<.01). A higher proportion of patients with CLD died or were discharged to hospice (14.2% vs 11.5% of patients with CHF and 9.3% of patients with COPD P<.01), and a smaller proportion had access to post-acute care (13.2% vs 23.2% of patients with CHF and 27.4% of patients with COPD; P<.01). A higher proportion of patients with CLD were readmitted to the hospital within 30 days (25% vs 21.9% of patients with CHF and 20.6% with COPD; P<.01). CONCLUSIONS: Patients with chronic liver disease, compared to selected other chronic diseases, had increasing rates of hospitalization, longer hospital stays, more readmissions, and, despite these adverse outcomes, less access to post-acute care. Disease management models for chronic liver disease are greatly needed to manage the anticipated increase in hospitalizations for CLD.

Ailon, T., J. S. Smith, C. I. Shaffrey, A. Soroceanu, V. Lafage, F. Schwab, D. Burton, R. Hart, H. J. Kim, J. Gum, R. Hostin, M. P. Kelly, S. Glassman, J. K. Scheer, S. Bess and C. P. Ames (2018). “Patients with Adult Spinal Deformity with Previous Fusions Have an Equal Chance of Reaching Substantial Clinical Benefit Thresholds in Health-Related Quality of Life Measures but Do Not Reach the Same Absolute Level of Improvement.” World Neurosurg. May 9. [Epub ahead of print].

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BACKGROUND: Substantial clinical benefit (SCB) represents a threshold above which patients recognize substantial improvement and represents a rational target for defining clinical success. In adult spinal deformity (ASD) surgery, previous fusions may impact outcomes after deformity correction. OBJECTIVE: To investigate the impact of previous spinal fusion on the likelihood of reaching SCB thresholds for 2-year health-related quality of life (HRQOL) after ASD surgery. METHODS: We conducted a retrospective review comparing baseline demographic, HRQOL, and radiographic features for patients with ASD undergoing primary versus revision procedures. The primary outcome measure was reaching SCB threshold in Oswestry Disability Index (ODI), SF-36 Physical Component Summary (PCS), and back and leg pain (numeric rating scale). Secondary outcomes included absolute and change scores in ODI, PCS, and back and leg pain. RESULTS: In total, 332 patients achieved 2-year follow-up (228 primary; 104 revision cases). Those undergoing revision surgery had similar demographic features (age 58.3/55.9, female 80.8%/82.9%) to patients undergoing primary surgery. They had worse baseline HRQOL (ODI 48.5/41.2, PCS 29.5/33.4, back 7.5/7.0, and leg pain 4.9/4.3; P < 0.001) and radiographic deformity (sagittal vertical axis 111.4/45.1, lumbopelvic mismatch 26.7/11.0, pelvic tilt 29.5/21.0; P < 0.0001). Nevertheless, the number of patients who reached SCB for ODI (38.3/36.3%), PCS (48.5/53.4%), back (53.1/60.5%), and leg pain numeric rating scale (28.6/36.9%) did not significantly differ. Revision patients had worse 2-year HRQOL for all measures. CONCLUSIONS: Patients undergoing revision surgery have worse baseline HRQOL and deformity. Although they do not achieve the same absolute level of 2-year HRQOL outcome, they have a similar likelihood of reaching SCB threshold for improvement in 2-year HRQOL.

Teixeira, P. G. R., C. V. R. Brown, B. Emigh, M. Long, M. Foreman, B. Eastridge, S. Gale, M. S. Truitt, S. Dissanaike, T. Duane, J. Holcomb, A. Eastman and J. Regner (2018). “Civilian Prehospital Tourniquet Use Is Associated with Improved Survival in Patients with Peripheral Vascular Injury.” J Am Coll Surg 226(5): 769-776.e761.

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BACKGROUND: Tourniquet use has been proven to reduce mortality on the battlefield. Although empirically transitioned to the civilian environment, data substantiating survival benefit attributable to civilian tourniquet use is lacking. We hypothesized that civilian prehospital tourniquet use is associated with reduced mortality in patients with peripheral vascular injuries. STUDY DESIGN: We conducted a multicenter retrospective review of all patients sustaining peripheral vascular injuries admitted to 11 Level I trauma centers (January 2011 through December 2016). The study population was divided into 2 groups based on prehospital tourniquet use. Baseline characteristics were compared and factors associated with mortality identified. Logistic regression, adjusting for demographic, physiologic and injury-related parameters, was used to evaluate the association between prehospital tourniquet use and mortality. Delayed amputation was the secondary end point. RESULTS: During 6 years, 1,026 patients with peripheral vascular injuries were admitted. Prehospital tourniquets were used in 181 (17.6%) patients. Tourniquet time averaged 77.3 +/- 63.3 minutes (interquartile range 39.0 to 92.3 minutes). Traumatic amputations occurred in 98 patients (35.7% had a tourniquet). Mortality was 5.2% in the non-tourniquet group compared with 3.9% in the tourniquet group (odds ratio 1.36; 95% CI 0.60 to 1.65; p = 0.452). After multivariable analysis, the use of tourniquets was found to be independently associated with survival (adjusted odds ratio 5.86; 95% CI 1.41 to 24.47; adjusted p = 0.015). Delayed amputation rates were not significantly different between the 2 groups (1.1% vs 1.1%; adjusted odds ratio 1.82; 95% CI 0.36 to 9.99; adjusted p = 0.473). CONCLUSIONS: Although still underused, civilian prehospital tourniquet application was independently associated with a 6-fold mortality reduction in patients with peripheral vascular injuries. More aggressive prehospital application of extremity tourniquets in civilian trauma patients with extremity hemorrhage and traumatic amputation is warranted.

May, P., C. Normand, J. B. Cassel, E. Del Fabbro, R. L. Fine, R. Menz, C. A. Morrison, J. D. Penrod, C. Robinson and R. S. Morrison (2018). “Economics of Palliative Care for Hospitalized Adults With Serious Illness: A Meta-analysis.” JAMA Intern Med. Apr 30. [Epub ahead of print].

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Importance: Economics of care for adults with serious illness is a policy priority worldwide. Palliative care may lower costs for hospitalized adults, but the evidence has important limitations. Objective: To estimate the association of palliative care consultation (PCC) with direct hospital costs for adults with serious illness. Data Sources: Systematic searches of the Embase, PsycINFO, CENTRAL, PubMed, CINAHL, and EconLit databases were performed for English-language journal articles using keywords in the domains of palliative care (eg, palliative, terminal) and economics (eg, cost, utilization), with limiters for hospital and consultation. For Embase, PsycINFO, and CENTRAL, we searched without a time limitation. For PubMed, CINAHL, and EconLit, we searched for articles published after August 1, 2013. Data analysis was performed from April 8, 2017, to September 16, 2017. Study Selection: Economic evaluations of interdisciplinary PCC for hospitalized adults with at least 1 of 7 illnesses (cancer; heart, liver, or kidney failure; chronic obstructive pulmonary disease; AIDS/HIV; or selected neurodegenerative conditions) in the hospital inpatient setting vs usual care only, controlling for a minimum list of confounders. Data Extraction and Synthesis: Eight eligible studies were identified, all cohort studies, of which 6 provided sufficient information for inclusion. The study estimated the association of PCC within 3 days of admission with direct hospital costs for each sample and for subsamples defined by primary diagnoses and number of comorbidities at admission, controlling for confounding with an instrumental variable when available and otherwise propensity score weighting. Treatment effect estimates were pooled in the meta-analysis. Main Outcomes and Measures: Total direct hospital costs. Results: This study included 6 samples with a total 133118 patients (range, 1020-82 273), of whom 93.2% were discharged alive (range, 89.0%-98.4%), 40.8% had a primary diagnosis of cancer (range, 15.7%-100.0%), and 3.6% received a PCC (range, 2.2%-22.3%). Mean Elixhauser index scores ranged from 2.2 to 3.5 among the studies. When patients were pooled irrespective of diagnosis, there was a statistically significant reduction in costs (-$3237; 95% CI, -$3581 to -$2893; P < .001). In the stratified analyses, there was a reduction in costs for the cancer (-$4251; 95% CI, -$4664 to -$3837; P < .001) and noncancer (-$2105; 95% CI, -$2698 to -$1511; P < .001) subsamples. The reduction in cost was greater in those with 4 or more comorbidities than for those with 2 or fewer. Conclusions and Relevance: The estimated association of early hospital PCC with hospital costs may vary according to baseline clinical factors. Estimates may be larger for primary diagnosis of cancer and more comorbidities compared with primary diagnosis of noncancer and fewer comorbidities. Increasing palliative care capacity to meet national guidelines may reduce costs for hospitalized adults with serious and complex illnesses.