Research Spotlight

Cichos, K. H., J. L. Churchill, S. G. Phillips, S. L. Watson, G. McGwin, Jr., E. S. Ghanem and B. A. Ponce (2018). “Metabolic syndrome and hip fracture: Epidemiology and perioperative outcomes.” Injury 49(11): 2036-2041.

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INTRODUCTION: Hip fractures and metabolic syndrome (MetS) are becoming major global healthcare burdens as populations age. This study sought to determine the impact of MetS in hip fracture patients on perioperative outcomes following operative fixation or arthroplasty. METHODS: Data from the 2004-2014 Nationwide Inpatient Sample was used to select 3,348,207 discharges with hip fracture. MetS patients were identified by having at least 3 of 4 component comorbidities: hypertension, dyslipidemia, obesity, and diabetes. Logistic regression was used to estimate odds ratios for the association between MetS and perioperative outcomes adjusted for age, gender, race, payer status, and comorbidities. RESULTS: Overall, 32% of hip fracture patients were treated with open reduction internal fixation (ORIF), 28% hemiarthroplasty (HA), 18% closed reduction with internal fixation (CRPP), and 3% primary total hip arthroplasty (THA). The remaining 19% of cases were either treated via unspecified procedure of hip repair (9%), managed non-operatively (2%), underwent multiple procedures during the hospital stay (6%), or the surgical procedure data was missing (2%) and were excluded from procedural analyses. The prevalence of MetS was 7.9% and increased among minorities, patients treated at urban hospitals, with comorbidities (heart failure, kidney disease, peripheral vascular disease), and with Medicare coverage. MetS was associated with increased odds of any adverse event (p < 0.0001), specifically: acute renal failure, myocardial infarction, acute posthemorrhagic anemia. MetS was also associated with increased LOS (p < 0.0001) and increased total charges (p < 0.0001). However, MetS was associated with reduced odds of postoperative pneumonia, deep vein thrombosis and pulmonary embolism, surgical site infection, septicemia, and in-hospital mortality (p < 0.0001). The above associations were maintained for MetS patients stratified according to their treatment groups: HA, CRPP, and ORIF. CONCLUSIONS: MetS is associated with increased odds of complications in hip fracture patients but decreased odds of in-hospital mortality. This may be related to patients' nutritional status and catabolic states in the perioperative period.

Chiruvolu, A., K. K. Miklis, E. Chen, B. Petrey and S. Desai (2018). “Delivery Room Management of Meconium-Stained Newborns and Respiratory Support.” Pediatrics Nov 1. [Epub ahead of print].

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BACKGROUND AND OBJECTIVES: Recently, the Neonatal Resuscitation Program (NRP) recommended against routine endotracheal suctioning of meconium-stained nonvigorous newborns but suggested resuscitation with positive pressure ventilation. Our purpose is to study the effects of this change in management. METHODS: In this multicenter cohort study, we compare 130 nonvigorous newborns born during the retrospective 1-year period before the implementation of new NRP guidelines (October 1, 2015, to September 30, 2016) to 101 infants born during the 1-year prospective period after implementation (October 1, 2016, to September 30, 2017). RESULTS: Endotracheal suctioning was performed predominantly in the retrospective group compared with the prospective group (70% vs 2%), indicating the change in practice. A significantly higher proportion of newborns were admitted to the NICU for respiratory issues in the prospective group compared with the retrospective group (40% vs 22%) with an odds ratio (OR) of 2.2 (95% confidence interval [CI]: 1.2-3.9). Similarly, a significantly higher proportion of infants needed oxygen therapy (37% vs 19%) with an OR of 2.5 (95% CI: 1.2-4.5), mechanical ventilation (19% vs 9%) with an OR of 2.6 (95% CI: 1.1-5.8), and surfactant therapy (10% vs 2%) with an OR of 5.8 (95% CI: 1.5-21.8). There were no differences in the incidence of other outcomes, including meconium aspiration syndrome. CONCLUSIONS: The recent NRP guideline change was not associated with an increased incidence of meconium aspiration syndrome but was associated with an increased incidence of NICU admissions for respiratory issues. Also, the need for mechanical ventilation, oxygen, and surfactant therapy increased.

Asrani, S. K., L. W. Jennings, J. F. Trotter, J. Levitsky, M. K. Nadim, W. R. Kim, S. A. Gonzalez, B. Fischbach, R. Bahirwani, M. Emmett and G. Klintmalm (2018). “A model for Glomerular filtration Rate Assessment In Liver disease (GRAIL) in the presence of renal dysfunction.” Hepatology Oct 19. [Epub ahead of print].

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Estimation of glomerular filtration rate (eGFR) in patients with liver disease is suboptimal in presence of renal dysfunction. We developed a model for GFR Assessment In Liver disease (GRAIL) before and after liver transplantation (LT). GRAIL was derived using objective variables (creatinine, blood urea nitrogen, age, gender, race, albumin) to estimate GFR based on timing of measurement relative to LT and degree of renal dysfunction. Measured GFR (mGFR) by iothalamate clearance (n=12,122, 1985-2015) at protocol time points before/after LT was used as reference. GRAIL was compared to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD-4, MDRD-6) equations for mGFR<30ml/min/1.73m(2) . Prediction of development of chronic kidney disease (mGFR < 20ml/min/1.73m(2) , initiation of chronic dialysis) and listing or receipt of kidney transplantation within 5 years was examined in internal cohort (n=785) and external validation (n=68,217, 2001-2015). GRAIL had less bias, was more accurate and precise as compared to CKD-EPI, MDRD-4 and MDRD-6 at time points before/after LT for low GFR. For mGFR<30ml/min/1.73m(2) , the median difference (eGFR-mGFR) was GRAIL: 5.24 [9.65] ml/min/1.73m(2) as compared to CKD-EPI: 8.70 [18.24]ml/min/1.73m(2) , MDRD-4: 8.82 [17.38]ml/min/1.73m(2) , and MDRD-6: 6.53[14.42] ml/min/1.73m(2) . Prior to LT, GRAIL correctly classified 75% as having mGFR<30ml/min/1.73m(2) vs. 36.1% (CKD-EPI), 36.1%(MDRD-4), and 52.8%(MDRD-6).(p<0.01) An eGFR<30ml/min/1.73m(2) by GRAIL predicted development of CKD (26.9% vs. 4.6% CKD-EPI, 5.9% MDRD-4, and 10.5% MDRD-6) in center data and needing kidney after LT (48.3% vs. 22.0% CKD-EPI vs. 23.1% MDRD-4 vs. 48.3% MDRD-6, p<0.01) in national data within 5 years after LT. CONCLUSION: GRAIL may serve as an alternative model to estimate GFR amongst patients with liver disease before and after LT at low GFR.

Asrani, S. K., L. Hall, M. Hagan, S. Sharma, S. Yeramaneni, J. Trotter, J. Talwalkar and F. Kanwal (2018). “Trends in Chronic Liver Disease-Related Hospitalizations: A Population-Based Study.” Am J Gastroenterol Oct 17. [Epub ahead of print].

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OBJECTIVES: In a population-based study, we examined time trends in chronic liver disease (CLD)-related hospitalizations in a large and diverse metroplex. METHODS: We examined all CLD-related inpatient encounters (2000-2015) in Dallas-Fort Worth (DFW) using data from the DFW council collaborative that captures claims data from 97% of all hospitalizations in DFW (10.7 million regional patients). RESULTS: There were 83,539 CLD-related hospitalizations in 48,580 unique patients across 84 hospitals. The age and gender standardized annual rate of CLD-related hospitalization increased from 48.9 per 100,000 in 2000 to 125.7 per 100,000 in 2014. Mean age at hospitalization increased from 54.0 (14.1) to 58.5 (13.5) years; the proportion of CLD patients above 65 years increased from 24.2% to 33.1%. HCV-related hospitalizations plateaued, whereas an increase was seen in hospitalizations related to alcohol (9.1 to 22.7 per 100,000) or fatty liver (1.4 per 100,000 to 19.5 per 100,000). The prevalence of medical comorbidities increased for CLD patients: coronary artery disease (4.8% to 14.3%), obesity (2.8% to 14.6%), chronic kidney disease (2.8% to 18.2%), and diabetes (18.0% to 33.2%). Overall hospitalizations with traditional complications of portal hypertension (ascites, varices, and peritonitis) remained stable over time. However, hospitalization with complications related to infection increased from 54.7% to 66.4%, and renal failure increased by sevenfold (2.7% to 19.5%). CONCLUSION: CLD-related hospitalizations have increased twofold over the last decade. Hospitalized CLD patients are older and sicker with multiple chronic conditions. Traditional complications of portal hypertension have been superseded by infection and renal failure, warranting a need to redefine what it means to have decompensated CLD.

Arora, K., J. M. Sequeira, J. M. Alarcon, B. Wasek, E. Arning, T. Bottiglieri and E. V. Quadros (2018). “Neuropathology of vitamin B12 deficiency in the Cd320(-/-) mouse.” FASEB J Oct 10: [Epub ahead of print].

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In humans, vitamin B12 deficiency causes peripheral and CNS manifestations. Loss of myelin in the peripheral nerves and the spinal cord (SC) contributes to peripheral neuropathy and motor deficits. The metabolic basis for the demyelination and brain disorder is unknown. The transcobalamin receptor-knockout mouse ( Cd320(-/-)) develops cobalamin (Cbl) deficiency in the nervous system, with mild anemia. A decreased S-adenosylmethionine: S-adenosylhomocysteine ratio and increased methionine were seen in the brain with no significant changes in neurotransmitter metabolites. The structural pathology in the SC presented as loss of myelin in the axonal tracts with inflammation. The sciatic nerve (SN) showed increased nonuniform, internodal segments suggesting demyelination, and remyelination in progress. Consistent with these changes, the Cd320(-/-) mouse showed an increased latency to thermal nociception. Further, lower amplitude of compound action potential in the SN suggested that the functional capacity of the heavily myelinated axons were preferentially compromised, leading to loss of peripheral sensation. Although the metabolic basis for the demyelination and the structural and functional alterations of the nervous system in Cbl deficiency remain unresolved, the Cd320(-/-) mouse provides a unique model to investigate the pathologic consequences of vitamin B12 deficiency. -Arora, K., Sequeira, J. M., Alarcon, J. M., Wasek, B., Arning, E., Bottiglieri, T., Quadros, E. V. Neuropathology of vitamin B12 deficiency in the Cd320(-/-) mouse.