Research Publications Spotlight

Smith PJ, Blumenthal JA, Snyder LD, Mathew JP, Durheim M, Hoffman BM, Rivelli S, Palmer SM. Depressive Symptoms and Early Mortality Following Lung Transplantation: A Pilot Study. Clin Transplant. 2016 Nov 16. [Epub ahead of print]


BACKGROUND: Impaired psychological function is common among lung transplant candidates and may affect clinical outcomes following transplantation. Although numerous studies have examined the relationship between pre-transplant depression, quality of life (QoL), and post-transplant outcomes, few have examined the relationship between depression and QoL shortly following transplantation and subsequent clinical outcomes. We therefore examined the association between depression, QoL, and short-term mortality in a consecutive series of lung transplant recipients

METHODS: Depression (Patient Health Questionnaire-9; Hospital Anxiety and Depression Scale; Centers for Epidemiologic Studies Depression Scale) and QoL (UCSD Shortness of Breath Questionnaire; Pulmonary Quality of Life Scale) were assessed prior to transplantation (median 0.9 months [IQR = 1.6]) and again approximately two weeks following transplantation (median = 0.5 months [IQR = 0.5]), in a series of 66 patients transplanted between March, 2013 and April, 2014. The association between psychiatric diagnoses from participants’ comprehensive pre-transplant assessment and mortality also was examined. Cox proportional hazards models were used to examine the association between depression, QoL, and mortality

RESULTS: During a median follow-up of 2.8 years (range 0.4 to 3.3), 21 patients died (32%). Greater depressive symptoms assessed shortly after transplant were associated with subsequent mortality (HR = 2.17 [1.01, 4.67], P = .048) and this relationship persisted after controlling for primary graft dysfunction, duration of transplant hospitalization, and gender. In contrast, neither pre-transplant depression, history of depression, nor QoL were associated with mortality

CONCLUSIONS: Greater post-transplant depressive symptoms are independently associated with mortality among lung transplant recipients.

Weiskopf RB, Beliaev AM, Shander A, Guinn NR, Cap AP, Ness PM, Silverman TA. Addressing the Unmet Need of Life-Threatening Anemia With Hemoglobin-Based Oxygen Carriers. Transfusion. 2016 Nov 18. [Epub ahead of print]

Browndyke JN, Berger M, Harshbarger TB, Smith PJ, White W, Bisanar TL, Alexander JH, Gaca JG, Welsh-Bohmer K, Newman MF, Mathew JP. Resting-State Functional Connectivity and Cognition After Major Cardiac Surgery in Older Adults without Preoperative Cognitive Impairment: Preliminary Findings. J Am Geriatr Soc. 2016 Nov 17. [Epub ahead of print]


OBJECTIVES: To look for changes in intrinsic functional brain connectivity associated with postoperative changes in cognition, a common complication in seniors undergoing major surgery, using resting-state functional magnetic resonance imaging.

DESIGN: Objective cognitive testing and functional brain imaging were prospectively performed at preoperative baseline and 6 weeks after surgery and at the same time intervals in nonsurgical controls.

SETTING: Academic medical center.

PARTICIPANTS: Older adults undergoing cardiac surgery (n = 12) and nonsurgical older adult controls with a history of coronary artery disease (n = 12); no participants had cognitive impairment at preoperative baseline (Mini-Mental State Examination score >27).

MEASUREMENTS: Differences in resting-state functional connectivity (RSFC) and global cognitive change relationships were assessed using a voxel-wise intrinsic connectivity method, controlling for demographic factors and pre- and perioperative cerebral white matter disease volume. Analyses were corrected for multiple comparisons (false discovery rate P < .01).

RESULTS: Global cognitive change after cardiac surgery was significantly associated with intrinsic RSFC changes in regions of the posterior cingulate cortex and right superior frontal gyrus-anatomical and functional locations of the brain’s default mode network (DMN). No statistically significant relationships were found between global cognitive change and RSFC change in nonsurgical controls.

CONCLUSION: Clinicians have long known that some older adults develop postoperative cognitive dysfunction (POCD) after anesthesia and surgery, yet the neurobiological correlates of POCD are not well defined. The current results suggest that altered RSFC in specific DMN regions is positively correlated with global cognitive change 6 weeks after cardiac surgery, suggesting that DMN activity and connectivity could be important diagnostic markers of POCD or intervention targets for potential POCD treatment efforts.

Terrando N, Yang T, Wang X, Fang J, Cao M, Andersson U, Erlandsson HH, Ouyang W, Tong J. Systemic HMGB1 Neutralization Prevents Postoperative Neurocognitive Dysfunction in Aged Rats. Front Immunol. 2016 Oct 24;7:441. eCollection 2016.


Postoperative neurocognitive disorders are common complications in elderly patients following surgery or critical illness. High mobility group box 1 protein (HMGB1) is rapidly released after tissue trauma and critically involved in response to sterile injury. Herein, we assessed the role of HMGB1 after liver surgery in aged rats and explored the therapeutic potential of a neutralizing anti-HMGB1 monoclonal antibody in a clinically relevant model of postoperative neurocognitive disorders. Nineteen to twenty-two months Sprague-Dawley rats were randomly assigned as: (1) control with saline; (2) surgery, a partial hepatolobectomy under sevoflurane anesthesia and analgesia, + immunoglobulin G as control antibody; (3) surgery + anti-HMGB1. A separate cohort of animals was used to detect His-tagged HMGB1 in the brain. Systemic anti-HMGB1 antibody treatment exerted neuroprotective effects preventing postoperative memory deficits and anxiety in aged rats by preventing surgery-induced reduction of phosphorylated cyclic AMP response element-binding protein in the hippocampus. Although no evident changes in the intracellular distribution of HMGB1 in hippocampal cells were noted after surgery, HMGB1 levels were elevated on day 3 in rat plasma samples. Experiments with tagged HMGB1 further revealed a critical role of systemic HMGB1 to enable an access to the brain and causing microglial activation. Overall, these data demonstrate a pivotal role for systemic HMGB1 in mediating postoperative neuroinflammation. This may have direct implications for common postoperative complications like delirium and postoperative cognitive dysfunction.