Christopher D. Raeburn

Postoperative Delirium in the Elderly : Risk Factors and Outcomes

Objective:The purpose of this study was to describe the natural history, identify risk factors, and determine outcomes for the development of postoperative delirium in the elderly. Background:Postoperative delirium is a common and deleterious complication in geriatric patients. Methods:Subjects older than 50 years scheduled for an operation requiring a postoperative intensive care unit admission were recruited. After preoperative informed written consent, enrolled subjects had baseline cognitive and functional assessments. Postoperatively, subjects were assessed daily for delirium using the confusion assessment method-intensive care unit. Patients were also followed for outcomes. Results:During the study period, 144 patients were enrolled before major abdominal (40%), thoracic (53%), or vascular (7%) operations. The overall incidence of delirium was 44% (64/144). The average time to onset of delirium was 2.1 ± 0.9 days and the mean duration of delirium was 4.0 ± 5.1 days. Several preoperative variables were associated with an increased risk of delirium including older age (P < 0.001), hypoalbuminemia (P < 0.001), impaired functional status (P < 0.001), pre-existing dementia (P < 0.001), and pre-existing comorbidities (P < 0.001). In a multivariable logistic regression model, pre-existing dementia remains the strongest risk factor for the development of postoperative delirium. Worse outcomes, including increased length of stay (P < 0.001), postdischarge institutionalization (P < 0.001), and 6 month mortality (P = 0.001), occurred in subjects who developed delirium. Conclusions:In the current study, delirium occurred in 44% of elderly patients after a major operation. Pre-existing cognitive dysfunction was the strongest predictor of the development of postoperative delirium. Outcomes, including an increased rate of 6 month mortality, were worse in patients who developed postoperative delirium.

The abdominal compartment syndrome is a morbid complication of postinjury damage control surgery.

BACKGROUND The abdominal compartment syndrome (ACS) is a recognized complication of damage control surgery (DCS). The purposes of this study were to (1) determine the effect of ACS on outcome after DCS, (2) identify patients at high risk for the development of ACS, and (3) determine whether ACS can be prevented by preemptive intravenous bag closure during DCS. METHODS Patients requiring postinjury DCS at our institution from January 1996 to June 2000 were divided into groups depending on whether or not they developed ACS. ACS was defined as an intra-abdominal pressure (IAP) greater than 20 mm Hg in association with increased airway pressure or impaired renal function. RESULTS ACS developed in 36% of the 77 patients who underwent DCS with a mean IAP prior to decompression of 26 +/- 1 mm Hg. The ACS versus non-ACS groups were not significantly different in patient demographics, Injury Severity Score, emergency department vital signs, or intensive care unit admission indices (blood pressure, temperature, base deficit, cardiac index, lactate, international normalized ratio, partial thromboplastin time, and 24-hour fluid). The initial peak airway pressure after DCS was higher in those patients who went on to develop ACS. The development of ACS after DCS was associated with increased ICU stays, days of ventilation, complications, multiorgan failure, and mortality. CONCLUSIONS ACS after postinjury DCS worsens outcome. With the exception of early elevation in peak airway pressure, we could not identify patients at higher risk for ACS; moreover, preemptive abdominal bag closure during initial DCS did not prevent this highly morbid complication.

Cytokines for surgeons

All cells maintain continuous communication. Hormones derive constitutively from specialized cells to effect total body homeostasis. Conversely, cytokines are produced sporadically from almost all nucleated cells in response to surgical ischemia/septic challenge. Surgical patients are a stew of pulsating cytokines, which serve as the language between all surgically stressed somatic and myeloid cells. Therapeutic manipulation of cytokines has already generated some exhilarating success stories and some crushing disappointments. This introduction to surgically relevant cytokines is presented with the conviction that cytokine-based therapies of surgical patients will (in the future) prove as beneficial to our patients as antibiotics have in the past.

Programmed Death-1+ T Cells and Regulatory T Cells Are Enriched in Tumor-Involved Lymph Nodes and Associated with Aggressive Features in Papillary Thyroid Cancer

CONTEXT Recurrent metastatic lymph node (LN) disease is common in patients with papillary thyroid cancer (PTC). Novel prognostic markers may be helpful in guiding a therapeutic approach. Our previous studies revealed that immune suppression is evident in PTC and associated with more severe disease. OBJECTIVE To characterize the immune response to metastatic PTC, we assessed CD4(+) T cell polarization in LN. In addition, we investigated the role of programmed death-1 (PD-1) and T cell exhaustion. DESIGN Uninvolved (UILN) and tumor-involved lymph nodes (TILN) were sampled ex vivo by fine-needle biopsy. T cell subsets were identified by flow cytometry. In parallel, archived TILN specimens were characterized by immunofluorescence. SETTING The study was conducted at the University of Colorado Hospital. PATIENTS Data were collected on 94 LN from 19 patients with PTC undergoing neck dissection. MAIN OUTCOME T cell subset frequencies were compared in UILN and TILN and assessed for correlation with recurrent disease and extranodal invasion. RESULTS Regulatory CD4(+) T cells (Treg) were enriched in TILN compared with UILN and further elevated in TILN from patients with recurrent disease. PD-1(+) T cells were present at high frequency in TILN and markedly enriched in TILN that showed evidence of extranodal invasion. In TILN, Treg frequency correlated with PD-1(+) T cell frequencies. Although PD-1(+) T cells produced interferon-γ, they failed to fully down-regulate CD27 and were not actively proliferating. CONCLUSIONS Increased Treg and PD-1(+) T cell frequencies in LN may be indicative of aggressive recurrent PTC. Future prospective studies are necessary to determine the prognostic and therapeutic value of these findings in PTC.

Low tryptophan levels are associated with postoperative delirium in the elderly.

BACKGROUND Postoperative delirium is a common complication in geriatric patients. Tryptophan is an amino acid precursor to the mood-stabilizing neurotransmitters serotonin and melatonin. We hypothesized that tryptophan levels are lower in elderly subjects who develop postoperative delirium. METHODS A prospective observational study was performed. Subjects older than 50 years undergoing surgery with an anticipated postoperative intensive care unit admission were recruited. Postoperative delirium assessment occurred daily using the Confusion Assessment Method-intensive care unit. Peripheral serum tryptophan levels were measured 2 days after surgery. RESULTS Forty-nine subjects (46 men) were enrolled, with an average age of 64 +/- 7 years. The incidence of delirium was 43% (21 of 49). The average duration of delirium was 2.9 +/- 3.0 days. Tryptophan levels were lower in the subjects who developed delirium (29.9 +/- 13.3 vs 48.5 +/- 19.8 microg/mL; P = .001). CONCLUSIONS Lower levels of tryptophan postoperatively were associated with the development of delirium in the elderly.

Management of duodenal and pancreaticobiliary perforations associated with periampullary endoscopic procedures

BACKGROUND The purpose of this study was to determine the incidence and outcome of pancreaticobiliary and duodenal (PB/D) perforations from periampullary endoscopic procedures and to examine whether clinical indexes are predictive of the need for operative management. METHODS A retrospective review compared patients who had operative intervention for PB/D perforation with those managed nonoperatively. RESULTS Thirty-two PB/D perforations occurred in 4,919 procedures (.6%). Twelve (37%) required operation; 20 (63%) were successfully managed nonoperatively. Radiographic imaging was not helpful in predicting the need for operation. A clinical scoring system was predictive of the need for operative management. The length of stay and morbidity rates were higher in the operatively managed patients. CONCLUSIONS Most endoscopic PB/D perforations can be successfully managed without operation and, clinical indices are most predictive in determining the need for surgery. Further prospective evaluation of this scoring system may help guide the need for and timing of operative intervention for PB/D perforations.

PD-1+Tim-3+ CD8+ T Lymphocytes Display Varied Degrees of Functional Exhaustion in Patients with Regionally Metastatic Differentiated Thyroid Cancer

Severson and colleagues show that exhaustion of PD-1+ T cells in tumor-involved lymph nodes from patients with metastatic differentiated thyroid cancer was not complete. While PD-1+CD8+ T cells were variably dysfunctional in their ability to produce cytokines, their proliferative capacity was maintained, and PD-1+CD4+ T cells remained functional. Regional metastatic differentiated thyroid cancer (mDTC) provides a unique model in which to study the tumor–immune interface. These lymph node metastases persist for years, generally without progression to distant metastases. Although the immune system likely impedes disease progression, it is unsuccessful in eliminating disease. Our previous studies revealed that programmed death-1 (PD-1)+ T cells were enriched in tumor-involved lymph nodes (TILN). Tumor-associated leukocytes and tumor cells were collected from grossly involved lymph nodes from 12 patients to further characterize the phenotype and functional potential of mDTC-associated PD-1+ T cells. PD-1+CD4+ and PD-1+CD8+ T cells were enriched in 8 of 12 TILN samples. PD-1+ T cells coexpressed Tim-3 and CD69 and failed to downregulate CD27. CD8+ T cells, but not CD4+ T cells, from these samples were variably deficient in their ability to produce effector cytokines when compared with control TILNs that lacked resident PD-1+ T cells. PD-1+CD8+ T cells were capable of exocytosis but lacked intracellular perforin. Surprisingly, T-cell proliferative capacity was largely maintained in all samples. Thus, although PD-1 expression by mDTC-associated CD8+ T cells was associated with dysfunction, exhaustion was not complete. Notably, molecular markers of exhaustion did not translate to dysfunction in all samples or in CD4+ T cells. Regulatory T cells (Treg), PD-L1, and galectin-9 were commonly found in mDTC and likely contributed to the initiation of T-cell exhaustion and disease progression. Therapies that release the effects of PD-1 and Tim-3 and reduce the suppressive effects of Tregs may encourage tumor elimination in patients with mDTC. Cancer Immunol Res; 3(6); 620–30. ©2015 AACR.

The computerized rounding report: implementation of a model system to support transitions of care.

OBJECTIVES In response to ACGME work-hour restrictions, residency programs that require continuous inpatient clinical care for educational objectives will be forced to increase the proportion of junior resident experience involved in shift work. Maintaining the balance of education over service at these levels will be a challenge, where a considerable amount of time must be spent gathering data for morning rounds and signing out patients at shift change. Patient safety is an issue with this new paradigm. We hypothesized that computerized sign-out would improve resident efficiency. MATERIALS AND METHODS A multidisciplinary clinical team collaborated to design a computerized rounding and sign-out (CSO) program to automate collection of clinical information in addition to a brief narrative describing ongoing care issues. Residents returned a self-administered questionnaire before (n = 168) and after implementation (n = 83) examining: pre-rounding time, missed patients, handoff quality, and duty hours. RESULTS Residents reported spending 11 fewer min/d pre-rounding (P = 0.006). After implementation, residents missed fewer patients on rounds (P = 0.01). A majority (70%) of responders stated that the new program helped them with duty hours. CONCLUSION The current study demonstrates the reproducibility of the University of Washington model system for rounding and sign-out at an independent site, using basic infrastructure and leadership common to all residency programs. Developing a CSO was associated with a modest reduction in pre-rounding time and fewer patients missed on rounds. Although automating resident tasks may improve workflow in an increasingly complex hospital environment, structured handoff education and other institutional changes are necessary.

Stem Cells and Myocardial Repair

Myocardial ischemia sends a warning signal to subtended cardiomyocytes that can both promote protection by preconditioning and result in contractile dysfunction or stunning. If the ischemic period is brief ( 20 minutes), cardiomyocytes survive, contractile function recovers, and the myocardium becomes relatively resistant to subsequent ischemic insult. With prolonged periods of ischemia, cardiomyocyte death occurs by either apoptosis or necrosis, resulting in myocardial infarction. For 75 years, infarcted myocardium has been perceived as irreparable. Surgeons have focused therapeutic attention at the potentially salvageable (but narrow) periinfarction rim, where cardiac cells become hypertrophic to compensate for the functional loss within a zone of infarction. Hyperdynamic cells at the infarct border zone are further challenged by regional deficiency in oxygen-substrate delivery, resulting in cardiac remodeling (pathologic ventricular dilatation). Consequent expansion of the infarct area is caused by enhanced myocyte apoptosis, tissue fibrosis, and heart failure. Traditional dogma suggests that hypoxia controls this entire sequence. The standard surgical approach to cardiac ischemic injury is to acknowledge the loss of the infarcted muscle and to revascularize the rest of the heart in the hope of averting further damage. Compelling evidence has now been presented that all myocardial cells might not be terminally differentiated. A subset of cardiac cells might be able to replicate and form new blood vessels, permitting repopulation of portions of the infarct zone. IS THERE A SELF-RENEWING SOURCE OF CARDIOMYOCYTES? During embryogenesis, the heart grows through cellular division of cardiomyocytes. At birth, cardiomyocytes enter a postmitotic state (Go), and further heart growth occurs by hypertrophy of existing cardiomyocytes. This developmental schema works well during conditions of normoxia, but during ischemia, the myocardium is limited in its capacity to regenerate injured areas by cellular replication. Indeed, the heart attempts to compensate for cardiomyocyte loss after myocardial infarction by further hypertrophy of viable cells, but this maladaptive response frequently results in pathologic ventricular remodeling. Compared with other species, human myocardium has a disproportionately high number of nuclei with increased ploidy. Over 50% of human cardiomyocytes are tetraploid (having two complete sets of chromosomes), so it appears that cellular division in cardiomyocytes is programmed to cease after DNA replication has already occurred. The cellular signals that halt cellular division of postnatal cardiomyocytes are poorly understood. Because fetal cardiomyocytes are capable of replication, attempts have been made to use them as a potential source of cells to repair infarcted myocardium. Several challenges must be overcome for this exciting new therapy to be realized. Implanted cells must be able to survive in the hostile, inflammatory environment of the infarct, and then, to increase myocardial function, they must differentiate into phenotypically mature cells that form intercalated discs and gap junctions with the host myocardium. Recent evidence suggests that limitation of infarct progression can occur after fetal cell transplant even in the absence of ultrastructural connection with the host myocardium. In rodents, fetal and neonatal cardiac cells injected into infarcted myocardium survive within host myocardium and incorporate through intercalated discs and gap junctions. Transplantation of fetal cardiomyocytes into myocardial infarcts of rats improves heart function. On the other hand, Etzion and colleagues No competing interests declared.

LAPAROSCOPIC APPROACH TO ADRENAL AND ENDOCRINE PANCREATIC TUMORS

Laparoscopic adrenalectomy quickly has become the procedure of choice for benign adrenal lesions because it results in less pain, shorter hospital stay, comparable safety, and more patient satisfaction overall. The laparoscopic approach requires advanced laparoscopic surgical skills. Surgeons should be familiar with these techniques and the open approaches before attempting this procedure. When first learning the technique, small left-sided lesions are likely the easiest, and a more experienced surgeon should be present for the initial few cases; however, at this point, the laparoscopic approach to pancreatic endocrine tumors does not have a clear benefit, and it should be considered primarily investigational without clearly established benefits.