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Aggressive resource utilization for patients with cancer at the end of life has been associated with poor outcomes for patients and their families. To our knowledge, no previous studies have characterized resource utilization as a proxy for quality end-of-life care in hospitalized patients awaiting discharge to hospice by physician and advanced practice providers (APPs). We conducted a retrospective cohort study to examine resource utilization and the quality metrics for end-of-life care in patients at Memorial Sloan Kettering Cancer Center from the date of hospice decision to discharge. Patients under the care of APP teams were less likely to receive laboratory testing (50% vs 59%, P =.046) and received fewer tests than those with house staff teams, though performance on end-of-life quality metrics was similar. Our findings suggest APPs may improve quality of end-of-life care by avoiding unnecessary or aggressive measures compared to house staff. [ABSTRACT FROM AUTHOR]

Yang, Shaolong, Douglas J. Koo, Mian Zhou, Irshad H. Chaudry, and Ping Wang. Gut-derived norepinephrine plays a critical role in producing hepatocellular dysfunction during early sepsis. Am J Physiol Gastrointest Liver Physiol 279: G1274-G1281, 2000.--Although plasma norepinephrine (NE) increases and hepatocellular function is depressed during early sepsis, it is unknown whether gut is a significant source of NE and, if so, whether gut-derived NE helps produce hepatocellular dysfunction. We subjected rats to sepsis by cecal ligation and puncture (CLP), and 2 h later (i.e., early sepsis) portal and systemic blood samples were collected and plasma levels of NE were assayed. Other rats were enterectomized before CLP. Hepatocellular function was assessed with an in vivo indocyanine green (ICG) clearance technique, systemic levels of tumor necrosis factor (TNF)-[Alpha], interleukin (IL)-1[Beta], and IL-6 were determined, and the effect of NE on hepatic ICG clearance capacity was assessed in an isolated, perfused liver preparation. Portal levels of NE were significantly higher than systemic levels at 2 h after CLP. Prior enterectomy reduced NE levels in septic animals. Thus gut appears to be the major source of NE release during sepsis. Enterectomy before sepsis also attenuated hepatocellular dysfunction and downregulated TNF-[Alpha], IL-1[Beta], and IL-6. Perfusion of the isolated livers with 20 nM NE (similar to that observed in sepsis) significantly reduced ICG clearance capacity. These results suggest that gut-derived NE plays a significant role in hepatocellular dysfunction and upregulating inflammatory cytokines. Modulation of NE release and/or hepatic responsiveness to NE should provide a novel approach for maintaining hepatocellular function in sepsis. indocyanine green clearance; enterectomy; isolated, perfused rat liver; cecal ligation and puncture; inflammatory cytokines

Ba, Zheng F., Ping Wang, Douglas J. Koo, Mian Zhou, William G. Cioffi, Kirby I. Bland, and Irshad H. Chaudry. Testosterone receptor blockade after trauma and hemorrhage attenuates depressed adrenal function. Am J Physiol Regulatory Integrative Comp Physiol 279: R1841-R1848, 2000.--Although the testosterone receptor antagonist flutamide restores the depressed immune function in males after trauma and hemorrhage, it remains unknown whether this agent has any salutary effects on adrenal function. To study this, male rats underwent laparotomy and were bled to and maintained at a blood pressure of 40 mmHg until 40% of the shed blood volume was returned in the form of Ringer lactate. Animals were then resuscitated and fiutamide (25 mg/kg body wt) was administered subcutaneously. Plasma adrenocorticotropic hormone (ACTH) and corticosterone, as well as adrenal corticosterone and cAMP were measured 20 h after resuscitation. In additional animals, ACTH was administered and ACTH-induced corticosterone release and adrenal cAMP were determined. The results indicate that adrenal contents of corticosterone and cAMP were significantly decreased and morphology was altered after hemorrhage. Administration of flutamide improved corticosterone content, restored cAMP content, and attenuated adrenal morphological alterations. Flutamide also improved the diminished ACTH-induced corticosterone release and adrenal cAMP response at 20 h after hemorrhage and resuscitation. Furthermore, the diminished corticosterone response to ACTH stimulation in the isolated adrenal preparation was improved with flutamide. These results suggest that flutamide is a useful adjunct for improving adrenal function in males following trauma and hemorrhage. adrenal function; isolated perfused adrenal preparation; corticosterone; adenosine 3',5'-cycle monophosphate; adrenocorticotropic hormone

Yang, Shaolong, Mian Zhou, Douglas J. Koo, Irshad H. Chaudry, and Ping Wang. Pentoxifylline prevents,; the transition from the hyperdynamic to hypodynamic response during sepsis. Am. J. Physiol. 277 (Heart Circ. Physiol. 46): H1036-H1044, 1999.--The cardiovascular response to sepsis includes an early, hyperdynamic phase followed by a late, hypodynamic phase. Although administration of pentoxifylline (PTX) produces beneficial effects in sepsis, it remains unknown whether this agent prevents the transition from the hyperdynamic to the hypodynamic response during the progression of sepsis. To study this, male adult rats were subjected to polymicrobial sepsis by ceca] ligation and puncture (CLP). At 1 h after CLP, PTX (50 mg/kg body wt) or vehicle was infused intravenously over 30 min. At 20 h after CLP (i.e., the late stage of sepsis), cardiac output and organ blood flow were measured by radioactive microspheres. Systemic and regional (i.e., hepatic, intestinal, and renal) oxygen delivery (D[O.sub.2]) and oxygen consumption (V[O.sub.2]) were determined. Moreover, plasma levels of lactate and alanine aminotransferase (ALT) were measured, and histological examinations were performed. In additional animals, the necrotic cecum was excised at 20 h after CLP, and mortality was monitored for 10 days thereafter. The results indicate that cardiac output, organ blood flow, and systemic and regional D[O.sub.2] decreased by 36-65% (P [is less than] 0.05) at 20 h after CLP. Administration of PTX early after the onset of sepsis, however, prevented reduction in measured hemodynamic parameters and increased systemic and regional D[O.sub.2] and V[O.sub.2] by 50-264% (P [is less than] 0.05). The elevated levels of lactate (by 173%, P [is less than] 0.05) and ALT (by 718%, P [is less than] 0.05), as well as the morphological alterations in the liver, small intestine, and kidneys during sepsis were attenuated by PTX treatment. In addition, PTX treatment decreased the mortality rate from 50 to 0% (P [is less than] 0.05) after CLP and cecal excision. Because PTX prevents the occurrence of hypodynamic sepsis, this agent appears to be a useful adjunct for maintaining hemodynamic stability and preventing lethality from sepsis. cecal ligation and puncture; regional blood flow; cardiovascular responses; oxygen delivery; oxygen consumption; lactate

Examines the role of gut-derived norepinephrine in producing hepatocellular dysfunction during early sepsis. Portal and systemic levels of norepinephrine and the effect of enterectomy on circulating norepinephrine; Alterations in in vivo indocyanine green; Alterations in indocyanine green clearance in isolated, perfused liver preparations.

Hypothesis: Since studies have found the liver enzyme α-glutathione S-transferase (αGST) to be a marker of hepatic injury after hemorrhagic shock, αGST also may serve as a sensitive indicator of hepatocellular damage during the early stage of polymicrobial sepsis. Design, Interventions, and Main Outcome Measures: Male adult rats were subjected to the cecal ligation and puncture (CLP) model of polymicrobial sepsis or sham operation, followed by fluid resuscitation with isotonic sodium chloride solution. Systemic blood samples were taken at 2, 5, 10, or 20 hours after CLP or sham operation. Plasma levels of αGST and lactate were determined using an enzyme immunoassay and enzymatic assay, respectively. Additional animals were examined for morphologic alterations in liver ultrastructure of septic animals using electron microscopy. Results: A similar level of αGST (mean ± SEM, 30.5 ± 3.5 µg/L) was found in the sham group at all measured time points. Although plasma levels of αGST did not change at 2 hours after CLP, they were elevated by 249% at 5 hours after the onset of sepsis and continued to increase throughout the septic course. Plasma lactate levels were significantly increased only at 20 hours after CLP (P<.001). Previous studies have shown that liver transaminase levels did not increase at 5 hours, but at 10 and 20 hours after CLP. In addition, electron microscopy revealed structural changes in hepatocyte morphology at 5 and 20 hours after CLP that were indicative of hepatocellular injury. Conclusion: Since plasma αGST levels increased earlier than plasma lactate and liver transaminase levels, αGST may be a more sensitive indicator of early liver injury and should be used in monitoring hepatocellular damage during the progression of sepsis. [ABSTRACT FROM AUTHOR]

Purpose: The Centers for Medicare and Medicaid Services recently initiated readmission reduction programs for certain noncancer index admissions. Intrinsic to this policy is the assumption that such readmissions are reasonably preventable and are due to inadequate management. For cancer patients, readmission frequency, characteristics, and their preventability have not been extensively evaluated., Methods: We first electronically searched medical records of patients on our gastrointestinal oncology inpatient service to identify patients who had been discharged and then readmitted within 30 days. However, electronic review resulted in insufficient granularity of clinical records. Therefore, 50 of them were randomly selected for exhaustive manual review to assess the reasons for index admission and readmission, the nature of the index admission discharge plan, and whether the readmission was reasonably preventable or not, based on prespecified criteria., Results: Between September 1, 2008, and March 1, 2013, 3995 gastrointestinal medical oncology patients had an index admission, of whom 876 (22%) had ≥ 1 readmission within 30 days. From the 50 manually reviewed records, the most common diagnosis categories for either the index admission or the readmission were infection, pain, and gastrointestinal issues. For 64% of these patients, the diagnoses of the index admission and the readmission were different. Disagreement between the care team and patient/family about the index admission discharge plan was documented in 10%. The readmission was determined to be preventable in 1 (2%) of the 50 manually reviewed cases., Conclusions: Readmissions in this cancer population are common and reflect the refractory nature of these diseases and the high disease burdens. The vast majority of readmissions in this population, by our criteria, were not preventable. Our ongoing research in this vulnerable population includes efforts to better characterize and communicate care options, especially in the cases in which there was disagreement between the care team and patient/family.