Gait speed is a biomarker of cancer-associated cachexia decline and recovery.

Background: Progressive functional decline is a key element of cancer-associated cachexia. No therapies have successfully translated to the clinic due to an inability to measure and improve physical function in cachectic patients. Major barriers to translating pre-clinical therapies to the clinic include lack of cancer models that accurately mimic functional decline and use of non-specific outcome measures of function, like grip strength. New approaches are needed to investigate cachexia-related function at both the basic and clinical science levels. Methods: Survival extension studies were performed by testing multiple cell lines, dilutions, and vehicle-types in orthotopic implantation of K-ras LSL.G12D/+ ; Trp53 R172H/+ ; Pdx-1-Cre (KPC) derived cells. 128 animals in this new model were then assessed for muscle wasting, inflammation, and functional decline using a battery of biochemical, physiologic, and behavioral techniques. In parallel, we analyzed a 156-subject cohort of cancer patients with a range of cachexia severity, and who required rehabilitation, to determine the relationship between gait speed via six-minute walk test (6MWT), grip strength (hGS), and functional independence measures (FIM). Cachectic patients were identified using the Weight Loss Grading Scale (WLGS), Fearon consensus criteria, and the Prognostic Nutritional Index (PNI). Results: Using a 100-cell dose of DT10022 KPC cells, we extended the survival of the KPC orthotopic model to 8-9 weeks post-implantation compared to higher doses used (p<0.001). In this Low-dose Orthotopic (LO) model, both progressive skeletal and cardiac muscle wasting were detected in parallel to systemic inflammation; skeletal muscle atrophy at the fiber level was detected as early as 3 weeks post-implantation compared to controls (p<0.001). Gait speed in LO animals declined as early 2 week post-implantation whereas grip strength change was a late event and related to end of life. Principle component analysis (PCA) revealed distinct cachectic and non-cachectic animal populations, which we leveraged to show that gait speed decline was specific to cachexia (p<0.01) while grip strength decline was not (p=0.19). These data paralleled our observations in cancer patients with cachexia who required rehabilitation. In cachectic patients (identified by WLGS, Fearon criteria, or PNI, change in 6MWT correlated with motor FIM score changes while hGS did not (r 2 =0.18, p<0.001). This relationship between 6MWT and FIM in cachectic patients was further confirmed through multivariate regression (r 2 =0.30, p<0.001) controlling for age and cancer burden. Conclusion: Outcome measures linked to gait are better associated with cachexia related function and preferred for future pre-clinical and clinical cachexia studies.

Relationship Between Cachexia and the Functional Progress of Patients With Cancer in Inpatient Rehabilitation.

PURPOSE: Although inpatient rehabilitation can improve functional independence in patients with cancer, the role of cachexia in this population is unknown. Our objectives were to:1) Establish prevalence of cachexia in a cohort of cancer patients receiving inpatient rehabilitation and its association with demographic and oncological history.2) Determine the relationship between the presence of cachexia and functional recovery and whether these patients in inpatient rehabilitation have a distinct prognosis. METHODS: This is a retrospective cohort study of 250 patients over 330 admissions to an inpatient rehabilitation facility. Body weight loss threshold and Weight Loss Grading Scale identified patients with and without cachexia. Main outcomes were functional independence measure scores, discharge destination, and 6-mo survival. RESULTS: Prevalence of cachexia in inpatient rehabilitation was 59% using consensus body weight loss criteria, and 77% of cancer patients had a Weight Loss Grading Scale score greater than 0. Patients with and without cachexia had similar motor and cognitive gains, although patients with severe cachexia had more limited functional gains ( P < 0.05) and increased odds of acute care return ( P < 0.01). Patients with a Weight Loss Grading Scale score of 4 had decreased survival at 6 mos ( P < 0.05) compared with noncachectic patients. CONCLUSIONS: These data suggest that there is a relationship between cachexia and recovery for cancer patients that should be further studied in rehabilitation settings.

Factors associated with unplanned transfers among cancer patients at a freestanding acute rehabilitation facility.

BACKGROUND: Cancer patients undergoing inpatient rehabilitation often have high risk of complications leading to unplanned transfer to acute care. Prior studies have identified factors associated with these transfers but have been limited to examining factors that pertain to initial admission to rehabilitation and were not conducted in a freestanding inpatient rehabilitation facility. OBJECTIVE: The study aimed to include these prerehabilitation factors in addition to factors upon initial assessment in rehabilitation. It was hypothesized that specific factors from each of these periods would be associated with unplanned transfer to acute care. DESIGN: Retrospective cohort study. SETTING: Freestanding academic inpatient rehabilitation facility affiliated with an academic tertiary care facility with a comprehensive cancer center. PATIENTS: Retrospective review of 330 specific encounters unique to 250 patients from March 2017 to September 2018. MAIN OUTCOME MEASURES: The outcome measure was unplanned transfer to acute care. A binary logistic regression model was used to examine the relationship between factors from oncologic history, acute care course, and factors upon admission to rehabilitation to unplanned transfer to acute care. RESULTS: From 330 encounters, there were 111 unplanned transfers (34%). Unplanned transfer to acute care was independently associated with gastrointestinal malignancy (odds ratio [OR] 4.4, p = .01), 6-minute walk test less than 90 m (OR 4.6, p = .003), and prior unplanned transfer (OR 3.5, p = .007). CONCLUSIONS: The study suggests that oncologic and functional prerehabilitation markers are associated with an increased likelihood of unplanned transfer during inpatient cancer rehabilitation. These findings will provide a framework for creating predictive tools for unplanned transfers in cancer rehabilitation patients.

Patients on state organ donor registries receive similar levels of intensive care compared to those who are not: an opportunity to increase public intent to donate.

The intent to donate organs is affected by the public perception that patients on state registries receive less aggressive life-saving care in order to allow organ donation to proceed. However, the association between first person authorization to donate organs and the actual care received by eventual organ donors in hospitals is unknown. From August 2010 to April 2011, all eight organ procurement organizations in United Network for Organ Sharing Region 5 prospectively recorded demographic data and organ utilization rates on all donors after neurologic determination of death (DNDDs). Critical care and physiologic parameters were also recorded at referral for imminent neurologic death and prior to authorization for donation to reflect the aggressiveness of provided care. There were 586 DNDDs and 23% were on a state registry. Compared to non-registered DNDDs, those on state registries were older but were noted to have similar critical care parameters at both referral and authorization. Furthermore, there was no significant difference in organs procured per donor or organs transplanted per donor between registered and non-registered DNDDs. Thus, DNDDs who are on state donor registries receive similar levels of intensive care compared to non-registered donors. The association noted in this study may therefore help to dispel a common misperception that decreases the intent to donate.

Impact of deceased organ donor demographics and critical care end points on liver transplantation and graft survival rates.

BACKGROUND: The criteria for organ acceptance remain inconsistent, which limits the ability to standardize critical care practices. We sought to examine predictors of liver graft use and survival to better guide the selection and management of potential organ donors. STUDY DESIGN: A prospective observational study of all donors managed by the 8 organ procurement organizations in United Network for Organ Sharing Region 5 was conducted from July 2008 to March 2011. Critical care end points that reflect the normal hemodynamic, acid-base, respiratory, endocrine, and renal status of the donor were collected at 3 time points. Critical care and demographic data associated with liver transplantation and graft survival rates were first determined using univariate analyses, and then logistic regression was used to identify independent predictors of these two outcomes. RESULTS: From 961 donors, 730 (76%) livers were transplanted and 694 (95%) were functioning after 74 ± 73 days of follow-up. After regression analysis, donor BMI (odds ratio [OR] = 0.94), male sex (OR = 1.89), glucose <150 mg/dL (OR = 1.97), lower dopamine dose (OR = 0.95), vasopressin use (OR = 1.95), and ejection fraction >50% (OR = 1.77) remained as independent predictors of liver use. Graft survival was associated with lower donor BMI (OR = 0.91) and sodium levels (OR = 0.95). CONCLUSIONS: After controlling for donor age, sex, and BMI, both hemodynamic and endocrine critical care end points were associated with increased liver graft use. Both donor BMI and lower sodium levels during the course of donor management were independently predictive of improved graft survival. These results may help guide the management and selection of potential organ donors after neurologic determination of death.

The impact of implementing a 24/7 open trauma bed protocol in the surgical intensive care unit on throughput and outcomes.

BACKGROUND: Increased emergency department (ED) length of stay (LOS) has been associated with increased mortality in trauma patients. In 2010, we implemented a 24/7 open trauma bed protocol in our designated trauma intensive care units (TICUs) to facilitate rapid admission from the ED. This required maintenance of a daily bump list and timely transferring of patients out of the TICU. We hypothesized that ED LOS and mortality would decrease after implementation. METHODS: The following data from patients admitted directly from the ED to any ICU were retrospectively compared before (2009) and after (2011) the implementation of a trauma bed protocol at a Level I trauma center: age, sex, Glasgow Coma Scale (GCS) score, shock on admission (systolic blood pressure < 90 mm Hg), mechanism, injury severity scores (Injury Severity Score [ISS] and Abbreviated Injury Scale [AIS] score), ED LOS, ICU readmission rates, and mortality. RESULTS: Of the patients, 267 (17%) of 1,611 before and 262 (21%) of 1,266 (p < 0.01) after the protocol were admitted directly to the ICU, despite similar characteristics. ED LOS decreased from 4.2 ± 4.0 hours to 3.1 ± 2.1 hours (p < 0.01) in all patients as well as patients with an ISS of greater than 24 (3.1 ± 2.5 vs. 2.2 ± 1.6, p < 0.05) and a head AIS score of greater than 2 (4.2 ± 4.9 vs. 3.1 ± 2.0, p = 0.01). Mortality was unchanged for all patients (9% vs. 8%, p = 0.58) but trends toward improved mortality were found after protocol implementation inpatients with an ISS of greater than 24 (30% vs. 13%, p = 0.07) and in patients with a head AIS score of greater than 2 (12% vs. 6%, p = 0.08). A greater proportion of total patients were admitted to a designated TICU after implementation (83% vs. 93%, p < 0.01). ICU readmissions were unchanged (0.3% vs. 1.5%, p = 0.21). CONCLUSION: The implementation of a 24/7 open trauma bed protocol in the surgery ICU was associated with a decreased ED LOS and increased admissions to designated TICUs in all patients. Improved throughput was achieved without increases in ICU readmissions. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Which central venous catheters have the highest rate of catheter-associated deep venous thrombosis: a prospective analysis of 2,128 catheter days in the surgical intensive care unit.

BACKGROUND: Catheter-associated deep venous thromboses (CADVTs) are a common occurrence in the surgical intensive care unit (SICU), necessitating central venous catheter (CVC) removal and replacement. Previous studies evaluating risk factors for CADVT in SICU patients are limited, and most lack a true denominator of all CVC days. We sought to determine the true incidence of and risk factors for CADVT based on patient characteristics as well as CVC site, type, and duration of insertion. METHODS: The following data from all SICU patients in two urban Level I trauma centers were prospectively collected from 2009 to 2012: demographics, risk factors for DVT, CVC site/type/duration, and duplex results. Sites included the subclavian (SC), internal jugular (IJ), arm (for peripherally inserted central catheter [PICC] lines), and femoral. Types included multilumen (ML), introducer/hemodialysis (I/HD), and PICC. High-risk patients received weekly screening duplex examinations and a CADVT was defined as a DVT being detected on duplex with a CVC in place or within 7 days of removal. Rates of CADVT were normalized per 1,000 CVC days, and independent predictors of CADVT were determined using logistic regression. RESULTS: Data were complete for 184 patients, 354 CVCs, and 2,128 CVC days. Fifty-nine CADVTs were diagnosed in 28% of patients. Rates of CADVT were 9 per 1,000 catheter days for SC, 61 for IJ (p < 0.01 vs. SC), 27 for arm (p < 0.01), 36 for femoral (p < 0.01), 22 for ML, 57 for I/HD (p < 0.01 vs. ML), and 27 for PICC (p = 0.24). After adjusting for patient risk factors, predictors of CADVT included the IJ and arm sites (odds ratio, 6.0 and 3.0 compared with SC) and the I/HD type (odds ratio, 2.6 compared with ML, all p < 0.05). CONCLUSION: The IJ and arm sites and I/HD type are associated with increased CADVT. These data may be used to determine the optimal site and type of CVC for insertion. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III.