Prognostication in Very Old Intensive Care Patients with Acute Kidney Injury.

BACKGROUND: Acute kidney injury (AKI) is a risk factor for morbidity and mortality during critical illness especially in very old patients admitted to intensive care units. OBJECTIVES: To identify prognostic markers for AKI patients. METHODS: This single-center retrospective study was based on a patient registry of a medical intensive care unit. Hospital records of patients aged 80 years or older admitted between 2005 and 2015 were examined. Patients who developed AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines within 4 days of admission were included in this study. RESULTS: The study comprised 96 patients with AKI and 81 age- and sex-matched controls without AKI. Mean acute physiology and chronic health evaluation (APACHE) II score was 30 with an ICU mortality of 27% in very old patients with AKI. The odds ratio of hospital mortality for these patients was 5.02 compared to controls (49% vs. 16%). APACHE II score and fluid balance in the first 2 days of ICU admission were the strongest predictors of ICU mortality with an area under the receiver operating characteristic of 0.76. Of the 47 patients with AKI who survived hospital admission, 30 were discharged home. CONCLUSIONS: Mortality was increased in very old ICU patients with AKI. Among survivors, two-thirds returned home.

Prognosis of Chronically Ventilated Patients in a Long-Term Ventilation Facility: Association with Age, Consciousness and Cognitive State.

Background: The number of adults requiring prolonged mechanical ventilation (PMV) including those with cognitive impairment or disorders of consciousness is escalating. We aimed to compare in a long-term acute care hospital (LTACH) mortality and length of stay (LOS) among three age groups (40-59y, 60-79y, ≥80y) of hospitalized PMV patients, and according to consciousness and cognitive state at admission. Methods: We obtained data from the health records of 308 adults aged ≥40 years requiring PMV hospitalized at a Chronic Ventilator Dependent Unit in a LTACH between 01/01/2015 to 06/30/2019 and followed-up until discharge or death or until 12/31/2019. Results: At admission to LTACH, 42.2% of PMV patients were in a vegetative state/ minimally conscious state (VS/MCS); 32.5% were severely cognitively impaired, 11.0% were mildly to moderately cognitively impaired, 12.3% had no cognitive impairment, and 1.9% had intellectual disability/psychiatric disorder. In-LTACH LOS (months) decreased from 34.6 ± 42.6 at age 40-59y, 19.1 ± 22.3 at 60-79y to 14.4 ± 19.3 at age ≥80y (p = .006). In-LTACH mortality was 30.6% for 40-59y, 41.1% for 60-79y and 54.8% for age ≥80y. In-LTACH LOS (months) was 23.8 ± 30.7 for VS/MCS, 15.1 ± 19.5 for the severely cognitively impaired, 10.0 ± 12.8 for mild to moderate cognitive impairment and 18.9 ± 21.9 for those without cognitive impairment (p = .02). In-LTACH mortality was 50.8% for VS/MCS, 58.0% for the severely cognitively impaired, 26.5% for mild to moderate cognitive impairment and 13.2% for those without cognitive impairment (p < .001). Conclusion: In this population requiring PMV, mortality and in-LTACH LOS worsened with age. In-LTACH LOS was longest for VS/MCS patients, who had a mean survival of about two years, followed by those without cognitive impairment and then those with severe cognitive impairment. Mortality was associated with worse consciousness and cognitive state. These findings highlight the importance of discussing end-of-life decisions with patients and family members regarding resuscitation/intubation and the long-term management of these patients.

Comparison of Patients Undergoing Tracheostomy in the Intensive Care Unit versus in the Wards.

BACKGROUND: In Israel, critically ill patients are ventilated and managed in intensive care units or general wards. OBJECTIVES: To compare the mortality rates and long-term cognitive and functional outcomes of ventilated patients who underwent tracheostomy insertion in the Medical ICU (MICU) versus those cared for in the in-patient wards. METHODS: The study comprised 170 patients who underwent percutaneous dilatational tracheostomy (PDT) over an 18-month period in the MICU (n=102) and in in-patient wards (internal medicine and neurology) (n=68). Telephone interviews were conducted with living patients and/or their relatives at least 6 months after discharge from the hospital. RESULTS: Ward patients were 10 years older than ICU patients undergoing PDT (P = 0.003). The length of stay (LOS) in the wards was longer than in the ICU (P < 0.001), whereas the total LOS in the hospital was similar (P = 0.43). ICU mortality was lower than in the wards (P = 0.001) but hospital mortality was comparable between the two groups (P = 0.17). At 6 months follow-up more ICU patients were fully conscious, weaned from ventilation, and decannulated. More patients in the ICU group were at home and were independent or had mildly impaired activities of daily living. More patients in the ward group were residing in long-term care facilities with functional limitations. CONCLUSIONS: MICU patients who undergo tracheostomy may have a good long-term functional and cognitive outcome. More studies are needed to further assess long-term outcomes in these patients.

Placental Stromal Cell Therapy for Experimental Autoimmune Encephalomyelitis: The Role of Route of Cell Delivery.

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS) with no effective treatment available for the chronic-progressive stage. Cell therapy is a promising therapeutic approach for attenuating the immune-mediated CNS process. Isolated and expanded human placental stromal cells (hPSCs) possess potent immunomodulatory and trophic properties, making them a good candidate for MS therapy. We examined the potential of hPSC therapy in preventing the onset or attenuating the course of established disease in a murine MS model of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. We examined the feasibility of hPSC systemic delivery by intramuscular (i.m.) implantation rather than the commonly used intravenous injection, which is dose-limiting and carries the risk of pulmonary obstruction. Our findings showed significant attenuation of the disease only when hPSCs were injected directly to the central nervous system. Intramuscular implanted hPSCs survived at the site of injection for at least 2 months and elicited extensive local immune responses. Intramuscular hPSC implantation before disease onset caused a delay in the appearance of clinical signs and reduced the severity of a relapse induced by repeated challenge with the autoantigen. Intramuscular implantation after disease onset did not affect its course. Thus, pathological analysis of CNS tissue did not show inhibition of neuroinflammation in i.m. hPSC-implanted mice. Moreover, no apparent effect was seen on the proliferative response of peripheral lymph node cells in these animals. We conclude that to maximize their therapeutic potential in MS, hPSCs should be delivered directly to the affected CNS. Stem Cells Translational Medicine 2017;6:1286-1294.

Intensive care unit occupancy after introduction of the emergency department 4-hour discharge rule at a tertiary referral hospital in Western Australia.

BACKGROUND: The 4-hour rule has been introduced in Western Australia, requiring that emergency department (ED) patients be admitted to hospital or discharged from the ED within 4 hours of presentation. We hypothesised that this rule might have been associated with changes in medical emergency team (MET) calls and intensive care unit exit bed block. METHODS: Hospital databases were examined to determine compliance with the 4-hour rule, the effect on ICU exit bed block, and the number of MET calls, in 2008 (before introduction of the 4-hour rule) and 2011 (after introduction of the 4-hour rule). We also measured background ICU and hospital activity in 2008 and 2011. RESULTS: Monthly compliance with the 4-hour rule ranged from 35%-46% in 2008 to 64%-75% in 2011 (P < 0.0001). There was a marked increase in bed block days for patients in the ICU between 2008 (before introduction of the 4-hour rule) and 2011 (after introduction of the 4-hour rule) (P = 0.05). The increase in ICU bed block-days could not be explained by a difference in ICU occupancy, as there was a reduction in ICU bed-days between 2008 and 2011 (P = 0.014). There was a reduction in hospital mortality rate between 2008 and 2011 (P < 0.001). There was no significant increase in the number of MET calls from 2008 to 2011 (P = 0.221). Hospital activity (separations) increased from 2008 to 2011 (P < 0.0001). DISCUSSION: The introduction of the 4-hour rule was associated with increased exit block from the ICU, but not with increased MET calls to attend to unstable or deteriorating ward patients. Introduction of the 4-hour rule was associated with a small reduction in hospital mortality.

Contradictions in end-of-life decisions for self and other, expressed by relatives of chronically ventilated patients.

OBJECTIVES: In certain populations, social, legal, and religious factors may influence end-of-life decisions in ventilator-dependent patients. This study aims to evaluate attitudes of first-degree relatives of chronically ventilated patients in Israel, toward end-of-life decisions regarding their loved ones, themselves, and unrelated others. MATERIALS AND METHODS: The study was conducted in a chronic ventilation unit. First-degree family members of chronically ventilated patients were interviewed about their end-of-life attitudes for patients with end-stage diseases. Distinctions were made between attitudes in the case of their ventilated relatives, themselves, and unrelated others; between conscious and unconscious patients; and between a variety of interventions. RESULTS: Thirty-one family members of 25 patients were interviewed. Median length of ventilation at the time of the interview was 13.4 months. Most interviewees wanted further interventions for their ventilated relatives, yet, for themselves, only 21% and 18% supported chronic ventilation and resuscitation, respectively, and 48% would want to be disconnected from the ventilator. Interventions were more likely to be endorsed for others (vs self), for the conscious self (vs unconscious self), and for artificial feeding (vs chronic ventilation and resuscitation). Interviewees were reluctant to disconnect patients from a ventilator. CONCLUSIONS: Family members often want escalation of treatment for their ventilated relatives; however, most would not wish to be chronically ventilated or resuscitated under similar circumstances. Advance directives may reconcile people's wishes at the end of their own lives with their reticence to make decisions regarding others.

Both raft- and non-raft proteins associate with CHAPS-insoluble complexes: some APP in large complexes.

Components of caveolae and lipid rafts are characterized by their buoyancy after detergent extraction. Using flotations in density gradients, we now show that non-raft membrane molecules are also associated with detergent-insoluble, buoyant assemblies. When Triton X-100 cellular extracts were spun to equilibrium in Nycodenz, only components of classical rafts floated. In contrast, with the zwitterionic detergent CHAPS, non-raft residents such as calnexin and APP also buoyed. When CHAPS extracts were spun in non-equilibrium (velocity) conditions, some raft components rapidly exited the input fractions while other raft markers and non-raft molecules remained relatively immobile. This pointed to size heterogeneities of CHAPS-insoluble complexes. Combined velocity/equilibrium gradients broadly divided CHAPS-insoluble membrane complexes into three size categories, which all contained cholesterol and the glycosphingolipid GM1. Large complexes were enriched in caveolin and ESA. Medium size complexes were enriched in PrP, whereas small complexes contained non-raft proteins, PrP, and some ESA. While Alzheimer's APP was primarily confined to small assemblies, a portion of its glycosylated form did buoy with large complexes. Large CHAPS-insoluble complexes resemble, but are not equal to, classical rafts. These findings extend considerably the range of detergent-insoluble membranal domains.