Impact of early ICU admission for critically ill cancer patients: Post-hoc analysis of a prospective multicenter multinational dataset.

Abstract Purpose Peripherally acting μ-opioid receptor antagonists such as methylnaltrexone (MNTX, Relistor®) are indicated for the treatment of opioid-induced constipation (OIC). The structural properties unique to MNTX restrict it from traversing the blood-brain barrier (BBB); however, the BBB may become more permeable in patients with brain metastases. We investigated whether the presence of brain metastases in cancer patients compromises the central effects of opioids among patients receiving MNTX for OIC. Methods This post hoc analysis of pooled data from 3 randomized, placebo-controlled trials included cancer patients with OIC who received MNTX or placebo. Endpoints included changes from baseline in pain scores, rescue-free laxation (RFL) within 4 or 24 h of the first dose, and treatment-emergent adverse events (TEAEs), including those potentially related to opioid withdrawal symptoms. Results Among 356 cancer patients in the pooled population, 47 (MNTX n = 27; placebo n = 20) had brain metastases and 309 (MNTX n = 172; placebo n = 137) did not have brain metastases. No significant differences in current pain, worst pain, or change in pain scores from baseline were observed between patients treated with MNTX or placebo. Among patients with brain metastases, a significantly greater proportion of patients who received MNTX versus placebo achieved an RFL within 4 h after the first dose (70.4% vs 15.0%, respectively, p = 0.0002). TEAEs were similar between treatment groups and were generally gastrointestinal in nature and not related to opioid withdrawal. Conclusion Focal disruptions of the BBB caused by brain metastases did not appear to alter central nervous system penetrance of MNTX.

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Association of protein intake with the outcomes of critically ill patients: a post hoc analysis of the PermiT trial

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqy189 ◽

2018 ◽

Vol 108 (5) ◽

pp. 988-996 ◽

Cited By ~ 7

Author(s):

Y M Arabi ◽

H M Al-Dorzi ◽

S Mehta ◽

H M Tamim ◽

S H Haddad ◽

...

Keyword(s):

Propensity Score ◽

Critically Ill ◽

Nitrogen Balance ◽

Critically Ill Patients ◽

Protein Intake ◽

Nitrogen Excretion ◽

Post Hoc Analysis ◽

Lower Protein ◽

Protein Group ◽

Post Hoc

ABSTRACT Background The optimal amount of protein intake in critically ill patients is uncertain. Objective In this post hoc analysis of the PermiT (Permissive Underfeeding vs. Target Enteral Feeding in Adult Critically Ill Patients) trial, we tested the hypothesis that higher total protein intake was associated with lower 90-d mortality and improved protein biomarkers in critically ill patients. Design In this post hoc analysis of the PermiT trial, we included patients who received enteral feeding for ≥3 consecutive days. Using the median protein intake of the cohort as a cutoff, patients were categorized into 2 groups: a higher-protein group (>0.80 g · kg–1 · d–1) and a lower-protein group (≤0.80 g · kg–1 · d–1). We developed a propensity score for receiving higher protein. Primary outcome was 90-d mortality. We also compared serial values of prealbumin, transferrin, 24-h urinary nitrogen, and 24-h nitrogen balance on days 1, 7, and 14. Results Among the 729 patients included in this analysis, the average protein intake was 0.8 ± 0.3 g · kg–1 · d–1 [1.0 ± 0.2 g · kg–1 · d–1 in the higher-protein group (n = 365) and 0.6 ± 0.2 g · kg–1 · d–1 in the lower-protein group (n = 364); P < 0.0001]. There was no difference in 90-d mortality between the 2 groups [88/364 (24.2%) compared with 94/363 (25.9%), propensity score–adjusted OR: 0.80; 95% CI: 0.56, 1.16; P = 0.24]. Higher protein intake was associated with an increase in 24-h urea nitrogen excretion compared with lower protein intake, but without a significant change in prealbumin, transferrin, or 24-h nitrogen balance. Conclusions In the PermiT trial, a moderate difference in protein intake was not associated with lower mortality. Higher protein intake was associated with increased nitrogen excretion in the urine without a corresponding change in prealbumin, transferrin, or nitrogen balance. Protein intake needs to be tested in adequately powered randomized controlled trials targeting larger differences in protein intake in high-risk populations.

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Patterns of ICU admissions and outcomes in patients with solid malignancies over the revolution of cancer treatment

Annals of Intensive Care ◽

10.1186/s13613-021-00968-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Clara Vigneron ◽

Julien Charpentier ◽

Sandrine Valade ◽

Jérôme Alexandre ◽

Samy Chelabi ◽

...

Keyword(s):

Survival Rate ◽

Adverse Events ◽

Cancer Patients ◽

Critically Ill ◽

Metastatic Disease ◽

Critical Conditions ◽

Icu Admission ◽

Solid Malignancies ◽

Single Centre Study ◽

Organ Failures

Abstract Background Major therapeutic advances including immunotherapy and targeted therapies have been changing the face of oncology and resulted in improved prognosis as well as in new toxic complications. The aim of this study is to appraise the trends in intensive care unit (ICU) admissions and outcomes of critically ill patients with solid malignancies. We performed a retrospective single-centre study over a 12-year period (2007–2018) including adult patients with solid malignancies requiring unplanned ICU admission. Admission patterns were classified as: (i) specific if directly related to the underlying cancer; (ii) non-specific; (iii) drug-related or procedural adverse events. Results 1525 patients were analysed. Lung and gastro-intestinal tract accounted for the two main tumour sites. The proportion of patients with metastatic diseases increased from 48.6% in 2007–2008 to 60.2% in 2017–2018 (p = 0.004). Critical conditions were increasingly related to drug- or procedure-related adverse events, from 8.8% of ICU admissions in 2007–2008 to 16% in 2017–2018 (p = 0.01). The crude severity of critical illness at ICU admission did not change over time. The ICU survival rate was 77.4%, without any significant changes over the study period. Among the 1279 patients with complete follow-up, the 1-year survival rate was 33.2%. Independent determinants of ICU mortality were metastatic disease, cancer in progression under treatment, admission for specific complications and the extent of organ failures (invasive and non-invasive ventilation, inotropes/vasopressors, renal replacement therapy and SOFA score). One-year mortality in ICU-survivors was independently associated with lung cancer, metastatic disease, cancer in progression under treatment, admission for specific complications and decision to forgo life-sustaining therapies. Conclusion Advances in the management and the prognosis of solid malignancies substantially modified the ICU admission patterns of cancer patients. Despite underlying advanced and often metastatic malignancies, encouraging short-term and long-term outcomes should help changing the dismal perception of critically ill cancer patients.

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Hepatic dysfunction impairs prognosis in critically ill patients with hematological malignancies: A post-hoc analysis of a prospective multicenter multinational dataset

Journal of Critical Care ◽

10.1016/j.jcrc.2020.11.023 ◽

2021 ◽

Vol 62 ◽

pp. 88-93

Author(s):

Magali Bisbal ◽

Michael Darmon ◽

Colombe Saillard ◽

Vincent Mallet ◽

Charlotte Mouliade ◽

...

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Hematological Malignancies ◽

Hepatic Dysfunction ◽

Post Hoc Analysis ◽

Post Hoc

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Effect of Vitamin D Supplementation on Survival of Digestive Tract Cancer Patients with Low Bioavailable 25-Hydroxyvitamin D Levels: A Post Hoc Analysis of the AMATERASU Randomized Clinical Trial

Cancers ◽

10.3390/cancers12020347 ◽

2020 ◽

Vol 12 (2) ◽

pp. 347 ◽

Cited By ~ 2

Author(s):

Mitsuyoshi Urashima ◽

Mai Okuyama ◽

Taisuke Akutsu ◽

Hironori Ohdaira ◽

Mutsumi Kaji ◽

...

Keyword(s):

Vitamin D ◽

Cancer Patients ◽

Digestive Tract ◽

Vitamin D Supplementation ◽

Digestive Tract Cancer ◽

Post Hoc Analysis ◽

Hydroxyvitamin D ◽

Tract Cancer ◽

25 Hydroxyvitamin D ◽

Post Hoc

Vitamin D has been shown to suppress the growth of cancer cells. Cancer cells are believed to take up bioavailable 25-hydroxyvitamin D (25[OH]D) (i.e., not bound to vitamin-D-binding protein (DBP)) more efficiently than DBP-bound 25(OH)D. Our aim was to use this bioavailable 25(OH)D, rather than total 25(OH)D, as a biomarker of vitamin D deficiency to investigate whether vitamin D supplementation improves the relapse-free survival (RFS) of patients with digestive tract cancer from the esophagus to the rectum by conducting a post hoc analysis of the AMATERASU trial (UMIN000001977). The bioavailable 25(OH)D levels were calculated via an equation using data of serum total 25(OH)D, albumin, and DBP levels, and DBP genotypes (rs7041 and rs4588). We estimated bioavailable 25(OH) levels in 355 patients. In a subgroup of patients with low bioavailable 25(OH)D levels (<median) (n = 177), 5 year RFS was 77% in the vitamin D group vs. 58% in the placebo group (hazard ratio, 0.54; 95% confidence interval, 0.31–0.95; p = 0.03), whereas no significant difference was seen in a subgroup of patients with high bioavailable 25(OH)D levels (p for interaction = 0.046). We hypothesize that vitamin D supplementation may be effective in improving RFS among digestive tract cancer patients with low bioavailable 25(OH)D levels.

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