Body composition in older acute stroke patients after treatment with individualized, nutritional supplementation while in hospital.

BACKGROUND: Individualized, nutritional support reduced undernutrition among older stroke patients and improved quality of life in our recent randomized, controlled trial. Weight control thus seems to be important after stroke, and methods for monitoring nutritional status need to be simple and non-invasive. Here we aimed to assess if the nutritional intervention altered body composition in men and women in this study cohort, and also to examine the correlation between the methods for assessing body-, fat- and fat-free mass. METHODS: Acute stroke patients > 65 years at nutritional risk were randomized to either individualized, nutritional treatment with energy- and protein rich supplementation (intervention, n = 58) or routine, nutritional care (control, n = 66) while in hospital. Body composition was assessed with anthropometry and bioelectrical impedance. The follow-up period was three months. RESULTS: During the first week while in hospital, weight loss was smaller in the intervention group compared with the controls (P = 0.013). After three months weight- and fat loss were significant in both men and women. Whereas no significant differences were found in changes in body composition between the male study groups, in the women both weight loss (P = 0.022) and fat loss (P = 0.005) was smaller in the intervention group compared with the controls. A high correlation (r = 0.87) between mid upper arm circumference (MUAC) and body mass index (BMI) was found. CONCLUSIONS: Individualized nutritional support to older stroke patients in hospital was beneficial for maintaining an adequate body mass and body composition the first week and seemed to have a preventive effect on fat loss among women, but not among men after three months. Measurement of MUAC may be used in the assessment of nutritional status when BMI cannot be obtained. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, number NCT00163007.

Clinical characterization of colitis arising from anti-PD-1 based therapy.

Colitis is a frequent, clinically-significant immune-related adverse event caused by anti-programmed death-1 (PD-1). The clinical features, timing, and management of colitis with anti-PD-1-based regimens are not well-characterized. Patients with advanced melanoma that received either anti-PD-1 monotherapy ("monotherapy") or combined with ipilimumab ("combination therapy") were screened from 8 academic medical centers, to identify those with clinically-relevant colitis (colitis requiring systemic steroids). Of 1261 patients who received anti-PD-1-based therapy, 109 experienced colitis. The incidence was 3.2% (30/937) and 24.4% (79/324) in the monotherapy and combination therapy cohorts, respectively. Patients with colitis from combination therapy had significantly earlier symptom onset (7.2 weeks vs 25.4 weeks, p < 0.0001), received higher steroid doses (median prednisone equivalent 1.5 mg/kg vs 1.0 mg/kg, p = 0.0015) and experienced longer steroid tapers (median 6.0 vs 4.0 weeks, p = 0.0065) compared to monotherapy. Infliximab use and steroid-dose escalation occurred more frequently in the combination therapy cohort compared to monotherapy. Nearly all patients had resolution of their symptoms although one patient died from complications. Anti-PD-1 associated colitis has a variable clinical presentation, and is more frequent and severe when associated with combination therapy. This variability in checkpoint-inhibitor associated colitis suggests that further optimization of treatment algorithms is needed.

[Nutrition for elderly acute stroke patients]. / Ernaering til eldre med akutt hjerneslag.

BACKGROUND: Elderly people have an increased risk of malnutrition due to biological and physiological changes and underlying disease. Almost 90% of the stroke patients are older than 65 years, and the consequences of acute stroke may lead to additional nutritional problems. This paper reviews nutritional therapy for stroke patients. MATERIAL AND METHOD: PubMed was searched (non-systematically) for prospective cohort studies of occurrence, diagnostics and consequences of undernutrition in stroke patients. Randomized trials were examined to identify clinical effects of oral protein and energy supplements or tube feeding on nutritional status and intake, functional status, infections, length of stay, quality of life and mortality. RESULTS: 8-35% of stroke patients are undernourished. Body weight is one of the most important parameters for assessment of nutritional status. Dysphagia occurs in up to 80% of patients with acute stroke and increases the risk of undernutrition, which again leads to prolonged length of stay, reduced functional status and poorer survival. Early nasogastric tube feeding does not increase the risk of pneumonia and may improve survival after six months. Oral supplements lead to a significantly improved nutritional intake in undernourished stroke patients, as well as improved nutritional status and survival in undernourished elderly. INTERPRETATION: Nutritional treatment can improve the clinical outcome after an acute stroke, provided that there are good procedures for follow-up and monitoring of the treatment.

Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis.

Importance: Immune checkpoint inhibitors (ICIs) are now a mainstay of cancer treatment. Although rare, fulminant and fatal toxic effects may complicate these otherwise transformative therapies; characterizing these events requires integration of global data. Objective: To determine the spectrum, timing, and clinical features of fatal ICI-associated toxic effects. Design, Setting, and Participants: We retrospectively queried a World Health Organization (WHO) pharmacovigilance database (Vigilyze) comprising more than 16 000 000 adverse drug reactions, and records from 7 academic centers. We performed a meta-analysis of published trials of anti-programmed death-1/ligand-1 (PD-1/PD-L1) and anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) to evaluate their incidence using data from large academic medical centers, global WHO pharmacovigilance data, and all published ICI clinical trials of patients with cancer treated with ICIs internationally. Exposures: Anti-CTLA-4 (ipilimumab or tremelimumab), anti-PD-1 (nivolumab, pembrolizumab), or anti-PD-L1 (atezolizumab, avelumab, durvalumab). Main Outcomes and Measures: Timing, spectrum, outcomes, and incidence of ICI-associated toxic effects. Results: Internationally, 613 fatal ICI toxic events were reported from 2009 through January 2018 in Vigilyze. The spectrum differed widely between regimens: in a total of 193 anti-CTLA-4 deaths, most were usually from colitis (135 [70%]), whereas anti-PD-1/PD-L1-related fatalities were often from pneumonitis (333 [35%]), hepatitis (115 [22%]), and neurotoxic effects (50 [15%]). Combination PD-1/CTLA-4 deaths were frequently from colitis (32 [37%]) and myocarditis (22 [25%]). Fatal toxic effects typically occurred early after therapy initiation for combination therapy, anti-PD-1, and ipilimumab monotherapy (median 14.5, 40, and 40 days, respectively). Myocarditis had the highest fatality rate (52 [39.7%] of 131 reported cases), whereas endocrine events and colitis had only 2% to 5% reported fatalities; 10% to 17% of other organ-system toxic effects reported had fatal outcomes. Retrospective review of 3545 patients treated with ICIs from 7 academic centers revealed 0.6% fatality rates; cardiac and neurologic events were especially prominent (43%). Median time from symptom onset to death was 32 days. A meta-analysis of 112 trials involving 19 217 patients showed toxicity-related fatality rates of 0.36% (anti-PD-1), 0.38% (anti-PD-L1), 1.08% (anti-CTLA-4), and 1.23% (PD-1/PD-L1 plus CTLA-4). Conclusions and Relevance: In the largest evaluation of fatal ICI-associated toxic effects published to date to our knowledge, we observed early onset of death with varied causes and frequencies depending on therapeutic regimen. Clinicians across disciplines should be aware of these uncommon lethal complications.

Baseline oxidative defense and survival after 5-7 years among elderly stroke patients at nutritional risk: Follow-up of a randomized, nutritional intervention trial.

BACKGROUND & AIMS: Patients at nutritional risk are particularly vulnerable to adverse outcomes of acute stroke. We previously found that increased energy- and protein intervention improved short-term survival among stroke patients with the highest baseline antioxidant capacity. We now examined survival of these patients after 5-7 years. METHODS: We studied 165 patients >65 years admitted to hospital for acute stroke and enrolled in a randomized nutritional intervention study in 2005-2007. Cox regression analysis was used to estimate the associations between all-cause mortality (through 2011) and baseline plasma levels of antioxidant markers (glutathione reducing capacity, alpha-tocopherol, vitamin C and total carotenoids). RESULTS: We found no significant difference (P = 0.86) in survival between the intervention and control group. Among the tested antioxidant markers, plasma levels above the median for total carotenoids were associated with reduced risk of death in the intervention group (adjusted hazard ratio, 0.29; 95% confidence interval, 0.12-0.71). CONCLUSIONS: Hospitalized patients that received enhanced dietary energy- and protein after acute stroke and with baseline plasma total carotenoids above median level, had reduced risk of death after 5-7 years. Further trials testing intervention with diets rich in antioxidants are warranted.

Individual, nutritional support prevents undernutrition, increases muscle strength and improves QoL among elderly at nutritional risk hospitalized for acute stroke: a randomized, controlled trial.

BACKGROUND & AIMS: Undernutrition after an acute stroke increases the risk of poor outcome. We wanted to examine the effect of individualized, nutritional support on weight loss and functional outcomes in stroke patients. METHODS: Acute stroke patients at nutritional risk were randomized to either individualized, nutritional care or routine care while in hospital. Patients in the intervention group received an individualized treatment plan aiming to prevent weight loss. In accordance with routine care, the controls did not have such a treatment plan. Patients were reviewed at follow-up after three months. Primary outcome measure was the percentage of patients with weight loss ≥5%. Secondary outcomes measures were quality of life (QoL), handgrip strength and length of hospital stay. This trial is registered with ClinicalTrials.gov, number NCT00163007. RESULTS: At follow-up, 20.7% of the intervention group (n = 58) lost ≥5% weight compared with 36.4% in the control group (n = 66) (P = 0.055). The intervention group had a significantly higher increase in QoL score (P = 0.009) and in handgrip strength (P = 0.002). There was no difference in length of hospital stay. CONCLUSIONS: Individualized, nutritional treatment strategy can prevent clinically significant weight loss and improve QoL in elderly acute stroke patients at nutritional risk.