Organ support therapy in the intensive care unit and return to work: a nationwide,register-based cohort study

Purpose

The association between severity of illness and ability to return to work is unclear. Therefore, we investigated return to work and associations with measures of illness severity in ICU survivors.

Methods

We conducted this cohort study using Danish registry data for the period 2005–2014 on ICU patients who were discharged alive from hospital, had an ICU length of stay (LOS) of at least 72 h, were not treated with dialysis before hospital admission and were working prior to admission. We assessed (1) the cumulative incidence (chance) of return to work (2005–2017) and receipt of social benefits after discharge from a hospital stay with ICU admission and (2) the association between organ support therapies (renal replacement therapy, cardiovascular support and mechanical ventilation), and during 2011–2014 SAPS II and ICU LOS, and return to work, using multivariable Cox regression.

Results

Among 5762 ICU survivors, 68% returned to work within 2 years after hospital discharge. Disability and sickness benefits constituted 89% of social benefits among patients not returning to work and 59% among patients withdrawing from work following an initial return to work. Mechanical ventilation (HR 0.70, 95% CI [0.65–0.77]), but not RRT (HR 0.85, 95% CI [0.71–1.02]), cardiovascular support (HR 0.93, 95% CI [0.82–1.07]) and increasing SAPS II, was associated with decreased chance of return to work. Increasing ICU LOS was also associated with a decreased chance of return to work.

Conclusions

The majority of a nationwide cohort of ICU survivors returned to work. Sick leave and receipt of disability pension were common following ICU admission. Mechanical ventilation and longer ICU LOS were associated with reduced chances of return to work.

     

Lesion-Specific and Vessel-Related Determinants of Fractional Flow Reserve Beyond Coronary Artery Stenosis

Objectives

The aims of the present study were: 1) to investigate the contribution of the extent of luminal stenosis and other lesion composition-related factors in predicting invasive fractional flow reserve (FFR); and 2) to explore the distribution of various combinations of morphological characteristics and the severity of stenosis among lesions demonstrating normal and abnormal FFR.

One-year follow-up study of patients with enterochromaffin-like cell carcinoids after treatment with octreotide long-acting release

OBJECTIVE: In a one-year study of 5 patients with chronic atrophic gastritis (CAG), pernicious anaemia (PA), hypergastrinaemia and enterochromaffin-like (ECL) cell tumours, the somatostatin analogue octreotide LAR (long-acting release) in a dose of 20 mg given intramuscularly at monthly intervals had an antiproliferative effect on the ECL cells. The aim of the present study was to follow neuroendocrine (NE) markers in the blood and macroscopic and histopathological changes in the stomach during a 12-month follow-up after discontinuation of octreotide LAR treatment. MATERIAL AND METHODS: Five patients underwent upper gastrointestinal endoscopy at 6 and 12 months' follow-up after octreotide LAR treatment. Biopsies from flat, oxyntic mucosa and from tumours were obtained. Sections were stained with haematoxylin-erythrosin and immunostained for the NE cell marker chromogranin A (CgA). Serum gastrin and CgA were measured every 3 months. RESULTS: The number of visible tumours was unchanged (7) at 12 months' follow-up. One lesion showed carcinoid tumour and the others various degrees of linear and micronodular NE hyperplasia. At the same time-point, biopsies from flat, oxyntic mucosa showed a slightly (non-significant) elevated number of CgA immunoreactive (IR) cells. Serum gastrin increased from 186+/-50 pM (mean+/-SEM) to 603+/-109 pM (normal < 40 pM); p<0.05, and serum CgA increased non-significantly from 25+/-2 ng/ml (normal < 30 ng/ml) to 61+/-11 ng/ml. CONCLUSIONS: During follow-up, slightly elevated levels of serum CgA and CgA IR cells in the oxyntic mucosa, without significant recurrence of ECL cell carcinoids, were observed.     

Evaluation of the causal relationship between crocidolite asbestos-induced lipid peroxidation and toxicity to macrophages

In vitro, crocidolite asbestos toxicity to macrophages is mediated by the production of reactive oxygen metabolites. We examined whether exposure of macrophages to crocidolite asbestos induced lipid peroxidation as measured by the thiobarbituric acid assay. When elicited mouse peritoneal macrophages were exposed to crocidolite, a dose- and time-dependent increase in lipid peroxidation breakdown products accompanied cell death. Superoxide dismutase plus catalase or deferoxamine prevented both lipid peroxidation and loss of viability caused by crocidolite. We tested whether crocidolite-induced lipid peroxidation was causally responsible for cell death. Macrophages were not killed by crocidolite when incubated with 10 mM 3-aminobenzamide. The level of thiobarbituric acid-reactive material was the same, however, for cells incubated with crocidolite in the presence or absence of 3-aminobenzamide. When macrophagaes were pretreated for 24 h with 25 microM vitamin E and then incubated with crocidolite, no thiobarbituric acid-reactive products were detected. Vitamin E, however, did not prevent crocidolite cytotoxicity. These results suggest that exposure of macrophages to crocidolite asbestos produces lipid peroxidation as measured by thiobarbituric acid-reactive products. This reaction, however, is not directly responsible for irreversible injury in this model system.     

The Association Between Serum Calcium Levels and Short-Term Mortality in Patients with Chronic Heart Failure

Background

Patients with chronic heart failure have vulnerable myocardial function and are susceptible to electrolyte disturbances. In these patients, diuretic treatment is frequently prescribed, though it is known to cause electrolyte disturbances. Therefore, we investigated the association between altered calcium homeostasis and the risk of all-cause mortality in chronic heart failure patients.

An altered composition of the microbiome in microscopic colitis is driven towards the composition in healthy controls by treatment with budesonide

Background and aim: Microscopic colitis (MC) is an inflammatory disease of the bowel, hypothetically induced by an immunologic response to a luminal microbial agent. We aimed to characterize the microbiome composition in MC and subtypes collagenous colitis (CC) and lymphocytic colitis (LC) and to identify a possible microbial effect of treatment.

Method: Stool samples were collected from MC patients prior to treatment, at 8 weeks (during treatment) and at 16 weeks (after treatment), and from healthy controls, not receiving treatment, at matched time-points. Microbiome composition was analyzed by sequencing of the 16S and 18S genes. Differences between patients and controls were analyzed by Shannon’s diversity index (mean, standard deviation (SD)) and principal coordinate analysis (PCoA) complemented with a permanova test of UniFrac distances.

Results: Ten LC patients, 10?CC patients and 10 controls were included. By PCoA, the bacterial composition in MC patients differed from controls at baseline (p?=?.02), but not during and after treatment (p?=?.09 and p?=?.33, respectively). At baseline, bacterial diversity was lower in MC patients compared to controls (2.5, SD: 0.5 vs 3.5, SD: 0.3, p?<?.05). Diversity in MC patients increased during (3.0, SD: 0.6) and after treatment and (2.9, SD: 0.5) compared with baseline (p?<?.01). Eukaryotes were detected in fewer samples from MC patients compared with controls (11/20 (55%) vs. 9/10 (90%), p?=?.06) with no effect of treatment.

Conclusion: Microbiome composition is altered in MC patients. During and after treatment with budesonide the microbiome composition in MC patients was driven towards the composition in healthy controls.     

In vitro and in vivo metabolism and detection of 3‐HO‐PCP,a synthetic phencyclidine,in human samples and pooled human hepatocytes using high resolution mass spectrometry

The new psychoactive substance (NPS) 3‐HO‐PCP, a phencyclidine (PCP) analog, was detected in a law enforcement seizure and in forensic samples in Denmark. Compared with PCP, 3‐HO‐PCP is known to be a more potent dissociative NPS, but no toxicokinetic investigations of 3‐HO‐PCP are yet available. Therefore, 3‐HO‐PCP was quantified in in vivo samples, and the following were investigated: plasma protein binding, in vitro and in vivo metabolites, and metabolic targets. All samples were separated by liquid chromatography and analyzed by mass spectrometry. The unbound fraction in plasma was determined as 0.72 ± 0.09. After in vitro incubation with pooled human hepatocytes, four metabolites were identified: a piperidine‐hydroxyl‐and piperidine ring opened N‐dealkyl‐COOH metabolite, and O‐glucuronidated‐ and O‐sulfate‐conjugated metabolites. In vivo, depending on the sample and sample preparation, fewer metabolites were detected, as the O‐sulfate‐conjugated metabolite was not detected. The N‐dealkylated‐COOH metabolite was the main metabolite in the deconjugated urine sample. in vivo analytical targets in blood and brain samples were 3‐HO‐PCP and the O‐glucuronidated metabolite, with 3‐HO‐PCP having the highest relative signal intensity. The drug levels of 3‐HO‐PCP quantified in blood were 0.013 and 0.095 mg/kg in a living and a deceased subject, respectively. The 3‐HO‐PCP concentrations in deconjugated urine in a sample from a living subject and in post‐mortem brain were 7.8 and 0.16 mg/kg, respectively. The post mortem results showed a 1.5‐fold higher concentration of 3‐HO‐PCP in the brain tissue than in the post mortem blood sample.     

Virulence and thrombocyte affectation of two Aspergillus terreus isolates differing in amphotericin B susceptibility

Aspergillus terreus-induced invasive infections exhibit high lethality, partly due to the intrinsic resistance for amphotericin B (AmB). We compared the virulence and pathogenesis of an AmB-resistant isolate of A. terreus (ATR) with that of a rare variant showing enhanced sensitivity for AMB (ATS). The modifications that result in enhanced AmB sensitivity of isolates are not associated with reduced virulence in vivo; instead, the ATS-infected mice died even faster than the ATR-infected animals. Since A. terreus enters the blood stream in most patients and frequently induces thrombosis, we studied a putative correlation between virulence of the two A. terreus isolates and their effect on thrombocytes. Those mice infected with the more virulent ATS isolate had lower thrombocyte numbers and more phosphatidylserine exposure on platelets than ATR-infected mice. In vitro experiments confirmed that ATS and ATR differ in their effect on thrombocytes. Conidia, aleurioconidia and hyphae of ATS were more potent than ATR to trigger thrombocyte stimulation, and thrombocytes adhered better to ATS than to ATR fungal structures. Furthermore, ATS secreted more soluble factors that triggered platelet stimulation than ATR. Thus, it might be suggested that the capacity of a fungal isolate to modulate thrombocyte parameters contributes to its virulence in vivo.