Predictors of Long-term Mortality after Hospitalization for Severe COPD Exacerbation.

Introduction:Chronic obstructive pulmonary disease (COPD) is a global health problem resulting in significant morbidity. Acute exacerbation of COPD (AECOPD) is a severe complication associated with increased short- and long-term mortality. Identifying predictors of long-term mortality after a severe AECOPD may improve management and long-term outcome of this disease. Materials and methods:A two-year prospective cohort study was undertaken in an academical medical center between 2016 and 2018. Patients with severe AECOPD who required non-invasive ventilation (NIV) were included. Baseline characteristics at inclusion, comorbidities (kidney dysfunction, left heart disease, diabetes), number of prior episodes of AECOPD and indication for long-term oxygen therapy (LTOT) or non-invasive ventilation (LTNIV) were recorded. Patients were monitored for a two-year period after initial admission. Outcomes were six-month, one-year and two-year mortality, irrespective of cause. Outcomes:51 patients (31 male, mean age 68.1) were included in the study. Mortality rates at six months, one year and two years were 20, 26 and 36%, respectively. Patients receiving LTOT and LTNIV at discharge had lower mortality at two years versus patients with no indication for LTOT and LTNIV at discharge. Absence of LTOT increased six-month mortality (OR .2, 95% CI, .04 to .90) and one-year mortality (p<.05). FEV1 and BMI were also correlated with long-term mortality in univariate analysis, p<.05. Age, number of prior episodes of AECOPD or the presence of comorbidities had no influence on long-term mortality. Conclusion:After an episode of severe AECOPD, LTOT is associated with lower long-term mortality when compared to patients with no severe hypoxemia at discharge. A decreased lung function and body mass index increase long-term mortality.

Overlapping regional distribution of CCK and TPPII mRNAs in Cynomolgus monkey brain and correlated levels in human cerebral cortex (BA 10).

UNLABELLED: Tripeptidyl peptidase II (TPPII) is a high molecular weight exopeptidase important in inactivating extracellular cholecystokinin (CCK). Our aims were to study the anatomical localization of TPPII and CCK mRNA in the Cynomolgus monkey brain as a basis for a possible functional anatomical connection between enzyme (TPPII) and substrate (CCK) and examine if indications of changes in substrate availability in the human brain might be reflected in changes of levels of TPPII mRNA. METHODS: mRNA in situ hybridization on postmortem brain from patients having had a schizophrenia diagnosis as compared to controls and on monkey and rat brain slices. RESULTS: overlapping distribution patterns of mRNAs for TPPII and CCK in rat and monkey. High amounts of TPPII mRNA are seen in the neocortex, especially in the frontal region and the hippocampus. TPPII mRNA is also present in the basal ganglia and cerebellum where CCK immunoreactivity and/or CCK B receptors have been found in earlier studies, suggesting presence of CCK-ergic afferents from other brain regions. Levels of mRNAs for CCK and TPPII show a positive correlation in postmortem human cerebral cortex Brodmann area (BA) 10. TPPII mRNA might be affected following schizophrenia. DISCUSSION: overall TPPII and CCK mRNA show a similar distribution in rat and monkey brain, confirming and extending earlier studies in rodents. In addition, correlated levels of TPPII and CCK mRNA in human BA 10 corroborate a functional link between CCK and TPPII in the human brain.

Pentagastrin test for anxiety--psychophysiology and personality.

RATIONALE: CCK(B) receptor agonists such as pentagastrin or CCK(4) have anxiogenic panic-like effects in humans. Our previous findings are in agreement with a relationship between C-peptide plasma levels (as a measure of insulin release) and sensitivity to psychotropic activation by CCK(B) receptor stimulation. OBJECTIVES: Our present aim was to study the transient humoral, physiological and psychotropic effects of pentagastrin bolus injection and whether personality might affect the outcome. METHODS: Pentagastrin was given in bolus i.v. injections to healthy volunteers at increasing doses (0.003, 0.012, 0.05 and 0.2 microg/kg). Physiological parameters were recorded before and during each pentagastrin challenge and humoral variables described previously were included in the analyzes. Subjects rated the discomfort following pentagastrin administration on the state anxiety and discomfort scale (SADS). The Karolinska scale of personality (KSP), anxiety sensitivity index (ASI) and Hamilton anxiety scale (HAS) were used to characterize the subjects before the test. RESULTS: Galvanic skin response (GSR) and heart rate (HR) were significantly increased within 1 min following 0.2 microg/kg pentagastrin, the GSR increase correlating negatively to the C-peptide increase and positively to ratings on SADS. Even the lower dose (0.05 microg/kg pentagastrin) induced a significant increase in GSR. ASI measures correlated weakly to the increase in ratings on SADS following 0.05 microg/kg and 0.2 microg/kg pentagastrin. CONCLUSIONS: We found correlations between psychophysiology, humoral response and subjective ratings following pentagastrin administration. CCK(B) receptor stimulation might reveal phenotype properties predictive of anxiety-related traits, measurable through serum levels of C-peptide. Furthermore, our results support the predictive value of ASI for fearfulness.

Anxiogenic effects of the CCK(B) agonist pentagastrin in humans and dose-dependent increase in plasma C-peptide levels.

RATIONALE: Cholecystokinin type B (CCK(B)) receptor agonists such as pentagastrin or CCK-4 have panic-like anxiogenic effects in humans. It has also been shown that CCK-4 can stimulate insulin release and thus C-peptide release from pancreatic islet cells. Combined, these mechanisms may provide a basis for a bioassay. OBJECTIVES: Our aim was to study if a pentagastrin bolus injection evokes insulin release (as measured by C-peptide) and if the levels of C-peptide correlate to the anxiogenic effect of pentagastrin. METHODS: Pentagastrin was given in bolus IV injections to healthy volunteers at increasing doses (0.003, 0.012, 0.05 and 0.2 microg/kg). RESULTS: A significant increase in the plasma level of C-peptide was observed 2-4 min after the highest dose of pentagastrin. This increase was accompanied by a transient panic-like anxiety within 2 min following pentagastrin, measured using a state anxiety scale. Also, 0.05 microg/kg pentagastrin gave a minor but significant subjective discomfort at the same time interval. The basal plasma level of C-peptide preceding the pentagastrin injection showed a positive correlation to the intensity of the subsequent pentagastrin-induced panic-like anxiety as rated on the state anxiety scale. In addition, basal plasma levels of cortisol were positively correlated to the subsequent pentagastrin-induced increase in plasma C-peptide levels. CONCLUSIONS: Our results imply a possible relationship between insulin/C-peptide release and sensitivity to psychotropic activation by CCK(B) receptor stimulation. Furthermore, we postulate that both basal and pentagastrin-induced plasma levels of C-peptide may possess characteristic phenotype properties for anxiety related traits.