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The anabolic effects of insulin-like growth factor-I (IGF-I) may involve a decrease of hepatic nitrogen (N) clearance, but this has never been studied in humans. Patients with cirrhosis have low levels of IGF-I and might benefit from IGF-I therapy. Conversely, a possible decrease in hepatic N clearance by IGF-I could increase the risk of hepatic encephalopathy. To examine the effects of 1-week IGF-I administration on the functional hepatic N clearance (FHNC), viz. the linear slope of the relationship between blood-α-amino-N concentration and urea-N synthesis rate as controlled by an infusion of alanine. A randomized sequence-crossover placebo-controlled study. Eight healthy volunteers and eight patients with alcoholic cirrhosis received injections of saline or IGF-I twice daily (50 μg/kg) for 7 days. IGF-I levels at baseline were lower in the patients than those in the controls. The IGF-I treatment normalized patient levels and caused an increase in the controls to supra-physiological levels. FHNC was lower in patients compared with healthy subjects (23.0 vs 36.5 L/h, P=0.03). IGF-I treatment reduced FHNC by 30% in healthy subjects (from 36.5 to 25.7 L/h, P=0.02), whereas no effect was found in the patients. IGF-I downregulates urea synthesis in normal subjects. This may be part of the explanation behind the anabolic effects of IGF-I. The normalization of IGF-I in cirrhosis patients without an effect on urea synthesis implies that the patients were resistant to IGF-I with regard to reduction of hepatic amino-N elimination. IGF-I treatment of cirrhosis patients evidently carries no risk of N accumulation. [ABSTRACT FROM AUTHOR]

Nielsen SS, Grøfte T, Tygstrup N, Vilstrup H. Effect of lipopolysaccharide onin vivoand genetic regulation of rat urea synthesis.Liver International 2005: 25: 177–183.© Blackwell Munksgaard 2005The acute phase response causes a negative nitrogen balance. It is unknown whether this involves regulation of hepatic urea synthesis.We examined thein vivocapacity of urea nitrogen synthesis (CUNS), mRNA levels of urea cycle enzyme genes and galactose elimination capacity (GEC) during moderate and severe acute phase response induced by low- and high-dose lipopolysaccharide (LPS) in rats.Low-dose LPS doubled CUNS (P<0.05), decreased the mRNA level of the rate-limiting urea cycle enzyme (arginino succinate synthetase (ASS) by 26% (P<0.05) and did not change GEC. High-dose LPS did not change CUNS, decreased the mRNA level of the flux-generating enzyme carbamoyl phosphate synthetase (CPS) by 11% (P<0.05) and the rate-limiting urea cycle enzyme (ASS) by 27% (P<0.05) and almost halved GEC (P<0.05).The moderate acute phase response up-regulatedin vivourea synthesis but had the opposite effect on gene level. The severe acute phase response decreased the functional liver massthatattenuated the increase in urea synthesis. [ABSTRACT FROM AUTHOR]

In contrast to GH, which induces hepatic and extra-hepatic insulin resistance, IGF-1 suppresses insulin secretion and results in enhanced insulin sensitivity. Due to significant sequence homology with insulin the latter effect may, however, reflect a cross-reaction of IGF-1 with insulin receptors rather than a direct effect of IGF-1 per se. To address this question and to determine whether the metabolic effects of IGF-1 are altered by a concomitant increase in GH, 8 healthy individuals were studied following either saline, IGF-1 (100 µg/kg) or combined IGF-1 and GH (0.1 IU/kg) injections. Following one-week treatment glucose disappearance (Rd) and endogenous glucose production (EGP) were measured prior to and during a 5-h hyperinsulinaemic (50 mU/m²/min) euglycaemic clamp. Glycogen synthesis was determined using indirect calorimetry. IGF-1 therapy resulted in an increase from baseline in total (200±19 vs. 500±50 µg/l; P<0.01) and free (0.23±0.02 vs. 0.61±0.06µg/l; P<0.01) IGF-1 concentrations, which further increased during combined GH and IGF-1 injections (total: 1013±113 µg/l; P<0.01, free: 1.09±0.11 µg/l; P<0.01). IGF-1 treatment resulted in lower glucose (P=0.06), insulin (P<0.01) and C-peptide (P<0.01) concentrations. These effects were reversed by GH. Energy expenditure (P<0.01) and lipid oxidation (P<0.05) were increased by IGF-1, whereas carbohydrate oxidation was unchanged (P=.84). Insulin action was unaltered by IGF-1 (P=0.86), but decreased during combined IGF-1 and GH treatment (P<0.01) due to hepatic and extra-hepatic insulin resistance. Rd was impaired as a result of a reduction in glycogen synthesis (P<0.01). The present experiments demonstrate that IGF-1 exerts its effects though suppression of insulin secretion, which results in lower insulin levels and increased lipid oxidation. These results may suggest a homeostatic mechanism by which carbohydrate fuel stores are preserved. Enhanced insulin action may result from cross-reaction with insulin receptors, but does not appear to be a primary effect of IGF-1 in healthy individuals. [ABSTRACT FROM AUTHOR]

Importance: Supplemental oxygen is ubiquitously used in patients with COVID-19 and severe hypoxemia, but a lower dose may be beneficial., Objective: To assess the effects of targeting a Pao2 of 60 mm Hg vs 90 mm Hg in patients with COVID-19 and severe hypoxemia in the intensive care unit (ICU)., Design, Setting, and Participants: Multicenter randomized clinical trial including 726 adults with COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 11 ICUs in Europe from August 2020 to March 2023. The trial was prematurely stopped prior to outcome assessment due to slow enrollment. End of 90-day follow-up was June 1, 2023., Interventions: Patients were randomized 1:1 to a Pao2 of 60 mm Hg (lower oxygenation group; n = 365) or 90 mm Hg (higher oxygenation group; n = 361) for up to 90 days in the ICU., Main Outcomes and Measures: The primary outcome was the number of days alive without life support (mechanical ventilation, circulatory support, or kidney replacement therapy) at 90 days. Secondary outcomes included mortality, proportion of patients with serious adverse events, and number of days alive and out of hospital, all at 90 days., Results: Of 726 randomized patients, primary outcome data were available for 697 (351 in the lower oxygenation group and 346 in the higher oxygenation group). Median age was 66 years, and 495 patients (68%) were male. At 90 days, the median number of days alive without life support was 80.0 days (IQR, 9.0-89.0 days) in the lower oxygenation group and 72.0 days (IQR, 2.0-88.0 days) in the higher oxygenation group (P = .009 by van Elteren test; supplemental bootstrapped adjusted mean difference, 5.8 days [95% CI, 0.2-11.5 days]; P = .04). Mortality at 90 days was 30.2% in the lower oxygenation group and 34.7% in the higher oxygenation group (risk ratio, 0.86 [98.6% CI, 0.66-1.13]; P = .18). There were no statistically significant differences in proportion of patients with serious adverse events or in number of days alive and out of hospital., Conclusion and Relevance: In adult ICU patients with COVID-19 and severe hypoxemia, targeting a Pao2 of 60 mm Hg resulted in more days alive without life support in 90 days than targeting a Pao2 of 90 mm Hg., Trial Registration: ClinicalTrials.gov Identifier: NCT04425031.

Purpose: The purpose of this study was to examine whether the addition of brain natriuretic peptide measurement to the routine diagnostic work-up by prehospital critical care team physicians improves triage in patients with severe dyspnoea., Methods: Prehospital critical care team physicians randomly assigned patients older than 18 years with severe dyspnoea to routine diagnostic work-up or diagnostic work-up with incorporated point-of-care N-terminal pro-brain natriuretic peptide (NT-proBNP) measurement. The primary endpoint was the proportion of patients with dyspnoea of primary cardiac origin triaged directly to a department of cardiology., Results: A total of 747 patients were randomly assigned and 711 patients consented to participate, 350 were randomly assigned to the NT-proBNP group and 361 to the routine work-up group. NT-proBNP was measured in 90% (315/350) of patients in the NT-proBNP group and in 19% (70/361) of patients in the routine work-up group. There was no difference in the proportion of patients with dyspnoea of primary cardiac origin triaged directly to a department of cardiology between the NT-proBNP group and the routine work-up group (75% vs. 69%, P=0.22) in the intention-to-treat analysis. Sensitivity analysis according to the de facto diagnostics performed showed results consistent with this. No differences in hospital length of stay, intensive care unit admission rates or mortality between the NT-proBNP group and the routine work-up group were observed., Conclusion: Routine supplementary point-of-care measurement of NT-proBNP in patients with severe dyspnoea did not improve triage of patients with dyspnoea primarily caused by heart disease. ClinicalTrials.gov identifier NCT02050282.

A 68-year-old man suffered from anaphylaxis and cardiac arrest following wasp sting. He was resuscitated and taken to hospital where he later died from anoxic brain injury. Previously he had had an anaphylactic reaction to wasp venom but did not carry his auto-adrenaline-injector. Patients with anaphylaxis due to insect venom must be referred to allergological investigations. Furthermore, they should be educated in recognition and handling of anaphylaxis and they should be provided with a management plan and an auto-adrenaline-injector along with a thorough instruction on the appropriate use.

Women with breast implants constitute a growing proportion of the female population in Denmark. Thoracic trauma can result in a different pathology and clinical presentation compared with women without breast implants. This case report illustrates an atypical manifestation of pneumothorax in a breast augmented woman who suffered thoracic trauma with communication between the thorax cavity and the space around the implant.

Severe heart failure is a significant risk factor in anaesthesia. We present a case of circulatory collapse and cardiac arrest during routine anaesthesia of a younger man, caused by occult dilated cardiomyopathy. We propose preoperative focus assessed transthoracic echocardiography as useful in detecting cardiopulmonary pathology.

Insulin is secreted as a series of punctuated secretory bursts superimposed on variable basal insulin release. The contribution of these secretory bursts to overall insulin secretion has been estimated on the basis of peripheral vein sampling in humans to encompass > or =75% of overall insulin release. A similar contribution of the pulsatile mode of release was inferred in a canine model by use of portal vein sampling. The primary regulation of insulin secretion is through perturbation of the mass and frequency of these secretory bursts. The mode of delivery of insulin into the circulation seems important for insulin action; therefore, physiological conditions that alter the pattern of insulin release may affect insulin action through this mechanism. Transhepatic intraportal shunt in humans may provide access to portal vein samples, thus potentially improving the sensitivity of detecting and quantitating the frequency, mass, and amplitude of secretory bursts along with basal release and the regularity of these variables. To establish the insulin-secretory mechanism in nondiabetic humans by the use of portal vein sampling, we here assessed the mass, frequency, amplitude, and overall contribution of pulsatile insulin secretion by deconvolution analysis of portal vein insulin profiles. We find that, in nondiabetic humans fasted overnight, the portal vein insulin concentration oscillates at a periodicity of 4.1 +/- 0.2 min/pulse and with secretory peak amplitudes averaging 660% of basal (interpulse) release. The frequency was confirmed by spectral and autocorrelation analyses. The punctuated insulin-secretory bursts partially overlap and are responsible for the majority (70 +/- 4%) of insulin release. After ingestion of a mixed meal, the insulin release was increased through amplification of the secretory burst mass (507 +/- 104 vs. 1,343 +/- 211 pmol x l(-1) x min(-1), P < 0.001), whereas frequency (4.4 +/- 0.2 vs. 4.3 +/- 0.2, P = 0.86) and basal secretion (62 +/- 14 vs. 91 +/- 22 pmol x l(-1) x min(-1), P = 0.33) were unaffected. One subject with diabetes and cirrhosis had a similar insulin-secretory pattern, whereas a subject with insulin-dependent diabetes mellitus and minimal insulin release had preserved pulsatile release. A single subject was entrained to show agreement between entrained frequency and portal vein insulin oscillations. We conclude that insulin release in the human portal vein occurs at a mean periodicity of 4.4 +/- 0.2 min with a high signal-to-noise ratio (pulse amplitude 660% of basal). The impact of noise on the detected high frequency cannot be excluded.