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Introduction Immobilization by casting induces disuse muscle atrophy (DMA). Methods Using wild type (WT) and caspase-3 knockout (KO) mice, we evaluated the effect of caspase-3 on muscle mass, apoptosis and inflammation during DMA. Results Caspase-3 deficiency significantly attenuated muscle mass decrease [gastrocnemius: 28 ± 1% in KO vs. 41 ± 3% in WT; soleus: 47 ± 2% in KO vs. 56 ± 2% in WT; (P < 0.05)] and gastrocnemius twitch tension decrease (23 ± 4% in KO vs. 36 ± 3% in WT, P < 0.05) at day 14 in immobilized versus contralateral hindlimb. Lack of caspase-3 decreased immobilization-induced increased apoptotic myonuclei (3.2-fold) and macrophage infiltration (2.2-fold) in soleus muscle and attenuated increased monocyte chemoattractant protein-1 mRNA expression (2-fold in KO vs. 18-fold in WT) in gastrocnemius. Conclusion Caspase-3 plays a key role in DMA and associated decreased tension, presumably by acting on the apoptosis and inflammation pathways.

Skeletal muscle wasting is an exacerbating factor in the prognosis of critically ill patients. Using a systemic burn injury model in mice, we have established a role of autophagy in the resulting muscle wasting that is distant from the burn trauma. We provide evidence that burn injury increases the autophagy turnover in the distal skeletal muscle by conventional postmortem tissue analyses and by a novel in vivo microscopic method using an autophagy reporter gene (tandem fluorescent LC3). The effect of tadalafil, a phosphodiesterase 5 inhibitor (PDE5I), on burn-induced skeletal muscle autophagy is documented and extends our published results that PDE5Is attenuates muscle degeneration in a muscular dystrophy model. We also designed a translational experiment to examine the impact of PDE5I on whole body and demonstrated that PDE5I administration lessened muscle atrophy, mitigated microcirculatory disturbance, and improved the survival rate after burn injury.

Purpose In the critically ill, hospital-acquired bloodstream infections (HA-BSI) are associated with significant mortality. Granular data are required for optimizing management, and developing guidelines and clinical trials. Methods We carried out a prospective international cohort study of adult patients (≥ 18 years of age) with HA-BSI treated in intensive care units (ICUs) between June 2019 and February 2021. Results 2600 patients from 333 ICUs in 52 countries were included. 78% HA-BSI were ICU-acquired. Median Sequential Organ Failure Assessment (SOFA) score was 8 [IQR 5; 11] at HA-BSI diagnosis. Most frequent sources of infection included pneumonia (26.7%) and intravascular catheters (26.4%). Most frequent pathogens were Gram-negative bacteria (59.0%), predominantly Klebsiella spp. (27.9%), Acinetobacter spp . (20.3%), Escherichia coli (15.8%), and Pseudomonas spp . (14.3%). Carbapenem resistance was present in 37.8%, 84.6%, 7.4%, and 33.2%, respectively. Difficult-to-treat resistance (DTR) was present in 23.5% and pan-drug resistance in 1.5%. Antimicrobial therapy was deemed adequate within 24 h for 51.5%. Antimicrobial resistance was associated with longer delays to adequate antimicrobial therapy. Source control was needed in 52.5% but not achieved in 18.2%. Mortality was 37.1%, and only 16.1% had been discharged alive from hospital by day-28. Conclusions HA-BSI was frequently caused by Gram-negative, carbapenem-resistant and DTR pathogens. Antimicrobial resistance led to delays in adequate antimicrobial therapy. Mortality was high, and at day-28 only a minority of the patients were discharged alive from the hospital. Prevention of antimicrobial resistance and focusing on adequate antimicrobial therapy and source control are important to optimize patient management and outcomes. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-022-06944-2.

Background: There is a possibility that physiological changes in respiratory mechanics

Previous models of disuse have invariably used surgical methods require repetitive plaster casts applications. A method of disuse atrophy that does not require repetitive application is described. A modified plastic pipette tubing was applied to one hindlimb from thigh to foot resulting in immobilization of knee in extension and ankle in plantar flexion position. This method resulted in loss of soleus muscle mass to 11, 22, 39, and 45% at 3, 7, 14 and 21 days, respectively, in association with a significant decrease of tibialis twitch (25%) and tetanic tensions (26%) at 21 days, compared to contralateral side and/or sham immobilized controls. Immunohistochemical analysis of soleus using fluorescent α-bungarotoxin revealed a significant increase in the number of synapses per unit area (818+31 vs 433+16/mm2) and increase in muscle fibers per unit area (117 vs 83/mm2) most likely related to atrophy of muscle fibers bringing synapses closer. A three fold increase in alpha7 acetylcholine receptor (α7AChR) protein expression along with increased expression of α1AChR subunit on immobilized vs contralateral side was observed. The physiology and pharmacology of the novel finding of upregulation of α7AChRs with disuse requires further study.

Atrial natriuretic peptide infusion did not show a renoprotective effect or cost-saving effect in the treatment of cardiac surgery-associated AKI.

We used target-controlled infusion (TCI) of dexmedetomidine (DEX) for awake intubation under sedation in 5 patients who had a risk of pulmonary aspiration or difficult airway. Dexmedetomidine level was escalated stepwise until the patients developed tolerance to laryngoscopy. The target DEX concentrations at the time of intubation were 2.10-5.95 ng/ml and were higher than those clinically used for sedation in the intensive care unit (ICU). Chin lift was applied in 1 case, and therefore no assisted ventilation was required and pulse oxygen saturation was maintained at >98% throughout the procedure. Simple pharmacological interventions for blood pressure changes induced by increased target plasma DEX concentrations were needed in 4 cases. However, hemodynamics was stable, and no cardiovascular drug was needed after tracheal intubation. Conditions at laryngoscopy were excellent in all cases, and conditions at tracheal intubation were good except in 1 case. Reflex to intubation was preserved in all cases, and coughing was observed in all cases. The patients had no memory of discomfort and/or intubation. Although further investigations are needed, this method may be useful for awake intubation under sedation.