Secondary Sclerosing Cholangitis in Critically Ill Patients Alters the Gut–Liver Axis: A Case Control Study

Secondary sclerosing cholangitis in critically ill patients (SC-CIP) occurs after long-term intensive care treatment. This study aimed to assess the gut–liver axis in SC-CIP. Stool microbiome composition, gut permeability, bacterial translocation and serum bile acid profiles of 18 SC-CIP patients compared to 11 patients after critical illness without liver disease (CIP controls), 21 patients with cirrhosis and 21 healthy controls were studied. 16S rDNA was isolated from stool and sequenced using the Illumina technique. Diamine oxidase, zonulin, soluble CD14 (sCD14) and lipopolysaccharide binding protein were measured in serum and calprotectin in stool. Serum bile acids were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Reduced microbiome alpha diversity and altered beta diversity were seen in SC-CIP, CIP controls and cirrhosis compared to healthy controls. SC-CIP patients showed a shift towards pathogenic taxa and an oralization. SC-CIP, CIP controls and cirrhotic patients presented with impaired gut permeability, and biomarkers of bacterial translocation were increased in SC-CIP and cirrhosis. Total serum bile acids were elevated in SC-CIP and cirrhosis and the bile acid profile was altered in SC-CIP, CIP controls and cirrhosis. In conclusions, observed alterations of the gut–liver axis in SC-CIP cannot solely be attributed to liver disease, but may also be secondary to long-term intensive care treatment

Lipid peroxidation product 4-hydroxynonenal as factor of oxidative homeostasis supporting bone regeneration with bioactive glasses

Bone regeneration is a process of vital importance since fractures of long bones and large joints have a highly deleterious impact on both, individuals and society. Numerous attempts have been undertaken to alleviate this severe medical and social problem by development of novel bioactive materials, among which bioactive glass is the most attractive because of its osteoconductive and osteostimulative properties. Since lipid peroxidation is an important component of systematic stress response in patients with traumatic brain injuries and bone fractures, studies have been undertaken of the molecular mechanisms of the involvement of 4-hydroxynonenal (HNE), an end product of lipid peroxidation, in cellular growth regulation. We found that HNE generated in bone cells grown in vitro on the surfaces of bioactive glasses 45S5 and 13-93. This raises an interesting possibility of combined action of HNE and ionic bioglass dissolution products in enhanced osteogenesis probably through a mitogen-activated protein kinase (MAPK) pathway. While the proposed mechanism still has to be elucidated, the finding of HNE generation on bioglass offers a new interpretation of the osteoinducting mechanisms of bioglass and suggests the possibility of tissue engineering based on manipulations of oxidative homeostasis

Respiratory function and respiratory complications in spinal cord injury: protocol for a prospective, multicentre cohort study in high-income countries

Contains fulltext : 227448.pdf (publisher's version ) (Open Access

Incidence and Risk Factors of Pneumonia in Individuals With Acute Spinal Cord Injury: A Multi-national, Multi-center, Prospective Cohort Study

Objective: To describe the occurrence of pneumonia in individuals with acute spinal cord injury (SCI) and identify its key predictors. Design: Multi-centric, longitudinal cohort study. Setting: 10 specialized SCI rehabilitation units in Europe and Australia. Participants: Eligible were 902 men and women with acute SCI, aged 18 years or older, with cervical or thoracic lesions and not dependent on 24-hour mechanical ventilation; 503 participated in the study (N=503). Interventions: Not applicable. Main Outcome Measures: We assessed demographics and lesion related parameters at study entry, and any pneumonia events throughout inpatient rehabilitation. Respiratory function, decubitus, and urinary tract infections were assessed at 1, 3, and 6 months post injury as well as at discharge from inpatient rehabilitation. Time to event (pneumonia) analyses were done using the Kaplan-Meier method, and potential predictors for pneumonia were analyzed with multivariable survival models. Results: Five hundred three patients with SCI were included, with 70 experiencing at least 1 pneumonia event. 11 participants experienced 2 or more events during inpatient rehabilitation. Most events occurred very early after injury, with a median of 6 days. Pneumonia risk was associated with tetraplegia (hazard ratio [HR]=1.78; 95% confidence interval [CI] 1.00-3.17) and traumatic etiology (HR=3.75; 95% CI 1.30-10.8) American Spinal Injury Impairment Scale (AIS) A (HR=5.30; 95% CI 2.28-12.31), B (HR=4.38; 95% CI 1.77-10.83), or C (HR=4.09; 95% CI 1.71-9.81) lesions. For every 10 cmH 2O increase in inspiratory muscle strength, pneumonia risk was reduced by 13% (HR=0.87; 95% CI 0.78-0.97)

Risk of venous thromboembolism during rehabilitation of patients with spinal cord injury.

Patients with spinal cord injury (SCI) are at risk of thrombosis and bleeding. Data on the risks during rehabilitation are inconsistent, and thromboprophylactic strategies are heterogeneous. We aimed to evaluate the thrombotic risk and bleeding events of SCI patients during rehabilitation.We retrospectively collected hospital record data of 263 consecutive SCI patients admitted at a rehabilitation clinic. 78 patients with acute venous thromboembolism (VTE) at the primary center, without acute trauma or lower extremity paresis, less than one month rehabilitation, or reasons for long-term therapeutic anticoagulation, were excluded. All patients received pharmacologic thromboprophylaxis throughout rehabilitation. Primary endpoint was objectively diagnosed VTE; secondary endpoint was bleeding.Of 185 patients, 162 (88%) were men; mean age was 47.8 years. 94 patients were tetraplegic, 91 paraplegic. During a mean (±SD) time of 5.1±2.1 months, VTE was diagnosed in 8 patients. After excluding five patients with VTE detected within 2 days after admission, the probability of developing VTE after 6 months of rehabilitation was 2% (95% CI 0-4.4%). Only high D-Dimer upon admission was associated with risk of VTE (adjusted HR 2.3, 95% CI 1.4-4.1). Of 24 bleedings, 14 (64%) occurred at the heparin injection site. Two patients had major bleeding and five had clinically relevant non major bleeding.SCI patients are at risk of VTE and bleeding during rehabilitation. Strategies need to be developed to identify these patients in order to initiate adequate anticoagulation. Direct oral anticoagulants, which have a favourable risk-benefit profile and are convenient, should be explored

Risk of venous thromboembolism during rehabilitation of patients with spinal cord injury

Background: Patients with spinal cord injury (SCI) are at risk of thrombosis and bleeding. Data on the risks during rehabilitation are inconsistent, and thromboprophylactic strategies are heterogeneous. We aimed to evaluate the thrombotic risk and bleeding events of SCI patients during rehabilitation. Methods: We retrospectively collected hospital record data of 263 consecutive SCI patients admitted at a rehabilitation clinic. 78 patients with acute venous thromboembolism (VTE) at the primary center, without acute trauma or lower extremity paresis, less than one month rehabilitation, or reasons for long-term therapeutic anticoagulation, were excluded. All patients received pharmacologic thromboprophylaxis throughout rehabilitation. Primary endpoint was objectively diagnosed VTEsecondary endpoint was bleeding. Results: Of 185 patients, 162 (88%) were menmean age was 47.8 years. 94 patients were tetraplegic, 91 paraplegic. During a mean (±SD) time of 5.1±2.1 months, VTE was diagnosed in 8 patients. After excluding five patients with VTE detected within 2 days after admission, the probability of developing VTE after 6 months of rehabilitation was 2% (95% CI 0–4.4%). Only high D-Dimer upon admission was associated with risk of VTE (adjusted HR 2.3, 95% CI 1.4–4.1). Of 24 bleedings, 14 (64%) occurred at the heparin injection site. Two patients had major bleeding and five had clinically relevant non major bleeding. Conclusion: SCI patients are at risk of VTE and bleeding during rehabilitation. Strategies need to be developed to identify these patients in order to initiate adequate anticoagulation. Direct oral anticoagulants, which have a favourable risk-benefit profile and are convenient, should be explored

Comparison of the Values of Basic Fibroblast Growth Factor Determined by an Immunoassay in the Sera of Patients with Traumatic Brain Injury and Enhanced Osteogenesis and the Effects of the Same Sera on the Fibroblast Growth In Vitro

Peer Reviewe

Incidence and Risk Factors of Pneumonia in Individuals With Acute Spinal Cord Injury: A Multi-national, Multi-center, Prospective Cohort Study

OBJECTIVE To describe the occurrence of pneumonia in individuals with acute spinal cord injury (SCI) and identify its key predictors. DESIGN Multi-centric, longitudinal cohort study. SETTING 10 specialized SCI rehabilitation units in Europe and Australia. PARTICIPANTS Eligible were 902 men and women with acute SCI, aged 18 years or older, with cervical or thoracic lesions and not dependent on 24-hour mechanical ventilation; 503 participated in the study (N=503). INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES We assessed demographics and lesion related parameters at study entry, and any pneumonia events throughout inpatient rehabilitation. Respiratory function, decubitus, and urinary tract infections were assessed at 1, 3, and 6 months post injury as well as at discharge from inpatient rehabilitation. Time to event (pneumonia) analyses were done using the Kaplan-Meier method, and potential predictors for pneumonia were analyzed with multivariable survival models. RESULTS Five hundred three patients with SCI were included, with 70 experiencing at least 1 pneumonia event. 11 participants experienced 2 or more events during inpatient rehabilitation. Most events occurred very early after injury, with a median of 6 days. Pneumonia risk was associated with tetraplegia (hazard ratio [HR]=1.78; 95% confidence interval [CI] 1.00-3.17) and traumatic etiology (HR=3.75; 95% CI 1.30-10.8) American Spinal Injury Impairment Scale (AIS) A (HR=5.30; 95% CI 2.28-12.31), B (HR=4.38; 95% CI 1.77-10.83), or C (HR=4.09; 95% CI 1.71-9.81) lesions. For every 10 cmH$_{2}$O increase in inspiratory muscle strength, pneumonia risk was reduced by 13% (HR=0.87; 95% CI 0.78-0.97). CONCLUSION Pneumonia is a major complication after SCI with the highest incidence very early after injury. Individuals with traumatic or AIS A, B, or C tetraplegia are at highest risk for pneumonia