scholarly journals A novel ex vivo model for critical illness neuromyopathy using freshly resected human colon smooth muscle

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Robert Patejdl ◽  
Felix Klawitter ◽  
Uwe Walter ◽  
Karim Zanaty ◽  
Frank Schwandner ◽  
...  

AbstractPatients suffering from critical illness are at risk to develop critical illness neuromyopathy (CINM). The underlying pathophysiology is complex and controversial. A central question is whether soluble serum factors are involved in the pathogenesis of CINM. In this study, smooth muscle preparations obtained from the colon of patients undergoing elective surgery were used to investigate the effects of serum from critically ill patients. At the time of blood draw, CINM was assessed by clinical rating and electrophysiology. Muscle strips were incubated with serum of healthy controls or patients in organ baths and isometric force was measured. Fifteen samples from healthy controls and 98 from patients were studied. Ratios of responses to electric field stimulation (EFS) before and after incubation were 118% for serum from controls and 51% and 62% with serum from critically ill patients obtained at day 3 and 10 of critical illness, respectively (p = 0.003, One-Way-ANOVA). Responses to carbachol and high-K+ were equal between these groups. Ratios of post/pre-EFS responses correlated with less severe CINM. These results support the existence of pathogenic, i.e. neurotoxic factors in the serum of critically ill patients. Using human colon smooth muscle as a bioassay may facilitate their future molecular identification.

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Mark Luedde ◽  
Fabian Benz ◽  
Jennifer Niedeggen ◽  
Mihael Vucur ◽  
Hans-Joerg Hippe ◽  
...  

Introduction. Omentin, a recently described adipokine, was shown to be involved in the pathophysiology of inflammatory and infectious diseases. However, its role in critical illness and sepsis is currently unknown. Materials and Methods. Omentin serum concentrations were measured in 117 ICU-patients (84 with septic and 33 with nonseptic disease etiology) admitted to the medical ICU. Results were compared with 50 healthy controls. Results. Omentin serum levels of critically ill patients at admission to the ICU or after 72 hours of ICU treatment were similar compared to healthy controls. Moreover, circulating omentin levels were independent of sepsis and etiology of critical illness. Notably, serum concentrations of omentin could not be linked to concentrations of inflammatory cytokines or routinely used sepsis markers. While serum levels of omentin were not predictive for short term survival during ICU treatment, low omentin concentrations were an independent predictor of patients’ overall survival. Omentin levels strongly correlated with that of other adipokines (e.g., leptin receptor or adiponectin), which have also been identified as prognostic markers in critical illness. Conclusions. Although circulating omentin levels did not differ between ICU-patients and controls, elevated omentin levels were predictive for an impaired patients’ long term survival.


2010 ◽  
Vol 104 (11) ◽  
pp. 1038-1043 ◽  
Author(s):  
Carsten Hafer ◽  
Jan Kielstein ◽  
Marion Haubitz ◽  
Hermann Haller ◽  
Svjetlana Lovric ◽  
...  

SummaryIn critically ill patients, the massive release of angiopoietin-2 (Ang-2) from Weibel-Palade bodies interferes with protective angiopoietin-1 (Ang-1)/Tie2 signalling in endothelial cells, thus leading to vascular inflammation and subsequent organ-dysfunction. We hypothesised that plasma exchange (PE) is efficient for lowering excess Ang-2 levels in critically ill patients with thrombocytic microangiopathy (TMA) or anti-glomerular basement membrane (anti-GBM) disease. Plasma Ang-1 and Ang-2 were measured by immuno-luminometric assays in patients with TMA (n=9) or anti-GBM disease (n=4) before and after up to four PE sessions. Twenty apparently healthy volunteers served as controls. Median (IQR) plasma levels of Ang-2 were markedly increased in patients with TMA (7.3 (2.4–21.1) ng/ml) and anti-GBM disease (5.8 (3.4–7.0) ng/ml) compared to healthy controls (1.0 (0.9–1.4) ng/ml, p <0.001). Moreover, Ang-1 plasma levels were decreased in both, TMA (1.02 (0.62–1.62) ng/ml) and anti-GBM disease patients (0.74 (0.59–3.62) ng/ml) compared to healthy controls (2.5 (1.93–3.47) ng/ ml, p <0.005). During a total of 32 treatments, PE effectively lowered elevated mean (SD) Ang-2 plasma levels by 36.7 ± 19.6 % per treatment (p <0.0001), whereas low Ang-1 plasma levels remained unchanged (0.3 ± 58.5 %; p =0.147). Ang-2 levels declined to almost normal values during ≤4 PE treatments (Friedman´s test p <0.0001). PE is an effective method to remove excess circulating Ang-2. It remains to be elucidated if the removal of Ang-2 is crucial to ameliorate endothelial damage in critically ill patients with severely altered endothelial integrity.


Author(s):  
Jonathan E. Sevransky ◽  
William Checkley ◽  
Timothy D. Girard ◽  
Steven M. Pastores ◽  
Sajid Shahul ◽  
...  

2021 ◽  
Vol 10 (13) ◽  
pp. 2935
Author(s):  
Jose Bordon ◽  
Ozan Akca ◽  
Stephen Furmanek ◽  
Rodrigo Silva Cavallazzi ◽  
Sally Suliman ◽  
...  

Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) pneumonia is the main cause of the pandemic’s death toll. The assessment of ARDS and time on invasive mechanical ventilation (IMV) could enhance the characterization of outcomes and management of this condition. This is a city-wide retrospective study of hospitalized patients with COVID-19 pneumonia from 5 March 2020 to 30 June 2020. Patients with critical illness were compared with those with non-critical illness. We examined the severity of ARDS and other factors associated with (i) weaning patients off IMV and (ii) mortality in a city-wide study in Louisville, KY. Of 522 patients with COVID-19 pneumonia, 219 (41.9%) were critically ill. Among critically ill patients, the median age was 60 years; 53% were male, 55% were White and 32% were African American. Of all critically ill patients, 52% had ARDS, and 38% of these had severe ARDS. Of the 25% of patients who were weaned off IMV, those with severe ARDS were weaned within eleven days versus five days for those without severe ARDS, p = 0.023. The overall mortality for critically ill patients was 22% versus 1% for those not critically ill. Furthermore, the 14-day mortality was 31% for patients with severe ARDS and 12% for patients without severe ARDS, p = 0.019. Patients with severe ARDS versus non-severe ARDS needed twice as long to wean off IMV (eleven versus five days) and had double the 14-day mortality of patients without severe ARDS.


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Alexander Koch ◽  
Ralf Weiskirchen ◽  
Jan Bruensing ◽  
Hanna Dückers ◽  
Lukas Buendgens ◽  
...  

In systemic inflammation and sepsis, endothelial activation and microvascular dysfunction are characteristic features that promote multiorgan failure. As symmetric dimethylarginine (SDMA) impacts vascular tension and integrity via modulating nitric oxide (NO) pathways, we investigated circulating SDMA in critical illness and sepsis. 247 critically ill patients (160 with sepsis, 87 without sepsis) were studied prospectively upon admission to the medical intensive care unit (ICU) and on day 7, in comparison to 84 healthy controls. SDMA serum levels were significantly elevated in critically ill patients at admission to ICU compared to controls and remained stably elevated during the first week of ICU treatment. The highest SDMA levels were found in patients with sepsis. SDMA levels closely correlated with disease severity scores, biomarkers of inflammation, and organ failure (renal, hepatic, and circulatory). We identified SDMA serum concentrations at admission as an independent prognostic biomarker in critically ill patients not only for short-term mortality at the ICU but also for unfavourable long-term survival. Thus, the significant increase of circulating SDMA in critically ill patients indicates a potential pathogenic involvement in endothelial dysfunction during sepsis and may be useful for mortality risk stratification at the ICU.


Author(s):  
Wandong Hong ◽  
Qin Chen ◽  
Songzan Qian ◽  
Zarrin Basharat ◽  
Vincent Zimmer ◽  
...  

ObjectivesThe objective of this study was to investigate the clinical features and laboratory findings of patients with and without critical COVID-19 pneumonia and identify predictors for the critical form of the disease.MethodsDemographic, clinical, and laboratory data of 63 COVID-19 pneumonia patients were retrospectively reviewed. Laboratory parameters were also collected within 3–5 days, 7–9 days, and 11–14 days of hospitalization. Outcomes were followed up until March 12, 2020.ResultsTwenty-two patients developed critically ill pneumonia; one of them died. Upon admission, older patients with critical illness were more likely to report cough and dyspnoea with higher respiration rates and had a greater possibility of abnormal laboratory parameters than patients without critical illness. When compared with the non-critically ill patients, patients with serious illness had a lower discharge rate and longer hospital stays, with a trend towards higher mortality. The interleukin-6 level in patients upon hospital admission was important in predicting disease severity and was associated with the length of hospitalization.ConclusionsMany differences in clinical features and laboratory findings were observed between patients exhibiting non-critically ill and critically ill COVID-19 pneumonia. Non-critically ill COVID-19 pneumonia also needs aggressive treatments. Interleukin-6 was a superior predictor of disease severity.


2017 ◽  
Vol 45 (12) ◽  
pp. 2078-2088 ◽  
Author(s):  
Djillali Annane ◽  
Stephen M. Pastores ◽  
Bram Rochwerg ◽  
Wiebke Arlt ◽  
Robert A. Balk ◽  
...  

2020 ◽  
Author(s):  
Shan Lin ◽  
Shanhui Ge ◽  
Wanmei He ◽  
Mian Zeng

Abstract Background: The effects of combined diabetes and glycemic control strategies on the short-term prognosis in patients with a critical illness are currently ambiguous. The objectives of our study were to determine whether comorbid diabetes affects short-term prognosis and the optimal range of glycemic control in critically ill patients.Methods: We performed this study with the critical care database. The primary outcomes were 28-day mortality in critically ill patients with comorbid diabetes and the optimal range of glycemic control. Association of comorbid diabetes with 28-day mortality was assessed by multivariable Cox regression model with inverse probability weighting. Smooth curves were applied to fit the association for glucose and 28-day mortality.Results: Of the 33,680 patients enrolled in the study, 8,701 (25.83%) had diabetic comorbidity. Cox model with inverse probability weighting showed that the 28-day mortality rate was reduced by 29% (HR=0.71, 95% CI 0.67-0.76) in the group with diabetes in comparison to the group without diabetes. The E value of 2.17 indicated robustness to unmeasured confounders. The effect of the association between comorbid diabetes and 28-day mortality was generally in line for all subgroup variables, significant interactions were observed for glucose on first day, admission type, and use of insulin or not (Interaction P <0.05). A V-shaped relationship was observed between glucose concentrations and 28-day mortality in patients without diabetes, with the lowest 28-day mortality corresponding to the glucose level was 101.75 mg/dl (95% CI 94.64-105.80 mg/dl); whereas in patients with comorbid diabetes, the effect of glucose concentration on 28-day mortality was structurally softer than in those with uncomorbid diabetes. Lastly, of all patients, hyperglycemia had the greatest deleterious effect on patients admitted to CSRU.Conclusions: Our study further confirmed the protective effect of comorbid diabetes on the short-term prognosis of critically ill patients, resulting in an approximately 29% reduction in 28-day mortality. Besides, we also demonstrated the personalized glycemic control strategy for critically ill patients. Lastly, clinicians should be aware of the occurrence and the prompt management of hyperglycemia in critically ill patients admitted to the CSRU.


Author(s):  
Priya S. Dhawan ◽  
Jennifer A. Tracy

Acquired weakness in critically ill patients is common, affecting between one-third to one-half of patients in the intensive care unit (ICU). Exposure to simultaneous stressors such as metabolic derangements, fluid and electrolyte shifts, infection, catabolic stress, and medications put patients in the ICU at risk for damage to both nerve and skeletal muscle with substantial and often lasting morbidity. Critical illness polyneuropathy is a length-dependent, axonal peripheral neuropathy occurring in patients in the ICU and unrelated to the primary illness. Critical illness myopathy is an ICU-associated muscle disorder occurring independently of denervation and uniquely identified by electrophysiologic and histologic characteristics.


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