Association of physiological reserve measures with adverse outcomes following liver transplantation

Abstract Background Primary sclerosing cholangitis (PSC) is a progressive cholestatic disease involving chronic inflammation and fibrosis of intra- and extra-hepatic ducts. Vitamin D is a secosteroid implicated in anti-inflammatory and anti-fibrotic pathways, and its deficiency has been associated with worse outcomes in chronic liver disease. Vitamin D status may also influence the course of PSC but studies evaluating this link are scarce. Aims To determine the association of vitamin D deficiency with the development of cirrhosis, mortality, and need for liver transplantation in patients with PSC. Methods Ninety-four patients with the diagnosis of PSC were evaluated and followed by the autoimmune liver disease clinic at the University of Alberta, Edmonton, Canada. Clinical data were recovered from medical charts. Vitamin D status was defined by the serum concentration of 25-hydroxyvitamin D3. Patients with levels <50 nmol/L (10 ng/ml) were defined as deficient. Univariate and multivariate analyses were constructed using the Cox proportional hazards regression models. Event-free survival was defined as time from vitamin D assessment to the time of liver transplant or death. Results Mean age at PSC diagnosis was 32±14 years, with 67% of patients being male. The mean vitamin D level was 69±33 nmol/L (range, 4–163 nmol/L) and 26 patients (28%) had vitamin D deficiency (<50 nmol/L). Among 85 patients without cirrhosis at diagnosis, 43 patients (51%) developed cirrhosis. By univariate Cox analysis, serum ALP, albumin, bilirubin and vitamin D deficiency were predictors of cirrhosis development. Vitamin D deficiency was independently associated with higher risk of developing cirrhosis (HR 2.11, 95% CI 1.002–4.44, P=0.049) after adjusting for other predictors. Median time to develop cirrhosis was shorter in patients with vitamin D deficiency (6.8 years; 95% CI, 1.7–11.8) compared to those without (10.8 years; 95% CI, 9.2 -12.4; P=0.007). Over a median follow-up period of 5.6 years, adverse outcomes (liver transplant or death) were observed in 34 patients (36%). Serum levels of albumin, ALP, bilirubin, INR, platelet count, ascites, variceal bleeding and vitamin D deficiency were associated with adverse outcomes in univariate analysis. Vitamin D deficiency was independently associated with higher risk of adverse endpoints (HR 2.87, 95% CI, 1.16–7.12, P=0.02) after adjusting for confounding factors. Event-free survival was shorter in the patients with vitamin D deficiency compared to those without deficiency (7.1 years; 95% CI, 2.4–11.9 vs. 11.4 years; 95% CI, 8.9–13.9, P=0.03, Figure 1). Conclusions Vitamin D deficiency was frequent in patients with PSC and was associated with higher risk of progression to cirrhosis, as well as decreased time to death and liver transplantation. The possibility of improving outcomes in PSC by vitamin D supplementation awaits further investigation. Funding Agencies Food and Health Innovation Initiative (Vitamin Fund), University of Alberta

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Liver Transplantation in Patients With Cardiac Disease

Seminars in Cardiothoracic and Vascular Anesthesia ◽

10.1177/1089253217736050 ◽

2017 ◽

Vol 22 (2) ◽

pp. 111-121 ◽

Cited By ~ 5

Author(s):

Christopher L. Wray

Keyword(s):

Cardiovascular Disease ◽

Liver Transplantation ◽

Perioperative Period ◽

Cardiovascular Complications ◽

Adverse Outcomes ◽

Treatment Modalities ◽

Cardiac Complications ◽

Major Step ◽

Cardiac Evaluation ◽

The Impact

Liver transplantation (LT) is a unique surgical procedure that has major hemodynamic and cardiovascular implications. Recently, there has been significant interest focused on cardiovascular issues that affect LT patients in all phases of the perioperative period. The preoperative cardiac evaluation is a major step in the selection of LT candidates. LT candidates are aging in concordance with the general population; cardiovascular disease and their risk factors are highly associated with older age. Underlying cardiovascular disease has the potential to affect outcomes in LT patients and has a major impact on candidate selection. The prolonged hemodynamic and metabolic instability during LT may contribute to adverse outcomes, especially in patients with underlying cardiovascular disease. Cardiovascular events are not unusual during LT; transplant anesthesiologists must be prepared for these events. Advanced cardiovascular monitoring techniques and treatment modalities are now routinely used during LT. Postoperative cardiovascular complications are common in both the early and late posttransplant periods. The impact of cardiac complications on posttransplant mortality is well recognized. Emerging knowledge regarding cardiovascular disease in LT patients and its impact on posttransplant outcomes will have an important role in guiding the future perioperative management of LT patients.

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Cardiovascular Disease and Frailty: What Are the Mechanistic Links?

Clinical Chemistry ◽

10.1373/clinchem.2018.287318 ◽

2019 ◽

Vol 65 (1) ◽

pp. 80-86 ◽

Cited By ~ 14

Author(s):

Ralph Stewart

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Daily Living ◽

Clinical Syndrome ◽

Adverse Outcomes ◽

Contributing Factors ◽

Aging Populations ◽

Physiological Reserve ◽

Common Risk Factors ◽

Poor Nutrition

Abstract BACKGROUND In aging populations, cardiovascular disease (CVD) and frailty are common and often coexist. It is possible that common risk factors and pathophysiological pathways increase the risk of both CVD and frailty. CONTENT Frailty is a complex clinical syndrome with multiple causes and contributing factors. It is characterized by multisystem impairment that decreases physiological reserve and increases vulnerability to stress. Diverse methods have been used to evaluate frailty. Most include 1 or several measures related to reduced exercise, physical function, cognition, activities of daily living, comorbidities, deficits and/or markers of physiological dysfunction. CVD and frailty may be linked by several mechanisms. CVD can accelerate frailty, and frailty increases the risk of adverse outcomes in patients with CVD. Common pathophysiological pathways are also important. Low physical activity, poor nutrition, diabetes, hypertension, and smoking may increase the risk of both CVD and frailty. Further research is needed to evaluate whether biomarkers of dysfunction across multiple body systems, which are known to be associated with aging, and with CV and non-CV morbidity and mortality, are also associated with frailty. SUMMARY Multiple pathophysiological pathways are associated with both CVD and frailty, which interact to further increase the risk of adverse outcomes.

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Clinical Features and Outcomes of Primary Sclerosing Cholangitis in the Highly Admixed Brazilian Population

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2021/7746401 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Mateus Jorge Nardelli ◽

Paulo Lisboa Bittencourt ◽

Guilherme Grossi Lopes Cançado ◽

Luciana Costa Faria ◽

Cristiane Alves Villela-Nogueira ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Liver Transplantation ◽

Primary Sclerosing Cholangitis ◽

Bowel Disease ◽

Sclerosing Cholangitis ◽

Clinical Characteristics ◽

Adverse Outcomes ◽

Male Predominance ◽

Clear Cut ◽

Inflammatory Bowel

Background. Primary sclerosing cholangitis (PSC) is associated with a broad phenotypic spectrum in different populations from diverse ethnic and racial backgrounds. This study aimed to describe the clinical characteristics and outcomes of PSC in a multicenter cohort of patients from Brazil. Methods. Data from the Brazilian Cholestasis Study Group were retrospectively reviewed to assess demographic information and clinical characteristics of PSC, as well as the outcomes, such as transplantation-free survival. Results. This cohort included 210 patients. After excluding 33 (15.7%) patients with PSC and overlap syndrome of autoimmune hepatitis, 177 (97 males, median age 33 (21–42) years) with clear-cut PSC were eligible for this study. Most of the patients (n = 139, 78.5%) were symptomatic, and 104 (58.7%) had advanced PSC at the time of diagnosis. Concurrent inflammatory bowel disease was observed in 78 (58.6%) of the investigated patients (n = 133), and most of them had ulcerative colitis (n = 61, 78.2%). The 1- and 5-year survival free of liver transplantation or death were 92.3 ± 2.1% and 66.9 ± 4.2%, respectively, and baseline advanced PSC, pruritus, and elevated bilirubin levels were independent risk factors for the composite adverse outcome. Females were significantly older and had lower bilirubin levels than males at baseline, but survival was not associated with sex. Approximately 12.4% (n = 22) of patients with PSC died, and 32.8% (n = 58) underwent liver transplantation at a median follow-up time of 5.3 and 3.2 years. Conclusion. Multiethnic Brazilian PSC patients exhibited a less pronounced male predominance and a lower frequency of inflammatory bowel disease than Caucasians. Adverse outcomes were more frequent, probably due to advanced disease at baseline.

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Extubation in the operating room results in fewer composite mechanical ventilation-related adverse outcomes in patients after liver transplantation: a retrospective cohort study

BMC Anesthesiology ◽

10.1186/s12871-021-01508-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yan Xu ◽

Yiding Zuo ◽

Li Zhou ◽

Xuechao Hao ◽

Xiao Xiao ◽

...

Keyword(s):

Mechanical Ventilation ◽

Liver Transplantation ◽

Kidney Injury ◽

Infectious Complications ◽

Pulmonary Complications ◽

Adverse Outcomes ◽

Total Hospital Cost ◽

Total Hospital ◽

Acute Kidney Injury Stage ◽

All Cause Mortality

Abstract Background To investigate the effect of extubation in the operating room (OR) on mechanical ventilation-related adverse outcomes in patients who undergo liver transplantation. Methods Patients who underwent liver transplantation between January 2016 and December 2019 were included. According to the timing of extubation, patients were divided into OR extubation group and intensive care unit (ICU) extubation group. The propensity score was used to match OR extubation group and ICU extubation group at a 1:2 ratio by demographical and clinical covariates. The primary outcome was a composite of mechanical ventilation-related adverse outcomes, including 30-day all-cause mortality, in-hospital acute kidney injury (stage 2 or 3), and in-hospital moderate to severe pulmonary complications. Secondary outcomes included in-hospital moderate to severe infectious complications, unplanned reintubation rates, ICU and postoperative hospital lengths of stay, and total hospital cost. Results A total of 438 patients were enrolled. After propensity score matching, 94 patients were in OR extubation group and 148 patients were in ICU extubation group. Incidence of the composite mechanical ventilation-related adverse outcomes was significantly lower in OR extubation group than ICU extubation group, even after adjusting for confounding factors (19.1% vs. 31.8%; Odds Ratio, 0.509; 95% Confidence Index [CI], 0.274-0.946; P=0.031). The duration of ICU stay was much shorter in OR extubation group than ICU extubation group (median 4, Interquartile range [IQR] (3 ~ 6) vs. median 6, IQR (4 ~ 8); P<0.001). Meanwhile, extubation in the OR led to a significant reduction of total hospital cost compared with extubation in the ICU (median 3.9, IQR (3.5 ~ 4.6) 10000 US dollars vs. median 4.1, IQR (3.8 ~ 5.1) 10000 US dollars; P=0.021). However, there were no statistically significant differences in moderate to severe infectious complications, unplanned reintubation rates, and the length of postoperative hospital stay between groups. Conclusions Among patients who underwent liver transplantation, extubation in the OR compared with extubation in the ICU, significantly reduced the primary composite outcome of 30-day all-cause mortality, in-hospital acute kidney injury (stage 2 or 3), or in-hospital moderate to severe pulmonary complications. Trial registration The trial was registered at www.clinicaltrials.gov with registration number NCT04261816. Retrospectively registered on 1st February 2020.

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Some mathematical models of frailty and their clinical implications

Reviews in Clinical Gerontology ◽

10.1017/s0959259802012236 ◽

2002 ◽

Vol 12 (2) ◽

pp. 109-117 ◽

Cited By ~ 73

Author(s):

Kenneth Rockwood ◽

Arnold B Mitnitski ◽

Chris MacKnight

Keyword(s):

Older Adults ◽

Mathematical Models ◽

Adverse Outcomes ◽

Alternative Methods ◽

Clinical Implications ◽

Dynamic Component ◽

Concept Of Function ◽

Alternative Means ◽

Physiological Reserve ◽

Over Time

Frailty is a term that is used often, but commonly not defined precisely. As reviewed elsewhere most definitions share several features. Typically, older adults who are frail have a greater rate of dependence on others, so-called ‘loss of physiological reserve’ and multiple diseases. A dynamic component is often included (e.g. ‘loss of reserve’ and such synonyms as ‘unstable disability’ and ‘impaired homeostenosis’) and is manifest when, over time, patients respond less well to stress, or when those with given levels of frailty have higher rates of adverse outcomes. Still, the imprecision of the term frailty has led some to question its merit, and either to develop alternative means of classification or to stay with the concept of function and disability. Alternative methods of classification are either broadly or narrowly focussed.

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