Association between Premorbid Renin-Angiotensin-Aldosterone System Blockade and the Risk of Acute Kidney Injury in Critically Ill Patients.

Background: Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are commonly used for hypertension and cardiovascular diseases. However, whether their use increases the risk of acute kidney injury (AKI) and should be discontinued during acute illness remains controversial. Methods: This retrospective study enrolled 952 dialysis-free patients who were admitted to intensive care units (ICUs) between 2015 and 2017, including 476 premorbid long-term (> 1 month) ACEi/ARB users. Propensity score matching was performed to adjust for age, gender, comorbidities, and disease severity. The primary endpoint was the occurrence of AKI during hospitalization, and the secondary endpoint was mortality or dialysis within 1 year. Results: Compared with non-users, the ACEi/ARB users were not associated with an increased AKI risk during hospitalization [66.8% vs. 70.4%; hazard ratio (HR): 1.13, 95% confidence interval (CI): 0.97-1.32, p = 0.126]. However, the ACEi/ARB users with sepsis (HR: 1.29, 95% CI: 1.04-1.60, p = 0.021) or hypotension (HR: 1.21, 95% CI: 1.02-1.14, p = 0.034) were found to have an increased AKI risk in subgroup analysis. Nevertheless, compared with the non-users, the ACEi/ARB users were associated with a lower incidence of mortality or dialysis within 1 year (log-rank p = 0.011). Conclusions: Premorbid ACEi/ARB usage did not increase the incidence of AKI, and was associated with a lower 1-year mortality and dialysis rate in patients admitted to ICUs. Regarding the results of subgroup analysis, renin-angiotensin-aldosterone system blockade may still be safe and beneficial in the absence of sepsis or circulation failure. Further large-scale studies are needed to confirm our findings.

Severe acute hypokalaemia associated with piperacillin/tazobactam in an HIV-infected patient under antiretroviral therapy with tenofovir alafenamide: case report and literature review.

Piperacillin/tazobactam is a commonly prescribed antimicrobial agent. Tenofovir alafenamide (TAF) is increasingly being used in antiretroviral therapy (ART) of HIV. Herein we report a case of a 57-year-old male with AIDS receiving TAF-containing ART in whom severe refractory hypokalaemia developed after coadministration of piperacillin/tazobactam for suspected hospital-acquired infection. Upon withdrawal of piperacillin/tazobactam, serum potassium concentrations returned to normal within 2 days. Hypokalaemia is a rare adverse effect of piperacillin/tazobactam and may be aggravated with the underlying use of TAF. We also reviewed past reported cases of hypokalaemia after piperacillin/tazobactam administration. We want to highlight that a more cautious approach should be considered when combining piperacillin/tazobactam and TAF in clinical practice.

Effect of Continuity of Care on Drug-Drug Interactions.

BACKGROUND: Drug-drug interaction (DDI) is a critical concern in health care systems because it is directly associated with patient outcomes and is generally preventable. However, few studies have been conducted on whether poor continuity of care (COC) is a determinant of DDIs and whether this effect varies by level of comorbidity. Patients with higher comorbidity normally require more complex treatment regimens than other patients, and hence their COC is more critical for ensuring the accuracy of their medication information. OBJECTIVE: This study investigated the association between COC and DDI, with COC being measured as physician and site COC. The effect of comorbidities on DDI events was also analyzed. METHODS: The Taiwan National Health Insurance claims data of ∼1,000,000 randomly selected insurance beneficiaries were used. Each person was longitudinally followed from 2005 to 2013. Negative nominal regressions were estimated to determine the effect of COC on DDI. RESULTS: Higher COC was found to decrease the risk of DDI, and this risk reduction was even greater with physician COC and a higher Charlson comorbidity index. In the 1-year observation interval, patients exhibited a 3% reduction in DDIs for every 0.1 increment in their COC index. The ability of COC to reduce DDIs increased with the level of comorbidity. Similar results were observed when the observation interval was increased. CONCLUSIONS: Improving COC is critical for reducing DDIs. The effect of high-quality COC on the reduction of DDI is more significant for patients with higher levels of comorbidity; thus, they should be targeted to improve COC.

Fibroblast Growth Factor 19 and Fibroblast Growth Factor 21 Regulation in Obese Diabetics, and Non-Alcoholic Fatty Liver Disease after Gastric Bypass.

BACKGROUND: Gastric bypass (GB) is an effective treatment for those who are morbidly obese with coexisting type 2 diabetes mellitus (T2DM) or non-alcoholic fatty liver disease (NAFLD). Fibroblast growth factors (FGFs) are involved in the regulation of energy metabolism. METHODS: We investigated the roles of FGF 19, FGF 21, and total bile acid among those with morbidly obese and T2DM undergoing GB. A total of 35 patients were enrolled. Plasma FGF 19, FGF 21, and total bile acid levels were measured before surgery (M0), 3 months (M3), and 12 months (M12) after surgery, while the hepatic steatosis index (HSI) was calculated before and after surgery. RESULTS: Obese patients with T2DM after GB presented with increased serum FGF 19 levels (p = 0.024) and decreased total bile acid (p = 0.01) and FGF 21 levels (p = 0.005). DM complete remitters had a higher FGF 19 level at M3 (p = 0.004) compared with DM non-complete remitters. Fatty liver improvers tended to have lower FGF 21 (p = 0.05) compared with non-improvers at M12. CONCLUSION: Changes in FGF 19 and FGF 21 play differential roles in DM remission and NAFLD improvement for patients after GB. Early increases in serum FGF 19 levels may predict complete remission of T2DM, while a decline in serum FGF 21 levels may reflect the improvement of NAFLD after GB.

The paradox of the glycemic gap: Does relative hypoglycemia exist in critically ill patients?

BACKGROUND & AIMS: Elevated glycemic gap, as the differences between measured glucose and hemoglobin A1c (HbA1c)-derived average glucose (ADAG) levels, is a marker of stress-induced hyperglycemia and is a predictor of mortality in critically ill patients. Whether low glycemic gaps are associated with outcomes in critically ill patients remains unclear. We investigated the association of different glycemic gaps on mortality in critically ill patients. METHODS: Totally 935 patients admitted to intensive care units (ICUs) were enrolled retrospectively after the exclusion of patients with absolute hypoglycemia, extreme hyperglycemia, and incomplete glycemic records. Patients were divided into 3 groups according to their glycemic gaps (<-29.7, -29.7-40, ≧40 mg/dL) at the time of ICU admission. The patients were followed for 1 year or until death. RESULTS: Patients with low glycemic gap (glycemic gap < -29.7 mg/dL), which implied relative hypoglycemia, had lower serum glucose levels, higher HbA1c levels, and greater disease severity. Compared with medium group (glycemic gap -29.7-40 mg/dL), both the low and the high glycemic gap (glycemic gap ≧40 mg/dL) groups had significantly greater 30-day (log-rank p = 0.0464) and 1-year mortality (log-rank p = 0.0016). However, only the low glycemic gap group was independently associated with greater in-hospital mortality after adjusting for comorbidities (adjusted OR 1.78, 95% CI 1.00-3.16, p = 0.048). CONCLUSION: This study revealed the presence of a U-shaped relationship between the glycemic gap and mortality in critically ill patients. Low glycemic gaps suggested relative hypoglycemia at the time of ICU admission, and were associated independently with greater in-hospital mortality.

Premorbid ß1-selective (but not non-selective) ß-blocker exposure reduces intensive care unit mortality among septic patients.

BACKGROUND: ß-blockers may protect against catecholaminergic myocardial injury in critically ill patients. Long-term ß-blocker users are known to have lower lactate concentrations and favorable sepsis outcomes. However, the effects of ß1-selective and nonselective ß-blockers on sepsis outcomes have not been compared. This study was conducted to investigate the impacts of different ß-blocker classes on the mortality rate in septic patients. METHODS: We retrospectively screened 2678 patients admitted to the medical or surgical intensive care unit (ICU) between December 2015 and July 2017. Data from patients who met the Sepsis-3 criteria at ICU admission were included in the analysis. Premorbid ß-blocker exposure was defined as the prescription of any ß-blocker for at least 1 month. Bisoprolol, metoprolol, and atenolol were classified as ß1-selective ß-blockers, and others were classified as nonselective ß-blockers. All patients were followed for 28 days or until death. RESULTS: Among 1262 septic patients, 209 (16.6%) patients were long-term ß-blocker users. Patients with premorbid ß-blocker exposure had lower heart rates, initial lactate concentrations, and ICU mortality. After adjustment for disease severity, comorbidities, blood pressure, heart rate, and laboratory data, reduced ICU mortality was associated with premorbid ß1-selective [adjusted hazard ratio, 0.40; 95% confidence interval (CI), 0.18-0.92; P = 0.030], but not non-selective ß-blocker use. CONCLUSION: Premorbid ß1-selective, but not non-selective, ß-blocker use was associated with improved mortality in septic patients. This finding supports the protective effect of ß1-selective ß-blockers in septic patients. Prospective studies are needed to confirm it.

Paradox of trimethylamine-N-oxide, the impact of malnutrition on microbiota-derived metabolites and septic patients.

BACKGROUND: Trimethylamine N-oxide (TMAO) is a microbiota-derived metabolite, which is linked to vascular inflammation and atherosclerosis in cardiovascular (CV) diseases. But its effect in infectious diseases remains unclear. We conducted a single-center prospective study to investigate association of TMAO with in-hospital mortality in septic patients admitted to an intensive care unit (ICU). METHODS: Totally 95 septic, mechanically ventilated patients were enrolled. Blood samples were obtained within 24 h after ICU admission, and plasma TMAO concentrations were determined. Septic patients were grouped into tertiles according to TMAO concentration. The primary outcome was in-hospital death, which further classified as CV and non-CV death. Besides, we also compared the TMAO concentrations of septic patients with 129 non-septic patients who were admitted for elective coronary angiography (CAG). RESULTS: Septic patients had significantly lower plasma TMAO levels than did subjects admitted for CAG (1.0 vs. 3.0 µmol/L, p < 0.001). Septic patients in the lowest TMAO tertile (< 0.4 µmol/L) had poorer nutrition status and were given longer antibiotic courses before ICU admission. Circulating TMAO levels correlated positively with daily energy intake, the albumin and prealbumin concentration. Compared with those in the highest TMAO tertile, septic patients in the lowest TMAO tertile were at greater risk of non-CV death (hazard ratio 2.51, 95% confidence interval 1.21-5.24, p = 0.014). However, TMAO concentration was no longer an independent predictor for non-CV death after adjustment for disease severity and nutritional status. CONCLUSION: Plasma TMAO concentration was inversely associated with non-CV death among extremely ill septic patients, which could be characterized as TMAO paradox. For septic patients, the impact of malnutrition reflected by circulating TMAO levels was greater than its pro-inflammatory nature.

Elevated serum galectin-1 concentrations are associated with increased risks of mortality and acute kidney injury in critically ill patients.

BACKGROUND: Galectin-1 (Gal-1), a member of the ß-galactoside binding protein family, is associated with inflammation and chronic kidney disease. However, the effect of Gal-1 on mortality and acute kidney injury (AKI) in critically-ill patients remain unclear. METHODS: From May 2018 to March 2020, 350 patients admitted to the medical intensive care unit (ICU) of Taipei Veterans General Hospital, a tertiary medical center, were enrolled in this study. Forty-one patients receiving long-term renal replacement therapy were excluded. Serum Gal-1 levels were determined within 24 h of ICU admission. The patients were divided into tertiles according to their serum Gal-1 levels (low, serum Gal-1 < 39 ng/ml; median, 39-70 ng/ml; high, ≥71 ng/ml). All patients were followed for 90 days or until death. RESULTS: Mortality in the ICU and at 90 days was greater among patients with elevated serum Gal-1 levels. In analyses adjusted for the body mass index, malignancy, sepsis, Sequential Organ Failure Assessment (SOFA) score, and serum lactate level, the serum Gal-1 level remained an independent predictor of 90-day mortality [median vs. low: adjusted hazard ratio (aHR) 2.11, 95% confidence interval (CI) 1.24-3.60, p = 0.006; high vs. low: aHR 3.21, 95% CI 1.90-5.42, p < 0.001]. Higher serum Gal-1 levels were also associated with a higher incidence of AKI within 48 h after ICU admission, independent of the SOFA score and renal function (median vs. low: aHR 2.77, 95% CI 1.21-6.34, p = 0.016; high vs. low: aHR 2.88, 95% CI 1.20-6.88, p = 0.017). The results were consistent among different subgroups with high and low Gal-1 levels. CONCLUSION: Serum Gal-1 elevation at the time of ICU admission were associated with an increased risk of mortality at 90 days, and an increased incidence of AKI within 48 h after ICU admission.

Comparison of knowledge on stroke for stroke patients and the general population in Burkina Faso: a cross-sectional study.

BACKGROUND: In many parts of Africa, there is limited information on awareness of symptoms of stroke, risk factors for stroke and willingness for stroke prevention, both in the general population and in people with stroke. Knowledge and preventive efforts for stroke in patients with a history of the illness are rarely investigated. This study aims to investigate awareness of stroke symptoms in stroke patients who were admitted to hospitals within 72 hours of a confirmed stroke event in Burkina Faso. This study also aims to investigate preventive behavior for stroke for the general population. METHODS: Face-to-face interviews were conducted with the participants. The sample included 110 first-time stroke patients who had been admitted to one of three tertiary teaching hospitals in Burkina Faso within 72 hours and 750 participants from the general population, who were recruited through clustered sampling. Knowledge of stroke warning signs and current and future efforts on stroke prevention were also assessed. RESULTS: Only 30.9% of the stroke patients believed that they were at risk before the stroke episode. Obvious warning signs were unfamiliar to both groups. Only 1.3% of the respondents from the general population group knew sudden weakness face arm or leg as a sign of stroke. For all future efforts in stroke prevention, stroke patients demonstrated significantly lower willingness to undertake behavioral changes than the general population. Sixty-six percent and 85% of the stroke patients and the general population, respectively, were willing to take steps to reduce blood pressure. CONCLUSION: Public education on stroke warning signs and strategies to increase willingness to engage in preventive behaviors are urgent in African countries. Strategies to improve public awareness for developing countries such as Burkina Faso should be designed differently from that of developed countries to incorporate local beliefs.

Associations of antithrombotic agent use with clinical outcomes in critically ill patients with troponin I elevation in the absence of acute coronary syndrome.

INTRODUCTION: To evaluate efficacy of antithrombotic agents in critically ill patients with elevated troponin I level during intensive care unit (ICU) admission. METHODS AND RESULTS: It was a retrospective observational study which was conducted in a tertiary teaching hospital in Taipei, Taiwan. All patients hospitalized in ICU for >3 days and with available serum troponin I data from December 2015 to July 2017 were included. Patients with definite diagnosis of acute myocardial infarction (AMI) were excluded. We divided patients with troponin I elevation into three groups; no prescription, chronic prescription and new prescription of antithrombotic agents during ICU admission. We defined new prescription when patients were on antithrombotic agents, including antiplatelet agents, direct oral anticoagulants, and warfarin after troponin I was found to be elevated at ICU admission and chronic prescription, if antithrombotic agents were on medication list more than 30 days before ICU admission. Primary outcomes were 30-day and one-year all-cause mortality. Of 597 subjects who met inclusion criteria, 407 (68%) patients had elevated troponin I (>0.1 ng/mL) on ICU admission. These patients had increased 30-day [hazard ratio (HR), 1.679; 95% confidence interval (CI), 1.132-2.491; p = 0.009] and one-year (HR, 1.568; 95% CI, 1.180-2.083; p = 0.002) all-cause mortality compared with those without elevated troponin I. In patients with elevated troponin I, there was no significant difference of 30-day all-cause mortality among three groups (p = 0.051) whereas patients on chronic prescription showed significant survival benefit in one-year all-cause mortality when compared to those without or with new prescription (p = 0.008). CONCLUSIONS: In critically ill patients, elevated troponin I in the absence of AMI was associated with poor prognosis. Newly prescribed antithrombotic agents in ICU didn't reveal the difference in short and long-term prognosis while chronic antithrombotic agent use was associated with better one-year survival rate, suggesting that these drugs play a protective role in this high-risk population.