Stress Hyperphenylalaninemia Is Associated With Mortality in Cardiac ICU: Clinical Factors, Genetic Variants, and Pteridines.

OBJECTIVES: Hyperphenylalaninemia predicts poor outcomes in patients with cardiovascular disease. However, the prognostic value and factors associated with stress hyperphenylalaninemia (SHP) were unknown in critical patients in the cardiac ICU. DESIGN: Prospective observational study. SETTING: Single-center, cardiac ICU in Taiwan. PATIENTS: Patients over 20 years old with Acute Physiology And Chronic Health Evaluation II scores greater than or equal to 15 and/or ventilatory support in the cardiac ICU. INTERVENTIONS: We measured plasma phenylalanine levels serially during patients' stays in the ICU to investigate their prognostic value for 90-day mortality. Gene array was performed to identify genetic polymorphisms associated with SHP (phenylalanine level ≥ 11.2 µmol/dL) and to develop a Genetic Risk Score (GRS). We analyzed the associations between SHP and clinical factors and genetic variants and identified the correlation between pteridines and genetic variants. MEASUREMENTS AND MAIN RESULTS: The study enrolled 497 patients. Increased phenylalanine concentration was independently associated with increased mortality risk. Patients with SHP had a higher mortality risk compared with those without SHP (log rank = 41.13; p < 0.001). SHP was associated with hepatic and renal dysfunction and with genetic polymorphisms on the pathway of tetrahydrobiopterin (BH4) synthesis (CBR1 and AKR1C3) and recycling (PCBD2). Higher GRSs were associated with lower BH4 bioavailability in response to stress ( p < 0.05). In patients without SHP at baseline, those with GRSs gretaer than or equal to 2 had a higher frequency of developing SHP during the ICU stay (31.5% vs 16.1%; p = 0.001) and a higher mortality risk ( p = 0.004) compared with those with GRSs less than 2. In patients with SHP at baseline, genetic variants did not provide additional prognostic value. CONCLUSIONS: SHP in patients admitted to the ICU was associated with a worse prognosis. In patients without SHP, genetic polymorphisms associated with SHP measured using a GRS of greater than or equal to 2 was associated with the subsequent SHP and higher mortality risk.

U-Shape Relationship between Plasma Leucine Level and Mortality in the Intensive Care Unit.

Patients in the intensive care unit (ICU) are at high risk of mortality which is not well predicted. Previous studies noted that leucine has prognostic value in a variety of diseases. This study investigated whether leucine concentration was a useful biomarker of metabolic and nutritional status and 6-month mortality in ICU. We recruited 454 subjects admitted to ICU (348 and 106 in the initiation and validation cohorts, respectively) with an acute physiology and chronic health evaluation (APACHE II) score ≥ 15. We measured plasma leucine concentrations, traditional biomarkers, and calculated APACHE II and sequential organ failure assessment (SOFA) scores. Leucine levels were weakly correlated with albumin, prealbumin, and transferrin levels (r = 0.30, 0.12, and 0.15, p = 0.001, 0.029, and 0.007, respectively). During follow-up, 116 (33.3%) patients died. Compared to patients with leucine levels between 109 and 174 µM, patients with leucine > 174 µM or <109 µM had a lower cumulative survival rate. Death was also associated with age, higher APACHE II and SOFA scores, C-reactive protein, and longer stays in the ICU, but with lower albumin, prealbumin, and transferrin. Patients with leucine levels > 174 µM had higher alanine aminotransferase levels, but no significant differences in other variables; patients with leucine levels < 109 µM had higher APACHE II and SOFA scores, higher incidence of using inotropic agents, longer ICU and hospital stays, but lower albumin and transferrin levels. Multivariable analysis demonstrated that leucine > 174 µM was an independent predictor of mortality, especially early mortality. However, among patients who stayed in ICU longer than two weeks, leucine < 109 µM was an independent predictor of mortality. In addition, leucine < 109 µM was associated with worse ventilator weaning profiles. These findings were similar in the validation cohort. Our study demonstrated a U-shape relationship between leucine levels and mortality rate in ICU.

[Experience of Implementing ABCDEF Bundle Care to Reduce Delirium in a Traumatic Brain Injury Patient].

Patients with traumatic brain injury (TBI) have a high incidence rate of delirium, which leads to poor prognoses. This case study describes a nursing experience of implementing ABCDEF bundle care to reduce delirium in a patient with TBI. The period of nursing care was April 23 to April 30, 2019. A comprehensive assessment of this patient's physical, psychological, familial, social, and spiritual dimensions was conducted via consultation, observation, and physical assessment. The assessment results showed that the patient suffered from acute delirium and cerebral perfusion impairment. In addition, the results showed that the patient's wife suffered from caregiver role strain that was further exacerbated by family difficulties. Multiple, individualized patient-tailored nursing interventions were developed under ABCDEF bundle care to alleviate delirium during the period of nursing care. These interventions included spontaneous awakening trials, spontaneous breathing trials, coordination, delirium assessment, early mobilization, and family engagement. Furthermore, family involvement and interprofessional cooperation with social workers were conducted concurrently to alleviate economic and care burdens and mitigate caregiver role strain in the patient's wife. It is hoped that this nursing care experience helps promote increased attention towards delirium, helps improve early detection of delirium in patients with TBI, and promotes the provision of individualized bundle care that draws on different perspectives in order to achieve holistic health care.

Elevated plasma phenylalanine predicts mortality in critical patients with heart failure.

AIMS: Previous studies found a relationship between elevated phenylalanine levels and poor cardiovascular outcomes. Potential strategies are available to manipulate phenylalanine metabolism. This study investigated whether increased phenylalanine predicted mortality in critical patients with either acute heart failure (HF) or acute on chronic HF, and its correlation with inflammation and immune cytokines. METHODS AND RESULTS: This study recruited 152 subjects, including 115 patients with HF admitted for critical conditions and 37 normal controls. We measured left ventricular ejection fraction (LVEF), plasma concentrations of phenylalanine, C-reactive protein, albumin, pre-albumin, transferrin, and pro-inflammatory and immune cytokines. Acute Physiology and Chronic Health Evaluation (APACHE II), Sequential Organ Failure Assessment (SOFA), and maximal vasoactive-inotropic scores (VISmax ) were calculated. Patients were followed up until death or a maximum of 1 year. The primary endpoint was all-cause death. Of the 115 patients, 37 (32.2%) were admitted owing to acute HF, and 78 (67.8%) were admitted owing to acute on chronic HF; 64 (55.7%) had ST elevation/non-ST elevation myocardial infarction. An LVEF measured during the hospitalization of <40%, 40-50%, and ≥50% was noted in 51 (44.3%), 15 (13.1%), and 49 (42.6%) patients, respectively. During 1 year follow-up, 51 (44.3%) patients died. Death was associated with higher APACHE II, SOFA, and VISmax scores; higher levels of C-reactive protein and phenylalanine; higher incidence of atrial fibrillation and use of inotropic agents; lower cholesterol, albumin, pre-albumin, and transferrin levels; and significant changes in pro-inflammatory and immune cytokines. Phenylalanine levels demonstrated an area under the receiver operating characteristic curve of 0.80 for mortality, with an optimal cut-off value set at 112 µM. Phenylalanine ≥ 112 µM was associated with a higher mortality rate than was phenylalanine < 112 µM (80.5% vs. 24.3%, P < 0.001) [hazard ratio = 5.07 (2.83-9.05), P < 0.001]. The Kaplan-Meier curves revealed that phenylalanine ≥ 112 µM was associated with a lower accumulative survival rate (log rank = 36.9, P < 0.001). Higher phenylalanine levels were correlated with higher APACHE II and SOFA scores, higher C-reactive protein levels and incidence of using inotropic agents, and changes in cytokines suggestive of immunosuppression, but lower levels of pre-albumin and transferrin. Further multivariable analysis showed that phenylalanine ≥ 112 µM predicted death over 1 year independently of age, APACHE II and SOFA scores, atrial fibrillation, C-reactive protein, cholesterol, pre-albumin, transferrin, and interleukin-8 and interleukin-10. CONCLUSIONS: Elevated phenylalanine levels predicted mortality in critical patients, phenotypically predominantly presenting with HF, independently of traditional prognostic factors and cytokines associated with inflammation and immunity.

Cardiovascular risk of sitagliptin in ischemic stroke patients with type 2 diabetes and chronic kidney disease: A nationwide cohort study.

Limited data are available about the cardiovascular (CV) safety and efficacy of sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, in ischemic stroke patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Ischemic stroke patients with T2DM and CKD were selected from the Taiwan National Health Insurance Research Database (NHIRD) from March 1, 2009 to December 31, 2011. A total of 1375 patients were divided into 2 age- and gender-matched groups: patients who received sitagliptin (n = 275; 20%) and those who did not (n = 1,100). Primary major adverse cardiac and cerebrovascular events (MACCE), including ischemic stroke, hemorrhagic stroke, myocardial infarction (MI), or CV death, were evaluated. During a mean 1.07-year follow-up period, 45 patients (16.4%) in the sitagliptin group and 165 patients (15.0%) in the comparison group developed MACCEs (Hazard ratio [HR] 1.05; 95% confidence interval [CI], 0.75-1.45). Compared to the non-sitagliptin group, the sitagliptin group had a similar risk of ischemic stroke (HR 0.82; 95% CI, 0.51-1.32.), hemorrhagic stroke (HR 1.50; 95% CI, 0.58-3.82), MI (HR 1.14; 95% CI, 0.49-2.65), and CV mortality (HR 1.06; 95% CI, 0.61-1.85). The use of sitagliptin in recent ischemic stroke patients with T2DM and CKD was not associated with increased or decreased risk of adverse CV events.

Two-dimensional myocardial deformation in coronary vasospasm-related Takotsubo cardiomyopathy: A case report of a serial echocardiographic study.

RATIONALE: Although transient reduction in the left ventricular ejection fraction is characteristic of Takotsubo cardiomyopathy, little is known about the time-course changes of myocardial deformation in coronary vasospasm-related Takotsubo cardiomyopathy. PATIENT CONCERNS: We retrospectively analyzed the time-course changes in left ventricle, right ventricle, and left atrium strain values in a patient with coronary vasospasm-related Takotsubo cardiomyopathy. We found that not only left ventricular strain but also left atrial strain was abnormal during acute Takotsubo cardiomyopathy due to coronary vasospasm. Right ventricular free wall strain was normal. DIAGNOSES: Coronary vasospasm-related Takotsubo cardiomyopathy. INTERVENTIONS: A serial echocardiographic study. OUTCOMES: The left ventricular strain was still subnormal despite a normalized left ventricular ejection fraction 2 months later. The left atrial strain was normal when the left ventricular ejection fraction normalized. LESSONS: From this limited experience, it is suggested that echocardiographic myocardial deformation analysis can provide more information than the standard ejection fraction in evaluating myocardial contractile function.

Layer-specific quantification of myocardial deformation in sepsis-induced Takotsubo cardiomyopathy: Three case reports of a serial 2-dimensional speckle-tracking echocardiographic study.

INTRODUCTION: Little is known about the time-course changes in left ventricular myocardial deformation in patients with Takotsubo cardiomyopathy (TC) using layer-specific quantification of myocardial deformation assessed by 2-dimensional speckle tracking echocardiography (2DSTE). CASE SUMMARY: In this retrospective 2DSTE follow-up study of 3 female patients with sepsis-induced TC, we examined changes in strain among the 3 myocardial layers, and examined the changes in left ventricular diastolic function and right ventricular systolic function. In all 3 patients, there was improvement of at least 15% in left ventricular ejection fractions, and improvement in left ventricular longitudinal and circumferential strains. The absolute differences in left ventricular global strains between the endocardium and epicardium, and between the first and the third 2DSTE studies reflect the following: a decrease in all 3 myocardial layers in patients with acute TC; and a slower improvement in mid-myocardial and epicardial function during recovery of TC. In addition, the right ventricular free wall strains were also impaired in the acute stage of TC with gradual improvement during recovery. CONCLUSIONS: Left ventricular strains did not fully recover even 1 month after acute TC. In addition, right ventricular free wall strains were also impaired in all 3 patients initially. In this case series, we found that layer-specific 2DSTE is a more sensitive method for myocardial function assessment than standard echocardiography.

Successful treatment of pediatric nail psoriasis with periodic pustular eruption using topical indigo naturalis oil extract.

Psoriasis of the nail greatly affects quality of life because of the difficulty in achieving long-lasting remission. Pustular psoriasis of the nail apparatus is characterized by the formation of sterile pustules, starting on one or two fingers or less often on the toes, and spontaneous improvement has rarely been observed. This case presents a girl with refractory nail psoriasis accompanied by periodic pustular eruption that responded well to topical treatment with indigo naturalis oil extract drops, achieving a remission of longer than 1 year.

Quality of life in patients with psoriasis in northern Taiwan.

BACKGROUND: Psoriasis has a significant negative impact on quality of life. The aim of this study was to identify factors associated with the quality of life of patients with psoriasis in Taiwan. METHODS: A retrospective study analyzing data from psoriasis patients who visited the outpatient clinics in the Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital at Taipei, Taoyuan and Keelung from July 2009 to January 2010 was performed. RESULTS: A total of 480 patients who had completed the assessment of disease severity and the dermatology life quality index (DLQI) questionnaire were analyzed. Of these patients, 67.5% were men. The mean score on the DLQI was 9.16 ± 6.3 and 67% of all patients reported a moderate to extremely large impact on their quality of life (DLQI > 6). A higher psoriasis area and severity index (PASI), younger age and initial lesions on the nails significantly negatively impacted patients' quality of life. Smoking, alcohol intake and gender were also weakly correlated. CONCLUSION: The clinical severity, age and site of initial lesions are associated with negative impacts on the quality of life of patients with psoriasis. These findings provide significant new insights into factors that affect the life quality of patients with psoriasis in Taiwan.