Journal of Investigative Medicine

Cirrhotic patients admitted with altered mental status (AMS) represent a clinical challenge, as many potentially life-threatening diseases must be considered. Although many patients with AMS have hepatic encephalopathy (HE), other causes of AMS occur, and we hypothesized that these may have different outcomes.

We aimed to understand the causes of AMS in cirrhotic patients admitted to the hospital and investigate their associated outcomes.

We performed a retrospective cohort study in 1218 inpatients with cirrhosis. Altered mental status was defined a priori (HE, sepsis/infectious, metabolic, exogenous drugs/toxins, structural lesions, or psychiatric abnormalities).

Patients with AMS had higher levels of serum bilirubin, international normalized ratio, blood urea nitrogen, creatinine, and lower levels of albumin and platelets than those with normal mental status (NMS) (P = < 0.001). The most common cause of AMS was HE, accounting for nearly half of all patients. Other causes of AMS included the following: sepsis/infection (23%), metabolic disorders (8%), drugs/toxins (7%), structural lesions (5%), psychiatric disorders (1%), or multiple causes (8%). Mortality in patients with AMS was 35% compared to 16% in those with NMS (P < 0.0001). Patients with sepsis/infection, structural lesions, or multiple disorders causing AMS had the highest mortality (61%, 68%, and 79%, respectively).

Nearly one third of admissions in cirrhotic patients were due to AMS, most commonly caused by HE. The overall mortality of patients admitted with AMS was greater than with NMS, particularly for those with infection or structural lesions, emphasizing the importance of a search for these causes of AMS in all patients with cirrhosis.

Obesity has been shown to have implications for chronic kidney disease (CKD); however, it has received minimal attention from scientists studying CKD among African Americans.

The purpose of this study was to examine the manner in which weight status has implications for CKD among this group through analysis of data drawn from the Jackson Heart Study (JHS).

Cross-sectional analysis of a single-site longitudinal population-based cohort.

The data for this study were drawn from the baseline examination of the Jackson Heart Study (JHS). The analytic cohort consisted of 3430 African American men and women (21–84 years of age) living in the tricounty area of the Jackson, Mississippi metropolitan areas with complete data to determine CKD status.

The primary dependent variable was CKD (defined as the presence of albuminuria or reduced estimated glomerular filtration rate <60 mL/min per 1.73 m²). Weight status, the primary predictor, was a 4-category measure based on body mass index.

Associations were explored through bivariable analyses and multivariable logistic regression analyses adjusting for CKD, weight status, diabetes, hypertension, and cardiovascular disease risk factors as well as demographic factors. The prevalence of CKD in the JHS was 20%. The proportion of overweight, class I, and class II obese individuals was 32.5%, 26.9%, and 26.2% respectively. In the pooled model, weight status was not found to be associated with CKD; however, subgroup analysis revealed that class II obesity was associated with CKD among men (odds ratio, 2.37; confidence interval, 1.34–4.19) but not among women (odds ratio, 1.32; confidence interval, 0.88–1.98). The relationship between CKD prevalence and diabetes and CKD prevalence and hypertension varied by sex and differed across weight categories.

Weight status has implications for CKD among the JHS participants, and this study underscores the need for additional research investigating the relationship between weight status, sex, and CKD among African Americans.

Aspirin-exacerbated respiratory disease (AERD) is nonatopic asthma, and the role of heat shock protein (HSP) 70 in AERD remains unknown. We analyzed HSP70 gene polymorphisms in Japanese patients with AERD.

The single-nucleotide polymorphisms in HSPA1B-179C>T and 1267A>G gene were examined in patients with AERD and those with aspirin-tolerant asthma (ATA). All patients were in a stable condition.

There were significant differences in total serum IgE levels, peripheral blood eosinophil count, and prevalence of atopy between AERD and ATA. The patients with AERD showed higher frequencies of the CT/TT genotype of the HSPA1B-179C>T than that of the CC genotype compared to ATA (P < 0.001). They showed higher frequencies of the GG genotype of the HSPA1B1267A>G than that of the GA/AA genotype compared to ATA (P < 0.001). These differences were irrespective of the sex for the genotypes analyzed. The frequency of HSPA1B-179C/1267A haplotype was significantly higher in AERD compared to ATA (P < 0.001; odds ratio, 3.154; 95% confidence interval, 1.916-5.193). Among the clinical and hematological characteristics investigated, AERD showed a significant variance in peripheral blood eosinophil count according to the association of the 2 HSP70 gene polymorphisms (P = 0.033), but not in ATA.

Our findings first suggest that the association between HSPA1B-179C>T and 1267A>G gene sequence variations might be implicated in the development of AERD.

The frequency and clinical correlates of global right ventricular (RV) dysfunction in patients treated with primary percutaneous coronary intervention for a first acute ST-elevation myocardial infarction (STEMI) without a coexisting RV infarction is not well known.

One hundred seven consecutive patients underwent conventional echocardiography and pulsed-wave tissue Doppler imaging (TDI) within 72 hours after a successful primary percutaneous coronary intervention to assess their RV function. Global RV function was quantified with the RV myocardial performance index (MPI) by pulsed-wave TDI. An abnormal TDI-derived RV MPI was defined as greater than the upper reference limit of 0.55.

Global RV dysfunction was present in 18 (17%) of the 107 patients enrolled. The patients with global RV dysfunction had significantly higher glucose levels on admission (216 ± 102 vs 163 ± 86 mg/dL; P = 0.027), higher peak creatine kinase (4027 ± 2171 vs 2660 ± 1980 IU/L; P = 0.014), and more frequently had anterior infarcts (89% vs 58%; P = 0.016) than those without RV dysfunction. Patients with global RV dysfunction also had a significantly lower left ventricular (LV) ejection fraction (45.1 ± 10.8% vs 51.1 ± 9.7%; P = 0.021), a higher global wall motion score index (1.9 ± 0.3 vs 1.7 ± 0.4; P = 0.007), and greater LV MPI (0.65 ± 0.19 vs 0.47 ± 0.11; P = 0.001) than patients without. With the use of multivariate regression analysis, TDI-derived LV MPI (odds ratio [OR], 3.40; 95% confidence interval [CI], 1.20–9.67; P = 0.022), the ratio of transmitral peak early (E) to late diastolic filling (A) velocities (E/A ratio) (OR, 0.41; 95% CI, 0.18–0.92; P = 0.031), and admission plasma glucose level (OR, 1.01; 95% CI, 1.0–1.02; P = 0.039) were independently associated with the presence of global RV dysfunction.

In patients with a first acute STEMI without an associated RV infarction, depressed global LV function reflected by increased TDI-derived LV MPI, a lower mitral E/A ratio, and a higher glucose level on admission are independent correlates of early global RV dysfunction. Routine assessment of global RV function should be implemented in patients with STEMI with these characteristics.

Myeloperoxidase (MPO) has been associated with the development of atrial fibrillation (AF), but its impact on the recurrence of AF after catheter ablation has not been explored. This study investigated the effect of plasma MPO on recurrence after catheter ablation of paroxysmal AF.

Two hundred eighty-eight consecutive patients with paroxysmal AF and who underwent circumferential pulmonary vein isolation were prospectively enrolled. After a mean ± SD follow-up of 516 ± 204 (91–910) days, the recurrence rates were 16.9%, 25.7%, 29.7%, and 38.0% from the lowest MPO quartile to the highest MPO quartile, respectively (P = 0.023). After adjustment for age, sex, left atrial diameter, high-sensitivity C-reactive protein, and pulmonary vein isolation, there was an increased risk of recurrence in the subjects with the highest MPO quartile compared with those with the lowest quartile (hazard ratio, 3.18; 95% confidence interval, 2.12–5.23; P = 0.024). As a continuous variable, MPO was also an independent predictor of recurrence (hazard ratio, 2.12; 95% confidence interval, 1.71–3.27; P = 0.032).

Patients with high MPO levels were at an increased risk of AF recurrence after catheter ablation.

Several cardiac biomarkers, especially brain natriuretic peptide (BNP) and N-terminal (NT)-proBNP, have been used as predictors of prognosis and negative remodeling in DCM. In the present study, we aimed to evaluate the prognostic value of tenascin-C in dilated cardiomyopathy (DCM) and whether it can be used to determine reverse remodeling in patients with DCM.

Sixty-six patients with DCM were followed up for 12 months after initiation of medical treatment including carvedilol, ramipril (candesartan if ramipril was not tolerated), spironolactone, and furosemide. Tenascin-C and NT-proBNP measurements and transthoracic echocardiography were performed at baseline and at 12 months.

At 12 months, a significant improvement in New York Heart Association class (2.57 ± 0.6 vs. 1.87 ± 0.5; P < 0.0001), left ventricular end-diastolic volume (217 ± 47 vs 203 ± 48; P < 0.0001), left ventricular ejection fraction (29.1 ± 5.5 vs 30.9 ± 3.8; P < 0.0001), NT-proBNP (2019 ± 558 vs 1462 ± 805; P < 0.0001), and tenascin-C (76 ± 19 vs 48 ± 28; P < 0.0001) values were observed, compared with baseline. Importantly, decrease in tenascin-C values were correlated with increase in left ventricular ejection fraction. Tenascin-C (odds ratio [OR], 1.896; <95% confidence interval [CI], 1.543–2.670; P = 0.02), diabetes mellitus (OR, 2.456; G95% CI, 1.987–3.234; P = 0.01) and hypertension (OR: 2.106, <95% CI, 1.876–2.897; P = 0.03) were independent predictors of mortality in patients with DCM.

Reverse ventricular remodeling obtained with carvedilol, ramipril/candesartan, and spironolacton is associated with decreases in left ventricular end-diastolic volume, left ventricular end-systolic volume, tenascin-C levels, and NT-proBNP levels. Consequently, tenascin-C may be used to evaluate reverse remodeling in patients with DCM.