Nonalcoholic Hepatic Steatosis Is a Strong Predictor of High-Risk Coronary-Artery Plaques as Determined by Multidetector CT

Background

Nonalcoholic fatty liver disease is associated with a risk of coronary artery disease (e.g., diabetes mellitus, dyslipidemia, metabolic syndrome). We evaluated whether nonalcoholic hepatic steatosis is associated with high-risk plaques as assessed by multidetector computed tomography (CT).

Methods

This retrospective study involved 414 participants suspected of having coronary artery disease. Nonalcoholic hepatic steatosis was defined as a liver-to-spleen fat ratio of <1.0 and the presence and appropriate characteristics of coronary-artery plaques as assessed by coronary CT angiography. High-risk plaques were identified, as were low-density plaques, positive remodeling, and spotty calcification.

Results

Compared with patients who did not have nonalcoholic hepatic steatosis, patients with nonalcoholic hepatic steatosis had more low-density plaques (21% vs. 44%, p<0.01), positive remodeling (41% vs. 58%, p = 0.01), and spotty calcification (12% vs. 36%, p<0.01). The number of high-risk plaques in patients with nonalcoholic hepatic steatosis was greater than in those without nonalcoholic hepatic steatosis (p<0.01). Patients with nonalcoholic hepatic steatosis were more likely to have high-risk plaques than were those with only an elevated level of visceral adipose tissue (≥86 cm²; 35% vs. 16%, p<0.01). Multivariate analyses that included nonalcoholic hepatic steatosis, amount of visceral adipose tissue, and the presence/absence of traditional risk factors demonstrated that nonalcoholic hepatic steatosis was an independent predictor of high-risk plaques (odds ratio: 4.60; 95% confidence interval: 1.94–9.07, p<0.01).

Conclusions

Diagnosis of nonalcoholic hepatic steatosis may be of value when assessing the risk of coronary artery disease.     

Genetic Variation in miR-146a Is Not Associated with Susceptibility to IgA Nephropathy in Adults from a Chinese Han Population

Background

MicroRNA 146a (miR-146a) is a 19 to 23 nucleotide long, small non-coding RNA with gene regulatory functions that has influence on the pathogenesis of many diseases. A single nucleotide polymorphism (rs2910164 C>G) in pre-miR-146a is correlated with the expression of miR-146a. The aim of this study was to perform an association analysis of rs2910164 with IgA nephropathy in adult patients from a Chinese Han population.

Methods

A total of 145 patients with renal biopsy-proved IgA nephropathy (IgAN) and 179 healthy controls were recruited to the current study. rs2910164 was genotyped by the polymerase chain reaction (PCR) and high-resolution melting methods (HRM). Clinical characteristics and pathology grading of patients with IgAN were recorded at the time of kidney biopsy.

Result

There were significant differences among the population of patients grouped by different age of onset in a co-dominant model (CG vs. CC vs. GG) (p = 0.033) and a recessive model (CG+CC vs. GG) (p = 0.001). However, no significant difference was observed in the distribution of genotypes between cases and controls (p = 0.144). There was also no significant difference between rs2910164 and patient quantitative traits (all p > 0.003) or different pathology grading (Lee’s grading system and tubular atrophy/interstitial fibrosis in the Oxford classification) (all p > 0.05).

Conclusions

There was no association of rs2910164 with susceptibility to IgAN in adults from a Chinese Han population. However, rs2910164 was correlated with the age of onset of IgAN in adult patients.     

Reliability and Validity of Selected PROMIS Measures in People with Rheumatoid Arthritis

Purpose

To evaluate the reliability and validity of 11 PROMIS measures to assess symptoms and impacts identified as important by people with rheumatoid arthritis (RA).

Methods

Consecutive patients (N = 177) in an observational study completed PROMIS computer adapted tests (CATs) and a short form (SF) assessing pain, fatigue, physical function, mood, sleep, and participation. We assessed test-test reliability and internal consistency using correlation and Cronbach’s alpha. We assessed convergent validity by examining Pearson correlations between PROMIS measures and existing measures of similar domains and known groups validity by comparing scores across disease activity levels using ANOVA.

Results

Participants were mostly female (82%) and white (83%) with mean (SD) age of 56 (13) years; 24% had ≤ high school, 29% had RA ≤ 5 years with 13% ≤ 2 years, and 22% were disabled. PROMIS Physical Function, Pain Interference and Fatigue instruments correlated moderately to strongly (rho’s ≥ 0.68) with corresponding PROs. Test-retest reliability ranged from .725–.883, and Cronbach’s alpha from .906–.991. A dose-response relationship with disease activity was evident in Physical Function with similar trends in other scales except Anger.

Conclusions

These data provide preliminary evidence of reliability and construct validity of PROMIS CATs to assess RA symptoms and impacts, and feasibility of use in clinical care. PROMIS instruments captured the experiences of RA patients across the broad continuum of RA symptoms and function, especially at low disease activity levels. Future research is needed to evaluate performance in relevant subgroups, assess responsiveness and identify clinically meaningful changes.     

The Role of Polymerase Chain Reaction of High-Risk Human Papilloma Virus in the Screening of High-Grade Squamous Intraepithelial Lesions in the Anal Mucosa of Human Immunodeficiency Virus-Positive Males Having Sex with Males

Objectives

To evaluate the advantages of cytology and PCR of high-risk human papilloma virus (PCR HR-HPV) infection in biopsy-derived diagnosis of high-grade squamous intraepithelial lesions (HSIL = AIN2/AIN3) in HIV-positive men having sex with men (MSM).

Methods

This is a single-centered study conducted between May 2010 and May 2014 in patients (n = 201, mean age 37 years) recruited from our outpatient clinic. Samples of anal canal mucosa were taken into liquid medium for PCR HPV analysis and for cytology. Anoscopy was performed for histology evaluation.

Results

Anoscopy showed 33.8% were normal, 47.8% low-grade squamous intraepithelial lesions (LSIL), and 18.4% HSIL; 80.2% had HR-HPV. PCR of HR-HPV had greater sensitivity than did cytology (88.8% vs. 75.7%) in HSIL screening, with similar positive (PPV) and negative predictive value (NPV) of 20.3 vs. 22.9 and 89.7 vs. 88.1, respectively. Combining both tests increased the sensitivity and NPV of HSIL diagnosis to 100%. Correlation of cytology vs. histology was, generally, very low and PCR of HR-HPV vs. histology was non-existent (<0.2) or low (<0.4). Area under the receiver operating characteristics (AUROC) curve analysis of cytology and PCR HR-HPV for the diagnosis of HSIL was poor (<0.6). Multivariate regression analysis showed protective factors against HSIL were: viral suppression (OR: 0.312; 95%CI: 0.099-0.984), and/or syphilis infection (OR: 0.193; 95%CI: 0.045-0.827). HSIL risk was associated with HPV-68 genotype (OR: 20.1; 95%CI: 2.04-197.82).

Conclusions

When cytology and PCR HR-HPV findings are normal, the diagnosis of pre-malignant HSIL can be reliably ruled-out in HIV-positive patients. HPV suppression with treatment protects against the appearance of HSIL.     

Ocular Dominance Is Associated with the Ganglion Cell-Inner Plexiform Layer Thickness Profile in the Macula

Purpose

To investigate the characteristics of macular ganglion cell-inner plexiform layer (GCIPL) thickness profiles associated with ocular dominance.

Setting

Private practice, Seoul, Republic of Korea.

Design

Comparative case-control study.

Methods

Both eyes of 199 participants with no ophthalmic abnormalities were included. Participants were imaged by spectral-domain optical coherence tomography, and underwent dominant eye testing using a hole-in-a-card test (sighting dominance) at the same visit. Macular GCIPL, as well as circumpapillary retinal nerve fiber layer (RNFL) thickness were compared for individual patients, according to ocular dominance.

Results

Ocular dominance occurred predominantly in the right eye (right vs. left: 72.36 vs. 27.60%; P < 0.001). In the comparison of macular GCIPL thickness, the average (81.27±5.01 μm vs. 80.66±6.31 μm in dominant vs. non-dominant eyes), inferonasal (81.39±5.47μm vs. 80.33±6.82μm, and inferior sectors (77.95±6.05μm vs. 76.97±8.15μm) were significantly different between dominant and non-dominant eyes (P = 0.040, 0.005, and 0.032, respectively). Significant predictors of average GCIPL thickness were spherical equivalent (β = 1.37, P<0.001), astigmatic power (β = 1.44, P = 0.009), disc area (β = 3.90, P < 0.001), average RNFL thickness (β = 0.22, P<0.001), average cup-to-disc ratio (β = 5.74, P = 0.002), difference between the inferior and superior quadrant RNFL thicknesses (β = 0.08, P = 0.024), and ocular dominance (β = 2.10, P = 0.020). On multivariate regression analysis, ocular dominance was correlated with average GCIPL thickness after adjusting for potential confounders (β = 1.63, P = 0.048).

Conclusions

Dominant eyes accompanied significantly thicker average macular GCIPL. This information suggests that macular GCIPL thickness may provide an indicator of the relative dominance of an eye.     

The Rate of Helicobacter pylori Seropositivity in a Group of Korean Patients with HLA-B27-Associated Acute Anterior Uveitis

Purpose

To investigate an association between Helicobacter pylori seropositivity and HLA-B27-positive acute anterior uveitis (AAU) in Korean patients.

Methods

Retrospective analysis was performed with data from 106 patients previously diagnosed with AAU without clinical evidence of spondyloarthropathy. Serum immunoglobulin G antibodies to H. pylori were measured by enzyme-linked immunosorbent assay, and HLA typing was performed using polymerase chain reaction of DNA amplification. We included 72 non-uveitis patients and 35 age- and sex-matched healthy controls in the study.

Results

Of the 106 patients with AAU, 41 (38.7%) were HLA-B27-positive, and 45 (42.5%) were seropositive for H. pylori. Patients with HLA-B27-positive AAU had a significantly lower prevalence of H. pylori seropositivity compared to those with HLA-B27-negative AAU and healthy controls (24.4% vs. 53.8%, p = 0.003; 24.4% vs. 57.1%, p = 0.004, respectively). In the non-uveitis group, however, HLA-B27-positive patients exhibited similar H. pylori seropositivity prevalence to HLA-B27-negative patients and healthy controls (45.5% vs. 55.7%, p = 0.529; 45.5% vs. 57.1%, p = 0.497, respectively). In multivariate analysis, a low prevalence of H. pylori seropositivity was significantly associated with HLA-B27-positive AAU (odds ratio = 0.340, 95% confidence interval 0.135–0.855, p = 0.022).

Conclusions

Our results suggest an inverse association between H. pylori seropositivity and HLA-B27-positive AAU. Further investigation of this association is needed, given the low prevalence of H. pylori seropositivity observed in patients with HLA-B27-positive AAU.     

Understanding the Evolution of Multimorbidity: Evidences from the North West Adelaide Health Longitudinal Study (NWAHS)

Objective

The aim of this study is to describe the evolution of multimorbidity.

Study Design and Setting

Data from 1854 South Australians who participated in the North West Adelaide longitudinal Health Study(NWAHS) was collected between baseline (2000–2002) and follow-up (2008–2010). Status for eight chronic diseases (CDs) was determined by biomedical measurement or self-report. Chronic disease (CD) mean age of occurrence and order of appearance was investigated.

Results

The prevalence of multimorbidity increased from 32% to 64% during the 7.8±1.1 years of follow-up. The estimated mean age of onset of a new CD was significantly older for hypertension, cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) and younger for hypercholesterolemia, asthma and other mental problem. Hypercholesterolemia was more likely to develop as a first than as a subsequent CD (39%vs.16%, p<0.0001) while CVD (1%vs.5%, p<0.0001), diabetes (5%vs.11%, p<0.001) and COPD (6%vs.16%, p<0.0001) were less likely. The presence of mood disorders at baseline was associated with an increased risk of developing other mental disorders (36%vs.12%, p<0.0001), diabetes (18%vs.9%, p<0.01) and asthma (30%vs.21%, p<0.05).

Conclusion

Longitudinal data could be used to study the evolution of multimorbidity and could provide information on CDs mean age of occurrence, order of appearance and impact on the development of future CDs.     

Decreased Risk of Ventilator-Associated Pneumonia in Sepsis Due to Intra-Abdominal Infection

Rationale

Experimental studies suggest that intra-abdominal infection (IAI) induces biological alterations that may affect the risk of lung infection.

Objectives

To investigate the potential effect of IAI at ICU admission on the subsequent occurrence of ventilator-associated pneumonia (VAP).

Methods

We used data entered into the French prospective multicenter Outcomerea database in 1997–2011. Consecutive patients who had severe sepsis and/or septic shock at ICU admission and required mechanical ventilation for more than 3 days were included. Patients with acute pancreatitis were not included.

Measurements and Main Results

Of 2623 database patients meeting the inclusion criteria, 290 (11.1%) had IAI and 2333 (88.9%) had other infections. The IAI group had fewer patients with VAP (56 [19.3%] vs. 806 [34.5%], P<0.01) and longer time to VAP (5.0 vs.10.5 days; P<0.01). After adjustment on independent risk factors for VAP and previous antimicrobial use, IAI was associated with a decreased risk of VAP (hazard ratio, 0.62; 95% confidence interval, 0.46–0.83; P<0.0017). The pathogens responsible for VAP were not different between the groups with and without IAI (Pseudomonas aeruginosa, 345 [42.8%] and 24 [42.8%]; Enterobacteriaceae, 264 [32.8%] and 19 [34.0%]; and Staphylococcus aureus, 215 [26.7%] and 17 [30.4%], respectively). Crude ICU mortality was not different between the groups with and without IAI (81 [27.9%] and 747 [32.0%], P = 0.16).

Conclusions

In our observational study of mechanically ventilated ICU patients with severe sepsis and/or septic shock, VAP occurred less often and later in the group with IAIs compared to the group with infections at other sites.     

A Clinical Study of Acquired Immunodeficiency Syndrome Associated Penicillium Marneffei Infection from a Non-Endemic Area in China

Objective

To investigate the clinical characteristics, diagnosis, treatment and prognosis of penicilliosis among the patients with acquired immunodeficiency syndrome (AIDS) in non-endemic areas of China, and then to discuss its incubation period and the diagnostic performance of serum galactomannan test for penicilliosis.

Methods

Medical records and travel histories of penicilliosis patients in Zhongnan hospital from January 2006 to December 2013, and the interval from when the patients left the endemic area to the onset of the disease was analyzed. Serum galactomannan levels of penicilliosis patients and AIDS patients with fever were measured by the Platelia Aspergillus Enzyme Immunoassay Kit.

Results

A total of 47 AIDS-associated penicilliosis were confirmed by fungal culture, which accounted for 4.8% of 981 AIDS-related admissions. The sensitivity and specificity of serum galactomannan test for penicilliosis were 95.8% (23/24) and 90.9% (30/33), respectively, (cutoff index = 1.0). Two independent predictors for early mortality (death within 12 weeks) of the patients (21.3%, 10/47) were a delayed diagnosis and no treatment with antifungal therapy. Among 14 patients who became ill after leaving endemic areas, ten patients presented with the onset symptoms within 12 months (from 11 days to 360 days). We found a patient living with asymptomatic P. marneffei fungemia who had not received any antifungal therapy until 18 months’ follow up.

Conclusions

The co-infection of P. marneffei and HIV was not uncommon in the non-endemic areas of penicilliosis in China. There exists a latent form of infection for P. marneffei. The incubation period of penicilliosis may be quite different from one patient to another. In AIDS patients, the serum galactomannan test has utility for the diagnosis of penicilliosis. When patients with penicilliosis/AIDS were diagnosed early and treated with standardized antifungal therapy and combined antiretroviral therapy, their prognosis improved.     

Serum Total Cholinesterase Activity on Admission Is Associated with Disease Severity and Outcome in Patients with Traumatic Brain Injury

Background

Traumatic brain injury (TBI) is one of the leading causes of neurological disability. In this retrospective study, serum total cholinesterase (ChE) activities were analyzed in 188 patients for diagnostic as well as predictive values for mortality.

Methods and Findings

Within 72 hours after injury, serum ChE activities including both acetylcholinesterase and butyrylcholinesterase were measured. Disease severity was evaluated with Acute Physiology and Chronic Health Evaluation (APACHE) II score, Glasgow Coma Score, length of coma, post-traumatic amnesia and injury feature. Neurocognitive and functional scores were assessed using clinical records. Of 188 patients, 146 (77.7%) survived and 42 (22.3%) died within 90 days. Lower ChE activities were noted in the non-survivors vs. survivors (5.94±2.19 vs. 7.04±2.16 kU/L, p=0.023), in septic vs. non-infected patients (5.93±1.89 vs. 7.31±2.45 kU/L, p=0.0005) and in patients with extremely severe injury vs. mild injury (6.3±1.98 vs. 7.57±2.48 kU/L, p=0.049). The trajectories of serum ChE levels were also different between non-survivors and survivors, septic and non-infected patients, mild and severely injured patients, respectively. Admission ChE activities were closely correlated with blood cell counts, neurocognitive and functional scores both on admission and at discharge. Receiver operating characteristic analysis showed that the area under the curve for ChE was inferior to that for either APACHE II or white blood cell (WBC) count. However, at the optimal cutoff value of 5 kU/L, the sensitivity of ChE for correct prediction of 90-day mortality was 65.5% and the specificity was 86.4%. Kaplan-Meier analysis showed that lower ChE activity (<5 kU/L) was more closely correlated with poor survival than higher ChE activity (>5 kU/L) (p=0.04). After adjusting for other variables, ChE was identified as a borderline independent predictor for mortality as analyzed by Binary logistic regression (P=0.078).

Conclusions

Lowered ChE activity measured on admission appears to be associated with disease severity and outcome for TBI patients.     

High Prevalence of Methicillin-Resistant Staphylococcus aureus among Patients with Septic Arthritis Caused by Staphylococcus aureus

Background

This study investigated the clinical characteristics of patients with septic arthritis caused by Staphylococcus aureus and tried to identify the risk factors for methicillin-resistant S. aureus (MRSA) arthritis.

Methods

Between January 2008 and December 2011, patients with septic arthritis caused by S. aureus were identified from the computerized databases of a regional hospital and a medical center in southern Taiwan. The medical records of these patients were retrospectively reviewed.

Results

A total of 93 patients with S. aureus arthritis were identified, and MRSA arthritis was found in 38 (40.9%) cases. The mean age of the patients was 58 years, and 86 (92.5%) episodes were classified as community-acquired infections. Diabetes mellitus (n = 41, 44.1%) was the most common underlying disease, followed by chronic kidney disease and liver cirrhosis. Patients with MRSA arthritis were more frequently elderly and found in the setting of healthcare-associated infection than patients with methicillin-susceptible S. aureus (MSSA) infections. No other significant differences in clinical manifestations and outcomes were noted between these two groups of patients. Overall, the in-hospital mortality rate was 5.4%, and diabetes mellitus was the only risk factor for mortality.

Conclusions

MRSA is emerging in the setting of community-acquired septic arthritis. MRSA septic arthritis is more likely to develop in the elderly and in healthcare-associated infections than MSSA septic arthritis.     

Characterization of Sleep Breathing Pattern in Patients with Type 2 Diabetes: Sweet Sleep Study

Background

Although sleep apnea-hypopnea syndrome (SAHS) is highly prevalent in patients with type 2 diabetes (T2D), it is unknown whether or not subjects with and without T2D share the same sleep breathing pattern.

Methodology/Principal findings

A cross-sectional study in patients with SAHS according to the presence (n = 132) or not (n = 264) of T2D. Both groups were matched by age, gender, BMI, and waist and neck circumferences. A subgroup of 125 subjects was also matched by AHI. The exclusion criteria included chronic respiratory disease, alcohol abuse, use of sedatives, and heart failure. A higher apnea hypopnea index (AHI) was observed in T2D patients [32.2 (10.2–114.0) vs. 25.6 (10.2–123.4) events/hours; p = 0.002). When sleep events were evaluated separately, patients with T2D showed a significant increase in apnea events [8.4 (0.1–87.7) vs. 6.3 (0.0–105.6) e/h; p = 0.044), as well as a two-fold increase in the percentage of time spent with oxygen saturation <90% [15.7 (0.0–97.0) vs. 7.9 (0.0–95.6) %; <0.001)], higher rates of oxygen desaturation events, and also higher daily sleepiness [7.0 (0.0–21.0) vs. 5.0 (0.0–21.0); p = 0.006)] than subjects without T2D. Significant positive correlations between fasting plasma glucose and AHI, the apnea events, and CT90 were observed. Finally, multiple linear regression analyses showed that T2D was independently associated with AHI (R² = 0.217), the apnea index (R² = 0.194), CT90 (R² = 0.222), and desaturation events.

Conclusions/significance

T2D patients present a different pattern of sleep breathing than subject without diabetes. The most important differences are the severity of hypoxemia and the number of apneas whereas the incidence of hypopnea episodes is similar.     

Multi-Parametric Evaluation of Chronic Kidney Disease by MRI: A Preliminary Cross-Sectional Study

Background

The current clinical classification of chronic kidney disease (CKD) is not perfect and may be overestimating both the prevalence and the risk for progressive disease. Novel markers are being sought to identify those at risk of progression. This preliminary study evaluates the feasibility of magnetic resonance imaging based markers to identify early changes in CKD.

Methods

Fifty-nine subjects (22 healthy, 7 anemics with no renal disease, 30 subjects with CKD) participated. Data using 3D volume imaging, blood oxygenation level dependent (BOLD) and Diffusion MRI was acquired. BOLD MRI acquisition was repeated after 20 mg of iv furosemide.

Results

Compared to healthy subjects, those with CKD have lower renal parenchymal volumes (329.6±66.4 vs. 257.1±87.0 ml, p<0.005), higher cortical R2* values (19.7±3.2 vs. 23.2±6.3 s⁻¹, p = 0.013) (suggesting higher levels of hypoxia) and lower response to furosemide on medullary R2* (6.9±3.3 vs. 3.1±7.5 s⁻¹, p = 0.02). All three parameters showed significant correlation with estimated glomerular filtration rate (eGFR). When the groups were matched for age and sex, cortical R2* and kidney volume still showed significant differences between CKD and healthy controls. The most interesting observation is that a small number of subjects (8 of 29) contributed to the increase in mean value observed in CKD. The difference in cortical R2* between these subjects compared to the rest were highly significant and had a large effect size (Cohen’s d = 3.5). While highly suggestive, future studies may be necessary to verify if such higher levels of hypoxia are indicative of progressive disease. Diffusion MRI showed no differences between CKD and healthy controls.

Conclusions

These data demonstrate that BOLD MRI can be used to identify enhanced hypoxia associated with CKD and the preliminary observations are consistent with the chronic hypoxia model for disease progression in CKD. Longitudinal studies are warranted to further verify these findings and assess their predictive value.     

Quality of Life in CAM and Non-CAM Users among Breast Cancer Patients during Chemotherapy in Malaysia

Background

Complementary and alternative medicine (CAM) use has become increasingly popular among patients with cancer. The purposes of this study were to compare the QOL in CAM users and non-CAM users and to determine whether CAM use influences QOL among breast cancer patients during chemotherapy.

Methodology

A cross-sectional survey was conducted at two outpatient chemotherapy centers. A total of 546 patients completed the questionnaires on CAM use. QOL was evaluated based on the European Organization for Research and Treatment of Cancer (EORTC) core quality of life (QLQ-C30) and breast cancer-specific quality of life (QLQ-BR23) questionnaires.

Results

A total of 70.7% of patients were identified as CAM users. There was no significant difference in global health status scores and in all five subscales of the QLQ C30 functional scales between CAM users and non-CAM users. On the QLQ-C30 symptom scales, CAM users (44.96±3.89) had significantly (p = 0.01) higher mean scores for financial difficulties than non-CAM users (36.29±4.81). On the QLQ-BR23 functional scales, CAM users reported significantly higher mean scores for sexual enjoyment (6.01±12.84 vs. 4.64±12.76, p = 0.04) than non-CAM users. On the QLQ-BR23 symptom scales, CAM users reported higher systemic therapy side effects (41.34±2.01 vs. 37.22±2.48, p = 0.04) and breast symptoms (15.76±2.13 vs. 11.08±2.62, p = 0.02) than non-CAM users. Multivariate logistic regression analysis indicated that the use of CAM modality was not significantly associated with higher global health status scores (p = 0.71).

Conclusion

While the findings indicated that there was no significant difference between users and non-users of CAM in terms of QOL, CAM may be used by health professionals as a surrogate to monitor patients with higher systemic therapy side effects and breast symptoms. Furthermore, given that CAM users reported higher financial burdens (which may have contributed to increased distress), patients should be encouraged to discuss the potential benefits and/or disadvantages of using CAM with their healthcare providers.     

Serum Cystatin C Reflects Angiographic Coronary Collateralization in Stable Coronary Artery Disease Patients with Chronic Total Occlusion

Objective

We investigated whether and to what extent cystatin C was associated with angiographic coronary collateralization in patients with stable coronary artery disease and chronic total occlusion.

Methods

Serum levels of cystatin C and high-sensitive C-reactive protein (hsCRP) and glomerular filtration rate (GFR) were determined in 866 patients with stable angina and angiographic total occlusion of at least one major coronary artery. The degree of collaterals supplying the distal aspect of a total occlusion from the contra-lateral vessel was graded as poor (Rentrop score of 0 or 1) or good coronary collateralization (Rentrop score of 2 or 3).

Results

In total, serum cystatin C was higher in patients with poor collateralization than in those with good collateralization (1.08 ± 0.32 mg/L vs. 0.90 ± 0.34 mg/L, P < 0.001), and correlated inversely with Rentrop score (adjusted Spearmen’s r = -0.145, P < 0.001). The prevalence of poor coronary collateralization increased stepwise with increasing cystatin C quartiles (P for trend < 0.001). After adjusting for age, gender, risk factors for coronary artery disease, GFR and hsCRP, serum cystatin C ≥ 0.97 mg/L remained independently associated with poor collateralization (OR 2.374, 95% CI 1.660 ~ 3.396, P < 0.001). The diagnostic value of cystatin C levels for detecting poor coronary collateralization persisted regardless of age, gender, presence or absence of diabetes, hypertension or renal dysfunction.

Conclusions

Serum cystatin C reflects angiographic coronary collateralization in patients with stable coronary artery disease, and cystatin C ≥ 0.97 mg/L indicates a great risk of poor coronary collaterals.     

Association between TNFA Gene Polymorphisms and Helicobacter pylori Infection: A Meta-Analysis

Background

Several host genetic factors are thought to affect susceptibility to Helicobacter pylori infection-related diseases, including tumor necrosis factor (TNF)-α. Previous studies have evaluated the association between TNFA gene polymorphisms and H. pylori infection, but the results were inconclusive. We conducted this meta-analysis to clarify the association between TNFA polymorphisms and H. pylori infection.

Methods

Published literature within PubMed, Embase, and the Cochrane Library were used in our meta-analysis. Data were analyzed with the Stata13.1 software package using pooled odds ratios (ORs) with 95% confidence intervals (CI).

Results

A total of 24 studies were included in our study. The TNFA -308G>A polymorphism was associated with decreasing H. pylori infection (AA vs. AG+GG, OR = 0.64, 95% CI = 0.43–0.97; AA vs. GG, OR = 0.64, 95% CI = 0.43–0.97). A significantly decreased risk was also found for -1031T>C polymorphism (CC vs. CT+TT, OR = 0.61, 95% CI = 0.44–0.84). -863C>A polymorphism was associated with increasing risk of H. pylori infection (AA+AC vs. CC, OR = 1.47, 95% CI = 1.16–1.86; A allele vs. C allele, OR = 1.40, 95% CI = 1.14–1.72). There was no significant association between -857C>T polymorphism and H. pylori infection. When stratified analysis was conducted on H. pylori infection detection methods, -857C>T and -863C>A polymorphisms were associated with H. pylori infection for the non-ELISA subgroup. When stratified for ethnicity or study design, -863C>A significantly increased the risk and -1031T>C decreased the risk for the Asian subgroup and hospital-based subgroup.

Conclusion

Results of our meta-analysis demonstrate that TNFA -308G>A and -1031 T>C polymorphisms may be protective factors against H. pylori infection, and -863C>A may be a risk factor, especially in Asian populations. Further studies with larger sample sizes are required to validate these results.     

Improved Outcome with Early Rifampicin Combination Treatment in Methicillin-Sensitive Staphylococcus aureus Bacteraemia with a Deep Infection Focus – A Retrospective Cohort Study

Introduction

Rifampicin has been used as adjunctive therapy in Staphylococcus aureus bacteraemia (SAB) with a deep infection focus. However, data for prognostic impact of rifampicin therapy is unestablished including the optimal initiation time point. We studied the impact of rifampicin therapy and the optimal initiation time for rifampicin treatment on prognosis in methicillin-sensitive S. aureus bacteraemia with a deep infection.

Methods

Retrospective, multicentre study in Finland including 357 SAB patients with a deep infection focus. Patients with alcoholism, liver disease or patients who died within 3 days were excluded. Patients were categorised according to duration of rifampicin therapy and according to whether rifampicin was initiated early (within 7 days) or late (7 days after) after the positive blood cultures. Primary end point was 90 days mortality.

Results

Twenty-seven percent of patients received no rifampicin therapy, 14% received rifampicin for 1-13 days whereas 59% received rifampicin ≥14 days. The 90 day mortality was; 26% for patients treated without rifampicin, 16% for rifampicin therapy of any length and 10% for early onset rifampicin therapy ≥14 days. Lack of rifampicin therapy increased (OR 1.89, p=0.026), rifampicin of any duration decreased (OR 0.53, p=0.026) and rifampicin therapy ≥14 days with early onset lowered the risk for a fatal outcome (OR 0.33, p<0.01) during 90 days follow-up.

Conclusion

Rifampicin adjunctive therapy for at least 14 days and initiated within 7 days of positive blood culture associated with improved outcome among SAB patients with a deep infection.     

East London Experience with Enteric Fever 2007-2012

Purpose

The clinical presentation and epidemiology for patients with enteric fever at two hospitals in East London during 2007–2012 is described with the aim to identify preventive opportunities and to reduce the cost of treatment.

Methods

A retrospective analysis of case notes from patients admitted with enteric fever during 2007 to 2012 with a microbiologically confirmed diagnosis was undertaken. Details on clinical presentation, travel history, demographic data, laboratory parameters, treatment, patient outcome and vaccination status were collected.

Results

Clinical case notes were available for 98/129 (76%) patients including 69 Salmonella enterica serovar Typhi (S. Typhi) and 29 Salmonella enterica serovar Paratyphi (S. Paratyphi). Thirty-four patients (35%) were discharged from emergency medicine without a diagnosis of enteric fever and then readmitted after positive blood cultures. Seventy-one of the 98 patients (72%) were UK residents who had travelled abroad, 23 (23%) were foreign visitors/new entrants to the UK and four (4%) had not travelled abroad. Enteric fever was not considered in the initial differential diagnosis for 48/98 (49%) cases. The median length of hospital stay was 7 days (range 0–57 days). The total cost of bed days for managing enteric fever was £454,000 in the two hospitals (mean £75,666/year). Median time to clinical resolution was five days (range 1–20). Seven of 98 (7%) patients were readmitted with relapsed or continued infection. Six of the 71 (8%) patients had received typhoid vaccination, 34 (48%) patients had not received vaccination, and for 31 cases (44%) vaccination status was unknown.

Conclusions

Further interventions regarding education and vaccination of travellers and recognition of the condition by emergency medicine clinicians in travellers to South Asia is required.     

A Genomic Approach to Resolving Relapse versus Reinfection among Four Cases of Buruli Ulcer

Background

Increased availability of Next Generation Sequencing (NGS) techniques allows, for the first time, to distinguish relapses from reinfections in patients with multiple Buruli ulcer (BU) episodes.

Methodology

We compared the number and location of single nucleotide polymorphisms (SNPs) identified by genomic screening between four pairs of Mycobacterium ulcerans isolates collected at the time of first diagnosis and at recurrence, derived from a collection of almost 5000 well characterized clinical samples from one BU treatment center in Benin.

Principal Findings

The findings suggest that after surgical treatment—without antibiotics—the second episodes were due to relapse rather than reinfection. Since specific antibiotics were introduced for the treatment of BU, the one patient with a culture available from both disease episodes had M. ulcerans isolates with a genomic distance of 20 SNPs, suggesting the patient was most likely reinfected rather than having a relapse.

Conclusions

To our knowledge, this study is the first to study recurrences in M. ulcerans using NGS, and to identify exogenous reinfection as causing a recurrence of BU. The occurrence of reinfection highlights the contribution of ongoing exposure to M. ulcerans to disease recurrence, and has implications for vaccine development.     

Epidemiology and Clinical Features of Pulmonary Nontuberculous Mycobacteriosis in Nagasaki,Japan

Background and Objectives

Recent reports indicate that the incidence of nontuberculous mycobacterial-lung disease (NTM-LD) is increasing. This study aimed to investigate the epidemiology and clinical features of NTM-LD patients in Nagasaki prefecture, Japan to identify the negative prognostic factors for NTM-LD in Japan.

Methods

The medical records of patients newly diagnosed with NTM-LD in eleven hospitals in Nagasaki prefecture between January 2001 and February 2010 were reviewed. Data regarding the annual population of each region and the incidence of all forms of tuberculosis were collected to assess geographic variations in NTM-LD incidence, isolates, and radiological features.

Results

A total 975 patients were diagnosed with NTM-LD. The incidence increased over the study period and reached 11.0 and 10.1 per 100,000 population in 2008 and 2009, respectively. M. intracellulare was the most common pathogen in the southern region, and M. avium most common in other regions. The most common radiographic pattern was the nodular-bronchiectatic pattern. Age >60 years, body mass index <18.5 kg/m², underlying lung disease, and cavitary pattern were the negative prognostic factors at the 1-year follow-up.

Conclusions

The incidence of NTM-LD has been increasing in Nagasaki prefecture. The isolates and radiographic features of patients vary markedly by region.