Fifteen-year study of the changing epidemiology of methicillin-resistant Staphylococcus aureus

Purpose

The study’s purpose was to elucidate the evolutionary, microbiologic, and clinical characteristics of methicillin-resistant Staphylococcus aureus (MRSA) infections.

Methods

MRSA cases from military medical facilities in San Diego, from 1990 to 2004, were evaluated and categorized as community-acquired or nosocomial. Sequence type, staphylococcal chromosomal cassette gene type, and Panton-Valentine leukocidin gene status were determined for a subset of isolates.

Results

Over the 15-year period, 1888 cases of MRSA were identified; 65% were community acquired. The incidence (155 infections/100 000 person-year in 2004) and household-associated cases rapidly increased since 2002. Among persons with community-acquired MRSA, 16% were hospitalized and only 17% were initially given an effective antibiotic. Community-acquired MRSA cases compared with nosocomial MRSA cases were more often soft-tissue and less often urinary, lung, or bloodstream infections (P < .001). Patients with community-acquired MRSA were younger (22 vs 64 years, P < .001) and less likely to have concurrent medical conditions (9% vs 98%, P < .001). Clindamycin resistance increased among community-acquired MRSA isolates during 2003 and 2004 compared with previous years (79% vs 13%, P < .001). Genetically, nosocomial MRSA isolates were significantly different than those acquired in the community. Although community-acquired MRSA isolates were initially diverse by 2004, one strain (staphylococcal chromosomal cassette type IV, sequence type 8, Panton-Valentine leukocidin gene positive) became the predominant isolate.

Conclusions

Community-acquired and intrafamilial MRSA infections have increased rapidly since 2002. Our 15 years of surveillance revealed the emergence of distinct community-acquired MRSA strains that were genetically unrelated to nosocomial MRSA isolates from the same community.     

Benefit of appropriate empirical antibiotic treatment: thirty-day mortality and duration of hospital stay

Purpose

We evaluated the effect of inappropriate antibiotic treatment on mortality and duration of hospital stay in medical inpatients with bacterial infections.

Subjects and methods

Two cohorts of febrile adult patients (excluding patients with acquired immune deficiency syndrome and organ transplant recipients), hospitalized in three medical centers in Israel, Italy, and Germany, were included. Patients’ data were collected prospectively. Initial empirical treatment was defined as appropriate if an antibiotic prescribed within 24 hours of the first encounter with the patient matched the in vitro susceptibility of a pathogen deemed to be the likely cause of infection. The results of cultures and serologic or direct tests, and data on outcomes were collected 30 days after initiation of empirical treatment.

Results

A total of 920 patients (26% of 3529 included patients) had microbiologically documented infections, and mortality data were available for 895 patients (97%). Inappropriate initial antibiotic treatment was prescribed in 36% of patients (N = 319). All-cause 30-day mortality rates were 20.1% (N = 64) and 11.8% (N = 68) in patients who received inappropriate and appropriate treatment, respectively (odds ratio = 1.88, 95% confidence interval [CI], 1.29-2.72, P = .001). When adjustment was made for medical center and other variables, the association between inappropriate with mortality was significant (odds ratio = 1.58, 95% CI, 0.99-2.54, P = .058). In all 3 medical centers, the mean duration of hospital stay was at least 2 days longer for patients who were prescribed inappropriate antibiotic treatment (overall P = .002). This association was consistent after adjusting for other variables (P = .006).

Conclusion

Appropriate empirical antibiotic treatment is associated with a better survival and shortened duration of hospital stay in medical patients with bacterial infections.     

Empiric outpatient therapy with trimethoprim-sulfamethoxazole, cephalexin, or clindamycin for cellulitis

Background

Limited data exist on optimal empiric oral antibiotic treatment for outpatients with cellulitis in areas with a high prevalence of community-associated methicillin-resistant Staphylococcus aureus (MRSA) infections.

Methods

We conducted a 3-year retrospective cohort study of outpatients with cellulitis empirically treated at a teaching clinic of a tertiary-care medical center in Hawaii. Patients who received more than 1 oral antibiotic, were hospitalized, or had no follow-up information were excluded. Treatment success rates for empiric therapy were compared among commonly prescribed antibiotics in our clinic: cephalexin, trimethoprim-sulfamethoxazole, and clindamycin. Risk factors for treatment failure were evaluated using multivariate logistic regression analysis.

Results

Of 544 patients with cellulitis, 405 met the inclusion criteria. The overall treatment success rate of trimethoprim-sulfamethoxazole was significantly higher than the rate of cephalexin (91% vs 74%; P < .001), whereas clindamycin success rates were higher than those of cephalexin in patients who had subsequently culture-confirmed MRSA infections (P = .01), had moderately severe cellulitis (P = .03), and were obese (P = .04). Methicillin-resistant S. aureus was recovered in 72 of 117 positive culture specimens (62%). Compliance and adverse drug reaction rates were not significantly different among patients who received these 3 antibiotics. Factors associated with treatment failure included therapy with an antibiotic that was not active against community-associated MRSA (adjusted odds ratio 4.22; 95% confidence interval, 2.25-7.92; P < .001) and severity of cellulitis (adjusted odds ratio 3.74; 95% confidence interval, 2.06-6.79; P < .001).

Conclusion

Antibiotics with activity against community-associated MRSA, such as trimethoprim-sulfamethoxazole and clindamycin, are preferred empiric therapy for outpatients with cellulitis in the community-associated MRSA-prevalent setting.     

Active Lipid Management In Coronary Artery Disease (ALMICAD) study

Purpose

Many providers have implemented specialized lipid clinics to more effectively identify, monitor, and treat hyperlipidemia in patients with coronary artery disease. The effectiveness of such a strategy is not known. We sought to investigate whether a specialized clinic achieves better lipid results and clinical outcomes than standard care.

Subjects and Methods

A total of 1233 patients who had coronary disease documented by coronary angiography were randomized to lipid clinic or standard care groups by their providers and followed for 2 years. The primary end point was a composite of death, myocardial infarction, repeat revascularization, and stroke.

Results

Lipid clinic (n = 617) and standard care (n = 616) groups had no significant baseline differences. After 2 years, the lipid clinic group had similar total cholesterol (166 ± 42 mg/dL vs 166 ± 41 mg/dL, P = .83), low-density lipoprotein cholesterol levels (84 ± 32 vs 85 ± 32, P = .28), and percentage of patients with low-density lipoprotein cholesterol less than 100 mg/dL (77.5% vs 77.6%, P = .97). There were no significant differences in the primary end point (12.3% vs 11.4%, P = .60) and mortality (7.6% vs 7.3%, P = .80) between the lipid clinic and standard care groups.

Conclusions

In patients identified by diagnostic coronary angiography and managed within a single health care system, implementation of a specialized lipid clinic did not achieve greater attainment of hyperlipidemia treatment goals or improved cardiac outcomes.     

Vitamin and micronutrient intake and the risk of community-acquired pneumonia in US women

Background

There are limited data regarding the role of dietary and supplemental vitamin intake and the risk of community-acquired pneumonia.

Methods

We prospectively examined, during a 10-year period, the association between dietary and supplemental vitamin intake and the risk of community-acquired pneumonia among 83,165 women in Nurses’ Health Study II who were between the ages of 27 and 44 years in 1991. We excluded women who had pneumonia before 1991, those who did not provide complete dietary information, or those with a history of cancer, cardiovascular disease, or asthma. Self-administered food frequency questionnaires were used to assess dietary and supplemental vitamin intake. Cases of pneumonia required a diagnosis by a physician and confirmation with a chest radiograph. The independent associations between specific vitamins and pneumonia risk were evaluated.

Results

There were 925 new cases of community-acquired pneumonia during 650,377 person-years of follow up. After adjusting for age, cigarette smoking, body mass index, physical activity, total energy intake, and alcohol consumption, there were no associations between dietary or total intake of any individual vitamin and risk of community-acquired pneumonia. Specifically, women in the highest quintile of vitamin A intake did not have a significantly lower risk of pneumonia than women in the lowest quintile (multivariate relative risk [RR] = 0.88; 95% confidence interval [CI], 0.70-1.09, P for trend = .16). Similarly, vitamin C (RR = 0.94; 95% CI, 0.76-1.16, P for trend = .81) and E (RR = 0.95; 95% CI, 0.76-1.17, P for trend = .74) intake did not alter risk of pneumonia.

Conclusions

Higher vitamin intake from diet and supplements is unlikely to reduce pneumonia risk in well nourished women.     

Relative validity of the 10-year cardiovascular risk estimate in a population cohort of the REGICOR study

Introduction and objectives

Cardiovascular risk screening requires accurate risk functions. The relative validity of the Framingham-based REGICOR adapted function is analyzed and the population distribution of cardiovascular 10-year cardiovascular events is described by risk group.

Methods

A population cohort of 3856 participants recruited between 1995 and 2000, aged 35 to 74 years from Girona without symptoms of cardiovascular diseases, was followed between 2006 and 2009. Standardized laboratory and blood pressure measurements, questionnaires, and case definitions were used. The follow-up combined cross-linkage of our databases with our regional mortality registry, reexamination, and telephone contact with participants. Coronary disease endpoints alone were considered.

Results

A total of 27 487 person-years were obtained (mean follow-up 7.1 years), and the follow-up was achieved in 97% of participants (120 coronary disease events). Validity was good: the regression coefficients estimated with the cohort data did not differ from those obtained in the original Framingham function. Function calibration was good: the observed incidence of cardiovascular events in the decile groups of risk did not differ from the function prediction (P = .127 in women, and P = .054 in men). The C statistic (discrimination) was 0.82 (95% confidence interval, 0.76-0.88) in women, and 0.78 (95% confidence interval, 0.73-0.83) in men. More than 50% of cardiovascular events occurred in participants whose 10-year risk was 5% to 14.9%.

Conclusions

The studied function accurately predicts coronary disease events at 10 years. Risk stratification could be simplified in 4 groups: low (<5%), moderate (5%-9.9%), high (10%-14.9%) and very high (≥15%).Full English text available from: www.revespcardiol.org     

Incidence and risk factors of venous thromboembolic events in lymphoma

Background

Cancer patients are at increased risk of venous thromboembolism; however, the incidence and risk factors for venous thromboembolism in lymphoma patients are not well defined.

Methods

Medical records of 422 newly referred lymphoma patients at our institution were reviewed over 2-year follow-up for all venous thromboembolism events and potential risk factors. Multivariate logistic regression model was used to identify risk factors predictive of venous thromboembolism.

Results

Among 422 patients, 72 (17.1 %) had 80 new episodes of venous thromboembolism: 59 had deep vein thrombosis, 17 had pulmonary embolism, and 4 had combined deep vein thrombosis and pulmonary embolism. Only 18 of 422 patients (4.3%) were on thromboprophylaxis at baseline. Interestingly, 64% (51/80) of the episodes occurred by the third cycle of chemotherapy. By multivariate logistic regression, female sex (odds ratio [OR] 3.51, P = .001), high hemoglobin (OR 1.26, P = .020), high serum creatinine (OR 3.23, P = .009), and doxorubicin- or methotrexate-based chemotherapy (OR 3.47, P = 0.003) were important risk factors for new venous thromboembolism.

Conclusions

Lymphoma patients are at high risk for venous thromboembolism in the initial cycles of chemotherapy; the risk was higher for women, patients with elevated hemoglobin or creatinine, or those receiving doxorubicin or methotrexate. Future studies might focus on validation of these risk factors to identify the high-risk cohort and the potential role of thromboprophylaxis, particularly during initial cycles of chemotherapy.     

Adequacy of Vitamin D Replacement in Severe Deficiency Is Dependent on Body Mass Index

Background

Obesity is associated with hypovitaminosis D. Whether body mass index (BMI) determines the replacement dose of vitamin D to achieve sufficiency is unclear.

Objective

To determine the relationship between BMI and serum 25-OH vitamin D concentrations and whether the increase in serum 25-OH vitamin D concentrations with vitamin D replacement is dependent on BMI.

Methods

Retrospective review of anthropometric data and serum 25-OH vitamin D concentrations in 95 patients attending an outpatient clinic in a tertiary hospital. In a second component of the study, 17 hospital inpatients with severe vitamin D deficiency (serum 25-OH D concentrations < 6 ng/mL [15 nmol/L]) were supplemented with 10,000 units vitamin D₃/day orally for 1 week. Biochemistry and anthropometric measurements were compared before and after vitamin D replacement.

Results

Serum 25-OH vitamin D concentrations correlated negatively with BMI in the 95 outpatients (r² = 0.11, P <.01). In the longitudinal study, BMI correlated positively with serum intact parathyroid hormone (r² = 0.84, P <.01) and negatively with 1.25-(OH)₂ vitamin D (r² = 0.19, P = .06) at baseline. Serum 25-OH D concentrations achieved following 1 week of vitamin D₃ replacement correlated negatively with BMI (r² = 0.63, P <.01).

Conclusion

Efficacy of vitamin D supplementation is dependent on BMI. Overweight and obese patients with hypovitaminosis D might require higher doses of vitamin D to achieve vitamin D repletion compared with individuals with normal body weight.     

Usefulness of endothelin-1 assessment in acute myocardial infarction

Introduction and objectives

High endothelin-1 (ET-1) levels have been linked to poor clinical outcomes after ST-segment elevation myocardial infarction (STEMI). Vasoconstriction of the coronary microcirculation seems to be the underlying mechanism. The aim of the study was to assess the effect of ET-1 on microvascular integrity, infarct size, left ventricular ejection fraction (LVEF) and myocardial salvage in evolving myocardial infarction (MI).

Methods

We measured ET-1 levels acutely (6-24 h) in 127 patients presenting with their first STEMI. Contrast-enhanced cardiac magnetic resonance (ce-CMR) was performed in 94 patients within 1 week to assess microvascular obstruction (MO), infarct size and LVEF. A myocardial salvage index (MSI) was defined as the percentage of at-risk angiographic area without necrosis on the ce-CMR.

Results

Mean age was 60.9 ± 11.8 years and 98 (77%) were males. Median ET-1 level within the first 24 h was 6.8 pg/mL (25^th -75^th percentile range: 5.4-8.5 pg/mL). Patients with ET-1 concentrations over the median presented higher percentage of MO (77.7% for ET-1 > 6.8 pg/mL vs. 16.6% for ET-1 ≤ 6.8 pg/mL, P < .001) and lower MSI values (13.8 ± 26% for ET-1 > 6.8 pg/mL vs. 37.4 (26%) for ET-1 ≤ 6.8 pg/mL, P = .02). ET-1 levels did not show a significant association with infarct size (P = .11) and LVEF (P = .16). Multivariate analysis found ET-1 to be a significant predictor of MO (OR = 2.78; CI 95% 1.16-6.66; P = .021) and MSI ≤ Percentile 25 (OR = 1.69, CI 95% 1.01-2.81; P = .04).

Conclusions

High ET-1 levels after myocardial infarction are associated with the presence of microvascular obstruction and lower myocardial salvage index.Full English text available from: www.revespcardiol.org     

Les patients très âgés sont-ils de bons candidats à l’angioplastie coronaire ? Une étude rétrospective monocentrique

Aim

To determine the feasibility of percutaneous coronary intervention (PCI) in very old patients.

Background

The elderly are a growing population with a high prevalence of ischemic heart disease and then subsequent possibility to benefit from coronary interventions.

Method

We have conducted a retrospective study using our PCI database since January 2000. Population characteristics, clinical presentation, type of lesions, technical procedure, immediate results and in hospital outcome are compare between patients older than 85 and the other.

Results

Between January 2008 and March 2009, 3130 patients benefit from coronary angioplasty. Among them, 85 patients were older than 85. There were more female in this group (24.7 vs. 14.3%, P = 0.007), but no difference in cardiovascular risk profile. The older was more symptomatic (acute coronary syndrome: 59.52 vs. 44%, P = 0.004; silent ischemia: 3.6 vs. 25.7%, P = 0.000003). The ejection fraction was worse (EF < 55%: 29.4 vs. 14.5%, P = 0.0001). The lesion was more complex (B2 and C: 67.2 vs. 57.1% P = 0.027) and concern more often the left descending artery (85.9 vs. 57.1%, P = 0.000001). The technical success was similar in the two groups (93.28 vs. 94.32%, P = 0.34) with similar rate of per procedure complications (2.35 vs. 1.5%, P = 0.37). Nevertheless, the in-hospital rate mortality was higher in the older patients (7 vs 1.38%, P = 0.0014).

Conclusion

PCI is safe and safety in very old patients despite significant but acceptable increasing in-hospital mortality due to more severe disease and co morbidities. Further evaluations are necessary in order to edict specific recommendations.     

Illness knowledge moderates the influence of coping style on quality of life among women with congestive heart failure

Objective

This study evaluated the relationship of coping style with quality of life (QoL) among women with congestive heart failure (CHF), and the role of illness knowledge in this relationship.

Methods

Thirty-five women with CHF completed measures of coping style (anger-in, alexithymia, and emotional expression), illness knowledge, and emotional/physical QoL.

Results

Symptoms of depression and anxiety were positively associated with anger-in (P < .001) and alexithymia (P < .01), and were negatively correlated with emotional expression (P = .05). Furthermore, illness knowledge moderated the relationship between anger-in and depressive symptoms (P = .01), such that high anger-in individuals with greater illness knowledge displayed greater depressive symptoms. Knowledge also moderated the relationship between emotional expression and anxiety (P = .02), indicating that low emotional expression was associated with greater anxiety among those with less illness knowledge. Depressive and anxiety symptoms, anger-in, alexithymia, and emotional expression were not correlated with physical QoL.

Conclusion

Illness knowledge is associated with poorer emotional QoL among those using denial-based coping styles, but a better QoL among those avoiding communication of their emotions.     

Adoption of Once-monthly Oral Bisphosphonates and the Impact on Adherence

Background

The extent of the adoption of once-monthly bisphosphonates into general clinical practice is not known, nor is it known if the novel formulation improves adherence.

Methods

We analyzed administrative claims 2003-2006 from a large employer-based health insurance database for incident use of oral bisphosphonates and stratified users by daily, weekly, and monthly dosing regimen. We measured adherence as the medication possession ratio (MPR) during the first year of therapy. We compared patient characteristics by dosing regimen and evaluated how the dosing regimen influenced the MPR.

Results

We identified 61,125 incident users of bisphosphonates (n = 1034 daily, n = 56,925 weekly, n = 3166 monthly). Monthly bisphosphonate users were, on average, slightly older than the other groups (mean age 66 years for monthly users vs 65 years for weekly users or 66 years for daily users, P <.05) and more often lived in the North Central or South United States (76% vs 72% weekly users or 69% daily users, P <.05). There were no detectable differences among the dosing groups in the history of serious gastrointestinal risk, comorbidity burden, or prior osteoporotic fractures. During the first year of bisphosphonate therapy, 49% of monthly users had MPR ≥ 80% compared with 49% of weekly users (not significant) or 23% of daily users (P <.0001).

Conclusion

We found little evidence of preferential prescribing of monthly bisphosphonates to certain types of patients. Furthermore, we found no evidence of improved bisphosphonate adherence with monthly dosing relative to weekly dosing, although adherence with either weekly or monthly dosing was significantly better than with daily dosing.     

Impact of duty hours restrictions on quality of care and clinical outcomes

Background

In July 2003, the Accreditation Council for Graduate Medical Education instituted residency duty-hours requirements in response to growing concerns regarding clinician fatigue and the incidence of medical errors. These changes, which limited maximum continuous hours worked and total hours per week, often resulted in increased discontinuity of care. The objective of this study was to assess the impact of the duty-hours restrictions on quality of care and outcomes of patients with acute coronary syndrome.

Methods

We performed a retrospective analysis of 1003 consecutive patients with acute coronary syndrome admitted to the University of Michigan Hospital between July 2002 and June 2004. Patients were stratified by hospital admission during academic year 2002-2003 (pre-duty-hours changes, n = 572) and academic year 2003-2004 (post-duty-hours changes, n = 431). Main outcome measures included differences in adherence to quality indicators, length of stay, and in-hospital and 6-month adverse events.

Results

Post-duty-hours changes, there was an increase in the usage of beta-blockers (85.8% vs 93.8%, P <.001), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (65.7% vs 71.8%, P = .046), and statins (76.2% vs 84.0%, P = .002) at time of discharge. Length of stay decreased from 3.1 days to 2.8 days, P = .002. There was no difference in in-hospital mortality (4.2% vs 2.8%, P = .23). Six-month mortality (8.0% vs 3.8%, P = .007) and risk-adjusted 6-month mortality (odds ratio 0.53, 95% confidence interval, 0.28-0.99, P = .05) decreased after the duty-hours changes.

Conclusions

Implementation of the Accreditation Council for Graduate Medical Education residency duty-hours restrictions on an academic inpatient cardiology service was associated with improved quality of care and efficiency in patients admitted with acute coronary syndrome. In addition, improved efficiency did not adversely impact patient outcomes, including mortality.     

Impact of Gender on Risk Stratification by Stress Echocardiography

Objective

To compare the prognostic value of stress echocardiography results in men and women with known and suspected coronary artery disease.

Methods

We analyzed the data of 8737 patients (5529 men and 3208 women) who underwent stress echocardiography (exercise in 523 patients, dipyridamole in 6227 patients, dobutamine in 1987) for evaluating known (n = 3857) or suspected (n = 4880) coronary artery disease. Patients were followed up for the occurrence of overall mortality or nonfatal myocardial infarction.

Results

During a median follow-up of 25 months, 1218 cardiac events (693 deaths and 525 infarctions) occurred. Moreover, 2263 patients (1731 men [31%] and 532 women [17%]; P < .0001) underwent coronary revascularization and were censored. Stress echocardiography results added prognostic information to that of clinical findings and resting wall motion score index in men and women with both known and suspected coronary artery disease. In patients with known coronary artery disease, women had a higher (P = .01) event rate than men in the presence of ischemia. The annual event rate was worse for nondiabetic women (P = .007) but not diabetic women; age had a neutral prognostic effect in the 2 sexes. In patients with suspected coronary artery disease, men without ischemia had a higher (P < .0001) event rate than women. The annual event rate was worse in men aged less than 65 years (P < .0001) or more than 65 years (P = .04), and those with (P = .03) or without (P < .0001) diabetes.

Conclusion

Prognosis is at least comparable in men and women with ischemia and in those with coronary artery disease and no ischemia at stress echocardiography. In these clinical settings, availability for major procedures should be similar for both genders.     

Body Weight, Insulin Resistance, and Serum Adipokine Levels 2 Years after 2 Types of Bariatric Surgery

Objective

Bariatric surgery reverses obesity-related comorbidities, including type 2 diabetes mellitus. Several studies have already described differences in anthropometrics and body composition in patients undergoing Roux-en-Y gastric bypass compared with laparoscopic adjustable gastric banding, but the role of adipokines in the outcomes after the different types of surgery is not known. Differences in weight loss and reversal of insulin resistance exist between the 2 groups and correlate with changes in adipokines.

Methods

Fifteen severely obese women (mean body mass index [BMI]: 46.7 kg/m²) underwent 2 types of laparoscopic weight loss surgery (Roux-en-Y gastric bypass = 10, adjustable gastric banding = 5). Weight, waist and hip circumference, body composition, plasma metabolic markers, and lipids were measured at set intervals during a 24-month period after surgery.

Results

At 24 months, patients who underwent Roux-en-Y were overweight (BMI 29.7 kg/m²), whereas patients who underwent gastric banding remained obese (BMI 36.3 kg/m²). Patients who underwent Roux-en-Y lost significantly more fat mass than patients who underwent gastric banding (mean difference 16.8 kg, P < .05). Likewise, leptin levels were lower in the patients who underwent Roux-en-Y (P = .003), and levels correlated with weight loss, loss of fat mass, insulin levels, and Homeostasis Model of Assessment 2. Adiponectin correlated with insulin levels and Homeostasis Model of Assessment 2 (r = −0.653, P = .04 and r = −0.674, P = .032, respectively) in the patients who underwent Roux-en-Y at 24 months.

Conclusion

After 2 years, weight loss and normalization of metabolic parameters were less pronounced in patients who underwent gastric banding compared with patients who underwent Roux-en-Y gastric bypass. Our findings require confirmation in a prospective randomized trial.     

Serum lipids in primary sclerosing cholangitis

Background

Limited data are available regarding the serum lipids in primary sclerosing cholangitis.

Aims

To determine the lipid levels in patients with primary sclerosing cholangitis.

Methods

We monitored the serum lipid levels annually for up to 6 years in 157 patients included in three previous trials of ursodeoxycholic acid.

Results

The baseline lipid values were: total cholesterol = 207 mg/dL (127-433); high-density lipoprotein = 56 mg/dL (26-132); low-density lipoprotein = 129 mg/dL (48-334); triglycerides = 102 mg/dL (41-698). Cirrhotic stage was associated with lower levels of total cholesterol (186 mg/dL vs. 217 mg/dL, p = .02). A significant correlation between the liver biochemistries and total and low-density lipoprotein cholesterol levels was observed. Ursodeoxycholic acid, as compared to placebo, significantly decreased total (−27 mg/dL vs. 22 mg/dL, p = .0004) and low-density lipoprotein cholesterol (−24 mg/dL vs. 17 mg/dL, p = .0001). After extended follow-up, small changes in the lipid levels were noticed. The incidence of coronary artery disease was 4%.

Conclusions

Our findings suggest that the lipid levels in primary sclerosing cholangitis are often above levels where treatment with lipid-lowering agents is recommended. However, primary sclerosing cholangitis patients seem to have no elevated risk for cardiovascular events. The correlation of total and low-density lipoprotein cholesterol with liver biochemistries implies that mechanisms linked to cholestasis may regulate cholesterol metabolism.     

VEGF gene polymorphism association with diabetic foot ulcer

Objective

Functional polymorphisms within vascular endothelial growth factor (VEGF) gene have shown association with various conditions including diabetic neuropathy and retinopathy. In this study we have performed a candidate gene association study in order to examine VEGF gene polymorphism association with diabetic foot ulcer (DFU).

Methods

The study group comprised of type 2 diabetes patients with (N = 247) and without (N = 241) DFU. Healthy control subjects (N = 98) were also recruited from the same area. The ARMS-PCR technique was applied for genotyping of VEGF gene SNPs at positions −7*C/T and −2578*C/A.

Results

The frequency of genotype AA was significantly decreased in patients with DFU compared with diabetic subjects without DFU (AA vs CA + CC, p = 0.003, OR = 0.44, CI = 0.24-0.80). Also there was a significant decrease in frequency of A allele in patients with DFU compared to the controls (p = 0.02, OR = 0.68, CI = 0.48-0.96).

Conclusion

It seems that lower frequency of A allele in patients with DFU is conferring a protective effect which might be as a result of increased angiogenesis in patients carrying this allele.     

Tumor necrosis factor antagonist responsiveness in a United States rheumatoid arthritis cohort

Objective

The study objective was to investigate responsiveness according to whether patients satisfy eligibility criteria from randomized controlled trials of tumor necrosis factor (TNF) antagonists in a multicentered US cohort.

Methods

Biologic-naïve patients with rheumatoid arthritis who were prescribed TNF antagonists (n = 465) in the Consortium of Rheumatology Researchers of North America registry were included. Patients were stratified by whether they met eligibility criteria from 3 major TNF antagonist trials. Two cohorts were examined: Cohort A (n = 336) included patients with complete American College of Rheumatology response criteria except acute phase reactants, and cohort B (n = 129) included patients with complete response criteria. Study outcomes included modified American College of Rheumatology 20% and 50% improvement responses (cohort A) and standard American College of Rheumatology improvement (cohort B).

Results

A minority of patients (5.4%-19.4%) prescribed TNF antagonists met trial eligibility criteria and predominantly had high disease activity (78.5%-100%). For patients who met eligibility criteria in cohort A, rates of 20% improvement (52.3%-63.6%) and 50% improvement (30.8%-45.5%) were achieved. Among patients failing to meet eligibility criteria, rates of 20% improvement (16.2%-20.4%) and 50% improvement (8.9%-10.8%) were consistently inferior (P <.05 all comparisons). For cohort B, similar differences were observed.

Conclusion

This multicentered US cohort study demonstrates that the majority of patients receiving TNF antagonists would not meet trial eligibility criteria and achieve lower clinical responses. These findings highlight the tradeoff between defining treatment responsive populations and achieving results that can be generalized for broader patient populations.     

The obesity gene and colorectal cancer risk: a population study in Northern Italy

Background

Representing the second cause of cancer-related death after lung cancer in men and breast cancer in women, colorectal cancer (CRC) is a major health problem in Italy. Obesity is reckoned to favor CRC; however, the underlying mechanisms are unclear. Recently, a single nucleotide polymorphism (SNP) in the fat mass and obesity associated (FTO) gene was found to be significantly associated with obesity.

Aims

To establish whether the FTO SNP rs9939609 may represent a risk factor for CRC and adenoma in the Italian population.

Patients and methods

1,037 subjects were enrolled in the study and divided in 3 groups: CRC (341 pts., M/F = 197/144, mean age = 65.17 ± 11.16 years), colorectal adenoma (385 pts., M/F = 247/138, mean age = 62.49 ± 13.01 years), healthy controls (311 pts., M/F = 150/161, mean age = 57.31 ± 13.84 years). DNA was extracted from whole blood, and stored frozen for rs9939609 genotyping by real-time PCR.

Results

The frequency of the obesity-associated mutated A allele (AA+AT) on the FTO gene was 69.77% among controls, and 71.85% and 65.71% respectively among CRC and polyp patients. Compared to control subjects the AA+AT genotype had no significant effect on the risk for either CRC (OR = 1.106; CI 95% = 0.788-1.550; p = 0.561) or colorectal adenomas (OR = 0.830; CI 95% = 0.602-1.144; p = 0.255). We did not observe any association between the AA genotype and CRC/polyp localization and age at diagnosis. As measured in a patient subset, carriership of the risk alleles did not reflect in a significantly altered BMI.

Conclusion

The obesity-linked FTO variants do not play a significant role in modulating the colorectal cancer risk in the Italian population.     

Association of diabetes mellitus with myocardial collagen accumulation and relaxation impairment in patients with dilated cardiomyopathy

Aims

To assess the effects of diabetes mellitus (DM) on myocardial collagen accumulation, myocardial relaxation, and prognosis in patients with dilated cardiomyopathy (DCM).

Methods

A total of 102 consecutive DCM patients with a New York Heart Association functional class of I or II were enrolled. Patients were allocated to two groups on the basis of the presence (DCM + DM group, n = 30) or absence (DCM − DM group, n = 72) of DM. Cardiac catheterization performed and left ventricular pressure were measured in all patients. The pressure half-time (T_1/2) was determined as an index of myocardial relaxation function. Endomyocardial specimens were subjected to histological analysis.

Results

The T_1/2 was significantly longer (P < 0.001) and the collagen volume fraction was significantly greater (P = 0.018) in the DCM + DM group than in the DCM − DM group. Multivariate analysis showed that DM was significantly associated with increased incidence of cardiac events (hazard ratio, 3.7; 95% confidence interval, 1.05 to 13.16; P = 0.03).

Conclusions

The prognosis of DCM patients with DM was worse than that of those without DM. Impairment of myocardial relaxation, increased myocardial fibrosis, and mitochondrial degeneration associated with DM may underlie this difference.