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.     

Statins Decrease the Occurrence of Venous Thromboembolism in Patients with Cancer

Background

Recent data suggest a reduction in the occurrence of venous thromboembolism in select groups of patients who use statins. The objective of this study is to evaluate the impact of statin use on the occurrence of venous thromboembolism in patients with solid organ tumor.

Methods

We conducted a retrospective, case-control study reviewing 740 consecutive patients with a diagnosis of solid organ tumor who were admitted to the Albert Einstein Medical Center, Philadelphia, Penn, between October 2004 and September 2007. Patients treated with anticoagulation therapy before their first admission were excluded. The occurrence of venous thromboembolism, risk factors for venous thromboembolism, and statin use were recorded. Patients who never used statins or had used them for less than 2 months were relegated to the control group.

Results

The mean age of the study population was 65 years, and 52% of the patients were women and 76% were African American. The occurrence of venous thromboembolism was 18% (N = 132), and 26% (N = 194) were receiving statins. Among patients receiving statins, 8% (N = 16) developed a venous thromboembolism compared with 21% (N = 116) in the control group (odds ratio 0.33; 95% confidence interval, 0.19-0.57). A logistic regression analysis including risk factors for venous thromboembolism (metastatic disease, use of chemotherapy, immobilization, smoking, and aspirin use) along with statin use yielded the same results.

Conclusion

This study suggests that the use of statins is associated with a significant reduction in the occurrence of venous thromboembolism. This pleiotropic effect warrants further investigation.     

Long-term low-molecular-weight heparin versus usual care in proximal-vein thrombosis patients with cancer

Purpose

A substantial clinical need exists for an alternative to vitamin K antagonists for treating deep-vein thrombosis in cancer patients who are at high risk of both recurrent venous thromboembolism and bleeding. Low-molecular-weight heparin, body-weight adjusted, avoids anticoagulant monitoring and has been shown to be more effective than vitamin-K-antagonist therapy.

Subjects and Methods

Subjects were patients with cancer and acute symptomatic proximal-vein thrombosis. We performed a multi-centre randomized, open-label clinical trial using objective outcome measures comparing long-term therapeutic tinzaparin subcutaneously once daily with usual-care long-term vitamin-K-antagonist therapy for 3 months. Outcomes were assessed at 3 and 12 months.

Results

Of 200 patients, 100 received tinzaparin and 100 received usual care. At 12 months, the usual-care group had an excess of recurrent venous thromboembolism; 16 of 100 (16%) versus 7 of 100 (7%) receiving low-molecular-weight heparin (P = .044; risk ratio = .44; absolute difference −9.0; 95% confidence interval [CI], −21.7 to −0.7). Bleeding, largely minor, occurred in 27 patients (27%) receiving tinzaparin and 24 patients (24%) receiving usual care (absolute difference −3.0; 95% CI, −9.1 to 15.1). In patients without additional risk factors for bleeding at the time of randomization, major bleeding occurred in 0 of 51 patients (0%) receiving tinzaparin and 1 of 48 patients (2.1%) receiving usual care. Mortality at 1 year was high, reflecting the severity of the cancers; 47% in each group died.

Conclusion

Our findings confirm the limited but benchmark data in the literature that long-term low-molecular-weight heparin is more effective than vitamin-K-antagonist therapy for preventing recurrent venous thromboembolism in patients with cancer and proximal venous thrombosis.     

Attribution of functional limitation to cancer decreases in the year following breast cancer diagnosis in older patients

Objectives

To examine the prevalence of self-reported functional limitations in a breast cancer population, identify whether these reported limitations are attributed to breast cancer versus other coexisting illnesses, and examine how this attribution changes over time from early in treatment to 9 months later.

Design

Longitudinal, observational study.

Setting

Community dwelling adults in Detroit metropolitan area.

Participants

2033 participants (1011 breast cancer patients, 1022 controls) aged 40-84 years.

Measurements

Participants were asked about each of 23 possible coexisting illnesses in addition to breast cancer and whether or not each illness, including breast cancer, caused any activity limitation.

Results

Of the 933 cancer patients who completed both baseline and follow-up evaluations, 45% were aged 65 years and older. At baseline, 56% of patients 65 years and older reported functional limitation compared with 50% of patients younger than 65 years (p = 0.005). Of those patients who reported limitation at baseline, 59% of older patients and 78% of younger patients attributed their limitation to breast cancer (p < 0.001). At follow-up, 53% of older and 37% of younger patients reported functional limitation (p < 0.001), with 27% of older patients compared with 57% of younger patients (p < 0.001) attributing limitation to breast cancer.

Conclusion

Self-reported functional limitations are common 3 months after breast cancer diagnosis, being attributed primarily to breast cancer. By 1 year after diagnosis, much of the limitation due to breast cancer resolves. Older women are less likely to have resolution of their limitations, which are most commonly due to other coexisting illnesses.     

Incidence of venous thromboembolism in patients hospitalized with cancer

Background

There are sparse data on the frequency of venous thromboembolism in patients with various types of cancer. We sought to determine the incidence and relative risk of venous thromboembolism, pulmonary embolism, and deep venous thrombosis in patients with malignancies.

Subjects and methods

The number of patients discharged with a diagnostic code for 19 types of malignancies, pulmonary embolism or deep venous thrombosis from 1979 through 1999 was obtained from the National Hospital Discharge Survey. Patients studied were men and women of all ages and races.

Results

In patients with any of the 19 malignancies studied, 827 000 of 40 787 000 (2.0%) had venous thromboembolism, which was twice the incidence in patients without these malignancies, 6 854 000 of 662 309 000 (1.0 %). The highest incidence of venous thromboembolism was in patients with carcinoma of the pancreas, 51 000 of 1 176 000 (4.3%), and the lowest incidences were in patients with carcinoma of the bladder and carcinoma of the lip, oral cavity or pharynx. The overall incidences of pulmonary embolism and deep venous thrombosis were also twice the rates in noncancer patients. Incidences with cancer were not age dependent. The incidence of venous thromboembolism in patients with cancer began to increase in the late 1980s.

Conclusion

Patients with cancer had twice the incidence of venous thromboembolism, pulmonary embolism and deep venous thrombosis as patients without cancer. The incidence of venous thromboembolism, pulmonary embolism and deep venous thrombosis associated with cancer differed according to the type of cancer, was comparable in elderly and younger patients, and increased in the late 1980s and 1990s.     

Outcome of direct current cardioversion for atrial arrhythmias in adults with congenital heart disease

Objectives

We sought to evaluate safety, efficacy, and outcome of direct current cardioversion (DCCV) for atrial arrhythmias in adults with congenital heart disease (CHD).

Background

Atrial arrhythmias are increasingly noted in adults with CHD. The outcome of DCCV for atrial arrhythmias in this population is unknown.

Methods

Our study was a retrospective review of patients 18 years or older with CHD who underwent DCCV between June 2000 and July 2003. This constituted the CHD group. Patient characteristics reviewed included the specific cardiac diagnosis and arrhythmia history. A subset of patients had transesophageal echocardiography (TEE) before DCCV; this subset was reviewed to evaluate spontaneous echocardiographic contrast. The outcome data evaluated included success of DCCV, complications, recurrence of arrhythmia, antiarrhythmic medication use, electrophysiology or pacemaker procedure in follow-up, and all-cause mortality. The recurrence rate of the arrhythmia was compared to a control group consisting of an age, gender, and rhythm matched group of patients who have no CHD and who underwent DCCV for atrial arrhythmias.

Results

Sixty-three patients in the CHD group underwent 80 DCCVs, 59 of which were TEE-guided. Atrial flutter was more common in the CHD group (37 of 80 DCCV, 46%) than in the control group (13 of 56, 23%) (p < 0.001). DCCV was successful in 75 (94%). Mean follow-up was 387 days. No thromboembolic events were noted. All-cause mortality on follow-up was 11%. There was no death related to DCCV. Twenty-five patients in the CHD group (40%) remained in sinus rhythm throughout follow-up. This was similar to that observed in the control group (30/56, 54%, p = 0.13). Recurrent arrhythmia in the CHD group was predicted by the presence of atrial fibrillation (p = 0.009) and less so spontaneous echo contrast in the left atrium (p = 0.05).

Conclusions

DCCV with appropriate anticoagulation is safe and effective for patients with CHD, even in the presence of an intracardiac shunt and spontaneous contrast on TEE. However, the recurrence rate is substantial. Spontaneous echo contrast in the left atrium along with atrial fibrillation predicts arrhythmia recurrence following DCCV in patients with CHD.     

Lipoprotein (a) and venous thromboembolism in adults: a meta-analysis

Background

Lipoprotein (a) [Lp(a)], a low-density lipoprotein particle linked to apolipoprotein (a), has been recently demonstrated to be an independent risk factor for arterial vascular diseases. However, despite increasing evidence of the association between high Lp(a) and arterial thrombotic diseases, few and conflicting results on the association between high Lp(a) levels and venous thromboembolism have been obtained. The aim of this article is to systematically examine the published data on the association between high Lp(a) levels and venous thromboembolism.

Methods

A systematic search of all publications listed in the electronic databases (Medline, EMBASE, Web of Science, and The Cochrane Library) up to November 2006, using keywords in combination both as MeSH terms and text words, was conducted.

Results

Six case-control studies were included, incorporating 1826 cases of venous thromboembolism and 1074 controls. The summary odds ratios of included case-control studies under a fixed-effects model showed a statistically significant association between Lp(a) levels >300 mg/L and venous thromboembolism: 1.87, 95% confidence interval (CI), 1.51-2.30; P <.0001. Furthermore, a random-effects model, which accounts for the interstudy variation, yielded a similar estimate of increased risk (odds ratio [OR] 1.77; 95% CI, 1.14-2.75; P = .01).

Conclusions

The present meta-analysis shows a significant association between high Lp(a) levels and the occurrence of venous thromboembolism in adults. Indeed, the detection of Lp(a) could be of clinical relevance for venous thromboembolism, especially among patients with absence of traditional and thrombophilic risk factors.     

Prevention of central venous catheter-associated thrombosis: a meta-analysis

Purpose

Anticoagulant prophylaxis in patients with central venous catheters is controversial. We performed a meta-analysis of randomized controlled trials of anticoagulant prophylaxis in patients with central venous catheters.

Methods

MEDLINE and EMBASE were searched up to May 2006, supplemented by manual searches of conference proceedings and bibliographies.

Results

Fifteen trials were included. Unfractionated heparin infusion, oral fixed low-dose vitamin K antagonist, and subcutaneous low-molecular-weight heparin were evaluated. For all catheter-associated deep vein thrombosis (symptomatic and asymptomatic combined), the summary relative risks ranged from 0.31 to 0.73 (all achieved statistical significance). For symptomatic deep vein thrombosis, the summary relative risks ranged from 0.28 to 0.72, but did not achieve statistical significance for any individual regimen.

Conclusion

Anticoagulant prophylaxis is effective for preventing all catheter-associated deep vein thrombosis in patients with central venous catheters. The effectiveness for preventing symptomatic venous thromboembolism, including pulmonary embolism, remains uncertain.     

Variability in the use of thromboprophylaxis and outcomes in critically ill medical patients

Purpose

To describe practices for preventing venous thromboembolism in critically ill medical patients and to identify associations between prophylactic measures and survival.

Methods

We reviewed the records of all medical admissions to the intensive care units of a university hospital and an affiliated Veterans Affairs hospital over a 1-year period. We recorded patients’ demographic characteristics, risk factors for venous thromboembolism, methods of prophylaxis, and in-hospital deaths.

Results

We identified 272 critically ill medical patients who received intensive care for at least 24 hours. Some form of prophylaxis was used in 205 patients (75%), including pharmacologic prophylaxis alone in 55 (20%), mechanical prophylaxis alone in 102 (38%), and both methods in 48 (18%). In-hospital mortality rates were 23% (24/103) for patients who received pharmacologic prophylaxis, and 36% (61/169) for those who received mechanical prophylaxis alone or no prophylaxis (P = .03). After adjusting for demographic characteristics, risk factors for thrombosis and severity of illness, the odds of death were 55% lower in patients who received pharmacologic prophylaxis (odds ratio [OR] = 0.45; 95% confidence interval (CI): 0.22 to 0.93; P = .03). Similar results were obtained in propensity-adjusted and propensity-stratified analyses. Use of mechanical prophylaxis was not associated with survival (OR = 0.88; 95% CI 0.44 to 1.77; P = .73).

Conclusion

In this cohort of critically ill medical patients, pharmacologic but not mechanical thromboprophylaxis was associated with reduced risk of in-hospital death. This hypothesis must be tested in randomized trials.     

Activated partial thromboplastin time and risk of future venous thromboembolism

Background

Lower activated partial thromboplastin times are associated with higher levels of some coagulation factors and may represent a procoagulant tendency.

Methods

In the Atherosclerosis Risk in Communities study, we studied the 13-year risk of venous thromboembolism in relation to baseline activated partial thromboplastin time in 13,880 individuals. We also studied 258 venous thromboembolism cases and 589 matched controls with measurements of additional coagulation factors.

Results

After adjustment for demographics and procoagulant factors reflected in the activated partial thromboplastin time (fibrinogen, factors VIII, IX, and XI, and von Willebrand factor), participants in the lowest 2 quartiles of activated partial thromboplastin time compared with the fourth quartile had 2.4-fold (95% confidence interval [CI], 1.4-4.2) and 1.9-fold (95% CI, 1.1-3.2) higher risks of venous thromboembolism. The risk associated with activated partial thromboplastin times below the median was higher for idiopathic (odds ratio 5.5; 95% CI, 2.0-15.5) than secondary venous thromboembolism (odds ratio 1.74; 95% CI, 0.88-3.43). Subjects with both activated partial thromboplastin times below the median and factor V Leiden were 12.6-fold (95% CI, 5.7-28.0) more likely to develop venous thromboembolism compared with those with neither risk factor (P interaction <.01). A lower activated partial thromboplastin time also added to the thrombosis risk associated with obesity and elevated D-dimer.

Conclusion

A single determination of the activated partial thromboplastin time below the median increased the risk of future venous thromboembolism. Findings were independent of coagulation factor levels, and a low activated partial thromboplastin time added to the risk associated with other risk factors.     

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.     

Upper extremity deep vein thrombosis: a community-based perspective

Purpose

The purpose of this study was to examine the magnitude, risk factors, management strategies, and outcomes in a population-based investigation of patients with upper, as compared with lower, extremity deep vein thrombosis diagnosed in 1999.

Methods

The medical records of all residents from Worcester, Massachusetts (2000 census = 478,000) diagnosed with ICD-9 codes consistent with possible deep vein thrombosis at all Worcester hospitals during 1999 were reviewed and validated.

Results

The age-adjusted attack rate (per 100,000 population) of upper extremity deep vein thrombosis was 16 (95% confidence interval [CI], 13-20) compared with 91 (95% CI, 83-100) for lower extremity deep vein thrombosis. Patients with upper extremity deep vein thrombosis were significantly more likely to have undergone recent central line placement, a cardiac procedure, or an intensive care unit admission than patients with lower extremity deep vein thrombosis. Although short-term and 1-year recurrence rates of venous thromboembolism and all-cause mortality were not significantly different between patients with upper, versus lower, extremity deep vein thrombosis, patients with upper extremity deep vein thrombosis were less likely to have pulmonary embolism at presentation or in follow-up.

Conclusions

Patients with upper extremity deep vein thrombosis represent a clinically important patient population in the community setting. Risk factors, occurrence of pulmonary embolism, and timing and location of venous thromboembolism recurrence differ between patients with upper as compared with lower extremity deep vein thrombosis. These data suggest that strategies for prophylaxis and treatment of upper extremity deep vein thrombosis need further study and refinement.     

Prior statin use is associated with improved outcomes in community-acquired pneumonia

Background

Statins have potent anti-inflammatory effects in laboratory studies of pulmonary inflammation. We investigated whether statin users had improved outcome when admitted with community-acquired pneumonia.

Methods

We carried out a prospective observational study of patients admitted to the hospital with community-acquired pneumonia between January 2005 and November 2007. The use of statins, angiotensin-converting enzyme inhibitors, beta-blockers, and aspirin were recorded. The outcomes of interest were 30-day mortality, need for mechanical ventilation or inotropic support, and the development of complicated pneumonia.

Results

On multivariate logistic regression, statin use was associated with significantly lower 30-day mortality (adjusted odds ratio [AOR] 0.46, 95% confidence interval [CI], 0.25-0.85, P = .01) and development of complicated pneumonia (AOR 0.44, 95% CI, 0.25-0.79, P = .006). There was no effect on requirement of mechanical ventilation or inotropic support (AOR 0.93, 95% CI, 0.49-1.76, P = .8). Patients prescribed statins had more severe pneumonia (median Pneumonia Severity Index 4, interquartile range [IQR] 3-4) compared with patients not prescribed cardiovascular drugs (median Pneumonia Severity Index 3, IQR 2-4, P < .0001). Despite this, C-reactive protein levels on admission were significantly lower in patients prescribed statins (median 119 mg/L, IQR 46-215) compared with patients prescribed no cardiovascular drugs (182 mg/L, IQR 66-326, P < .0001). On multivariate logistic regression, statin use was independently protective against a C-reactive protein that failed to fall by 50% or more at day 4 (AOR 0.50, 95% CI 0.27-0.92, P = .02).

Conclusions

Statin use is associated with reduced markers of systemic inflammation and improved outcomes in patients admitted with community-acquired pneumonia.     

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.     

Incidence of Thrombocytopenia in Hospitalized Patients with Venous Thromboembolism

Purpose

To determine the incidence of heparin-associated thrombocytopenia in patients receiving prophylaxis or treatment for venous thromboembolism.

Methods

We assessed the database of the National Hospital Discharge Survey from 1979 through 2005 and complemented this with a meta-analysis of published literature.

Result

Among 10,554,000 patients discharged from short-stay hospitals throughout the US with venous thromboembolism during the 27 years of study, secondary thrombocytopenia was coded in 38,000 patients (0.36%). From 1979 through 1992, secondary thrombocytopenia was coded in only 0.15% of hospitalized patients with venous thromboembolism. The frequency increased sharply to 0.54% from 1993 through 2005. Secondary thrombocytopenia was rarely diagnosed among 1,446,000 patients aged <40 years and among 77,000 women who had venous thromboembolism with deliveries. Meta-analysis of published literature showed a higher incidence among patients who received unfractionated heparin (UFH) for prophylaxis than those who received low-molecular-weight heparin (LMWH) for prophylaxis. Treatment resulted in smaller differences of the incidence between UFH and LMWH.

Conclusion

Heparin-associated thrombocytopenia is rare among patients aged <40 years and women following delivery. The risk of heparin-associated thrombocytopenia is more duration-related than dose-related, and higher with UFH when used for an extended duration. Our findings and those of the literature suggest that although heparin-associated thrombocytopenia is uncommon, the incidence can be minimized by use of LMWH, particularly if extended prophylaxis or extended treatment is required.     

Greater hand-grip strength predicts a lower risk of developing type 2 diabetes over 10 years in leaner Japanese Americans

Aims

Much is known about body composition and type 2 diabetes risk but less about body function such as strength. We assessed whether hand-grip strength predicted incident diabetes.

Methods

We followed 394 nondiabetic Japanese-American subjects (mean age 51.9) for the development of diabetes. We fit a logistic regression model to examine the association between hand-grip strength at baseline and type 2 diabetes risk over 10 years, adjusted for age, sex, and family history.

Results

A statistically significant (p = 0.008) and negative (coefficient −0.208) association was observed between hand-grip strength and diabetes risk that diminished at higher BMI levels. Adjusted ORs for a 10-pound hand-grip strength increase with BMI set at the 25th, 50th or 75th percentiles were 0.68, 0.79, and 0.98, respectively.

Conclusions

Among leaner individuals, greater hand-grip strength was associated with lower risk of type 2 diabetes, suggesting it may be a useful marker of risk in this population.     

Improvement of left ventricular diastolic function induced by β-blockade: a comparison between nebivolol and metoprolol

Objectives

Enhanced adrenergic drive is involved in the development of left ventricular (LV) diastolic dysfunction observed in metabolic syndrome (MS). Thus, β-blockers might improve LV dysfunction observed in MS, but whether this occurs is unknown.

Methods

We assessed in Zucker fa/fa rats the effects of short- (5 days) and long-term (90 days) metoprolol (‘pure’ β-blockade; 80 mg/kg/day) or nebivolol (β-blocker with vasodilating properties; 5 mg/kg/day) treatment on LV hemodynamics and remodeling, as well as the long-term effects on coronary and peripheral endothelial dysfunction.

Results

At identical degree of β₁-receptor blockade, metoprolol and nebivolol decreased heart rate to the same extent and preserved cardiac output via increased stroke volume. None of the β-blockers, either after long- or short-term administration, modified LV end-systolic pressure-volume relation. Both β-blockers reduced, after long-term administration, LV end-diastolic pressure, Tau and end-diastolic pressure-volume relation, and this was associated with reduced LV collagen density, but not heart weight. Similar hemodynamic effects were also observed after short-term nebivolol, but not short-term metoprolol. These short-term effects of nebivolol were abolished by NO synthase inhibition. At the vascular level, nebivolol, and to a lesser extend metoprolol, improved NO dependent coronary vasorelaxation, which was abolished by NO synthase inhibition.

Conclusions

In a model of MS, the β-blockers metoprolol and nebivolol improve to the same extent LV hemodynamics, remodeling and diastolic function, but nebivolol prevent more markedly endothelium dependent vasorelaxation involving a more marked enhancement of NO bio-availability.     

Outcomes for Inpatients with Normal Findings on Whole-leg Ultrasonography: A Prospective Study

Background

Ultrasonography is used routinely for ruling out suspected deep vein thrombosis in hospitalized patients, although most evidence supporting this strategy is derived from the outpatient setting. This study aimed to estimate the rate of venous thromboembolism when anticoagulant therapy was withheld from inpatients with normal findings on whole-leg ultrasonography.

Methods

As part of a prospective multicenter cohort study, 1926 medical and surgical inpatients with clinically suspected deep vein thrombosis during their stay were enrolled. Ultrasonography of all lower extremities was performed by board-certified vascular medicine physicians using a standardized examination protocol. Deep vein thrombosis was detected in 395 patients (20%). Anticoagulant therapy was withheld from patients with normal findings, and 523 of them were randomly selected for follow-up. The main outcome measure was 3-month incidence of symptomatic venous thromboembolism.

Results

A total of 513 patients with normal findings on ultrasonography successfully completed 3 months of follow-up, 9 patients were lost to follow-up, and 1 patient received anticoagulant therapy during follow-up. Three patients (0.6%) experienced nonfatal symptomatic venous thromboembolic events confirmed by objective testing. The cause of death was judged to be possibly related to pulmonary embolism for 7 other patients (1.3%). Overall, the 3-month rate of venous thromboembolism was 1.9% (10/513; 95% confidence interval, 0.9-3.5).

Conclusion

Although withholding anticoagulant therapy after a single negative whole-leg ultrasonography seems to be safe, up to 3.5% of inpatients may nevertheless develop venous thromboembolism in the next 3 months. Further study is warranted to determine whether this strategy is equivalent to serial compression ultrasonography limited to proximal veins.     

The relationship between visfatin and HOMA-IR in hypertensive patients, and the effect of antihypertensive drugs on visfatin and HOMA-IR in hypertensive patients with insulin resistance

Objective

To investigate the correlation between serum visfatin and insulin resistance (IR) in non-diabetic essential hypertensive (EH) patients with and without IR, and to evaluate the effect of antihypertensive treatment on serum visfatin and IR in these patients.

Methods

A total of 81 non-diabetic EH patients, including 54 with IR and 27 without IR, were enrolled. After two weeks wash-out, patients with IR were randomly assigned to telmisartan (group T) or amlodipine (group A) for 6 months. Blood samples were taken before and after treatment for measurement of routine biochemical parameters, visfatin and insulin resistance (measured by HOMA-IR).

Results

Visfatin was independently correlated with HOMA-IR (r = 0.845, P = 0.000). After 6 months of treatment, both drugs lowered HOMA-IR, more significantly so in group T than group A (P = 0.010). Serum visfatin levels increased in group T but decreased in group A.

Conclusion

Serum visfatin levels were higher in non-diabetic EH patients with IR compared with those without IR. Visfatin is independently correlated with HOMA-IR. Telmisartan lowers HOMA-IR to a greater extent than amlodipine. Interestingly, serum visfatin increased with telmisartan yet decreased with amlodipine treatment.     

Can we increase the chance of sphincter saving surgery in rectal cancer with neoadjuvant treatments: lessons from a systematic review of recent randomized trials

Purpose

A common hypothesis is that neo-adjuvant treatment in rectal cancer, is able to increase sphincter saving surgery. This review studies data relevant to this question.

Study selection

A total of 17 randomized trials were analysed.

Results

Since 1976, the rate of sphincter saving surgery increased from 20% to 75%. In none of the 17 trials it was possible to demonstrate a significant benefit of the neo-adjuvant regimens on the rate of sphincter saving surgery. There was a reduction in the risk of 5-year local recurrence partly due to these neo-adjuvant treatments. These neo-adjuvant regimens had no significant impact on the overall 5-year survival.

Conclusions

None of the neo-adjuvant treatments tested was able to demonstrate an increase in the rate of sphincter saving surgery. The improvement in conservative surgery is mainly due to technical changes in surgery. Organ preservation after complete clinical response appears as an interesting hypothesis to test.