My Treatment Approach to Management of the Pregnant Patient With Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is frequently diagnosed in women of childbearing age. Of paramount concern are questions about the effect of the disease on a woman's ability to conceive and carry the pregnancy safely to term, as well as the effect of the disease and its therapies on the health of the fetus. For health care providers, there is also the issue of medication dose adjustments and management of flares during pregnancy. Growing experience with IBD in pregnancy suggests that most women will have good outcomes; however, concerns and uncertainty remain for both the patient and the physician. This article outlines our approach to the treatment of these patients with respect to preconception counseling and management during pregnancy and the postpartum period.     

A DPYD Variant (Y186C) Specific to Individuals of African Descent in a Patient With Life-Threatening 5-FU Toxic Effects: Potential for an Individualized Medicine Approach

5-Fluorouracil (5-FU) is commonly administered as a therapeutic agent for the treatment of various aggressive cancers. Severe toxic reactions to 5-FU have been associated with decreased levels of dihydropyrimidine dehydrogenase (DPD) enzyme activity. Manifestations of 5-FU toxicity typically include cytopenia, diarrhea, stomatitis, mucositis, neurotoxicity, and, in extreme cases, death. A variety of genetic variations in DPYD, the gene encoding DPD, are known to result in decreased DPD enzyme activity and to contribute to 5-FU toxic effects. Recently, it was reported that healthy African American individuals carrying the Y186C DPYD variant (rs115232898) had significantly reduced DPD enzyme activity compared with noncarriers of Y186C. Herein, we describe for the first time, to our knowledge, an African American patient with cancer with the Y186C variant who had severe toxic effects after administration of the standard dose of 5-FU chemotherapy. The patient lacked any additional toxic effect–associated variations in the DPYD gene or the thymidylate synthase (TYMS) promoter. This case suggests that Y186C may have contributed to 5-FU toxicity in this patient and supports the use of Y186C as a predictive marker for 5-FU toxic effects in individuals of African ancestry.     

Transcranial Magnetic Stimulation as an Antidepressant Alternative in a Patient With Brugada Syndrome and Recurrent Syncope

Brugada syndrome (BrS) is a common occult cause of sudden cardiac arrest in otherwise healthy-appearing adults. The pathognomonic electrocardiographic pattern may be unmasked only by certain medications, many of which are unknown. We report a case of a depressed but otherwise healthy man with an asymptomatic right bundle branch block on electrocardiography who experienced antidepressant-induced BrS and ultimately recovered with transcranial magnetic stimulation (TMS). After an initial trial of nortriptyline, the patient’s depressive symptoms improved; however, he experienced a syncopal event and was subsequently diagnosed as having BrS. Cross titration to bupropion, which had not previously been known to exacerbate BrS, was followed by another cardiac event. As a result, the patient was referred for TMS as a substitute for pharmacotherapy. After 31 TMS sessions over 8 weeks, the patient demonstrated significant improvement by subjective report and objective reduction in his Patient Health Questionnaire-9 scores from 10 (moderate) to 1 (minimal). Transcranial magnetic stimulation is a Food and Drug Administration–approved nonpharmacologic treatment for depression. Given the potential lethality of BrS with known and unknown psychopharmacologic agents, providers should consider TMS as first-line therapy in this patient population. Bupropion should be added to the list of agents known to exacerbate this disease.     

Myocardial Infarction Risk Among Patients With Fractures Receiving Bisphosphonates

ObjectiveTo determine if bisphosphonates are associated with reduced risk of acute myocardial infarction (AMI).Patients and MethodsA cohort of 14,256 veterans 65 years or older with femoral or vertebral fractures was selected from national administrative databases operated by the US Department of Veterans Affairs and was derived from encounters at Veterans Affairs facilities between October 1, 1998, and September 30, 2006. The time to first AMI was assessed in relationship to bisphosphonate exposure as determined by records from the Pharmacy Benefits Management Database. Time to event analysis was performed using multivariate Cox proportional hazards regression. An adjusted survival analysis curve and a Kaplan-Meier survival curve were analyzed.ResultsAfter controlling for atherosclerotic cardiovascular disease risk factors and medications, bisphosphonate use was associated with an increased risk of incident AMI (hazard ratio, 1.38; 95% CI, 1.08-1.77; P=.01). The timing of AMI correlated closely with the timing of bisphosphonate therapy initiation.ConclusionOur observations in this study conflict with our hypothesis that bisphosphonates have antiatherogenic effects. These findings may alter the risk-benefit ratio of bisphosphonate use for treatment of osteoporosis, especially in elderly men. However, further analysis and confirmation of these findings by prospective clinical trials is required.     

Bedside to Bench: Role of Muscarinic Receptor Activation in Ultrarapid Growth of Colorectal Cancer in a Patient With Pheochromocytoma

An elderly man with long-standing, nonresectable pheochromocytoma had rapid development of rectal adenocarcinoma despite close endoscopic surveillance. We determined that the patient’s colorectal cancer overexpressed muscarinic receptor subtype 3, whereas his pheochromocytoma expressed choline acetyltransferase, an enzyme required to produce acetylcholine, which is a muscarinic receptor agonist. These findings suggested that acetylcholine release from the pheochromocytoma stimulated rapid growth of the rectal neoplasm. As proof of principle, we found that culture media conditioned by pheochromocytoma cells stimulates proliferation of a human colon cancer cell line, an effect attenuated by atropine, a muscarinic receptor inhibitor. Our observations provide both clinical and laboratory evidence that muscarinic receptor agonists promote the growth of colorectal neoplasia.     

My Treatment Approach to Chronic Hepatitis C Virus

The treatment of chronic hepatitis C virus (HCV) is evolving rapidly. In 2014, the standard of care and new backbone of HCV treatment is the polymerase inhibitor sofosbuvir (SOF). Our treatment approach in patients with HCV genotype 1 is 12 weeks of SOF, peginterferon (PEGINF), and ribavirin (RBV). In patients with cirrhosis or extrahepatic manifestations of HCV who cannot tolerate PEGINF, we use 12 weeks of SOF and simeprevir. The latter is less costly and more effective than SOF and RBV for 24 weeks. Our treatment approach in all patients with genotype 2 is SOF and RBV for 12 weeks. Hepatitis C virus genotype 3 is now the most costly and difficult to cure. Our approach to treatment-naive patients with genotype 3 is SOF and RBV for 24 weeks. In patients who have previously undergone PEGINF and RBV treatment, we use PEGINF, SOF, and RBV for 12 weeks, which is equally if not more effective and less costly than SOF and RBV for 24 weeks. Patients with cirrhosis who cannot tolerate PEGINF should be treated for 24 weeks with SOF and RBV, although the sustained virologic response is suboptimal.     

Association of Coronary Artery Calcification With Hepatic Steatosis in Asymptomatic Individuals

ObjectiveTo determine the association of coronary artery calcification with hepatic steatosis in asymptomatic volunteers.Patients and MethodsThe study group comprised 400 asymptomatic volunteers, enrolled from April 1, 2011, to September 30, 2012, without known coronary artery disease who were self-referred for screening noncontrast computed tomography to determine coronary calcium score (CCS). Computed tomographic images were used to determine the presence of hepatic steatosis. An a priori model was created to predict a CCS of 100 Agatston units (AU) or higher on the basis of Framingham risk factors, diabetes mellitus, and metabolic syndrome. Hepatic steatosis was then added to this model. Computation of the odds ratio (OR) for hepatic steatosis predicting a CCS of 100 AU or higher was performed. Finally, the OR for a CCS of 100 AU or higher being associated with hepatic steatosis was calculated.ResultsWhen hepatic steatosis was added to traditional coronary risk factors, it was independently associated with a CCS of 100 AU or higher (OR, 2.85). This was greater than the OR of Framingham factors, diabetes mellitus, or metabolic syndrome. A CCS of 100 AU or higher was independently associated with an increased risk for hepatic steatosis (OR, 2.4). This OR was higher than traditional hepatic steatosis risk factors or metabolic syndrome.ConclusionHepatic steatosis is a strong independent predictor of a CCS of 100 AU or higher in asymptomatic patients. It is associated with an increased risk of coronary artery disease beyond that expected from traditional coronary risk factors and/or metabolic syndrome. Additional studies are needed to clarify the role of hepatic steatosis as a possible independent risk factor for the development of coronary artery disease.     

Comparative Effectiveness of Telaprevir-Based Triple Therapy in Patients With Chronic Hepatitis C

ObjectiveTo examine the effectiveness and tolerability of triple therapy with pegylated interferon (p-IFN), ribavirin (RBV), and telaprevir in patients with chronic hepatitis C receiving treatment in an academic practice setting and in a more clinically diverse population compared with patients receiving treatment in phase 3 trials.Patients and MethodsA prospective database of all patients with viral hepatitis undergoing antiviral therapy from January 1, 2006, to July 1, 2012, was queried to identify treatment-naive and -experienced patients with chronic hepatitis C receiving dual and triple therapies. On-treatment response categories included rapid virologic response, extended rapid virologic response, early virologic response, and sustained virologic response. These patients were compared with matched controls, namely, patients who underwent dual therapy with p-IFN and RBV. Matching was performed for age, cirrhosis status, and prior treatment.ResultsThere were 55 patients who received triple therapy and met the eligibility criteria, consisting of treatment-naive (n=35) and -experienced patients (n=20: those with relapse, 9; those with nonresponse, 9; and those who terminated the treatment early, 2). Rapid virologic response was achieved in 41% of the patients, extended rapid virologic response in 41%, and early virologic response in 75%. Sustained virologic response was observed in 51% (18/35) of treatment-naive patients, 67% (6/9) of the patients with prior nonresponse, and 56% (5/9) of those with prior relapse. Corresponding results after dual therapy were 37% (23/62), 11% (2/18), and 27% (3/11), respectively. The mean decrease in the hemoglobin level at weeks 4, 8, and 24 of triple therapy was 2.8, 3.8, and 3.2 mg/dL compared with 2.4, 2.6, and 2.4 mg/dL with dual therapy (to convert mg/dL to mmol/L, multiply values by 0.0259).ConclusionTelaprevir-based triple therapy in clinical practice is considerably more effective than dual therapy with p-IFN and RBV despite the significant degree of anemia that complicated therapy, requiring RBV dose reduction and erythropoietin support.     

Evaluation and Management of Patients With Heart Disease and Cancer: Cardio-Oncology

The care for patients with cancer has advanced greatly over the past decades. A combination of earlier cancer diagnosis and greater use of traditional and new systemic treatments has decreased cancer-related mortality. Effective cancer therapies, however, can result in short- and long-term comorbidities that can decrease the net clinical gain by affecting quality of life and survival. In particular, cardiovascular complications of cancer treatments can have a profound effect on the health of patients with cancer and are more common among those with recognized or unrecognized underlying cardiovascular diseases. A new discipline termed cardio-oncology has thus evolved to address the cardiovascular needs of patients with cancer and optimize their care in a multidisciplinary approach. This review provides a brief introduction and background on this emerging field and then focuses on its practical aspects including cardiovascular risk assessment and prevention before cancer treatment, cardiovascular surveillance and therapy during cancer treatment, and cardiovascular monitoring and management after cancer therapy. The content of this review is based on a literature search of PubMed between January 1, 1960, and February 1, 2014, using the search terms cancer, cardiomyopathy, cardiotoxicity, cardio-oncology, chemotherapy, heart failure, and radiation.     

Moderate Cardiorespiratory Fitness Is Positively Associated With Resting Metabolic Rate in Young Adults

ObjectiveTo determine whether moderate cardiorespiratory fitness (CRF) or moderate to vigorous physical activity (MVPA) is associated with elevations in resting metabolic rate (RMR) similar to findings previously observed in endurance athletes.Participants and MethodsUsing a cross-sectional design, we measured CRF, RMR, body composition, energy expenditure, and time in MVPA via an arm-based activity monitor in 423 young adults (mean age, 27.6 years). Based on the results of a fitness test, participants were classified into CRF tertiles (low, moderate, or high) by sex.ResultsThere were significant differences among the low-, moderate-, and high-CRF groups for mean ± SD body mass index (calculated as the weight in kilograms divided by the height in meters squared) (28.1±4.1, 25.1±3.4, and 23.6±2.5, respectively; P<.001) and fat mass (28.8±9.7, 20.5±8.2, and 14.8±6.5 kg, respectively; P<.001) but not fat-free mass (53.1±11.5, 53.5±12.4, and 54.7±12.1 kg, respectively; P=.49). There were no differences in mean ± SD unadjusted RMR among the groups (1533.2±266.2, 1519.7±267.6, and 1521.9±253.9 kcal/d, respectively). However, after statistical adjustment for differences in body composition, the moderate- and high-CRF groups had a higher RMR compared with low-CRF individuals by 39.7 and 59.9 kcal/d, respectively (P<.05). After further adjustment for MVPA, RMR was higher in the high-CRF group compared with the low-CRF group by 51.2 kcal/d (P<.05).ConclusionIn this large sample of young adults representing a range of CRF, there was a positive stepwise gradient in RMR across tertiles of CRF independent of body composition. Also, MVPA was independently associated with RMR, although this relationship was modest. These findings underscore the multidimensional role of CRF and MVPA on health.Trial Registrationclinicaltrials.gov Identifier: NCT01746186     

Body Composition and Mortality in a Large Cohort With Preserved Ejection Fraction: Untangling the Obesity Paradox

ObjectiveTo evaluate the effects of body composition as a function of lean mass index (LMI) and body fat (BF) on the correlation between increasing body mass index (BMI; calculated as the weight in kilograms divided by the height in meters squared) and decreasing mortality, which is known as the obesity paradox.Patients and MethodsWe retrospectively assessed 47,866 patients with preserved left ventricular ejection fraction (≥50%). We calculated BF by using the Jackson-Pollock equation and LMI using (1 − BF) × BMI. The population was divided according to the sex-adjusted BMI classification, sex-adjusted LMI classification, and sex-adjusted BF tertiles. The population was analyzed by using multivariate analysis for total mortality over a mean follow-up duration of 3.1 years by using the National Death Index, adjusting for left ventricular ejection fraction, left ventricular mass index, age, sex, and relative wall thickness.ResultsIn the entire population, higher BMI was narrowly associated (hazard ratio [HR], 0.99; P<.001) with lower mortality. The higher LMI group was clearly protective (HR, 0.71; P<.001), whereas BF tertile was associated with lower mortality only if no adjustment was made for LMI (HR, 0.87; P<.001 without LMI; HR, 0.97; P=.23 with LMI). In the lean patients, low BMI was clearly associated with higher mortality (HR, 0.92; P<.001) and lower BF tertile was associated with lower mortality only if no adjustment was made for LMI (HR, 0.80; P<.001 without LMI; HR, 1.01; P=.83 with LMI). The underweight patients stratified by BF seemed to have an increased mortality (HR, 1.91; 95% CI, 1.56-2.34) that was independent of LMI. However, in obese patients, both BMI (HR, 1.03; P<.001) and BF (HR, 1.18; P=.003) were associated with higher mortality, even after adjusting for LMI, which remained protective (HR, 0.57; P<.001) independently of BF.ConclusionBody composition could explain the inverse J shape of the mortality curve noted with increasing BMI. Body fat seems to be protective in this cohort only if no adjustment was made for LMI, although being underweight stratified by BF seems to be an independent risk factor. Lean mass index seems to remain protective in obese patients even when BMI is not.     

Prognostic Factors and Outcomes of Adults With Hemophagocytic Lymphohistiocytosis

ObjectiveTo describe the prognostic factors and outcomes of adults with hemophagocytic lymphohistiocytosis (HLH), a rare disorder caused by pathologic activation of the immune system.Patients and MethodsThe study population consisted of a consecutive cohort of adult (age ≥18 years) patients treated at Mayo Clinic in Rochester, Minnesota, from January 1, 1996, through December 31, 2011, in whom a diagnosis of HLH was suspected and subsequently confirmed by retrospective review using the HLH-04 diagnostic criteria.ResultsOf 250 adult patients suspected of having HLH, 62 met the HLH-04 diagnostic criteria and were included in the final analysis. The median age was 49 years (range, 18-87 years), and 42 (68%) were male. The underlying cause of HLH was malignant tumor in 32 patients (52%), infection in 21 patients (34%), autoimmune disorder in 5 patients (8%), and idiopathic disease in 4 patients (6%). After a median follow-up of 42 months, 41 patients (66%) had died. The median overall survival of the entire cohort was 2.1 months. The median overall survival of patients with tumor–associated HLH was 1.4 months compared with 22.8 months for patients with non-tumor–associated HLH (P=.01). The presence of a malignant tumor and hypoalbuminemia were significant predictors of inferior survival on multivariate analysis.ConclusionIn this large series of adults with secondary HLH treated at a single tertiary care center, patients with low serum albumin levels and tumor–associated HLH had a markedly worse survival. Hemophagocytic lymphohistiocytosis remains elusive and challenging to clinicians who must maintain a high index of suspicion. The recent discovery of several novel diagnostic and therapeutic modalities may improve outcomes of adult patients with HLH.     

Bone Mass in Individuals With Chronic Spinal Cord Injury: Associations With Activity-Based Therapy,Neurologic and Functional Status,a Retrospective Study

ObjectiveTo describe the prevalence of osteoporosis and its association with functional electrical stimulation (FES) use in individuals with spinal cord injury (SCI)-related paralysis.DesignRetrospective cross-sectional evaluation.SettingClinic.ParticipantsConsecutive persons with SCI (N=364; 115 women, 249 men) aged between 18 and 80 years who underwent dual-energy x-ray absorptiometry (DXA) examinations.InterventionsNot applicable.Main Outcome MeasurePrevalence of osteoporosis defined as DXA T score ≤−2.5.ResultsThe prevalence of osteoporosis was 34.9% (n=127). Use of FES was associated with 31.2% prevalence of osteoporosis compared with 39.5% among persons not using FES. In multivariate adjusted logistic regression analysis, FES use was associated with 42% decreased odds of osteoporosis after adjusting for sex, age, body mass index, type and duration of injury, Lower Extremity Motor Scores, ambulation, previous bone fractures, and use of calcium, vitamin D, and anticonvulsant; (adjusted odds ratio [OR]=.58; 95% confidence interval [CI], .35–.99; P=.039). Duration of injury >1 year was associated with a 3-fold increase in odds of osteoporosis compared with individuals with injury <1 year; (adjusted OR=3.02; 95% CI, 1.60–5.68; P=.001).ConclusionsFES cycling ergometry may be associated with a decreased loss of bone mass after paralysis. Further prospective examination of the role of FES in preserving bone mass will improve our understanding of this association.     

Comparison of the Quality of Patient Referrals From Physicians,Physician Assistants,and Nurse Practitioners

ObjectiveTo compare the quality of referrals of patients with complex medical problems from nurse practitioners (NPs), physician assistants (PAs), and physicians to general internists.Patients and MethodsWe conducted a retrospective comparison study involving regional referrals to an academic medical center from January 1, 2009, through December 31, 2010. All 160 patients referred by NPs and PAs combined and a random sample of 160 patients referred by physicians were studied. Five experienced physicians blinded to the source of referral used a 7-item instrument to assess the quality of referrals. Internal consistency, interrater reliability, and dimensionality of item scores were determined. Differences between item scores for patients referred by physicians and those for patients referred by NPs and PAs combined were analyzed by using multivariate ordinal logistical regression adjusted for patient age, sex, distance of the referral source from Mayo Clinic, and Charlson Index.ResultsFactor analysis revealed a 1-dimensional measure of the quality of patient referrals. Interrater reliability (intraclass correlation coefficient for individual items: range, 0.77-0.93; overall, 0.92) and internal consistency for items combined (Cronbach α=0.75) were excellent. Referrals from physicians were scored higher (percentage of agree/strongly agree responses) than were referrals from NPs and PAs for each of the following items: referral question clearly articulated (86.3% vs 76.0%; P=.0007), clinical information provided (72.6% vs 54.1%; P=.003), documented understanding of the patient's pathophysiology (51.0% vs 30.3%; P<.0001), appropriate evaluation performed locally (60.3% vs 39.0%; P<.0001), appropriate management performed locally (53.5% vs 24.1%; P<.0001), and confidence returning patient to referring health care professional (67.8% vs 41.4%; P<.0001). Referrals from physicians were also less likely to be evaluated as having been unnecessary (30.1% vs 56.2%; P<.0001).ConclusionThe quality of referrals to an academic medical center was higher for physicians than for NPs and PAs regarding the clarity of the referral question, understanding of pathophysiology, and adequate prereferral evaluation and documentation.     

Characteristics Associated With Postdischarge Medication Errors

ObjectiveTo examine the association of patient- and medication-related factors with postdischarge medication errors.Patients and MethodsThe Vanderbilt Inpatient Cohort Study includes adults hospitalized with acute coronary syndromes and/or acute decompensated heart failure. We measured health literacy, subjective numeracy, marital status, cognition, social support, educational attainment, income, depression, global health status, and medication adherence in patients enrolled from October 1, 2011, through August 31, 2012. We used binomial logistic regression to determine predictors of discordance between the discharge medication list and the patient-reported list during postdischarge medication review.ResultsAmong 471 patients (mean age, 59 years), the mean total number of medications reported was 12, and 79 patients (16.8%) had inadequate or marginal health literacy. A total of 242 patients (51.4%) were taking 1 or more discordant medication (ie, appeared on either the discharge list or patient-reported list but not both), 129 (27.4%) failed to report a medication on their discharge list, and 168 (35.7%) reported a medication not on their discharge list. In addition, 279 participants (59.2%) had a misunderstanding in indication, dose, or frequency in a cardiac medication. In multivariable analyses, higher subjective numeracy (odds ratio [OR], 0.81; 95% CI, 0.67-0.98) was associated with lower odds of having discordant medications. For cardiac medications, participants with higher health literacy (OR, 0.84; 95% CI, 0.74-0.95), with higher subjective numeracy (OR, 0.77; 95% CI, 0.63-0.95), and who were female (OR, 0.60; 95% CI, 0.46-0.78) had lower odds of misunderstandings in indication, dose, or frequency.ConclusionMedication errors are present in approximately half of patients after hospital discharge and are more common among patients with lower numeracy or health literacy.     

Relation of Age With Symptom Severity and Quality of Life in Patients With Fibromyalgia

ObjectiveTo examine the relation of age with symptom severity and quality of life (QOL) in patients with fibromyalgia, and to compare physical and mental health of our female patients with those of the US female general population.Patients and MethodsWe studied 978 patients with fibromyalgia from May 1, 2001 through April 30, 2004, and divided them into age groups of young (≤39 years), middle-aged (40-59 years), and older (≥60 years). They completed the Fibromyalgia Impact Questionnaire and the Short Form-36 Health Status Questionnaire (SF-36). Standardized SF-36 physical and mental health summary scores were compared with those of the US female general population of similar age. One-way analysis of variance and post hoc paired t test analyses were performed to detect differences across age groups.ResultsPairwise comparison found young and middle-aged patients having worse fibromyalgia symptoms in all subscales except the anxiety subscale compared with older patients (P≤.01). Similarly, these young and middle-aged patients had worse QOL in the SF-36 mental component summary, as well as SF-36 general health perceptions, vitality, social functioning, and mental health index, compared with older patients (all P<.001). When the QOL of our female patients was compared with that of the US female general population of similar age with standardized SF-36 scores, all age groups had lower QOL in physical, as well as mental, health, with more reduction in physical health, particularly in young patients.ConclusionOur study shows that symptom severity and QOL differ across age groups in patients with fibromyalgia, with young and middle-aged patients having poorer QOL and worse fibromyalgia symptoms than do older patients. QOL in physical health was reduced more than in mental health, particularly in young patients, compared with the general population.     

Prognostic Value of Exercise Capacity in Patients With Coronary Artery Disease: The FIT (Henry Ford ExercIse Testing) Project

ObjectiveTo examine the prognostic value of exercise capacity in patients with nonrevascularized and revascularized coronary artery disease (CAD) seen in routine clinical practice.Patients and MethodsWe analyzed 9852 adults with known CAD (mean ± SD age, 61±12 years; 69% men [n=6836], 31% black race [n=3005]) from The Henry Ford ExercIse Testing (FIT) Project, a retrospective cohort study of patients who underwent physician-referred stress testing at a single health care system between January 1, 1991, and May 31, 2009. Patients were categorized by revascularization status (nonrevascularized, percutaneous coronary intervention [PCI], or coronary artery bypass graft [CABG] surgery) and by metabolic equivalents (METs) achieved on stress testing. Using Cox regression models, hazard ratios for mortality, myocardial infarction (MI), and downstream revascularizations were calculated after adjusting for potential confounders, including cardiac risk factors, pertinent medications, and stress testing indication.ResultsThere were 3824 all-cause deaths during median follow-up of 11.5 years. In addition, 1880 MIs, and 1930 revascularizations were ascertained. Each 1-MET increment in exercise capacity was associated with a hazard ratio (95% CI) of 0.87 (0.85-0.89), 0.87 (0.85-0.90), and 0.86 (0.84-0.89) for mortality; 0.98 (0.96-1.01), 0.88 (0.84-0.92), and 0.93 (0.90-0.97) for MI; and 0.94 (0.92-0.96), 0.91 (0.88-0.95), and 0.96 (0.92-0.99) for downstream revascularizations in the nonrevascularized, PCI, and CABG groups, respectively. In each MET category, the nonrevascularized group had similar mortality risk as and higher MI and downstream revascularization risk than the PCI and CABG surgery groups (P<.05).ConclusionExercise capacity was a strong predictor of mortality, MI, and downstream revascularizations in this cohort. Furthermore, patients with similar exercise capacities had an equivalent mortality risk, irrespective of baseline revascularization status.     

New-Onset Heart Failure in Association With Severe Hypertension During Trastuzumab Therapy

Heart failure is a dreaded complication of trastuzumab therapy in women with breast cancer overexpressing the human epidermal growth factor receptor (HER)-2. Experimental studies have pointed out that the HER-2 signaling pathway is important in the adaptation to high afterload conditions and its inactivation leads to cardiac decompensation. Herein, we report on 2 patients with breast cancer who were receiving trastuzumab monotherapy and required hospital admission for new-onset heart failure. This occurred at a time of unprecedented blood pressure elevations, in one case due to cessation of antihypertensive medications and in the other case due to a scleroderma crisis. Although trastuzumab may not have been the precipitating factor for blood pressure dyscontrol in these patients, severe, uncontrolled hypertension may have been the precipitating factor for trastuzumab-related acute heart failure. These 2 cases add to previous reports recognizing systemic hypertension as a risk factor for the development of trastuzumab cardiotoxicity and translate experimental observations of the significance of the HER-2 signaling pathway to the bedside. Pending further confirmation, the present observations may raise awareness of the need for appropriate monitoring and control of systemic hypertension in patients receiving trastuzumab, or potentially any other HER-2–targeted therapy.     

Biomedical System Dynamics to Improve Anemia Control With Darbepoetin Alfa in Long-Term Hemodialysis Patients

ObjectiveTo determine the value of a biomedical system dynamics (BMSD) approach for optimization of anemia management in long-term hemodialysis patients because elevated hemoglobin levels and high doses of erythropoiesis-stimulating agents (ESAs) may negatively affect survival in this population.Patients and MethodsA model of erythropoiesis and its response to ESAs on the basis of a BMSD method (Mayo Clinic Anemia Management System [MCAMS]) was developed. Thereafter, an open-label, prospective, nonrandomized practice quality improvement project was performed with retrospective analysis in 8 community-based outpatient hemodialysis facilities. All prevalent hemodialysis patients seen from January 1, 2007, through December 31, 2010 (300-342 patients per month), were included with darbepoetin as the ESA. The primary outcome was the percentage of patients who attained the desired hemoglobin level. Secondary outcome measures included the percentage of patients with hemoglobin values above the desired range and mean dose of darbepoetin used.ResultsThe 3 treatment periods were (1) standard ESA protocol in 2007, (2) transition to the MCAMS (2008 to June 2009), and (3) stability period with the MCAMS used in all hemodialysis facilities (2009 to 2010). In the first 6 months of 2007, 69% of patients were in the desired range and 26% were above the range. In comparison, during the first 5 months of 2010, 83% were in and 6% were above the range (P<.001). The mean monthly darbepoetin dose per patient decreased from 304 μg in 2007 to 173 μg by the second half of 2009 (P<.001).ConclusionWith the introduction of the MCAMS, more patients had hemoglobin levels in the desired range and fewer patients exceeded the target range, with a concomitant 40% reduction in darbepoetin use.     

Pneumatosis Intestinalis With a Focus on Hyperbaric Oxygen Therapy

Pneumatosis intestinalis is a rare condition of air in the bowel wall. Pneumatosis intestinalis is most often secondary to another medical condition. The diagnosis is most often made radiologically with a computed tomography scan. The disease severity ranges from benign to life-threatening. Predictors of poor outcomes include pH less than 7.3, bicarbonate level of less than 20 mEq/L, lactate level of more than 2 mmol/L, amylase level of more than 200 U/L, and portal venous gas on imaging. Early recognition of life-threatening signs and symptoms is critical. Treatment options include bowel rest, antibiotics, surgery, and, more recently, the use of hyperbaric oxygen therapy. Hyperbaric oxygen therapy is extremely safe, with no reported complications in the literature when used for pneumatosis intestinalis. When surgery is not emergently needed, symptomatic pneumatosis intestinalis can be safely treated with hyperbaric oxygen with a high likelihood of success without any considerable adverse effects.