Risk factors for early primary graft dysfunction after lung transplantation: a registry study.

BACKGROUND: Primary graft dysfunction (PGD) is a leading cause of early morbidity and mortality in lung transplantation. We sought to identify risk factors for PGD using the United Network for Organ Sharing/International Society for Heart and Lung Transplant (UNOS/ISHLT) Registry. METHODS: A total of 6984 lung transplants between 1994 and 2002 were available for analysis. Potential risk factors were tested for association with PGD and multivariable logistic regression was applied to adjust for confounding. RESULTS: The overall incidence of PGD was 10.7% (95% CI 9.9-11.4). In multivariable analyses, factors independently associated with PGD were donor age >45 yr (p < 0.001); donor head trauma (p = 0.03); recipient body mass index >25 kg/m(2) (p = 0.005); recipient female gender (p = 0.001); use of Eurocollins preservation solution (p = 0.001); single lung transplant (p = 0.005); increased ischemic time (p < 0.001); and elevated recipient pulmonary artery systolic pressure at transplant (p < 0.001). Recipient transplant diagnosis was strongly associated with PGD, with primary or secondary pulmonary hypertension (p < 0.001 for both), and idiopathic (p < 0.001) or secondary pulmonary fibrosis (p = 0.011) as significant and independent risk factors for PGD. CONCLUSIONS: Risk factors for PGD in the UNOS/ISHLT registry are consistent with prior smaller studies. Recipient, donor, and therapy variables are independently associated with PGD, as defined in a large registry.

Destabilization of interleukin-6 mRNA requires a putative RNA stem-loop structure, an AU-rich element, and the RNA-binding protein AUF1.

Interleukin-6 mRNA is unstable and degraded with a half-life of 30 min. Instability determinants can entirely be attributed to the 3' untranslated region. By grafting segments of this region to stable green fluorescent protein mRNA and subsequent scanning mutagenesis, we have identified two conserved elements, which together account for most of the instability. The first corresponds to a short noncanonical AU-rich element. The other, 80 nucleotides further 5', comprises a sequence predicted to form a stem-loop structure. Neither element alone was sufficient to confer full instability, suggesting that they might cooperate. Overexpression of myc-tagged AUF1 p37 and p42 isoforms as well as suppression of endogenous AUF1 by RNA interference stabilized interleukin-6 mRNA. Both effects required the AU-rich instability element. Similarly, the proteasome inhibitor MG132 stabilized interleukin-6 mRNA probably through an increase of AUF1 levels. The mRNA coimmunoprecipitated specifically with myc-tagged AUF1 p37 and p42 in cell extracts but only when the AU-rich instability element was present. These results indicate that AUF1 binds to the AU-rich element in vivo and promotes IL-6 mRNA degradation.

Primary pericardial mesothelioma unique case and literature review.

A 72-year-old woman, on warfarin therapy and with a remote history of breast cancer and radiation treatment, presented with a 10-day history of nausea, dyspnea, dry cough, and dizziness. An electrocardiogram showed new-onset atrial fibrillation. Computed tomography of the chest revealed multiple pulmonary emboli and a pericardial effusion. Echocardiography showed a pericardial effusion with tamponade characteristics. The patient's condition deteriorated, and a pericardiectomy was performed. Histologic evaluation confirmed primary pericardial mesothelioma. She underwent palliative treatment and died 3 months after discharge from the hospital. We discuss the patient's case and the nature of primary pericardial mesothelioma, a rare oncologic entity.

Recurrent takotsubo cardiomyopathy in the setting of transient neurological symptoms: a case report.

INTRODUCTION: First described in Japan, takotsubo cardiomyopathy is increasingly becoming recognized worldwide as a cause of sudden and reversible diminished left ventricular function characterized by left apical ballooning and hyperkinesis of the basal segments, often with symptoms mimicking a myocardial infarction. Associated with physical or emotional stress, its exact pathogenesis has not been established, though evidence supports a neurohumoral etiology. Additionally, recurrence of this condition is rare. In this report, we present a rare case of recurrent takotsubo cardiomyopathy in a post-menopausal woman who presented with transient neurological complaints on both occasions. CASE PRESENTATION: We present a rare case of a 76-year-old Caucasian woman with no history of congestive heart failure who presented to our emergency department twice with transient neurological complaints. On the first occasion, she was found to have transient aphasia which resolved within 24 hours, yet during that period she also developed symptoms of congestive heart failure and was noted to have a new, significantly depressed ejection fraction with apical akinesis and possible apical thrombus. One month after her presentation a repeat echocardiogram revealed complete resolution of all wall motion abnormalities and a return to baseline status. Seven months later she presented with ataxia, was diagnosed with vertebrobasilar insufficiency, and again developed symptoms and echocardiography findings similar to those of her first presentation. Once again, at her one-month follow-up examination, all wall motion abnormalities had completely resolved and her ejection fraction had returned to normal. CONCLUSION: Though the exact etiology of takotsubo cardiomyopathy is unclear, a neurohumoral mechanism has been proposed. Recurrence of this disorder is rare, though it has been reported in patients with structural brain abnormalities. This report is the first to describe recurrent takotsubo cardiomyopathy in a patient with transient neurological symptoms. In our patient, as expected in patients with this condition, complete resolution of all left ventricular abnormalities occurred within a short period of time. It is important for clinicians to be aware of this increasingly recognized syndrome, including its association with recurrence, especially in the clinical setting of neurologic dysfunction.

Overuse of stress ulcer prophylaxis in the critical care setting and beyond.

BACKGROUND: Patients admitted to the intensive care unit (ICU) are susceptible to stress ulcers. We hypothesize that despite recommendations, stress ulcer prophylaxis (SUP) is still overused in the ICU and often continued after resolution of risk factors for bleeding. METHODS: We retrospectively studied all ICU admissions for 4 months. Risk factors for stress ulcer bleeding were collected. Patients were categorized into 4 groups: (1) >or=1 major risk factor; (2) >or=1 minor risk factors; (3) no risk factors; (4) preadmission use of acid-suppressive medication. The rate of SUP was calculated by group during ICU stay, on transfer from the ICU, and at hospital discharge. RESULTS: Two hundred ten patients were studied. Of all the ICU admissions, 87.1% received SUP. Among patients with no risk factors, 68.1% were placed on prophylaxis on ICU admission; 60.4% continued on treatment upon transfer from the ICU; 31.0% were discharged home on an agent without a new indication. CONCLUSIONS: Although judicious use of SUP in high-risk patients can decrease the incidence of gastrointestinal bleeding, inappropriate use may increase drug reactions, unnecessary hospital costs, and personal monetary burden. Our findings argue for improvement measures to reduce initial inpatient overuse of SUP and to prompt discontinuation before hospital discharge.