Clinical Outcomes of Weight-Based Norepinephrine Dosing in Underweight and Morbidly Obese Patients: A Propensity-Matched Analysis.

BACKGROUND: Weight-based dosing strategy for norepinephrine in septic shock patients with extremes of body mass index has been lesser studied. METHODS: This historical study of adult septic shock patients was conducted from January 1, 2010, to December 31, 2015, at all intensive care units (ICUs) in Mayo Clinic, Rochester. Patients with documented body mass index were classified into underweight (body mass index <18.5 kg/m2), normal weight (18.5-24.9 kg/m2), and morbidly obese (≥40 kg/m2) patients. Patients with repeat ICU admissions, ICU stay <1 day, and body mass index 25 to 39.9 kg/m2 were excluded. The primary outcome was in-hospital mortality, and secondary outcomes included cumulative norepinephrine exposure acute kidney injury, cardiac arrhythmias, and 1-year mortality. Two-tailed P < .05 was considered statistically significant. RESULTS: From 2010 to 2015, 2016 patients met inclusion-145, 1406, and 466 patients, respectively, in underweight, normal weight, and morbidly obese cohorts. Underweight patients used the highest peak dose and absolute exposure was greatest for morbidly obese patients. In-hospital mortality decreased with increasing log10 body mass index: 41.4% (underweight), 28.4% (normal weight), and 24.7% (morbidly obese), respectively (P < .001); however, this relationship was not noted at 1 year. Unadjusted log10 norepinephrine cumulative exposure (mg) was associated with higher in-hospital mortality, acute kidney injury, cardiac arrhythmias, and 1-year mortality. After adjustment for demographics, body mass index, comorbidity, and illness severity, log10 norepinephrine exposure was an independent predictor of in-hospital mortality (odds ratio 2.4 [95% confidence interval, 2.0-2.8]; P < .001) and 1-year mortality (odds ratio 1.7 [95% confidence interval, 1.5-2.0]; P < .001). In a propensity-matched analysis of 1140 patients, log10 norepinephrine was an independent predictor of in-hospital mortality (odds ratio 2.2 [95% confidence interval, 1.8-2.6]; P < .001). CONCLUSIONS: Morbidly obese patients had lower in-hospital mortality but had higher 1-year mortality compared to normal weight and underweight patients. Cumulative norepinephrine exposure was highest in morbidly obese patients. Total norepinephrine exposure was an independent mortality predictor in septic shock.

Cytomegalovirus infection in autologous stem cell transplant recipients in the era of rituximab.

The incidence of cytomegalovirus (CMV) reactivation/disease after autologous stem cell transplant (ASCT) is much lower than that after allogeneic stem cell transplantation. With the recent use of rituximab during cancer chemotherapy or conditioning regimens prior to transplantation, there has been an increasing concern of opportunistic infections including CMV. In the present study, we reviewed the patients undergoing ASCT from December 2007 to December 2013 to identify those developing CMV reactivation/disease. Out of the 978 patients who underwent ASCT at the Karmanos Cancer Institute, 239 patients were tested for symptomatic CMV reactivation based on clinical suspicion. Of the tested patients, 7/239 (2.9 %) were documented to have CMV reactivation within 90 days of ASCT. The median time to develop CMV viremia was 32 days from transplantation. Of the 239 patients tested, CMV viremia was detected in 3 out of 72 patients who received rituximab as compared to 4 out of 167 patients who did not. Three of these seven viremic patients were treated with anti-viral drugs; viremia resolved in all patients at a median of 24 days. Three patients were found to develop other bacterial and/or fungal infections following CMV viremia. Two of the seven patients died during 1-year follow-up, due to primary disease progression or Candida sepsis. None of the patients developed proven tissue-invasive CMV disease. The study did not evaluate the incidence of asymptomatic CMV infection/reactivation. Despite prior publications based on limited data, rituximab does not appear to contribute to an increased frequency of symptomatic CMV reactivation following ASCT.

New insights on patient-related risk factors for venous thromboembolism in patients with solid organ cancers.

Patient-related risk factors for venous thromboembolism (VTE) are infrequently studied. We compared the role of patient-related risk factors for VTE in patients with solid organ cancers to their role in patients without cancer using National Inpatient Sample (NIS) data. Patients with cancer: risk of VTE hospitalization; Increased: chronic pulmonary disease (OR 1.172, 95% CI 1.102-1.247), obesity (OR 1.369, 95% CI 1.244-1.506). Decreased: liver disease (OR 0.654, 95% CI 0.562-0.762), chronic kidney disease (CKD) (OR 0.539, 95% CI 0.491-0.593), end-stage renal disease (ESRD) (OR 0.247, 95% CI 0.187-0.326). Patients without cancer: Risk of VTE hospitalization; Increased: age (OR 1.024, 95% CI 1.022-1.025), congestive heart failure (OR 1.221, 95% CI: 1.107-1.346), chronic pulmonary disease (OR 1.372, 95% CI 1.279-1.473), obesity (OR 2.627, 95% CI 2.431-2.838). Decreased: female gender (OR 0.772, 95% CI 0.730-0.816), diabetes (OR 0.756, 95% CI 0.701-0.815), ESRD (OR 0.315, 95% CI 0.252-0.395). In conclusion, chronic pulmonary disease and obesity increase VTE hospitalization risk in patients with and without cancer and the risk decreases in cancer patients with liver disease, CKD or ESRD.

Complete resolution of erythrodermic psoriasis with first-line apremilast monotherapy.

Erythrodermic psoriasis (EP) is the most serious type of psoriasis with high morbidity and mortality. First-line recommended therapies for EP, cyclosporine and infliximab have significant adverse effects. Cyclosporine increases the risk of hypertension, leucopenia, infections and renal failure. Infliximab increases the risk of reactivation of tuberculosis, hepatitis B and histoplasmosis, and increases risk for hepatitis, autoantibody formation, congestive heart failure, demyelinating disorders, pancytopenia, lymphoma and skin cancer. An effective drug with a much safer side effect profile will be of significant benefit in EP. The phosphodiesterase 4 inhibitor apremilast is U.S Food and Drug Administration (FDA) approved for plaque psoriasis and psoriatic arthritis. Adverse effects of apremilast reported are headache, nausea, diarrhoea, upper respiratory tract infection, potential for depression and weight loss. We report complete and long-standing resolution of EP with first-line apremilast monotherapy. Apremilast may be an effective option with comparatively minor side effects for EP.

A Rare Case of Diffuse Large B Cell Lymphoma Presenting as a Cardiac Mass.

BACKGROUND Primary mediastinal diffuse large B cell lymphoma (DLBCL) presenting as a large intracardiac tumor is extremely rare and has not been significantly reported in the literature. Cardiac lymphoma consists of 2 subtypes: mediastinal DLBCL invading the heart and primary cardiac lymphoma. Both subtypes have a poor prognosis and are treated similarly. Mediastinal DLBCL is a life-threatening condition that, if diagnosed early, has a better survival rate. This is a rare case of a mediastinal DLBCL invading the right atrium as a large intracardiac mass, causing partial obstruction of the tricuspid valve without hemodynamic compromise. CASE REPORT A 57-year-old female presented with unintentional weight loss, fatigue, exertional dyspnea, and cough for 8 weeks. Transesophageal echocardiogram showed a mass (3.5×3.5 cm) in the posterior wall of the right atrium partially obstructing the tricuspid valve. Biopsy revealed DLBCL. Given new-onset lymphoma, a human immunodeficiency virus (HIV) test was done and came back positive. CD4 count was 100 cells/mm³. Chemotherapy was initiated with rituximab, cyclophosphamide, epirubicin, vincristine, and prednisone (R-CHOP). Highly active anti-retroviral (HAART) therapy was started for HIV. After treatment with R-CHOP and HAART, the patient had complete resolution of the mass and symptoms on follow-up imaging and evaluation at 6 months. CONCLUSIONS Mediastinal DLBCL invading the heart is a life-threatening form of non-Hodgkin's lymphoma (NHL) and early diagnosis and treatment is critical as prognosis is poor especially if diagnosed in later stages of the disease. Testing for HIV is important as 5% of HIV patients are susceptible to developing NHL.

Cardiorenal syndrome in sepsis: A narrative review.

Multi-organ dysfunction is seen in nearly 40-60% of all patients presenting with sepsis, including renal and cardiac dysfunction. Cardiorenal syndrome type-5 reflects concomitant cardiac and renal dysfunction secondary to a systemic condition that primarily affects both organs, such as sepsis. There are limited data on the etiology, pathogenesis and clinical implications of cardiorenal syndrome in sepsis. Cardiac dysfunction and injury can be measured with cardiac biomarkers, echocardiographic dysfunction, and hemodynamic parameters. Acute kidney injury is systematically evaluated using serum creatinine and urine output criteria. This review seeks to systematically describe the epidemiology, risk factors, pathogenesis, diagnosis and management of cardiorenal syndrome type-5 in the setting of sepsis.

Development and performance of a novel vasopressor-driven mortality prediction model in septic shock.

BACKGROUND: Vasoactive medications are essential in septic shock, but are not fully incorporated into current mortality prediction risk scores. We sought to develop a novel mortality prediction model for septic shock incorporating quantitative vasoactive medication usage. METHODS: Quantitative vasopressor use was calculated in a cohort of 5352 septic shock patients and compared using norepinephrine equivalents (NEE), cumulative vasopressor index and the vasoactive inotrope score models. Having best discrimination prediction, log10NEE was selected for further development of a novel prediction model for 28-day and 1-year mortality via backward stepwise logistic regression. This model termed 'MAVIC' (Mechanical ventilation, Acute Physiology And Chronic Health Evaluation-III, Vasopressors, Inotropes, Charlson comorbidity index) was then compared to Acute Physiology And Chronic Health Evaluation-III (APACHE-III) and Sequential Organ Failure Assessment (SOFA) scores in an independent validation cohort for its accuracy in predicting 28-day and 1-year mortality. MEASUREMENTS AND MAIN RESULTS: The MAVIC model was superior to the APACHE-III and SOFA scores in its ability to predict 28-day mortality (area under receiver operating characteristic curve [AUROC] 0.73 vs. 0.66 and 0.60) and 1-year mortality (AUROC 0.74 vs. 0.66 and 0.60), respectively. CONCLUSIONS: The incorporation of quantitative vasopressor usage into a novel 'MAVIC' model results in superior 28-day and 1-year mortality risk prediction in a large cohort of patients with septic shock.

Impact of Age on Outcomes in Hospitalized Patients with Hereditary Hemorrhagic Telangiectasia.

BACKGROUND: There is little published literature regarding the impact of age on outcomes amongst hospitalized HHT (hereditary hemorrhagic telangiectasia) patients. METHODS: The Nationwide Inpatient Sample (NIS) was used to obtain data on all hospital discharges occurring in HHT patients from 2000 to 2012. The association between admission age and HHT-related complications and outcomes were studied. RESULTS: 10293 hospitalizations in HHT patients from 2000 to 2012 were included. Patients > 50 accounted for 77% of all admissions with 30% of admissions occurring in the 51-65 age group. Bleeding related complications were the most frequent (62.7%, n = 6455 hospitalizations), followed by cardiovascular (41%, n = 4216), neurological (12.4%, n = 1276), and hepatobiliary (6.4%, n = 660) complications. Patients older than 50 accounted for 83% of bleeding events, 90% of cardiovascular events, 58% of neurologic events, and 81% of hepatobiliary events. The vast majority (83%) of medical and surgical procedures were performed in those older than 50 years of age. Older patients also experienced higher rates of death. CONCLUSION: Aging has significant adverse impacts on rates of hospitalization, complications, and outcomes amongst HHT patients in the United States. Except for neurologic complications, the vast majority of this disease burden is borne by patients older than 50 years.

Intravenous Bevacizumab for Refractory Hereditary Hemorrhagic Telangiectasia-Related Epistaxis and Gastrointestinal Bleeding.

OBJECTIVE: To present a multiyear clinical experience with intravenous bevacizumab for the management of severe gastrointestinal bleeding and/or epistaxis in patients with hereditary hemorrhagic telangiectasia (HHT). PATIENTS AND METHODS: All patients treated with intravenous bevacizumab for severe hereditary hemorrhagic telangiectasia-related bleeding from June 1, 2013, through January 31, 2017, were included in this report. Severity of epistaxis (determined using the Epistaxis Severity Score questionnaire); hemoglobin, iron, and ferritin levels; and quality of life data were collected serially in all patients. RESULTS: Intravenous bevacizumab was administered to 34 patients using a standardized treatment protocol. Anemia was primarily related to severe epistaxis (n=15, 44%), severe gastrointestinal bleeding (n=4, 12%), or both (n=15, 44%), with a median baseline hemoglobin level of 9.1 g/dL (range, 8.3-10.5 gm/dL; to convert to mmol/L, multiply by 0.62). Red blood cell (RBC) transfusions had been administered to 28 patients (82%). Of these, 16 patients (47%) were RBC transfusion dependent and had received a median of 75 RBC transfusions (range, 4->500 RBC units) before bevacizumab initiation. The median length of follow-up was 17.6 months from the beginning of bevacizumab treatment (range, 3-42.5 months). There was a significant reduction in epistaxis severity scores (P<.001) and RBC transfusion requirements (P=.007) after completion of the initial bevacizumab treatment cycle. New-onset or worsened hypertension was noted in 4 patients, with 1 patient experiencing hypertensive urgency with a temporary decline in renal function. CONCLUSION: Intravenous bevacizumab is an effective treatment option for patients with severe anemia related to epistaxis and/or gastrointestinal bleeding. Further studies are needed to establish a dose-response relationship as well as clinical, genetic, and biomarker predictors of response.

Multifocal micronodular pneumocyte hyperplasia (MMPH) in a patient with tuberous sclerosis-evidence for long term stability.

Multifocal micronodular pneumocyte hyperplasia (MMPH) is rare entity seen mostly in patients with the tuberous sclerosis complex (TSC). We present the case of a 50 year old woman with TSC (confirmed TSC2 mutation) found to have multiple ground glass opacities with an upper lobe predominance on a screening chest CT. No abnormalities were detected in other viscera. A thoracoscopic lung biopsy obtained from right upper lobe confirmed the diagnosis of MMPH. There were no lesions suggestive of lymphangioleiomyomatosis (LAM) either on the chest CT or lung biopsy. A repeat CT chest obtained on follow up 9 years after initial diagnosis continued to show stability of all MMPH ground glass lesions. This case highlights the distinct patterns of lung involvement in TSC, with MMPH having a benign and stable nature as compared to LAM which is often relentlessly progressive with associated lung function decline.

Saddle vs Nonsaddle Pulmonary Embolism: Clinical Presentation, Hemodynamics, Management, and Outcomes.

OBJECTIVE: To understand the clinical significance, hemodynamic presentation, management, and outcomes of patients presenting with saddle pulmonary embolism (PE). METHODS: All patients with saddle PE diagnosed at Mayo Clinic in Rochester, Minnesota, from January 1, 1999, through December 31, 2014, were included in this study. These patients were age and simplified Pulmonary Embolism Severity Index (sPESI) matched (1:1) to a nonsaddle PE cohort. Both groups were then classified into massive, submassive, and low-risk PE based on established criteria and compared for clinical presentation, management, and outcomes. RESULTS: A total of 187 consecutive patients with saddle PE were identified. The saddle PE group presented more frequently with massive PE (31% vs 20%) and submassive PE (49% vs 32%), whereas low-risk PE was more common in the nonsaddle PE group (48% vs 20%). Systemic thrombolysis was used more frequently in the saddle PE group on admission (10% vs 4%; P=.04) and later during hospitalization (3.2% vs 0%; P=.03). Late major adverse events were similar in both groups except for mechanical ventilation (6% in saddle PE vs 1% in nonsaddle PE; P=.02). Overall in-hospital mortality did not differ between the 2 groups (4.3% in saddle PE vs 5.4% in nonsaddle PE; P=.81). CONCLUSION: Although patients with saddle PE presented with higher rates of hemodynamic compromise and need for thrombolysis and mechanical ventilation, we found no difference in short-term outcomes compared with an age- and severity-matched nonsaddle PE cohort. Overall, in-hospital mortality was low in both groups.

Prevalence of Clostridium difficile infection in acute care hospitals, long-term care facilities, and outpatient clinics: Is Clostridium difficile infection underdiagnosed in long-term care facility patients?

Clostridium difficile infection is a common cause of diarrhea in long-term care facility (LTCF) patients. The high prevalence of C difficile infection in LTCFs noted in our study calls for a critical need to educate LTCF staff to send diarrheal stool for C difficile testing to identify more cases and prevent transmission.