The authors capture the historical importance of the MANDELA trial and its unique study design, which examines two renal‐sparing strategies, not including a standard calcineurin inhibitor arm, after ...heart transplant to illustrate the ongoing challenge of balancing acute rejection and drug‐induced nephrotoxicity. See the original article from Barten et al on page 3006.
Measles virus (MeV) is highly infectious by the respiratory route and remains an important cause of childhood mortality. However, the process by which MeV infection is efficiently established in the ...respiratory tract is controversial with suggestions that respiratory epithelial cells are not susceptible to infection from the apical mucosal surface. Therefore, it has been hypothesized that infection is initiated in lung macrophages or dendritic cells and that epithelial infection is subsequently established through the basolateral surface by infected lymphocytes. To better understand the process of respiratory tract initiation of MeV infection, primary differentiated respiratory epithelial cell cultures were established from rhesus macaque tracheal and nasal tissues. Infection of these cultures with MeV from the apical surface was more efficient than from the basolateral surface with shedding of viable MeV-producing multinucleated giant cell (MGC) syncytia from the surface. Despite presence of MGCs and infectious virus in supernatant fluids after apical infection, infected cells were not detected in the adherent epithelial sheet and transepithelial electrical resistance was maintained. After infection from the basolateral surface, epithelial damage and large clusters of MeV-positive cells were observed. Treatment with fusion inhibitory peptides showed that MeV production after apical infection was not dependent on infection of the basolateral surface. These results are consistent with the hypothesis that MeV infection is initiated by apical infection of respiratory epithelial cells with subsequent infection of lymphoid tissue and systemic spread.
Leptospirosis is the leading cause of zoonotic morbidity and mortality globally, yet little is known about the immune mechanisms that may contribute to pathogenesis and severe disease. Although ...neutrophils are a key component of early immune responses to infection, they have been associated with tissue damage and inflammation in some febrile infections. To assess whether neutrophils contribute to the pathogenesis observed in severe leptospirosis, we quantitated levels of neutrophil activation markers in patients with varying disease severities. Hospitalized leptospirosis patients had significantly higher levels of toll-like receptors 2 and 4 (TLR2 and TLR4, respectively) on peripheral neutrophils than healthy controls, with the highest levels detected in patients with organ dysfunction. We observed no significant differences in other neutrophil baseline activation markers (CD62L and CD11b) or activation capacity (CD62L and CD11b levels following stimulation), regardless of disease severity. Our results provide preliminary evidence supporting the hypothesis that higher initial bacterial loads or inadequate or delayed neutrophil responses, rather than TLR-driven inflammation, may drive severe disease outcomes.
Multiple imaging modalities are available to evaluate aneurysms post-flow diverter (FD) placement. Though digital subtraction angiography (DSA) is the gold standard imaging modality post-FD ...placement, it is not perfect, and neither are other techniques, including contrast-enhanced magnetic resonance angiography (CE-MRA) and magnetic resonance imaging (MRI). We present a case of a 73-year-old woman with a right internal carotid artery (ICA) aneurysm treated with a pipeline embolization device (PED). Initial follow-up post-PED placement by three-dimensional time-of-flight (3D-TOF) MRA demonstrated aneurysm occlusion, which was confirmed by computed tomography angiography (CTA) and CE-MRA in subsequent follow-up appointments. However, repeat CE-MRA two years later suggested recanalization of the aneurysm. After discussion with neuroradiologists and follow-up with a dynamic MRA, this finding was determined to be false. These findings shed light on the potential pitfall of using CE-MRA alone or any single imaging modality in the assessment of aneurysms post-PED placement. Our case report explores various imaging modalities used in the assessment of aneurysms post-PED placement and highlights the need to use multiple techniques for an accurate assessment.
Objective: Leptospirosis pulmonary hemorrhage syndrome (LPHS) is a severe form of leptospirosis, with a case fatality rate exceeding 50%. Recently, LPHS has become the principal cause of mortality in ...leptospirosis patients in Salvador, Brazil. This study aims to describe the epidemiology of LPHS since 2003, characterize its clinical presentation, and identify risk factors. Methods: Patients admitted between January 1, 2003 and December 31, 2012 in the active hospital-based surveillance who met the clinical case definition for leptospirosis were included in the study. A standardized questionnaire was used to collect data from patient charts and in-person interviews. Unadjusted logistic regression models identified individual-level risk factors. Maps showing spatial distribution and clustering of leptospirosis cases were created to identify areas of high risk. Results: We identified 1,316 patients meeting our case definition, which included 113 LPHS, 184 NHPL, and 1019 NPL cases. Males were at greater risk for LPHS in all age groups. The LPHS-associated mortality was 65.5% (95% CI: 56.33-73.63), compared to 30.4% and 6.2% for NHPL and NPL cases, respectively. A lower microagglutination test (MAT) titer compared for LPHS compared to NPL cases in the acute phase suggests the absence of an early robust immune response. A high-risk LPHS cluster (p= 0.01) was identified and rat sightings was associated with NHPL patients (OR: 2.77, 95% CI: 1.23-6.23). Limited unique clinical correlates observed in patients with pulmonary manifestations compared to non-pulmonary forms of leptospirosis. Conclusion: We describe the clinical features and epidemiology of LPHS in Salvador, Brazil, since its emergence in 2003. Few clinical correlates were identified between LPHS and NHPL patients, suggesting that leptospirosis is a disease on a clinical spectrum. Multidimensional control measures focusing on areas of high risk are necessary to reduce the burden of leptospirosis.
The aim of this paper is to describe the utility of various recruitment modalities utilized in the Working to Increase Stability through Exercise (WISE) study. WISE is a pragmatic randomized trial ...that is testing the impact of a 3-year, multicomponent (strength, balance, aerobic) physical activity program led by trained volunteers or delivered via DVD on the rate of serious fall-related injuries among adults 65 and older with a past history of fragility fractures (e.g., vertebral, fall-related). The modified goal was to recruit 1130 participants over 2 years in three regions of Pennsylvania.
The at-risk population was identified primarily using letters mailed to patients of three health systems and those over 65 in each region, as well as using provider alerts in the health record, proactive recruitment phone calls, radio advertisements, and presentations at community meetings.
Over 24 months of recruitment, 209,301 recruitment letters were mailed, resulting in 6818 telephone interviews. The two most productive recruitment methods were letters (72% of randomized participants) and the research registries at the University of Pittsburgh (11%). An average of 211 letters were required to be mailed for each participant enrolled. Of those interviewed, 2854 were ineligible, 2,825 declined to enroll and 1139 were enrolled and randomized. Most participants were female (84.4%), under age 75 (64.2%), and 50% took an osteoporosis medication. Not having a prior fragility fracture was the most common reason for not being eligible (87.5%). The most common reason provided for declining enrollment was not feeling healthy enough to participate (12.6%).
The WISE study achieved its overall recruitment goal. Bulk mailing was the most productive method for recruiting community-dwelling older adults at risk of serious fall-related injury into this long-term physical activity intervention trial, and electronic registries are important sources and should be considered.
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