Skeletal muscle BOLD MRI: from underlying physiological concepts to its usefulness in clinical conditions

Blood oxygenation-level dependent (BOLD) MRI has gained particular attention in functional brain imaging studies, where it can be used to localize areas of brain activation with high temporal resolution. To a higher degree than in the brain, skeletal muscles show extensive but transient alterations of blood flow between resting and activation state. Thus, there has been interest in the application of the BOLD effect in studying the physiology of skeletal muscles (healthy and diseased) and its possible application to clinical practice. This review outlines the potential of skeletal muscle BOLD MRI as a diagnostic tool for the evaluation of physiological and pathological alterations in the peripheral limb perfusion, such as in peripheral arterial occlusive disease. Moreover, current knowledge is summarized regarding the complex mechanisms eliciting BOLD effect in skeletal muscle. We describe technical fundaments of the procedure that should be taken into account when performing skeletal muscle BOLD MRI, including the most often applied paradigms to provoke BOLD signal changes and key parameters of the resulting time courses. Possible confounding effects in muscle BOLD imaging studies, like age, muscle fiber type, training state, and drug effects are also reviewed in detail.     

Patellar resurfacing as a second stage procedure for persistent anterior knee pain after primary total knee arthroplasty

Purpose

Knee pain after total knee arthroplasty may be caused by an unresurfaced patella. Secondary isolated resurfacing of the previously unresurfaced patella in total knee arthroplasty remains controversial. The aim of this retrospective study was to evaluate the outcome after patellar resurfacing as a second stage procedure.

Methods

The study included 22 patients (13 female/nine male) who underwent resurfacing of the patella with a mean follow-up of 61.8 ± 39.2 months. The mean age of the patients was 60 ± 9.7 years at the time of operation. The average period between total knee arthroplasty and patellar resurfacing was 26.3 ± 15.2 months. The patient’s subjective satisfaction was assessed by a custom-made questionnaire.

Results

The mean Knee Society Score improved significantly from 60.1 ± 8.3 to 77.0 ± 6.3 (p = 0.0063). The mean functional score also improved significantly from 42.7 ± 2.3 to 60.2 ± 3.9 (p = 0.001). Three patients (13.6%) needed further operative revision.

Conclusions

Although clinical scores showed significant improvement some patients continued to have pain and remained dissatisfied without detecting a specific reason. Further studies are needed to better elucidate the benefit of patellar resurfacing as second stage procedure.     

Prediction of volume responsiveness using pleth variability index in patients undergoing cardiac surgery after cardiopulmonary bypass

Background

The pleth variability index (PVI) is derived from analysis of the plethysmographic curve and is considered to be a noninvasive parameter for prediction of volume responsiveness. The aim of our prospective clinical study was to evaluate if volume responsiveness can be predicted by PVI in patients undergoing cardiac surgery after cardiopulmonary bypass.

Methods

Eighteen patients were prospectively studied. Directly after cardiac surgery, PVI, stroke volume variation (SVV), and cardiac index (CI) were recorded. Colloid infusion (4?ml/kg body weight) was used for volume loading, and volume responsiveness was defined as increase of CI more than 10?%.

Results

SVV and PVI measures were found to be highly correlated at r?=?0.80 (p?<?0.001). Receiver operating characteristics curve (ROC) analysis resulted in an area under the curve of 0.87 for SVV and 0.95 for PVI, which values did not differ statistically significant from each other (p?>?0.05). The optimal threshold value given by ROC analysis was ≥11?% for SVV with a sensitivity and specificity of 100?% and 72.2?%. For PVI, optimal threshold value was ≥16?% with a sensitivity and specificity of 100?% and 88.9?%. Positive and negative predictive values estimating an increase of CI ≥10?% for SVV were 44.4?% and 100?% and 66.7?% and 100?% for PVI.

Conclusions

For consideration of fluid responsiveness PVI is as accurate as SVV in patients after cardiopulmonary bypass. Methodological limitations such as instable cardiac rhythm after cardiopulmonary bypass and right- or left ventricular impairment seem to be responsible for low specificity and positive predictive values in both parameters PVI and SVV.     

Transcatheter Valve-in-Valve Therapies: Patient Selection, Prosthesis Assessment and Selection, Results, and Future Directions

The development of transcatheter valve implantations (TAVI) has induced profound changes in the treatment of valvular heart disease over the past decade. At the same time, due to excellent clinical results, bioprostheses continuously outperformed mechanical prostheses. The increasing number of elderly patients has led to numerous patients presenting with deteriorated bioprostheses needing reoperation. In selected high-risk patients or patients with unreasonable surgical risk, valve-in-valve TAVI has advanced to a viable alternative to conventional redo surgery. High procedural success, good hemodynamics and acceptable clinical results were reported up until now. Valve-in-valve TAVI seems to be safe and effective in treatment of deteriorated valve prostheses in high-risk patients. The valve-in-valve concept presents the next step toward an individual treatment strategy for patients at prohibitive risk for conventional surgery. Present studies were reviewed with special concern to patient selection, prosthesis assessment, device selection, clinical outcome and technical challenging aspects as well.     

From the Cover: PNAS Plus: Comprehensive analysis of dengue virus-specific responses supports an HLA-linked protective role for CD8+ T cells

The role of CD8⁺ T cells in dengue virus infection and subsequent disease manifestations is not fully understood. According to the original antigenic sin theory, skewing of T-cell responses induced by primary infection with one serotype causes less effective response upon secondary infection with a different serotype, predisposing individuals to severe disease. A comprehensive analysis of CD8⁺ responses in the general population from the Sri Lankan hyperendemic area, involving the measurement of ex vivo IFNγ responses associated with more than 400 epitopes, challenges the original antigenic sin theory. Although skewing of responses toward primary infecting viruses was detected, this was not associated with impairment of responses either qualitatively or quantitatively. Furthermore, we demonstrate higher magnitude and more polyfunctional responses for HLA alleles associated with decreased susceptibility to severe disease, suggesting that a vigorous response by multifunctional CD8⁺ T cells is associated with protection from dengue virus disease.Dengue virus (DENV) is the etiologic agent of dengue fever (DF), the most significant mosquito-borne viral disease in humans. Disease can be caused by any of the four DENV serotypes (DENV1 to -4), which share 67–75% sequence homology with one another (1). DENV transmission occurs in more than 100 countries and is an increasing public health problem in tropical and subtropical regions (2). Demographic changes, urbanization, and international travel contribute to the expansion of geographical areas where transmission occurs, and all four DENV serotypes are now circulating in Asia, Africa, and the Americas (3, 4). Up to 100 million DENV infections occur every year (5), and severity can range from asymptomatic to an acute self-limiting febrile illness (DF). In a small proportion of patients, the disease can exacerbate and progress to dengue hemorrhagic fever (DHF) and/or dengue shock syndrome (DSS), characterized by severe vascular leakage, thrombocytopenia, and hemorrhagic manifestations (4).Although natural infection by any of the four DENV serotypes (primary infection) produces a lasting protective immunity against reinfection by the same serotype, it does not protect against infections with other serotypes (secondary infections) (6, 7). Epidemiologic studies have shown that the majority of individuals that develop DHF/DSS had been previously infected with a different serotype (8). Consequently, the development of DENV vaccines has been hampered by the potential risk of vaccine-related adverse events and the requirement to induce long-lasting protective immune responses against all four DENV serotypes simultaneously (9). The cause for the increased frequency of DHF following secondary infections has not been fully elucidated. One hypothesis is that serotype cross-reactive antibodies exacerbate disease by increasing infection of cells bearing Fcγ receptors, resulting in higher viral loads and more severe disease via this antibody-dependent enhancement (ADE) of infection (10, 11). Indeed, nonhuman primate and murine models have demonstrated that antibodies can lead to enhancement of DENV infection and disease in vivo (12–15).Another hypothesis postulates that T cells raised against the first infecting serotype dominate during a secondary heterologous infection in a phenomenon termed “original antigenic sin” (16, 17). This term was first applied to the humoral response to influenza epidemics (18) but has also been observed in CD8⁺ T-cell responses against lymphocytic choriomeningitis virus (19). This hypothesis postulates that, during secondary infection, expansion of preexisting lower avidity cross-reactive memory T cells dominate the responses over that of naïve T cells that are of higher avidity for the new DENV serotype. This expansion of low avidity T cells results in less efficient elimination of DENV-infected cells.A role for T cells in control of DENV infection is suggested by several studies that implicate HLA associations as a genetic component to variable susceptibility to DENV disease (20–26). However, it has not been addressed whether these associations might indicate a positive or detrimental role for T-cell responses. One major obstacle to the elucidation of the function of T cells is the lack of a comprehensive characterization of HLA-restricted DENV responses in the context of natural infection.Herein, we present a comprehensive analysis of functional T-cell memory against DENV and are able to correlate this with HLA alleles expressed in the very same donors. Collectively, the data suggest an HLA-linked protective role of CD8⁺ T-cell responses and do not support a causative role for CD8⁺ T cells in the induction of severe disease following secondary heterologous infection.