Georgi I. Wassilew

Human memory T cells from the bone marrow are resting and maintain long-lasting systemic memory

Significance Memory T cells are essential components of immunological memory. In the apparent absence of antigen, numbers of recirculating antigen-specific memory T cells dwindle, provoking the question of whether there is immunological memory without memory T cells. Here we show that human memory T cells can reside in the bone marrow as resting cells in terms of proliferation, transcription, and mobility. The repertoire of bone marrow memory T cells is enriched for systemic pathogens representing persistent, recent, and childhood challenges. In terms of absolute numbers, memory T cells specific for systemic antigens are maintained predominantly in the bone marrow, in particular those representing historic encounters. In the bone marrow, a population of memory T cells has been described that promotes efficient secondary immune responses and has been considered to be preactivated, owing to its expression of CD69 and CD25. Here we show that human bone marrow professional memory T cells are not activated but are resting in terms of proliferation, transcription, and mobility. They are in the G0 phase of the cell cycle, and their transcriptome is that of resting T cells. The repertoire of CD4+ bone marrow memory T cells compared with CD4+ memory T cells from the blood is significantly enriched for T cells specific for cytomegalovirus-pp65 (immunodominant protein), tetanus toxoid, measles, mumps, and rubella. It is not enriched for vaccinia virus and Candida albicans-MP65 (immunodominant protein), typical pathogens of skin and/or mucosa. CD4+ memory T cells specific for measles are maintained nearly exclusively in the bone marrow. Thus, CD4+ memory T cells from the bone marrow provide long-term memory for systemic pathogens.

The Expression of Proinflammatory Cytokines and Matrix Metalloproteinases in the Synovial Membranes of Patients With Osteoarthritis Compared With Traumatic Knee Disorders

PURPOSE The aim of this study was to evaluate a subset of matrix metalloproteinases (MMPs) and proinflammatory cytokines within the synovium, from traumatic knee disorders (TKDs) and nontraumatic osteoarthritis (OA). METHODS MMP-1, MMP-3, interleukin 1beta, and tumor necrosis factor (TNF) alpha gene expression was quantified by use of TaqMan-based real-time polymerase chain reaction (Applied Biosystems, Foster City, CA) in synovial tissue samples obtained from 12 patients with OA and 32 with TKDs. In addition, the levels of serum inflammatory parameter C-reactive protein (CRP) were recorded. At arthroscopy, the amount of chondral damage was graded based on the Outerbridge classification. RESULTS Quantitative analysis showed no significant differences in the expression levels of MMPs, interleukin 1beta, or TNF-alpha messenger RNA between the synovial tissues of patients with OA and TKD, but CRP level was significantly increased in the OA group. A significant correlation was also seen regarding the gene expression levels between MMP-1 and -3, as well as between CRP and MMPs tested. Furthermore, significant relations between TNF-alpha and MMP-1 plus MMP-3 were observed in the OA synovial tissue. The level of TNF-alpha in the synovial tissue correlated with the time after injury as well as chondral damage in patients with TKD. CONCLUSIONS This study shows similar changes in the inflammatory patterns of synovial tissue of TKD and OA suggesting a likely disease progression. Moreover, the correlation between CRP and MMP expression levels indicates their essential role in joint degeneration in synovial tissue of primary OA patients. CLINICAL RELEVANCE TNF-alpha could provide a factor to quantify individual risk for the development of OA.

The weighted optimal common shape technique improves identification of the hip joint center of rotation in vivo.

Functional methods present a promising approach for the identification of skeletal kinematics, but their accuracy is limited by soft tissue artifacts (STAs). We hypothesized that consideration of the nonuniform distribution of STAs across the segment can lead to a significant improvement in the determination of the center of rotation at the hip. Twenty‐four total hip arthroplasty (THA) patients performed repetitions of a star‐arc movement. The location of the hip centers of rotation (CoRs) were estimated from the motion data using the Symmetrical Center of Rotation Estimation (SCoRE), both with and without procedures to minimize the effect of STAs. The precision of the CoR estimations was evaluated using the SCoRE residual, a measure of joint precision. Application of the newly developed weighted Optimal Common Shape Technique (wOCST) achieved the best CoR estimations with a precision of better than 3 mm, while the precision using raw data alone was up to seven times worse. Furthermore, consideration of the nonuniform distribution of STA across the surface of the skin using the wOCST produced an improvement of ∼24% over kinematics data processed using the standard OCST. Functional determination of the CoR at the hip using the newly developed wOCST can now identify the joint CoR with a precision of millimeters. Such approaches therefore offer improved precision in the assessment of skeletal kinematics and may aid in evaluating clinical treatment success and differentiating between therapy outcomes.

Standardized AP radiographs do not provide reliable diagnostic measures for the assessment of acetabular retroversion

Diagnosis of acetabular retroversion is essential in femoroacetabular impingement (FAI), but its assessment from radiographs is complicated by pelvic tilt and the two‐dimensional nature of plain films. We performed a study to validate the diagnostic accuracy of the cross‐over sign (COS) and the posterior wall sign (PWS) in identifying acetabular retroversion. COS and PWS were evaluated from radiographs and computed tomography (CT) scans as the standard of reference in 50 hips of subjects with symptoms of FAI. A CT‐based method using three‐dimensional (3D) models was developed to measure the COS, PWS, true acetabular version, and pelvic tilt relative to the anterior pelvic plane. The new CT‐based method aimed to eliminate errors resulting from variations in the position and orientation of the pelvis during imaging. A low level of agreement for COS and PWS was found between radiographs and CT scans. A positive COS strongly correlated with pelvic tilt. These results suggest that COS and PWS determined from anteroposterior radiographs are considerably limited by pelvic tilt and inherent limitations of radiographs. Their use as the sole basis for deciding whether or not surgical intervention is indicated seems questionable.

Real Time Visualization of Femoroacetabular Impingement and Subluxation Using 320-Slice Computed Tomography

We visualized extreme ranges of motion of the hip and located femoroacetabular impingement (FAI) and subluxations using 4dimensional (D) volume computed tomography (CT). In dynamic 4D CT, 30 patients with hip pain (>3 months) and positive clinical and radiological signs of impingement were prospectively analyzed. The investigations were performed in flexion, abduction, and external rotation. The accuracy of the CT visualization of FAI was compared with the intraoperative findings during surgical dislocation, which served as the gold standard. Compared to the intraoperative visualization of FAI, the dynamic CT images showed a high degree of accuracy. 4D CT is a suitable method to dynamically visualize the functional consequences of anatomical FAI pathologies. The location of impingement can be accurately determined, and when combined with information about possible labral tears and chondral damage supplied by magnetic resonance arthrography, allows the surgeon to select the optimal surgical access and plan the required operation for minimal invasiveness.

Improvement in the detection rate of PJI in total hip arthroplasty through multiple sonicate fluid cultures

The microbiological culture of sonicate fluid (SFC) of explanted endoprosthetic components has increased the rate of bacterial isolation in comparison to conventional microbiological methods. However, this creates the problem of interpreting cases of singular bacterial isolation through SFC, while all other microbiological samples remain negative. The aim of this study was to reference these singular positive SFC against, the histological classification of the periprosthetic membrane (PM), and the utilization of multiple SFC (separate sonication of individual endoprosthetic components). In this prospective study we compared the effect of multiple SFC for detection of periprosthetic joint infection (PJI) in patients with total hip revision surgery. All microbiological results were referenced against PM. Of the 102 cases there were 37 cases of PJI. Single SFC achieved the highest sensitivity of all individual parameters with 89% and a specificity of 72%. When multiple SFC were employed the sensitivity and specificity increased to 100%. There was a concordance of 86% between the PM and SFC. SFC achieved the highest sensitivity and it was possible to further improve the sensitivity and specificity when using multiple cultures. Multiple SFC and PM are beneficial to help reference singular bacterial isolations and achieve the diagnosis of PJI.

Use of an ultrasound-based navigation system for an accurate acetabular positioning in total hip arthroplasty: a prospective, randomized, controlled study.

The purpose of this study was to compare an ultrasound-based navigation system with an imageless navigation system with surface registration in the postoperative acetabular cup position. A prospective randomized controlled study of 2 groups of 40 patients each was performed. In the first group, cup positioning was assisted by an ultrasound-based navigation system, and in the second group, the cup was assisted by imageless navigation system with surface registration. There was significantly more outliers in the imageless navigation group. In addition, there was statistical significance in the anteversion angles and in the anteversion error between the imageless navigation and ultrasound-based navigation groups. Ultrasound-based navigation improves cup positioning in total hip arthroplasty better than an imageless navigation system by reducing the outliers, achieving a higher accuracy of anteversion.

Significant muscle damage after multiple revision total hip replacements through the direct lateral approach

Intact abductors of the hip play a crucial role in preventing limping and are known to be damaged through the direct lateral approach. The extent of trauma to the abductors after revision total hip replacement (THR) is unknown. The aim of this prospective study was to compare the pre- and post-operative status of the gluteus medius muscle after revision THR. We prospectively compared changes in the muscle and limping in 30 patients who were awaiting aseptic revision THR and 15 patients undergoing primary THR. The direct lateral approach as described by Hardinge was used for all patients. MRI scans of the gluteus medius and functional analyses were recorded pre-operatively and six months post-operatively. The overall mean fatty degeneration of the gluteus medius increased from 35.8% (1.1 to 98.8) pre-operatively to 41% (1.5 to 99.8) after multiple revision THRs (p = 0.03). There was a similar pattern after primary THR, but with considerably less muscle damage (p = 0.001), indicating progressive muscle damage. Despite an increased incidence of a positive Trendelenburg sign following revision surgery (p = 0.03) there was no relationship between the cumulative fatty degeneration in the gluteus medius and a positive Trendelenburg sign (p = 0.26). The changes associated with other surgical approaches to the hip warrant investigation.

Kinematic analysis of the flexion axis for correct femoral component placement

PurposeThis study evaluates a new method for intraoperative determination of femoral component rotation by a navigation system (flexion axis, FA) driven by joint stability over the range of motion.MethodsSeventy-five patients were treated with a navigated total knee replacement. Intraoperatively, the posterior condylar axis (PCA), the Whiteside′s line (WL), and the surgical epicondylar axis (EA) were palpated, the flexion gap (FG) was determined, and the FA was calculated. The anatomical landmarks, lines, and angles were determined based on a postoperative computed tomography in all knees. The femoral rotation was intraoperatively determined by the surgeon based on the knowledge of the EA, the PCA, and the FG but not the FA.ResultsThe deviation of the palpated EA was 3.5° [0°–13.8°], of the PCA externally rotated by 3° was 2.2° [0°–9.6°], of the WL was 3.8° [0.1°–10.0°], of the FG was 2.5° [0.2°–8.8°], and of the FA was 2.5° [0°–10.0°].ConclusionsThe FA is a new functionally acquired axis for the determination of optimal femoral component alignment. Whether the FA leads to clinically superior results must be clarified by subsequent studies.Level of evidence I.

Frontal plane alignment: An imageless method to predict the mechanical femoral–tibial angle (mFTA) based on functional determination of joint centres and axes

Lower limb alignment is important for the internal loading conditions in the knee. In this study, we aimed to evaluate a new imageless, non-invasive method for quantifying frontal plane alignment by direct comparison against CT. To determine the mechanical femoral-tibial angle (mFTA), functional posture analysis was performed in 15 limbs (13 individuals) using previously published methods for the minimisation of skin marker artefact together with the functional identification of joints, and compared against a published regression method. Whilst the average Functional-mFTA (1.3 + or - 2.3) was not significantly different (p > 0.25) from the CT-mFTA (1.5 + or - 2.1), the Regression-mFTA (4.7 + or - 5.6) showed a significant error (p < 0.01). The Functional-mFTA correlated significantly (R = 0.91; p < 0.0001), with a small bias (0.3 degrees) and agreed better with the CT-mFTA than the Regression-mFTA (R = 0.76; p < 0.001), which had a bias of 3.4 degrees. The results demonstrate that the mFTA can be quantified accurately using an imageless, non-invasive functional approach, which also offers greater accuracy over regression methods.These new techniques could provide an accurate, non-invasive approach for quantifying frontal plane alignment, particularly in cases where X-rays may not be available.