Understanding the antibody response to HIV-1 in humans that show broad neutralizing serologic activity is a crucial step in trying to reproduce such responses by vaccination. Investigating antibodies with cross clade reactivity is particularly important as these antibodies may target conserved epitopes on the HIV envelope gp160 protein. To this end we have used a clade B YU-2 gp140 trimeric antigen and single-cell antibody cloning methods to obtain 189 new anti-gp140 antibodies representing 51 independent B cell clones from the IgG memory B cells of 3 patients infected with HIV-1 clade A or B viruses and exhibiting broad neutralizing serologic activity. Our results support previous findings showing a diverse antibody response to HIV gp140 envelope protein, characterized by differentially expanded B-cell clones producing highly hypermutated antibodies with heterogenous gp140-specificity and neutralizing activity. In addition to their high-affinity binding to the HIV spike, the vast majority of the new anti-gp140 antibodies are also polyreactive. Although none of the new antibodies are as broad or potent as VRC01 or PG9, two clonally-related antibodies isolated from a clade A HIV-1 infected donor, directed against the gp120 variable loop 3, rank in the top 5% of the neutralizers identified in our large collection of 185 unique gp140-specific antibodies in terms of breadth and potency.

Passive transfer of broadly neutralizing human antibodies against HIV-1 protects macaques against infection. However, HIV-1 uses several strategies to escape antibody neutralization, including mutation of the gp160 viral surface spike, a glycan shield to block antibody access to the spike, and expression of a limited number of viral surface spikes, which interferes with bivalent antibody binding. The latter is thought to decrease antibody apparent affinity or avidity, thereby interfering with neutralizing activity. To test the idea that increasing apparent affinity might enhance neutralizing activity, we engineered bispecific anti–HIV-1 antibodies (BiAbs) that can bind bivalently by virtue of one scFv arm that binds to gp120 and a second arm to the gp41 subunit of gp160. The individual arms of the BiAbs preserved the binding specificities of the original anti-HIV IgG antibodies and together bound simultaneously to gp120 and gp41. Heterotypic bivalent binding enhanced neutralization compared with the parental antibodies. We conclude that antibody recognition and viral neutralization of HIV can be improved by heteroligation.

Aims The aim of this study was to investigate the occurrence of myocardial injury and cardiac dysfunction after an endurance race by biomarkers and cardiac magnetic resonance in triathletes with and without myocardial fibrosis. Methods and results Thirty asymptomatic male triathletes (45 ± 10 years) with over 10 training hours per week and 55 ± 8 ml/kg per minute maximal oxygen uptake during exercise testing were studied before (baseline) and 2.4 ± 1.1 hours post-race. Baseline cardiac magnetic resonance included cine, T1/T2, late gadolinium enhancement (LGE) and extracellular volume imaging. Post-race non-contrast cardiac magnetic resonance included cine and T1/T2 mapping. Non-ischaemic myocardial fibrosis was present in 10 triathletes (LGE+) whereas 20 had no fibrosis (LGE–). At baseline, LGE + triathletes had higher peak exercise systolic blood pressure with 222 ± 21 mmHg compared to LGE– triathletes (192 ± 30 mmHg, P < 0.01). Post-race troponin T and creatine kinase MB were similarly increased in both groups, but there was no change in T2 and T1 from baseline to post-race with 54 ± 3 ms versus 53 ± 3 ms ( P = 0.797) and 989 ± 21 ms versus 989 ± 28 ms ( P = 0.926), respectively. However, post-race left atrial ejection fraction was significantly lower in LGE + triathletes compared to LGE– triathletes (53 ± 6% vs. 59 ± 6%, P < 0.05). Furthermore, baseline atrial peak filling rates were lower in LGE –  triathletes (121 ± 30 ml/s/m2) compared to LGE + triathletes (161 ± 34 ml/s/m2, P < 0.01). Post-race atrial peak filling rates increased in LGE– triathletes to 163 ± 46 ml/s/m2, P < 0.001), but not in LGE + triathletes (169 ± 50ml/s/m2, P = 0.747). Conclusion Despite post-race troponin T release, we did not find detectable myocardial oedema by cardiac magnetic resonance. However, the unfavourable blood pressure response during exercise testing seemed to be associated with post-race cardiac dysfunction, which could explain the occurrence of myocardial fibrosis in triathletes.

Patellofemoral maltracking predisposes the patellofemoral joint to instability. The purpose of this study was to provide a reliable dynamic magnetic resonance imaging (MRI) measuring technique for patellofemoral maltracking, and to investigate the influence of anatomical risk factors (AF) on patellar maltracking. Ten patients (2 males,8 females, average 19 years) with clinical maltracking and 20 controls (10 males,10 females,average 28 years) were examined with a dynamic, multi-slice gradient-echo MRI sequence, during repetitive flexion(40°) and full extension, in an open-chain-active-movement. In a 30-s time frame three simultaneous transverse slices were acquired. Dynamic mediolateral translation and dynamic tilt were measured at defined positions, by two independent examiners. Reproducibility was tested in a set of five knees. Common AFs for patellar maltracking (tibial-tuberosity-to-trochlear-groove-(TT-TG)-distances, trochlea-sulcus-angle, trochlea-sulcus-depth, lateral-trochlear-inclination and Caton-Deschamps-Index) were analyzed in consensus, using standard static MRI sequences. In patients, dynamic mediolateral translation was significantly greater in patients (12.4 ± 6.9 mm vs. − 0.1 ± 2.3 mm, p < 0.001) and the patella was positioned significantly more laterally (17.5 ± 6.9 mm vs. 3.1 ± 2.4 mm, p < 0.001) compared to controls. During movement, the patella tilted 16.3 ± 13.1° laterally in patients and 1.9 ± 4.3° medially in controls (dynamic tilt) (p < 0.002). All AFs were significantly different between patients and controls. Pathological TT-TG-distances, Caton-Deschamps-Indices and trochlea-sulcus-angles strongly correlated with dynamic patellar translation and dynamic patellar tilt (p < 0.001). In the patient population, the primary pathologies for maltracking were lateralized-tibial-tubercle (n = 5), trochlea dysplasia n = 2, patella alta (n = 3). Interrater-reliability for translation and tilt-measurement was excellent (0.971/0.976, 95% CIs 0.939–0.986/0.950–0.988). Dynamic MRI reliably differentiates between abnormal and physiological patellar tracking. Dynamic tracking and tilt strongly correlate with measurable AFs, which reinforces their clinical use and validates the presented technique.

Introduction ACL injury is one of the most common injuries of the knee joint in sports. As accompanying osseous injuries of the ACL rupture a femoral impression the so-called lateral femoral notch sign and a posterolateral fracture of the tibial plateau are described. However, frequency, concomitant ligament injuries and when and how to treat these combined injuries are not clear. There is still a lack of understanding with which ligamentous concomitant injuries besides the anterior cruciate ligament injury these bony injuries are associated. Materials and methods One hundred fifteen MRI scans with proven anterior cruciate ligament rupture performed at our center were retrospectively evaluated for the presence of a meniscus, collateral ligament injury, a femoral impression, or a posterolateral impression fracture. Femoral impressions were described according to their local appearance and posterolateral tibial plateau fractures were described using the classification of Menzdorf et al. Results In 29 cases a significant impression in the lateral femoral condyle was detected. There was a significantly increased number of lateral meniscal (41.4% vs. 18.6% p = 0.023) and medial ligament (41.4% vs. 22.1%; p = 0.040) injuries in the group with a lateral femoral notch sign. 104 patients showed a posterolateral bone bruise or fracture of the tibial plateau. Seven of these required an intervention according to Menzdorf et al. In the group of anterior cruciate ligament injuries with posterolateral tibial plateau fracture significantly more lateral meniscus injuries were seen (p = 0.039). Conclusion In the preoperative planning of ACL rupture accompanied with a positive femoral notch sign, attention should be paid to possible medial collateral ligament and lateral meniscus injuries. As these are more likely to occur together. A posterolateral impression fracture of the tibial plateau is associated with an increased likelihood of the presence of a lateral meniscal injury. This must be considered in surgical therapy and planning and may be the indication for necessary early surgical treatment.

Objectives To evaluate systolic cardiac dysfunction in paediatric MFS patients with chest wall deformity using cardiac magnetic resonance (CMR) imaging and feature-tracking strain analysis. Methods Forty paediatric MFS patients (16 ± 3 years, range 8−22 years) and 20 age-matched healthy controls (16 ± 4 years, range 11−24 years) were evaluated retrospectively. Biventricular function and volumes were determined using cine sequences. Feature-tracking CMR was used to assess global systolic longitudinal (GLS), circumferential (GCS) and radial strain (GRS). A dedicated balanced turbo field echo sequence was used to quantify chest wall deformity by measuring the Haller index (HI). Results LV volumes and ejection fraction (EF) were similar in MFS patients and controls. There was a trend for lower right ventricular (RV) volume (75 ± 17 vs. 81 ± 10 ml/m2, p = 0.08), RV stroke volume (41 ± 12 vs. 50 ± 5 ml/m2, p < 0.001) and RVEF (55 ± 10 vs. 62 ± 6%, p < 0.01) in MFS patients. A subgroup of MFS patients had an increased HI compared to controls (4.6 ± 1.7 vs. 2.6 ± 0.3, p < 0.001). They demonstrated a reduced RVEF compared to MFS patients without chest wall deformity (50 ± 11% vs. 58 ± 8%, p = 0.01) and controls (p < 0.001). LV GLS was attenuated when HI ≥ 3.25 (- 16 ± 2 vs. - 18 ± 3%, p = 0.03), but not GCS and GRS. LV GLS (p < 0.01) and GCS (p < 0.0001) were attenuated in MFS patients compared to controls, but not GRS (p = 0.31). RV GLS was attenuated in MFS patients compared to controls (- 21 ± 3 vs. - 23 ± 3%, p < 0.05). Conclusion Chest wall deformity in paediatric MFS patients is associated with reduced RV volume, ejection fraction and GLS. Feature-tracking CMR also indicates impairment of systolic LV function in paediatric MFS patients. Key Points • Paediatric Marfan patients demonstrate reduced RV volume and ejection fraction compared to healthy controls. • A concordant attenuation in RV global longitudinal strain was observed in Marfan patients, while the RV global circumferential strain was increased, indicating a possible compensatory mechanism. • Subgroup analyses demonstrated alterations in RV ejection fraction and RV/LV global strain parameters, indicating a possible association of severe chest wall deformity with biventricular dysfunction in paediatric Marfan patients.

Background Throughout the literature, patellofemoral instability (PI) is defined as an increased risk of re-/luxation of the patella within the patellofemoral joint (PFJ). In most patients it is caused by traumatic patella luxation or the existence of a range of predisposing anatomic risk factors leading to an unphysiological movement sequence within the PFJ also known as patellofemoral maltracking. In order to provide an individualized therapy approach, clinical and radiological evaluation of those risk factors of variable magnitude becomes essential. Diagnostic imaging such as magnetic resonance imaging (MRI), plain radiography, and computed tomography (CT) are straightforward diagnostic tools in terms of evaluation and treatment of PI. Method In this review we performed a precise analysis of today’s literature concerning the radiological evaluation of anatomic risk factors leading to PI. The purpose of the review is to present a logical compilation of the different anatomical risk factors causing PI and provide a straight overview of valuable radiological imaging techniques. Results and Conclusion PI is frequently based on a multifactorial disposition. The most relevant predisposing risk factors are trochlea dysplasia, rupture of the medial patellofemoral ligament (MPFL), patella alta, abnormal tibial tubercle to trochlea groove distance (TT-TG), femoral torsion deformities, and genu valgum. Although plain X-rays may provide basic diagnostic value, cross-sectional imaging (MRI, CT) is the standard radiological tool in terms of evaluation and detection of severity of predisposing anatomic variants leading to PI. Key Points:  Citation Format

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