Memory B Cell Antibodies to HIV-1 gp140 Cloned from Individuals Infected with Clade A and B Viruses

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

Lateral femoral notch sign and posterolateral tibial plateau fractures and their associated injuries in the setting of an anterior cruciate ligament rupture

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

Tumor Response Evaluation Using iRECIST: Feasibility and Reliability of Manual Versus Software-Assisted Assessments

Objectives: To compare the feasibility and reliability of manual versus software-assisted assessments of computed tomography scans according to iRECIST in patients undergoing immune-based cancer treatment. Methods: Computed tomography scans of 30 tumor patients undergoing cancer treatment were evaluated by four independent radiologists at baseline (BL) and two follow-ups (FU), resulting in a total of 360 tumor assessments (120 each at BL/FU1/FU2). After image interpretation, tumor burden and response status were either calculated manually or semi-automatically as defined by software, respectively. The reading time, calculated sum of longest diameter (SLD), and tumor response (e.g., “iStable Disease”) were determined for each assessment. After complete data collection, a consensus reading among the four readers was performed to establish a reference standard for the correct response assignments. The reading times, error rates, and inter-reader agreement on SLDs were statistically compared between the manual versus software-assisted approaches. Results: The reading time was significantly longer for the manual versus software-assisted assessments at both follow-ups (median [interquartile range] FU1: 4.00 min [2.17 min] vs. 2.50 min [1.00 min]; FU2: 3.75 min [1.88 min] vs. 2.00 min [1.50 min]; both p < 0.001). Regarding reliability, 2.5% of all the response assessments were incorrect at FU1 (3.3% manual; 0% software-assisted), which increased to 5.8% at FU2 (10% manual; 1.7% software-assisted), demonstrating higher error rates for manual readings. Quantitative SLD inter-reader agreement was inferior for the manual compared to the software-assisted assessments at both FUs (FU1: ICC = 0.91 vs. 0.93; FU2: ICC = 0.75 vs. 0.86). Conclusions: Software-assisted assessments may facilitate the iRECIST response evaluation of cancer patients in clinical routine by decreasing the reading time and reducing response misclassifications

Highly reduced-dose CT of the lumbar spine in a human cadaver model.

PurposeFeasibility of a highly reduced-dose lumbar spine CT protocol using iterative reconstruction (IR) in a human cadaver model.Materials and methodsThe lumbar spine of 20 human cadavers was repeatedly examined using three different reduced-dose protocols (RDCT) with decreasing reference tube current-exposure time products (RDCT-1: 50 mAs; RDCT-2: 30 mAs; RDCT-3: 10 mAs) at a constant tube voltage of 140 kV. A clinical standard-dose protocol (SDCT) served as the reference (reference tube current-exposure time product: 70 mAs; tube voltage: 140 kV). Images were reconstructed using filtered back projection (FBP) and two increasing levels of IR: IRL4 and IRL6. A five-point scale was used by two observers to assess the diagnostic quality of anatomical structures (cortical and trabecular bone, intervertebral foramina, pedicles and intervertebral joints, spinous and transverse processes). Objective image noise (OIN) was measured. Results were interpreted using a linear mixed-effects regression model.ResultsRDCT-2 with IRL6 (1.2 ± 0.5mSv) was the lowest reduced-dose protocol which provided diagnostically acceptable and equivalent image quality compared to the SDCT (2.3 ± 1.1mSV) with FBP (p > 0.05). All RDCT protocols achieved a significant reduction of the mean (±SD) effective radiation doses (RDCT-1: 1.7±0.9mSv; RDCT-2: 1.2±0.5mSv; RDCT-3: 0.4±0.2mSv; p ConclusionHighly reduced-dose lumbar spine CT providing diagnostically acceptable image quality is feasible using IR in this cadaver model and may be transferred into a clinical setting

Acute impact of an endurance race on biventricular and biatrial myocardial strain in competitive male and female triathletes evaluated by feature-tracking CMR

Objectives!#!Cardiac adaptation in endurance athletes is a well-known phenomenon, but the acute impact of strenuous exercise is rarely reported on. The aim of this study was to analyze the alterations in biventricular and biatrial function in triathletes after an endurance race using novel feature-tracking cardiac magnetic resonance (FT-CMR).!##!Methods!#!Fifty consecutive triathletes (45 ± 10 years; 80% men) and twenty-eight controls were prospectively recruited, and underwent 1.5-T CMR. Biventricular and biatrial volumes, left ventricular ejection fraction (LVEF), FT-CMR analysis, and late gadolinium imaging (LGE) were performed. Global systolic longitudinal (GLS), circumferential (GCS), and radial strain (GRS) were assessed. CMR was performed at baseline and following an endurance race. High-sensitive troponin T and NT-proBNP were determined. The time interval between race completion and CMR was 2.3 ± 1.1 h (range 1-5 h).!##!Results!#!Post-race troponin T (p &amp;lt; 0.0001) and NT-proBNP (p &amp;lt; 0.0001) were elevated. LVEF remained constant (62 ± 6 vs. 63 ± 7%, p = 0.607). Post-race LV GLS decreased by tendency (- 18 ± 2 vs. - 17 ± 2%, p = 0.054), whereas GCS (- 16 ± 4 vs. - 18 ± 4%, p &amp;lt; 0.05) and GRS increased (39 ± 11 vs. 44 ± 11%, p &amp;lt; 0.01). Post-race right ventricular GLS (- 19 ± 3 vs. - 19 ± 3%, p = 0.668) remained constant and GCS increased (- 7 ± 2 vs. - 8 ± 3%, p &amp;lt; 0.001). Post-race left atrial GLS (30 ± 8 vs. 24 ± 6%, p &amp;lt; 0.0001) decreased while right atrial GLS remained constant (25 ± 6 vs. 24 ± 6%, p = 0.519).!##!Conclusions!#!The different alterations of post-race biventricular and biatrial strain might constitute an intrinsic compensatory mechanism following an acute bout of endurance exercise. The combined use of strain parameters may allow a better characterization of ventricular and atrial function in endurance athletes.!##!Key points!#!• Triathletes demonstrate a decrease of LV global longitudinal strain by tendency and constant RV global longitudinal strain following an endurance race. • Post-race LV and RV global circumferential and radial strains increase, possibly indicating a compensatory mechanism after an acute endurance exercise bout. • Subgroup analyses of male triathletes with focal myocardial fibrosis did not demonstrate alterations in biventricular and biatrial strain after an endurance race