Natural killer/T-cell lymphoma (NKTCL) is a rare subtype of non-Hodgkin lymphoma that is associated with a poor outcome. Currently, the treatment needs of NKTCL remain unmet, and efforts to further improve treatment are urgently needed. Herein, seven patients with NKTCL who failed to respond to various types of chemotherapies were treated with the anti-programmed death 1 (anti-PD-1) antibody pembrolizumab at 100 mg every 3 weeks. After a median of four cycles of treatment (range 2–18), four out of seven patients responded (two complete response, two partial response, overall response rate 57%). Expression of PD1-ligand available was 50, 20, 30, 70, and 30% of five patients respectively. It is negative in one patient and not tested in one patient. Adverse events, which mostly ranged from grade I to grade III, were tolerable and could be safely handled, although immune-related pneumonitis was notable. Overall, PD-1 blockade with pembrolizumab represents a favorable strategy for the treatment of refractory/relapsed NKTCL.

Availability of accurate three-dimensional (3D) kinematics of lumbar vertebrae is necessary to understand normal and pathological biomechanics of the lumbar spine. Due to the technical challenges of imaging the lumbar spine motion in vivo, it has been difficult to obtain comprehensive, 3D lumbar kinematics during dynamic functional tasks. The present study demonstrates a recently developed technique to acquire true 3D lumbar vertebral kinematics, in vivo, during a functional load-lifting task. The technique uses a high-speed dynamic stereo-radiography (DSX) system coupled with a volumetric model-based bone tracking procedure. Eight asymptomatic male participants performed weight-lifting tasks, while dynamic X-ray images of their lumbar spines were acquired at 30 fps. A custom-designed radiation attenuator reduced the radiation white-out effect and enhanced the image quality. High resolution CT scans of participants' lumbar spines were obtained to create 3D bone models, which were used to track the X-ray images via a volumetric bone tracking procedure. Continuous 3D intervertebral kinematics from the second lumbar vertebra (L2) to the sacrum (S1) were derived. Results revealed motions occurring simultaneously in all the segments. Differences in contributions to overall lumbar motion from individual segments, particularly L2–L3, L3–L4, and L4–L5, were not statistically significant. However, a reduced contribution from the L5–S1 segment was observed. Segmental extension was nominally linear in the middle range (20%–80%) of motion during the lifting task, but exhibited nonlinear behavior at the beginning and end of the motion. L5–S1 extension exhibited the greatest nonlinearity and variability across participants. Substantial AP translations occurred in all segments (5.0 ± 0.3 mm) and exhibited more scatter and deviation from a nominally linear path compared to segmental extension. Maximum out-of-plane rotations (<1.91 deg) and translations (<0.94 mm) were small compared to the dominant motion in the sagittal plane. The demonstrated success in capturing continuous 3D in vivo lumbar intervertebral kinematics during functional tasks affords the possibility to create a baseline data set for evaluating the lumbar spinal function. The technique can be used to address the gaps in knowledge of lumbar kinematics, to improve the accuracy of the kinematic input into biomechanical models, and to support development of new disk replacement designs more closely replicating the natural lumbar biomechanics.

In this paper, we present a new methodology for subject-specific finite element modeling of the tibiofemoral joint based on in vivo computed tomography (CT), magnetic resonance imaging (MRI), and dynamic stereo-radiography (DSX) data. We implemented and compared two techniques to incorporate in vivo skeletal kinematics as boundary conditions: one used MRI-measured tibiofemoral kinematics in a nonweight-bearing supine position and allowed five degrees of freedom (excluding flexion-extension) at the joint in response to an axially applied force; the other used DSX-measured tibiofemoral kinematics in a weight-bearing standing position and permitted only axial translation in response to the same force. Verification and comparison of the model predictions employed data from a meniscus transplantation study subject with a meniscectomized and an intact knee. The model-predicted cartilage-cartilage contact areas were examined against “benchmarks” from a novel in situ contact area analysis (ISCAA) in which the intersection volume between nondeformed femoral and tibial cartilage was characterized to determine the contact. The results showed that the DSX-based model predicted contact areas in close alignment with the benchmarks, and outperformed the MRI-based model: the contact centroid predicted by the former was on average 85% closer to the benchmark location. The DSX-based FE model predictions also indicated that the (lateral) meniscectomy increased the contact area in the lateral compartment and increased the maximum contact pressure and maximum compressive stress in both compartments. We discuss the importance of accurate, task-specific skeletal kinematics in subject-specific FE modeling, along with the effects of simplifying assumptions and limitations.

A growing body of evidence supports the importance of anatomic tunnel positioning in the success of anterior cruciate ligament (ACL) reconstruction, which stimulates the need for technologies to aid surgeons in achieving accurate anatomic tunnel placement. Intraoperative fluoroscopy is potentially one such technology, while its efficacy and usability have yet to be established. To investigate the performance of an intraoperative fluoroscopic overlay in guiding tunnel placement during ACL reconstruction. Controlled laboratory study. Twenty cadaveric knees underwent computed tomography (CT) scans and arthroscopic digitization of ACL insertion sites. The outlines of the digitized insertion sites were mapped to the corresponding CT-acquired bone models through a co-registration procedure. Twenty orthopaedic surgeons performed simulated ACL reconstructions, each on a randomly assigned cadaveric knee, first without and then with the aid of a fluoroscopic overlay system. The overlay system displayed on a lateral fluoroscopic image targets points representing the locations of the ACL insertion sites estimated from the literature data. Surgeons were allowed to adjust their tunnel positions under the guidance of the fluoroscopic image. Their initial, intermediate, and final positions were documented and compared with the target points as well as the native insertion sites. Surgeons demonstrated significant (P < .01) improvements in femoral and tibial tunnel placements relative to the target points from an average distance of 3.9 mm to 1.6 mm on the femur and 2.1 mm to 0.9 mm on the tibia. The improvements toward the knee-specific actual insertion sites were significant on the tibial side but not on the femoral side. Surgeons can be successfully guided with fluoroscopy to create more consistent femoral and tibial tunnels during ACL reconstruction. More research is warranted to develop better population representations of the locations of natural insertion sites. Intraoperative fluoroscopy can be an effective, easy, and safe method for improving tunnel positioning during ACL reconstruction.