Kinematics of Different Components of the Posterolateral Corner of the Knee in the Lateral Collateral Ligament-intact State: A Human Cadaveric Study.

PURPOSE: To determine the static stabilizing effects of different anatomical structures of the posterolateral corner (PLC) of the knee in the lateral collateral ligament (LCL)-intact state. METHODS: Thirteen fresh-frozen human cadaveric knees were dissected and tested using an industrial robot with an optical tracking system. Kinematics were determined for 134 N anterior/posterior loads, 10 N m valgus/varus loads, and 5 N m internal/external rotatory loads in 0°, 20°, 30°, 60°, and 90° of knee flexion. The PLC structures were dissected and consecutively released: (I) intact knee joint, (II) with released posterior cruciate ligament (PCL), (III) popliteomeniscal fibers, (IV) popliteofibular ligament, (V) arcuat and popliteotibial fibers, (VI) popliteus tendon (PLT), and (VII) LCL. Repeated-measures analysis of variance was performed with significance set at P < .05. RESULTS: After releasing the PCL, posterior tibial translation increased by 5.2 mm at 20° to 9.4 mm at 90° of joint flexion (P < .0001). A mild 1.8° varus instability was measured in 0° of flexion (P = .0017). After releasing the PLC structures, posterior tibial translation further increased by 2.9 mm at 20° to 5.9 mm at 90° of flexion (P < .05) and external rotation angle increased by 2.6° at 0° to 7.9° at 90° of flexion (P < .05, vs II). Varus stability did not decrease. Mild differences between states V and VI were found in 60° and 90° external rotation tests (2.1° and 3.1°; P < .05). CONCLUSIONS: The connecting ligaments/fibers to the PLT act as a primary static stabilizer against external rotatory loads and a secondary stabilizer against posterior tibial loads (when PCL is injured). After releasing these structures, most static stabilizing function of the intact PLT is lost. The PLC has no varus-stabilizing function in the LCL-intact knee. CLINICAL RELEVANCE: Anatomy and function of these structures for primary and secondary joint stability should be considered for clinical diagnostics and when performing surgery in the PLC.

Nanoliposomal irinotecan in combination with leucovorin and 5-fluorouracil in advanced biliary tract cancers.

Biliary tract cancers (BTC) are rare but aggressive. Due to limited anti-tumor effects of current second- and later-line treatment regimens, novel treatment options are required. Nanoliposomal irinotecan in combination with leucovorin and 5-fluorouracil (FOLFnal-IRI) achieved promising results as a second-line treatment in patients with pancreatic cancer, warranting further investigation in BTC. In the present study, a retrospective analysis of patients receiving FOLFnal-IRI after initial platinum-based chemotherapy for advanced BTC between January 2016 and August 2020 at the University Hospital Cologne (Cologne, Germany) was performed. A total of 11 patients were identified who met the inclusion criteria. A total of 4 patients (36.4%) were female and the median age was 54 years. The proportion of patients suffering from gallbladder carcinoma, intrahepatic and extrahepatic cholangiocarcinoma was 18.2, 63.6 and 9.1%, respectively. Furthermore, 7 patients (63.6%) received FOLFnal-IRI as their second-, 3 (27.3%) as third- and one (9.1%) as their fourth-line therapy. The disease control rate was 54.5% and 3 grade III toxicities were recorded. Progression-free survival and overall survival (OS) after initiation of FOLFnal-IRI was 5.1 and 12.4 months, respectively. OS after initial diagnosis was 24.7 months. FOLFnal-IRI demonstrated promising antitumor potential with an acceptable safety profile as a subsequent therapy regimen in advanced biliary tract malignancies. Further randomized controlled trials of its value as a treatment option for BTC appear justified.

Auxiliary Subunits Regulate the Dendritic Turnover of AMPA Receptors in Mouse Hippocampal Neurons.

Different families of auxiliary subunits regulate the function and trafficking of native α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the central nervous system. While a facilitatory role of auxiliary subunits in ER export and forward trafficking of newly synthesized AMPA receptors is firmly established, it is unclear whether auxiliary subunits also control endosomal receptor turnover in dendrites. Here, we manipulated the composition of AMPA receptor complexes in cultured hippocampal neurons by overexpression of two auxiliary subunits, transmembrane AMPAR regulatory protein (TARP) γ-8 or cysteine knot AMPAR-modulating protein (CKAMP) 44a, and monitored dendritic receptor cycling in live-cell imaging experiments. Receptor surface delivery was assayed using a modified AMPA receptor subunit carrying the pH-dependent fluorophore superecliptic pHluorin (SEP-GluA1), which regains its fluorescence during receptor exocytosis, when transiting from the acidic lumen of transport organelles to the neutral extracellular medium. Strikingly, we observed a dramatic reduction in the spontaneous fusion rate of AMPA receptor-containing organelles in neurons overexpressing either type of auxiliary subunit. An analysis of intracellular receptor distribution also revealed a decreased receptor pool in dendritic recycling endosomes, suggesting that incorporation of TARPγ-8 or CKAMP44a in receptor complexes generally diminishes cycling through the endosomal compartment. To directly analyze dendritic receptor turnover, we also generated a new reporter by N-terminal fusion of a self-labeling HaloTag to an AMPA receptor subunit (HaloTag-GluA1), which allows for selective, irreversible staining of surface receptors. Pulse chase-experiments with HaloTag-GluA1 indeed demonstrated that overexpression of TARPγ-8 or CKAMP44a reduces the constitutive internalization rate of surface receptors at extrasynaptic but not synaptic sites. Thus, our data point to a yet unrecognized regulatory function of TARPγ-8 and CKAMP44a, by which these structurally unrelated auxiliary subunits delay local recycling and increase surface lifetime of extrasynaptic AMPA receptors.

Should the Ipsilateral Hamstrings Be Used for Anterior Cruciate Ligament Reconstruction in the Case of Medial Collateral Ligament Insufficiency? Biomechanical Investigation Regarding Dynamic Stabilization of the Medial Compartment by the Hamstring Muscles.

BACKGROUND: Semitendinosus and gracilis muscles are frequently harvested for autologous tendon grafts for cruciate ligament reconstruction. This study investigated the joint-stabilizing effects of these hamstring muscles in cases of insufficiency of the medial collateral ligament (MCL). HYPOTHESES: First, both the semitendinosus and gracilis muscles can actively stabilize the joint against valgus moments in the MCL-deficient knee. Second, the stabilizing influence of these muscles decreases with an increasing knee flexion angle. STUDY DESIGN: Controlled laboratory study. METHODS: The kinematics was examined in 10 fresh-frozen human cadaveric knees using a robotic/universal force moment sensor system and an optical tracking system. The knee kinematics under 5- and 10-N·m valgus moments were determined in the different flexion angles of the (1) MCL-intact and (2) MCL-deficient knee using the following simulated muscle loads: (1) 0-N (idle) load, (2) 200-N semitendinosus (ST) load, and (3) 280-N (200/80-N) combined semitendinosus/gracilis (STGT) load. RESULTS: Cutting the MCL increased the valgus angle under all tested conditions and angles compared with the MCL-intact knee by 4.3° to 8.1° for the 5-N·m valgus moment and 6.5° to 11.9° for the 10-N·m valgus moment ( P < .01). The applied 200-N simulated ST load reduced the valgus angle significantly at 0°, 10°, 20°, and 30° of flexion under 5- and 10-N·m valgus moments ( P < .05). At 0°, 10°, and 20° of flexion, these values were close to those for the MCL-intact joint under the respective moments (both P > .05). The combined 280-N simulated STGT load significantly reduced the valgus angle in 0°, 10°, and 20° of flexion under 5- and 10-N·m valgus moments ( P < .05) to values near those for the intact joint (5 N·m: 0°, 10°; 10 N·m: 0°, 10°, 20°; P > .05). In 60° and 90° of flexion, ST and STGT loads did not decrease the resulting valgus angle of the MCL-deficient knee without hamstring loads ( P > .05 vs deficient; P = .0001 vs intact). CONCLUSION: In this human cadaveric study, semitendinosus and gracilis muscles successfully stabilize valgus moments applied to the MCL-insufficient knee when the knee is near extension. CLINICAL RELEVANCE: In the valgus-unstable knee, these data suggest that the hamstring muscles should be preserved in (multi-) ligament surgery when possible.