Opposition Transfer Using the Extensor Indicis Muscle and the Extensor Pollicis Brevis Tendon.

Purpose: This study aimed to introduce a novel technique using the extensor pollicis brevis and extensor indicis proprius tendons as power sources for thumb opposition reconstruction in cases of severe carpal tunnel syndrome (CTS) associated with thenar muscle atrophy. Furthermore, the efficacy of this novel method and the traditional Camitz technique was compared. Methods: Patients with severe CTS and thumb opposition dysfunction who underwent surgery using the novel technique (n = 7 and 9 surgeries) or the Camitz technique (n = 8 and 8 surgeries) were included in the analysis. The pre- and postoperative palmar abduction angle, thumb-ring finger opposition angle, and Kapandji score were assessed. The repeated measures analysis of variance and the Mann-Whitney U test were used for statistical analysis. Results: The novel technique was associated with a significant postoperative improvement in palmar abduction angle, thumb-ring finger opposition angle, and Kapandji score. In particular, the thumb-ring finger opposition angle of patients who underwent surgery using this technique was superior to that of patients who underwent surgery using the Camitz technique. Therefore, the novel technique was highly effective in improving thumb pronation. Conclusion: The novel technique using the extensor pollicis brevis and extensor indicis proprius tendons is promising for thumb opposition reconstruction in severe CTS cases. Unlike the traditional Camitz technique, this approach promotes stable thumb opposition function without requiring a pulley, thereby yielding satisfactory outcomes. Nevertheless, further studies with a larger sample size should be conducted to validate these findings. Type of study/level of evidence: Therapeutic 4; Surgical technique.

Biomechanical characterization of the central fibrous region of the forearm interosseous Membrane: Implications for finite element modeling.

The interosseous membrane (IOM) of the forearm plays a crucial role in facilitating forearm function and mechanical load transmission between the radius and ulna. Accurate characterization of its biomechanical properties is essential for developing realistic finite element models of the forearm. This study aimed to investigate the mechanical behavior and material properties of the central fibrous regions of the IOM using fresh frozen cadavers. Ten forearms from five cadavers were dissected, preserving the IOM and identifying the distal accessory band (DAB), central band (CB), and proximal accessory band (PAB). Bone-ligament-bone specimens were prepared and subjected to uniaxial tensile testing, with the loading direction aligned with the fiber orientation. Force-displacement curves were obtained and converted to force-strain and stress-strain curves using premeasured fiber lengths and cross-sectional areas. The results demonstrated distinct mechanical responses among the IOM regions, with the PAB exhibiting significantly lower force-strain behavior compared to the DAB and CB. The derived force-strain and stress-strain relationships provide valuable insights into the regional variations in stiffness and strength of the IOM, highlighting the importance of considering these differences when modeling the IOM in finite element analysis. In conclusion, this study establishes a foundation for the development of advanced finite element models of the forearm that accurately capture the biomechanical behavior of the IOM.

LTX-315 triggers anticancer immunity by inducing MyD88-dependent maturation of dendritic cells.

LTX-315 is a synthetic cationic oncolytic peptide with potent anticancer activity but limited toxicity for non-malignant cells. LTX-315 induces both immunogenic tumor cell death and generation of tumor-specific immune responses in multiple experimental tumor models. Given the central role of dendritic cell (DC) maturation in the induction of antigen-specific immunity, we investigated the effect of LTX-315 treatment on the maturation of tumor-infiltrating DCs (TiDCs) and the generation of anti-melanoma immunity. We found that LTX-315 treatment induces the maturation of DCs, both indirectly through the release of cancer cell-derived damage-associated molecular patterns (DAMPs)/alarmins and nucleic acids (DNA and RNA) capable of triggering distinct Toll-like receptor (TLR) signaling, and, directly by activating TLR7. The latter results in the ignition of multiple intracellular signaling pathways that promotes DC maturation, including NF-κB, mitogen activated protein kinases (MAPKs), and inflammasome signaling, as well as increased type 1 interferon production. Critically, the effects of LTX-315 on DCs the consequent promotion of anti-melanoma immunity depend on the cytosolic signal transducer myeloid differentiation response gene 88 (MyD88). These results cast light on the mechanisms by which LTX-315 induces DC maturation and hence elicits anticancer immunity, with important implications for the use of LTX-315 as an anticancer immunotherapeutic.

Iron Chelation Therapy Elicits Innate Immune Control of Metastatic Ovarian Cancer.

Iron accumulation in tumors contributes to disease progression and chemoresistance. While targeting this process can influence various hallmarks of cancer, the immunomodulatory effects of iron chelation in the tumor microenvironment are unknown. Here, we report that treatment with deferiprone, an FDA-approved iron chelator, unleashes innate immune responses that restrain ovarian cancer. Deferiprone reprogrammed ovarian cancer cells towards an immunostimulatory state characterized by production of type I interferon (IFN) and overexpression of molecules that activate natural killer (NK) cells. Mechanistically, these effects were driven by innate sensing of mitochondrial DNA in the cytosol and concomitant activation of nuclear DNA damage responses triggered upon iron chelation. Deferiprone synergized with chemotherapy and prolonged the survival of mice with ovarian cancer by bolstering type I IFN responses that drove NK cell-dependent control of metastatic disease. Hence, iron chelation may represent an alternative immunotherapeutic strategy for malignancies that are refractory to current T cell-centric modalities.