Effect of anti-claudin 18.2 monoclonal antibody zolbetuximab alone or combined with chemotherapy or programmed cell death-1 blockade in syngeneic and xenograft gastric cancer models.

The development of targeted cancer therapies based on monoclonal antibodies against tumor-associated antigens has progressed markedly over recent decades. This approach is dependent on the identification of tumor-specific, normal tissue-sparing antigenic targets. The transmembrane protein claudin-18 splice variant 2 (CLDN18.2) is frequently and preferentially displayed on the surface of primary gastric adenocarcinomas, making it a promising monoclonal antibody target. Phase 3 studies of zolbetuximab, a chimeric immunoglobulin G1 monoclonal antibody targeting CLDN18.2, combined with 5-fluorouracil/leucovorin plus oxaliplatin (modified FOLFOX6) or capecitabine plus oxaliplatin (CAPOX) in advanced or metastatic first-line gastric or gastroesophageal junction (G/GEJ) adenocarcinoma have demonstrated favorable clinical results with zolbetuximab. In studies using xenograft or syngeneic models with gastric cancer cell lines, zolbetuximab mediated death of CLDN18.2-positive human cancer cell lines via antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity in vitro and demonstrated anti-tumor efficacy as monotherapy and combined with chemotherapy in vivo. Mice treated with zolbetuximab plus chemotherapy displayed a significantly higher frequency of tumor-infiltrating CD8+ T cells versus vehicle/isotype control-treated mice. Furthermore, zolbetuximab combined with an anti-mouse programmed cell death-1 antibody more potently inhibited tumor growth compared with either agent alone. These results support the potential of zolbetuximab as a novel treatment option for G/GEJ adenocarcinoma.

Relationship between increased knee joint line obliquity after medial open-wedge high tibial osteotomy and patient-reported outcome measures.

INTRODUCTION: This study evaluated the correlation between postoperative knee joint line obliquity after medial open-wedge high tibial osteotomy and patient-reported outcome measures excluding excessively overcorrected knees. This study further identified preoperative radiological factors related to the increased postoperative knee joint line obliquity. MATERIALS AND METHODS: We retrospectively evaluated patients who underwent medial open-wedge high tibial osteotomy between March 2013 and March 2021. Postoperative excessively overcorrected knees with hip-knee-ankle angle > 7° were excluded. We investigated radiological parameters and patient-reported outcome measures preoperatively and at the last follow-up. The following radiologic parameters were measured: hip-knee-ankle angle, weight-bearing line ratio, mechanical medial proximal tibial angle, mechanical lateral distal femoral angle, lateral distal tibial angle, joint line convergent angle, knee joint line obliquity, ankle joint line obliquity, hip abduction angle, tibial posterior slope, Carton-Deschamps index, and patella tilting angle. Clinical outcomes were evaluated using Japanese knee outcome measures. This assessment criterion is based on the Western Ontario McMaster Universities Arthritis Index and MOS Short Form 36. Multiple regression analysis was performed to evaluate the association between postoperative knee joint line obliquity and patient-reported outcome measures or preoperative radiological factors (P < .05). RESULTS: A total of 52 knees were included. The mean age at the time of the surgery was 61.6 ± 9.0 years and the mean follow-up period was 30.6 ± 10.1 months. Increased postoperative knee joint line obliquity was associated with lower Japanese knee outcome measures. The preoperative hip-knee-ankle angle was significantly associated with postoperative knee joint line obliquity. CONCLUSIONS: Increased knee joint line obliquity after medial open-wedge high tibial osteotomy is associated with inferior clinical outcomes. Care should be given to the center of the rotational angulation in around-knee osteotomy to avoid postoperative increased knee joint line obliquity. LEVEL OF EVIDENCE: Retrospective comparative study, Level III.

Pediatric Synovial Osteochondromatosis of the Knee with Leg Length Discrepancy: A Case Report.

Introduction: Synovial chondromatosis (SC) is very rare among children. We are aware of no reports of patients with SC accompanied by leg length discrepancy (LLD). Case Report: We describe a case of synovial osteochondromatosis of a 7-year-old boy complicated by LLD. We performed epiphysiodesis of the distal femur and arthroscopic resection of loose bodies and total synovectomy. Three years after surgery, LLD had been corrected and there was no sign of recurrence. Conclusion: Physicians should be aware of synovial osteochondromatosis complicated by LLD in childhood and take radiographs of the whole length of lower legs when this condition is suspected.

Factors affecting the post-operative over-constraint after anatomic double-bundle anterior cruciate ligament reconstruction.

Objective: Initial tension at graft fixation is one of key factors for good outcomes in anterior cruciate ligament (ACL) reconstruction. Identifying the pre-operative factors that influence postoperative knee laxity under the anterior tibial load is useful in determining the initial tension at graft fixation. Thus, the purpose of this study was to clarify the pre-operative factors affecting the side-to-side difference in anterior laxity immediately after the anatomic double-bundle ACL reconstruction with a constant initial tension. Methods: Fifty-five patients underwent the anatomic double-bundle ACL reconstruction with hamstring tendon grafts. Anterior tibial displacement (ATD) was measured on both knees using KT-2000 Knee Arthrometer under anterior drawer load of 67 N, 89 N, 134 N and manual maximum load at 30° of flexion before ACL reconstruction under anesthesia, and was also measured on the operated knees under 89 N immediately after ACL reconstruction under anesthesia. Then, side-to-side difference (SSD) before and immediately after ACL reconstruction was calculated. Correlative relation between the SSD immediately after ACL reconstruction and the ATD/the SSD in each condition was analyzed. Results: The side-to-side difference of ATD immediately after surgery was -3.8 ± 1.7 mm (0 to -8mm) in response of 89 N of anterior load. There was correlation between the SSD immediately after ACL reconstruction and all ATD on both knees except for the ATD under manual maximum load on the injured knee, while little correlation between the SSD immediately after ACL reconstruction and that before ACL reconstruction was found. Especially, ATD under 89 N on the opposite knees and ATD under 134 N on the injured knees showed selective correlation with the SSD immediately after surgery in the step-wise multiple regression analysis. Conclusion: As the anterior tibial displacements under 89 N on the contra-lateral knee and under 134 N on the injured knee had a significant correlation with the SSD immediately after ACL reconstruction, those values may be helpful in determining the increase or decrease in initial tension at graft fixation.

Variation among individual beef cattle in methane-to-carbon dioxide ratio measured under on-farm conditions using the sniffer method.

This study proposed a method for measuring the methane (CH4 )/carbon dioxide (CO2 ) ratio from individual beef cattle under on-farm conditions and estimated the variance components of the CH4 /CO2 ratio. Gas measurements were conducted using 166 Japanese Black cattle group-housed in pens equipped with individual feed bins. The gas containing the animal's breath was measured individually after concentrate feeding by covering the feed bin with a sheet with sampling inlets. Measurements were performed six times (three consecutive days, twice daily) per individual. Most of the sampled gas contained more than 1000 ppm of the mean background-corrected CO2 , suggesting that the method proposed in this study successfully collected sufficient breath concentration to accurately measure the CH4 /CO2 ratio. The between-animal variance accounted for 31.7% of the total variance in the CH4 /CO2 ratio. The results showed that the gas collection method proposed in this study could be a useful tool for measuring the CH4 /CO2 ratio under on-farm conditions. The variance component obtained from this study will help to establish protocols for generating data for genetic evaluation and performing dietary experiments with sufficient statistical power.

In vitro and in vivo evaluation of biohybrid tissue-engineered vascular grafts with transformative 1H/19F MRI traceable scaffolds.

Biohybrid tissue-engineered vascular grafts (TEVGs) promise long-term durability due to their ability to adapt to hosts' needs. However, the latter calls for sensitive non-invasive imaging approaches to longitudinally monitor their functionality, integrity, and positioning. Here, we present an imaging approach comprising the labeling of non-degradable and degradable TEVGs' components for their in vitro and in vivo monitoring by hybrid 1H/19F MRI. TEVGs (inner diameter 1.5 mm) consisted of biodegradable poly(lactic-co-glycolic acid) (PLGA) fibers passively incorporating superparamagnetic iron oxide nanoparticles (SPIONs), non-degradable polyvinylidene fluoride scaffolds labeled with highly fluorinated thermoplastic polyurethane (19F-TPU) fibers, a smooth muscle cells containing fibrin blend, and endothelial cells. 1H/19F MRI of TEVGs in bioreactors, and after subcutaneous and infrarenal implantation in rats, revealed that PLGA degradation could be faithfully monitored by the decreasing SPIONs signal. The 19F signal of 19F-TPU remained constant over weeks. PLGA degradation was compensated by cells' collagen and α-smooth-muscle-actin deposition. Interestingly, only TEVGs implanted on the abdominal aorta contained elastin. XTT and histology proved that our imaging markers did not influence extracellular matrix deposition and host immune reaction. This concept of non-invasive longitudinal assessment of cardiovascular implants using 1H/19F MRI might be applicable to various biohybrid tissue-engineered implants, facilitating their clinical translation.