Polyposis of gastrointestinal tract after COVID-19 mRNA vaccination: a report of two cases.

Cronkhite-Canada syndrome is a rare gastrointestinal polyposis syndrome with distinctive clinical features and endoscopic findings. Diagnosis can be challenging without suspicion, and the disease carries high mortality due to complications such as infection, gastrointestinal bleeding, and malignancies. This paper presents two cases of Cronkhite-Canada syndrome occurring after coronavirus disease 2019 (COVID-19) mRNA vaccination. Both cases exhibited typical clinical findings, including hypogeusia, onychodystrophy, alopecia, and weight loss. Typical polyposis in the gastrointestinal tract was confirmed through endoscopies. As symptomatic treatment did not improve the symptoms, corticosteroids were administered, and symptoms and laboratory test results improved immediately. The patients improved upon corticosteroids tapering. These cases illustrate typical presentations of Cronkhite-Canada syndrome and the course of the disease following corticosteroid treatment. Additionally, they suggest the possibility that Cronkhite-Canada syndrome may be triggered by COVID-19 mRNA vaccination.

Postoperative Decrease in Bone Marrow Lesion Associated With Better Clinical Outcomes Following Medial Open-Wedge High Tibial Osteotomy.

PURPOSE: To assess serial changes of preoperative bone marrow lesion (BML) following medial open-wedge high tibial osteotomy (MOWHTO) up to 2 years and evaluate whether postoperative change of BML affected patient-reported outcome measures (PROMs) at 2 years' follow-up. Factors related to the postoperative changes in BML also were evaluated. METHODS: The current study retrospectively assessed prospectively collected data of consecutive patients between December 2016 and March 2018 who underwent MOWHTO for symptomatic knee osteoarthritis with varus malalignment (≥5°) and a minimum 2-year follow-up. Serial magnetic resonance imaging scans at preoperative and postoperative 3, 6, 18, and 24 months were performed, and the extent of BML was evaluated consecutively using 2 validated methods. Clinically, preoperative and postoperative PROMs and their achievement of minimal clinically important difference values were evaluated. The associations of the extent of BMLs with PROMs at each follow-up period over time were analyzed using a linear mixed model. Furthermore, factors related to the postoperative changes of BML were assessed. RESULTS: Of 26 patients, 21 (80.8%) had preoperative BML at medial femoral and tibial condyles. The postoperative decrease in BML was noted in 17 (81.0%) and 18 (85.7%) at medial femoral and tibial condyles. The BML decreased at postoperative 3 months and, thereafter, the extent of BML gradually reduced until postoperative 24 months. The proportion of patients achieved minimal clinically important difference was 84.6% for total Western Ontario and McMaster Universities Osteoarthritis Index scores and 80.8%, 76.9%, and 84.6% for KOOS symptom, pain, and activity of daily living subscales. Postoperative decrease in BML was significantly associated with better PROMs over postoperative 24 months. Furthermore, normo-correction (2°-5° valgus) was a significant factor for decreased BML following MOWHTO. CONCLUSIONS: Preoperative BML gradually decreased with time following MOWHTO, and the postoperative decrease in BML related with better PROMs over postoperative 24 months. Moreover, postoperative valgus alignment was a significant factor relating the postoperative decrease of BML. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Multicentric Epithelioid Angiosarcoma of Bones Showing Angiotropic Spread: A Case Report.

Epithelioid angiosarcoma is a rare variant of angiosarcoma characterized by an epithelioid morphology that mimics carcinoma. Therefore, multicentric epithelioid angiosarcoma is easily misdiagnosed as bone metastasis from carcinoma and has an aggressive clinical course. Here, we present a rare case of a 61-year-old male with multicentric epithelioid angiosarcoma of the bone. Plain radiography, CT, and MRI revealed multiple osteolytic lesions in both femurs; some lesions showed soft tissue extension with cortical bone destruction. Interestingly, PET-CT revealed that the lesions were only distributed along the bones of the lower extremities, including the pelvic bones, femurs, and tibiae. Despite histological analysis initially suggesting metastatic carcinoma, after additional immunohistological staining, including that for vascular markers (CD31 and ERG), the final diagnosis was epithelioid angiosarcoma. A better understanding of the clinicoradiological features of this disease may help eliminate diagnostic confusion and provide better management.

Conversion of Host Cell Receptor into Virus Destructor by Immunodisc to Neutralize Diverse SARS-CoV-2 Variants.

The decreasing efficacy of antiviral drugs due to viral mutations highlights the challenge of developing a single agent targeting multiple strains. Using host cell viral receptors as competitive inhibitors is promising, but their low potency and membrane-bound nature have limited this strategy. In this study, the authors show that angiotensin-converting enzyme 2 (ACE2) in a planar membrane patch can effectively neutralize all tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that emerged during the COVID-19 pandemic. The ACE2-incorporated membrane patch implemented using nanodiscs replicated the spike-mediated membrane fusion process outside the host cell, resulting in virus lysis, extracellular RNA release, and potent antiviral activity. While neutralizing antibodies became ineffective as the SARS-CoV-2 evolved to better penetrate host cells the ACE2-incorporated nanodiscs became more potent, highlighting the advantages of using receptor-incorporated nanodiscs for antiviral purposes. ACE2-incorporated immunodisc, an Fc fusion nanodisc developed in this study, completely protected humanized mice infected with SARS-CoV-2 after prolonged retention in the airways. This study demonstrates that the incorporation of viral receptors into immunodisc transforms the entry gate into a potent virucide for all current and future variants, a concept that can be extended to different viruses.

Comparison of Fixation Methods Between Transosseous Pull-Out Suture and Separate Vertical Wiring for Inferior Pole Fracture of Patella: A Systematic Review and Meta-Analysis.

OBJECTIVES: To compare, in a systematic review, Krakow transosseous (KT) suturing and separate vertical wiring (VW) fixation methods in inferior pole fractures of the patella and to evaluate whether the supplementary fixation affected bone union. DATA SOURCES: The MEDLINE, Embase, and Cochrane databases were searched from inception to January 15, 2023. The keywords were "patella inferior pole fracture", "patella distal pole fracture", "transosseous", "pull-out suture", "reattachment", and "vertical wiring". STUDY SELECTION: All clinical studies describing KT or VW techniques for inferior pole fracture of the patella and reporting bone union-related complications were included. DATA EXTRACTION: This meta-analysis included 16 studies with 274 patellae. Demographic data, surgical techniques, clinical outcomes, and complication rates were recorded. The Methodological Index for Non-Randomized Studies criteria were used to assess their quality. DATA SYNTHESIS: A meta-analysis was performed using random-effects models and meta-regression. The meta-analytic estimate of bone union-related complications was 3.8% (95% CI, 1.6%-6.0%) for either PO or VW techniques in inferior pole fractures of the patella. The bone union-related complication rates did not differ significantly between the two techniques (KT, 5.7%; VW, 3.0%; P = .277). Meanwhile, supplementation fixation was significantly associated with decrease in bone union-related complication rates ( p = .013). CONCLUSIONS: Fixation of inferior pole fractures of the patella using either KT or VW techniques provided satisfactory and similar clinical results with minimal bone union-related complications. Supplementary fixation has a positive impact on reducing bone union-related complications in inferior pole fractures of the patella following KT and VW techniques. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Influence of Previous Arthroscopic Meniscectomy on Midterm to Long-term Outcomes After Medial Open-Wedge High Tibial Osteotomy.

Background: Few studies have evaluated the clinical and radiological outcomes of medial open-wedge high tibial osteotomy (MOWHTO) in patients who had previously undergone arthroscopic meniscectomy. Purpose: To verify whether previous arthroscopic meniscectomy affects the clinical and radiological outcomes of MOWHTO. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 183 consecutive knees that underwent MOWHTO and had a minimum 5 years of follow-up were retrospectively reviewed. We compared the preoperative and postoperative clinical and radiological data of 32 knees with a history of meniscectomy (previous meniscectomy group) to 151 control knees without a history of meniscectomy. Cartilage status was also compared at first- and second-look arthroscopic surgery according to the International Cartilage Repair Society grading system. Failure was defined as conversion to total knee arthroplasty or revision MOWHTO. On subgroup analysis, the previous meniscectomy group was divided into 2 subgroups based on the time from meniscectomy to MOWHTO (<3 vs ≥3 years). Results: The mean age at the time of surgery was 55.9 years (range, 38-70 years), and the mean follow-up period was 86.2 months (range, 60-164 months). The mean time between meniscectomy and MOWHTO was 48.9 months (range, 5-156 months), and all meniscectomy procedures were performed on the medial side. Preoperative patient characteristics were similar between the study groups. Clinical and radiological outcomes were not significantly different between the groups at the latest follow-up, and no significant between-group differences were observed regarding postoperative cartilage status on arthroscopic examination. One knee in the control group underwent conversion to total knee arthroplasty at 7 years postoperatively for arthritic progression. Subgroup analysis of the previous meniscectomy group indicated no significant differences in clinical outcomes based on the time from meniscectomy to MOWHTO. Conclusion: Based on the results, a history of meniscectomy did not adversely affect the midterm to long-term outcomes of MOWHTO. Furthermore, the time between previous meniscectomy and MOWHTO was not associated with the clinical outcomes of MOWHTO.

The effect of combining prewarming with intraoperative phenylephrine infusion on the prevention of hypothermia in patients undergoing urological surgery: a prospective, randomized, and controlled trial.

Background: Hypothermia is common in patients undergoing urological surgery; however, no single preventative modality is completely effective. This study evaluated the effects of combining prewarming with intraoperative phenylephrine infusion for the prevention of hypothermia in patients undergoing urological surgery. Methods: This prospective study enrolled 58 patients scheduled for urological surgery under general anesthesia. The patients were randomized into two groups (n = 29). Patients in the experimental (prewarming and phenylephrine infusion) group (PP group) received prewarming for 20 min and intraoperative phenylephrine infusion, whereas those in the control group (C group) received no active prewarming with only intermittent administration of vasoactive agents. The patient's sublingual temperatures before and after anesthesia and nasopharyngeal temperature during anesthesia were recorded as core temperatures. Results: The incidence of intraoperative hypothermia was higher in the C group than in the PP group (57.7% [15/26] vs. 23.1% [6/26], P = 0.01). The severity of intraoperative hypothermia was higher in the C group than in the PP group (P = 0.004). The nasopharyngeal temperature at the end of surgery was lower in the C group than in the PP group (35.8 ± 0.6°C vs. 36.3 ± 0.4°C, P = 0.002). The trend of core temperature decline during the first hour after anesthesia induction differed between the two groups (P = 0.003; its decline was more gradual in the PP group). Conclusions: The combination of prewarming for 20 min and intraoperative phenylephrine infusion reduced the incidence and severity of intraoperative hypothermia and modified the trend of decreasing core temperatures in patients undergoing urological surgery.

No difference in biomechanical properties of simple, horizontal mattress, and double row repair in Bankart repair: a systematic review and meta-analysis of biomechanical studies.

BACKGROUND: Arthroscopic Bankart repair is the most common procedure in patients with anterior shoulder instability. Various repair techniques using suture anchors have been used to improve the strength of fixation and surgical outcomes in arthroscopic Bankart surgery. However, evidence regarding which method is superior is lacking. This systematic review and meta-analysis study was designed to compare the biomechanical results of simple versus horizontal mattress versus double-row mattress for Bankart repair. METHODS: A systematic search of the MEDLINE, Embase, and Cochrane Library databases was performed to identify comparative biomechanical studies comparing the simple, horizontal mattress, and double-row techniques commonly used in Bankart repair for anterior shoulder instability. Biomechanical results included the ultimate load to failure, stiffness, cyclic displacement, and mode of failure after the ultimate load. The methodological quality was assessed based on the Quality Appraisal for Cadaveric Studies (QUACS) scale for biomechanical studies. RESULTS: Six biomechanical studies comprising 125 human cadavers were included in this systematic review. In biomechanical studies comparing simple and horizontal mattress repair and biomechanical studies comparing simple and double-row repair, there were no significant differences in the ultimate load to failure, stiffness, or cyclic displacement between the repair methods. The median QUACS scale was 11.5 with a range from 10 to 12, indicating a low risk of bias. CONCLUSION: There was no biomechanically significant difference between the simple, horizontal mattress, and double-row methods in Bankart repair. Clinical evidence such as prospective randomized controlled trials should be conducted to evaluate clinical outcomes according to the various repair methods. LEVEL OF EVIDENCE: Systematic review, Therapeutic level IV.

Deep learning for sex determination: Analyzing over 200,000 panoramic radiographs.

The objective of this study is to assess the performance of an innovative AI-powered tool for sex determination using panoramic radiographs (PR) and to explore factors affecting the performance of the convolutional neural network (CNN). The study involved 207,946 panoramic dental X-rays and their corresponding reports from 15 clinical centers in São Paulo, Brazil. The PRs were acquired with four different devices, and 58% of the patients were female. Data preprocessing included anonymizing the exams, extracting pertinent information from the reports, such as sex, age, type of dentition, and number of missing teeth, and organizing the data into a PostgreSQL database. Two neural network architectures, a standard CNN and a ResNet, were utilized for sex classification, with both undergoing hyperparameter tuning and cross-validation to ensure optimal performance. The CNN model achieved 95.02% accuracy in sex estimation, with image resolution being a significant influencing factor. The ResNet model attained over 86% accuracy in subjects older than 6 years and over 96% in those over 16 years. The algorithm performed better on female images, and the area under the curve (AUC) exceeded 96% for most age groups, except the youngest. Accuracy values were also assessed for different dentition types (deciduous, mixed, and permanent) and missing teeth. This study demonstrates the effectiveness of an AI-driven tool for sex determination using PR and emphasizes the role of image resolution, age, and sex in determining the algorithm's performance.

Greater Knee Rotatory Instability After Posterior Meniscocapsular Injury Versus Anterolateral Ligament Injury: A Proposed Mechanism of High-Grade Pivot Shift.

Background: For anterolateral rotatory instability as a result of secondary soft tissue injuries in anterior cruciate ligament (ACL)-deficient knees, there is increasing interest in secondary stabilizers to prevent internal rotation (IR) of the tibia. Purpose: To determine which secondary stabilizer is more important in anterolateral rotatory instability in ACL-deficient knees. Study Design: Controlled laboratory study. Methods: The lower extremities of 10 fresh-frozen cadavers (20 extremities) without anterior-posterior or rotational instability were included. Matched-pair randomization was performed, with each side per specimen assigned to 1 of 2 groups. In group 1, the ACL was sectioned, followed by the anterolateral ligament (ALL); in group 2, the ACL was sectioned, followed by sequential sectioning of the posterolateral meniscocapsular complex (PLMCC) and posteromedial meniscocapsular complex (PMMCC). The primary outcome was the change in relative tibial IR during a simulated pivot-shift test with 5 N·m of IR torque and 8.9 N of valgus force. The secondary outcomes were the International Knee Documentation Committee grade in the pivot-shift test and the incidence of the grade 3 pivot shift. Results: In group 1, compared with baseline, the change in relative tibial IR at 0° of knee flexion was 1.4° (95% CI, -0.1° to 2.9°; P = .052) after ALL release. In group 2, it was 2.5° (95% CI, 0.4° to 4.8°; P = .007) after PLMCC release and 4.1° (95% CI, 0.5° to 7.8°; P = .017) after combined PLMCC and PMMCC release. Combined PLMCC and PMMCC release resulted in greater change of tibial IR with statistical significance at 0°, 15°, and 30° of knee flexion (P = .008, .057, and .004, respectively) compared with ALL release. The incidence of grade 3 pivot shifts was 10% in group 1 and 90% in group 2. Conclusion: Posterior meniscocapsular laxity caused an increase in relative tibial IR as much as ALL injury in ACL-deficient knees in our simulated laboratory test, and greater anterolateral rotatory instability occurred with posterior meniscocapsular injury compared with ALL injury. Clinical Relevance: Repair of the injured posterior meniscocapsular complex may be an important treatment option for reducing anterolateral rotatory instability in the ACL-deficient knee.

What Is New in Stage 3 of the 2019 Revised Association Research Circulation Osseous Staging System of Osteonecrosis of the Femoral Head: A Relationship to Bone Resorption.

PURPOSE: The aim of the study is to evaluate the stage 3 findings of the 2019 revision of the Association Research Circulation Osseous (ARCO) staging system for osteonecrosis of the femoral head between 3A and 3B and the relationship with bone resorption area. MATERIALS AND METHODS: We retrospectively enrolled 87 patients with ARCO stage 3 osteonecrosis of the femoral head, divided into stage 3A (n = 73) and 3B (n = 14). The revised stage 3 findings included subchondral fracture, fracture in necrotic portion, and flattening of the femoral head and were compared between stage 3A and 3B. The association between these findings and the causative features of bone resorption area was also evaluated. RESULTS: All stage 3 cases had subchondral fractures. In stage 3A, these fractures were generated by crescent sign (41.1%) and by fibrovascular reparative zone in 58.9%; however, in stage 3B, fibrovascular reparative zone generated 92.9% of these fractures and crescent sign only 7.1% with statistical significance ( P = 0.034). Necrotic portion fracture was noted in 36.7% and femoral head flattening was observed in 14.9% of all stage 3. Necrotic portion fracture (92.9% vs 26.0%) and femoral head flattening (71.4% vs 4.1%) were observed more frequently in stage 3B than 3A ( P < 0.001). Almost all subchondral fractures by fibrovascular reparative zone (96.4%) and necrotic portion fracture (96.9%), and all femoral head flattening was presented with bone resorption area with expanding areas. CONCLUSIONS: The ARCO stage 3 descriptions reflect severity in this order: subchondral fracture, necrotic portion fracture, and femoral head flattening. More severe findings are usually associated with expanding bone resorption areas.

Engineering bispecific T-cell engagers to deplete eosinophils for the treatment of severe eosinophilic asthma.

Severe eosinophilic asthma (SEA) is characterized by elevated eosinophil counts in the blood and airway mucosa. While monoclonal antibody therapies targeting interleukin-5 (IL-5) and its receptor (IL-5Rα) have improved treatment, some patients remain unresponsive. We propose an alternative approach to eliminate eosinophils using T cells by engineering IL-5Rα × CD3 bispecific T-cell engagers (bsTCEs) that target both IL-5Rα on eosinophils and CD3 on T cells. We designed different formats of IL-5Rα × CD3 bsTCEs, incorporating variations in valency, geometry, and affinity for the target antigen binding. We identified the single-chain variable fragment (scFv)-Fc format with the highest affinity toward the membrane-proximal domain of IL-5Rα in the IL-5Rα-binding arm showed the most potent cytotoxicity against IL-5Rα-expressing peripheral eosinophils by activating autologous primary T cells from healthy donors. This study proposes IL-5Rα × CD3 bsTCEs as potential alternatives for SEA treatment. Importantly, it demonstrates the first application of bsTCEs in eliminating disease-associated cells, including eosinophils, beyond cancer cells.

Evaluating methane emissions from rice paddies: A study on the cultivar and transplanting date.

Climate change, driven by increased greenhouse gas emissions, is a pressing environmental issue worldwide. Flooded rice paddy soils are a predominant source of methane (CH4) emissions, accounting for approximately 11 % of global emissions. Factors such as rice (Oryza sativa L.) cultivar, transplanting date, water management, and soil characteristics significantly influence these emissions. This study aimed to evaluate the CH4 emissions from rice paddies in relation to the cultivar and transplanting date. The experiment included two rice cultivars (an early-maturing cultivar, Unkwang, and a medium-late-maturing cultivar, Samkwang) and four transplanting dates (Times 1-4). In the present study, CH4 emissions were higher with earlier transplanting dates and decreased significantly with delayed transplanting. Weather conditions, such as cumulative mean air temperature, cumulative soil temperature, and total sunshine hours, were positively correlated with total CH4 emissions. The recommended regional transplanting date (Time 3) resulted in the highest rice grain yields for both cultivars. However, the earlier transplanting dates (Time 1 and Time 2) were more effective in improving plant growth characteristics such as rice straw weight, root biomass weight, and chlorophyll content. A significant positive correlation was observed between the root biomass weight of the rice and CH4 emissions in both cultivars, implying that an increase in root biomass weight led to an increase in CH4 emissions. Consequently, adhering to the advised regional transplanting dates is the most sensible approach for transplanting rice seedlings. This ensured lower CH4 emissions without compromising rice productivity or quality for both cultivars. Further research should focus on identifying the most appropriate rice-transplanting dates and management practices to effectively reduce CH4 emissions without compromising rice production.

Toxicity of a 90-day repeated oral dose of a collagen peptide derived from skate (Raja kenojei) skin: a rat model study.

Collagen peptides are widely employed as therapeutic materials due to their numerous beneficial properties, including for the following uses: antiaging, antioxidant applications, antibacterial applications, wound healing, tissue engineering, medication delivery, and cosmetics. Although collagen peptides are useful in these applications, to our knowledge, few published studies have been undertaken on their repeated-dose toxicity. We evaluated the possible subchronic toxicity of a collagen peptide derived from skate (Raja kenojei) skin (CPSS) in Sprague-Dawley rats by administering repeated oral doses over 90 days. Rats of both sexes were assigned randomly to one of four experimental groups, respectively receiving 0, 500, 1000, or 2000 mg/kg/day of CPSS. At all doses tested, repeated oral CPSS administration had no treatment-related adverse effects in terms of clinical signs, body weight, food consumption, detailed clinical observation, sensory reactivity, functional assessment, urinalysis, ophthalmic examination, gross pathology, hematology, serum biochemistry, hormone analysis, organ weight, and histopathology. Even though there were some alterations in hematologic parameters, serum biochemistry parameters, organ weight, and histopathological findings, these did not follow a dose-response pattern and were within historical limits for control rats. The oral no-observed-adverse-effect level (NOAEL) of the CPSS was 2000 mg/kg/day for both male and female rats in the applied experimental circumstances, and no target organs were identified.

The Effect of Neuromuscular Blockade Reversal Agents on Postoperative Pulmonary Complications in Patients undergoing Femur Fracture Repair Surgery: A Retrospective Observational Study.

BACKGROUND: Femoral fracture repair surgery under general anesthesia is associated with postoperative pulmonary complications (PPCs). However, information on PPCs caused by residual neuromuscular blockade following perioperative use of neuromuscular blockers is limited. This study aimed to identify the differences in the incidence of PPCs according to the type of neuromuscular blockade reversal agent used in femoral fracture repair surgery, as well as the risk factors for PPCs. METHODS: We retrospectively analyzed the electronic medical records of 604 patients aged >18 years who underwent general anesthesia for femoral fracture repair surgery at a single university hospital between March 2017 and March 2022. Patients in whom sugammadex or anticholinesterase was used to reverse the neuromuscular block were subjected to propensity score matching. Multivariate logistic regression analysis was performed to identify risk factors for PPCs. RESULTS: Among the 604 patients, 108 were matched in each group. The incidence rates of PPCs overall and in the anticholinesterase and sugammadex groups were 7.0%, 8.3%, and 5.6%, respectively, with no significant differences between the groups. Older age, higher ASA (American Society of Anesthesiologists) physical status, and lower preoperative oxygen saturation were risk factors, whereas emergency surgery was a preventive factor. CONCLUSIONS: Our results demonstrated that the incidence of PPC did not differ significantly between sugammadex and anticholinesterase in patients undergoing femur fracture repair under general anesthesia. Identifying the risk factors and confirming complete recovery from neuromuscular blockade might be more important.

Does COVID-19 Infection within 1 Week after Total Knee Arthroplasty Affect Patients' Early Clinical Outcomes? A Matched Case-Control Study.

Recent studies have reported the impact of previous COVID-19 infection on the early clinical outcome after total knee arthroplasty (TKA). However, the timing of infection before the surgery was not constant and a study on patients with COVID-19 infection within 1 week after TKA is lacking. This study aimed to determine the effect of COVID-19 infection within one week after TKA on the postoperative outcomes and to compare the early clinical outcomes to those who were not infected with COVID-19 before and after surgery. No significant differences were observed between the two groups in terms of clinical outcomes or complications. The length of the hospital stay (LOS) was significantly longer for the COVID-19 group than for the non-COVID-19 group (p < 0.05). The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were higher for the study group on postoperative days 9 and 12 than for those in the control group (p < 0.05). However, D-dimer levels were not significantly different between the two groups. We should cautiously consider that COVID-19 infection within 1 week after TKA may be associated with increased ESR, CRP levels, and length of hospital stay, but they are not associated with the worsening of early clinical outcomes or the occurrence of complications.

Prediction of local recurrence in tenosynovial giant cell tumor of the knee: Based on preoperative MRI evaluation into disease subtypes and severity.

OBJECTIVE: Tenosynovial giant cell tumors (TSGCTs) of the knee differ in their clinical outcome according to disease subtypes and severity. The aim of this study was to determine the predictive MRI features related to local recurrence in TSGCT of the knee regarding disease subtypes and severity. METHODS: This retrospective study included 20 patients with pathology-proven TSGCT of the knee who underwent preoperative MRI and surgery from Jan. 2007 to Jan. 2022. The anatomical point of the lesion was determined with a knee mapping. And then MRI features related to disease subtype including nodularity (single vs. multinodular); margin (circumscribed vs. infiltrative); peripheral hypointenseity (present vs. absent); internal hypointensity reflecting hemosiderin deposition (speckled vs. granular) were assessed. Third, MRI features related to disease severity including involvement of bone, cartilage, and tendon were evaluated. MRI features for predicting local recurrence of TSGCT were tested using chi-square test and logistic regression analysis. RESULTS: Ten patients with diffuse-type TSGCT (D-TSGCT) and 10 patients with localized-type TSGCT (L-TSGCT) were included. There were six cases of local recurrence and all of them were D-TSGCT and none for L-TSGCT with statistical difference (P = 0.015). D-TSGCT that was direct risk factor for local recurrence showed more multinodular (80.0% vs. 10.0%; P = 0.007), infiltrative margin (90.0% vs. 10.0%; P = 0.002), and absent peripheral hypointensity (100.0% vs. 20.0%; P = 0.001) than L-TSGCT. Multivariate analysis showed infiltrative margin (odds ratio [OR], 81.0; P = 0.003) was independent MRI factor for D-TSGCT. Disease severity for risk of local recurrence included cartilage (66.7% vs. 7.1%; P = 0.024) and tendon (100.0% vs. 28.6%; P = 0.015) involvement compared to no local recurrence. Multivariate analysis showed tendon involvement (OR, 12.5; P = 0.042) was predictive MRI parameter for local recurrence. By combining tumor margin and tendon involvement, local recurrence was predicted sensitively on preoperative MRI (sensitivity, 100%; specificity, 50%; accuracy, 65%). CONCLUSION: D-TSGCTs was associated with local recurrence and showed multinodularity infiltrative margin, and absent peripheral hypointensity. Disease severity including cartilage and tendon involvement was associated with local recurrence. Preoperative MRI evaluation by combining disease subtypes and severity can predict local recurrence sensitively.

Clinical Efficacy and Safety of the Intra-articular Injection of Autologous Adipose-Derived Mesenchymal Stem Cells for Knee Osteoarthritis: A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Intra-articular injection of autologous culture-expanded adipose-derived mesenchymal stem cells (ADMSCs) has introduced a promising treatment option for knee osteoarthritis. Although the clinical efficacy and safety of ADMSCs have been reported, the treatment remains controversial owing to the small sample sizes and heterogeneous osteoarthritis grades in previous studies. PURPOSE: To assess the efficacy and safety of intra-articular injection of ADMSCs as compared with placebo in alleviating pain and improving functional capacity in a large sample of patients with knee osteoarthritis of Kellgren-Lawrence (K-L) grade 3. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: This phase III multicenter clinical trial was a double-blind randomized controlled study that included 261 patients with K-L grade 3 symptomatic knee osteoarthritis who were administered a single injection of autologous culture-expanded ADMSCs or placebo. Clinical data were assessed at baseline and at 3 and 6 months after the injection. The primary endpoints were improvements in 100-mm visual analog scale (VAS) for pain and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for function at 6 months after the injection. The secondary endpoints included clinical and radiologic examinations and safety after injection. The changes in cartilage defects after injection were assessed by magnetic resonance imaging at 6 months. RESULTS: The ADMSC and control groups included 125 and 127 patients available for follow-up, respectively. At 6 months, the ADMSC group showed significantly better improvements in 100-mm VAS (ADMSC vs control, 25.2 vs 15.5; P = .004) and total WOMAC score (21.7 vs 14.3; P = .002) as compared with the control group. The linear mixed model analysis indicated significantly better improvements in all clinical outcomes in the ADMSC group after 6 months. At 6 months, the ADMSC group achieved significantly higher proportions of patients above the minimal clinically important difference in 100-mm VAS and WOMAC score. Radiologic outcomes and adverse events did not demonstrate significant differences between the groups. No serious treatment-related adverse events were observed. Magnetic resonance imaging revealed no significant difference in change of cartilage defects between the groups at 6 months. CONCLUSION: Intra-articular injection of autologous culture-expanded ADMSCs provided significant pain relief and functional improvements in patients with K-L grade 3 osteoarthritis. Long-term results are needed to determine the disease-modifying effects of ADMSCs, such as structural changes, and the duration of effect of intra-articular injection of ADMSCs in knee osteoarthritis. REGISTRATION: NCT03990805 (ClinicalTrials.gov identifier).

Protective Effects of Hemp (Cannabis sativa) Root Extracts against Insulin-Deficient Diabetes Mellitus In Mice.

The pharmacological potential of industrial hemp (Cannabis sativa) has been widely studied. However, the majority of studies have focused on cannabidiol, isolated from the inflorescence and leaf of the plant. In the present study, we evaluated the anti-diabetic potential of hemp root water (HWE) and ethanol extracts (HEE) in streptozotocin (STZ)-induced insulin-deficient diabetic mice. The administration of HWE and HEE ameliorated hyperglycemia and improved glucose homeostasis and islet function in STZ-treated mice (p < 0.05). HWE and HEE suppressed ß-cell apoptosis and cytokine-induced inflammatory signaling in the pancreas (p < 0.05). Moreover, HWE and HEE normalized insulin-signaling defects in skeletal muscles and apoptotic response in the liver and kidney induced by STZ (p < 0.05). Gas chromatography-mass spectrometry analysis of HWE and HEE showed possible active compounds which might be responsible for the observed anti-diabetic potential. These findings indicate the possible mechanisms by which hemp root extracts protect mice against insulin-deficient diabetes, and support the need for further studies geared towards the application of hemp root as a novel bioactive material.