Arthroscopic Electromechanical Assessment of Human Articular Cartilage Injury Correlates with ICRS Scores.

PURPOSE: This study aimed to conduct arthroscopic evaluation of cartilage electromechanical properties and establish their correlation with International Cartilage Repair Society (ICRS) grading scores. METHODS: In 18 patients, quantitative parameter (QP) measurements were taken on the weight-bearing surface of the medial femoral condyle. Adjacently, the same site was graded using ICRS scores (0-4). Electromechanical QPs for ICRS grades 0 to 3 were obtained during arthroscopy, while complete grade 4 injuries were assessed using femur cartilage-bone blocks from knee arthroplasty. The QP values for ICRS grades 0 to 2 were compared with grades 3 and 4 using Welch t test. The corresponding QP values were assigned to ICRS grades 0 to 4 and compared using Welch ANOVA (analysis of variance). Pearson's coefficient evaluated QP-ICRS grade relationship. RESULTS: Healthy grade 0 cartilage displayed a mean QP value of 10.5 (±2.8 SD, n = 4). The ICRS grade 1 and grade 2 injuries were associated with QP values of 12 (±0.7, n = 2) and 13.25 (±1.77, n = 2), respectively. The grade 3 defects had QP values of 20.43 (±4.84, n = 4), whereas complete grade 4 defects showed electromechanical values of 30.17 (±2.19, n = 6). Significant differences in QP values were observed between ICRS grades 0 to 2 (mean QP 11.56 ± 2.3, n = 8) and grades 3 and 4 (26.27 ± 6, n = 10; P < 0.0001). Pearson's correlation coefficient of 0.9 indicated a strong association between higher ICRS cartilage injury grades and elevated QP values (P < 0.0001). CONCLUSION: Arthroscopic electromechanical QP assessment robustly correlates with ICRS scores. The QP values for ICRS grades 0 to 2 are significantly lower, compared with grades 3 and 4.

Lagophthalmos-induced corneal perforation in a patient with congenital erythropoietic porphyria.

Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive disorder in which the activity of uroporphyrinogen III synthase (UROS) is decreased. This results in the accumulation of photoreactive porphyrinogens, primarily in the skin and bone marrow. We describe a case of a patient with CEP who initially presented with scarring and shortening of the anterior and posterior lid lamella, which led to the development of lagophthalmos. Vascularized hyperkeratotic plaques in both corneas were also present. Despite treatment with topical ocular surface lubricants, corneal perforation with iris and uvea prolapse developed and evisceration of the right eye under local anesthesia was performed. The presented case suggests that despite topical therapy, ocular complications may exacerbate requiring surgical intervention, especially in the presence of lagophthalmos.

Dupilumab-Induced, Tralokinumab-Induced, and Belantamab Mafodotin-Induced Adverse Ocular Events-Incidence, Etiology, and Management.

ABSTRACT: Emerging monoclonal antibody therapies are assuming greater importance in the management of severe and refractory forms of immunity-driven and oncological disorders. However, some have been found to induce adverse ocular events (AOEs) leading to discontinuation of treatment or additional multidisciplinary management. We present the current knowledge concerning AOEs associated with 3 monoclonal antibody therapies: dupilumab, tralokinumab, and belantamab mafodotin. We examine the manifestations of their AOEs, proposed pathophysiological mechanisms, and current treatment recommendations. We identified and reviewed all studies for dupilumab, tralokinumab, and belantamab mafodotin using the keywords "dupilumab," "tralokinumab," "belantamab mafodotin," "conjunctivitis," and "keratopathy" from January 2016 to November 2021. Conjunctivitis was the most frequently reported AOE in patients with atopic dermatitis receiving dupilumab or tralokinumab. Mild cases were managed with warm compresses for associated meibomian gland dysfunction, artificial tears, and antihistamine/mast cell stabilizer eye drops. In more severe cases, additional anti-inflammatory therapy, with corticosteroid eye drops or ointments, or topical calcineurin inhibitors-such as tacrolimus or ciclosporin-were required. Patients with resistant or refractory multiple myeloma treated with belantamab mafodotin often developed keratopathy, which could necessitate contact lens fitting, or for cycles of belantamab mafodotin to be delayed.

Cartilage regeneration using improved surface electrospun bilayer polycaprolactone scaffolds loaded with transforming growth factor-beta 3 and rabbit muscle-derived stem cells.

Polycaprolactone (PCL) has recently received significant attention due to its mechanical strength, low immunogenicity, elasticity, and biodegradability. Therefore, it is perfectly suitable for cartilage tissue engineering. PCL is relatively hydrophobic in nature, so its hydrophilicity needs to be enhanced before its use in scaffolding. In our study, first, we aimed to improve the hydrophilicity properties after the network of the bilayer scaffold was formed by electrospinning. Electrospun bilayer PCL scaffolds were treated with ozone and further loaded with transforming growth factor-beta 3 (TGFß3). In vitro studies were performed to determine the rabbit muscle-derived stem cells' (rMDSCs) potential to differentiate into chondrocytes after the cells were seeded onto the scaffolds. Statistically significant results indicated that ozonated (O) scaffolds create a better environment for rMDSCs because collagen-II (Coll2) concentrations at day 21 were higher than non-ozonated (NO) scaffolds. In in vivo studies, we aimed to determine the cartilage regeneration outcomes by macroscopical and microscopical/histological evaluations at 3- and 6-month time-points. The Oswestry Arthroscopy Score (OAS) was the highest at both mentioned time-points using the scaffold loaded with TGFß3 and rMDSCs. Evaluation of cartilage electromechanical quantitative parameters (QPs) showed significantly better results in cell-treated scaffolds at both 3 and 6 months. Safranin O staining indicated similar results as in macroscopical evaluations-cell-treated scaffolds revealed greater staining with safranin, although an empty defect also showed better results than non-cell-treated scaffolds. The scaffold with chondrocytes represented the best score when the scaffolds were evaluated with the Mankin histological grading scale. However, as in previous in vivo evaluations, cell-treated scaffolds showed better results than non-cell-treated scaffolds. In conclusion, we have investigated that an ozone-treated scaffold containing TGFß3 with rMDSC is a proper combination and could be a promising scaffold for cartilage regeneration.

Functionalized Electrospun Scaffold-Human-Muscle-Derived Stem Cell Construct Promotes In Vivo Neocartilage Formation.

Polycaprolactone (PCL) is a non-cytotoxic, completely biodegradable biomaterial, ideal for cartilage tissue engineering. Despite drawbacks such as low hydrophilicity and lack of functional groups necessary for incorporating growth factors, it provides a proper environment for different cells, including stem cells. In our study, we aimed to improve properties of scaffolds for better cell adherence and cartilage regeneration. Thus, electrospun PCL-scaffolds were functionalized with ozone and loaded with TGF-ß3. Together, human-muscle-derived stem cells (hMDSCs) were isolated and assessed for their phenotype and potential to differentiate into specific lineages. Then, hMDSCs were seeded on ozonated (O) and non-ozonated ("naïve" (NO)) scaffolds with or without protein and submitted for in vitro and in vivo experiments. In vitro studies showed that hMDSC and control cells (human chondrocyte) could be tracked for at least 14 days. We observed better proliferation of hMDSCs in O scaffolds compared to NO scaffolds from day 7 to day 28. Protein analysis revealed slightly higher expression of type II collagen (Coll2) on O scaffolds compared to NO on days 21 and 28. We detected more pronounced formation of glycosaminoglycans in the O scaffolds containing TGF-ß3 and hMDSC compared to NO and scaffolds without TGF-ß3 in in vivo animal experiments. Coll2-positive extracellular matrix was observed within O and NO scaffolds containing TGF-ß3 and hMDSC for up to 8 weeks after implantation. These findings suggest that ozone-treated, TGF-ß3-loaded scaffold with hMDSC is a promising tool in neocartilage formation.

Do TRIB1 and IL-9 Gene Polymorphisms Impact the Development and Manifestation of Pituitary Adenoma?

BACKGROUND/AIM: To evaluate the association between TRIB1(rs6987702) and IL-9(rs1859430, rs2069870) genotypes with the development and manifestation of pituitary adenoma (PA). MATERIALS AND METHODS: The study group included 141 patients with PA and the control group consisted of 287 healthy people. The genotyping of rs6987702, rs1859430 and rs2069870 was carried out using a real-time polymerase chain reaction. RESULTS: Statistically significant results were obtained regarding the rs1859430, but there were no significant results regarding rs6987702. We found that the rs1859430 A/A genotype increased the odds of having recurrent PA six times (p=0.006) under the co-dominant model and four times (p=0.021) under the recessive model. Furthermore, the analysis showed that the G/A genotype increased the odds of having recurrent PA 2.3 times (p=0.003) under the co-dominant model, while G/A and A/A genotypes increased the odds 2.7 times (p=0.011) under the over-dominant model. CONCLUSION: Certain genotypes of rs1859430 can be associated with PA recurrence.

Nondestructive Assessment of Articular Cartilage Electromechanical Properties after Osteochondral Autologous and Allogeneic Transplantation in a Goat Model.

OBJECTIVE: To determine the applicability of a minimally invasive diagnostic device to evaluate the quality of articular cartilage following autologous (OAT) and allogeneic (OCA) osteochondral graft transplantation in goat model. DESIGN: OAT grafts were harvested from lateral femoral condyles (LFCs) and transplanted into osteochondral defects created in medial femoral condyles (MFCs) of contralateral knees. OCA grafts were transplanted into MFC condyles after in vitro storage. Autologous platelet-rich plasma (PRP) was administered intraarticularly after the surgery and at 1 and 2 months postoperatively. OAT and OCA grafts were evaluated macroscopically (Oswestry arthroscopy score [OAS]), electromechanically (quantitative parameter, QP), and histologically (O'Driscoll score, safranin O staining intensity) at 3 and 6 months after transplantation. Results were compared with preoperative graft evaluation. RESULTS: Transplanted cartilage deteriorated within 6 months in all groups. Cartilage quality was better retained in OAT group compared with a decline in OCA group. QP and OAS scores were comparable in OAT and OCA groups at 3 months, but superior in OAT group at 6 months, according to all the methods applied. PRP injections significantly improved QP and OAS score at 6 months compared with 3 months in OAT group. QP moderately correlated with OAS, O'Driscoll score, and safranin O staining intensity. CONCLUSIONS: Grafts did not retain preoperative quality parameters at 6 months follow-up; however, OAT were superior to OCA grafts. PRP may have a beneficial effect on macroscopic and electromechanical properties of cartilage; however, histological improvement is yet to be proved. Electromechanical diagnostic device enables reliable assessment of transplanted cartilage.

Quantitative Arthroscopic Assessment of Articular Cartilage Quality by Means of Cartilage Electromechanical Properties.

Arthroscopic surgery has grown rapidly in recent decades. Despite accurately diagnosed clinical cases, the previous pain is retained in some patients after the operation, even though no visible chondral lesions are found during the procedure. A minimally invasive arthroscopic method of measuring articular cartilage electromechanical properties enables rapid and reliable intraoperative articular cartilage quality evaluation.

Impact of storage conditions on electromechanical, histological and histochemical properties of osteochondral allografts.

BACKGROUND: Osteochondral allograft transplantation has a good clinical outcome, however, there is still debate on optimization of allograft storage protocol. Storage temperature and nutrient medium composition are the most critical factors for sustained biological activity of grafts before implantation. In this study, we performed a time-dependent in vitro experiment to investigate the effect of various storage conditions on electromechanical, histological and histochemical properties of articular cartilage. METHODS: Osteochondral grafts derived from goat femoral condyles were frozen at -70 °C or stored at 4 °C and 37 °C in the medium supplemented with or without insulin-like growth factor-1 (IGF-1). After 14 and 28 days the cartilage samples were quantitatively analysed for electromechanical properties, glycosaminoglycan distribution, histological structure, chondrocyte viability and apoptosis. The results were compared between the experimental groups and correlations among different evaluation methods were determined. RESULTS: Storage at -70 °C and 37 °C significantly deteriorated cartilage electromechanical, histological and histochemical properties. Storage at 4 °C maintained the electromechanical quantitative parameter (QP) and glycosaminoglycan expression near the normal levels for 14 days. Although hypothermic storage revealed reduced chondrocyte viability and increased apoptosis, these parameters were superior compared with the storage at -70 °C and 37 °C. IGF-1 supplementation improved the electromechanical QP, chondrocyte viability and histological properties at 37 °C, but the effect lasted only 14 days. Electromechanical properties correlated with the histological grading score (r = 0.673, p < 0.001), chondrocyte viability (r = -0.654, p < 0.001) and apoptosis (r = 0.416, p < 0.02). In addition, apoptosis correlated with glycosaminoglycan distribution (r = -0.644, p < 0.001) and the histological grading score (r = 0.493, p = 0.006). CONCLUSIONS: Our results indicate that quality of allografts is better preserved at currently established 4 °C storage temperature. Storage at -70 °C or at 37 °C is unable to maintain cartilage function and metabolic activity. IGF-1 supplementation at 37 °C can enhance chondrocyte viability and improve electromechanical and histological properties of the cartilage, but the impact persists only 14 days. The correlations between cartilage electromechanical quantitative parameter (QP) and metabolic activity were detected. Our findings indicate that non-destructive assessment of cartilage by Arthro-BST is a simple and reliable method to evaluate allograft quality, and could be routinely used before implantation.

Comparison of osteochondral autologous transplantation, microfracture, or debridement techniques in articular cartilage lesions associated with anterior cruciate ligament injury: a prospective study with a 3-year follow-up.

PURPOSE: To compare the concomitant treatment of articular cartilage damage in the medial femoral condyle with osteochondral autologous transplantation (OAT), microfracture, or debridement procedures at the time of anterior cruciate ligament (ACL) reconstruction. METHODS: Between 2006 and 2009, 102 patients with a mean age of 34.1 years and with an ACL rupture and articular cartilage damage in the medial femoral condyle of the knee were randomized to undergo OAT, microfractures, or debridement at the time of ACL reconstruction. A matched control group was included, comprising 34 patients with intact articular cartilage at the time of ACL reconstruction. There were 34 patients in the OAT-ACL group, 34 in the microfracture (MF)-ACL group, 34 in the debridement (D)-ACL group, and 34 in the control group with intact articular cartilage (IAC-ACL group). The mean time from ACL injury to operation was 19.32 ± 3.43 months, and the mean follow-up was 36.1 months (range, 34 to 37 months). Patients were evaluated with the International Knee Documentation Committee (IKDC) score, Tegner activity score, and clinical assessment. RESULTS: Of 102 patients, 97 (95%) were available for the final follow-up. According to the subjective IKDC score, all 4 groups fared significantly better at the 3-year follow-up than preoperatively (P < .005). The OAT-ACL group's IKDC subjective knee evaluation was significantly better than that of the MF-ACL group (P = .024) and D-ACL group (P = .018). However, the IKDC subjective score of the IAC-ACL group was significantly better than the OAT-ACL group's IKDC evaluation (P = .043). There was no significant difference between the MF-ACL and D-ACL groups' IKDC subjective scores (P = .058). Evaluation of manual pivot-shift knee laxity according to the IKDC knee examination form showed similar findings for the 4 groups immediately postoperatively and at 3-year follow-up, and the findings were rated as normal or nearly normal (IKDC grade A or B) in 29 of 33 patients (88%) in the OAT-ACL group, 28 of 32 patients (88%) in the MF-ACL group, 27 of 32 patients (84%) in the D-ACL group, and 31 of 34 patients (91%) in the IAC-ACL group. CONCLUSIONS: Our study shows that intact articular cartilage during ACL reconstruction yields more favorable IKDC subjective scores compared with any other articular cartilage surgery type. However, if an articular defect is present, the subjective IKDC scores are significantly better for OAT versus microfracture or debridement after a mean period of 3 years. Anterior knee stability results were not significantly affected by the different articular cartilage treatment methods. LEVEL OF EVIDENCE: Level II, prospective comparative study.

Concomitant autologous chondrocyte implantation with osteochondral grafting for treatment of a massive osteochondral defect in the bilateral knees of a child.

We report the case of a 15-year-old patient who underwent concomitant autologous chondrocyte implantation and osteochondral grafting for the treatment of a massive osteochondritis dissecans defect in the left knee and autologous chondrocyte implantation in the right knee joint. Magnetic resonance imaging showed large osteochondral defects in both the knee joints measuring 8-9 cm(2). Both defects were located in the weight-bearing areas of the medial femoral condyles. Therefore, simultaneous autologous chondrocyte implantation (ACI) and osteochondral autograft transplantation (OAT) for the left knee defect and ACI for the right knee joint were performed. Osteochondral plugs were harvested from the patellofemoral joint of the same left knee and grafted into the most dorsal regions of the large osteochondral defect of the left knee. The remaining osteochondral defect was covered with ACI using collagen type I and III membrane and chondrocyte cells. The membrane was implanted into more proximal part of the osteochondral defect of the left knee. Time interval between operations of the left and right knee joints was 6 months. Magnetic resonance imaging at 6 months after each knee surgery showed good preservation of the OAT and ACI grafts. The most recent follow-up examination, performed 12 months after surgeries, has shown excellent results with an International Knee Documentation Committee score of 95.59±4.64 and 96.88±4.69 for the right and left knee joints, respectively, and full range of knee motions with no symptoms. In this clinical case, the combination of ACI and OAT methods in a one-step procedure produced a good reconstruction of the joint surface with excellent clinical outcomes in the both knee joints of the same patient. Autologous osteochondral grafting and autologous chondrocyte implantation can be combined for the treatment of large osteochondral defects of the knee.

Arthroscopic coracoid transposition for recurrent shoulder anterior instability: an operative technique.

We report a technique of an arthroscopic concomitant Bankart repair with a transfer of the coracoid bone block and conjoint tendons for revision anterior shoulder instability. The operative procedure consists of an arthroscopic transfer of the conjoined tendon with a coracoid and arthroscopic Bankart repair. First, a typical Bankart suture anchor procedure with two suture anchors was performed into the antero-inferior part of the glenoid rim. After, tenodesis of the coraco-biceps tendon was performed in the middle of the subscapularis tendon fixing the coracoid bony fragment into a glenoid socket with a bioabsorbable interference screw. This operative technique is an alternative in the treatment of revision anterior shoulder instability in patients with deficient anterior capsule.

Monitoring changes in heart tissue temperature and evaluation of graft function after coronary artery bypass grafting surgery.

Thermography is a relatively new contact-free method used in experimental and clinical studies and in cardiovascular surgery to investigate the myocardium and coronary artery function. Objects of complex study included mongrel dogs and patients with coronary artery disease who underwent cardiac surgery. For active dynamic thermography, we used a thermovision camera "A20V" (FLIR Systems, USA). Our data indicate that both experimental and clinical study performed on beating hearts could be an important approach to interoperation inspection of autovenous graft function. An infrared camera also can be successfully used to determine the extent of ischemic damage to the myocardium, heart, and blood vessels during surgery as a significant prognostic tool for evaluating outcome after cardiac operation.