Effect of the defect localization and size on the success of third-generation autologous chondrocyte implantation in the knee joint

Introduction. Femoral and patellar cartilage defects with a defect size > 2.5 cm2 are a potential indication for an autologous chondrocyte implantation (ACI). However, the influence of the localization and the absolute and relative defect size on the clinical outcome has not yet been determined. The purpose of this study is to analyze the influence of the localization and the absolute and relative defect size on the clinical outcome after third-generation autologous chondrocyte implantation. Methods. A total of 50 patients with cartilage defects of the knee were treated with third-generation autologous chondrocyte implantation (Novocart® 3D). A match paired analysis was performed of 25 treated femoral and 25 treated patella defects with a follow-up of three years. MRI data was used to do the manual segmentation of the cartilage layer throughout the knee joint. The defect size was determined by taking the defect size measured in the MRI in relation to the whole cartilage area. The clinical outcome was measured by the IKDC score and VAS pre-operatively and after six, 12, 24, and 36 months post-operatively. Results. IKDC and VAS scores showed a significant improvement from the baseline in both groups. Femoral cartilage defects showed significantly superior clinical results in the analyzed scores compared to patellar defects. The femoral group improved IKDC from 33.9 (SD 18.1) pre-operatively to 71.5 (SD 17.4) after three years and the VAS from 6.9 (SD 2.9) pre-operatively to 2.4 (SD 2.5) after three years. In the patellar group, IKDC improved from 36.1 (SD 12.6) pre-operatively to 54.7 (SD 20.3) after three years and the VAS improved from 6.7 (SD 2.8) pre-operatively to 3.4 (SD 2.) after three years. Regarding the defect size, results showed that the same absolute defect size at med FC (4.8, range 2–15) and patella (4.6, range 2–12) has a significantly different share of the total cartilaginous size of the joint compartment (med FC: 6.7, range 1.2–13.9; pat: 18.9, range 4.0–47.0). However, there was no significant influence of the relative defect size on the clinical outcome in either patellar or femoral localization. Conclusion. Third-generation autologous chondrocyte implantation in ACI-treated femoral cartilage defects leads to a superior clinical outcome in a follow-up of three years compared with patellar defects. No significant influence of the defect size was found in either femoral or patellar cartilage defects

Graft Hypertrophy After Third-Generation Autologous Chondrocyte Implantation Has No Correlation With Reduced Cartilage Quality: Matched-Pair Analysis Using T2-Weighted Mapping

Background: Graft hypertrophy is common after matrix-based autologous chondrocyte implantation (ACI) in the knee joint. However, it is not clear whether graft hypertrophy is a complication or an adjustment reaction in the cartilage regeneration after ACI. Purpose: To analyze the cartilage quality of the ACI regeneration with graft hypertrophy using T2-weighted mapping. Study Design: Cohort study;Level of evidence, 2. Methods: A total of 91 patients with isolated cartilage defects (International Cartilage Repair Society [ICRS] grade III-IV) of the knee were treated with Novocart 3D, a third-generation, matrix-based, ACI procedure in the knee joint. All patients were evaluated with a standardized magnetic resonance imaging protocol after 3, 6, 12, 24, 36, and 48 months postoperatively. For morphological and biochemical assessment, the T2-weighted relaxation times of the ACI grafts as well as the healthy surrounding cartilage were determined. The results of the 20 patients with graft hypertrophy (hypertrophic group) were compared with the results of 21 matched patients without graft hypertrophy (nonhypertrophic group) after ACI. Match-paired analysis was performed by comparison of age, defect size, and body mass index. Results: The T2-weighted relaxation times of the ACI graft showed significant improvement, with values decreasing from 52.1 milliseconds to 33.3 milliseconds after 48 months. After 12 months, the T2-weighted relaxation times were constant and comparable with the healthy surrounding cartilage. Graft hypertrophy was seen in 22% (n = 20) of the patients who underwent ACI. A significant difference in T2-weighted relaxation times between the hypertrophic and nonhypertrophic ACI grafts could not be found except after 36 months (hypertrophic T2-weighted relaxation time/nonhypertrophic T2-weighted relaxation time: 3 months, 48.0/56.4 ms, P = .666;6 months, 45.6/42.5 ms, P = .280;12 months, 39.3/34.7 ms, P = .850;24 months, 34.8/32.2 ms, P =.742;36 months, 34.6/38.2 ms, P = .030;48 months, 34.2/32.3 ms, P = .693). Conclusion: The T2-weighted relaxation time of the ACI graft cartilage showed significant improvements over the observation period of 4 years postoperatively. After 2 years, graft maturation was completed. Graft hypertrophy after ACI was seen in 22% of the patients. Reduced cartilage quality could not be found in patients with graft hypertrophy after ACI

Decreased Compressional Sound Velocity Is an Indicator for Compromised Bone Stiffness in X-Linked Hypophosphatemic Rickets (XLH)

Objectives: To assess the diagnostic potential of bidirectional axial transmission (BDAT) ultrasound, and high-resolution peripheral quantitative computed tomography (HR-pQCT) in X-linked hypophosphatemia (XLH, OMIM #307800), a rare genetic disorder of phosphate metabolism caused by mutations in the PHEX gene. Methods: BDAT bone ultrasound was performed at the non-dominant distal radius (33% relative to distal head) and the central left tibia (50%) in eight XLH patients aged between 4.2 and 20.8 years and compared to twenty-nine healthy controls aged between 5.8 and 22.4 years. In eighteen controls, only radius measurements were performed. Four patients and four controls opted to participate in HR-pQCT scanning of the ultradistal radius and tibia. Results: Bone ultrasound was feasible in patients and controls as young as 4 years of age. The velocity of the first arriving signal (νFAS) in BDAT ultrasound was significantly lower in XLH patients compared to healthy controls: In the radius, mean νFAS of XLH patients and controls was 3599 ± 106 and 3866 ± 142 m/s, respectively (-6.9%; p < 0.001). In the tibia, it was 3578 ± 129 and 3762 ± 124 m/s, respectively (-4.9%; p = 0.006). HR-pQCT showed a higher trabecular thickness in the tibia of XLH patients (+16.7%; p = 0.021). Conclusions: Quantitative bone ultrasound revealed significant differences in cortical bone quality of young XLH patients as compared to controls. Regular monitoring of XLH patients by a radiation-free technology such as BDAT might provide valuable information on bone quality and contribute to the optimization of treatment. Further studies are needed to establish this affordable and time efficient method in the XLH patients

Mutation analysis of BRCA1 and BRCA2 genes in Iranian high risk breast cancer families

Background: Telomerase is a ribonucleoprotein enzyme that synthesises telomeres after cell division and maintains chromosomal stability leading to cellular immortalization. Telomerase has been associated with negative prognostic indicators in some studies. The present study aims to detect any association between telomerase sub-units: hTERT and hTR and the prognostic indicators including tumour's size and grade, nodal status and patient's age. Methods: Tumour samples from 46 patients with primary invasive breast cancer and 3 patients with benign tumours were collected. RT-PCR analysis was used for the detection of hTR, hTERT, and PGM1 (as a housekeeping) genes expression. Results: The expression of hTR and hTERT was found in 31(67.4%) and 38 (82.6%) samples respectively. We observed a significant association between hTR gene expression and younger age at diagnosis (p = 0.019) when comparing patients ≤ 40 years with those who are older than 40 years. None of the benign tumours expressed hTR gene. However, the expression of hTERT gene was revealed in 2 samples. No significant association between hTR and hTERT expression and tumour's grade, stage and nodal status was seen. Conclusion: The expression of hTR and hTERT seems to be independent of tumour's stage. hTR expression probably plays a greater role in mammary tumourogenesis in younger women (≤ 40 years) and this may have therapeutic implications in the context of hTR targeting strategies

TRATAMIENTO DE RECESIONES GINGIVALES MÚLTIPLES EN SECTOR ANTEROSUPERIOR CON EL USO DE MATRIZ DÉRMICA ACELULAR, ANTECEDENTES Y REPORTE DE UN CASO.

Objetivo: El objetivo de este reporte de caso es utilizar la matriz dérmica acelular&nbsp; como alternativa&nbsp; para el cubrimiento radicular mediante el desplazado coronal. Material y métodos: Paciente de sexo femenino de 53 años de edad que acude a la Maestría de Periodoncia de la Facultad de Odontología en la Universidad Autónoma de Coahuila, Unidad Torreón con motivo de consulta: “se me bajó la encía y traigo mucha sensibilidad”. En el examen clínico se observan recesiones gingivales clase I de Miller en los OD 13, 11, 21 y 33, así como agenesia de incisivos laterales (12 y 22), se realiza la cirugía utilizando una matriz dérmica acelular para minimizar la incomodidad y dolor postoperatorios. Resultados: El uso de una matriz dérmica acelular ayuda a obtener resultados en cuanto a cobertura radicular similares a los del injerto de tejido conectivo autólogo en el manejo de recesiones múltiples de clase I de Miller, minimizando las molestias postoperatorias del paciente. Palabras clave: matriz dérmica acelular, colgajo desplazado coronalmente, cobertura radicular. DeCS [Internet]. ed. 2017. Sao Paulo (SP): BIREME / OPS / OMS. 2017 [actualizado 2017 May 18; citado 2017 Jun 13]. Disponible en: http://decs.bvsalud.org/E/homepagee.ht

<i>In Vitro</i> Antibacterial Activity of Microbial Natural Products against Bacterial Pathogens of Veterinary and Zoonotic Relevance

Antimicrobial resistance (AMR) is considered one of the greatest threats to both human and animal health. Efforts to address AMR include implementing antimicrobial stewardship programs and introducing alternative treatment options. Nevertheless, effective treatment of infectious diseases caused by bacteria will still require the identification and development of new antimicrobial agents. Eight different natural products were tested for antimicrobial activity against seven pathogenic bacterial species (Brachyspira sp., Chlamydia sp., Clostridioides sp., Mannheimia sp., Mycobacterium sp., Mycoplasma sp., Pasteurella sp.). In a first pre-screening, most compounds (five out of eight) inhibited bacterial growth only at high concentrations, but three natural products (celastramycin A [CA], closthioamide [CT], maduranic acid [MA]) displayed activity at concentrations Pasteurella sp. and two of them (CA and CT) also against Mannheimia sp. Those results were confirmed by testing a larger collection of isolates encompassing 64 Pasteurella and 56 Mannheimia field isolates originating from pigs or cattle, which yielded MIC90 values of 0.5, 0.5, and 2 µg/mL against Pasteurella and 0.5, 4, and >16 µg/mL against Mannheimia for CA, CT, and MA, respectively. CA, CT, and MA exhibited higher MIC50 and MIC90 values against Pasteurella isolates with a known AMR phenotype against commonly used therapeutic antimicrobial agents than against isolates with unknown AMR profiles. This study demonstrates the importance of whole-cell antibacterial screening of natural products to identify promising scaffolds with broad- or narrow-spectrum antimicrobial activity against important Gram-negative veterinary pathogens with zoonotic potential

Hepatitis C virus replication in mouse cells is restricted by IFN-dependent and -independent mechanisms.

Current treatment strategies for hepatitis C virus (HCV) infection include pegylated interferon (IFN)-alfa and ribavirin. Approximately 50% of patients control HCV infection after treatment, but the broad range of patients' outcomes and responses to treatment, among all genotypes, indicates a role for host factors. Although the IFN system is important in limiting HCV replication, the virus has evolved mechanisms to circumvent the IFN response. However, direct, IFN-independent antiviral processes also might help control HCV replication. We examined the role of IFN-independent responses against HCV replication

The Immune Phenotype of Isolated Lymphoid Structures in Non-Tumorous Colon Mucosa Encrypts the Information on Pathobiology of Metastatic Colorectal Cancer

The gut-associated lymphoid tissue represents an integral part of the immune system. Among the powerful players of the mucosa-associated lymphoid tissue are isolated lymphoid structures (ILSs), which as information centers, drive the local (and systemic) adaptive immune responses. Germinal center reactions, taking place within ILSs, involve the coordinated action of various immune cell types with a central role given to B cells. In the current study, we aimed at dissecting the impact of ILSs within non-tumorous colon tissue (NT) on the pathobiology of colorectal cancer (CRC) with metastasis in the liver (CRCLM). In particular, we focused on the immune phenotypes of ILSs and ectopic lymphoid structures (ELSs), built up at matching primary and metastatic tumor sites. We implemented an integrative analysis strategy on the basis of tissue image cytometry and clonality assessment to explore the immune phenotype of ILS/ELS at three tissue entities: NT, CRC, and CRCLM (69 specimens in total). Applying a panel of lineage markers used for immunostaining, we characterized and compared the anatomical features, the cellular composition, the activation, and proliferation status of ILSs and ELSs, and assessed the clinical relevance of staining-derived data sets. Our major discovery was that ILS characteristics at the NT site predefine the immune phenotype of ELSs at CRC and CRCLM. Thereby, B-cell-enriched (CD20) and highly proliferative (Ki67) ILSs and ELSs were found to be associated with improved clinical outcome in terms of survival and enabled patient stratification into risk groups. Moreover, the data revealed a linkage between B-cell clonality at the NT site and the metastatic characteristics of the tumor in the distant liver tissue. Consolidation of immunostaining-based findings with the results of compendium-wide transcriptomic analysis furthermore proposed CD27 as a novel marker of T follicular helper cells within lymphoid structures. Overall, the study nominates the ILS immune phenotype as a novel prognostic marker for patients with metastatic CRC

Secreted microvesicular miR-31 inhibits osteogenic differentiation of mesenchymal stem cells

10.1111/acel.12484AGING CELL154744-75