Subchondral bone: An emerging target for the treatment of articular surface lesions of the knee.

Purpose: When dealing with the health status of the knee articular surface, the entire osteochondral unit has gained increasing attention, and in particular the subchondral bone, which plays a key role in the integrity of the osteochondral unit. The aim of this article was to discuss the current evidence on the role of the subchondral bone. Methods: Experts from different geographical regions were involved in performing a review on highly discussed topics about the subchondral bone, ranging from its etiopathogenetic role in joint degeneration processes to its prognostic role in chondral and osteochondral defects, up to treatment strategies to address both the subchondral bone and the articular surface. Discussion: Subchondral bone has a central role both from an aetiologic point of view and as a diagnostic tool, and its status was found to be relevant also as a prognostic factor in the follow-up of chondral treatment. Finally, the recognition of its importance in the natural history of these lesions led to consider subchondral bone as a treatment target, with the development of osteochondral scaffolds and procedures to specifically address osteochondral lesions. Conclusion: Subchondral bone plays a central role in articular surface lesions from different points of view. Several aspects still need to be understood, but a growing interest in subchondral bone is to be expected in the upcoming future towards the optimization of joint preservation strategies. Level of Evidence: Level V, expert opinion.

Autologous chondrocyte implantation for the treatment of osteochondral lesions of the talus: What happens after 20 years?

BACKGROUND: The purpose of this study was to assess the long-term clinical efficacy of first-generation autologous chondrocyte implantation (ACI) technique for osteochondral lesions of the ankle joint. METHODS: Eleven patients with symptomatic OLTs underwent ACI from December 1997 to October 2002. A total of 9 patients (5 men, 4 women, age 25.2 ± 6.3) were evaluated at baseline and at 1, 3, 10 years, and at final follow-up of minimum 20 years with AOFAS ankle-hindfoot score, NRS for pain, and with the Tegner score. RESULTS: The AOFAS score improved significantly from the baseline value of 40.4 ± 19.8 to 82.7 ± 12.9 at the final follow-up (p < 0.0005). The NRS for pain improved significantly from 7.8 ± 0.7 at baseline to 4.8 ± 2.1 at the final follow-up (p < 0.0005). Moreover, the Tegner score underwent a modification from the pre-operative median value of 1 (range: 1-3) and from a pre-injury value of 5 (range: 3-7) to 3 (range: 2-4) at the final follow-up (p < 0.0005). CONCLUSIONS: ACI has proven to be an effective treatment option for patients suffering from OLTs, leading to a long-lasting clinical improvement even beyond 20 years of follow-up. LEVEL OF EVIDENCE: Level IV.

Sex does not influence the long-term outcome of matrix-assisted autologous chondrocyte transplantation.

PURPOSE: Regenerative techniques for articular cartilage lesions demonstrated heterogeneous clinical results. Several factors may influence the outcome, with sex being one of the most debated. This study aimed at quantifying the long-term influence of sex on the clinical outcome obtained with a regenerative procedure for knee chondral lesions. METHODS: Matrix-assisted autologous chondrocyte transplantation (MACT) was used to treat 235 knees which were prospectively evaluated with the International Knee Documentation Committee (IKDC), EuroQol visual analogue scale, and Tegner scores at 14-year mean follow-up. A multilevel analysis was performed with the IKDC subjective scores standardised according to the age/sex category of each patient and/or the selection of a match-paired subgroup to compare homogeneous men and women patients. RESULTS: At 14 years, men and women showed a failure rate of 10.7% and 28.8%, respectively (p < 0.0005). An overall improvement was observed in both sexes. Women had more patellar lesions and men more condylar lesions (p = 0.001), and the latter also presented a higher preinjury activity level (p < 0.0005). Men had significantly higher IKDC subjective scores at all follow-ups (at 14 years: 77.2 ± 18.9 vs. 62.8 ± 23.1; p < 0.0005). However, the analysis of homogeneous match-paired populations of men and women, with standardised IKDC subjective scores, showed no differences between men and women (at 14 years: -1.6 ± 1.7 vs. -1.9 ± 1.6). CONCLUSION: Men and women treated with MACT for knee chondral lesions presented a significant improvement and stable long-term results. When both sexes are compared with homogeneous match-paired groups, they have similar results over time. However, women present more often unfavourable lesion patterns, which proved more challenging in terms of long-term outcome after MACT. LEVEL OF EVIDENCE: Level II.

The 'placebo effect' in the conservative treatment of plantar fasciitis: a systematic review and meta-analyses.

Purpose: The study of the placebo effect is key to elucidate the 'real effect' of conservative interventions for plantar fasciitis. The aim of this meta-analysis was to quantify the impact of placebo in the different conservative treatments of plantar fasciitis. Methods: A systematic literature review was performed on double-blind placebo-controlled trials (RCTs) according to PRISMA guidelines on PubMed, Embase, and Web of Science. The meta-analysis primary outcome was the 0-10 pain variation after placebo treatments analyzed at 1 week, 1, 3, 6, and 12 months. The risk of bias was assessed using the RoB 2.0 tool, while the overall quality of evidence was graded according to the GRADE guidelines. Results: The placebo effect for conservative treatments was studied in 42 double-blind RCTs on 1724 patients. The meta-analysis of VAS pain showed a statistically significant improvement after placebo administration of 2.13/10 points (P < 0.001), being highest at 12 months with 2.79/10 points (P < 0.001). The improvement of the placebo groups was higher in the extracorporeal shock wave therapy studies compared to the injection studies (2.59 vs 1.78; P = 0.05). Eight studies had a low risk of bias, 23 studies had 'some concerns,' and 4 studies had a high risk of bias. The GRADE evaluation showed an overall high quality of evidence. Conclusion: This systematic review and meta-analysis demonstrated that the placebo effect represents an important component of all conservative approaches to treat plantar fasciitis. This effect is statistically and clinically significant, increases over time, and depends on the type of conservative treatment applied to address plantar fasciitis.

Severe hallux valgus can be treated using a distal metatarsal osteotomy: Results of 144 cases treated with the SERI technique.

PURPOSE: Aim of this study is to analyze the clinical and radiographic results of the simple, effective, rapid and inexpensive (SERI) technique, a linear distal metatarsal osteotomy, for treating severe hallux valgus (HV). METHODS: Clinical outcomes were assessed pre- and postoperatively using the AOFAS, MOxFQ and VAS score. Pre and postoperative HV angle (HVA) and intermetatarsal angle (IMA) were measured. RESULTS: 117 consecutive patients for a total of 144 feet were included. Pre and postoperatively, mean AOFAS changed from 44.8 ± 16.7 to 89 ± 10.3 (p < .001), mean MOxFQ changed from 76.2 ± 15.8 to 23.4 ± 7.9 (p < .001) and mean VAS score improved from 6.7 ± 2.1 to 1.5 ± 1.5 (p < .001). HVA diminished from 40.6° ± 6.9 preoperatively to 16.0° ± 7.3 postoperatively (p < .001). IMA decreased from 15.1° ± 2.8 preoperatively to 6.5° ± 2.4 postoperatively (p < .001). The main complication reported was stiffness (10.4 %). CONCLUSION: SERI technique applied to severe HV showed positive clinical and radiological outcomes. A careful patient selection and a low grade first MTPJ arthritis are essential to obtain favorable results. LEVEL OF EVIDENCE: IV.

Hyaluronic scaffold transplantation with bone marrow concentrate for the treatment of osteochondral lesions of the talus: durable results up to a minimum of 10 years.

PURPOSE: The aim of this study was to evaluate the long-term clinical results of the transplantation of a hyaluronic acid membrane augmented with bone marrow aspirate concentrate (BMAC) in an one-step technique for the treatment of patients affected by osteochondral lesions of the talus (OLT). METHODS: A total of 101 patients (64 men, 37 women, age 32.9 ± 10.9) were evaluated for a minimum of 10 years of follow-up (151.5 ± 18.4 months) The mean lesion size was 2.2 ± 1.4 cm2, the lesion had a post-traumatic origin in 73 patients, 15 patients previously had an ankle fracture, 22 patients had ankle osteoarthritis. All patients were clinically evaluated at baseline and at 2, 5, and a minimum of 10 years after treatment using the AOFAS score, the NRS for pain, and the Tegner score. A survival analysis was performed to check the survival to failure up to the last follow-up. RESULTS: The AOFAS score significantly improved from baseline (59.6 ± 13.9) to the final follow-up (82.3 ± 14.2) (p < 0.0005). A significant reduction in the AOFAS score was found from 2 to 10 years (p < 0.0005). The NRS for pain changed from 7.0 ± 1.3 at baseline to 3.9 ± 2.7 at the final follow-up (p < 0.0005). A significant worsening was documented between 5 years and the final follow-up (p < 0.0005). The Tegner score improved from the preoperative value of 2.0 (range 1-7) to 3.0 (range 1-7) at the final follow-up (p < 0.0005), although it remained lower as compared to the preinjury level of 4.0 (range 1-9) (p < 0.0005). Better results were documented in male and younger patients with smaller lesions, without the previous surgery, and without the previous ankle fractures or osteoarthritis. At the final follow-up, 85 patients considered their general health status "satisfactory" and 84 patients reported feeling "better" than the preoperative condition. Five patients were considered failures and underwent prosthetic ankle replacement or repeated the same surgery. CONCLUSION: This one-step technique showed to be an effective procedure for the treatment of OLT, providing a low failure rate and offering durable clinical improvements up to a minimum of 10 years of follow-up. However, this technique demonstrated a small yet significant decrease over the years in terms of pain and function and poor results in terms of sports activity level. LEVEL OF EVIDENCE: Level IV.

Terminology for osteochondral lesions of the ankle: proceedings of the International Consensus Meeting on Cartilage Repair of the Ankle.

BACKGROUND: The evidence supporting best practice guidelines in the field of cartilage repair of the ankle is based on both low quality and low levels of evidence. Therefore, an international consensus group of experts was convened to collaboratively advance toward consensus opinions based on the best available evidence on key topics within cartilage repair of the ankle. The purpose of this article is to report the consensus statements on "terminology for osteochondral lesions of the ankle" developed at the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. METHODS: Forty-three international experts in cartilage repair of the ankle representing 20 countries were convened and participated in a process based on the Delphi method of achieving consensus. Questions and statements were drafted within four working groups focusing on specific topics within cartilage repair of the ankle, after which a comprehensive literature review was performed, and the available evidence for each statement was graded. Discussion and debate occurred in cases where statements were not agreed on in unanimous fashion within the working groups. A final vote was then held, and the strength of consensus was characterised as follows: consensus, 51%-74%; strong consensus, 75%-99%; unanimous, 100%. RESULTS: A total of 11 statements on terminology and classification reached consensus during the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. Definitions are provided for osseous, chondral and osteochondral lesions, as well as bone marrow stimulation and injury chronicity, among others. An osteochondral lesion of the talus can be abbreviated as OLT. CONCLUSIONS: This international consensus derived from leaders in the field will assist clinicians with the appropriate terminology for osteochondral lesions of the ankle.

Bone marrow aspirate concentrate and scaffold for osteochondral lesions of the talus in ankle osteoarthritis: satisfactory clinical outcome at 10 years.

PURPOSE: To evaluate at long-term follow-up patients undergoing a one-step procedure of debridement and BMAC seeded in situ onto a scaffold for the treatment of osteochondral lesions of the talus (OLT) in ankles affected by osteoarthritis (OA), documenting the duration of the clinical benefit and its efficacy in postponing end-stage procedures. METHODS: This series included 56 consecutive patients. Patients were evaluated preoperatively and up to a mean of 10 years of follow-up with the AOFAS score and the AOS scale, including pain and disability subscales. Furthermore, patients were asked to rate the satisfaction and failures were documented as well. RESULTS: The AOFAS score improved from 52.3 ± 14.3 to 73.5 ± 23.1 at 10 years (p < 0.0005); the AOS pain and disability subscales decreased from 70.9 ± 14.1 to 37.2 ± 32.7 and from 69.0 ± 14.8 to 34.2 ± 29.3, respectively (both p < 0.0005). The overall rate of satisfaction was 61.8 ± 41.2 and 68.6% of patients would undergo again the surgical procedure. A total of 17 failures was documented, for a failure rate of 33.3%. Older patients and those with more complex cases requiring previous or combined surgeries had lower outcomes, as well as those affected by grade 3 OA, who experienced a high failure rate of 71.4%. CONCLUSIONS: This one-step technique for the treatment of OLT in OA ankles showed to be safe and to provide a satisfactory outcome, even if patients with end stage OA presented a high revision rate at 10 years. Moreover, this procedure was effective over time, with overall good results maintained up to a long-term follow-up. However, older age, more complex cases requiring previous or combined surgeries, and advanced OA led to an overall worst outcome and a significantly higher failure rate.

Evidence on ankle injections for osteochondral lesions and osteoarthritis: a systematic review and meta-analysis.

PURPOSE: To evaluate the evidence supporting safety and effectiveness of intra-articular injective treatments for ankle lesions ranging from osteochondral lesions of the talus (OLT) to osteoarthritis (OA). METHODS: A systematic review and a meta-analysis were performed on PubMed, Embase, and Cochrane Library in March 2020. Safety was evaluated through the reported side effects and effectiveness through the scores used. The quality of the studies was assessed using the Cochrane Collaboration Risk of Bias 2.0 tool and the Downs and Black checklist. For each outcome, the quality of evidence was graded according to GRADE guidelines. RESULTS: Twenty-four studies (21 for OA, 3 for OLT) were included on hyaluronic acid (HA), platelet-rich plasma (PRP), saline, methylprednisolone, botulinum toxin type A (BoNT-A), mesenchymal stem cells (MSCs), and prolotherapy. No severe adverse events were reported. For OLT, a comparison was possible between HA and PRP showing no significant difference. For ankle OA, a significant difference favouring HA versus saline was documented at six months (p < 0.001). The GRADE level of evidence was very low. CONCLUSION: This meta-analysis supports the safety of intra-articular treatment for ankle OA and OLT, while only a very low evidence supports the efficacy of HA in terms of better results versus placebo for the treatment of ankle OA, and other conclusions are hindered by the scarcity of the available literature. This urges further and stronger trials to specifically investigate potential and limitations of these different injective approaches for the treatment of OLT and ankle OA.

Treatment of hallux rigidus by a novel bi-phasic aragonite-based implant: results of a two year multi-centre clinical trial.

PURPOSE: The two year results of a multi-centre clinical trial were examined to evaluate surgical treatment of hallux rigidus using a novel, bi-phasic, biodegradable, and cell-free aragonite-based scaffold (Agili-C™, CartiHeal Ltd, Israel). METHODS: Twenty patients with moderate-to-severe hallux rigidus were recruited. After thorough metatarsophalangeal joint (MTPJ-1) debridement, the scaffolds were implanted into the defect centre. Eight patients received concomitant osteotomy. Treatment outcome was followed clinically (Pain VAS, FAAM-ADL, FAAM-Sport, AOFAS-HMIS, maximum active range of extension ROM-EXT, and flexion ROM-FLEX), and by medical imaging, at six month intervals for two years. Adverse events were recorded throughout the study follow-up period. RESULTS: Significant clinical improvement over time was observed in all evaluated parameters (screening to final evaluation averages: Pain VAS 59 to 26, FAAM-ADL 57 to 77, FAAM-Sport 39 to 66, AOFAS-HMIS 51 to 81, ROM-EXT 18° to 36°), except for ROM-FLEX. Radiographs showed stable MTPJ-1 width over the two years in 17/18 cases (94%). MRI demonstrated progressive implant biodegradation, coupled with articular cartilage and subchondral bone regeneration, with a repair tissue defect fill of 75-100% in 14/17 (82%) subjects at their final visit. Revision surgery with implant removal was performed in two patients. CONCLUSION: Bi-phasic, osteochondral, biodegradable, aragonite-based scaffold demonstrated positive clinical outcome and a good safety profile in the treatment of medium-to-advanced hallux rigidus. According to the medical imaging, this implant has the potential to restore the entire osteochondral unit of metatarsal head.

Complex Osteochondral Lesions of the Talus Treated With a Novel Bi-Phasic Aragonite-based Implant.

To present initial results of a novel, bi-phasic, porous, biodegrade, and cell-free aragonite-based scaffold for treating complex osteochondral lesions of the talus (OLT). Four subjects (2 males and 2 females; 34-61 years old) were operated on their ankles due to chronic and deep OLT-Hepple grades 4 or 5 (1.8-2.2 cm2). Three subjects had OLT on the medial central trochlea, and 1 had a combined medial and lateral lesions. OLT were exposed through medial malleolus osteotomy, with an additional lateral arthrotomy in the combined lesions. Bi-phasic porous osteochondral scaffolds (single implant or 2 implants) were implanted in a press-fit manner using a designated surgical toolset. Treatment outcome was followed clinically (Foot and Ankle Outcome Score, EQ-5D 3L, Tegner activity scale) and by medical imaging (radiographs, magnetic resonance imaging) from 18 to 32 months. All Foot and Ankle Outcome Score values increased from preoperative to final follow-up values (Symptoms 62 to 71, Pain 53 to 84, ADL 60 to 89, Sport 19 to 65, and QoL 18 to 47). EQ-5D 3L increased from 0.59 to 0.76, and Tegner activity values increased from 1.5 to 3. Kellgren-Lawrence ankle radiographic scores remained stable (2 to 2). Postoperative MR evaluation demonstrated cartilage defect fill of 75% to 100% respect to the native cartilage in 3 subjects (4 OLTs), while 1 lesion was filled 25% to 50%. No graft related serious adverse events or graft failures were reported. The use of a bi-phasic osteochondral biodegradable aragonite-based scaffold in the treatment of complex OLT during the reported period presented positive and promising clinical and radiologic outcome, without serious adverse events or graft failures.

Coronavirus disease 2019 pandemic: should we delay cartilage regenerative procedures and accept the consequences, or can we find a new normality?

The COVID-19 pandemic changed elective surgery routine. During the initial spread of the novel coronavirus, elective surgery has been stopped and only emergency and trauma and oncologic procedures were allowed. Following the decrease of the contagion curve, elective surgery is slowly being recovered. The hospitals should create a pre-hospitalization path to identify possible infected patient and further postpone surgery. In this setting, cartilage repair surgery should not be neglected, because this could potentially lead to an increase of patients needing major joint replacement surgery.

Phase I studies: a test bench for Italian clinical research.

BACKGROUND: The Agenzia Italiana del Farmaco (AIFA) Determination 809/2015 sets all the requirements that clinical units and laboratories must meet in order to conduct phase I studies. Requirements include buildings, equipment, personnel, emergency management, as well as quality requirements defined in a set of standard operating procedures. METHODS: In September 2018, the Italian Association of Medical Oncology working group, Clinical Research Coordinator, created an anonymous survey addressed to 51 medical directors of oncologic/hematologic clinical phase I units and all medical directors of generic and transversal units located in Italy and listed at the AIFA website. RESULTS: Questionnaires from 24 institutions were collected, 9 previously inspected by competent authorities. All surveyed structures are certified to conduct profit studies and 1 is authorized to include healthy volunteers; 15 units implemented a Clinical Trial Quality Team in order to conduct nonprofit studies. At the time of data collection, a total of 398 proposals for phase I trials have been received, more than 50% coming from 3 institutes. A total of 144 phase I studies were active, with a median of 2.5 (Q1-Q3=0-6) studies for each center and asymmetric distribution of proposals. CONCLUSION: The considerable number of proposals received from the interviewed centers indicates that Italy plays an important role in the international pharmaceutical scene, despite bureaucratic procedures that threaten exclusion from decision-making. The AIFA Determination will be an important opportunity to acquire a competitive working approach.

Mini Bone Block Distraction Subtalar Arthrodesis (SAMBB) in the Management of Acquired Adult Flatfoot with Subtalar Arthritis: A Modification to the Grice-Green Procedure.

Adult acquired flatfoot encompasses a wide range of deformities. The goal of surgical treatment of adult acquired flatfoot is to achieve proper alignment of the hindfoot and maintain as much flexibility as possible in the foot and ankle complex; nevertheless, if subtalar arthritis is present, subtalar arthrodesis is usually mandatory. A lateral approach over the sinus tarsi is performed and subtalar joint is prepared removing remaining cartilage, reduced up to 5 degrees of heel valgus, and stabilized with a Kirschner wire. The site of insertion of the corticocancellous bone graft, harvested from the ipsilateral proximal tibia, is prepared carving a vertical groove into the talar and calcaneal edges. Additional autologous cancellous chips, harvested from the proximal tibia, can be positioned and pressed with a beater into the sinus tarsi to enhance fusion. The technique described is a modification of the extra-articular arthrodesis originally proposed by Grice. mini bone block distraction subtalar arthrodesis is a simple and effective technique which permits a subtalar fusion with a restored orientation of the hindfoot and ankle alignment in acquired flatfoot with subtalar arthritis.

High Rate of Failure After Matrix-Assisted Autologous Chondrocyte Transplantation in Osteoarthritic Knees at 15 Years of Follow-up.

BACKGROUND: Chondral and osteochondral lesions in osteoarthritic knees of young patients remain challenging for orthopaedic surgeons, due to a combination of high functional demands and limited indications for joint replacement in this population. The possibility of extending the indication of cartilage regenerative procedures to these patients may allow the delay of metal resurfacing. PURPOSE: To analyze the potential of a cartilage regenerative approach to provide clinical benefits in young patients with osteoarthritic knees, documenting outcomes in terms of clinical improvement as well as failures, in particular regarding knee replacement, at long-term follow-up. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 41 patients (mean ± SD age, 43 ± 9 years) who had cartilage lesions (4 ± 2 cm2) in osteoarthritic knees (Kellgren-Lawrence grade 2 or 3) underwent matrix-assisted autologous chondrocyte transplantation (MACT) as a salvage procedure. Patients were evaluated with International Knee Documentation Committee (IKDC), EuroQol visual analog scale (EQ-VAS), and Tegner scores before surgery; at 1, 2, 5, and 9 years after surgery; and at a final follow-up at a mean of 15 years after surgery (range, 14-18 years). Failures were also recorded. RESULTS: An improvement was observed in all scores after surgery, but a progressive worsening over time was noted. The mean ± SD IKDC score improved from 38.6 ± 16.2 to a maximum of 66.0 ± 18.6 at 2 years (P < .0005), with a subsequent deterioration until the final evaluation at 56.2 ± 21.7 (P = .024). A similar trend was confirmed by EQ-VAS scores. Tegner scores improved at all follow-up points but did not reach the preinjury level. Patients who underwent combined surgery obtained significantly lower results. Only 13 patients (32%) had an IKDC score higher than 70. During the follow-up period, 21 patients underwent reoperation (18 with knee replacement) and 3 more patients experienced clinical failure, for a total surgical and clinical failure rate of 59% at 15 years. CONCLUSION: The use of cartilage regenerative surgical procedures, such as MACT, as salvage procedures for young, active patients affected by chondral and osteochondral lesions in osteoarthritic knees led to a limited improvement, with the majority of patients experiencing failure at long-term follow-up. Although a minor subpopulation experienced favorable and stable improvement, the use of MACT for such a challenging indication remains questionable until responding patients can be profiled.

Revision and Salvage Management: Proceedings of the International Consensus Meeting on Cartilage Repair of the Ankle.

BACKGROUND: The evidence supporting best practice guidelines in the field of cartilage repair of the ankle are based on both low quality and low levels of evidence. Therefore, an international consensus group of experts was convened to collaboratively advance toward consensus opinions based on the best available evidence on key topics within cartilage repair of the ankle. The purpose of this article was to report on the consensus statements on "Revision and Salvage Management" developed at the 2017 International Consensus Meeting on Cartilage Repair of the Ankle. METHODS: Seventy-five international experts in cartilage repair of the ankle representing 25 countries and 1 territory were convened and participated in a process based on the Delphi method of achieving consensus. Questions and statements were drafted within 11 working groups focusing on specific topics within cartilage repair of the ankle, after which a comprehensive literature review was performed and the available evidence for each statement was graded. Discussion and debate occurred in cases where statements were not agreed on in unanimous fashion within the working groups. A final vote was then held, and the strength of consensus was characterized as follows: consensus, 51% to 74%; strong consensus, 75% to 99%; unanimous, 100%. RESULTS: A total of 8 statements on revision and salvage management reached consensus during the 2017 International Consensus Meeting on Cartilage Repair of the Ankle. One achieved unanimous support and 7 reached strong consensus (greater than 75% agreement). All statements reached at least 85% agreement. CONCLUSIONS: This international consensus derived from leaders in the field will assist clinicians with revision and salvage management in the cartilage repair of the ankle.

TRIPLETE: a randomised phase III study of modified FOLFOXIRI plus panitumumab versus mFOLFOX6 plus panitumumab as initial therapy for patients with unresectable RAS and BRAF wild-type metastatic colorectal cancer.

BACKGROUND: FOLFOXIRI plus bevacizumab is considered a standard option in the upfront treatment of clinically selected patients with metastatic colorectal cancer irrespective of RAS and BRAF molecular status. The randomised MACBETH and VOLFI studies showed that a modified FOLFOXIRI regimen in combination with cetuximab or panitumumab, respectively, achieved high therapeutic activity in RAS and BRAF wild-type patients with an acceptable toxicity profile. Drawing from these considerations, we designed TRIPLETE study aiming at comparing two different chemotherapy backbones (mFOLFOXIRI or mFOLFOX6) in combination with panitumumab in the first-line treatment of patients with RAS and BRAF wild-type metastatic colorectal cancer. METHODS: This is a prospective, open-label, multicentre phase III trial in which initially unresectable and previously untreated RAS and BRAF wild-type metastatic colorectal cancer patients are randomised to receive a standard treatment with mFOLFOX6 plus panitumumab or an experimental regimen with modified FOLFOXIRI (irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, L-leucovorin 200 mg/m2, 5-fluoruracil 2400 mg/m2 48-hour continuous infusion) plus panitumumab up to 12 cycles, followed by panitumumab plus 5-fluorouracil and L-leucovorin until disease progression. The primary endpoint is overall response rate according to RECIST 1.1 criteria. DISCUSSION: The relative benefit of chemotherapy intensification when using an anti-EGFR-based regimen in molecularly selected patients is unknown; TRIPLETE study aims at filling this gap of knowledge. The study is sponsored by the Gruppo Oncologico Nord Ovest Cooperative Group and is currently ongoing at 42 Italian centres. CLINICAL TRIAL INFORMATION: NCT03231722.

Regenerative treatment of osteochondral lesions of distal tibial plafond.

OBJECTIVES: Osteochondral lesions of the distal tibial plafond (OLTP) are rare and far less common than osteochondral lesions of the talus. Literature data do not report clinical records with significant number of cases and follow-up. The aim of our study was to evaluate clinical and MRI outcomes following arthroscopic treatment of distal tibia osteochondral lesions and to report our results with treating these rare lesions. METHODS: Between October 2010 and November 2011, a consecutive series of 27 patients, 15 males and 12 females, were treated arthroscopically with the one-step BMDCT for OLTPs. Exclusion criteria were: age < 18 or > 50 years, patients with severe osteoarthritis (stage III according to Van Dijk classification), presence of kissing lesions of the ankle and patients with rheumatoid or hemophilic arthritis. All patients were evaluated through X-rays; MRI was performed preoperatively and at the final follow-up with MOCART score; clinical evaluation was assessed by AOFAS score at various follow-ups of 12, 24, 36, 60 and 72 months. RESULTS: No complications were observed post-surgery or during the rehabilitation period. The AOFAS score improved from 52.4 preoperatively to 80.6 at the mean final follow-up. All the patients were satisfied with the procedure. In 14 cases the MRI showed a complete filling of the osteochondral defect, in three patients a hypertrophic tissue was observed, and in the other two patients an incomplete repair of the lesion associated with a persistent slight subchondral edema was reported. A topographic study was also performed. CONCLUSIONS: Osteochondral lesions of the distal tibia represent a challenge for the orthopedic surgeon because of their difficulty diagnostic and rarities. The high incidence of good outcome in our series indicates that the one-step BMDCT could be a valid option for the treatment of this rare type of lesions. Further studies with a longer follow-up and more accurate imaging studies are necessary to confirm these results.

Autologous Chondrocyte Implantation for Talar Osteochondral Lesions: Comparison Between 5-Year Follow-Up Magnetic Resonance Imaging Findings and 7-Year Follow-Up Clinical Results.

Autologous chondrocyte implantation (ACI) is an established surgical procedure that has provided satisfactory results. The aim of the present study was to correlate the clinical outcomes of a series of 20 patients treated by ACI at a 7-year follow-up examination with the magnetic resonance imaging (MRI) T2-mapping 5-year follow-up findings. We evaluated 20 patients using the American Orthopaedic Foot and Ankle Society (AOFAS) score preoperatively and the established follow-up protocol until 87.2 ± 14.5 months. MRI T2-mapping sequences were acquired at the 5-year follow-up examination. At the MRI examination (60 ± 12 months), the mean AOFAS score improved from 58.7 ± 15.7 to 83.9 ± 18.4. At the final follow-up examination at 87.2 ± 14.5 months, the AOFAS score was 90.9 ± 12.7 (p = .0005). Those patients who experienced an improvement between 5 and 7 years after surgery had a significant greater percentage of T2-map value of 35 to 45 ms (hyaline cartilage) compared with those patients who did not improve (p = .038). MRI T2 mapping was shown to be a valuable tool capable of predicting reproducible clinical outcomes after ACI even 7 years after surgery. The quality of the regenerated tissue and the degree of defect filling became statistically significant to the clinical results at the final follow-up examination.