Matteo Formica

What is the preclinical evidence on platelet rich plasma and intervertebral disc degeneration

PurposeIntervertebral disc degeneration is a common disease that usually starts from the third decade of life and it represents a significant cause of socio-economic problems. The accepted surgical treatment for disc degeneration is disc removal and vertebral fusion or, in selected cases, intervertebral disc arthroplasty. Several studies have demonstrated the ability of platelet rich plasma (PRP) to stimulate cell proliferation and extracellular matrix regeneration. However, literature results are still limited and more studies are required to clarify the role of PRP in the prevention or in the treatment of degenerative disc disease. The aim of this review is to summarize and critically analyze the current preclinical evidence about the use of PRP in intervertebral disc degeneration.MethodsLiterature search was performed through various combinations of the following keywords: Intervertebral Disc Degeneration, Platelet Rich Plasma, PRP, Intervertebral disc regeneration. Papers included in our review cover the period between 2006 and 2014. The PRISMA 2009 checklist was followed.ResultsAt the end of the review process, 12 articles were included in our final manuscript, including 6 “in vitro” and 6 “in vivo” studies. All the included studies lead to positive preclinical results. No standardization of methodological analysis was observed.ConclusionIt is not possible to draw definitive evidence about the use of PRP in IVD regeneration. We advise a proper standardization of the methodological analysis in order to compare the available data and achieve definitive results. This should be the cornerstone for future clinical applications.

Kümmell disease: illustrative case for definition criteria

Kümmell disease (KD) is defined as a clinical condition in which patients develop a painful progressive angular kyphosis as a result of a delayed vertebral body collapse after a minor spinal trauma [1–3]. The most supported etiopathogenetic hypothesis is a posttraumatic avascular necrosis of the vertebral body [4]. The main cornerstones of KD are history of trauma with a negative x-ray investigation, an asymptomatic period, and a recurrence of symptoms that results in painful kyphosis deformity of the affected spine [5]. Intravertebral vacuum cleft is a widely reported radiological sign associated with KD [6,7]. Literature on this subject is limited and characterized by some inaccuracies and wrong diagnosis. Kümmell disease needs to be distinguished from other clinical situations, such as osteoporosis vertebral fractures or idiopathic

Which patients risk segmental kyphosis after short segment thoracolumbar fracture fixation with intermediate screws

INTRODUCTION The use of intermediate screws in fractured vertebrae has been proposed to decrease the number of fused levels in thoracolumbar fractures and to enable short fixations. The aim of this study was to evaluate the results of this technique and to establish predictive factors involved in loss of segmental kyphosis correction (LKC). METHODS Forty-three patients who underwent short-segment spinal fixation with intermediate screws for a thoracolumbar spine fracture in a two-year time period were enrolled in the study. Patients had AO-type A3, A4 and B2 thoracolumbar fractures. Radiological parameters included segmental kyphosis (SK), vertebral wedge angle (VWA) and loss of anterior and posterior vertebral body height. Patients were evaluated up to one-year follow-up. The correlation between LKC and potential risk factors, such as smoking habit, sex, age, neurological status and BMI was evaluated. RESULTS Mean preoperative SK was 16.5°±6.5°, and it decreased to 3.4°±3.5° postoperatively (P<0.01). At the one-year follow-up mean SK dropped to 5.5°±3.9° (P<0.01). Mean preoperative VWA was 20.0°±8.1°, and significantly improved to 6.3°±3.1° after surgery (P<0.01). There was a mean LKC of 1.8°±2.1°at one year. LKC mildly correlated with body mass index (BMI, r: +0.31), and obese patients (BMI>30) had an increased risk of LKC at the one-year follow-up (P=0.03; odds ratio [OR]=3.2). DISCUSSION Analysis of the radiological data at one-year follow-up showed that all the evaluated parameters were associated with a mild loss of correction, with no impact on the clinical outcomes or implant failure. These findings confirm the trends reported in the literature. The correlation between LKC and clinical features, such as BMI, age, sex, smoking habit and preoperative neurological status was investigated. Interestingly, a positive correlation was observed between BMI and LKC, and obese patients with BMI>30 had an increased risk of LKC at one-year follow-up (OR 3.2); to our knowledge this finding has never before been reported. CONCLUSION Short-segment fixation with intermediate screws is a viable technique with positive clinical and radiological outcomes at one-year follow-up. However, surgeons should be aware that in obese patients (BMI>30) this technique is associated with an increased risk of LKC. LEVEL OF EVIDENCE 3.

Culture Medium Supplements Derived from Human Platelet and Plasma: Cell Commitment and Proliferation Support

Present cell culture medium supplements, in most cases based on animal sera, are not fully satisfactory especially for the in vitro expansion of cells intended for human cell therapy. This paper refers to (i) an heparin-free human platelet lysate (PL) devoid of serum or plasma components (v-PL) and (ii) an heparin-free human serum derived from plasma devoid of PL components (Pl-s) and to their use as single components or in combination in primary or cell line cultures. Human mesenchymal stem cells (MSC) primary cultures were obtained from adipose tissue, bone marrow, and umbilical cord. Human chondrocytes were obtained from articular cartilage biopsies. In general, MSC expanded in the presence of Pl-s alone showed a low or no proliferation in comparison to cells grown with the combination of Pl-s and v-PL. Confluent, growth-arrested cells, either human MSC or human articular chondrocytes, treated with v-PL resumed proliferation, whereas control cultures, not supplemented with v-PL, remained quiescent and did not proliferate. Interestingly, signal transduction pathways distinctive of proliferation were activated also in cells treated with v-PL in the absence of serum, when cell proliferation did not occur, indicating that v-PL could induce the cell re-entry in the cell cycle (cell commitment), but the presence of serum proteins was an absolute requirement for cell proliferation to happen. Indeed, Pl-s alone supported cell growth in constitutively activated cell lines (U-937, HeLa, HaCaT, and V-79) regardless of the co-presence of v-PL. Plasma- and plasma-derived serum were equally able to sustain cell proliferation although, for cells cultured in adhesion, the Pl-s was more efficient than the plasma from which it was derived. In conclusion, the cells expanded in the presence of the new additives maintained their differentiation potential and did not show alterations in their karyotype.

Conservative treatment of meniscal tears in anterior cruciate ligament reconstruction

BACKGROUND Management of small and stable meniscal tears within the vascular zone at the time of anterior cruciate ligament (ACL) reconstruction is controversial. The purpose of this study was to evaluate the outcome of meniscal tear left in situ at the time of ACL reconstruction. METHODS Using the IKDC, KT-1000 and the Tegner Activity Score (TAS), we retrospectively analysed 175 cases of ACL reconstruction with meniscal tears performed from 2006 to 2012. Patients with residual laxity on clinical assessment were identified and considered as a subgroup. Clinical outcome and failure rate were evaluated. RESULTS In 83 patients (47.4%), a meniscal tear was left in situ at the time of ACL reconstruction: 45 were medial and 38 were lateral. Patients were clinically reassessed with a minimum follow-up of 24 months. The overall failure rate of conservative meniscal treatment in patients with objective residual laxity was 87.5%, and 6.7% in patients with a stable knee (P<0.001). Those with stable knees had higher postoperative IKDC subjective scores (P=0.0022) and TAS (P<0.0001). Patients without residual laxity had higher failure rate for the medial meniscus compared with lateral meniscus - 10.5% versus 2.7% (P=0.36)-and the red-red zone had lower revision rate compared with the red-white zone (P=0.0322). CONCLUSIONS The conservative treatment of small and stable peripheral tears of the medial and lateral menisci had low failure rate and no described complications. In our series residual laxity significantly increased the failure rate. LEVEL OF EVIDENCE level IV, therapeutic case series.

Is it possible to preserve lumbar lordosis after hybrid stabilization? Preliminary results of a novel rigid-dynamic stabilization system in degenerative lumbar pathologies

AbstractPurpose of the studyTo evaluate the results of a novel rigid–dynamic stabilization technique in lumbar degenerative segment diseases (DSD), expressly pointing out the preservation of postoperative lumbar lordosis (LL).Materials and methods Forty-one patients with one level lumbar DSD and initial disc degeneration at the adjacent level were treated. Circumferential lumbar arthrodesis and posterior hybrid instrumentation were performed to preserve an initial disc degeneration above the segment that has to be fused. Clinical and spino-pelvic parameters were evaluated pre- and postoperatively.ResultsAt 2-year follow-up, a significant improvement of clinical outcomes was reported. No statistically significant difference was noted between postoperative and 2-year follow-up in LL and in disc/vertebral body height ratio at the upper adjacent fusion level.ConclusionsWhen properly selected, this technique leads to good results. A proper LL should be achieved after any hybrid stabilization to preserve the segment above the fusion.

Clinical Outcome of Arthroscopic Lateral Retinacular Release for Symptomatic Bipartite Patella in Athletes

PURPOSE To report the results of arthroscopic lateral retinacular release without excision of the accessory fragment for treatment of symptomatic bipartite patella with a minimum 2-year follow-up. METHODS We retrospectively reviewed all cases of symptomatic type III bipartite patella confirmed by radiographs, computed tomography, and magnetic resonance imaging and treated with arthroscopic lateral release from 2005 to 2015. Patients with history of knee fractures or surgery, concomitant meniscal or anterior cruciate ligament (ACL) procedures, and severe arthritic changes of the patellofemoral joint were excluded. Patients were assessed by Kujala score, visual analog scale (VAS), Tegner Activity Scale (TAS), and time to return to sporting activities. RESULTS Ten patients (11 knees) were clinically reassessed after 69.6 ± 33.3 (range: 25-132; 95% confidence interval [CI]: 47.29-91.99) months from surgery. There was a significant improvement in Kujala (P < .05) and VAS scores (P < .05), and no differences were found between pre- and postoperative TAS scores (P > .05). No complications occurred during the follow-up period. All patients returned to sport after 42.3 ± 11.3 (range: 30-60; 95% CI: 34.71-49.84) days after surgery. CONCLUSIONS The arthroscopic lateral retinacular release of a symptomatic type III bipartite patella without excision of the accessory fragment allowed early return to sporting activities, with excellent symptom relief. Patients had significantly improved mean Kujala and VAS scores without a decrease in the mean TAS scores. LEVEL OF EVIDENCE Level IV, case series.

What is the clinical evidence on regenerative medicine in intervertebral disc degeneration

PurposeThis review aims to explore and summarize the current clinical evidence about the use of regenerative medicine such as mesenchymal stem cells or platelet-rich plasma in intervertebral disc regeneration, in order to clarify the state of art of these novel approaches.Materials and methodsWe performed a research of the available literature about regenerative medicine strategies aiming to prevent intervertebral disc degeneration. All preclinical trials and in vitro studies were excluded. Only clinical trials were critically analysed.ResultsThe manuscript selection produced a total of 7 articles concerning the use of regenerative therapies in intervertebral disc degeneration, covering the period between 2010 and 2016. Articles selected were 4 about the injection of mesenchymal stem cells-related results and 3 using platelet-rich plasma. The total population of patients treated with regenerative medicine strategies were 104 patients.ConclusionsRegenerative medicine, such as the use of mesenchymal stem cells or platelet-rich plasma, in intradiscal disc degeneration has shown preclinical and clinical positive results. Randomized clinical trials studying the potential of MSCs intradiscal injection have not been conducted, and PRP effect has been studied only preliminarily. Additional more powered high-quality studies are needed to really appreciate the long-term safety and efficacy of regenerative medicine approaches in IDD.

Autologous US-guided PRP injection versus US-guided focal extracorporeal shock wave therapy for chronic lateral epicondylitis: A minimum of 2-year follow-up retrospective comparative study:

Purpose: To compare the efficacy of two independent groups of patients treated with ultrasound (US)-guided extracorporeal shock wave (ESW) therapy and with US-guided injection of platelet-rich plasma (PRP) for chronic lateral epicondylitis (LE) with a minimum of 2-year follow-up. Methods: We retrospectively evaluated 63 patients treated for chronic LE (31 patients with autologous US-guided PRP injection and 32 patients with US-guided focal ESW therapy) from 2009 to 2014. All the patients were evaluated by means of Roles–Maudsley (RM) score, quick Disabilities of Arm, Shoulder, and Hand (QuickDASH) score, visual analogic scale (VAS) and patient-rated tennis elbow evaluation (PRTEE) to retrospectively assess the pain relief, level of activity, the self-reported function and subjective satisfaction at minimum of 2-year follow-up. Results: Both US-guided autologous PRP injection and US-guided focal ESW administration proved effective in chronic LE with significant improvement in the QuickDASH, VAS, RM and PRTEE scores (p < 0.0001). No adverse effects or complications were recorded in any groups. No differences were found in recurrence rate and final results of the QuickDASH, VAS, RM and PRTEE scores between the two groups (p > 0.05). The mean time between treatment and symptom resolution was significantly shorter for the PRP treatment (p = 0.0212); furthermore, the mean time to return to the normal activities was quicker for PRP group (p = 0.0119). Conclusion: Both PRP injection and ESW therapy are feasible and safe options for the treatment of chronic LE with low risk of complications and with good long-term follow-up results. US-guided PRP injection has quick efficacy when compared with US-guided focal ESW therapy.

Vertebral body osteonecrosis: proposal of a treatment-oriented classification system

AbstractPurposeTo present a classification system for vertebral body osteonecrosis (VBON) based on imaging findings and sagittal alignment and consequently to propose treatment guidelines.MethodsChart review and classification of imaging and clinical findings. An analysis of literature about VBON has been evaluated to conceive the classification. The current data allows to correlate radiological findings with different stages of the pathophysiological process and consequently to propose a patient-tailored treatment plan.ResultsThe classification identifies 4 stages: stage 0 (theoretical phase), stage 1 (early phase), stage 2 (instability phase) and stage 3 (fixed deformity phase). Local (angular kyphosis expressed as anterior–posterior wall height ratio) and global (sagittal vertical axis and pelvic tilt) sagittal alignment are considered as complementary modifiers to tailor the most suitable treatment. Stage 1 is generally managed conservatively. Stage 2 and 3 often require different surgical approaches according to local and global sagittal alignment.ConclusionsThe classification allows a systematic staging of this disease and can help establish a proper and patient-oriented treatment plan. Further researches are advocated to fully validate the proposed classification system.Graphical abstract These slides can be retrieved under Electronic Supplementary Material.