Silvio Patella - Academia.edu (original) (raw)
Papers by Silvio Patella
The American Journal of Sports Medicine, 2013
Dear Editor: In the February 2013 issue of The American Journal of Sports Medicine, Patel et al p... more Dear Editor: In the February 2013 issue of The American Journal of Sports Medicine, Patel et al published a randomized trial (‘‘Treatment With Platelet-Rich Plasma Is More Effective Than Placebo for Knee Osteoarthritis’’) that showed the efficacy of platelet-rich plasma (PRP) over a placebo saline injection in the treatment of knees affected by osteoarthritis (OA), with no difference in the beneficial effect between 1 or 2 PRP injections. For this study, a total of 74 patients with bilateral OA were divided randomly into 3 groups, treated, and followed up to 6 months. Platelet-rich plasma relies on the use of autologous platelet-derived growth factors to favor tissue regeneration in tissues with a low healing potential; this is a fashionable topic with an increasing interest among researchers as well as clinicians and with a widespread clinical application that is however not supported by solid data on the real potential and indications of this biological approach. Only a few comparative studies are currently available on PRP and none with saline as a control. In this context, this article has the merit of being the first to show the superiority of platelet concentrate injections over placebo. However, there are some methodological aspects that have to be pointed out. First of all, the authors performed a power analysis based on a visual analog scale for pain, while they used the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score as a primary outcome; the WOMAC has a much higher standard deviation that would have required a much higher sample size. The number of patients is clearly low to compare 3 groups (26, 25, and 23 patients, respectively). This is also due to an unusually large effect size driven by the choice to have the predicted difference equal to the standard deviation. Bhandari et al have produced a compelling argument that, despite what a power analysis may show, at least 100 patients are required, and a similar study on blood derivatives with 3 arms showed that more than 300 patients were appropriate. Thus, while the comparison with saline could still be acceptable because it found a statistical significance even in such small groups, the results of the comparison of the 2 treatment groups are questionable. This is not the only limitation in the statistical analysis. The authors evaluated patients with bilateral knee OA; therefore, the questionnaires used cannot independently score both knees of 1 patient because the results of 1 knee might affect the contralateral knee. This would require a proper statistical evaluation, and a test with ‘‘correction for patient’’ such as a general linear model with the patient as a random effect should be used. Another statistical limitation is that the post hoc Kruskal-Wallis (MannWhitney) test should be corrected for multiple comparisons (such as Sidak or Bonferroni). Also, patients affected by bilateral OA have often different degrees of OA in their knees, different levels of pain and function, and different responses to treatment, which might be confounded in the general functional scores applied. Moreover, some important patient characteristics appear not to be significantly different among the small study groups, but the fact that they are not significantly heterogeneous does not mean that they are homogeneous. Thus, the different percentages of higher degrees of OA (more in the saline group: 46% vs 26% and 25%, respectively), as well as the different numbers in women (more in the 2-injection and saline groups vs the 1-injection group: 80%, 74%, and 59%, respectively), who are characterized by lower scores than men even in healthy conditions and might therefore influence the mean score obtained, might be important biases in the comparison of such small groups. Furthermore, 2 failed knees were not considered in the final evaluation of the group of 1 PRP injection because the patient underwent knee prosthesis. This is methodologically wrong because failed patients have to be considered up to the final evaluation, reporting the last value before undergoing reoperation: they do not have to be excluded; otherwise, the mean score results in an artificial increase. Other aspects are questionable: the design of the randomization is not fully clear. The authors declare that their study is a double-blind trial, but they should specify how they kept the group of patients with 2 injections blinded. It is of interest to notice that, if the 2-injection group was not blinded and the 1-injection group was blinded, the same results obtained by the 2 PRP groups demonstrate that there is no placebo effect at all in patients knowing they are undergoing a ‘‘new growth factors–based promising regenerative treatment,’’ which actually we saw, in our experience, to play a major role in the results observed. This is also in contrast with a recent meta-analysis on patients with OA that found that a placebo group presents The American Journal of Sports…
ISOKINETIC XX Congresso Internazionale di Riab. Sport. e Traumat. "La salute del calciatore"., 2011
icrs 2012, 2012
INTRODUCTION The menisci play a fundamental biomechanical role in the knee and also help in the m... more INTRODUCTION The menisci play a fundamental biomechanical role in the knee and also help in the maintaining of the articular homeostasis; thus, either a lesion or the complete absence of the menisci can invalidate the physiological function of the knee causing important damages, even at long term. Unfortunately, meniscal tears are often found during the ordinary orthopaedic practice while the regenerative potential of this kind of tissue is very low and limited to its peripheral-vascularized part; this is why the majority of these common arthroscopic findings are not reparable and often the surgeon is almost forced to perform a partial, subtotal or even total meniscectomy, regardless of the well-known consequences of this kind of surgery. MATERIALS AND METHODS Recently a porous, biodegradable scaffold made of an aliphatic polyurethane (Actifit(tm),Orteq Ltd) has been developed for the arthroscopic treatment of partial and irreparable meniscal tears; thanks to its particular structure, this scaffold facilitates the regeneration of the removed meniscal part, preventing the potential cartilage damage due to its complete or partial lack. We performed a prospective clinical study on 17 patients affected by a massive loss of meniscal substance either medial or lateral associated with intraarticular or global knee pain and/or swelling. We analyzed the patient both clinically and by using the International Knee Document Committee9s (IKDC) Subjective and Objective Knee Evaluation Form. We also assessed the sport activity resumption by comparing the Tegner score at the time of the very first visit with the presurgery and prelesional ones. Finally, we also organized a control MRI at 6 and 12 months after surgery. DISCUSSION Our preliminary results are encouraging and they confirm the clinical experiences of other study groups. Apparently, the properties of this scaffold help in vessels formation and tissue regeneration potentially allowing the restoration of the surgically removed portion and preventing, or delaying at least, both chondral and articular degeneration. We also performed some biopsy associated arthroscopic “second-looks” that reinforced the already good clinical results; the biopsies also confirmed the new tissue ingrowth into the biomaterial, potentially leading to the replacement of the previously removed damaged tissue. CONCLUSIONS Preliminary results suggest that this surgical procedure can be considered a really promising method for the treatment of both inveterate and symptomatic meniscal tears; however, other randomized studies with a longer follow-up should be done to confirm its reliability and potentialities.
L'incidenza delle patologie della cartilagine articolare \ue8 in aumento a causa dlel'inc... more L'incidenza delle patologie della cartilagine articolare \ue8 in aumento a causa dlel'incremento di attivit\ue0 sportib\uecve ed all'enfasi rivolta all'attivit\ue0 fisica ad ogni et\ue0
CLINICAL CASES IN MINERAL AND BONE METABOLISM, 2009
Osteoporotic fractures represent one of the most common cause of disability and one of the major ... more Osteoporotic fractures represent one of the most common cause of disability and one of the major voice in the health economic budget in many countries of the world. Fragility fractures are especially meta-epiphyseal fractures, in skeletal sites with particular biomechanic characteristic (hip, vertebrae), complex and with more fragments, with slow healing process (mineralization and remodeling) and co-morbidity. The healing of a fracture in osteoporotic bone passes through the normal stages and concludes with union of the fracture although the healing process is prolonged. Fractures in the elderly osteoporotic patients represent a challenge to the orthopaedic surgeons. Osteoporosis does not only increase the risk of fracture but also represents a problem in osteofixation of fractures in fracture treatment. The major technical problem that surgeons face, is the difficulty to obtain a stable fixation of an implant due to osteoporotic bone. The load transmitted at the bone-implant inter...
Summary It has been at least two decades since the introduction of Extracorporeal Shock-Wave Trea... more Summary It has been at least two decades since the introduction of Extracorporeal Shock-Wave Treatment (ESWT) for the treatment of non-unions; despite conflicting opinions in the literature, it is recently achieving good results also in acute fractures. This paper reports Authors’ clinical experience with electromagnetic shock-waves in the treatment of delayed unions and fresh fractures. Nonunion cases experienced remarkable successful results at an average of 8-10 weeks after ESWT; high success rate is been also found for the acute fractures. It can be concluded that this therapy constitutes an important aid in treatment of non-unions and can be useful also in fresh bone fractures.
The osteoclastogenesis is regulated by a complex signaling system between the pro-apoptotic facto... more The osteoclastogenesis is regulated by a complex signaling system between the pro-apoptotic factors (Bax-Cyclin E2-Cdk2) and the tumor necrosis factor family (RANKL-RANK-OPG). Extracorporeal Shock Waves Therapy (ESWT) have recently been used in orthopaedic treatments to induce bone repair, but their mechanisms of action are not sufficiently investigated. So we studied the effect of shock-waves on murine osteoblastic cells. Osteoblast cultures were subjected to a single shock-wave with combinations of low energy intensities (0.05mJ/mm2) and 500 number of shocks (impulses), whereas control cells received no treatment. We valued the cell viability quantifying the expressions of Bax and Opg by PCR. We found an immediate negative effect on cell viability, that occurs with an increase of Bax protein expression after 3 hours of treatment. After a longer time lapse a stimulatory effect on cell proliferation, as reflected by the increase of a G(1)-S phase marker, was observed. In fact, in th...
The American Journal of Sports Medicine, 2013
Dear Editor: In the February 2013 issue of The American Journal of Sports Medicine, Patel et al p... more Dear Editor: In the February 2013 issue of The American Journal of Sports Medicine, Patel et al published a randomized trial (‘‘Treatment With Platelet-Rich Plasma Is More Effective Than Placebo for Knee Osteoarthritis’’) that showed the efficacy of platelet-rich plasma (PRP) over a placebo saline injection in the treatment of knees affected by osteoarthritis (OA), with no difference in the beneficial effect between 1 or 2 PRP injections. For this study, a total of 74 patients with bilateral OA were divided randomly into 3 groups, treated, and followed up to 6 months. Platelet-rich plasma relies on the use of autologous platelet-derived growth factors to favor tissue regeneration in tissues with a low healing potential; this is a fashionable topic with an increasing interest among researchers as well as clinicians and with a widespread clinical application that is however not supported by solid data on the real potential and indications of this biological approach. Only a few comparative studies are currently available on PRP and none with saline as a control. In this context, this article has the merit of being the first to show the superiority of platelet concentrate injections over placebo. However, there are some methodological aspects that have to be pointed out. First of all, the authors performed a power analysis based on a visual analog scale for pain, while they used the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score as a primary outcome; the WOMAC has a much higher standard deviation that would have required a much higher sample size. The number of patients is clearly low to compare 3 groups (26, 25, and 23 patients, respectively). This is also due to an unusually large effect size driven by the choice to have the predicted difference equal to the standard deviation. Bhandari et al have produced a compelling argument that, despite what a power analysis may show, at least 100 patients are required, and a similar study on blood derivatives with 3 arms showed that more than 300 patients were appropriate. Thus, while the comparison with saline could still be acceptable because it found a statistical significance even in such small groups, the results of the comparison of the 2 treatment groups are questionable. This is not the only limitation in the statistical analysis. The authors evaluated patients with bilateral knee OA; therefore, the questionnaires used cannot independently score both knees of 1 patient because the results of 1 knee might affect the contralateral knee. This would require a proper statistical evaluation, and a test with ‘‘correction for patient’’ such as a general linear model with the patient as a random effect should be used. Another statistical limitation is that the post hoc Kruskal-Wallis (MannWhitney) test should be corrected for multiple comparisons (such as Sidak or Bonferroni). Also, patients affected by bilateral OA have often different degrees of OA in their knees, different levels of pain and function, and different responses to treatment, which might be confounded in the general functional scores applied. Moreover, some important patient characteristics appear not to be significantly different among the small study groups, but the fact that they are not significantly heterogeneous does not mean that they are homogeneous. Thus, the different percentages of higher degrees of OA (more in the saline group: 46% vs 26% and 25%, respectively), as well as the different numbers in women (more in the 2-injection and saline groups vs the 1-injection group: 80%, 74%, and 59%, respectively), who are characterized by lower scores than men even in healthy conditions and might therefore influence the mean score obtained, might be important biases in the comparison of such small groups. Furthermore, 2 failed knees were not considered in the final evaluation of the group of 1 PRP injection because the patient underwent knee prosthesis. This is methodologically wrong because failed patients have to be considered up to the final evaluation, reporting the last value before undergoing reoperation: they do not have to be excluded; otherwise, the mean score results in an artificial increase. Other aspects are questionable: the design of the randomization is not fully clear. The authors declare that their study is a double-blind trial, but they should specify how they kept the group of patients with 2 injections blinded. It is of interest to notice that, if the 2-injection group was not blinded and the 1-injection group was blinded, the same results obtained by the 2 PRP groups demonstrate that there is no placebo effect at all in patients knowing they are undergoing a ‘‘new growth factors–based promising regenerative treatment,’’ which actually we saw, in our experience, to play a major role in the results observed. This is also in contrast with a recent meta-analysis on patients with OA that found that a placebo group presents The American Journal of Sports…
ISOKINETIC XX Congresso Internazionale di Riab. Sport. e Traumat. "La salute del calciatore"., 2011
icrs 2012, 2012
INTRODUCTION The menisci play a fundamental biomechanical role in the knee and also help in the m... more INTRODUCTION The menisci play a fundamental biomechanical role in the knee and also help in the maintaining of the articular homeostasis; thus, either a lesion or the complete absence of the menisci can invalidate the physiological function of the knee causing important damages, even at long term. Unfortunately, meniscal tears are often found during the ordinary orthopaedic practice while the regenerative potential of this kind of tissue is very low and limited to its peripheral-vascularized part; this is why the majority of these common arthroscopic findings are not reparable and often the surgeon is almost forced to perform a partial, subtotal or even total meniscectomy, regardless of the well-known consequences of this kind of surgery. MATERIALS AND METHODS Recently a porous, biodegradable scaffold made of an aliphatic polyurethane (Actifit(tm),Orteq Ltd) has been developed for the arthroscopic treatment of partial and irreparable meniscal tears; thanks to its particular structure, this scaffold facilitates the regeneration of the removed meniscal part, preventing the potential cartilage damage due to its complete or partial lack. We performed a prospective clinical study on 17 patients affected by a massive loss of meniscal substance either medial or lateral associated with intraarticular or global knee pain and/or swelling. We analyzed the patient both clinically and by using the International Knee Document Committee9s (IKDC) Subjective and Objective Knee Evaluation Form. We also assessed the sport activity resumption by comparing the Tegner score at the time of the very first visit with the presurgery and prelesional ones. Finally, we also organized a control MRI at 6 and 12 months after surgery. DISCUSSION Our preliminary results are encouraging and they confirm the clinical experiences of other study groups. Apparently, the properties of this scaffold help in vessels formation and tissue regeneration potentially allowing the restoration of the surgically removed portion and preventing, or delaying at least, both chondral and articular degeneration. We also performed some biopsy associated arthroscopic “second-looks” that reinforced the already good clinical results; the biopsies also confirmed the new tissue ingrowth into the biomaterial, potentially leading to the replacement of the previously removed damaged tissue. CONCLUSIONS Preliminary results suggest that this surgical procedure can be considered a really promising method for the treatment of both inveterate and symptomatic meniscal tears; however, other randomized studies with a longer follow-up should be done to confirm its reliability and potentialities.
L'incidenza delle patologie della cartilagine articolare \ue8 in aumento a causa dlel'inc... more L'incidenza delle patologie della cartilagine articolare \ue8 in aumento a causa dlel'incremento di attivit\ue0 sportib\uecve ed all'enfasi rivolta all'attivit\ue0 fisica ad ogni et\ue0
CLINICAL CASES IN MINERAL AND BONE METABOLISM, 2009
Osteoporotic fractures represent one of the most common cause of disability and one of the major ... more Osteoporotic fractures represent one of the most common cause of disability and one of the major voice in the health economic budget in many countries of the world. Fragility fractures are especially meta-epiphyseal fractures, in skeletal sites with particular biomechanic characteristic (hip, vertebrae), complex and with more fragments, with slow healing process (mineralization and remodeling) and co-morbidity. The healing of a fracture in osteoporotic bone passes through the normal stages and concludes with union of the fracture although the healing process is prolonged. Fractures in the elderly osteoporotic patients represent a challenge to the orthopaedic surgeons. Osteoporosis does not only increase the risk of fracture but also represents a problem in osteofixation of fractures in fracture treatment. The major technical problem that surgeons face, is the difficulty to obtain a stable fixation of an implant due to osteoporotic bone. The load transmitted at the bone-implant inter...
Summary It has been at least two decades since the introduction of Extracorporeal Shock-Wave Trea... more Summary It has been at least two decades since the introduction of Extracorporeal Shock-Wave Treatment (ESWT) for the treatment of non-unions; despite conflicting opinions in the literature, it is recently achieving good results also in acute fractures. This paper reports Authors’ clinical experience with electromagnetic shock-waves in the treatment of delayed unions and fresh fractures. Nonunion cases experienced remarkable successful results at an average of 8-10 weeks after ESWT; high success rate is been also found for the acute fractures. It can be concluded that this therapy constitutes an important aid in treatment of non-unions and can be useful also in fresh bone fractures.
The osteoclastogenesis is regulated by a complex signaling system between the pro-apoptotic facto... more The osteoclastogenesis is regulated by a complex signaling system between the pro-apoptotic factors (Bax-Cyclin E2-Cdk2) and the tumor necrosis factor family (RANKL-RANK-OPG). Extracorporeal Shock Waves Therapy (ESWT) have recently been used in orthopaedic treatments to induce bone repair, but their mechanisms of action are not sufficiently investigated. So we studied the effect of shock-waves on murine osteoblastic cells. Osteoblast cultures were subjected to a single shock-wave with combinations of low energy intensities (0.05mJ/mm2) and 500 number of shocks (impulses), whereas control cells received no treatment. We valued the cell viability quantifying the expressions of Bax and Opg by PCR. We found an immediate negative effect on cell viability, that occurs with an increase of Bax protein expression after 3 hours of treatment. After a longer time lapse a stimulatory effect on cell proliferation, as reflected by the increase of a G(1)-S phase marker, was observed. In fact, in th...