Showing papers by "Nicola Maffulli published in 2021"
TL;DR: In this paper, small interfering RNAs (siRNAs), acting on gene regulation, can therefore participate in the process of tendon healing and are useful to study reparative processes of tendons and identify possible therapeutic targets in tendon healing.
Abstract: Background Tenogenesis and tendon homeostasis are guided by genes encoding for the structural molecules of tendon fibres. Small interfering RNAs (siRNAs), acting on gene regulation, can therefore participate in the process of tendon healing. Sources of data A systematic search of different databases to October 2020 identified 17 suitable studies. Areas of agreement SiRNAs can be useful to study reparative processes of tendons and identify possible therapeutic targets in tendon healing. Areas of controversy Many genes and growth factors involved in the processes of tendinopathy and tendon healing can be regulated by siRNAs. It is however unclear which gene silencing determines the expected effect. Growing points Gene dysregulation of growth factors and tendon structural proteins can be influenced by siRNA. Areas timely for developing research It is not clear whether there is a direct action of the siRNAs that can be used to facilitate the repair processes of tendons.
55 citations
TL;DR: In this paper, the role of human leukocyte antigens (HLA) genotypes on individual responses to SARS-CoV-2 infection and/or progression is discussed.
Abstract: The COVID-19 pandemic has markedly impacted on cultural, political, and economic structures all over the world. Several aspects of its pathogenesis and related clinical consequences have not yet been elucidated. Infection rates, as well morbidity and mortality differed within countries. It is intriguing for scientists to understand how patient genetics may influence the outcome of the condition, to clarify which aspects could be related the clinical variability of SARS-CoV-2 disease. We reviewed the studies exploring the role of human leukocyte antigens (HLA) genotypes on individual responses to SARS-CoV-2 infection and/or progression, discussing also the contribution of the immunological patterns MHC-related. In March 2021, the main online databases were accessed. All the articles that investigated the possible association between the HLA genotypes and related polymorphisms with susceptibility, severity and progression of COVID-19 were considered. Although both genetic and environmental factors are certainly expected to influence the susceptibility to or protection of individuals, the HLA and related polymorphisms can influence susceptibility, progression and severity of SARS-CoV-2 infection. The crucial role played by HLA molecules in the immune response, especially through pathogen-derived peptide presentation, and the huge molecular variability of HLA alleles in the human populations could be responsible for the different rates of infection and the different patients following COVID-19 infection.
49 citations
TL;DR: Universities and hospitals have not only reduced the impact on the learning process of resident and students but also turn this pandemic into a moment of personal and professional growth for the new generation of healthcare professionals.
Abstract: Background The covid-19 pandemic has dramatically changed lives of residents and medical students. In particular, the learning process has undergone widely changes, especially due to the rules of social distancing which have forced universities and various institutes to modify lessons, work shifts and internships. Purpose The purpose of our review is to evaluate how the various institutes have faced the covid-19 emergency and guaranteed the perpetuation of the learning process of resident and students. Methods A comprehensive search of the medical literature in PubMed and Google Scholar was performed including all the works explaining how the institutes have reorganized teaching for resident and undergraduate students. Main findings The use of internet for the dissemination of teaching material and educational meetings has built bridges, albeit virtual, between resident and teachers. New techniques for teaching and conducting exams have been introduced. The rotating team system allowed the continuation of the teaching activity in safety. Conclusion Thanks to remodulation of the teach modalities, the massive use of internet platforms, a wise distribution of work shifts, and others, universities and hospitals have not only reduced the impact on the learning process of resident and students but also turn this pandemic into a moment of personal and professional growth for the new generation of healthcare professionals.
44 citations
TL;DR: In this article, the authors investigated the current reconstructive strategies for large bone defect after trauma, infections, or tumour excision, discussed advantages and disadvantages of each technique, debated available techniques and materials, and evaluated complications and new perspectives.
Abstract: Large bone defects resulting from musculoskeletal tumours, infections, or trauma are often unable to heal spontaneously. The challenge for surgeons is to avoid amputation, and provide the best functional outcomes. Allograft, vascularized fibular or iliac graft, hybrid graft, extracorporeal devitalized autograft, distraction osteogenesis, induced-membrane technique, and segmental prostheses are the most common surgical strategies to manage large bone defects. Given its optimal osteogenesis, osteoinduction, osteoconduction, and histocompatibility properties, along with the lower the risk of immunological rejection, autologous graft represents the most common used strategy for reconstruction of bone defects. However, the choice of the best surgical technique is still debated, and no consensus has been reached. The present study investigated the current reconstructive strategies for large bone defect after trauma, infections, or tumour excision, discussed advantages and disadvantages of each technique, debated available techniques and materials, and evaluated complications and new perspectives.
33 citations
TL;DR: In this article, a Bayesian network meta-analysis compared the effects of current anti-osteoporosis drugs on bone mineral density (BMD) in postmenopausal women.
Abstract: Background Osteoporosis affects mostly postmenopausal women, leading to deterioration of the microarchitectural bone structure and low bone mass, with an increased fracture risk with associated disability, morbidity and mortality. This Bayesian network meta-analysis compared the effects of current anti-osteoporosis drugs on bone mineral density. Methods The present systematic review and network meta-analysis follows the PRISMA extension statement to report systematic reviews incorporating network meta-analyses of health care interventions. The literature search was performed in June 2021. All randomised clinical trials that have investigated the effects of two or more drug treatments on BMD for postmenopausal osteoporosis were accessed. The network comparisons were performed through the STATA Software/MP routine for Bayesian hierarchical random-effects model analysis. The inverse variance method with standardised mean difference (SMD) was used for analysis. Results Data from 64 RCTs involving 82,732 patients were retrieved. The mean follow-up was 29.7 ± 19.6 months. Denosumab resulted in a higher spine BMD (SMD -0.220; SE 3.379), followed by pamidronate (SMD -5.662; SE 2.635) and zoledronate (SMD -10.701; SE 2.871). Denosumab resulted in a higher hip BMD (SMD -0.256; SE 3.184), followed by alendronate (SMD -17.032; SE 3.191) and ibandronate (SMD -17.250; SE 2.264). Denosumab resulted in a higher femur BMD (SMD 0.097; SE 2.091), followed by alendronate (SMD -16.030; SE 1.702) and ibandronate (SMD -17.000; SE 1.679). Conclusion Denosumab results in higher spine BMD in selected women with postmenopausal osteoporosis. Denosumab had the highest influence on hip and femur BMD. Level of evidence Level I, Bayesian network meta-analysis of RCTs.
32 citations
TL;DR: There is no evidence that adding a lateral release impacts positively on the outcome of MPFL reconstruction, and the role of the lateral retinaculum in patellofemoral instability is still debated.
Abstract: The role of the lateral retinaculum in patellofemoral instability is still debated. Lateral retinacular release (LRR), has been extensively performed in combination with different surgical procedures, including reconstruction of medio-patellofemoral ligament (MPFL). Despite controversial indications, the results from these studies seem promising. The present study conducts a systematic review about current biomechanical and clinical evidence concerning the role of LRR in combination with MPFL reconstruction. We performed a comprehensive literature research, comparing the outcomes of MPFL reconstruction with and without LRR. This systematic review was conducted according to the PRISMA guidelines. The literature search was performed in August 2020. All articles describing the outcome of isolated MPFL reconstruction alone or in combination with a LRR in patients with recurrent patellofemoral instability were considered for inclusion. Only articles reporting data on patients with a minimum of 12-month follow-up were included. Only articles reporting quantitative data under the outcomes of interest were included. A total of 63 articles were eligible for this systematic review, including 2131 knees. The mean follow-up was 40.87 ± 24.1 months. All scores of interests improved in favour of the combined group: Kujala + 3.8% (P = 0.01), Lysholm + 4.2% (P = 0.004), Tegner + 0.8 points (P = 0.04), IKDC + 9.8% (P = 0.02). The ROM was comparable between the two groups (P = 0.4). Similarity was found in terms of positivity to the apprehension test (P = 0.05), rate of complications (P = 0.1), re-dislocations (P = 0.8), and revision surgeries (P = 0.1). There is no evidence that adding a lateral release impacts positively on the outcome of MPFL reconstruction. Level of evidence: IV, Systematic review
31 citations
TL;DR: In this paper, a 3D biomimetic environment with the capacity to direct stem cell commitment towards a chondrogenic phenotype was used for cartilage repair and regeneration, where a collagen matrix was functionalized with the addition of poly-lactic-co-glycolic acid microcarriers (PLGA-MCs) carrying a human TFG-β1 payload.
Abstract: Tissue engineering strategies can be relevant for cartilage repair and regeneration. A collagen matrix was functionalized with the addition of poly-lactic-co-glycolic acid microcarriers (PLGA-MCs) carrying a human Transforming Growth Factor β1 (hTFG-β1) payload, to provide a 3D biomimetic environment with the capacity to direct stem cell commitment towards a chondrogenic phenotype. PLGA-MCs (mean size 3 ± 0.9 μm) were prepared via supercritical emulsion extraction technology and tailored to sustain delivery of payload into the collagen hydrogel for 21 days. PLGA-MCs were coseeded with human Bone Marrow Mesenchymal Stem Cells (hBM-MSCs) in the collagen matrix. Chondrogenic induction was suggested when dynamic perfusion was applied as indicated by transcriptional upregulation of COL2A1 gene (5-fold; p < 0.01) and downregulation of COL1A1 (0.07-fold; p < 0.05) and COL3A1 (0.11-fold; p < 0.05) genes, at day 16, as monitored by qRT-PCR. Histological and quantitative-immunofluorescence (qIF) analysis confirmed cell activity by remodeling the synthetic extracellular matrix when cultured in perfused conditions. Static constructs lacked evidence of chondrogenic specific gene overexpression, which was probably due to a reduced mass exchange, as determined by 3D system Finite Element Modelling (FEM) analysis. Proinflammatory (IL-6, TNF, IL-12A, IL-1β) and anti-inflammatory (IL-10, TGF-β1) cytokine gene expression by hBM-MSC was observed only in dynamic culture (TNF and IL-1β 10-fold, p < 0.001; TGF-β1 4-fold, p < 0.01 at Day 16) confirming the cells' immunomodulatory activity mainly in relation to their commitment and not due to the synthetic environment. This study supports the use of 3D hydrogel scaffolds, equipped for growth factor controlled delivery, as tissue engineered models for the study of in vitro chondrogenic differentiation and opens clinical perspectives for injectable collagen-based advanced therapy systems.
28 citations
TL;DR: In this paper, the success of traditional management, including isometric or eccentric exercises combined with shockwave therapy and even surgery, is limited, and therefore, the authors propose a new approach for knee tendinopathy management.
Abstract: Background:Patellar tendinopathy is common. The success of traditional management, including isometric or eccentric exercises combined with shockwave therapy and even surgery, is limited. Therefore...
27 citations
TL;DR: Denosumab resulted in most effective, particularly in reducing the occurrence of non-vertebral fractures, while Romosozumab and Ibandronate resulted best to prevent, respectively, vertebral fractures and hip fractures.
Abstract: Objectives: Postmenopausal osteoporosis carries a high risk of fractures, which decrease quality of life and are associated with high morbidity, mortality, and economic burden. The best pharmacolog...
25 citations
TL;DR: Microencapsulation of two human growth factors exhibited extremely low cytotoxicity when evaluated in Chinese Hamster Ovary cells, and low reactivity on human peripheral blood mononuclear cells (hPBMCs), suggesting their safety and potential use in tissue engineering protocols.
23 citations
TL;DR: In this article, platelet-rich plasma (PRP) and other novel blood-derived products developed specifically for osteoarthritis (OA) can provide pain relief and potential benefits in disease progression.
Abstract: Intra-articular injections of platelet-rich plasma (PRP) and other novel blood-derived products developed specifically for osteoarthritis (OA) can provide pain relief and potential benefits in disease progression Meta-analyses show the clinical superiority of PRP compared with other intra-articular injections, but results are modest and the effect sizes are small PRP injections in knee OA are performed indiscriminately, but the clinical response varies enormously between patients because of an array of mixed OA phenotypes Subgroup analyses are scarce; some studies stratify patients according to radiographic severity and found better results in early OA, without consensus for more advanced stages of the condition Parallel identification of soluble and imaging biomarkers is essential to personalise and leverage PRP therapies The inflammatory phenotype is most interesting from the PRP perspective because PRPs modulate inflammation by releasing a large pool of chemokines and cytokines, which interact with synovial fibroblasts and macrophages; in addition, they can modulate the innate immune response No soluble biomarkers have been discovered that have implications for OA research and PRP interventions Clinical examination of patients based on their inflammatory phenotype and imaging identification of pain sources and structural alterations could help discern who will respond to PRP Synovial inflammation and bone marrow lesions are sources of pain, and intra-articular injections of PRP combined with subchondral bone injection can enhance clinical outcomes Further refining ultrasound phenotypes may aid in personalising PRP therapies Intra-articular delivery combined with injections in altered ligamentous structures, medial and coronal ligaments or premeniscal pes anserinus showed positive clinical outcomes Although the evidence supporting these approaches are weak, they merit further consideration to refine PRP protocols and target the right OA phenotypes
TL;DR: The present study shows that the potential differences in clinical outcomes between ATFL remnant repair and non-repair are likely not relevant when performing an all-inside arthroscopic Broström-Gould procedure for CLAI.
Abstract: The Brostrom-Gould procedure, with the repair of the anterior talofibular ligament (ATFL) combined with the transfer of the extensor retinaculum, is considered the gold standard procedure for the management of chronic lateral ankle instability (CLAI). Lateral ligament reconstruction is considered if the ATFL remnant quality is poor or the ATFL has been damaged beyond the ability to suture it. It remains unclear whether not repairing the ATFL remnant produces comparable functional outcomes to the classical Brostrom-Gould procedure. This retrospective cohort study included 84 patients with CLAI undergoing either repair or non-repair of the ATFL remnant using an all-inside arthroscopic Brostrom-Gould procedure from 2015 to 2018. The Visual Analogue Scale (VAS) scores, American Orthopedic Foot and Ankle Society (AOFAS) scores, Karlsson Ankle Functional Score (KAFS), Anterior Talar Translation (ATT), Active Joint Position Sense (AJPS), and the rate of return to sports were compared in both groups. All the functional scores (VAS, AOFAS, KAFS, ATT, AJPS) significantly improved in both groups at 1 and 2 years after surgery. At all the follow-up time points, the VAS, AOFAS, KAFS, ATT, AJPS, and the rate of return to sport scores were comparable between the repair and non-repair group. There are no statistically significant differences in postoperative outcomes between ATFL remnant repair and non-repair for the management of CLAI using the all-inside arthroscopic Brostrom-Gould procedure. From the clinical viewpoint, the present study shows that the potential differences in clinical outcomes between ATFL remnant repair and non-repair are likely not relevant when performing an all-inside arthroscopic Brostrom-Gould procedure for CLAI. III.
TL;DR: In patients with femoral head osteonecrosis, core decompression combined with BMCTs demonstrated reduced pain and lower rate of total hip arthroplasty compared to core decompressed as an isolated procedure.
Abstract: Objectives: The regenerative capabilities of bone marrow-derived cell therapies (BMCTs) have been employed in combination with core decompression (CD) in the management of osteonecrosis of the femo...
TL;DR: In this paper, the authors compared primary isolated AMIC versus microfracture (MFx) for focal unipolar chondral defects of the patellar facet joints at midterm follow-up.
Abstract: Introduction: Evidence on the management of chondral defects of the patella arises from studies in which the patellofemoral joint was treated together with the femorotibial joint and primary and revision settings. Furthermore, the superiority of Autologous Matrix Induced Chondrogenesis (AMIC) over microfractures (MFx) for patellar chondral defects is uncertain. Therefore, the present study compared primary isolated AMIC versus MFx for focal unipolar chondral defects of the patellar facet joints at midterm follow-up. Methods: Patients undergoing AMIC or isolated MFx surgery for borderline-sized focal unipolar chondral defects of the patellar facet joints were followed at our institution. All surgeries were performed in the same fashion by experienced surgeons. A parapatellar arthrotomy was adopted in all surgeries. The outcomes of interest were: Visual Analogic Scale (VAS), Tegner Activity Scale, International Knee Documentation Committee (IKDC), and the Lysholm scores. The Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) was assessed by a blinded radiologist, who had not been involved in the clinical management of the patients. Results: 38 patients were enrolled in the present study: 27 underwent AMIC, and 11 MFx. The mean follow-up was 45.1 months. The mean age of the patients at baseline was 34.5 years. The mean size of the defect was 2.6 cm2. The MFx cohort experienced a shorter length of the hospitalization (P = 0.008). There was no difference in terms of follow-up and previous symptoms duration, mean age, sex, side, defect size, and BMI. At last follow-up, the AMIC cohort reported greater IKDC (P = 0.01), Lysholm (P = 0.009), and Tegner (P = 0.02), along with a low rate of failure (P = 0.02). VAS was lower in the AMIC group (P = 0.002). No difference was found in the MOCART score (P = 0.09), rates of revision (P = 0.06), and arthroplasty (P = 0.2). Conclusion: The AMIC procedure achieves greater IKDC and Lysholm score, and a significant reduction of the VAS score in the management of patellar chondral defects. The Tegner scale demonstrated greater activity after AMIC procedure. Finally, the AMIC group evidenced a lower rate of failure. Similarity was found on MOCART score, rates of revision, and arthroplasty between the two procedures.
TL;DR: In this paper, the results after isolated MPFL reconstruction in patients with patellofemoral instability were analyzed, and a subgroup analysis of patients presenting pathoanatomical risk factors was made.
Abstract: The medial patellofemoral ligament (MPFL) is always damaged after patellar dislocation. In selected patients, MPFL reconstruction is necessary to restore a correct patellar tracking. Despite the large number of different techniques reported to reconstruct the MPFL, there is no consensus concerning the optimal procedure, and debates is still ongoing. The present study analysed the results after isolated MPFL reconstruction in patients with patellofemoral instability. Furthermore, a subgroup analysis of patients presenting pathoanatomical risk factors was made. In November 2020, the main electronic databases were accessed. All articles reporting the results of primary isolated MPFL reconstruction for recurrent patellofemoral instability were considered for inclusion. Only articles reporting a minimum 12-month follow-up were eligible. Data from a total of 1777 knees were collected. The mean age of the patients involved was 22.8 ± 3.4 years. The mean follow-up was 40.7 ± 25.8 months. Overall, the range of motion (+ 27.74; P < 0.0001) and all the other scores of interests improved at last follow-up: Kujala (+ 12.76; P = 0.0003), Lysholm (+ 15.69; P < 0.0001), Tegner score (+ 2.86; P = 0.006). Seventy-three of 1780 patients (4.1%) showed a positive apprehension test. Thirty of 1765 patients (1.7%) experienced re-dislocations, while 56 of 1778 patients (3.2%) showed persisting joint instability. Twenty-five of 1786 patients (1.4%) underwent revision surgeries. Isolated MPFL reconstruction for recurrent patellofemoral instability provides reliable surgical outcomes. Patients with pathoanatomical predisposing factors reported worse surgical outcomes.
TL;DR: Only baclofen, duloxetine, NSAIDs, and opiates showed to improve pain and disability levels in patients with LBP, but the patients’ demographics are heterogeneous, and the results must be interpreted with caution and in the light of possible adverse events connected to the use of these drugs.
Abstract: Treating chronic low back pain (LBP) can be challenging, and the most effective pharmacological therapy is controversial. The present systematic review investigated the efficacy of various pharmaco...
TL;DR: The present Bayesian network meta-analysis encourages the use of celecoxib as a prophylaxis for HO after total hip arthroplasty and detects no statistically significant inconsistency in all the comparisons.
Abstract: Non-steroidal anti-inflammatory drugs (NSAID) have been recommended to prevent of heterotopic ossification (HO) after total hip arthroplasty (THA), but debates are still ongoing. The present Bayesian network meta-analysis of randomized clinical trials (RCTs) compared all available pathways of NSAID treatment as prophylaxis for HO after THA. The present Bayesian network meta-analysis was conducted according to The PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions guidelines. All randomized clinical trials comparing two or more interventions to prevent HO after THA were considered for analysis. HO was classified according to Brooker. The quality of the methodological assessment was performed through the risk of bias summary tool of the Review Manager Software 5.3 (The Cochrane Collaboration, Copenhagen). The network meta-analysis was performed through a STATA routine for Bayesian hierarchical random-effects model analysis, with log odd ratio (LOR) effect measure. Data from 26 studies (6396 THAs; 58% females) were collected. The mean follow-up was 10.50 ± 5.7 months. ANOVA showed good comparability among mean age and gender (P > 0.5). Celecoxib demonstrated the highest rate of Brooker class 0 (LOR 6.96), followed by diclofenac (LOR 6.94). Naproxen demonstrated the lowest rate of Brooker I HO (LOR 2.82), followed by celecoxib (LOR 3.52). Celecoxib demonstrated lowest rate of Brooker class II HO (LOR 1.66), class III (LOR), and class IV (LOR 0.25). The equation for global linearity detected no statistically significant inconsistency (P > 0.5) in all the comparisons. The present Bayesian network meta-analysis encourages the use of celecoxib as a prophylaxis for HO. These conclusions must be interpreted in light of the limitations of the present study. Future investigations are required to establish more definitely the role of celecoxib. Level of Evidence: I, Bayesian network analysis of RCTs.
TL;DR: A comprehensive review of the sports medicine literature was conducted to determine the nature and extent of PPSIs affecting the EPM complex of the extremities among youth sports participants and the potential for consequent skeletal growth disturbance and resultant limb deformity associated with these injuries.
Abstract: Overuse injuries are common in sporting children and adolescents. These injuries are a particular concern when they involve the epiphyseal–physeal–metaphyseal (EPM) complex given their potential to disturb skeletal growth. Specifically, the limits of mechanical tolerance of the EPM complex to repetitive stress may be exceeded by the intense and continuous training characteristic of many youth sports today. This article describes the present status of knowledge on the occurrence and outcome of primary periphyseal stress injuries (PPSIs) affecting the EPM complex in the extremities of children and adolescents involved in youth sports. A comprehensive review of the sports medicine literature was conducted to determine the nature and extent of PPSIs affecting the EPM complex of the extremities among youth sports participants and the potential for consequent skeletal growth disturbance and resultant limb deformity associated with these injuries. Our initial search uncovered 128 original published scientific articles reporting relevant data on PPSIs. There were 101 case reports/series, 19 cross-sectional, 1 case–control, and 7 cohort studies with relevant data. The case reports/series studies reported 448 patients with PPSIs involving the extremities. Children and adolescents representing a variety of high impact repetitive youth sports activities—including baseball, badminton, climbing, cricket, dance, gymnastics, rugby, soccer, swimming, tennis, and volleyball—may sustain PPSIs involving the shoulder, elbow, hand and wrist, knee, and ankle and foot. Although incidence data from prospective cohort studies are lacking, data arising from cross-sectional studies suggest that PPSIs may be common in select groups of youth athletes—including the shoulder in baseball players (0–36.6%), wrist in gymnasts (10–83%) and platform divers (52.6%), and fingers in rock climbers (5–58%). Notably, not all stress-related skeletal changes detected on imaging were symptomatic in these studies. When diagnosed and treated with an appropriate period of rest and rehabilitation, most patients studied were able to return to their sport activities. However, our data also show that 57/448 PPSIs (12.7%) produced growth disturbance, and that 28/448 patients (6.2%) underwent surgery for their injuries. Absence of treatment, delayed presentation and diagnosis, and non-compliance with a rest regimen were common in cases that produced growth disturbance. PPSIs may affect the extremities of children and adolescents engaged in a variety of youth sports, especially at advanced levels of training and competition. Most skeletally immature patients with PPSIs respond well to timely treatment; however, in extreme cases, PPSIs can progress to produce skeletal growth disruption which may necessitate surgical intervention. Clearly, establishing the early diagnosis of PPSIs and providing timely treatment of these injuries are needed to ensure the skeletal health of youth sports participants. Rigorous prospective longitudinal epidemiological and imaging studies designed to provide incidence rates of PPSIs and to determine the effect of PPSIs on long-term skeletal health are also necessary.
TL;DR: In this paper, the potential role of bone turnover (BTMs) as therapy monitoring was evaluated in patients with postmenopausal osteoporosis, and a multivariate analysis was performed to assess associations between these biomarkers and clinical outcomes and rate of adverse events.
Abstract: Biochemical markers of bone turnover (BTMs), such as bone alkaline phosphatase (bALP), procollagen type I N propeptide (PINP), serum cross-linked C-telopeptides of type I collagen (bCTx), and urinary cross-linked N-telopeptides of type I collagen (NTx), are commonly used for therapy monitoring purposes for osteoporotic patients. The present study evaluated the potential role of BTMs as therapy monitoring. All randomized clinical trials (RCTs) comparing two or more pharmacological treatments for postmenopausal osteoporosis were accessed. Only studies that reported the value of bALP, PINP, bCTx, and NTx at last follow-up were included. A multivariate analysis was performed to assess associations between these biomarkers and clinical outcomes and rate of adverse events in patients with postmenopausal osteoporosis. A multiple linear model regression analysis through the Pearson product-moment correlation coefficient was used. A total of 16 RCTs (14,446 patients) were included. The median age was 67 years, and the median BMI 25.4 kg/m2. The median vertebral BMD was 0.82, hip BMD 0.79, and femur BMD 0.64 g/cm2. The ANOVA test found optimal within-group variance concerning mean age, body mass index, and BMD. Greater bALP was associated with lower femoral BMD (P = 0.01). Greater NTx was associated with a greater number of non-vertebral fractures (P = 0.02). Greater NTx was associated with greater rate of therapy discontinuation (P = 0.04). No other statistically significant associations were detected. Our analysis supports the adoption of BTMs in therapy monitoring of osteoporotic patients. Level I, systematic review of RCTs.
TL;DR: In this article, the authors summarized the current evidence on the management of fragility fractures, discussing risk factors, prevention, diagnosis, and actual limitations of the clinical therapeutic options, putting forward new ideas for further scientific investigation.
Abstract: Given the progressive ageing of Western populations, the fragility fractures market has a growing socioeconomic impact. Fragility fractures are common in the elderly, negatively impacting their quality of life, limiting autonomy, increasing disability, and decreasing life expectancy. Different causes contribute to the development of a fractures in frail individuals. Among all, targeting fragile patients before the development of a fracture may represent the greatest challenge, and current diagnostic tools suffer from limitations. This study summarizes the current evidence on the management of fragility fractures, discussing risk factors, prevention, diagnosis, and actual limitations of the clinical therapeutic options, putting forward new ideas for further scientific investigation.
TL;DR: In this article, the safety and efficacy of intraarticular injection of umbilical cord-derived Wharton's Jelly (UC-derived WJ) for treatment of knee OA symptoms were evaluated.
Abstract: Osteoarthritis (OA) is the most common joint disorder in the USA, and knee OA has the highest prevalence. Inflammation and decrease in vascularization are key factors in the degeneration of articular cartilage and the associated pain and decrease in function. To combat this process, the use of biologics including umbilical cord-derived Wharton’s Jelly (UC-derived WJ) has grown. UC-derived WJ contains large quantities of regenerative factors, including growth factors (GFs), cytokines (CKs), hyaluronic acid (HA), and extracellular vesicles (EVs). The proposed study evaluates the safety and efficacy of intraarticular injection of UC-derived WJ for treatment of knee OA symptoms. This is a non-randomized, open-label, multi-center, prospective study in which the safety and efficacy of intraarticular UC-derived WJ in patients suffering from grade II/III OA will be assessed. Twelve patients with grade II/III OA who meet the inclusion and exclusion criteria will be recruited for this study which will be conducted at up to two sites within the USA. The participants will be followed for 1 s. Participants will be assessed using the Numeric Pain Rating Scale (NPRS), Knee Injury and Osteoarthritis Outcome Score (KOOS), 36-item short form survey (SF-36), Single Assessment Numeric Evaluation (SANE), physical exams, plain radiography, and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score for improvements in pain, satisfaction, function, and cartilage regeneration. This prospective study will contribute to the limited amount of data on UC-derived WJ, particularly with regard to its safety and efficacy. The outcomes from this study will also lay the groundwork for a large placebo-controlled trial of intraarticular UC-derived WJ for symptomatic knee OA. ClinicalTrials.gov NCT04719793
. Registered on 22 January 2021
TL;DR: In this paper, an increasing trend for arthroscopic surgery for femoroacetabular impingement (FAI) is reported in adolescent athletes, and the results of several clinical studies show that FAI is highly prevalent in adolescents.
Abstract: Background:Femoroacetabular impingement (FAI) is highly prevalent in adolescent athletes. There has been an increasing trend for arthroscopic surgery for FAI, and the results of several clinical st...
TL;DR: In this paper, the authors summarize current knowledge on functions of stem cells and macrophages in skeletal muscle repairs and their roles as components of a promising cell-based therapies for muscle repair and regeneration.
Abstract: In severe muscle injury, skeletal muscle tissue structure and functionality can be repaired through the involvement of several cell types, such as muscle stem cells, and innate immune responses. However, the exact mechanisms behind muscle tissue regeneration, homeostasis, and plasticity are still under investigation, and the discovery of pathways and cell types involved in muscle repair can open the way for novel therapeutic approaches, such as cell-based therapies involving stem cells and peripheral blood mononucleate cells. Indeed, peripheral cell infusions are a new therapy for muscle healing, likely because autologous peripheral blood infusion at the site of injury might enhance innate immune responses, especially those driven by macrophages. In this review, we summarize current knowledge on functions of stem cells and macrophages in skeletal muscle repairs and their roles as components of a promising cell-based therapies for muscle repair and regeneration.
TL;DR: In this article, the potential of these biomarkers in predicting the clinical outcomes in terms of BMD, t-score, rate of fractures, and adverse events during the therapy setting in postmenopausal osteoporosis was analyzed.
Abstract: Biochemical markers of bone turnover (BTMs), such as the bone alkaline phosphatase (bALP), procollagen type I N propeptide (PINP), serum cross-linked C-telopeptides of type I collagen (bCTx), and urinary cross-linked N-telopeptides of type I collagen (NTx), are used to manage therapy monitoring in osteoporotic patients. This systematic review analyzed the potential of these BMTs in predicting the clinical outcomes in terms of BMD, t-score, rate of fractures, and adverse events during the therapy setting in postmenopausal osteoporosis. All randomized clinical trials (RCTs) reporting data on biomarkers for postmenopausal osteoporosis were accessed. Only articles reporting quantitative data on the level of biomarkers at baseline and on the outcomes of interest at the last follow-up were eligible. A total of 36,706 patients were retrieved. Greater values of bALP were associated with a greater rate of vertebral (P = 0.001) and non-vertebral fractures (P = 0.0001). Greater values of NTx at baseline were associated with a greater rate of adverse events at the last follow-up (P = 0.02). Greater values of CTx at baseline were associated with a greater rate of adverse events leading to discontinuation (P = 0.04), gastrointestinal adverse events (P = 0.0001), musculoskeletal adverse events (P = 0.04), and mortality (P = 0.04). Greater values of PINP at baseline were associated with greater rates of gastrointestinal adverse events (P = 0.02) at the last follow-up. The present analysis supports the adoption of BMTs during pharmacological therapy setting of patients suffering from osteoporosis. I, systematic review of RCTs
TL;DR: In this paper, the authors assessed the decline in muscle mass and functional outcomes following hip fracture surgery and found significant losses in ADL were identified at the 1-year follow-up, at which time only 43% of patients had regained their preinjury ADL status.
Abstract: Introduction Hip fractures in the elderly impact negatively on functional dependence, and carry great social costs and morbidity. We assessed the decline in muscle mass and functional outcomes following hip fracture surgery . Material and methods Thirty patients with a hip fracture (mean age: 80.8 years) were assessed using dual-energy X-ray absorptiometry and reassessed for changes in body composition 1 year after hip surgery. Baseline demographic data, sarcopenia, and bone mineral density were recorded. Body mass index (BMI), handgrip strength, appendicular skeletal muscle mass (ASM), total body fat percentage, and responses to questionnaires measuring quality of life and activities of daily living (ADL) before injury and 1 year after hip surgery were analyzed to identify changes. Associations with changes in ADL or quality of life were analyzed with time-variant independent variables. Results Significant losses in ADL were identified at the 1-year follow-up, at which time only 43% of patients had regained their preinjury ADL status. Additionally, the participants had lost an average of 4.63% of ASM. ASM loss was significantly higher in patients with baseline sarcopenia than in those without (mean loss: 9.18% and 1.15%, respectively). When confounders were controlled for, a greater loss of ASM and handgrip strength and larger increase in BMI were associated with greater decrease in ADL 1 year after hip surgery. Conclusion Geriatric hip fracture patients may experience a significant loss of muscle mass, associated with impaired functional recovery 1 year after hip surgery, highlighting a potential treatment target of maintaining muscle mass to improve prognosis in these patients.
TL;DR: In this article, the potential of autologous matrix-induced chondrogenesis (AMIC) to restore unipolar focal chondral defects of the knee is promising, but the outcome compared to microfracturing (MFx) for certain defect sizes (2-3 cm2) is still uncertain.
Abstract: Introduction: The potential of autologous matrix-induced chondrogenesis (AMIC) to restore unipolar focal chondral defects of the knee is promising. However, the outcome compared to microfracturing (MFx) for certain defect sizes (2–3 cm2) is still uncertain. Therefore, the present study compared primary isolated AMIC versus MFx in a cohort of patients with borderline sized focal unipolar chondral defects of the knee at midterm follow-up. Methods: Patients with chondral defects of the knee who underwent AMIC or MFx were compared. An arthroscopic approach was used for MFx, and a minimally invasive parapatellar arthrotomy for AMIC. For those patients who underwent AMIC, a collagen membrane was used with fibrin glue. The patients answered independently: Visual Analogic Scale (VAS), Tegner Activity Scale, International Knee Documentation Committee (IKDC), and the Lysholm scores. Results: A total of 83 patients with a mean age of 30.2 and body mass index (BMI) of 26.9 kg/m2 were recruited. Of them, 33.7% (28 of 83) were women, and 55.4% (46 of 83 patients) had defects in the right knee. The mean length of symptoms before surgery was 43.3 months. The mean size of the defect was 2.7 cm2. The mean length of follow-up was 42.1 months. No difference was found in terms of symptoms and follow-up length, mean age and BMI, mean size of defect, sex, and side. The AMIC cohort reported greater IKCD (p > 0.0001), Lysholm (p = 0.002), VAS (p = 0.01), Tegner (p = 0.004) scores. The AMIC cohort reported lower rate of failure (p = 0.005) and revision surgery (p = 0.02). No difference was found in the rate of arthroplasty (p = 0.2). No delamination or hypertrophy were detected. Conclusion: AMIC demonstrated superiority over MFx for focal unipolar chondral defects of the knee. At approximately 40 months follow-up, the IKDC, Lysholm, and VAS scores were greater in the AMIC group. Patients treated with AMIC also demonstrated a higher level of sport activity, and lower rates of failure and revision surgeries.
TL;DR: The physical properties of hyaluronic acid within tendons are still poorly investigated as discussed by the authors, despite the absence of consensus in the literature regarding the classification according to molecular weight, the properties of hydroxymethylpolysilicon (HLS) have been investigated.
Abstract: The physical–chemical, structural, hydrodynamic, and biological properties of hyaluronic acid within tendons are still poorly investigated. Medical history and clinical applications of hyaluronic acid for tendinopathies are still debated. In general, the properties of hyaluronic acid depend on several factors including molecular weight. Several preclinical and clinical experiences show a good efficacy and safety profile of hyaluronic acid, despite the absence of consensus in the literature regarding the classification according to molecular weight. In in vitro and preclinical studies, hyaluronic acid has shown physical–chemical properties, such as biocompatibility, mucoadhesivity, hygroscopicity, and viscoelasticity, useful to contribute to tendon healing. Additionally, in clinical studies, hyaluronic acid has been used with promising results in different tendinopathies. In this narrative review, findings encourage the clinical application of HA in tendinopathies such as rotator cuff, epicondylitis, Achilles, and patellar tendinopathy.
TL;DR: In this paper, the authors assess the role of surgical techniques in offloading to heal and possibly prevent diabetic foot ulceration, and identify healing, remission-rates, return to ambulation, complications and limitations.
Abstract: Introduction Diabetic peripheral neuropathy leads to foot deformity, soft tissues damage, and gait imbalance, all of which can increase the mechanical stress imposed on the foot and give rise to Charcot neuroarthropathy. The current International Working Group of the Diabetic Foot International Guidelines on offloading focus on managing neuropathic foot ulcers related to pressure: only 2 of their 9 recommendations deal with surgical interventions. We assess the role of surgical techniques in off-loading to heal and possibly prevent diabetic foot ulceration. Methods We systematically analysed published data from January 2000 to November 2020 to assess methods of surgical offloading and associated outcomes for the surgical reconstruction. We tried to identify healing, remission-rates, return to ambulation, complications and limitations. Results Five discrete categories of surgical offloading are used in recalcitrant ulcers: 1. Lesser toe tenotomies; 2. Metatarsal head resection ± Achilles tendon release; 3. Hallux procedures; 4. Bony off-loading procedures in the form of exostectomy; and 5. Complex surgical foot reconstruction. Adjuvant modalities including surgically placed antibiotic delivery systems show promise, but further studies are required to clarify their role and effect on systemic antibiotic requirements. Conclusions and implications Surgery is important to mechanically stabilise and harmonise the foot for long term off-loading and foot-protection. Surgery should not be reserved for recalcitrant cases only, but extended to ulcer prevention and remission. Further comparative studies will benefit surgical decision making to avoid recurrence and define time point when surgical off-loading could protect against irretrievable tissue loss/re-ulceration.
TL;DR: In this paper, the role of allografts versus auto-grafts for medial patellofemoral ligament (MPFL) reconstruction in patients with POMI was discussed.
Abstract: This study updates the current evidence on the role of allografts versus autografts for medial patellofemoral ligament (MPFL) reconstruction in patients with patellofemoral instability. The study was performed according to the PRISMA guidelines. In March 2021, a literature search in the main online databases was performed. Studies reporting quantitative data concerning primary MPFL reconstruction using an allograft were considered for inclusion. The Coleman Methodology Score was used to assess the methodological quality of the selected articles. Data from 12 studies (474 procedures) were retrieved. The mean follow-up was 42.2 (15–78.5) months. The mean age was 21.1 ± 6.2 years. 64.9% (285 of 439) of patients were female. At the last follow-up, the Tegner (p < 0.0001), Kujala (p = 0.002) and the Lysholm (p < 0.0001) scores were minimally greater in the autografts. The similarity was found in the rate of persistent instability sensation and revision. The allograft group evidenced a lower rate of re-dislocations (p = 0.003). Allografts may represent a feasible alternative to traditional autograft for MPFL reconstruction in selected patients with patellofemoral instability. Allograft tendons yielded similar PROMs, rates of persistent instability, and revision. Allograft reconstructions tended to have modestly lower re-dislocation rates. IV.
TL;DR: In this article, a systematic review evaluated the outcome of arthroscopic cartilage debridement as the primary treatment of focal knee chondral lesions in adults, and defined its indications and role as a primary treatment for focal cartilage lesion.
Abstract: Background and purpose of the study Arthroscopic debridement, the most commonly applied surgical technique for focal cartilage lesions in the knee, is not included in most treatment algorithms because of discouraging results in the management of osteoarthritis of the knee. The present systematic review evaluates the outcome of arthroscopic cartilage debridement as the primary treatment of focal knee chondral lesions in adults, and defines its indications and role as the primary treatment of focal knee chondral lesions. Methods Two independent investigators searched PubMed, Cochrane CENTRAL, and Virtual Health Library databases using the terms “knee”, “cartilage”, “chondral”, “lesions”, “injury”, “damage”, “debridement”, “chondroplasty”, “chondrectomy”, alone and in combination. Clinical studies evaluating the effect of mechanical cartilage debridement in adults with symptomatic focal cartilage lesions in the knee joint regardless of the defect size and depth were included. We excluded studies if patients had a concomitant ligament or meniscus injury, and/or had additional debridement with monopolar radiofrequency energy. Main findings Available studies suggest good to excellent short and medium-term functional outcomes (KOOS, LKSS, Tegner scale) for focal cartilage lesions treated with debridement regardless of the defect size and depth. Data are lacking comparing cartilage debridement versus other cartilage repair techniques. Conclusions Arthroscopic debridement of focal articular cartilage lesions of the knee is associated with good to excellent short and medium-term postoperative outcomes, especially in terms of functional improvement. Arthroscopic debridement may be considered in the primary treatment of focal cartilage injuries regardless of the defect size and depth. However, available studies are limited and the level of evidence is low.