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Osteoarthritis (OA) is one of the main causes of disability worldwide and is caused by the progressive degeneration of joint tissues, ultimately leading to chronic pain and loss of function. Intraarticular delivery of mesenchymal stromal cells, such as adipose-derived stromal cells (ASCs), is being actively investigated due to their trophic properties observed in both preclinical and clinical studies. However, cell expansion and handling involve costly and time-consuming processes that limit their application. Recently, several devices and kits have been developed to isolate and process the stromal vascular fraction (SVF), a high biologically active compound of the adipose tissue, right at the patient’s bedside. In this study, we introduce a novel technique to obtain an SVF graft with a high content of ASCs for intraarticular injection directly from liposuction and with minimal equipment. In this technical note, we describe in detail the steps of the surgical technique as well as strategies to avoid common pitfalls and complications.

Study design Systematic review. Objective To investigate the efficacy of nonsurgical interventional treatments for chronic low back pain (LBP) caused by facet joint syndrome (FJS). Methods A systematic review of the literature was conducted to identify studies that compared interventional treatments for LBP due to FJS among them, with usual care or sham procedures. Studies were evaluated for pain, physical function, disability, quality of life and employment status. The RoB-2 and MINORS tools were utilized to assess the risk of bias in included studies. Results Eighteen studies published between January 2000 and December 2021 were included (1496 patients, mean age: 54.31 years old). Intraarticular (IA) facet joint (FJ) injection of hyaluronic acid (HA) did not show significant difference compared to IA corticosteroids (CCS) in terms of pain and satisfaction. FJ denervation using radiofrequency (RF) displayed slightly superior or similar outcomes compared to IA CCS, physical therapy, or sham procedure. IA CCS showed better outcomes when combined with oral diclofenac compared to IA CCS or oral diclofenac alone but was not superior to IA local anesthetic and Sarapin. IA platelet-rich plasma (PRP) led to an improvement of pain, disability and satisfaction in the long term compared to IA CCS. Conclusion FJS is a common cause of LBP that can be managed with several different strategies, including nonsurgical minimally invasive approaches such as IA HA, CCS, PRP and FJ denervation. However, available evidence showed mixed results, with overall little short-term or no benefits on pain, disability, and other investigated outcomes.

Study design Systematic Review. Objectives The aim of this systematic review is to evaluate the efficacy of non-invasive procedures in relieving chronic pain due to Failed Back Surgery Syndrome (FBSS). Methods Since patients who suffered from FBBS are often non-responders to analgesics, we compared Visual Analogical Scale for low back and leg pain, Oswestry Disability Index, trial success rate, adverse events and complications between conservative treatment groups and control groups. Results The included studies were 15. Spinal Cord Stimulation (SCS) was performed in 11 trials; 4 studies assessed the efficacy of different epidural injections; one study evaluated repetitive Transcranial Magnetic Stimulation. All the studies reported back and leg pain relief after treatment with SCS, with a significant superiority in high frequences (HFS) group, compared to low frequences (LFS) group. Moreover, disability decreased with each non-invasive treatment evaluated. Epidural injections of steroids and hyaluronidase have shown controversial results. Adverse events were described in 7 studies: lead migration, hardware-related events, infection and incisional pain were the most reported. Finally, trial success rate showed better outcomes for HFS. Conclusions Our systematic review highlights the efficacy of conservative treatments in FBSS patients, with an improvement in pain scores and a decrease in disability index, especially after SCS with HFS. However, due to the lack of homogeneity among trials and population characteristics, further studies are needed to confirm the effectiveness of non-invasive interventions in patients affected by FBSS.

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Introduction The aim of the narrative review was to analyse the applications of nuclear medicine (NM) techniques such as PET/CT with different tracers in combination with radiotherapy for the clinical management of glioblastoma patients. Materials and methods Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used. Results This paper contains a narrative report and a critical discussion of NM approaches in combination with radiotherapy in glioma patients. Conclusions NM can provide the Radiation Oncologist several aids that can be useful in the clinical management of glioblastoma patients. At the same, these results need to be validated in prospective and multicenter trials.

Introduction: Intradiscal mesenchymal stromal cell (MSC) therapies for intervertebral disc degeneration (IDD) have been gaining increasing interest due to their capacity to ameliorate intervertebral disc metabolism and relieve low back pain (LBP). Recently, novel investigations have demonstrated that most of MSC anabolic effects are exerted by secreted growth factors, cytokines, and extracellular vesicles, collectively defined as their secretome. In this study, we aimed to evaluate the effect of bone-marrow-MSCs (BM-MSCs) and adipose-derived stromal cells (ADSCs) secretomes on human nucleus pulposus cells (hNPCs) in vitro.Methods: BM-MSCs and ADSCs were characterized according to surface marker expression by flow cytometry and multilineage differentiation by Alizarin red, Red Oil O and Alcian blue staining. After isolation, hNPCs were treated with either BM-MSC secretome, ADSC secretome, interleukin (IL)-1β followed by BM-MSC secretome or IL-1β followed by ADSC secretome. Cell metabolic activity (MTT assay), cell viability (LIVE/DEAD assay), cell content, glycosaminoglycan production (1,9-dimethylmethylene blue assay), extracellular matrix and catabolic marker gene expression (qPCR) were assessed.Results: 20% BM-MSC and ADSC secretomes (diluted to normal media) showed to exert the highest effect towards cell metabolism and were then used in further experiments. Both BM-MSC and ADSC secretomes improved hNPC viability, increased cell content and enhanced glycosaminoglycan production in basal conditions as well as after IL-1β pretreatment. BM-MSC secretome significantly increased ACAN and SOX9 gene expression, while reducing the levels of IL6, MMP13 and ADAMTS5 both in basal conditions and after in vitro inflammation with IL-1β. Interestingly, under IL-1β stimulation, ADSC secretome showed a catabolic effect with decreased extracellular matrix markers and increased levels of pro-inflammatory mediators.Discussion: Collectively, our results provide new insights on the biological effect of MSC-derived secretomes on hNPCs, with intriguing implications on the development of cell-free approaches to treat IDD.

Introduction: Adipose tissue is widely exploited in regenerative medicine thanks to its trophic properties, mainly based on the presence of adipose-derived stromal cells. Numerous devices have been developed to promote its clinical use, leading to the introduction of one-step surgical procedures to obtain minimally manipulated adipose tissue derivatives. However, only a few studies compared their biological properties. This study aimed to characterize micro-fragmented (MAT) and nanofat adipose tissue (NAT) obtained with two different techniques.Methods: MAT, NAT and unprocessed lipoaspirate were collected from surgical specimens. RNA extraction and collagenase isolation of stromal vascular fraction (SVF) were performed. Tissue sections were analysed by histological and immunohistochemical (collagen type I, CD31, CD34 and PCNA) staining to assess tissue morphology and cell content. qPCR was performed to evaluate the expression of stemness-related (SOX2, NANOG and OCT3/4), extracellular matrix (COL1A1) and inflammatory genes (IL1β, IL6 and iNOS). Furthermore, multilineage differentiation was assessed following culture in adipogenic and osteogenic media and staining with Oil Red O and Alizarin red. ASC immunophenotype was assessed by flow cytometric analysis of CD90, CD105, CD73 and CD45.Results: Histological and immunohistochemical results showed an increased amount of stroma and a reduction of adipocytes in MAT and NAT, with the latter displaying the highest content of collagen type I, CD31, CD34 and PCNA. From LA to MAT and NAT, an increasing expression of NANOG, SOX2, OCT3/4, COL1A1 and IL6 was noted, while no significant differences in terms of IL1β and iNOS emerged. No statistically significant differences were noted between NAT and SVF in terms of stemness-related genes, while the latter demonstrated a significantly higher expression of stress-related markers. SVF cells derived from all three samples (LA, MAT, and NAT) showed a similar ASC immunoprofile as well as osteogenic and adipogenic differentiation.Discussion: Our results showed that both MAT and NAT techniques allowed the rapid isolation of ASC-rich grafts with a high anabolic and proliferative potential. However, NAT showed the highest levels of extracellular matrix content, replicating cells, and stemness gene expression. These results may provide precious clues for the use of adipose tissue derivatives in the clinical setting.

Background Autologous hamstrings and patellar tendon have historically been considered the gold standard grafts for anterior cruciate ligament reconstruction (ACLR). In the last decades, the utilization of synthetic grafts has re-emerged due to advantageous lack of donor site morbidity and more rapid return to sport. The Ligament Augmentation and Reconstruction System (LARS) has demonstrated to be a valid and safe option for ACLR in the short term. However, recent studies have pointed out the notable frequency of associated complications, including synovitis, mechanical failure, and even chondrolysis requiring joint replacement. Case presentation We report the case of a 23-year-old male who developed a serious foreign body reaction with wide osteolysis of both femoral and tibial tunnels following ACLR with LARS. During first-stage arthroscopy, we performed a debridement of the pseudocystic mass incorporating the anterior cruciate ligament (ACL) and extending towards the tunnels, which were filled with autologous anterior iliac crest bone graft chips. Histological analysis revealed the presence of chronic inflammation, fibrosis, and foreign body giant cells with synthetic fiber inclusions. Furthermore, physicochemical analysis showed signs of fiber depolymerization, increased crystallinity and formation of lipid peroxidation-derived aldehydes, which indicate mechanical aging and instability of the graft. After 8 months, revision surgery was performed and ACL revision surgery with autologous hamstrings was successfully carried out. Conclusions The use of the LARS grafts for ACLR should be cautiously contemplated considering the high risk of complications and early failure.

Introduction: The incidence of melanoma increased considerably in recent decades, representing a significant public health problem. We aimed to evaluate the ability of non-specialists for the preliminary screening of skin lesions to identify melanoma-suspect lesions. Materials and Methods: A medical student and a dermatologist specialist examined the total body scans of 50 patients. Results: The agreement between the expert and the non-specialist was 87.75% (κ = 0.65) regarding the assessment of clinical significance. The four parameters of the ABCD rule were evaluated on the 129 lesions rated as clinically significant by both observers. Asymmetry was evaluated similarly in 79.9% (κ = 0.59), irregular borders in 74.4% (κ = 0.50), color in 81.4% (κ = 0.57), and diameter in 89.9% (κ = 0.77) of the cases. The concordance of the two groups was 96.9% (κ = 0.83) in the case of the detection of the Ugly Duckling Sign. Conclusions: Although the involvement of GPs is part of routine care worldwide, emphasizing the importance of educating medical students and general practitioners is crucial, as many European countries lack structured melanoma screening training programs targeting non-dermatologists.

The association between diabetes and cardiovascular diseases is well known. Related diabetes macro- and microangiopathies frequently induce hypoxia and consequently energy failure to satisfy the jeopardized myocardium basal needs. Additionally, it is widely accepted that diabetes impairs endothelial nitric oxide synthase (eNOS) activity, resulting in diminished nitric oxide (NO) bioavailability and consequent endothelial cell dysfunction. In this study, we analyzed the embryonic heart-derived H9c2 cell response to hypoxic stress after administration of a high glucose concentration to reproduce a condition often observed in diabetes. We observed that 24 h hypoxia exposure of H9c2 cells reduced cell viability compared to cells grown in normoxic conditions. Cytotoxicity and early apoptosis were increased after exposure to high glucose administration. In addition, hypoxia induced a RhoA upregulation and a Bcl-2 downregulation and lowered the ERK activation observed in normoxia at both glucose concentrations. Furthermore, a significant cell proliferation rate increases after the 1400 W iNOS inhibitor administration was observed. Again, hypoxia increased the expression level of myogenin, a marker of skeletal muscle cell differentiation. The cardiomyocyte gene expression profiles and morphology changes observed in response to pathological stimuli, as hypoxia, could lead to improper ventricular remodeling responsible for heart failure. Therefore, understanding cell signaling events that regulate cardiac response to hypoxia could be useful for the discovery of novel therapeutic approaches able to prevent heart diseases.

In vitro study.To investigate the effect of irisin on human nucleus pulposus cells (hNPCs) in vitro.Physical exercise (PE) favours weight loss and ameliorates function in patients with low back pain. Although there is no biologic evidence that the intervertebral disc (IVD) can respond to PE, recent studies have shown that running is associated with increased IVD hydration and hypertrophy. Irisin, a myokine released upon muscle contraction, has demonstrated anabolic effects on different cell types, including chondrocytes.hNPCs were exposed to 5, 10 and 25 ng/mL irisin. Cell proliferation, glycosaminoglycan (GAG) content, metabolic activity, gene expression of collagen type II (COL2), matrix metalloproteinase (MMP)-13, tissue inhibitor of matrix metalloproteinase (TIMP)-1 and -3, aggrecan (ACAN), interleukin (IL)-1β, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5 were assessed. In addition, MTT assay and ADAMTS-5, COL2, TIMP-1 and IL-1β gene expression were evaluated following incubation with irisin for 24 hours and subsequent culture with 10 ng/ml IL-1β and vice versa (incubation for 24 hours with IL-1β and subsequent culture with irisin).Irisin increased hNPC proliferation, metabolic activity, and GAG content, as well as COL2, ACAN, TIMP-1 and -3 gene expression, while decreasing MMP-13 and IL-1β mRNA levels. Irisin pretreatment of hNPCs cultured in pro-inflammatory conditions resulted in a rescue of metabolic activity and a decrease of IL-1β levels. Similarly, incubation of hNPCs with IL-1β and subsequent exposure to irisin led to an increment of metabolic activity, COL2 gene expression and a reduction of IL-1β and ADAMTS-5 levels.Irisin increases hNPC proliferation, GAG content, metabolic activity and promotes anabolic gene expression while reducing catabolic markers. Irisin may be one of the mediators by which PE and muscle tissues modulate IVD metabolism, suggesting the existence of a biological crosstalk between the muscle and IVD.

Objective Preoperative planning in spine surgery is a fundamental step of the surgical workup and is often assisted by direct visualization of anatomical 2-dimensional images. This process is time-consuming and may excessively approximate the 3-dimensional (3D) nature of spinal anatomy. Virtual reality (VR) is an emerging technology capable of reconstructing an interactive 3D anatomical model that can be freely explored and manipulated. Methods Sixty patients with adolescent idiopathic scoliosis underwent correction of the scoliotic curve by posterior arthrodesis after preoperative planning using traditional on-screen visualization of computed tomography scans (control group, n = 30) or exploration of a 3D anatomical model in VR using Google Cardboard (Google Inc.) (VR group, n = 30). Mean operative time, blood loss, length of hospital stay, and surgeon's satisfaction were assessed after surgery. Results The use of VR led to a significant decrease in operative time and bleeding while increasing the surgeon's satisfaction compared to the control group. Conclusion Preoperative planning with VR turned out to be effective in terms of operative time and blood loss reduction. Moreover, such technology proved to be reproducible, costeffective, and more satisfactory compared to conventional planning.

Nasopharyngeal (NP) swab sampling is a simple procedure that has become extremely popular in the coronavirus disease 2019 (COVID-19) era, with hundreds of million specimens collected every day. However, rare but serious complications have been reported following NP swab acquisition. Here we present a case of paroxysmal atrial fibrillation associated with NP specimen collection in a healthy healthcare provider undergoing COVID-19 testing during departmental screening. This response may have been caused by an exaggerated vagal tone triggered by the trigeminocardiac reflex. Less invasive collection methods, such as saliva testing, may be warranted in predisposed individuals.

Low Back Pain (LBP) is currently the first cause of disability in the world, with a significant socioeconomic burden. Diagnosis and treatment of LBP often involve a multidisciplinary, individualized approach consisting of several outcome measures and imaging data along with emerging technologies. The increased amount of data generated in this process has led to the development of methods related to artificial intelligence (AI), and to computer-aided diagnosis (CAD) in particular, which aim to assist and improve the diagnosis and treatment of LBP. In this manuscript, we have systematically reviewed the available literature on the use of CAD in the diagnosis and treatment of chronic LBP. A systematic research of PubMed, Scopus, and Web of Science electronic databases was performed. The search strategy was set as the combinations of the following keywords: “Artificial Intelligence”, “Machine Learning”, “Deep Learning”, “Neural Network”, “Computer Aided Diagnosis”, “Low Back Pain”, “Lumbar”, “Intervertebral Disc Degeneration”, “Spine Surgery”, etc. The search returned a total of 1536 articles. After duplication removal and evaluation of the abstracts, 1386 were excluded, whereas 93 papers were excluded after full-text examination, taking the number of eligible articles to 57. The main applications of CAD in LBP included classification and regression. Classification is used to identify or categorize a disease, whereas regression is used to produce a numerical output as a quantitative evaluation of some measure. The best performing systems were developed to diagnose degenerative changes of the spine from imaging data, with average accuracy rates >80%. However, notable outcomes were also reported for CAD tools executing different tasks including analysis of clinical, biomechanical, electrophysiological, and functional imaging data. Further studies are needed to better define the role of CAD in LBP care.

In March 2019, the World Health Organization (WHO) recognized the COVID-19 pandemic as a global issue. To reduce the spread of this disease, health safety pathways were implemented worldwide. These extraordinary measures changed people’s lifestyles, e.g., by being forced to isolate, and in many cases, to work remotely from home. Low back pain (LBP), the most common cause of disability worldwide, is often a symptom of COVID-19. Moreover, it is often associated with different lifestyle features (type of job, physical activity, body weight). Therefore, the purpose of this systematic review and meta-analysis was to estimate the effect of the COVID-19 lockdown on LBP intensity and prevalence compared with LBP rates before the pandemic. A systematic search was performed on Scopus, PubMed, and Cochrane Central. Overall, eight studies with 2365 patients were included in the analysis. We used the Joanna Briggs Institute (JBI) critical appraisal tool to evaluate the risk of bias: six studies (75%) were at moderate risk of bias and two studies (25%) were at low risk of bias. These studies showed an increase in both the prevalence and intensity of LBP during the COVID-19 lockdown.

The current coronavirus disease 2019 (COVID-19) pandemic has revolutionized global healthcare in an unprecedented way and with unimaginable repercussions. Resource reallocation, socioeconomic confinement and reorganization of production activities are current challenges being faced both at the national and international levels, in a frame of uncertainty and fear. Hospitals have been restructured to provide the best care to COVID-19 patients while adopting preventive strategies not to spread the infection among healthcare providers and patients affected by other diseases. As a consequence, the concept of urgency and indications for elective treatments have been profoundly reshaped. In addition, several providers have been recruited in COVID-19 departments despite their original occupation, resulting in a profound rearrangement of both inpatient and outpatient care. Orthopaedic daily practice has been significantly affected by the pandemic. Surgical indications have been reformulated, with elective cases being promptly postponed and urgent interventions requiring exceptional attention, especially in suspected or COVID-19+ patients. This has made a strong impact on inpatient management, with the need of a dedicated staff, patient isolation and restrictive visiting hour policies. On the other hand, outpatient visits have been limited to reduce contacts between patients and the hospital personnel, with considerable consequences on post-operative quality of care and the human side of medical practice.In this review, we aim to analyze the effect of the COVID-19 pandemic on the orthopaedic practice. Particular attention will be dedicated to opportune surgical indication, perioperative care and safe management of both inpatients and outpatients, also considering repercussions of the pandemic on resident education and ethical implications.

Instrumented spine procedures have been performed for decades to treat a wide variety of spinal disorders. New technologies have been employed to obtain a high degree of precision, to minimize risks of damage to neurovascular structures and to diminish harmful exposure of patients and the operative team to ionizing radiations. Robotic spine surgery comprehends 3 major categories: telesurgical robotic systems, robotic-assisted navigation (RAN) and virtual augmented reality (AR) systems, including AR and virtual reality. Telesurgical systems encompass devices that can be operated from a remote command station, allowing to perform surgery via instruments being manipulated by the robot. On the other hand, RAN technologies are characterized by the robotic guidance of surgeon-operated instruments based on real-time imaging. Virtual AR systems are able to show images directly on special visors and screens allowing the surgeon to visualize information about the patient and the procedure (i.e., anatomical landmarks, screw direction and inclination, distance from neurological and vascular structures etc.). The aim of this review is to focus on the current state of the art of robotics and AR in spine surgery and perspectives of these emerging technologies that hold promises for future applications.

Low back pain (LBP) is one of the most frequent symptoms associated with intervertebral disc degeneration (IDD) and affects more than 80% of the population, with strong psychosocial and economic impacts. The main cause of IDD is a reduction in the proteoglycan content within the nucleus pulposus (NP), eventually leading to the loss of disc hydration, microarchitecture, biochemical and mechanical properties. The use of mesenchymal stem cells (MSCs) has recently arisen as a promising therapy for IDD. According to numerous reports, MSCs mediate their regenerative and immunomodulatory effects mainly through paracrine mechanisms. Recent studies have suggested that extracellular vesicles (EVs) extracted from MSCs may be a promising alternative to cell therapy in regenerative medicine. EVs, including exosomes and microvesicles, are secreted by almost all cell types and have a fundamental role in intercellular communication. Early results have demonstrated the therapeutic potential of MSCs-derived EVs for the treatment of IDD through the promotion of tissue regeneration, cell proliferation, reduction in apoptosis and modulation of the inflammatory response. The aim of this review is to focus on the biological properties, function, and regulatory properties of different signaling pathways of MSCs-derived exosomes, highlighting their potential applicability as an alternative cell-free therapy for IDD.

Overweight represents a major issue in contemporary orthopaedic practice. A higher body mass index (BMI) is associated with an increase of perioperative complications following several orthopaedic procedures, in particular total hip arthroplasty (THA). However, the influence of overweight on THA surgical time is controversial. In this study, we investigated the association between BMI and surgical time analyzing the role of patients’ comorbidities. We conducted a retrospective study on 748 patients undergoing THA at our institutions between 2017 and 2018. Information regarding medical diseases was investigated and the burden of comorbidity was quantified using the Charlson score (CCI). Surgical time and blood loss were also recorded. Median surgical time was 76.5 min. Patients with surgical time above the median had both a higher BMI (28.3 vs. 27.1 kg/m2; p = 0.002); and CCI (1 vs. 0; p = 0.016). According to linear regression, surgical time was associated with BMI in the unadjusted model (p < 0.0001), after adjusting for age and sex (p < 0.0001), and in the multivariable model (p = 0.005). Furthermore, BMI was associated with increased surgical time only in patients with a Charlson score above the median, but not in others. Obesity is associated with increased surgical time during THA, especially in pluricomorbid patients, with a higher risk of perioperative complications.

Chronic Low Back Pain (LBP) is a symptom that may be caused by several diseases, and it is currently the leading cause of disability worldwide. The increased amount of digital images in orthopaedics has led to the development of methods related to artificial intelligence, and to computer vision in particular, which aim to improve diagnosis and treatment of LBP. In this manuscript, we have systematically reviewed the available literature on the use of computer vision in the diagnosis and treatment of LBP. A systematic research of PubMed electronic database was performed. The search strategy was set as the combinations of the following keywords: “Artificial Intelligence”, “Feature Extraction”, “Segmentation”, “Computer Vision”, “Machine Learning”, “Deep Learning”, “Neural Network”, “Low Back Pain”, “Lumbar”. Results: The search returned a total of 558 articles. After careful evaluation of the abstracts, 358 were excluded, whereas 124 papers were excluded after full-text examination, taking the number of eligible articles to 76. The main applications of computer vision in LBP include feature extraction and segmentation, which are usually followed by further tasks. Most recent methods use deep learning models rather than digital image processing techniques. The best performing methods for segmentation of vertebrae, intervertebral discs, spinal canal and lumbar muscles achieve Sørensen–Dice scores greater than 90%, whereas studies focusing on localization and identification of structures collectively showed an accuracy greater than 80%. Future advances in artificial intelligence are expected to increase systems’ autonomy and reliability, thus providing even more effective tools for the diagnosis and treatment of LBP.

Bone cancer is a demanding challenge for contemporary medicine due to its high frequency of presentation and significant heterogeneity of malignant lesions developing within the bone. To date, available treatments are rarely curative and are primarily aimed at prolonging patients’ survival and ameliorating their quality of life. Furthermore, both pharmacological and surgical therapies are aggravated by a consistent burden of adverse events and subsequent disability due to the loss of healthy bone structural and functional properties. Therefore, great research efforts are being made to develop innovative biomaterials able to selectively inhibit bone cancer progression while reducing the loss of bone structural properties secondary to local tissue invasion. In this review, we describe the state of the art of innovative biomaterials for the treatment of bone cancer. Along with physiological bone remodeling, the development of bone metastasis and osteosarcoma will be depicted. Subsequently, recent advances on nanocarrier-based drug delivery systems, as well as the application of novel, multifunctional biomaterials for the treatment of bone cancer will be discussed. Eventually, actual limitations and promising future perspectives regarding the employment of such approaches in the clinical scenario will be debated.

Low back pain (LBP) is currently the leading cause of disability worldwide and the most common reason for workers’ compensation (WC) claims. Studies have demonstrated that receiving WC is associated with a negative prognosis following treatment for a vast range of health conditions. However, the impact of WC on outcomes after spine surgery is still controversial. The aim of this meta-analysis was to systematically review the literature and analyze the impact of compensation status on outcomes after lumbar spine surgery. A systematic search was performed on Medline, Scopus, CINAHL, EMBASE and CENTRAL databases. The review included studies of patients undergoing lumbar spine surgery in which compensation status was reported. Methodological quality was assessed through ROBINS-I and quality of evidence was estimated using the GRADE rating. A total of 26 studies with a total of 2668 patients were included in the analysis. WC patients had higher post-operative pain and disability, as well as lower satisfaction after surgery when compared to those without WC. Furthermore, WC patients demonstrated to have a delayed return to work. According to our results, compensation status is associated with poor outcomes after lumbar spine surgery. Contextualizing post-operative outcomes in clinical and work-related domains helps understand the multifactorial nature of the phenomenon.

Background: Low back pain (LPB) is the main cause of disability worldwide with enormous socioeconomic burdens. A major cause of LBP is intervertebral disc degeneration (IDD): a chronic, progressive process associated with exhaustion of the resident cell population, tissue inflammation, degradation of the extracellular matrix and dehydration of the nucleus pulposus. Eventually, IDD may lead to serious sequelae including chronic LBP, disc herniation, segmental instability, and spinal stenosis, which may require invasive surgical interventions. However, no treatment is actually able to directly tackle IDD and hamper the degenerative process. In the last decade, the intradiscal injection of stem cells is raising as a promising approach to regenerate the intervertebral disc. This review aims to describe the rationale behind a regenerative stem cell therapy for IDD as well as the effect of stem cells following their implantation in the disc environment according to preclinical studies. Furthermore, actual clinical evidence and ongoing trials will be discussed, taking into account the future perspective and current limitations of this cutting-edge therapy. Methods: A literature analysis was performed for this narrative review. A database search of PubMed, Scopus and ClinicalTrials.gov was conducted using “stem cells” combined with “intervertebral disc”, “degeneration” and “regeneration” without exclusion based on publication date. Articles were firstly screened on a title-abstract basis and, subsequently, full-text were reviewed. Both preclinical and clinical studies have been included. Results: The database search yielded recent publications from which the narrative review was completed. Conclusions: Based on available evidence, intradiscal stem cell therapy has provided encouraging results in terms of regenerative effects and reduction of LBP. However, multicenter, prospective randomized trials are needed in order confirm the safety, efficacy and applicability of such a promising treatment.

After coronavirus disease 2019 (COVID-19) caused a global pandemic, vaccines were rapidly developed to control the spread of the virus. Although they were effective in most of the cases at protecting people from becoming seriously ill and being hospitalized, they showed side effects, too. Among other adverse vaccine reactions, cutaneous eruptions following SARS-CoV-2 have been described in the literature, but they are not well-characterized yet. We described the morphology and timing of the spectrum of cutaneous reactions following most of the COVID-19 vaccines available in Italy, which were observed in outpatients referred to our non-invasive diagnostic clinic. Most of these reactions appeared after the second or third COVID-19 vaccine dose (most of them after mRNA COVID-19 vaccines). Our data support that cutaneous reactions to COVID-19 vaccination are generally self-limited; in addition, history of allergic reaction to a specific food, medicine or vaccine should not discourage vaccination in the general population, although patients with immune dysregulation should be accurately selected and monitored. Further research is necessary to better assess the true prevalence and preventive measures of skin reactions to COVID-19 vaccination.

The purpose of the present pilot study was to evaluate the effect of a hydrogel composed of hyaluronic acid (HA) and platelet-rich plasma (PRP) as a carrier for human mesenchymal stem cells (hMSCs) for intervertebral disc (IVD) regeneration using a disc organ culture model. HA was mixed with batroxobin (BTX) and PRP to form a hydrogel encapsulating 1 × 106 or 2 × 106 hMSCs. Bovine IVDs were nucleotomized and filled with hMSCs suspended in ~200 μL of the PRP/HA/BTX hydrogel. IVDs collected at day 0 and nucleotomized IVDs with no hMSCs and/or hydrogel alone were used as controls. hMSCs encapsulated in the hydrogel were also cultured in well plates to evaluate the effect of the IVD environment on hMSCs. After 1 week, tissue structure, scaffold integration, hMSC viability and gene expression of matrix and nucleus pulposus (NP) cell markers were assessed. Histological analysis showed a better preservation of the viability of the IVD tissue adjacent to the gel in the presence of hMSCs (~70%) compared to the hydrogel without hMSCs. Furthermore, disc morphology was maintained, and the hydrogel showed signs of integration with the surrounding tissues. At the gene expression level, the hydrogel loaded with hMSCs preserved the normal metabolism of the tissue. The IVD environment promoted hMSC differentiation towards a NP cell phenotype by increasing cytokeratin-19 (KRT19) gene expression. This study demonstrated that the hydrogel composed of HA/PRP/BTX represents a valid carrier for hMSCs being able to maintain a good cell viability while stimulating cell activity and NP marker expression.

Tendinopathy is a chronic and often painful condition affecting both professional athletes and sedentary subjects. It is a multi-etiological disorder caused by the interplay among overload, ageing, smoking, obesity (OB) and type 2 diabetes (T2D). Several studies have identified a strong association between tendinopathy and T2D, with increased risk of tendon pain, rupture and worse outcomes after tendon repair in patients with T2D. Moreover, consequent immobilization due to tendon disorder has a strong impact on diabetes management by reducing physical activity and worsening the quality of life. Multiple investigations have been performed to analyse the causal role of the individual metabolic factors occurring in T2D on the development of tendinopathy. Chronic hyperglycaemia, advanced glycation end-products, OB and insulin resistance have been shown to contribute to the development of diabetic tendinopathy. This review aims to explore the relationship between tendinopathy and T2D, in order to define the contribution of metabolic factors involved in the degenerative process and to discuss possible strategies for the clinical management of diabetic tendinopathy.

Diabetes is a worldwide disease also affecting the sports field. The two main forms of diabetes, namely type 1 diabetes (T1D) and type 2 diabetes (T2D), differ in both their pathological and pharmacological characteristics and thus require a distinct nutritional treatment. Diet plays an important role in the management of athletes with diabetes and is crucial to achieving their best performance. This review aims to investigate the objectives of nutritional therapy before, during and after training, in order to improve the best composition of macronutrients during meals. In this review, we provide a brief overview of recent studies about nutritional approaches to people with diabetes for performance optimization and for the control of diabetes-related complications. Thereafter, we discuss the differences between macronutrients and dietary intake before, during and after training. It can be concluded that each sport has particular characteristics in terms of endurance and power, hence demanding a specific energy expenditure and consequent nutritional adjustments. Therefore, the management of athletes with diabetes must be personalized and supported by medical professionals, including a diabetologist, physiologist and a nutritionist.

Low back pain (LBP) is one of the leading causes of disability worldwide, with a significant socioeconomic burden on healthcare systems. It is mainly caused by degenerative disc disease (DDD), a progressive, chronic, and age-related process. With its capacity to accurately characterize intervertebral disc (IVD) and spinal morphology, magnetic resonance imaging (MRI) has been established as one of the most valuable tools in diagnosing DDD. However, existing technology cannot detect subtle changes in IVD tissue composition and cell metabolism. In this review, we summarized the state of the art regarding innovative quantitative MRI modalities that have shown the capacity to discriminate and quantify changes in matrix composition and integrity, as well as biomechanical changes in the early stages of DDD. Validation and implementation of this new technology in the clinical setting will allow for an early diagnosis of DDD and ideally guide conservative and regenerative treatments that may prevent the progression of the degenerative process rather than intervene at the latest stages of the disease.