Surgical interventions for treating hallux valgus and bunions.

BACKGROUND: Hallux valgus (lateral angulation of the great toe towards the lesser toes, commonly known as bunions) presents in 23% to 35% of the population. This condition leads to poor balance and increases the risk of falling, adding to the difficulty in fitting into shoes and pain. Conservative (non-surgical) interventions treating pain rather than curing deformity are usually first-line treatments. When surgery is indicated, the overall best surgical procedure is an ever-evolving topic of discussion. OBJECTIVES: To assess the benefits and harms of different types of surgery compared with placebo or sham surgery, no treatment, non-surgical treatments and other surgical interventions for adults with hallux valgus. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and trial registries to 20 April 2023. We did not apply any language or publication restrictions. SELECTION CRITERIA: We included randomised controlled trials evaluating surgical interventions for treating hallux valgus compared to placebo surgery or sham surgery, no treatment, non-surgical treatment or other surgical interventions. The major outcomes were pain, function, quality of life, participant global assessment of treatment success, reoperation (treatment failure), adverse events and serious adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted data, and assessed risk of bias and the certainty of evidence using GRADE. MAIN RESULTS: We included 25 studies involving 1597 participants with hallux valgus. All studies included adults and most were women. One study compared surgery (V-shaped osteotomy) with no treatment and with non-surgical treatment. Fifteen studies compared different surgical techniques, including a V-shaped osteotomy (Chevron osteotomy), to other types of osteotomy. Nine studies compared different simple osteotomy techniques to each other or to a mid-shaft Z-shaped osteotomy (Scarf osteotomy). Most trials were susceptible to bias: in particular, selection (80%), performance (88%), detection (96%) and selective reporting (64%) biases. Surgery versus no treatment Surgery may result in a clinically important reduction in pain. At 12 months, mean pain was 39 points (0 to 100 visual analogue scale, 100 = worst pain) in the no treatment group and 21 points in the surgery group (mean difference (MD) -18.00, 95% confidence interval (CI) -26.14 to -9.86; 1 study, 140 participants; low-certainty evidence). Evidence was downgraded for bias due to lack of blinding and imprecision. Surgery may result in a slight increase in function. At 12 months, mean function was 66 points (0 to 100 American Orthopedics Foot and Ankle Scale (AOFAS), 100 = best function) in the no treatment group and 75 points in the surgery group (MD 9.00, 95% CI 5.16 to 12.84; 1 study, 140 participants; low-certainty evidence). Evidence was downgraded for bias due to lack of blinding and imprecision. Surgery may result in little to no difference in quality of life. At 12 months, mean quality of life (0 to 100 on 15-dimension scale, 100 = higher quality of life) was 93 points in both groups (MD 0, 95% CI -2.12 to 2.12; 1 study, 140 participants; low-certainty evidence). Evidence was downgraded for bias due to lack of blinding and imprecision. Surgery may result in a slight increase in participant global assessment of treatment success. At 12 months, mean participant global assessment of treatment success was 61 points (0 to 100 visual analogue scale, 100 = completely satisfied) in the no treatment group and 80 points in the surgery group (MD 19.00, 95% CI 8.11 to 29.89; 1 study, 140 participants; low-certainty evidence). Evidence was downgraded for bias due to lack of blinding and imprecision. Surgery may have little effect on reoperation (relative effect was not estimable), adverse events (risk ratio (RR) 8.75, 95% CI 0.48 to 159.53; 1 study, 140 participants; very low-certainty evidence), and serious adverse events (relative effect was not estimable), but we are uncertain. Surgery versus non-surgical treatment Surgery may result in a clinically important reduction in pain; a slight increase in function and participant global assessment of treatment success; and little to no difference in quality of life (1 study, 140 participants; low-certainty evidence). We are uncertain about the effect on reoperation, adverse events and serious adverse events (1 study, 140 participants; very low-certainty evidence). Complex versus simple osteotomies Complex osteotomies probably result in little to no difference in pain compared with simple osteotomies (7 studies, 414 participants; moderate-certainty evidence). Complex osteotomies may increase reoperation (7 studies, 461 participants; low-certainty evidence), and may result in little to no difference in participant global assessment of treatment success (8 studies, 462 participants; low-certainty evidence) and serious adverse events (12 studies; data not pooled; low-certainty evidence). We are uncertain about the effect of complex osteotomies on function and adverse events (very low-certainty evidence). No study reported quality of life. AUTHORS' CONCLUSIONS: There were no trials comparing surgery to placebo or sham. Surgery may result in a clinically important reduction in pain when compared to no treatment or non-surgical treatment. Surgery may also result in a slight increase in function and participant global assessment of treatment success compared to no treatment or non-surgical treatment. There may be little to no difference in quality of life between surgery and no treatment or non-surgical treatment. We are uncertain about the effect of surgery on reoperation (treatment failure), adverse events or serious adverse events, when compared to no treatment or non-surgical treatment. Complex and simple osteotomies demonstrated similar results for pain. Complex osteotomies may increase reoperation (treatment failure) and may result in little to no difference in participant global assessment of treatment success and serious adverse events compared to simple osteotomies. We are uncertain about the effect of complex osteotomies on function, quality of life and adverse events.

Comparative Effects of Intra-Articular versus Intravenous Mesenchymal Stromal Cells Therapy in a Rat Model of Osteoarthritis by Destabilization of Medial Meniscus.

Transplanted mesenchymal stromal cells (MSCs) exhibit a robust anti-inflammatory and homing capacity in response to high inflammatory signals, as observed in studies focused on rheumatic diseases that target articular cartilage (AC) health. However, AC degradation in osteoarthritis (OA) does not necessarily coincide with a highly inflammatory joint profile. Often, by the time patients seek medical attention, they already have damaged AC. In this study, we examined the therapeutic potential of a single bone marrow MSC transplant (2 × 106 cells/kgbw) through two different routes: intra-articular (MSCs-IAt) and intravenous (MSCs-IVt) in a preclinical model of low-grade inflammatory OA with an established AC degeneration. OA was induced through the destabilization of the medial meniscus (DMM) in female Wistar Kyoto rats. The animals received MSCs 9 weeks after surgery and were euthanized 4 and 12 weeks post-transplant. In vivo and ex vivo tracking of MSCs were analyzed via bioluminescence and imaging flow cytometry, respectively. Cytokine/chemokine modulation in serum and synovial fluid was measured using a multiplex panel. AC degeneration was quantified through histology, and hindlimb muscle balance was assessed with precision weighing. To our knowledge, we are the first group to show the in vivo (8 h) and ex vivo (12 h) homing of cells to the DMM-OA joint following MSCs-IVt. In the case of MSCs-IAt, the detection of cellular bioluminescence at the knee joint persisted for up to 1 week. Intriguingly, intra-articular saline injection (placebo-IAt) resulted in a worse prognosis of OA when compared to a non-invasive control (placebo-IVt) without joint injection. The systemic cytokines/chemokines profile exhibited a time-dependent variation between transplant routes, displaying a transient anti-inflammatory systemic response for both MSCs-IVt and MSCs-IAt. A single injection of MSCs, whether administered via the intra-articular or intravenous route, performed 9 weeks after DMM surgery, did not effectively inhibit AC degeneration when compared to a non-invasive control.

Monitoring health as an opportunity to categorize preventative and early-treatment actions in a self-care journey: our experience with a Healthcare Magenta Scorecard.

Background: Applying a digital health intervention to measure health and wellbeing status offers opportunities to guide and augment healthcare and promotion. In our scenario, we consider mainly digital-native patients and present an evaluation of a new Healthcare Magenta Scorecard towards this end. Methods: Grounded in the six domains of health and promotion (physical activity; sleep quality; nutrition; habits/lifestyle; mental health; quality of life) we developed a health Magenta Scorecard (Magenta Score), a mobile based Electronic Patient Reported Outcomes (e-PRO) that measures patients health and wellbeing every 3-5 months. The Magenta Scorecard was derived from previously published evidence-based instruments. We collected data as patients were onboarded into our healthcare system (T0 and T1, time span between measurements, 141 days) and provided correlations among our domains of care. Results: A total of 1,622 participants responded to T0 and T1 our Magenta Scorecard. Participants mean age was 31.3 [95% confidence interval (CI): 31.2-31.5] years and female (63.4%). Fifty-five percent (n=892) of our sample were categorized as relating to Health and Wellbeing promotion, 8.5% (n=138) disease management, 35.7% (n=579) self-care care support and only 0.8% (n=13) pertained to case management. From our care coordination guided approach, our Magenta Scorecards reported mean improvement across the study cohort of 26 ± standard deviation (SD) points, from T0 (649, 95% CI: 643-656) to T1 (675, 95% CI: 668-682). Our Magenta Scorecard domains had significant, albeit weak spearman correlations. Conclusions: We demonstrated our Magenta Scorecard rationale and its guided approach. The Magenta Scorecard displayed adequate responsiveness and was significantly correlated across all of the domains investigated. Further prospective research is needed to validate our results in the long term.

Assessment of the Risk Factors Related to the Length of Hospital Stay and Postoperative Complications in Patients Undergoing Primary Total Knee Arthroplasty.

Objective To assess the risk factors involving longer hospital stays and early postoperative complications (first 30 days after surgery) in patients undergoing total knee arthroplasty (TKA). Materials and Methods A cross-sectional study was conducted with collection of data of patients who underwent TKA in a private hospital between 2015 and 2019. The following data were collected: age, gender, body mass index, and clinical comorbidities. We also collected intraoperative data such as the grade on the classification of the American Society of Anesthesiologists (ASA), the duration of the surgery, the length of stay, the postoperative complications, and readmission within 30 days. Statistical models were used to investigate the possible risk factors associated with longer hospital stays and postoperative complications. Results There was evidence of an increase in the length of hospital stay in older patients, with higher grades on the ASA classification or who suffered postoperative complications. For each increase in 1 year of age, we expect the length of stay to be multiplied by 1.008 (95% confidence interval [95%CI]: 1.004 to 1.012; p < 0,001). In patients who were ASA grade III, the time is expected to be multiplied by 1.297 (95%CI: 1.083 to 1.554; p = 0,005) when compared with grade-I patients. In patients who suffered postoperative complications, the time is expected to be multiplied by 1.505 (95%CI: 1.332 to 1.700; p < 0.001) compared with patients without complications. Conclusion The present study demonstrated that, in patients who underwent primary TKA, preoperative characteristics such as older age and ASA grade ≥ III, as well as the development of postoperative complications, independently predict the increase in the length of hospital stay.

Assessment of the Risk Factors Related to the Length of Hospital Stay and Postoperative Complications in Patients Undergoing Primary Total Knee Arthroplasty / Avaliação dos fatores de risco relacionados ao tempo de internação e às complicações pós-operatórias em pacientes submetidos a artroplastia total primária do joelho

Abstract Objective To assess the risk factors involving longer hospital stays and early postoperative complications (first 30 days after surgery) in patients undergoing total knee arthroplasty (TKA). Materials and Methods Across-sectional study was conducted with collection of data of patients who underwent TKA in a private hospital between 2015 and 2019. The following data were collected: age, gender, body mass index, and clinical comorbid-ities. We also collected intraoperative data such as the grade on the classification of the American Society of Anesthesiologists (ASA), the duration of the surgery, the length of stay, the postoperative complications, and readmission within 30 days. Statistical models were used to investigate the possible risk factors associated with longer hospital stays and postoperative complications. Results There was evidence of an increase in the length of hospital stay in older patients, with higher grades on the ASA classification or who suffered postoperative complications. For each increase in 1 year of age, we expect the length of stay to be multiplied by 1.008 (95% confidence interval [95%CI]: 1.004 to 1.012; p < 0,001). In patients who were ASA grade III, the time is expected to be multiplied by 1.297 (95%CI: 1.083 to 1.554; p = 0,005) when compared with grade-I patients. In patients who suffered postoperative complications, the time is expected to be multiplied by 1.505 (95%CI: 1.332 to 1.700; p < 0.001) compared with patients without complications. Conclusion The present study demonstrated that, in patients who underwent primary TKA, preoperative characteristics such as older age and ASA grade > III, as well as the development of postoperative complications, independently predict the increase in the length of hospital stay.

Resumo Objetivo Avaliar os fatores de risco relacionados a um tempo de internação mais longo e às complicações pós-operatórias precoces (primeiros 30 dias após a cirurgia) em pacientes submetidos a artroplastia total do joelho (ATJ). Materiais e Métodos Este é um estudo transversal com coleta de dados de pacientes submetidos a ATJ em um hospital privado entre 2015 e 2019. Os seguintes dados foram coletados: idade, gênero, índice de massa corporal, e comorbidades clínicas. Também coletamos dados intraoperatórios, como o grau na classificação da American Society of Anesthesiologists (ASA) e a duração da cirurgia, além do tempo de internação, as complicações pós-operatórias, e a readmissão em 30 dias. Os possíveis fatores de risco associados a um tempo de internação mais longo e às taxas de complicações pós-operatórias foram investigados por meio de modelos estatísticos. Resultados Os pacientes mais velhos, com graus mais elevados na classificação da ASA ou que sofreram complicações pós-operatórias, ficaram internados por mais tempo. Para cada aumento em um ano de idade, esperamos que o tempo de internação seja multiplicado por 1,008 (intervalo de confiança de 95% [IC95%]: 1,004 a 1,012; p < 0,001). Em pacientes de grau III na classificação da ASA, espera-se que o tempo seja multiplicado por 1,297 (IC95%: 1,083 a 1,554; p = 0,005) em comparação com pacientes de grau I. Em pacientes com complicações pós-operatórias, espera-se que o tempo seja multiplicado por 1,505 (IC95%: 1,332 a 1,700; p < 0,001) em comparação com pacientes sem complicações. Conclusão Este estudo demonstrou que, em pacientes submetidos a ATJ primária, características pré-operatórias, como idade avançada e grau ≥ III na classificação da ASA, e o desenvolvimento de complicações pós-operatórias predizem o aumento do tempo de internação hospitalar de forma independente.

Quality of Life and Satisfaction in Patients Above and Under 65 Years Old Submitted to Total Knee Arthroplasty.

Objective To compare the level of quality of life and satisfaction after two years of total knee arthroplasties between individuals above and below 65 years of age and to identify predictor factors of poor clinical outcome and low level of satisfaction in patients undergoing arthroplasty. Methods This is a retrospective cohort with data from patients diagnosed with knee osteoarthritis submitted to primary total knee arthroplasty from 2014 to 2018 ( n = 190). Clinical outcomes were assessed using the following scores: visual analog scale (VAS) of pain, EQ-5D-3L and EUROQOL-VAS (quality of life scales), patient satisfaction level, and functional scale of the Knee Injury and Osteoarthritis Outcome Score (KOOS), collected through a questionnaire applied preoperatively, as well as 1, 3, 12 and 24 months after surgery. Results Patients < 65 years old presented significantly lower values (clinical worsening) in KOOS-pain and KOOS-symptoms. There are no differences in the principal clinical scores that assess pain, function, and quality of life after the procedure, as well as in the rate of satisfaction with the procedure, among patients < 65 years old when compared with patients ≥ 65 years old. It was also observed that patients who were not satisfied with the procedure in the 24-month evaluation presented clinical results in some analyzed scores (KOOS-pain and EQ-VAS) similar to patients who declared themselves satisfied. Conclusion Scores that assess pain, function, quality of life, as well as satisfaction rate are similar between patients < 65 years old and those ≥ 65 years old.

Quality of Life and Satisfaction in Patients Above and Under 65 Years Old Submitted to Total Knee Arthroplasty / Qualidade de vida e satisfação de pacientes com idade superior ou inferior a 65 anos submetidos a artroplastia total de joelho

Abstract Objective To compare the level of quality of life and satisfaction after two years of total knee arthroplasties between individuals above and below 65 years of age and to identify predictor factors of poor clinical outcome and low level of satisfaction in patients undergoing arthroplasty. Methods This is a retrospective cohort with data from patients diagnosed with knee osteoarthritis submitted to primary total knee arthroplasty from 2014 to 2018 (n= 190). Clinical outcomes were assessed using the following scores: visual analog scale (VAS) of pain, EQ-5D-3L and EUROQOL-VAS (quality of life scales), patient satisfaction level, and functional scale of the Knee Injury and Osteoarthritis Outcome Score (KOOS), collected through a questionnaire applied preoperatively, as well as 1, 3, 12 and 24 months after surgery. Results Patients < 65 years old presented significantly lower values (clinical worsening) in KOOS-pain and KOOS-symptoms. There are no differences in the principal clinical scores that assess pain, function, and quality of life after the procedure, as well as in the rate of satisfaction with the procedure, among patients < 65 years old when compared with patients ≥ 65 years old. It was also observed that patients who were not satisfied with the procedure in the 24-month evaluation presented clinical results in some analyzed scores (KOOS-pain and EQ-VAS) similar to patients who declared themselves satisfied. Conclusion Scores that assess pain, function, quality of life, as well as satisfaction rate are similar between patients < 65 years old and those ≥ 65 years old.

Resumo Objetivo Comparar a qualidade de vida e satisfação 2 anos após a artroplastia total de joelho em indivíduos com idade ≥ e < 65 anos e identificar fatores preditivos de pior evolução clínica e baixo nível de satisfação nestes pacientes. Métodos Trata-se de uma coorte retrospectiva de dados de pacientes com diagnóstico de osteoartrite de joelho submetidos a artroplastia total primária de joelho entre 2014 e 2018 (n= 190). Os resultados clínicos foram avaliados de acordo com os seguintes escores: escala visual analógica (EVA) de dor, EQ-5D-3L e EUROQOL-VAS (escalas de qualidade de vida), nível de satisfação do paciente e escala funcional do Knee Injury and Osteoarthritis Outcome Score (KOOS, na sigla em inglês). Estes dados foram coletados por meio de questionário aplicado no período pré-operatório e 1, 3, 12 e 24 meses após a cirurgia. Resultados Os pacientes < 65 anos apresentaram valores significativamente menores (piora clínica) nas escalas KOOS-dor e KOOS-sintomas. Não houve diferenças nas principais pontuações clínicas de dor, função e qualidade de vida após o procedimento, nem no índice de satisfação com a cirurgia, entre pacientes < 65 anos em comparação com aqueles ≥ 65 anos. Observamos também que os pacientes não satisfeitos com o procedimento à avaliação de 24 meses apresentaram resultados clínicos em alguns escores analisados (KOOS-dor e EQ-VAS) semelhantes aos dos pacientes que se declararam satisfeitos. Conclusão Os escores que avaliam dor, função, qualidade de vida e índice de satisfação são semelhantes entre os pacientes < 65 anos e aqueles ≥ 65 anos.

Impact of Hyaluronic Acid on the Viability of Mesenchymal Cells Derived from Adipose Tissue Grown in Collagen Type I/III Membrane.

Objective To evaluate in vitro the viability of mesenchymal stem cells derived from adipose tissue (AD-MSCs) in different commercial solutions of hyaluronic acid (HA) before and after being sowed in collagen I/III membrane. Methods In the first stage, the interaction between AD-MSCs was analyzed with seven different commercial products of HA, phosphate buffered saline (PBS), and bovine fetal serum (BFS), performed by counting living and dead cells after 24, 48 and 72 hours. Five products with a higher number of living cells were selected and the interaction between HA with AD-MSCs and type I/III collagen membrane was evaluated by counting living and dead cells in the same time interval (24, 48 and 72 hours). Results In both situations analyzed (HA + AD-MSCs and HA + AD-MSCs + membrane), BFS presented the highest percentage of living cells after 24, 48 and 72 hours, a result higher than that of HA. Conclusion The association of HA with AD-MSCs, with or without membrane, showed no superiority in cell viability when compared with BFS.

Impact of Hyaluronic Acid on the Viability of Mesenchymal Cells Derived from Adipose Tissue Grown in Collagen Type I/III Membrane / Impacto do ácido hialurônico na viabilidade das células mesenquimais derivadas do tecido adiposo cultivadas em membrana de colágeno tipo I/III

Abstract Objective To evaluate in vitro the viability of mesenchymal stem cells derived from adipose tissue (AD-MSCs) in different commercial solutions of hyaluronic acid (HA) before and after being sowed in collagen I/III membrane. Methods In the first stage, the interaction between AD-MSCs was analyzed with seven different commercial products of HA, phosphate buffered saline (PBS), and bovine fetal serum (BFS), performed by counting living and dead cells after 24, 48 and 72 hours. Five products with a higher number of living cells were selected and the interaction between HA with AD-MSCs and type I/III collagen membrane was evaluated by counting living and dead cells in the same time interval (24, 48 and 72 hours). Results In both situations analyzed (HA + AD-MSCs and HA + AD-MSCs + membrane), BFS presented the highest percentage of living cells after 24, 48 and 72 hours, a result higher than that of HA. Conclusion The association of HA with AD-MSCs, with or without membrane, showed no superiority in cell viability when compared with BFS.

Resumo Objetivo Avaliar in vitro a viabilidade das células-tronco mesenquimais derivadas do tecido adiposo (AD-CTMs) em diferentes soluções comerciais de ácido hialurônico (AH) antes e após serem semeadas em membrana de colágeno I/III. Métodos Na primeira etapa, analisou-se a interação entre AD-CTMs com sete diferentes produtos comerciais de AH, salina tamponada com fosfato (PBS, na sigla em inglês) e soro fetal bovino (SFB), realizada pela contagem das células vivas e mortas após 24, 48 e 72 horas. Foram selecionados cinco produtos com maior número de células vivas e avaliou-se a interação entre o AH com AD-CTMs e a membrana de colágeno tipo I/III pela contagem de células vivas e mortas no mesmo intervalo de tempo (24, 48 e 72 horas). Resultados Em ambas as situações analisadas (AH + AD-CTM e AH + AD-CTM + membrana), o SFB apresentou a maior porcentagem de células vivas após 24, 48 e 72 horas, resultado superior ao do AH. Conclusão A associação do AH com as AD-CTMs, com ou sem a membrana, não demonstrou superioridade na viabilidade celular quando comparado com SFB.

Report of a clinical and laboratory management of cell therapy for knee cartilage in the face of mycoplasma contamination.

To describe a case of autologous chondrocyte implantation after cell culture contamination by Mycoplasma pneumoniae and the measures taken to successfully complete cell therapy in a patient with focal chondral lesion. A 45-year-old male patient, complaining of chronic pain on the knee and no history of trauma. He had a chondral lesion in the trochlear region of the femur and clinical tests compatible with pain in the anterior compartment of the knee. Conservative treatment failed to alleviate symptoms. Surgical treatment was indicated, but due to the size of the lesion, membrane-assisted autologous chondrocyte implantation was the technique of choice. Cartilage biopsies were collected from the intercondylar region of the distal femur. After isolation, chondrocytes were expanded ex vivo in a trained laboratory, for three weeks, and seeded onto a commercially available collagen membrane prior to implantation in the knee. Two days before surgery, a cell culture sample tested positive for Mycoplasma pneumoniae. The source of contamination was found to be autologous blood serum, extracted from the patient´s peripheral vein, and used to supplement the cell culture medium. After treating the patient with antibiotics, all procedures were repeated and the new final cell product, free from contaminants, was successfully implanted. We discuss the strategies available to deal with this situation, and describe the results of this particular case, which led to modifications in the autologous chondrocyte implant protocol.

Clinical outcome analysis in surgical patients enrolled in a Second Opinion Program in spine surgery.

OBJECTIVE: To analyze pain, functional capacity, quality of life, anxiety and depression outcomes in patients undergoing lumbar spine surgery following use of the Second Opinion Program, and to present disagreements regarding diagnoses and therapeutic indications between the first and second opinions. METHODS: A prospective, observational cohort study with 100 patients enrolled in the Second Opinion Program who underwent lumbar spine surgery. Questionnaires addressing pain intensity, level of disability, quality of life, anxiety and depression were applied prior to and within 1, 3, 6 and 12 months of surgery. Descriptive and comparative statistical analyses were performed. The following clinical outcomes were analyzed: pain intensity, level of disability, quality of life, anxiety, and depression. RESULTS: In this sample, 88% and 12% out of 100 patients were submitted to lumbar decompression and arthrodesis, respectively. Patients reported improvements in function, pain intensity, and quality of life factors following surgery and were able to attain the minimal clinically important difference relative to the preoperative period. Agreement between the first and second opinions was observed in 44% of diagnoses, and in 27% of therapeutic indications. CONCLUSION: Patients had favorable postoperative outcomes regarding pain, disability, and quality of life. These findings and the high rates of diagnostic and therapeutic indication disagreements corroborate the need of a second opinion in cases of spine disease with surgical indications.

Minimally invasive swine spine surgery training: technical aspects, benefits, and anatomical limitations.

OBJECTIVE: To describe the technical specificities and feasibility of simulation of minimally invasive spine surgery in live pigs, as well as similarities and differences in comparison to surgery in humans. METHODS: A total of 22 Large White class swine models, weighing between 60 and 80kg, were submitted to surgical simulations, performed during theoretical-practical courses for training surgical techniques (microsurgical and endoscopic lumbar decompression; percutaneous pedicular instrumentation; lateral access to the thoracic spine, and anterior and retroperitoneal to the lumbar spine, and management of complications) by 86 spine surgeons. For each surgical technique, porcine anatomy (similarities and differences in relation to human anatomy), access route, and dimensions of the instruments and implants used were evaluated. Thus, the authors describe the feasibility of each operative simulation, as well as suggestions to optimize training. Study results are descriptive, with figures and drawings. RESULTS: Neural decompression surgeries (microsurgeries and endoscopic) and pedicular instrumentation presented higher similarities to surgery on humans. On the other hand, intradiscal procedures had limitations due to the narrow disc space in swines. We were able to simulate situations of surgical trauma in surgical complication scenarios, such as cerebrospinal fluid fistulas and excessive bleeding, with comparable realism to surgery on humans. CONCLUSION: A porcine model for simulation of minimally invasive spinal surgical techniques had similarities with surgery on humans, and is therefore feasible for surgeon training.

Matrix-assisted autologous chondrocyte transplantation for treatment of focal chondral lesions in the knee: the Hospital Israelita Albert Einstein experience

ABSTRACT Objective Phase 1 clinical trial to determine feasibility, safety, and efficacy of a new advanced cell therapy product for treatment of knee articular cartilage injuries. Methods Three participants with knee focal chondral lesions were included, with no signs of osteoarthritis. Chondrocytes were obtained through knee arthroscopy, cultured in collagen membrane for 3 weeks at the laboratory, subjected to tests to release the cell therapy product, and implanted. All patients underwent a specific 3-month rehabilitation protocol, followed by assessments using functional and imaging scales. The main outcome was the incidence of severe adverse events. Results Three participants were included and completed the 2-year follow-up. There was one severe adverse event, venous thrombosis of distal leg veins, which was no associated with therapy, was treated and left no sequelae. The clinical and radiological scales showed improvement in the three cases. Conclusion The preliminary results, obtained with the described methodology, allow concluding that this product of advanced cell therapy is safe and feasible. ReBEC platform registration number: RBR-6fgy76

Report of a clinical and laboratory management of cell therapy for knee cartilage in the face of mycoplasma contamination

ABSTRACT To describe a case of autologous chondrocyte implantation after cell culture contamination by Mycoplasma pneumoniae and the measures taken to successfully complete cell therapy in a patient with focal chondral lesion. A 45-year-old male patient, complaining of chronic pain on the knee and no history of trauma. He had a chondral lesion in the trochlear region of the femur and clinical tests compatible with pain in the anterior compartment of the knee. Conservative treatment failed to alleviate symptoms. Surgical treatment was indicated, but due to the size of the lesion, membrane-assisted autologous chondrocyte implantation was the technique of choice. Cartilage biopsies were collected from the intercondylar region of the distal femur. After isolation, chondrocytes were expanded ex vivo in a trained laboratory, for three weeks, and seeded onto a commercially available collagen membrane prior to implantation in the knee. Two days before surgery, a cell culture sample tested positive for Mycoplasma pneumoniae. The source of contamination was found to be autologous blood serum, extracted from the patient´s peripheral vein, and used to supplement the cell culture medium. After treating the patient with antibiotics, all procedures were repeated and the new final cell product, free from contaminants, was successfully implanted. We discuss the strategies available to deal with this situation, and describe the results of this particular case, which led to modifications in the autologous chondrocyte implant protocol.

Minimally invasive swine spine surgery training: technical aspects, benefits, and anatomical limitations

ABSTRACT Objective To describe the technical specificities and feasibility of simulation of minimally invasive spine surgery in live pigs, as well as similarities and differences in comparison to surgery in humans. Methods A total of 22 Large White class swine models, weighing between 60 and 80kg, were submitted to surgical simulations, performed during theoretical-practical courses for training surgical techniques (microsurgical and endoscopic lumbar decompression; percutaneous pedicular instrumentation; lateral access to the thoracic spine, and anterior and retroperitoneal to the lumbar spine, and management of complications) by 86 spine surgeons. For each surgical technique, porcine anatomy (similarities and differences in relation to human anatomy), access route, and dimensions of the instruments and implants used were evaluated. Thus, the authors describe the feasibility of each operative simulation, as well as suggestions to optimize training. Study results are descriptive, with figures and drawings. Results Neural decompression surgeries (microsurgeries and endoscopic) and pedicular instrumentation presented higher similarities to surgery on humans. On the other hand, intradiscal procedures had limitations due to the narrow disc space in swines. We were able to simulate situations of surgical trauma in surgical complication scenarios, such as cerebrospinal fluid fistulas and excessive bleeding, with comparable realism to surgery on humans. Conclusion A porcine model for simulation of minimally invasive spinal surgical techniques had similarities with surgery on humans, and is therefore feasible for surgeon training.

Clinical outcome analysis in surgical patients enrolled in a Second Opinion Program in spine surgery

ABSTRACT Objective To analyze pain, functional capacity, quality of life, anxiety and depression outcomes in patients undergoing lumbar spine surgery following use of the Second Opinion Program, and to present disagreements regarding diagnoses and therapeutic indications between the first and second opinions. Methods A prospective, observational cohort study with 100 patients enrolled in the Second Opinion Program who underwent lumbar spine surgery. Questionnaires addressing pain intensity, level of disability, quality of life, anxiety and depression were applied prior to and within 1, 3, 6 and 12 months of surgery. Descriptive and comparative statistical analyses were performed. The following clinical outcomes were analyzed: pain intensity, level of disability, quality of life, anxiety, and depression. Results In this sample, 88% and 12% out of 100 patients were submitted to lumbar decompression and arthrodesis, respectively. Patients reported improvements in function, pain intensity, and quality of life factors following surgery and were able to attain the minimal clinically important difference relative to the preoperative period. Agreement between the first and second opinions was observed in 44% of diagnoses, and in 27% of therapeutic indications. Conclusion Patients had favorable postoperative outcomes regarding pain, disability, and quality of life. These findings and the high rates of diagnostic and therapeutic indication disagreements corroborate the need of a second opinion in cases of spine disease with surgical indications.

Lumbar Decompression Versus Spinal Fusion ina Private Outpatient Setting: A Retrospective Study with Three Years of Follow-up / Descompressão lombar versus fusão espinhal em ambiente ambulatorial privado: Um estudo retrospectivo com três anos de acompanhamento

Abstract Objective To compare pain, function, quality of life and adverse events of lumbar decompression and spinal fusion in patients with degenerative spinal pathologies who participated in a second opinion program for spinal surgeries with a 36-month followup. Methods The data for this retrospective cohort were withdrawn from a private healthcare system between June 2011 and January 2014. The study sample consisted of 71 patients with a lumbar spine surgical referral. The outcomes for the comparisons between lumbar decompression and spinal fusion were quality of life (evaluated through the EuroQoL 5D), pain (measured by the Numerical Rating Scale) and function (assessed through the Roland Morris Disability Questionnaire) measured at baseline, and at 12 and 36 months after the surgical procedures. The definitions of recovery were established by the minimal clinically important difference (MCID). The baseline differences between the groups were analyzed by non-paired t-test, and the differences in instrument scores between time points, by generalized mixed models. The results were presented as mean values adjusted by the models and 95% confidence intervals. Results Concerning the surgical techniques, 22 patients were submitted to spinal fusion and 49 patients, to lumbar decompression. As for the comparisons of the findings before and after the surgical interventions, the MCID was achieved in all outcomes regarding quality of life, pain and function at both time points when compared to baseline scores Moreover, concerning the complication rates, only lumbar decompression presented a surgical rate of 4% (n = 3) for recurrence of lumbar disc hernia. Conclusion Patients with degenerative spinal pathologies present improvements in long-term outcomes of pain, function and quality of life which are clinically significant, no matter the surgical intervention.

Resumo Objetivo Comparar a dor, a função, a qualidade de vida e os eventos adversos da descompressão lombar e da fusão espinhal em pacientes com patologias degenerativas da coluna vertebral que participaram de um programa de segunda opinião para cirurgias de coluna com acompanhamento de 36 meses. Métodos Os dados desta coorte retrospectiva foram obtidos de um sistema de saúde privado entre junho de 2011 e janeiro de 2014. A amostra do estudo foi composta por 71 pacientes encaminhados para cirurgia de coluna lombar. Os desfechos para comparações entre a descompressão lombar e a fusão espinhal foram qualidade de vida (avaliada pelo questionário EuroQoL 5D), dor (medida pela Escala Numérica de Classificação de Dor) e função (avaliada pelo Questionário de Incapacidade de Roland Morris) no início do estudo e aos 12 e 36 meses de acompanhamento pós-cirúrgico. As definições de recuperação foram estabelecidas pela diferença mínima clinicamente importante (DMCI). As diferenças basais entre os grupos foram analisadas por teste t não pareado, e as diferenças nas pontuações dos instrumentos entre os momentos, por modelos mistos generalizados. Os resultados foram apresentados como valores médios ajustados pelos modelos e intervalos de confiança de 95%. Resultados No total, 22 pacientes foram submetidos à artrodese, e 49 pacientes, à descompressão lombar. Quanto às comparações de achados antes e depois das intervenções cirúrgicas, a DMCI foi alcançada em todos os desfechos de qualidade de vida, dor e função nos dois pontos de acompanhamento em relação aos escores basais Em relação às complicações, apenas a descompressão lombar apresentou 4% (n = 3) de taxa cirúrgica de recidiva da hérnia de disco lombar. Conclusão Pacientes com patologias espinhais degenerativas apresentam melhoras nos desfechos de dor, função e qualidade de vida em longo prazo que são clinicamente significativas e independentes da intervenção cirúrgica.

Clinical pathway improves medical practice in total knee arthroplasty.

PURPOSE: Clinical pathways in total knee arthroplasty (TKA) consist of general guidelines, including several topics as early rehabilitation and antibiotic systematization, which are used to improve patient's management, decrease complication rates and enhance clinical outcomes. The primary purpose of this study was to assess whether the use of a clinical pathway for TKA can contribute to reduce LOS and healthcare costs in a private hospital, without an increase in the hospital readmission rate. We also aimed to assess whether care providers adhered to the recommendations mainly antibiotic use and physical therapy. METHODS: Retrospective cohort study of 485 patients who underwent TKA at private hospital. Patients were analyzed in two groups: Group I (GI), composed by 220 TKA patients, prior to the clinical pathway implementation, and Group 2 (GII), with 265 TKA patients post-clinical pathway. Several outcomes were analyzed: length of hospital stay, time from use of prophylactic antibiotic therapy, readmission within 30 days, physical therapy and costs associated to procedures and hospitalization rates. RESULTS: The implementation of the clinical pathway was related with the reduction of the length of hospital stay from 6.3 days to 4.9 days (p = 0.021) without increase in readmissions. The physical therapy on the first postoperative day was most frequent in GII than GI (96.2% vs 78.1%, p < 0.001). Prophylactic ATB 60 minutes prior the surgery was significantly more used in GII than GI (99.2% vs 87.4%, p < 0.001). In addition, ATB suspension within 48 hours was significantly more frequent in GII than GI (84.7% vs. 51.6%, p < 0.001). The cost procedure of TKA showed a reduction of US$1,252.00 in GII when compared with GI (p<0,001). CONCLUSION: The implementation of a clinical pathway, with focus on early rehabilitation, for patients underwent TKA, contributed to a reduction of LOS and costs during hospital stay, with no increase in the readmission rate. We also concluded that there was adherence to the clinical pathway by care providers in our institution.

Individual response to mTOR inhibition in delaying replicative senescence of mesenchymal stromal cells.

BACKGROUND AIMS: Delaying replicative senescence and extending lifespan of human mesenchymal stromal cells (MSCs) may enhance their potential for tissue engineering and cell based therapies. Accumulating evidence suggests that inhibitors of the mTOR signaling pathway, such as rapamycin, constitute promising pharmacological agents to retard senescence and extend stemness properties of various progenitor cell types. Here, we investigated whether the ability of rapamycin to postpone replicative senescence varies among bone marrow MSC samples (BM-MSCs) derived from different healthy donors, and explored the molecular mechanisms that drive rapamycin-mediated lifespan increment. METHODS: BM-MSCs at early passages were serially passaged either in absence or continuous presence of rapamycin and the number of cell population doublings until growth arrest was measured. The inhibition of mTOR signaling was assessed by the phosphorylation status of the downstream target RPS6. The expression levels of several senescence and pluripotency markers at early and late/senescent passages were analyzed by RT-qPCR, flow cytometry and western blot. RESULTS: We found that the lifespan extension in response to the continuous rapamycin treatment was highly variable among samples, but effective in most BM-MSCs. Despite all rapamycin-treated cells secreted significantly reduced levels of IL6, a major SASP cytokine, and expressed significantly higher levels of the pluripotency marker NANOG, the expression patterns of these markers were not correlated with the rapamycin-mediated increase in lifespan. Interestingly, rapamycin-mediated life-span extension was significantly associated only with repression of p16INK4A protein accumulation. CONCLUSIONS: Taken together, our results suggest that some, but not all, BM-MSC samples would benefit from using rapamycin to postpone replicative arrest and reinforce a critical role of p16INK4A protein downregulation in this process.

Evaluation of different commercial hyaluronic acids as a vehicle for injection of human adipose-derived mesenchymal stem cells / Avaliação de diferentes ácidos hialurônicos comerciais como veículo de injeção para células mesenquimais humanas derivadas do tecido adiposo

ABSTRACT Objective: The main purpose of this study is to evaluate, in vitro, the cytotoxicity of different commercial brands of hyaluronic acids to be used as a vehicle for injection of human adipose-derived mesenchymal stem cells (AD-MSCs). Methods: AD-MSCs were divided into seven groups: one control group where AD-MSCs were cultivated with phosphate-buffered saline (PBS) and six other groups where AD-MSCs were cultivated with different commercial brands of hyaluronic acid. AD-MSC viability analysis was performed after 4, 24, and 48 h in contact with each treatment, using the trypan staining method on a Countess automated cell counter (Thermo Fisher Scientific). Results: The results clearly demonstrated a significant difference in cell viability when AD-MSCs were exposed to different hyaluronic acids when compared with the control group. Conclusion: These data suggest that hyaluronic acid can be used as a vehicle for injection of human AD-MSCs, but caution is needed to choose the best product, aiming at its future therapeutic application.

RESUMO Objetivo: Avaliar in vitro, de forma direta, a citotoxicidade de ácidos hialurônicos como veículo de injeção para linhagens de células-tronco mesenquimais (CTMs) obtidas de tecido adiposo humano. Métodos: As CTMs foram divididas em sete grupos, os quais foram expostos ao ácido hialurônico de seis marcas comerciais, além do contato com tampão fosfato-salino PBS (grupo controle). Após quatro, 24 e 48 horas, foi feita a análise da viabilidade celular através do contador Countess pelo método de coloração com Trypan Blue (Thermo Fisher Scientific). Resultados: Os resultados demonstraram uma diferença significativa na viabilidade celular quando essas linhagens de CTMs foram expostas aos diferentes ácidos hialurônicos em comparação com o grupo controle. Conclusão: Os dados sugerem que o ácido hialurônico pode ser usado como veículo de injeção para CTMs, porém é necessária cautela na escolha do melhor produto para aplicação terapêutica futura.