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Article ; Online: Lumbar Decompression Versus Spinal Fusion ina Private Outpatient Setting

Isadora Orlando de Oliveira / Mario Lenza / Eliane Antonioli / Mario Ferretti

Revista Brasileira de Ortopedia, Vol 56, Iss 6, Pp 766-

A Retrospective Study with Three Years of Follow-up

2022 Volume 771

Abstract: 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 ... ...

Abstract	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 Methods The data for this retrospective cohort were withdrawn from a private healthcare system between June 2011 and January 2014.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.
Keywords	outcome assessment ; health care ; musculoskeletal diseases ; back pain ; spine ; surgical interventions ; Medicine ; R ; Orthopedic surgery ; RD701-811
Subject code	616
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Sociedade Brasileira de Ortopedia e Traumatologia
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Clinical outcome analysis in surgical patients enrolled in a Second Opinion Program in spine surgery

Rebeca Barqueiro de Oliveira / Isadora Orlando de Oliveira / Eliane Antonioli / Mario Lenza / Mario Ferretti

Einstein (São Paulo), Vol

2022 Volume 20

Abstract: 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 ... ...

Abstract	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.
Keywords	Spinal diseases/surgery ; Arthrodesis ; Pain management ; Low back pain ; Anxiety ; Depression ; Treatment outcome ; Referral and consultation ; Quality of life ; Medicine ; R
Subject code	610 ; 616
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	Instituto Israelita de Ensino e Pesquisa Albert Einstein
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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

Felipe Bruno Dias de Oliveira / Eliane Antonioli / Olívia Furiama Metropolo Dias / Jean Gabriel de Souza / Sudha Agarwal / Ana Marisa Chudzinski-Tavassi / Mario Ferretti

International Journal of Molecular Sciences, Vol 24, Iss 21, p

2023 Volume 15543

Abstract: 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 ... ...

Abstract	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 × 10 6 cells/kg bw ) 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 ...
Keywords	osteoarthritis ; mesenchymal stromal cell ; mesenchymal stem cell ; intra-articular ; intravenous ; inflammation ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Individual response to mTOR inhibition in delaying replicative senescence of mesenchymal stromal cells.

Eliane Antonioli / Natália Torres / Mario Ferretti / Carla de Azevedo Piccinato / Andrea Laurato Sertie

PLoS ONE, Vol 14, Iss 1, p e

2019 Volume 0204784

Abstract: 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 ... ...

Abstract	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.
Keywords	Medicine ; R ; Science ; Q
Subject code	571
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Matrix-assisted autologous chondrocyte transplantation for treatment of focal chondral lesions in the knee

Alessandro Rozim Zorzi / Eliane Antonioli / Camila Cohen Kaleka / Moisés Cohen / Juliana Aparecida Preto de Godoy / Andrea Tiemi Kondo / José Mauro Kutner / Mario Lenza / Mario Ferretti

Einstein (São Paulo), Vol

the Hospital Israelita Albert Einstein experience

2022 Volume 20

Abstract: 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, ...

Abstract	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
Keywords	Cartilage ; Knee injuries ; Pain ; Chondrocytes ; Cell- and tissue-based therapy ; Regenerative medicine ; Medicine ; R
Subject code	616
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Instituto Israelita de Ensino e Pesquisa Albert Einstein
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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

Alessandro Rozim Zorzi / Eliane Antonioli / Juliana Aparecida Preto de Godoy / Oswaldo Keith Okamoto / Andrea Tiemi Kondo / José Mauro Kutner / Camila Cohen Kaleka / Moisés Cohen / Mario Ferretti

Einstein (São Paulo), Vol

2022 Volume 20

Abstract: 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, ...

Abstract	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.
Keywords	Knee ; Cartilage ; Cell-and tissue-based therapy ; Chondrocytes ; Mycoplasma ; Cell culture techniques ; Medicine ; R
Subject code	616
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	Instituto Israelita de Ensino e Pesquisa Albert Einstein
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Clinical outcomes and cost–utility of rotator cuff repair surgery by open and arthroscopic techniques

Rafael Pierami / Eliane Antonioli / Isadora Oliveira / Isabela Queirós Castro / Felipe Manente / Paula Fairbanks / Eduardo da Frota Carrera / Bruno Akio Matsumura

BMJ Open, Vol 10, Iss

study protocol for a randomised clinical trial

2020 Volume 12

Abstract: Introduction Rotator cuff injuries account for up to 70% of pain in the shoulder. However, there remains no consensus on the best surgical treatment for patients with rotator cuff injuries, in terms of the cost-effectiveness and cost–utility of open and ... ...

Abstract	Introduction Rotator cuff injuries account for up to 70% of pain in the shoulder. However, there remains no consensus on the best surgical treatment for patients with rotator cuff injuries, in terms of the cost-effectiveness and cost–utility of open and arthroscopic methods for rotator cuff repair. The objective of this trial is to compare the efficacy, cost-effectiveness and cost–utility of open and arthroscopic procedures for rotator cuff repair.Methods and analysis The trial is a two-group, parallel-design, randomised controlled trial. A total of 100 patients with symptomatic rotator cuff lesions will be allocated in either open or arthroscopic technique in a 1:1 ratio, considering smoking (yes or no), lesion size (≤3 cm or >3 cm) and diabetes (present or absent) as stratification factors. All patients will be included in the same rehabilitation programme after the intervention. The primary outcome measure will be the Constant-Murley Score and the EuroQol-5D-3L score at 48 weeks postsurgery. Secondary outcomes include cost-effectiveness, cost–utility, pain, complications and clinical analysis, using the Simple Shoulder Test, Visual Analogue Pain Scale (VAS), integrity of the repair evaluated through MRI, and complications and failures of the proposed methods. For the cost-effectiveness analysis, we will use the VAS and the Constant-Murley Score as measures of effectiveness. For the cost–utility analysis, we will use the EuroQol-5D-3L as a measure of utility in terms of incremental cost per quality-adjusted life-years.Ethics and dissemination The study has been approved by the local research ethics committee of both institutions: Hospital Israelita Albert Einstein and Hospital Alvorada Moema/Hospital Pró-Cardíaco. The results will be published in a peer-reviewed, open access journal.Trial registration number NCT04146987.
Keywords	Medicine ; R
Subject code	616
Language	English
Publishing date	2020-12-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Analysis of 500 anterior cruciate ligament reconstructions from a private institutional register.

Lauro Augusto Costa / Noel Oizerovici Foni / Eliane Antonioli / Rogério Teixeira de Carvalho / Isabela Dias Paião / Mário Lenza / Mário Ferretti

PLoS ONE, Vol 13, Iss 1, p e

2018 Volume 0191414

Abstract: The aims of this study are to describe the epidemiological characteristics of anterior cruciate ligament reconstructions in a private hospital in Brazil and to determine trends in medical practice for comparison with previous studies.We retrospectively ... ...

Abstract	The aims of this study are to describe the epidemiological characteristics of anterior cruciate ligament reconstructions in a private hospital in Brazil and to determine trends in medical practice for comparison with previous studies.We retrospectively reviewed the anterior cruciate ligament institutional register to obtain data from all patients who underwent primary anterior cruciate ligament reconstruction from July 2014 to June 2016. Descriptive statistics were used to summarize the sample. Specific statistical tests were used to assess associations between the meniscal lesion and other variables.During the study period, 72.6% out of 500 patients were male. The mean age at surgery was 35.1 years. The mean age was higher among females than among males (37.3 ± 12.1 vs 34.3 ± 10.8 years). The median time from injury to surgery was 44 days. The most common femoral and tibial fixations used were suspensory fixation (60.8%) and interference screw (96%), respectively. The most commonly used graft was hamstring tendon (70.2%), followed by bone-patellar tendon-bone (28.8%). A meniscal lesion was noted in 44.8% of cases. Partial meniscectomy was performed in 69.5% of meniscal lesions, and meniscal repair was performed in 14.1% of lesions. The mean length of hospital stay was 1.4 days. The proportion of men in the group of patients with an associated meniscal lesion was higher than that in the group of patients without a meniscal lesion (p = 0.007).In this study, we identified that the vast majority of surgeries were performed in male patients in all age groups, and patients older than 30 years and with a short time from injury to surgery predominated. Concerning surgical technique, we noted a low rate of meniscal repair and a higher preference for the use of hamstring graft and suspensory fixation on the femoral side.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Clinical pathway improves medical practice in total knee arthroplasty.

Noel Oizerovici Foni / Lauro Augusto Veloso Costa / Isabela Dias Paião / Isadora Orlando de Oliveira / Rogério Teixeira de Carvalho / Mario Lenza / Eliane Antonioli / Mario Ferretti

PLoS ONE, Vol 15, Iss 5, p e

2020 Volume 0232881

Abstract: 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 ... ...

Abstract	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 ...
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: High OCT4 and Low p16INK4A Expressions Determine In Vitro Lifespan of Mesenchymal Stem Cells

Carla A. Piccinato / Andrea L. Sertie / Natália Torres / Mario Ferretti / Eliane Antonioli

Stem Cells International, Vol

2015 Volume 2015

Abstract: After long-term culture, mesenchymal stem cells alter their biological properties and enter into a state of replicative senescence. Although several classical biomarkers have been used for quantitative assessment of cellular senescence, no hallmark has ... ...

Abstract	After long-term culture, mesenchymal stem cells alter their biological properties and enter into a state of replicative senescence. Although several classical biomarkers have been used for quantitative assessment of cellular senescence, no hallmark has been proven completely unique to the senescent state in cells. We used bone marrow-derived MSCs (BM-MSCs) from different healthy young donors and an in vitro model with well-defined senescence end points to identify a set of robust markers that could potentially predict the expansion capacity of MSCs preparations before reaching senescence. For each early passage BM-MSC sample (5th or 6th passages), the normalized protein expression levels of senescence-associated markers p16INK4A, p21WAF1, SOD2, and rpS6S240/244; the concentration of IL6 and IL8 in cell culture supernatants; and the normalized gene expression levels of pluripotency markers OCT4, NANOG, and SOX2 were correlated with final population doubling (PD) number. We revealed that the low expression of p16INK4A protein and a high OCT4 gene expression, rather than other evaluated markers, might be potential hallmarks and predictors of greater in vitro lifespan and growth potential, factors that can impact the successful therapeutic use of MSCs preparations.
Keywords	Internal medicine ; RC31-1245
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Hindawi Publishing Corporation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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