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Carcinoma Adenoide Cístico , Neoplasias da Traqueia , Humanos , Carcinoma Adenoide Cístico/radioterapia , Carcinoma Adenoide Cístico/patologia , Carcinoma Adenoide Cístico/diagnóstico por imagem , Neoplasias da Traqueia/diagnóstico por imagem , Neoplasias da Traqueia/patologia , Neoplasias da Traqueia/radioterapia , Tratamentos com Preservação do Órgão/métodos , Masculino , FemininoRESUMO
PURPOSE: The purpose of this retrospective review was to determine the prevalence of osteochondral lesions (OCLs) of the lateral talar dome in patients with anterior ankle impingement with an associated hypertrophic distal fascicle of the anterior tibio-fibular ligament. METHODS: Retrospective chart review identified 40 patients who underwent anterior ankle arthroscopy for the management of anterior ankle impingement. Clinical outcomes assessed included pre- and postoperative foot and ankle outcome score (FAOS), visual analogue scale (VAS), complications, failures, secondary surgical procedures, return-to-work data and return-to-sport data. RESULTS: Thirty-two patients with a mean follow-up time of 29.3 ± 10.4 months were included. The hypertrophic distal fascicle of the anterior tibio-fibular ligament was hypertrophic in 29 patients (90.6%), with a mean thickness of 2.5 ± 0.4 mm on MRI. There were 22 OCLs of the lateral talar dome (75.9%) with an associated hypertrophic distal fascicle of the anterior tibio-fibular ligament visualized during arthroscopy. The international cartilage repair society gradings of the lesions included 3 (13.6%) grade I lesions, 15 (68.1%) grade II lesions, 3 (13.6%) grade III lesions, and 1 (4.6%) grade IV lesion. There was a statistically significant improvement in mean FAOS and VAS scores from preoperative to postoperative (p < 0.001). No cases of syndesmotic instability were observed following resection of hypertrophic distal fascicle of the anterior tibio-fibular ligament. CONCLUSION: This retrospective case series demonstrated that a hypertrophic distal fascicle of the anterior tibio-fibular ligament was associated with an OCL of the lateral talar dome identified during arthroscopic evaluation. In addition, preoperative MRI demonstrated poor sensitivity for the detection of these OCLs. Heightened awareness is warranted for potential lateral talar dome OCLs in patients presenting with anterolateral ankle impingement with a hypertrophic ATiFLdf identified on preoperative MRI in the absence of an associated OCLs. LEVEL OF EVIDENCE: Level IV, Retrospective case series.
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Purulent pericarditis secondary to bacterial infections is rarely seen in the current era of broad-spectrum antibiotics. Complications tend to be higher in comparison to viral or idiopathic etiologies in cases of bacterial pericarditis. Staphylococcal aureus, Streptococcus pneumoniae, or Haemophilus influenza are the more commonly identified pathogens in cases of bacterial pericarditis. We report a case of purulent pericarditis from Bacteroides thetaiotaomicron and Streptococcus milleri occurring in conjunction in a 56-year-old male. To our knowledge, there are no published case reports describing purulent pericarditis from B. thetaiotaomicron and S. milleri occurring simultaneously in the literature.
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Purpose: Knowing the surgical safety of anterior chamber liquid biopsies will support the increased use of proteomics and other molecular analyses to better understand disease mechanisms and therapeutic responses in patients and clinical trials. Manual review of operative notes from different surgeons and procedures in electronic health records (EHRs) is cumbersome, but free-text software tools could facilitate efficient searches. Design: Retrospective case series. Participants: A total of 1418 aqueous humor liquid biopsies from patients undergoing intraocular surgery. Methods: Free-text EHR searches were performed using the Stanford Research Repository cohort discovery tool to identify complications associated with anterior chamber paracentesis and subsequent endophthalmitis. Complications of the surgery unrelated to the biopsy were not reviewed. Main Outcome Measures: Biopsy-associated intraoperative complications and endophthalmitis. Results: A total of 1418 aqueous humor liquid biopsies were performed by 17 experienced surgeons. EHR free-text searches were 100% error-free for surgical complications, >99% for endophthalmitis (<1% false positive), and >93.6% for anesthesia type, requiring manual review for only a limited number of cases. More than 85% of cases were performed under local anesthesia without ocular muscle akinesia. Although the most common indication was cataract (50.1%), other diagnoses included glaucoma, diabetic retinopathy, uveitis, age-related macular degeneration, endophthalmitis, retinitis pigmentosa, and uveal melanoma. A 50- to 100-µL sample was collected in all cases using either a 30-gauge needle or a blunt cannula via a paracentesis. The median follow-up was >7 months. There was only one minor complication (0.07%) identified: a case of a small tear in Descemet membrane without long-term sequelae. No other complications occurred, including other corneal injuries, lens or iris trauma, hyphema, or suprachoroidal hemorrhage. There was no case of postoperative endophthalmitis. Conclusions: Anterior chamber liquid biopsy during intraocular surgery is a safe procedure and may be considered for large-scale collection of aqueous humor samples for molecular analyses. Free-text EHR searches are an efficient approach to reviewing intraoperative procedures. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Valgus instability can occur after total knee arthroplasty (TKA) due to traumatic medial collateral ligament (MCL) injury, component malpositioning, or progressive ligamentous laxity. Although revision TKA with exchange of the polyethylene to a varus-valgus-constrained liner can reduce laxity due to MCL insufficiency, isolated liner exchange in the setting of collateral ligament insufficiency may lead to greater strain at the cement-bone or implant-cement interface and possibly a greater rate of aseptic loosening. Anatomic MCL reconstruction can be performed in conjunction with liner exchange to restore stability and reduce strain compared with liner exchange alone. The purpose of this Technical Note is to describe a technique for MCL reconstruction and liner exchange for treatment of valgus instability after TKA.
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PURPOSE: To evaluate long-term outcomes of patients treated with posterior medial meniscal root tear (PMMRT) repair through assessment of functional outcome scores and to identify patient surgical and magnetic resonance imaging (MRI) characteristics associated with improved outcomes. METHODS: This was a single-centre, retrospective study evaluating patients who had undergone a PMMR repair using a transtibial suture pullout technique with two locking cinch sutures. This was performed as a follow-up to previously published 2-year and 5-year outcome studies, using the same cohort. All patients from the prior short-term and midterm studies were invited to participate. Patient-reported outcome (PROs) scores, including the International Knee Documentation Committee (IKDC) and Lysholm scores, were collected. Previously collected demographic data were updated based on review of the electronic medical record. Patient outcomes were assessed preoperatively, as well as at 2-year, 5-year and 8-year postoperatively. MRI outcome measurements were assessed at 2-year and 5-year follow-ups. All statistical analysis was performed using SPSS version 26. RESULTS: Seventeen patients of the original 18 patients (94.4%) were included in the final analysis. Additionally, three patients who had additional ipsilateral surgery were excluded from the analysis of PROs. The IKDC score significantly increased from 44.7 ± 11.6 at preoperative baseline to 71.2 ± 21.3 at 8-year post-operation (p = 0.001). There were no significant differences in IKDC score between 2-year and 8-year follow-ups (p = n.s.) or 5-year and 8-year follow-ups (p = n.s.). The Lysholm score significantly increased from 49.6 ± 7.3 at preoperative baseline to 76.4 ± 17.2 at 8-year follow-up (p < 0.001). There was no significant difference in Lysholm scores between 2-year and 8-year follow-ups (p = n.s.) or 5-year and 8-year follow-ups (p = n.s.). A linear regression analysis found that 5-year IKDC scores were significantly correlated with 8-year IKDC scores (ß = 0.681, p = 0.038). At 8-year follow-up, four (23.5%) patients required additional procedures on their operative knee (one total knee arthroplasty conversion). CONCLUSION: Patients treated with repair of PMMRT had maintenance of clinical outcome improvements at long-term follow-up despite worsening MRI outcomes at short-term and medium-term follow-ups. While a high proportion of patients required additional procedures on their operative knee at 8-year follow-up, few of these patient's additional procedures were related to failure of their primary surgery. Providers and patients may expect durable clinical outcomes following the repair of PMMRT, irrespective of radiographic appearance. LEVEL OF EVIDENCE: Level IV.
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OBJECTIVE: The purpose of this study was to compare the short-term clinical outcomes of matrix-induced autologous chondrocyte implantation (MACI) to those seen following traditional autologous chondrocyte implantation (ACI) in the management of symptomatic cartilage lesions of the knee. METHODS: This was a retrospective cohort study of patients who underwent either ACI or MACI from January 2011 to March 2018. Patients with a minimum postoperative follow-up of 18 months were contacted. Demographic information, intraoperative findings, and patient-reported functional outcomes scores were collected. Comparisons were made between the two cell-based cartilage repair techniques. RESULTS: Fifty-six patients were included in the study (39 ACI, 17 MACI). Visual analog scale (VAS) for pain scores improved significantly in both groups, with MACI patients demonstrating significantly lower postoperative pain scores compared to those treated with ACI. In the ACI group, there was a decrease in the Tegner Activity score compared to the preoperative baseline, while no significant difference was seen between pre- and postoperative activity levels in the MACI group. Patients were generally satisfied with the outcome of their procedures, and there was no significant difference in satisfaction between groups. No patients re-quired additional surgery during the follow-up period. CONCLUSION: Both ACI and MACI demonstrated good short-term postoperative clinical results with improved pain and activity levels compared to the preoperative baseline. Patients treated with the MACI technique demonstrated greater reductions in pain scores compared to ACI, and while ACI resulted in a decrease in levels of postoperative activity, activity levels for MACI remained stable.
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Condrócitos , Articulação do Joelho , Transplante Autólogo , Humanos , Condrócitos/transplante , Estudos Retrospectivos , Feminino , Masculino , Adulto , Resultado do Tratamento , Articulação do Joelho/cirurgia , Articulação do Joelho/fisiopatologia , Pessoa de Meia-Idade , Cartilagem Articular/cirurgia , Medição da Dor , Satisfação do Paciente , Adulto JovemRESUMO
Background: Elbow ulnar collateral ligament (UCL) reconstruction (UCLR) is the gold standard for operative treatment of UCL tears, with renewed interest in UCL repairs. Purpose: To (1) assess trends in rates of UCLR and UCL repair and (2) identify predictors of complications by demographic, socioeconomic, or surgical center volume factors. Study Design: Descriptive epidemiology study. Methods: Patients who underwent UCLR or UCL repair at New York State health care facilities between 2010 and 2019 were retrospectively identified; concomitant ulnar nerve procedures among the cohort were also identified. Surgical center volumes were classified as low (<99th percentile) or high (≥99th percentile). Patient information, neighborhood socioeconomic status quantified using the Area Deprivation Index, and complications within 90 days were recorded. Poisson regression analysis was used to compare trends in UCLR versus UCL repair. Multivariable regression was used to determine whether center volume, demographic, or socioeconomic variables were independent predictors of complications. Results: A total of 1448 UCL surgeries were performed, with 388 (26.8%) concomitant ulnar nerve procedures. UCLR (1084 procedures; 74.9%) was performed more commonly than UCL repair (364 procedures; 25.1%), with patients undergoing UCL repair more likely to be older, female, and not privately ensured and having undergone a concomitant ulnar nerve procedure (all P < .001). With each year, there was an increased incidence rate ratio for UCL repair versus UCLR (ß = 1.12 [95% CI, 1.02-1.23]; P = .022). The authors identified 2 high-volume centers (720 UCL procedures; 49.7%) and 131 low-volume centers (728 UCL procedures; 50.3%). Patients undergoing UCL procedures at high-volume centers were more likely to be younger and male and receive workers' compensation (all P < .001). UCL repair and ulnar nerve-related procedures were both more commonly performed at low-volume centers (P < .001). There were no significant differences in 3-month infection, ulnar neuritis, instability, arthrofibrosis, heterotopic ossification, or all-cause complication rates between low- and high-volume centers. The only significant predictor for all-cause complication was Medicaid insurance (OR, 2.91 [95% CI, 1.20-6.33]; P = .011). Conclusion: A rising incidence of UCL repair compared with UCLR was found in New York State, especially among female patients, older patients, and nonprivate payers. There were no differences in 3-month complication rates between high- and low-volume centers, and Medicaid insurance status was a predictor for overall complications within 90 days of operation.
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The purpose of this study was to assess the biomechanical contributions of the nail and the plate individually to a complete nail-plate construct in the setting of comminuted distal femur fractures. For this biomechanical study, comminuted extra-articular distal femur fractures were created in 24 synthetic osteoporotic femur models. These were then split into three groups: the nail-only group, the plate-only group, and the nail-plate group. After fixation, each specimen underwent sequential axial and torsional loading, and axial and torsional stiffness were calculated and compared. The addition of a nail to a plate-only construct increased axial stiffness by 19.7% and torsional stiffness by 59.4%. The plate-only group and nail-plate group both demonstrated significantly greater axial and torsional stiffness than the nail-only group at all levels of axial and torsional load. (p < 0.001) At 1000 and 2000 N of cyclic loading, the nail-plate group demonstrated significantly greater axial stiffness than the plate-only group (p ≤ 0.018). The nail-plate group demonstrated greater torsional stiffness than the plate-only groups at all levels of torsional loading (p < 0.001). In osteoporotic comminuted distal femur fracture models, most of the axial stiffness in a nail-plate construct comes from the plate. While the combination of the two constructs is not fully additive, the plate contributes the majority of the axial and torsional stiffness in a nail-plate construct. The supplementation of the plate with a nail primarily helps to increase resistance to rotational forces. Level of Evidence: III.
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This comparative effectiveness research study assesses the rate of tissue loss in ultrathin Descemet stripping automated endothelial keratoplasty grafts vs descemet membrane endothelial keratoplasty grafts during eye bank processing.
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Bancos de Olhos , Humanos , Masculino , Feminino , Doadores de Tecidos , Pessoa de Meia-Idade , IdosoRESUMO
INTRODUCTION: Ehlers-Danlos syndromes (EDS) are genetic connective tissue disorders affecting multiple organ systems that frequently result in connective tissue hyperlaxity and early osteoarthritis. Short- and long-term outcomes after primary total hip arthroplasty (THA) in this patient population remain poorly characterised. The primary purpose of this study is to compare postoperative outcomes and survivorship after primary THA in patients with and without EDS. METHODS: The New York Statewide Planning and Research Cooperative System (SPARCS) database was queried for all patients undergoing primary elective THA between September 2009 and December 2020. Patients with EDS were identified using ICD9 and ICD10 diagnosis codes. Given the relatively low incidence of EDS in this patient population, the cohort was propensity-matched 1:10 to patients without diagnosis of EDS based on demographics characteristics and medical comorbidities as measured by the Elixhauser Comorbidity Index. RESULTS: A total of 66 THA patients with and 660 without EDS were included in each group after 1:10 propensity-matching. There were no significant differences in baseline characteristics or THA indications. Early postoperative outcomes such as length of hospital stay and discharge disposition were similar. Emergency Room visits and inpatient readmission rates at 3 months postoperatively did not significantly differ between groups. Patients with EDS had a higher overall revision rate compared to those without (15.0% vs. 3.2%, p < 0.001). Revision free survival after primary THA in patients with EDS was significantly lower than those without EDS at 9-year follow-up. Cox proportional hazard regression demonstrated EDS patients had 7-times higher risk of revision (hazard ratio [HR] 7.43; 95% CI, 3.46-16.00; p < 0.001). Lastly, revision due to instability insignificantly trended higher in the EDS cohort (HR 2.29; 95% CI, 0.95-5.49; p = 0.063). CONCLUSIONS: EDS patients undergoing primary THA have increased rate of all cause revision and demonstrate decreased revision free survival compared to non-EDS THA patients.
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Artroplastia de Quadril , Síndrome de Ehlers-Danlos , Humanos , Artroplastia de Quadril/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Síndrome de Ehlers-Danlos/complicações , Adulto , New York/epidemiologia , Resultado do Tratamento , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Bases de Dados Factuais , Reoperação/estatística & dados numéricos , Osteoartrite do Quadril/cirurgiaRESUMO
A 55-year-old male with acute pericarditis presented with low-pressure cardiac tamponade (LPCT) unresponsive to volume infusion. Subsequent pericardiocentesis resulted in hemodynamic improvement and unmasking of pericardial constriction. This case provides illustrative hemodynamic tracings of LPCT. Additionally, the presence of concurrent pericardial constriction that may indicate a plausible underlying mechanism for the blunted responsiveness to fluid expansion in LPCT. The underlying physiologic processes and the associated hemodynamic tracings are discussed.
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Tamponamento Cardíaco , Hemodinâmica , Pericardiocentese , Humanos , Tamponamento Cardíaco/fisiopatologia , Tamponamento Cardíaco/etiologia , Tamponamento Cardíaco/diagnóstico por imagem , Tamponamento Cardíaco/cirurgia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Pericardite/fisiopatologia , Pericardite/terapia , Pericardite/diagnóstico por imagem , Pericardite/etiologia , Pericardite/diagnóstico , Doença AgudaRESUMO
The bone marrow adjusts blood cell production to meet physiological demands in response to insults. The spatial organization of normal and stress responses are unknown owing to the lack of methods to visualize most steps of blood production. Here we develop strategies to image multipotent haematopoiesis, erythropoiesis and lymphopoiesis in mice. We combine these with imaging of myelopoiesis1 to define the anatomy of normal and stress haematopoiesis. In the steady state, across the skeleton, single stem cells and multipotent progenitors distribute through the marrow enriched near megakaryocytes. Lineage-committed progenitors are recruited to blood vessels, where they contribute to lineage-specific microanatomical structures composed of progenitors and immature cells, which function as the production sites for each major blood lineage. This overall anatomy is resilient to insults, as it was maintained after haemorrhage, systemic bacterial infection and granulocyte colony-stimulating factor (G-CSF) treatment, and during ageing. Production sites enable haematopoietic plasticity as they differentially and selectively modulate their numbers and output in response to insults. We found that stress responses are variable across the skeleton: the tibia and the sternum respond in opposite ways to G-CSF, and the skull does not increase erythropoiesis after haemorrhage. Our studies enable in situ analyses of haematopoiesis, define the anatomy of normal and stress responses, identify discrete microanatomical production sites that confer plasticity to haematopoiesis, and uncover unprecedented heterogeneity of stress responses across the skeleton.
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Hematopoese , Células-Tronco Hematopoéticas , Estresse Fisiológico , Animais , Feminino , Masculino , Camundongos , Envelhecimento/fisiologia , Infecções Bacterianas/patologia , Infecções Bacterianas/fisiopatologia , Vasos Sanguíneos/citologia , Linhagem da Célula , Eritropoese , Fator Estimulador de Colônias de Granulócitos/metabolismo , Hematopoese/fisiologia , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Hemorragia/patologia , Hemorragia/fisiopatologia , Linfopoese , Megacariócitos/citologia , Células-Tronco Multipotentes/citologia , Células-Tronco Multipotentes/metabolismo , Mielopoese , Crânio/irrigação sanguínea , Crânio/patologia , Crânio/fisiopatologia , Esterno/irrigação sanguínea , Esterno/citologia , Esterno/metabolismo , Estresse Fisiológico/fisiologia , Tíbia/irrigação sanguínea , Tíbia/citologia , Tíbia/metabolismoRESUMO
BACKGROUND: Patients with diabetes undergoing total ankle arthroplasty tend to be at greater risk for complications than those without diabetes. However, the effect of diabetes severity and how it impacts the risk for perioperative complications is less clear. The purpose of this study was to compare (1) complications, (2) length of hospital stay, and (3) readmissions within 30 days for total ankle arthroplasty (TAA) patients without diabetes, patients with non-insulin-dependent diabetes, and patients with insulin-dependent diabetes. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database, a total of 1803 patients undergoing TAA between 2007 and 2019 were collected. The relationship between diabetes status (no diabetes [n = 1,589], insulin-dependent [n = 169], and non-insulin-dependent [n = 45]) and outcomes were compared. Multivariate linear regression models were used to adjust for confounding variables such as age, sex, race, body mass index, smoking, steroid use, hypertension, chronic obstructive pulmonary disease, anesthesia type, dyspnea, and outpatient status. Statistical significance was set at P <.05. RESULTS: Insulin-dependent diabetes was an independent risk factor for increased odds of infection within 30 days (odds ratio 6.47, 95% CI 0.79-33.66; P = .043). Hospital length of stay was also increased in patients with non-insulin-dependent diabetes (ß = 0.21, 95% CI 0.02-0.40; P = .031) and insulin-dependent diabetes (ß = 0.40, 95% CI 0.04-0.76; P = .028). However, neither diabetic state demonstrated a statistically significant increase in readmissions or wound complications within 30 days. CONCLUSION: Patients with insulin-dependent diabetes included in this cohort were at increased risk of having an infection within 30 days after TAA. Additionally, patients with diabetes status had an increased hospital length of stay. These results can inform patients on their potential outcomes after total ankle arthroplasty based on their diabetes status.
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Artroplastia de Substituição do Tornozelo , Tempo de Internação , Complicações Pós-Operatórias , Humanos , Artroplastia de Substituição do Tornozelo/efeitos adversos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Complicações Pós-Operatórias/epidemiologia , Tempo de Internação/estatística & dados numéricos , Diabetes Mellitus Tipo 1/complicações , Fatores de Risco , Estudos Retrospectivos , Diabetes Mellitus Tipo 2/complicações , Readmissão do Paciente/estatística & dados numéricosRESUMO
PURPOSE: Moderate-to-severe hallux rigidus is a debilitating pathology that is optimally treated with surgical intervention. Arthrodesis produces reliable clinical outcomes but is limited by restriction in 1st metatarsophalangeal joint range of motion. The advent of polyvinyl alcohol hydrogel (PVA) implants have produced early promise based on initial trials, but more recent studies have called into question the efficacy of this procedure. The purpose of this systematic review was to evaluate the clinical and radiological outcomes following the use of PVA for hallux rigidus. METHODS: The MEDLINE, EMBASE and Cochrane library databases were systematically reviewed using the preferred reporting items for systematic reviews and meta-analyses guidelines. 18 studies were included. RESULTS: In total, 1349 patients (1367 feet) underwent PVA at a weighted mean follow-up of 24.1 ± 11.1 months. There were 168 patients (169 feet) included in the cheilectomy cohort and 322 patients (322 feet) included in the arthrodesis cohort. All 3 cohorts produced comparable improvements in subjective clinical outcomes. Postoperative imaging findings in the PVA cohort included joint space narrowing, peri-implant fluid, peri-implant edema and erosion of the proximal phalanx. The complication rate in the PVA cohort, cheilectomy cohort and arthrodesis cohort was 27.9%, 11.8% and 24.1%, respectively. The failure rates in the PVA cohort, cheilectomy cohort and arthrodesis cohort was 14.8%, 0.3% and 9.0%, respectively. CONCLUSION: This systematic review demonstrated that PVA produced a high complication rate (27.9%) together with concerning postoperative imaging findings at short-term follow-up. In addition, a moderate failure rate (14.8%) and secondary surgical procedure rate (9.5%) was noted for the PVA cohort. The findings of this review calls into question the efficacy and safety of PVA for the treatment of hallux rigidus. LEVEL OF EVIDENCE: IV.
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Hallux Rigidus , Álcool de Polivinil , Humanos , Álcool de Polivinil/uso terapêutico , Hallux Rigidus/cirurgia , Hallux Rigidus/diagnóstico por imagem , Artrodese/métodos , Artrodese/efeitos adversos , Artrodese/instrumentação , Seguimentos , Complicações Pós-Operatórias/etiologia , Articulação Metatarsofalângica/cirurgia , Hidrogéis/uso terapêutico , Falha de Prótese , Feminino , Amplitude de Movimento Articular , Resultado do Tratamento , MasculinoRESUMO
Mitochondrial fatty acid oxidation (FAO) is essential for hematopoietic stem cell (HSC) self-renewal; however, the mechanism by which mitochondrial metabolism controls HSC fate remains unknown. Here, we show that within the hematopoietic lineage, HSCs have the largest mitochondrial NADPH pools, which are required for proper HSC cell fate and homeostasis. Bioinformatic analysis of the HSC transcriptome, biochemical assays, and genetic inactivation of FAO all indicate that FAO-generated NADPH fuels cholesterol synthesis in HSCs. Interference with FAO disturbs the segregation of mitochondrial NADPH toward corresponding daughter cells upon single HSC division. Importantly, we have found that the FAO-NADPH-cholesterol axis drives extracellular vesicle (EV) biogenesis and release in HSCs, while inhibition of EV signaling impairs HSC self-renewal. These data reveal the existence of a mitochondrial NADPH-cholesterol axis for EV biogenesis that is required for hematopoietic homeostasis and highlight the non-stochastic nature of HSC fate determination.
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Vesículas Extracelulares , Células-Tronco Hematopoéticas , NADP/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Diferenciação Celular/fisiologia , Autorrenovação CelularRESUMO
BACKGROUND: Retinal degeneration results from disruptions in retinal homeostasis due to injury, disease, or aging and triggers peripheral leukocyte infiltration. Effective immune responses rely on coordinated actions of resident microglia and recruited macrophages, critical for tissue remodeling and repair. However, these phagocytes also contribute to chronic inflammation in degenerated retinas, yet the precise coordination of immune response to retinal damage remains elusive. Recent investigations have demonstrated that phagocytic cells can produce extracellular traps (ETs), which are a source of self-antigens that alter the immune response, which can potentially lead to tissue injury. METHODS: Innovations in experimental systems facilitate real-time exploration of immune cell interactions and dynamic responses. We integrated in vivo imaging with ultrastructural analysis, transcriptomics, pharmacological treatments, and knockout mice to elucidate the role of phagocytes and their modulation of the local inflammatory response through extracellular traps (ETs). Deciphering these mechanisms is essential for developing novel and enhanced immunotherapeutic approaches that can redirect a specific maladaptive immune response towards favorable wound healing in the retina. RESULTS: Our findings underscore the pivotal role of innate immune cells, especially macrophages/monocytes, in regulating retinal repair and inflammation. The absence of neutrophil and macrophage infiltration aids parenchymal integrity restoration, while their depletion, particularly macrophages/monocytes, impedes vascular recovery. We demonstrate that macrophages/monocytes, when recruited in the retina, release chromatin and granular proteins, forming ETs. Furthermore, the pharmacological inhibition of ETosis support retinal and vascular repair, surpassing the effects of blocking innate immune cell recruitment. Simultaneously, the absence of ETosis reshapes the inflammatory response, causing neutrophils, helper, and cytotoxic T-cells to be restricted primarily in the superficial capillary plexus instead of reaching the damaged photoreceptor layer. CONCLUSIONS: Our data offer novel insights into innate immunity's role in responding to retinal damage and potentially help developing innovative immunotherapeutic approaches that can shift the immune response from maladaptive to beneficial for retinal regeneration.
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Armadilhas Extracelulares , Degeneração Retiniana , Animais , Camundongos , Macrófagos/metabolismo , Degeneração Retiniana/metabolismo , Imunidade Inata/fisiologia , Inflamação/metabolismo , Camundongos Knockout , LasersRESUMO
Hyaluronan (HA), a negatively charged linear glycosaminoglycan, is a key macromolecular component of the articular cartilage extracellular matrix. The differential effects of HA are determined by a spatially/temporally regulated display of HA receptors, such as CD44 and receptor for hyaluronan-mediated motility (RHAMM). HA signaling through CD44 with RHAMM has been shown to stimulate inflammation and fibrotic processes. This study shows an increased expression of RHAMM in proinflammatory macrophages. Interfering with HA/RHAMM interactions using a 15-mer RHAMM-mimetic, HA-binding peptide, together with high-molecular-weight (HMW) HA reduced the expression and release of inflammatory markers and increased the expression of anti-inflammatory markers in proinflammatory macrophages. HA/RHAMM interactions were interfered in vivo during the regeneration of a full-thickness cartilage defect after microfracture surgery in rabbits using three intra-articular injections of 15-mer RHAMM-mimetic. HA-binding peptide together with HMWHA reduced the number of proinflammatory macrophages and increased the number of anti-inflammatory macrophages in the injured knee joint and greatly improved the repair of the cartilage defect compared with intra-articular injections of HMWHA alone. These findings suggest that HA/RHAMM interactions play a key role in cartilage repair/regeneration via stimulating inflammatory and fibrotic events, including increasing the ratio of proinflammatory/anti-inflammatory macrophages. Interfering with these interactions reduced inflammation and greatly improved cartilage repair.
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Cartilagem Articular , Receptores de Hialuronatos , Ácido Hialurônico , Macrófagos , Animais , Receptores de Hialuronatos/metabolismo , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Coelhos , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Ácido Hialurônico/metabolismo , Ácido Hialurônico/farmacologia , Proteínas da Matriz Extracelular/metabolismo , Polaridade Celular/efeitos dos fármacos , Polaridade Celular/fisiologia , Regeneração/efeitos dos fármacos , Regeneração/fisiologia , Inflamação/metabolismo , Inflamação/patologiaRESUMO
Medtronic launched the Hugo Robotic-Assisted Surgery (RAS) System in 2021, offering a modular alternative to the incumbent market leader in surgical robotics, the Intuitive da Vinci (dV) surgical system. A detailed technical review of the Hugo RAS was conducted to explore the strengths and weaknesses of this new robotic surgical system. Each component of the system-vision tower, arm cart, and surgeon console-was compared against the existing dV systems. The docking process, instrumentation, and external arm movement trajectories were analyzed. The modular Hugo RAS provides the possibility of operating using up to four arm carts. It has certain design features that are unique to itself, and others that have been implemented to address the shortcomings of the dV Si. While Medtronic's first-generation robot offers distinct advantages over the older Intuitive systems, the true test of its mettle will be its performance compared to the latest dV Xi.
Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Cirurgiões , Humanos , Procedimentos Cirúrgicos Robóticos/métodosRESUMO
BACKGROUND: There are currently no guidelines on peri-arthroscopic management of immunosuppressive (IS) treatment in rheumatic disease patients. PURPOSE: The purpose of this study is to characterize the rheumatic disease patient population undergoing arthroscopy, compare the incidence of postoperative complications among patients who either remained on IS perioperatively, held IS perioperatively or were not on IS at baseline, and compare the incidence of postoperative complications by rheumatic disease type, medication type, and procedure. METHODS: We conducted a retrospective review of all arthroscopic sports medicine surgeries in patients with a rheumatic disease diagnosis at our institution over an 11-year period. Patients on IS at baseline were grouped into those who remained on IS perioperatively or held all IS before the date of their surgery. These two groups were compared to patients who were not on IS at baseline. Incidence of postoperative complications was calculated for the three cohorts and by medication class, rheumatic disease type, and procedure risk. Analysis of variance (ANOVA), chi-squared, and Fisher's exact tests were used to determine the statistical significance of between-group differences in postoperative complication incidence. RESULTS: We identified 1,316 rheumatic disease patients undergoing arthroscopy, with 214 of them taking IS medications at baseline. In total, 8.4% (n = 110) remained on IS perioperatively, 7.9% (n = 104) held IS perioperatively, and 83.7% (n = 1102) were not on IS at baseline. In all cohorts, seven patients experienced postoperative complications; six of whom experienced infections. Two (1.82%) occurred in patients remaining on IS perioperatively, zero infections occured in patients who held all IS, and four (0.36%) occured in patients who were not on any IS at baseline. There was no statistically significant difference in postoperative infections or complication rates among the three cohorts or further subgroups. CONCLUSION: The risk of postoperative complications including infectious, major, and minor complications in patients on IS at the time of arthroscopy is low and acceptable.