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1.
Artigo em Inglês | MEDLINE | ID: mdl-38651565

RESUMO

PURPOSE: Extensor mechanism injuries, which comprise patella fractures, patella tendon tears and quadriceps tendon tears, are severely debilitating injuries and a common cause of traumatic knee pathology that requires surgical intervention. Risk factors for short-term surgical complications and venous thromboembolism (VTE) in this population have not been well characterised. The aim of this study was to identify perioperative risk factors associated with these short-term complications. METHODS: The National Surgical Quality Improvement Program database was used to identify patients who underwent an isolated, primary extensor mechanism repair from 2015 to 2020. Patients were stratified by injury type. Demographic data were collected and compared. A multivariate logistic regression was used to control for demographic and comorbid factors while assessing risk factors for developing short-term complications. RESULTS: A total of 8355 patients were identified for inclusion in this study. Overall, 3% of patients sustained short-term surgical complications and 1% were diagnosed with VTE within 30 days of surgery. Patella fracture fixation had a nearly twofold higher risk for surgical complications compared to quadriceps tendon repair (p = 0.004). Patella tendon repair had a twofold higher risk for VTE (p = 0.045), specifically deep vein thrombosis (p = 0.020), compared to patella fracture fixation. Increasing age, smoking and American Society of Anesthesiologists Classifications 3 and 4 were also found to be risk factors for surgical complications (p = 0.012, p = 0.004, p = 0.011 and p = 0.032, respectively). CONCLUSION: This study used a nationally representative, widely validated, peer-reviewed database to provide valuable insights into risk factors for short-term postoperative complications associated with extensor mechanism repair procedures, revealing notable differences in risk profiles among distinct surgical procedures. The results of this study will inform surgeons and patients in enhancing risk assessment, guiding procedure-specific decision-making, optimising preoperative care, improving postoperative monitoring and contributing to future research of extensor mechanism injuries. LEVEL OF EVIDENCE: Level III.

2.
Arthroscopy ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38537725

RESUMO

PURPOSE: To evaluate and synthesize the available literature related to platelet-rich plasma (PRP) treatment of knee pathologies and to provide recommendations to inform future research in the field. METHODS: PubMed, CINAHL, and Scopus databases were queried on October 6, 2023. All identified citations were collated and uploaded into Covidence for screening and data extraction. Studies were included if they were human studies published in English with adult cohorts that received PRP as a procedural injection or surgical augmentation for knee pathologies with patient-reported outcome measures (PROMs) and level of evidence Levels I-IV. RESULTS: Our search yielded 2,615 studies, of which 155 studies from 2006 to 2023 met the inclusion criteria. Median follow-up was 9 months (±11.2 months). Most studies (75.5%) characterized the leukocyte content of PRP, although most studies (86%) did not use a comprehensive classification scheme. In addition, most studies were from Asia (50%) and Europe (32%) and were from a single center (96%). In terms of treatment, 74% of studies examined PRP as a procedural injection, whereas 26% examined PRP as an augmentation. Most studies (68%) examined treatment of knee osteoarthritis. Many studies (83%) documented significant improvements in PROMs, including 93% of Level III/IV evidence studies and 72% of Level I/II evidence studies, although most studies (70%) failed to include minimal clinically important difference values. The visual analog scale was the most-used PROM (58% of studies), whereas the Short Form Health Survey 36-item was the least-used PROM (5% of studies). CONCLUSIONS: Most published investigations of knee PRP are performed in Asia, investigate procedural injection for osteoarthritis, and show significant outcome improvements. In addition, this review highlights the need for better classification of PRP formulations. LEVEL OF EVIDENCE: Level IV, scoping Review of level I-IV studies.

3.
bioRxiv ; 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38328205

RESUMO

Mammalian behavior and physiology undergo dramatic changes in early life. Young animals rely on conspecifics to meet their homeostatic needs, until weaning and puberty initiate nutritional independence and sex-specific social interactions, respectively. How neuronal populations regulating homeostatic functions and social behaviors develop and mature during these transitions remains unclear. We used paired transcriptomic and chromatin accessibility profiling to examine the developmental trajectories of neuronal populations in the hypothalamic preoptic region, where cell types with key roles in physiological and behavioral control have been identified1-6. These data reveal a remarkable diversity of developmental trajectories shaped by the sex of the animal, and the location and behavioral or physiological function of the corresponding cell types. We identify key stages of preoptic development, including the perinatal emergence of sex differences, postnatal maturation and subsequent refinement of signaling networks, and nonlinear transcriptional changes accelerating at the time of weaning and puberty. We assessed preoptic development in various sensory mutants and find a major role for vomeronasal sensing in the timing of preoptic cell type maturation. These results provide novel insights into the development of neurons controlling homeostatic functions and social behaviors and lay ground for examining the dynamics of these functions in early life.

4.
Cell Rep Methods ; 4(2): 100711, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38382523

RESUMO

In vivo 2-photon calcium imaging has led to fundamental advances in our understanding of sensory circuits in mammalian species. In contrast, few studies have exploited this methodology in birds, with investigators primarily relying on histological and electrophysiological techniques. Here, we report the development of in vivo 2-photon calcium imaging in awake pigeons. We show that the genetically encoded calcium indicator GCaMP6s, delivered by the adeno-associated virus rAAV2/7, allows high-quality, stable, and long-term imaging of neuronal populations at single-cell and single-dendrite resolution in the pigeon forebrain. We demonstrate the utility of our setup by investigating the processing of colors in the visual Wulst, the avian homolog of the visual cortex. We report that neurons in the Wulst are color selective and display diverse response profiles to light of different wavelengths. This technology provides a powerful tool to decipher the operating principles that underlie sensory encoding in birds.


Assuntos
Cálcio , Columbidae , Animais , Neurônios/fisiologia , Diagnóstico por Imagem , Cálcio da Dieta , Mamíferos
5.
Phys Rev Lett ; 132(4): 043802, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38335343

RESUMO

We suggest the use of broadband frequency modulation to construct a novel type of optical interferometer. This interferometer is insensitive to optical phase and allows measurement of the group velocity and group velocity dispersion without the need for short pulse apparatus.

6.
Placenta ; 2024 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-38245404

RESUMO

INTRODUCTION: Cultured mouse trophoblast stem cells (mTSC) maintain proliferation/normal stemness (NS) under FGF4, which when removed, causes normal differentiation (ND). Hypoxic, or hyperosmotic stress forces trophoblast giant cells (TGC) differentiate. Hypoxic, hyperosmotic, and genotoxic benzo(a)pyrene (BaP), which is found in tobacco smoke, force down-regulation of inhibitor of differentiation (Id)2, enabling TGC differentiation. Hypoxic and hyperosmotic stress induce TGC by SAPK-dependent HAND1 increase. Here we test whether BaP forces mTSC-to-TGC while inducing SAPK and HAND1. METHODS: Hand1 and SAPK activity were assayed by immunoblot, mTSC-to-TGC growth and differentiation were assayed at Tfinal after 72hr exposure of BaP, NS, ND, Retinoic acid (RA), or sorbitol. Nuclear-stained cells were micrographed automatically by a live imager, and assayed by ImageJ/FIJI, Biotek Gen 5, AIVIA proprietary artificial intelligence (AI) software or open source, CellPose artificial intelligence/AI software. RESULTS: BaP (0.05-1µM) activated SAPK and HAND1 without diminishing growth. TSC-to-TGC differentiation was assayed with increasingly accuracy for 2-4 N cycling nuclei and >4 N differentiating TGC nuclei, using ImageJ/FIJI, Gen 5, AIVIA, or CellPose AI software. The AIVIA and Cellpose AI software matches human accuracy. The lowest BaP effects on SAPK activation/HAND1 increase are >10-fold more sensitive than similar effects for mESC. RA induces 44-47% 1st lineage TGC differentiation, but the same RA dose induces only 1% 1st lineage mESC differentiation. DISCUSSION: First, these pilot data suggest that mTSC can be used in high throughput screens (HTS) to predict toxicant exposures that force TGC differentiation. Second, mTSC differentiated more cells than mESC for similar stress exposures, Third, open source AI can replace human micrograph quantitation and enable a miscarriage-predicting HTS.

7.
Arthroscopy ; 40(1): 136-145, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37355187

RESUMO

PURPOSE: To investigate the biomechanical effects of tape-reinforced graft suturing and graft retensioning for all-soft tissue quadriceps tendon (ASTQT) anterior cruciate ligament reconstruction (ACLR) in a full-construct human cadaveric model. METHODS: Harvested cadaveric ASTQT grafts were assigned to either (1) double-suspensory adjustable-loop cortical button device (ALD) fixation in which both graft ends were fixed with a suspensory fixation device with (n = 5) or without (n = 5) tape-reinforced suturing or (2) single-suspensory distal tendon fixation in which only the patellar end was fixed with an ALD (n = 5) or fixed-loop cortical button device (FLD) (n = 5). All specimens were prepared using a No. 2 whipstitch technique, and tape-reinforced specimens had an integrated braided tape implant. Graft preparation time was recorded for double-suspensory constructs. Samples were tested on an electromechanical testing machine using a previously published protocol simulating rehabilitative kinematics and loading. RESULTS: Tape-reinforced graft suturing resulted in greater graft load retention after cycling (11.9% difference, P = .021), less total elongation (mean [95% confidence interval (CI)], 5.57 mm [3.50-7.65 mm] vs 32.14 mm [25.38-38.90 mm]; P < .001), greater ultimate failure stiffness (mean [95% CI], 171.9 N/mm [158.8-185.0 N/mm] vs 119.4 N/mm [108.7-130.0 N/mm]; P < .001), and less graft preparation time (36.4% difference, P < .001) when compared with unreinforced specimens. Retensioned ALD constructs had less cyclic elongation compared with FLD constructs (mean total elongation [95% CI], 7.04 mm [5.47-8.61 mm] vs 12.96 mm [8.67-17.26 mm]; P = .004). CONCLUSIONS: Tape-reinforced graft suturing improves time-zero ASTQT ACLR construct biomechanics in a cadaveric model with 83% less total elongation, 44% greater stiffness, and reduced preparation time compared with a whipstitched graft without tape reinforcement. ALD fixation improves construct mechanics when compared with FLD fixation as evidenced by 46% less total elongation. CLINICAL RELEVANCE: Tape-reinforced implants and graft retensioning using ALDs improve time-zero ACLR graft construct biomechanics in a time-zero biomechanical model. Clinical studies will be necessary to determine whether these implants improve clinical outcomes including knee laxity and the incidence of graft rupture.


Assuntos
Reconstrução do Ligamento Cruzado Anterior , Ligamento Cruzado Anterior , Humanos , Ligamento Cruzado Anterior/cirurgia , Fenômenos Biomecânicos , Autoenxertos , Tendões/cirurgia , Reconstrução do Ligamento Cruzado Anterior/métodos , Cadáver
8.
Knee Surg Sports Traumatol Arthrosc ; 31(12): 5463-5476, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37804345

RESUMO

PURPOSE: Research regarding revision anterior cruciate ligament reconstruction (RACLR) with quadriceps tendon (QT) autografts is lacking. The purpose of this study was to perform a systematic review and meta-analysis of RACLR with QT and compare its patient outcomes to RACLR with hamstring tendon (HT) and bone-patellar tendon-bone (BTB) autografts. METHODS: Adhering to PRISMA guidelines, a search for studies using QT in RACLR was performed within PubMed, Scopus, and CINAHL from database date of inception through December 26, 2022. Primary outcomes sought included: failure rate, Lysholm scores, International Knee Documentation Committee (IKDC) scores, IKDC grades, arthrometric knee side-to-side differences (STSD), pivot shift grade, donor site morbidity, return to sport, visual analog scale (VAS) pain scores. RESULTS: Nine studies were included consisting of 606 RACLR: 349 QT, 169 HT, and 88 BTB. Overall failure rates were 7.6% QT, 13.3% HT, and 8.7% BTB. Mean weighted Lysholm scores were 85.8 ± 3.8 QT, 82.5 ± 3.8 HT and 86.6 ± 4.5 BTB. IKDC average scores were 82.3 ± 1.6 QT, 80.1 ± 1.7 HT, and 81.7 ± 5.5BTB. Combined rates of IKDC A/B grades were 88.4% and 80.0% for QT and HT, respectively. VAS average scores were 0.9 ± 1.1 QT, 1.4 ± 0.2 HT, and 0.7 ± 0.8 for BTB. Side-to-side difference was reported for QT and HT with average values of 1.7 ± 0.6 mm and 2.1 ± 0.5 mm, respectively. Grade 0 or 1 pivot shifts were reported in 96.2% of QT patients and 91.3% of HT. Donor site morbidity, only reported for QT and HT, was 14.6 ± 9.7% and 23.6 ± 14.1%, respectively. QT resulted in a mean Tegner score of 5.9 ± 1.5 versus HT 5.7 ± 1.5. Rate of return to pivoting sports was 38.0% QT, 48.6% HT, and 76.9% BTB. Across all outcomes, there was no significant difference when comparing QT to HT, QT to BTB, and QT compared to HT and BTB combined. CONCLUSIONS: RACLR with QT yields satisfactory patient reported outcomes, satisfactory improvement in knee laxity, expected return to sport rates, and has an overall 7.6% failure rate. Outcomes are comparative to those of HT and BTB making it an acceptable graft choice for RACLR. Surgeons should consider using QT autograft for RACLR, especially when other autografts are unavailable. LEVEL OF EVIDENCE: IV.


Assuntos
Lesões do Ligamento Cruzado Anterior , Tendões dos Músculos Isquiotibiais , Ligamento Patelar , Humanos , Tendões dos Músculos Isquiotibiais/transplante , Autoenxertos/cirurgia , Ligamento Patelar/cirurgia , Lesões do Ligamento Cruzado Anterior/cirurgia , Tendões/transplante , Transplante Autólogo , Enxerto Osso-Tendão Patelar-Osso
9.
Cancer Res ; 83(19): 3252-3263, 2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37339176

RESUMO

Outcomes for patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) are poor, with median overall survival (OS) ranging from 6 to 18 months. For those who progress on standard-of-care (chemo)immunotherapy, treatment options are limited, necessitating the development of rational therapeutic strategies. Toward this end, we targeted the key HNSCC drivers PI3K-mTOR and HRAS via the combination of tipifarnib, a farnesyltransferase (FTase) inhibitor, and alpelisib, a PI3Kα inhibitor, in multiple molecularly defined subsets of HNSCC. Tipifarnib synergized with alpelisib at the level of mTOR in PI3Kα- or HRAS-dependent HNSCCs, leading to marked cytotoxicity in vitro and tumor regression in vivo. On the basis of these findings, the KURRENT-HN trial was launched to evaluate the effectiveness of this combination in PIK3CA-mutant/amplified and/or HRAS-overexpressing R/M HNSCC. Preliminary evidence supports the clinical activity of this molecular biomarker-driven combination therapy. Combined alpelisib and tipifarnib has potential to benefit >45% of patients with R/M HNSCC. By blocking feedback reactivation of mTORC1, tipifarnib may prevent adaptive resistance to additional targeted therapies, enhancing their clinical utility. SIGNIFICANCE: The mechanistically designed, biomarker-matched strategy of combining alpelisib and tipifarnib is efficacious in PIK3CA- and HRAS-dysregulated head and neck squamous carcinoma and could improve outcomes for many patients with recurrent, metastatic disease. See related commentary by Lee et al., p. 3162.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Serina-Treonina Quinases TOR/metabolismo , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Biomarcadores , Proteínas Proto-Oncogênicas p21(ras)/genética
10.
Birth Defects Res ; 115(12): 1109-1119, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37243321

RESUMO

BACKGROUND: A survey of laboratories in North American and Europe that routinely conduct fetal skeletal examinations was performed with the purpose of (1) understanding current terminology used for classifying skeletal findings in developmental toxicity (DT) studies and (2) understanding the criteria used to identify relatively common findings that sufficiently deviate from normal. The goal was to promote terminology harmonization and improve interlaboratory consistency in the criteria used to identify developmental anomalies. METHODS: The survey, designed based on terminology for developmental anomalies recommended by an international collaboration (Makris et al., Congenital Anomalies, 2009;49(3):123-246), was conducted by a subgroup (authors of this publication) of the Royal Society of Biology's International Register of Fetal Morphologists (IRFM). RESULTS: Individual and summarized anonymized responses are provided here. The authors, who are expert fetal morphologists with experience performing fetal examinations, reviewed the responses and generated recommendations on preferred terminology and criteria for determining when morphological variations deviate from normal and warrant recording of the findings for skeletal observations in Sprague Dawley (SD) fetal rats. The objective of these recommendations is to complement Makris et al. (Congenital Anomalies, 2009;49(3):123-246). CONCLUSION: The broad application will improve interlaboratory harmonization of recording fetal skeleton findings in developmental toxicity studies intended for regulatory submissions, including SEND (Standard for Exchange of Nonclinical Data).


Assuntos
Feto , Cuidado Pré-Natal , Ratos , Animais , Humanos , Gravidez , Feminino , Ratos Sprague-Dawley , Feto/anormalidades , Europa (Continente)
11.
Hastings Cent Rep ; 53(1): 33-45, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36840335

RESUMO

This ethnographic study introduces the term "distressed work" to describe the emergence of chronic frictions between moral imperatives for health care workers to keep working and the dramatic increase in distress during the Covid-19 pandemic. Interviews and observant participation conducted in a hospital intensive care unit during the Covid-19 pandemic reveal how health care workers connected job duties with extraordinary emotional, physical, and moral burdens. We explore tensions between perceived obligations of health care professionals and the structural contexts of work. Key findings cluster around the moral imperatives of health care work and the distress that work engendered as work spaces, senses of vocation, patient and family interactions, and end-of-life care shifted. While the danger of working beyond limits has long been an ordinary feature of health care work, it has now become a chronic crisis. Assessing this problem in terms of distressed work and its structural contexts can better address effective, worker-informed responses to current health care labor dilemmas.


Assuntos
COVID-19 , Estresse Psicológico , Humanos , Estresse Psicológico/psicologia , Pandemias , Emoções , Cuidados Críticos , Princípios Morais
12.
Nat Ecol Evol ; 7(1): 92-101, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36471120

RESUMO

There have been recent renewed commitments to increase the extent of protected areas to combat the growing biodiversity crisis but the underpinning evidence for their effectiveness is mixed and causal connections are rarely evaluated. We used data gathered by three large-scale citizen science programmes in the UK to provide the most comprehensive assessment to date of whether national (Sites of Special Scientific Interest) and European (Special Protection Areas/Special Areas of Conservation) designated areas are associated with improved state (occurrence, abundance), change (rates of colonization, persistence and trend in abundance), community structure and, uniquely, demography (productivity) on a national avifauna, while controlling for differences in land cover, elevation and climate. We found positive associations with state that suggest these areas are well targeted and that the greatest benefit accrued to the most conservation-dependent species since positive associations with change were largely restricted to rare and declining species and habitat specialists. We suggest that increased productivity provides a plausible demographic mechanism for positive effects of designation.


Assuntos
Biodiversidade , Conservação dos Recursos Naturais , Animais , Ecossistema , Aves , Reino Unido
14.
Nat Commun ; 13(1): 6328, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319621

RESUMO

Seagrass conservation is critical for mitigating climate change due to the large stocks of carbon they sequester in the seafloor. However, effective conservation and its potential to provide nature-based solutions to climate change is hindered by major uncertainties regarding seagrass extent and distribution. Here, we describe the characterization of the world's largest seagrass ecosystem, located in The Bahamas. We integrate existing spatial estimates with an updated empirical remote sensing product and perform extensive ground-truthing of seafloor with 2,542 diver surveys across remote sensing tiles. We also leverage seafloor assessments and movement data obtained from instrument-equipped tiger sharks, which have strong fidelity to seagrass ecosystems, to augment and further validate predictions. We report a consensus area of at least 66,000 km2 and up to 92,000 km2 of seagrass habitat across The Bahamas Banks. Sediment core analysis of stored organic carbon further confirmed the global relevance of the blue carbon stock in this ecosystem. Data from tiger sharks proved important in supporting mapping and ground-truthing remote sensing estimates. This work provides evidence of major knowledge gaps in the ocean ecosystem, the benefits in partnering with marine animals to address these gaps, and underscores support for rapid protection of oceanic carbon sinks.


Assuntos
Ecossistema , Tubarões , Animais , Sequestro de Carbono , Mudança Climática , Carbono
15.
Arthroscopy ; 38(8): 2368-2369, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35940736

RESUMO

Anterior cruciate ligament (ACL) reconstruction is one of the most commonly performed knee operations. An "all-inside" technique creates bone sockets for ACL graft passage, as opposed to more traditional full bone tunnels, and typically incorporates suspensory fixation instead of screw fixation to secure the graft. This technique may be indicated for any ACL reconstruction surgery, where adequate bone stock exists to drill sockets and to use cortical fixation. The technique may be used with all soft tissue, as well as bone plug ACL grafts and autograft hamstring or quadriceps tendon; most allograft tendon options may be performed with an all-inside technique. Advantages include anatomic tunnel/socket placement, decreased postoperative pain and swelling, minimal hardware, appropriate graft tensioning and retensioning, and circumferential graft to bone healing. Tips for successful all-inside surgery include matching graft diameter to socket diameter, drilling appropriate length sockets based on individual graft length, so as not to "bottom out" the graft and confirming cortical button fixation intraoperatively. Potential complications include graft-socket mismatch, full-tunnel reaming, and loss of cortical fixation. Multiple studies have shown the all-inside technique to have similar or superior biomechanical properties and clinical outcomes compared to the more traditional full-tunnel ACL reconstruction techniques.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior/métodos , Parafusos Ósseos , Humanos , Tendões/transplante , Transplante Autólogo
16.
Clin Cancer Res ; 28(11): 2270-2277, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35344029

RESUMO

PURPOSE: FGFR genomic alterations (amplification, mutations, and/or fusions) occur in ∼8% of gliomas, particularly FGFR1 and FGFR3. We conducted a multicenter open-label, single-arm, phase II study of a selective FGFR1-3 inhibitor, infigratinib (BGJ398), in patients with FGFR-altered recurrent gliomas. PATIENTS AND METHODS: Adults with recurrent/progressive gliomas harboring FGFR alterations received oral infigratinib 125 mg on days 1 to 21 of 28-day cycles. The primary endpoint was investigator-assessed 6-month progression-free survival (PFS) rate by Response Assessment in Neuro-Oncology criteria. Comprehensive genomic profiling was performed on available pretreatment archival tissue to explore additional molecular correlations with efficacy. RESULTS: Among 26 patients, the 6-month PFS rate was 16.0% [95% confidence interval (CI), 5.0-32.5], median PFS was 1.7 months (95% CI, 1.1-2.8), and objective response rate was 3.8%. However, 4 patients had durable disease control lasting longer than 1 year. Among these, 3 had tumors harboring activating point mutations at analogous positions of FGFR1 (K656E; n = 2) or FGFR3 (K650E; n = 1) in pretreatment tissue; an FGFR3-TACC3 fusion was detected in the other. Hyperphosphatemia was the most frequently reported treatment-related adverse event (all-grade, 76.9%; grade 3, 3.8%) and is a known on-target toxicity of FGFR inhibitors. CONCLUSIONS: FGFR inhibitor monotherapy with infigratinib had limited efficacy in a population of patients with recurrent gliomas and different FGFR genetic alterations, but durable disease control lasting more than 1 year was observed in patients with tumors harboring FGFR1 or FGFR3 point mutations or FGFR3-TACC3 fusions. A follow-up study with refined biomarker inclusion criteria and centralized FGFR testing is warranted.


Assuntos
Glioma , Recidiva Local de Neoplasia , Adulto , Seguimentos , Glioma/tratamento farmacológico , Glioma/genética , Humanos , Proteínas Associadas aos Microtúbulos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Compostos de Fenilureia , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética
17.
Prim Care Diabetes ; 16(2): 223-244, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35183458

RESUMO

Type 2 diabetes and its associated comorbidities are growing more prevalent, and the complexity of optimising glycaemic control is increasing, especially on the frontlines of patient care. In many countries, most patients with type 2 diabetes are managed in a primary care setting. However, primary healthcare professionals face the challenge of the growing plethora of available treatment options for managing hyperglycaemia, leading to difficultly in making treatment decisions and contributing to treatment and therapeutic inertia. This position statement offers a simple and patient-centred clinical decision-making model with practical treatment recommendations that can be widely implemented by primary care clinicians worldwide through shared-decision conversations with their patients. It highlights the importance of managing cardiovascular disease and elevated cardiovascular risk in people with type 2 diabetes and aims to provide innovative risk stratification and treatment strategies that connect patients with the most effective care.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperglicemia , Comorbidade , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Europa (Continente)/epidemiologia , Humanos , Atenção Primária à Saúde
18.
JSES Rev Rep Tech ; 2(3): 323-331, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37588857

RESUMO

Hypothesis: The purpose of this study was to perform a systematic review of the available literature evaluating surgical outcomes after chronic distal biceps tendon rupture. Surgical techniques, including primary repair, autograft reconstruction, and allograft reconstruction, were compared, as well as subjective and objective clinical outcomes and complication rates. Methods: A systematic literature search of Level I-IV studies reporting outcomes of surgically treated chronic distal biceps tendon ruptures were performed via PubMed, Cochrane Collaboration, Science Direct, and Google Scholar databases. Twenty-two papers were identified in the review, with 236 patients. A Modified Coleman Methodological Score (CMS) was determined for every article to assess study quality. Patient-reported outcomes, postoperative range of motion, flexion and supination strength, and postoperative complications were recorded. MAYO elbow scores (MEPS) were reported more consistently than the other outcome tools. Results: No Level I or level II studies were identified in our search, and the heterogeneity of outcome measures precluded meta-analysis. Studies demonstrated mean MEPS scores ranging between 86 and 100, regardless of the surgical technique utilized. All studies reported a mean flexion-extension arc equal to or greater than 5-130°. The reported mean postoperative flexion strength was within 10% of the unaffected contralateral side. The most common complication for both direct repair and reconstruction groups was paresthesia of the lateral antebrachial cutaneous nerve [direct repair: 18-16.8%; reconstruction: 8-6.2% (allograft: 4-6%; autograft: 4-7%)]. Rerupture was uncommon and occurred in three patients who had undergone direct repair and in one patient after autograft reconstruction. Conclusions: Surgical treatment of chronic distal biceps injuries yields favorable objective and subjective outcomes. Currently, available evidence suggests that direct repair, autograft reconstruction, or allograft reconstruction are all viable treatment options with similar outcomes.

19.
Phys Sportsmed ; 50(6): 541-545, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-34478355

RESUMO

OBJECTIVES: COVID-19 altered National Football League (NFL) player and team training during the 2020 offseason. All preseason games were cancelled resulting in absence of game play before the first week of the regular season. Thus, concerns exist regarding injury susceptibility of players during regular season games. The purpose of this study was to evaluate and compare injury rates during the 2020 NFL season versus injury rates from the unaffected 2017-2019 seasons. We hypothesized there would be an increased injury rate and an increased rate of season ending injuries during the modified 2020 season. METHODS: The NFL's public injury database was queried to identify players placed on the injury lists throughout the 2017-2020 seasons. All players listed as "out" and on the injured reserve due to physical injury were included in the data set. For further stratification, injury incidence was separated based on position. Time missed due to COVID-19 illness was not included. Injury rates were expressed as injuries per 1000 athlete exposures (AE). RESULTS: Overall, 893 individual players missed games due to injury during the 2020 NFL regular season compared to an average of 743 over the 2017-2019 seasons. Defensive players at all positions had a statistically significant increase in injury incidence from an average of 7.54 to 10.20 injuries per 1000 AE. Defensive backs were most affected with a 46% increase in players injured. There was no statistically significant difference in season ending injuries for any position. CONCLUSIONS: The COVID-19 stricken 2020 NFL regular season saw an increased rate and incidence of injuries. Specifically, defensive players had a higher incidence of injury overall with defensive backs experiencing the greatest increase in injury rates.


Assuntos
COVID-19 , Futebol Americano , Futebol , Humanos , Futebol Americano/lesões , Estações do Ano , COVID-19/epidemiologia , Atletas
20.
Ann R Coll Surg Engl ; 104(1): 35-40, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34414807

RESUMO

INTRODUCTION: Trochleoplasty is a surgical procedure used to treat patellar instability by modifying the trochlear groove. Analysis of the groove with a handheld scanner would enable accurate real-time planning and facilitate tailormade correction. We aimed to measure trochlear depth, sulcus angle, trochlear facet ratio, trochlear angle and lateral trochlear inclination angle and to establish inter- and intra-rater reliability for knee models to determine reliability and repeatability. METHODS: The trochlear grooves of three knee models were scanned by two investigators. Three-dimensional reference models were created and surface-matched. Custom software was used to determine the desired parameters. The intraclass correlation coefficient (ICC) was used to determine test-retest reliability and the parameter results for each model that showed best reproducibility. RESULTS: There was good interobserver reliability (trochlear depth, 1.0mm; sulcus angle, 2.7°; trochlear angle, 4.0°; lateral trochlear inclination angle, 4.0°), except in the trochlear facet ratio (32.0%) of one knee model. With outliers removed, the ICC was moderate to excellent in 73.34% of measurements, with trochlear depth showing the best reproducibility. DISCUSSION: This feasibility study showed a handheld scanner in conjunction with supporting software can measure trochlear parameters with good to excellent inter- and intra-observer reliability.


Assuntos
Simulação por Computador , Modelos Biológicos , Articulação Patelofemoral/anatomia & histologia , Humanos , Estudo de Prova de Conceito , Reprodutibilidade dos Testes , Software
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