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BACKGROUND: Clinical care pathways help guide and provide structure to clinicians and providers to improve healthcare delivery and quality. The Quality Improvement and Patient Safety Committee (QIPS) of the American Society for Metabolic and Bariatric Surgery (ASMBS) has previously published care pathways for the performance of laparoscopic sleeve gastrectomy (LSG) and pre-operative care of patients undergoing Roux-en-Y gastric bypass (RYGB). OBJECTIVE: This current RYGB care pathway was created to address intraoperative care, defined as care occurring on the day of surgery from the preoperative holding area, through the operating room, and into the postanesthesia care unit (PACU). METHODS: PubMed queries were performed from January 2001 to December 2019 and reviewed according to Level of Evidence regarding specific key questions developed by the committee. RESULTS: Evidence-based recommendations are made for care of patients undergoing RYGB including the pre-operative holding area, intra-operative management and performance of RYGB, and concurrent procedures. CONCLUSIONS: This document may provide guidance based on recent evidence to bariatric surgeons and providers for the intra-operative care for minimally invasive RYGB.
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The purpose of this work was to provide a simple method to determine reactive strength during the 6-meter timed hop test (6mTH) and evaluate its association with isokinetic peak torque in patients following anterior cruciate ligament reconstruction (ACLR). Twenty-nine ACLR patients who were at least four months from surgery were included in this analysis. Participants were brought into the laboratory on one occasion to complete functional testing. Quadriceps and hamstring isokinetic testing was completed bilaterally at 60, 180, and 300 degâs-1, using extension peak torque from each speed as the outcome measure. The 6mTH was completed bilaterally using a marker-based motion capture system, and reactive strength ratio (RSR) was calculated from the vertical velocity of the pelvis during the test. An adjustment in RSR was made using the velocity of the 6mTH test to account for different strategies employed across participants. Repeated measures correlations were used to determine associations among isokinetic and hop testing variables. A two-way mixed analysis of variance was used to determine differences in isokinetic and hop testing variables between operated and non-operated legs and across male and female participants. Moderate positive associations were found between RSR (and adjusted RSR) and isokinetic peak torque at all speeds (r = .527 to .577). Mean comparisons showed significant main effects for leg and sex. Patients showed significant deficits in their operated versus non-operated legs in all isokinetic and hop testing variables, yet only isokinetic peak torque and timed hop time showed significant differences across male and female groups. Preliminary results are promising but further development is needed to validate other accessible technologies available to calculate reactive strength during functional testing after ACLR. Pending these developments, the effects of movement strategies, demographics, and levels of participation on RSR can then be explored to translate this simple method to clinical environments.
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Reconstrução do Ligamento Cruzado Anterior , Força Muscular , Torque , Humanos , Masculino , Reconstrução do Ligamento Cruzado Anterior/métodos , Feminino , Adulto , Força Muscular/fisiologia , Adulto Jovem , Teste de Esforço/métodos , Lesões do Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/fisiopatologia , Músculo Quadríceps/fisiologia , Músculo Quadríceps/fisiopatologia , Desempenho Físico Funcional , Adolescente , Ligamento Cruzado Anterior/cirurgia , Ligamento Cruzado Anterior/fisiopatologia , Músculos Isquiossurais/fisiopatologia , Músculos Isquiossurais/fisiologiaRESUMO
Mandibular distraction has variable outcomes in Treacher-Collins syndrome. Dual syndromic diagnosis is a rare occurrence that complicates management. Here, the authors present a patient with Treacher-Collins syndrome and severe retrognathia requiring tracheostomy who failed repeat mandibular distraction and decannulation. A genetic workup later revealed Angelman syndrome with severe developmental delay. We discuss explanations for difficulties encountered during mandibular distraction as well as surgical options for patients with Treacher-Collins who fail multiple attempts at decannulation. Overall, patients with dual diagnoses can exhibit an underlying problem in bone formation and mineralization, which challenges any attempt at craniofacial manipulation.
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BACKGROUND: In adults with anterior cruciate ligament (ACL) tears, bone bruises on magnetic resonance imaging (MRI) scans provide insight into the underlying mechanism of injury. There is a paucity of literature that has investigated these relationships in children with ACL tears. PURPOSE: To examine and compare the number and location of bone bruises between contact and noncontact ACL tears in pediatric patients. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Boys ≤14 years and girls ≤12 years of age who underwent primary ACL reconstruction surgery between 2018 and 2022 were identified at 3 separate institutions. Eligibility criteria required detailed documentation of the mechanism of injury and MRI performed within 30 days of the initial ACL tear. Patients with congenital lower extremity abnormalities, concomitant fractures, injuries to the posterolateral corner and/or posterior cruciate ligament, previous ipsilateral knee injuries or surgeries, or closed physes evident on MRI scans were excluded. Patients were stratified into 2 groups based on a contact or noncontact mechanism of injury. Preoperative MRI scans were retrospectively reviewed for the presence of bone bruises in the coronal and sagittal planes using fat-suppressed T2-weighted images and a grid-based mapping technique of the tibiofemoral joint. RESULTS: A total of 109 patients were included, with 76 (69.7%) patients sustaining noncontact injuries and 33 (30.3%) patients sustaining contact injuries. There were no significant differences between the contact and noncontact groups in terms of age (11.8 ± 2.0 vs 12.4 ± 1.3 years; P = .12), male sex (90.9% vs 88.2%; P > .99), time from initial injury to MRI (10.3 ± 8.1 vs 10.4 ± 8.9 days; P = .84), the presence of a concomitant medial meniscus tear (18.2% vs 14.5%; P = .62) or lateral meniscus tear (69.7% vs 52.6%; P = .097), and sport-related injuries (82.9% vs 81.8%; P = .89). No significant differences were observed in the frequency of combined lateral tibiofemoral (lateral femoral condyle + lateral tibial plateau) bone bruises (87.9% contact vs 78.9% noncontact; P = .41) or combined medial tibiofemoral (medial femoral condyle [MFC] + medial tibial plateau) bone bruises (54.5% contact vs 35.5% noncontact; P = .064). Patients with contact ACL tears were significantly more likely to have centrally located MFC bruising (odds ratio, 4.3; 95% CI, 1.6-11; P = .0038) and less likely to have bruising on the anterior aspect of the lateral tibial plateau (odds ratio, 0.27; 95% CI, 0.097-0.76; P = .013). CONCLUSION: Children with contact ACL tears were 4 times more likely to present with centrally located MFC bone bruises on preoperative MRI scans compared with children who sustained noncontact ACL tears. Future studies should investigate the relationship between these bone bruise patterns and the potential risk of articular cartilage damage in pediatric patients with contact ACL tears.
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Lesões do Ligamento Cruzado Anterior , Contusões , Imageamento por Ressonância Magnética , Humanos , Masculino , Feminino , Lesões do Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/diagnóstico por imagem , Criança , Contusões/diagnóstico por imagem , Adolescente , Estudos Retrospectivos , Reconstrução do Ligamento Cruzado Anterior , Tíbia/diagnóstico por imagemRESUMO
INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) is currently the most common bariatric procedure performed in adolescents and young adults in the United States (USA), but there are limited data available on long-term postoperative weight outcomes in these patients. This single-institution US study follows longitudinal weight data in a diverse group of patients undergoing LSG at age 25 years or younger. METHODS: We retrospectively reviewed records of all patients 25 years or younger who underwent LSG at our institution between 2013 and 2020. All weight data documented in the medical record through January 2023 was included. We calculated weight change postoperatively as percent total weight loss (%TWL) relative to preoperative weight. RESULTS: One hundred forty-one patients underwent LSG, at a mean age of 23.1 years. Within this cohort, 56.1% identified as non-Hispanic Black or Hispanic, and 39.7% had private health insurance. The mean %TWL at weight nadir was 28.5% at a mean of 1.35 years postoperatively. The mean long-term %TWL (in patients with ≥ 4 years of follow-up) was 11.8% at a mean of 5.6 years postoperatively, with 43 of the 84 patients with long-term weight data (51%) within 10% of their preoperative weight at most recent follow-up. CONCLUSION: Adolescents and young adults undergoing LSG at our institution had weight nadir comparable to published results during the first 1 to 2 years postoperatively, but the majority developed significant weight recurrence over the ensuing years. Our findings highlight the need for adjuvant weight loss strategies to improve the durability of weight outcomes after LSG in this population.
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Gastrectomia , Laparoscopia , Obesidade Mórbida , Redução de Peso , Humanos , Feminino , Adulto Jovem , Estudos Retrospectivos , Masculino , Adolescente , Gastrectomia/métodos , Obesidade Mórbida/cirurgia , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto , Cirurgia Bariátrica/estatística & dados numéricos , Cirurgia Bariátrica/métodosRESUMO
ATTR amyloidosis is caused by deposition of large, insoluble aggregates (amyloid fibrils) of cross-ß-sheet TTR protein molecules on the intercellular surfaces of tissues. The process of amyloid formation from monomeric TTR protein molecules to amyloid deposits has not been fully characterized and is therefore modeled in this paper. Two models are considered: 1) TTR monomers in the blood spontaneously fold into a ß-sheet conformation, aggregate into short proto-fibrils that then circulate in the blood until they find a complementary tissue where the proto-fibrils accumulate to form the large, insoluble amyloid fibrils found in affected tissues. 2) TTR monomers in the native or ß-sheet conformation circulate in the blood until they find a tissue binding site and deposit in the tissue or tissues forming amyloid deposits in situ. These models only differ on where the selection for ß-sheet complementarity occurs, in the blood where wt-wt, wt-v, and v-v interactions determine selectivity, or on the tissue surface where tissue-wt and tissure-v interactions also determine selectivity. Statistical modeling in both cases thus involves selectivity in fibril aggregation and tissue binding. Because binding of protein molecules into fibrils and binding of fibrils to tissues occurs through multiple weak non-covalent bonds, strong complementarity between ß-sheet molecules and between fibrils and tissues is required to explain the insolubility and tissue selectivity of ATTR amyloidosis. Observation of differing tissue selectivity and thence disease phenotypes from either pure wildtype TTR protein or a mix of wildtype and variant molecules in amyloid fibrils evidences the requirement for fibril-tissue complementarity. Understanding the process that forms fibrils and binds fibrils to tissues may lead to new possibilities for interrupting the process and preventing or curing ATTR amyloidosis.
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Amiloide , Pré-Albumina , Pré-Albumina/metabolismo , Pré-Albumina/química , Humanos , Amiloide/metabolismo , Amiloide/química , Neuropatias Amiloides Familiares/metabolismo , Neuropatias Amiloides Familiares/patologia , Amiloidose/metabolismo , Modelos Moleculares , Conformação Proteica em Folha betaRESUMO
Knee pathology, including anterior cruciate ligament (ACL) tears, meniscal tears, articular cartilage lesions, and intra-articular masses or cysts are common clinical entities treated by orthopedic surgeons with arthroscopic surgery. Preoperatively, magnetic resonance imaging (MRI) is now standard in confirming knee pathology, particularly detecting pathology less evident with history and physical examination alone. The radiologist's MRI interpretation becomes essential in evaluating intra-articular knee structures. Typically, the radiologist that interprets the MRI does not have the opportunity to view the same pathology arthroscopically. Thus, the purpose of this article is to illustratively reconcile what the orthopedic surgeon sees arthroscopically with what the radiologist sees on magnetic resonance imaging when viewing the same pathology. Correlating virtual and actual images can help better understand pathology, resulting in more accurate MRI interpretations. In this article, we present and review a series of MR and correlating arthroscopic images of ACL tears, meniscal tears, chondral lesions, and intra-articular masses and cysts. Short teaching points are included to highlight the importance of radiological signs and pathological MRI appearance with significant clinical and arthroscopic findings.
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Highlighting here a patient case with neuroblastoma, renal cancer & GIST from germline SDHA.
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Mutação em Linhagem Germinativa , Neoplasias Renais , Neuroblastoma , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neuroblastoma/genética , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/patologia , Masculino , Complexo II de Transporte de Elétrons/genética , Mosaicismo , Feminino , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/patologiaRESUMO
INTRODUCTION: Combat boots are special shoes designed for soldiers to wear during activities in rough terrain, such as long marches or military training. Combat boots have been known to cause high plantar pressure and increase the injury rate of the lower extremities. Therefore, this study aimed to compare the difference in in-shoe plantar pressure between Korean combat boots and running shoes. We hypothesised that the newest Korean combat boots would have comparable plantar pressure distribution with running shoes. METHODS: We prospectively recruited 30 asymptomatic male participants, who are candidates for military services, from the local area. Two types of shoes (the newly developed Korean combat boots and running shoes) were examined. Pedobarographic measurements were collected using the pedar-X in-shoe pressure measurement system. Peak pressure (PP), pressure time integral (PTI), contact area and contact time were analysed. RESULTS: Both PP and PTI at the region of central and lateral forefeet (FF) were significantly higher in combat boots. The contact area of combat boots was significantly lower at the region of the hallux, second-fifth toes, medial FF, central FF and midfoot. Contact time at the region of central FF and medial heel was significantly higher in combat boots. CONCLUSIONS: Understanding the plantar pressure distribution of combat boots can be helpful for developing combat boots and preventing injury. Based on the results of our study, the next-generation Korean combat boots should be developed to increase contact area and distribute impulse under the head of the metatarsal bone.
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Much of the toxicity in oil sands process-affected water in Athabasca oil sands tailings has been attributed to naphthenic acids (NAs) and associated naphthenic acid fraction compounds (NAFCs). Previous work has characterized the environmental behaviour and fate of these compounds, particularly in the context of constructed treatment wetlands. There is evidence that wetlands can attenuate NAFCs in natural and engineered contexts, but relative contributions of chemical, biotic, and physical adsorption with sequestration require deconvolution. In this work, the objective was to evaluate the extent to which prospective wetland substrate material may adsorb NAFCs using a peat-mineral mix (PMM) sourced from the Athabasca Oil Sands Region (AOSR). The PMM and NAFCs were first mixed and then equilibrated across a range of NAFC concentrations (5-500 mg/L) with moderate ionic strength and hardness (â¼200 ppm combined Ca2+ and Mg2+) that approximate wetland water chemistry. Under these experimental conditions, low sorption of NAFCs to PMM was observed, where sorbed concentrations of NAFCs were approximately zero mg/kg at equilibrium. When NAFCs and PMM were mixed and equilibrated together at environmentally relevant concentrations, formula diversity increased more than could be explained by combining constituent spectra. The TOC present in this PMM was largely cellulose-derived, with low levels of thermally recalcitrant carbon (e.g., lignin, black carbon). The apparent enhancement of the concentration and diversity of components in PMM/NAFCs mixtures are likely related to aqueous solubility of some PMM-derived organic materials, as post-hoc combination of dissolved components from PMM and NAFCs cannot replicate enhanced complexity observed when the two components are agitated and equilibrated together.
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Ácidos Carboxílicos , Campos de Petróleo e Gás , Solo , Áreas Alagadas , Adsorção , Ácidos Carboxílicos/química , Solo/química , Minerais/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/análise , Areia/químicaRESUMO
Importance: Angiosarcoma is an aggressive vascular malignant neoplasm presenting either as a primary or secondary cancer, often arising after radiotherapy or in the context of preexisting lymphedema. Comprehensive data describing its incidence and presentation patterns are needed. Objective: To describe the incidence, presenting characteristics, and change over time of angiosarcoma in the US. Design, Setting, and Participants: This retrospective cross-sectional study used data from the US Cancer Statistics (USCS) National Program of Cancer Registries-Surveillance, Epidemiology, and End Results Combined Database, which captures more than 99% of newly diagnosed cancers in the US. The study included all 19â¯289 patients in the US with a new diagnosis of angiosarcoma between 2001 and 2020 captured in the USCS database. Statistical analysis was performed from June to September 2023. Main Outcomes and Measures: Incidence of angiosarcoma, demographics of patients with angiosarcoma, and extent of disease at presentation. Results: The study included 19â¯289 patients (median age, 71 years [IQR, 59-80 years]; 10â¯506 women [54.5%]) with a new diagnosis of angiosarcoma. The US incidence of angiosarcoma doubled between 2001 (657 cases) and 2019 (1312 cases), reflecting both an increase in the adjusted incidence rate of 1.6% per year (P = .001), to 3.3 cases per 1â¯000â¯000 person-years (95% CI, 3.1-3.5 cases per 1â¯000â¯000 person-years), and an increase in the population at risk. In 2020, the reported incidence rate (3.0 cases per 1â¯000â¯000 person-years) and cases of angiosarcoma (n = 1159) were modestly lower than in 2019. Overall, 72.3% of cases of angiosarcoma (n = 13â¯955) were cutaneous, subcutaneous, or breast angiosarcomas; 24.4% were visceral (n = 4701); and 3.3% were located in unknown or rare primary sites (n = 633). Secondary breast and chest wall angiosarcomas among women represented the largest contribution to increasing incidence. Among breast angiosarcomas, 99.2% (2684 of 2705) were in women and 71.9% (1944 of 2705) were secondary. A total of 80.4% of chest wall or thorax cases among women (1861 of 2316) were secondary vs 26.5% among men (112 of 422), and 63.9% of upper extremity cases among women (205 of 321) were secondary vs 26.8% (56 of 209) among men (P = .001). Rates of secondary angiosarcoma in the abdomen and lower extremities were similar between men and women. The incidence rate of visceral angiosarcoma was also found to be increasing (1.5% per year; P = .001). Conclusions and Relevance: This cross-sectional study describes angiosarcoma presentation patterns and incidence rates in the US over a 20-year period and shows that the number of cases in men and women increased, with the greatest increase among women with secondary angiosarcoma of the chest, breast, and upper extremity. These data increase awareness of a rare but highly morbid disease and highlight the need for improved early detection of angiosarcoma among patients at high risk, such as women with a history of breast cancer.
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Neoplasias da Mama , Hemangiossarcoma , Masculino , Humanos , Feminino , Idoso , Incidência , Hemangiossarcoma/epidemiologia , Estudos Transversais , Estudos RetrospectivosRESUMO
AIM: To compare the image quality of virtual noncontrast (VNC) and true noncontrast (TNC) CT images and to evaluate the clinical feasibility of VNC CT images for assessing osteochondral lesions of the talus (OLTs). MATERIALS AND METHODS: Forty-five OLT patients who underwent ankle CT arthrography (CTA) using dual-layer spectral detector CT were enrolled. Reconstruction of VNC and three-dimensional volume rendering images was performed. Afterward, image noise, the signal-to-noise ratio (SNR), and the contrast-to-noise ratio (CNR) were measured. For the subjective evaluation, two board-certified musculoskeletal radiologists [R2-1] assessed spatial resolution, overall image quality, and lesion conspicuity. The accuracy rate for OLT grading was determined in 23 patients who underwent arthroscopic surgery. RESULTS: While VNC images showed significantly less noise than TNC images, TNC images showed better SNRs and CNRs (p<.01). In the subjective analysis, TNC images showed better overall image quality (p<.001). For the 3D volume rendering images, VNC images scored significantly higher for lesion conspicuity (p<.001). The accuracy rates of CTA and CTA with VNC images for OLT grading were 79.2% and 83.3%, respectively. Regarding confidence level, when CTA and VNC images were evaluated together, the confidence level was significantly higher than that when only CTA images were evaluated (p<.001). CONCLUSION: VNC imaging can provide better confidence level of OLT grading and evaluation of the integrity of the subchondral bone plate when combined with conventional CTA without additional radiation dose to the patient. In addition, VNC images-based 3D volume rendering reconstruction would be helpful for preoperative planning in OLT patients.
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Artrografia , Estudos de Viabilidade , Tálus , Tomografia Computadorizada por Raios X , Humanos , Tálus/diagnóstico por imagem , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Artrografia/métodos , Imageamento Tridimensional/métodos , Adulto Jovem , Idoso , Adolescente , Razão Sinal-Ruído , Estudos Retrospectivos , Interpretação de Imagem Radiográfica Assistida por Computador/métodosRESUMO
AIMS: Patients with heart failure and reduced ejection fraction (HFrEF) exhibit skeletal muscle pathology, which contributes to symptoms and decreased quality of life. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve clinical outcomes in HFrEF but their mechanism of action remains poorly understood. We aimed, therefore, to determine whether SGLT2i influence skeletal muscle pathology in patients with HFrEF. METHODS AND RESULTS: Muscle biopsies from 28 male patients with HFrEF (New York Heart association class I-III) treated with SGLT2i (>12 months) or without SGLT2i were compared. Comprehensive analyses of muscle structure (immunohistochemistry), transcriptome (RNA sequencing), and metabolome (liquid chromatography-mass spectrometry) were performed, and serum inflammatory profiling (ELISA). Experiments in mice (n = 16) treated with SGLT2i were also performed. Myofiber atrophy was ~20% less in patients taking SGLT2i (p = 0.07). Transcriptomics and follow-up measures identified a unique signature in patients taking SGLT2i related to beneficial effects on atrophy, metabolism, and inflammation. Metabolomics identified influenced tryptophan metabolism in patients taking SGLT2i: kynurenic acid was 24% higher and kynurenine was 32% lower (p < 0.001). Serum profiling identified that SGLT2i treatment was associated with lower (p < 0.05) pro-inflammatory cytokines by 26-64% alongside downstream muscle interleukin (IL)-6-JAK/STAT3 signalling (p = 008 and 0.09). Serum IL-6 and muscle kynurenine were correlated (R = 0.65; p < 0.05). Muscle pathology was lower in mice treated with SGLT2i indicative of a conserved mammalian response to treatment. CONCLUSIONS: Treatment with SGLT2i influenced skeletal muscle pathology in patients with HFrEF and was associated with anti-atrophic, anti-inflammatory, and pro-metabolic effects. These changes may be regulated via IL-6-kynurenine signalling. Together, clinical improvements following SGLT2i treatment in patients with HFrEF may be partly explained by their positive effects on skeletal muscle pathology.
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Insuficiência Cardíaca , Músculo Esquelético , Inibidores do Transportador 2 de Sódio-Glicose , Volume Sistólico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Masculino , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/metabolismo , Humanos , Volume Sistólico/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Animais , Camundongos , Pessoa de Meia-Idade , Idoso , BiópsiaRESUMO
ATR is a key kinase in the DNA-damage response (DDR) that is synthetic lethal with several other DDR proteins, making it an attractive target for the treatment of genetically selected solid tumors. Herein we describe the discovery of a novel ATR inhibitor guided by a pharmacophore model to position a key hydrogen bond. Optimization was driven by potency and selectivity over the related kinase mTOR, resulting in the identification of camonsertib (RP-3500) with high potency and excellent ADME properties. Preclinical evaluation focused on the impact of camonsertib on myelosuppression, and an exploration of intermittent dosing schedules to allow recovery of the erythroid compartment and mitigate anemia. Camonsertib is currently undergoing clinical evaluation both as a single agent and in combination with talazoparib, olaparib, niraparib, lunresertib, or gemcitabine (NCT04497116, NCT04972110, NCT04855656). A preliminary recommended phase 2 dose for monotherapy was identified as 160 mg QD given 3 days/week.
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Neoplasias , Humanos , Proteínas Mutadas de Ataxia Telangiectasia , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , GencitabinaRESUMO
ABSTRACT: Cohen, JL, Cade, WH, Harrah, TC, Costello II, JP, and Kaplan, LD. The surgical management of NCAA Division 1 college football injuries post COVID-19: A single institution retrospective review. J Strength Cond Res 38(5): 906-911, 2024-The unprecedented COVID-19 pandemic had a significant impact on college football operations, including athletes' training regimens. As a result of these changes, concern for increased injury susceptibility post COVID-19 regulations has become a point of discussion. The current study sought to evaluate the incidence of surgical injury among NCAA Division 1 college football players at the authors' institution during the first full season after start of the COVID-19 pandemic compared with previous years. Retrospective chart review was performed for all players who sustained injuries requiring surgery while a member of the NCAA Division 1 football program during the 2009-2021 seasons. A p -value of ≤0.05 was used to determine significance. A total of 23 surgical injuries occurred in 22 players during the 2021 season compared with 121 in 118 players in the 12 previous seasons combined ( p = 0.0178; RR = 1.47). There was a significant increase in shoulder injuries ( n = 13 vs. n = 31; p = <0.0001; RR = 3.05) and specifically a significant increase in labral tears ( n = 10 vs. n = 30; p = 0.0003; RR = 2.74). No difference was seen in knee injuries ( n = 10 vs. n = 77; p = 0.27; RR = 1.35) and specifically no difference in anterior cruciate ligament injuries ( n = 3 vs. n = 31; p = 0.77; RR = 1.17). This phenomenon is multifactorial in nature, but alterations to players' training and preparations because of the COVID-19 pandemic likely resulted in suboptimal conditioning, leading to the increased incidence of surgical injuries emphasizing the importance of adequate strength training and conditioning.
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Traumatismos em Atletas , COVID-19 , Futebol Americano , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos Retrospectivos , Futebol Americano/lesões , Masculino , Traumatismos em Atletas/epidemiologia , Traumatismos em Atletas/cirurgia , Universidades , Lesões do Ombro/epidemiologia , Incidência , Adulto Jovem , SARS-CoV-2 , Traumatismos do Joelho/cirurgia , Traumatismos do Joelho/epidemiologia , Lesões do Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/epidemiologiaRESUMO
RAF, a core signaling component of the MAPK kinase cascade, is often mutated in various cancers, including melanoma, lung, and colorectal cancers. The approved inhibitors were focused on targeting the BRAFV600E mutation that results in constitutive activation of kinase signaling through the monomeric protein (Class I). However, these inhibitors also paradoxically activate kinase signaling of RAF dimers, resulting in increased MAPK signaling in normal tissues. Recently, significant attention has turned to targeting RAF alterations that activate dimeric signaling (class II and III BRAF and NRAS). However, the discovery of a potent and selective inhibitor with biopharmaceutical properties suitable to sustain robust target inhibition in the clinical setting has proven challenging. Herein, we report the discovery of exarafenib (15), a highly potent and selective inhibitor that intercepts the RAF protein in the dimer compatible αC-helix-IN conformation and demonstrates anti-tumor efficacy in preclinical models with BRAF class I, II, and III and NRAS alterations.
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Melanoma , Proteínas Proto-Oncogênicas B-raf , Humanos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Linhagem Celular Tumoral , Melanoma/patologia , Sistema de Sinalização das MAP Quinases , MutaçãoRESUMO
BACKGROUND: Rapid adoption of sleeve gastrectomy (SG) in the last decade aptly reflects the desire of patients and surgeons for alternatives to RYGB and DS. While SG provides good outcomes, other options that address specific patient needs are warranted. Recently approved by ASMBS, SADI, and OAGB have garnered increasing interest due to their single anastomosis technique. METHODS: Using the Metabolic and Bariatric Surgery Quality Improvement Program database, we examined laparoscopic and robotic cases from 2018 to 2021 to understand the percentage of primary bariatric surgery cases that are SADI and OAGB. We used coarsened exact matching to match patients who underwent SADI or OAGB to patients who underwent Roux-en-Y gastric bypass (RYGB). We examined outcomes of matched patients using logistic regression. RESULTS: Of the 667,979 patients that underwent bariatric-metabolic surgery, 1326 (0.2%) underwent SADI, and 2541 (0.4%) underwent OAGB. SADI was not identified in the database until 2020. In 2020, there were 487 SADI procedures compared to 839 in 2021. From 2018 to 2021, OAGBs went from 149 to 940. Compared with RYGB, SADI was associated with higher rates of anastomotic or staple line leak (OR 2.21 (95% CI 1.08-4.53)) and sepsis (OR 3.62 (95% CI 1.62-8.12)). Compared with RYGB, OAGB was associated with lower rates of gastrointestinal bleeding (OR 0.29 (95% CI 0.12-0.71)) and bowel obstruction (OR 0.10 (95% CI 0.02-0.39)). Of note, there were no differences between these procedures and RYGB for 30-day mortality. CONCLUSION: More SADIs and OAGBs are being performed. However, there were higher complication rates associated with the SADI procedure. Further studies will be needed to better understand the key drivers for these outcomes.
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Cirurgia Bariátrica , Derivação Gástrica , Obesidade Mórbida , Humanos , Derivação Gástrica/métodos , Obesidade Mórbida/cirurgia , Melhoria de Qualidade , Gastrectomia/métodos , América do Norte/epidemiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Despite the growing use of next-generation sequencing (NGS) in the management of advanced non-small-cell lung cancer (NSCLC), there is little evidence that its use leads to improved clinical outcomes. This study aimed to compare the effectiveness of NGS with that of single-gene testing (SGT) alone in patients with advanced NSCLC. MATERIALS AND METHODS: This was a retrospective cohort study conducted on patients diagnosed with advanced lung adenocarcinoma between 2017 and 2018 from a nationwide, population-based database. We identified patients who had SGT exclusively (SGT group) or underwent upfront NGS or NGS following SGT as an initial evaluation (NGS group). Patients were followed up until death or the end of the study (31 December 2019). The adjusted hazard ratio (aHR) for death was estimated using the Cox proportional hazards model. The factors affecting the adoption of NGS were identified. RESULTS: Of 8566 patients diagnosed with advanced lung adenocarcinoma, 402 and 6932 patients were assigned to the NGS and SGT groups, respectively. More NGS was carried out in younger patients, those with higher incomes, and those living in urban areas. After balancing these confounders through matching, no difference was observed in the median overall survival and risk of death between the NGS and SGT groups [18.5 versus 19.7 months, log-rank P = 0.783; aHR 0.98, 95% confidence interval (CI) 0.84-1.14, respectively]. Only in a subgroup for whom epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) inhibitors were not indicated, NGS was associated with better survival outcomes (14.1 versus 9.0 months, log-rank P = 0.006; aHR 0.82, 95% CI 0.69-0.97). CONCLUSIONS: In the real world, NGS for all-comers in patients with advanced NSCLC did not increase survival outcomes. When health care resources to support equal access to NGS are limited, upfront SGT followed by NGS may be a more efficient strategy.
Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/diagnóstico , Estudos Retrospectivos , Mutação , Inibidores de Proteínas Quinases , Adenocarcinoma de Pulmão/genética , Sequenciamento de Nucleotídeos em Larga Escala , Sistema de RegistrosRESUMO
BACKGROUND: Total mesorectal excision using conventional straight fixed devices may be technically difficult because of the narrow and concave pelvis. Several laparoscopic articulating tools have been introduced as an alternative to robotic systems. The aim of this study was to compare perioperative outcomes between laparoscopic low anterior resection using ArtiSential® and robot-assisted surgery for rectal cancer. METHODS: This retrospective study included 682 patients who underwent laparoscopic or robotic low anterior resection for rectal cancer from September 2018 to December 2021. Among them, 82 underwent laparoscopic surgery using ArtiSential® (group A) and 201 underwent robotic surgery (group B). A total of 73 [group A; 66.37 ± 11.62; group B 65.79 ± 11.34] patients were selected for each group using a propensity score matching analysis. RESULTS: There was no significant difference in the baseline characteristics between group A and B. Mean operative time was longer in group B than A (163.5 ± 61.9 vs 250.1 ± 77.6 min, p < 0.001). Mean length of hospital stay was not significantly different between the two groups (6.2 ± 4.7 vs 6.7 ± 6.1 days, p = 0.617). Postoperative complications, reoperation, and readmission within 30 days after surgery were similar between the two groups. Pathological findings revealed that the circumferential resection margins were above 10 mm in both groups (11.00 ± 7.47 vs 10.17 ± 6.25 mm, p = 0.960). At least 12 lymph nodes were sufficiently harvested, with no significant difference in the number harvested between the groups (20.5 ± 9.9 vs 19.7 ± 7.3, p = 0.753). CONCLUSIONS: Laparoscopic low anterior resection using ArtiSential® can achieve acceptable clinical and oncologic outcomes. ArtiSential®, a multi-joint and articulating device, may serve a feasible alternative approach to robotic surgery in rectal cancer.
Assuntos
Laparoscopia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Humanos , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Retais/cirurgiaRESUMO
Fibroblast growth factor receptor (FGFR) alterations are present as oncogenic drivers and bypass mechanisms in many forms of cancer. These alterations can include fusions, amplifications, rearrangements, and mutations. Acquired drug resistance to current FGFR inhibitors often results in disease progression and unfavorable outcomes for patients. Genomic profiling of tumors refractory to current FGFR inhibitors in the clinic has revealed several acquired driver alterations that could be the target of next generation therapeutics. Herein, we describe how structure-based drug design (SBDD) was used to enable the discovery of the potent and kinome selective pan-FGFR inhibitor KIN-3248, which is active against many acquired resistance mutations. KIN-3248 is currently in phase I clinical development for the treatment of advanced tumors harboring FGFR2 and/or FGFR3 gene alterations.