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Background: Chronic pain is common and costly. Antidepressants are prescribed to reduce pain. However, there has not been a network meta-analysis examining all antidepressants across all chronic pain conditions, so effectiveness and safety for most antidepressants for pain conditions remain unknown. Objective: To assess the efficacy and safety of antidepressants for chronic pain (except headache) in adults. Our primary outcomes were as follows: substantial pain relief (50%), pain intensity, mood and adverse events. Our secondary outcomes were as follows: moderate pain relief (30%), physical function, sleep, quality of life, Patient Global Impression of Change, serious adverse events and withdrawal. Design: This was a systematic review with a network meta-analysis. We searched CENTRAL, MEDLINE, EMBASE, CINAHL, LILACS, AMED and PsycINFO databases for randomised controlled trials of antidepressants for chronic pain conditions up until 4 January 2022. The review was registered in PROSPERO (CRD42020171855), and the protocol was published in the Cochrane Library (https://doi.org/10.1002/14651858.CD014682). Setting: We analysed trials from all settings. Participants: We included trials in which participants had chronic pain, defined as longer than 3 months, from any condition excluding headache. Interventions: We included all antidepressants. Main outcome measures: Our primary outcome was substantial pain relief, defined as a reduction Ëâ 50%. We also measured pain intensity, mood and adverse events. Secondary measures included moderate pain relief (above 30% reduction), physical function, sleep, quality of life, Global Impression of Change, serious adverse events, and withdrawal from trial. Results: We identified 176 studies with a total of 28,664 participants. Most studies were placebo-controlled (n = 83) and parallel armed (n = 141). The most common pain conditions examined were fibromyalgia (59 studies), neuropathic pain (49 studies) and musculoskeletal pain (40 studies). The average length of randomised controlled trials was 10 weeks. Most studies measured short-term outcomes only and excluded people with low mood and other mental health conditions. Across efficacy outcomes, duloxetine was consistently the highest-ranked antidepressant with moderate- to high-certainty evidence. Standard dose was equally efficacious as high dose for the majority of outcomes. Milnacipran was often ranked as the next most efficacious antidepressant, although the certainty of evidence was lower than that for duloxetine. There was insufficient evidence to draw robust conclusions for the efficacy and safety of any other antidepressant for chronic pain. Limitations: The evidence for antidepressants other than duloxetine is poor. For duloxetine, it is not clear whether the effect applies to groups with both pain and low mood, since these groups were excluded from trials. There is also insufficient evidence on long-term outcomes and on adverse effects. Conclusions: There is only reliable evidence for duloxetine in the treatment of chronic pain. Duloxetine was moderately efficacious across all outcomes at standard dose. There is also promising evidence for milnacipran, although further high-quality research is needed to be confident in these conclusions. Data for all other antidepressants were of low certainty. However, the findings should not be read as an encouragement to prescribe antidepressants where other non-pharmacological intervention could be equally effective, especially in the absence of good evidence on side effects and safety. Future work: There is a need for large, methodologically sound trials testing the effectiveness of antidepressants for chronic pain. These trials should examine long-term outcomes (> 6 months) and include people with low mood. There should also be better reporting of adverse events, tolerance of drugs, and long-term compliance. Study registration: This study is registered as PROSPERO CRD42020171855. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR128782) and is published in full in Health Technology Assessment; Vol. 28, No. 62. See the NIHR Funding and Awards website for further award information.
Chronic pain is pain that lasts for more than 3 months. Over one-third of people across the world experience chronic pain. This often has a detrimental impact on people's mood, disability and well-being. Antidepressants are often prescribed to reduce pain, but we are not sure which antidepressants work best for different types of pain, or whether they are safe. We wanted to find out whether antidepressants were effective and safe for management of chronic pain. We searched for studies that had compared any antidepressant with any other treatment for any type of chronic pain (except headache). We compared all the treatments against each other using a statistical method called network meta-analysis. This method allows us to rank the treatments in order of best to worst for each outcome. We found 176 studies that included a total of 28,664 people with chronic pain. Most of the studies (83/176) compared an antidepressant with a placebo (which looks like the real medicine but does not have any medicine in it). The evidence from our analysis suggests that: Duloxetine is the antidepressant that we have the most confidence in. It was the best antidepressant for reducing pain and improving physical function. A standard dose of duloxetine was equally as effective for reducing pain as a high dose of duloxetine. Milnacipran was also effective at reducing pain, but we are not as confident in this result as in the one for duloxetine because there were fewer studies with fewer people involved. Aside from duloxetine and milnacipran, we do not have confidence in the results from any other antidepressant included in this review, and even for duloxetine and milnacipran, we do not know the long-term effects. It is important to recognise that the lack of evidence for the majority of antidepressants in this review does not necessarily equal a lack of benefit. Rather, this means that the large, high-quality trials required for us to be certain of an antidepressant's effectiveness have not been undertaken. Altogether, although duloxetine and milnacipran are effective, the results of this review should not be read as an encouragement to prescribe antidepressants where other non-pharmacological intervention could be equally effective, especially in the absence of good evidence on side effects and safety. These conclusions were informed by our patient and public involvement group.
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Antidepressivos , Dor Crônica , Manejo da Dor , Adulto , Humanos , Antidepressivos/uso terapêutico , Antidepressivos/efeitos adversos , Dor Crônica/tratamento farmacológico , Metanálise em Rede , Manejo da Dor/métodos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Cancer-related cognitive impairment (CRCI) is a broad term encompassing subtle cognitive problems to more severe impairment. CRCI severity is influenced by host, disease, and treatment factors and affects patients prior to, during, and following cancer treatment. The National Cancer Institute (NCI) Symptom Management and Health-Related Quality of Life Steering Committee (SxQoL SC) convened a Clinical Trial Planning Meeting (CTPM) to review the state of the science on CRCI and to develop both Phase II/III intervention trials aimed at improving cognitive function in cancer survivors with non-central nervous system (CNS) disease and longitudinal studies to understand the trajectory of cognitive impairment and contributing factors. Participants included experts in the field of CRCI, members of the SxQOL SC, patient advocates, representatives from all seven NCI Community Oncology Research Program (NCORP) Research Bases, and the NCI. Presentations focused on the following topics: measurement, lessons learned from pediatric and geriatric oncology, biomarker and mechanism endpoints, longitudinal study designs, and pharmacologic and behavioral intervention trials. Panel discussions provided guidance on priority cognitive assessments, considerations for remote assessments, inclusion of relevant biomarkers, and strategies for ensuring broad inclusion criteria. Three CTPM working groups (longitudinal studies and pharmacologic and behavioral intervention trials) convened for one year to discuss and report on top priorities and to design studies. The CTPM experts concluded sufficient data exist to advance Phase II/Phase III trials utilizing selected pharmacologic and behavioral interventions for the treatment of CRCI in the non-CNS setting with recommendations included herein.
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Bone toxicities are common among paediatric patients treated for acute lymphoblastic leukaemia (ALL) with potentially major negative impact on patients' quality of life. To identify the underlying genetic contributors, we conducted a genome-wide association study (GWAS) and a transcriptome-wide association study (TWAS) in 260 patients of European-descent from the DFCI 05-001 ALL trial, with validation in 101 patients of European-descent from the DFCI 11-001 ALL trial. We identified a significant association between rs844882 on chromosome 20 and bone toxicities in the DFCI 05-001 trial (p = 1.7 × 10-8). In DFCI 11-001 trial, we observed a consistent trend of this variant with fracture. The variant was an eQTL for two nearby genes, CD93 and THBD. In TWAS, genetically predicted ACAD9 expression was associated with an increased risk of bone toxicities, which was confirmed by meta-analysis of the two cohorts (meta-p = 2.4 × 10-6). In addition, a polygenic risk score of heel quantitative ultrasound speed of sound was associated with fracture risk in both cohorts (meta-p = 2.3 × 10-3). Our findings highlight the genetic influence on treatment-related bone toxicities in this patient population. The genes we identified in our study provide new biological insights into the development of bone adverse events related to ALL treatment.
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Poverty-exposed children with cancer are more likely to experience adverse outcomes. Supplemental Nutrition Assistance Program (SNAP) benefits improve food insecurity and child health outcomes, and could be used to mitigate disparities. We conducted a secondary analysis of parent-reported data collected in a frontline pediatric leukemia trial (NCT03020030) to assess SNAP eligibility (proxied by other means-tested program participation) and participation. At diagnosis, 105/287 families (37%) were SNAP-eligible, of whom 53 (50%) were SNAP participants. At 6 months, 104/257 families (41%) were SNAP-eligible, and 59 (57%) were SNAP participants. Interventions to increase benefits participation during childhood cancer treatment represent an immediate opportunity to reduce disparities.
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Assistência Alimentar , Humanos , Feminino , Assistência Alimentar/estatística & dados numéricos , Masculino , Criança , Pré-Escolar , Pobreza , Insegurança Alimentar , Leucemia/terapia , Adolescente , Seguimentos , LactenteRESUMO
Neurological damage is the pathological substrate of permanent disability in various neurodegenerative disorders. Early detection of this damage, including its identification and quantification, is critical to preventing the disease's progression in the brain. Tau, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL), as brain protein biomarkers, have the potential to improve diagnostic accuracy, disease monitoring, prognostic assessment, and treatment efficacy. These biomarkers are released into the cerebrospinal fluid (CSF) and blood proportionally to the degree of neuron and astrocyte damage in different neurological disorders, including stroke, traumatic brain injury, multiple sclerosis, neurodegenerative dementia, and Parkinson's disease. Here, we review how Tau, GFAP, and NfL biomarkers are detected in CSF and blood as crucial diagnostic tools, as well as the levels of these biomarkers used for differentiating a range of neurological diseases and monitoring disease progression. We also discuss a biosensor approach that allows for the real-time detection of multiple biomarkers in various neurodegenerative diseases. This combined detection system of brain protein biomarkers holds significant promise for developing more specific and accurate clinical tools that can identify the type and stage of human neurological diseases with greater precision.
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Biomarcadores , Proteína Glial Fibrilar Ácida , Doenças Neurodegenerativas , Proteínas de Neurofilamentos , Proteínas tau , Humanos , Biomarcadores/líquido cefalorraquidiano , Biomarcadores/sangue , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Proteínas de Neurofilamentos/sangue , Proteína Glial Fibrilar Ácida/líquido cefalorraquidiano , Proteína Glial Fibrilar Ácida/sangue , Proteínas tau/líquido cefalorraquidiano , Proteínas tau/sangue , Doenças Neurodegenerativas/líquido cefalorraquidiano , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/sangue , Encéfalo/metabolismo , Encéfalo/patologiaRESUMO
SUMMARY: The inferior glenoid and scapular neck are common locations for scapular fractures. Operative exposures for reduction and fixation can be challenging, and frequently, the proximal fracture planes are not conducive to optimal fixation with a plate alone. The purpose of this article was to describe a new technique for enhancing fixation in specific inferior glenoid fractures using a single cortical lag screw.
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Parafusos Ósseos , Fixação Interna de Fraturas , Fraturas Ósseas , Escápula , Humanos , Escápula/lesões , Escápula/cirurgia , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/instrumentação , Fraturas Ósseas/cirurgia , Masculino , Resultado do Tratamento , Feminino , Adulto , Pessoa de Meia-Idade , Cavidade Glenoide/cirurgia , Cavidade Glenoide/lesõesRESUMO
PURPOSE: The purpose of the study was to evaluate the relationships between brentuximab vedotin (BV) pharmacokinetics, age, and body weight (BW) with efficacy and safety in pediatric and young adult patients with previously untreated, high-risk classical Hodgkin lymphoma in the phase III AHOD1331 study. EXPERIMENTAL DESIGN: Overall, 296 patients (age 2-21 years) in the overall population were randomized to and received BV + chemotherapy; the pharmacokinetic subpopulation comprised 24 patients (age <13 years). Age- and/or BW-based (pharmacokinetic surrogates) subgroup analyses of efficacy and safety were conducted for the overall population. Exposure-response analyses were limited to the pharmacokinetic subpopulation. RESULTS: There were no visible trends in disease characteristics across pediatric age subgroups, whereas BW increased with age. Observed antibody-drug conjugate exposures in patients ages <12 years were lower than those in adults administered BV 1.8 mg/kg every 3 weeks, as exposure increased with BW. Nevertheless, no detrimental impact on event-free survival was seen in younger subgroups: 3-year event-free survival rates were 96.2% (2-<12 years) and 92.0% (12-<18 years), with no events observed in those ages <6 years. Neither early response nor lack of need for radiation therapy was associated with high pharmacokinetic exposure. No evidence of exposure-driven grade ≥2 or ≥3 peripheral neuropathy or grade ≥3 neutropenia was seen in exposure-safety and BW-based subgroup analyses; the incidence of these safety events was comparable across pediatric age subgroups, despite lower exposure in younger children. CONCLUSIONS: No further adjustments based on age or BW are required for the BV dosage (1.8 mg/kg every 3 weeks) approved in children.
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Peso Corporal , Brentuximab Vedotin , Doença de Hodgkin , Humanos , Brentuximab Vedotin/administração & dosagem , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Doença de Hodgkin/diagnóstico , Adolescente , Criança , Feminino , Masculino , Adulto Jovem , Pré-Escolar , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Imunoconjugados/administração & dosagem , Imunoconjugados/farmacocinética , Imunoconjugados/efeitos adversos , Imunoconjugados/uso terapêuticoRESUMO
Background: Ankle fractures are a common injury treated by orthopaedic surgeons. Unstable, displaced ankle fractures are often fixed with open reduction internal fixation (ORIF) using different implant constructs at various cost. No study to date has looked at transparency in ankle implant costs to surgeon behavior. Our surgeons self-identified that the biggest barrier for lowering implant cost was the lack of cost transparency. This was a surgeon-led-study to evaluate whether increased transparency in implant costs affected surgeon behavior. Methods: Monthly operative logs from December 2021 to September 2022 were reviewed at our level 1 trauma center for operative fixation of ankle fractures. The cost data of each fixation construct was reported to trauma-trained surgeons at the end of each month from March 2022 to June 2022. Average costs of implants were compared before and after education. A linear mixed model was used to explore what factors were associated with changes in costs. Surgeons also participated in a poststudy survey. Results: The implant costs of 110 ankle fracture fixations were reviewed over the period before education (n = 60), during education (n = 30), and after education (n = 20). The mean implant cost difference for unimalleolar fractures was -$204.80 (P = .68), whereas the mean cost difference for bimalleolar fractures was -$9.82 (P = .98). Trimalleolar fractures had a mean cost difference of +$94.47 (P = .84). Linear mixed model demonstrated fracture pattern as the only factor significantly associated with implant costs (P < .01). Post-education surgeon survey revealed that 6 of 7 surgeons felt that monthly updates affected their implant selection. However, only 2 surgeons demonstrated a change in practice with decreased implant costs during the study. Conclusion: The majority of surgeons self-reported being influenced by the implant cost education, but the detected change in implant cost was only observed in less than one-third of surgeons. Our results suggest implant selection and related costs are not influenced by increased cost transparency education alone. Level of Evidence: Level III, case control study.
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ABSTRACT: Several single-arm studies have explored the inclusion of brentuximab vedotin (BV) in salvage chemotherapy followed by autologous stem cell transplantation (ASCT) for relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL). However, no head-to-head comparisons with standard salvage chemotherapy have been performed. This study presents a propensity score-matched analysis encompassing individual patient data from 10 clinical trials to evaluate the impact of BV in transplant-eligible patients with R/R cHL. We included 768 patients, of whom 386 were treated with BV with or without chemotherapy (BV cohort), whereas 382 received chemotherapy alone (chemotherapy cohort). Propensity score matching resulted in balanced cohorts of 240 patients each. No significant differences were observed in pre-ASCT complete metabolic response (CMR) rates (P = .69) or progression free survival (PFS; P = .14) between the BV and chemotherapy cohorts. However, in the BV vs chemotherapy cohort, patients with relapsed disease had a significantly better 3-year PFS of 80% vs 70%, respectively (P = .02), whereas there was no difference for patients with primary refractory disease (56% vs 62%, respectively; P = .67). Patients with stage IV disease achieved a significantly better 3-year PFS in the BV cohort (P = .015). Post-ASCT PFS was comparable for patients achieving a CMR after BV monotherapy and those receiving BV followed by sequential chemotherapy (P = .24). Although 3-year overall survival was higher in the BV cohort (92% vs 80%, respectively; P < .001), this is likely attributed to the use of other novel therapies in later lines for patients experiencing progression, given that studies in the BV cohort were conducted more recently. In conclusion, BV with or without salvage chemotherapy appears to enhance PFS in patients with relapsed disease but not in those with primary refractory cHL.
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Brentuximab Vedotin , Doença de Hodgkin , Pontuação de Propensão , Humanos , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Brentuximab Vedotin/uso terapêutico , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Terapia de Salvação , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva , Adulto Jovem , Adolescente , Resultado do Tratamento , Idoso , Recidiva Local de Neoplasia/tratamento farmacológico , Resistencia a Medicamentos AntineoplásicosRESUMO
There is a growing understanding and identification of costal cartilage injuries, however, diagnosis of these injuries remains difficult. We present a novel radiodensity based coloring technique, termed the True-Blue technique, to manipulate 3D CT imaging and more accurately diagnose costochondral injuries.
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Parede Torácica , Parede Torácica/diagnóstico por imagem , Costelas/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVES: The purpose of this study was to report patterns of scapular fractures and define them with a contemporary methodology. METHODS: . DESIGN: Retrospective study, 2015-2021. SETTING: Single, academic, Level 1 trauma center. PATIENT SELECTION CRITERIA: Consecutive patients ≥18 years, presenting with unilateral scapula fracture, with thin-slice (≤0.5-mm) bilateral computed tomography (CT) scans of the entirety of both the injured and uninjured scapulae. OUTCOME MEASURES AND COMPARISONS: Thin-slice (0.5-mm) CT scans of injured and normal scapulae were obtained to create three-dimensional (3D) virtual models. 3D modeling software (Stryker Orthopedics Modeling and Analytics, Stryker Trauma GmbH, Kiel, Germany aka SOMA) was used to create a 3D map of fracture location and frequency. Fracture zones were delineated using anatomic landmarks to characterize fracture patterns. RESULTS: Eighty-seven patients were identified with 75 (86%) extra-articular and 12 (14%) intra-articular fractures. The dominant fracture pattern emanated from the superior lateral border (zone E) to an area inferior to the spinomedial angle (zone B) and was present in 80% of extra-articular fractures. A second-most common fracture line propagated from the primary (most-common) line toward the inferior medial scapular border with a frequency of 36%. Bare zones (with 1 or no fractures present) were identified in 4 unique areas. Furthermore, intra-articular fractures were found to be heterogenous. CONCLUSIONS: The 3D fracture map created in this study confirmed that extra-articular scapular fractures occur in certain patterns with a relatively high frequency. Results provide greater insight into scapular fracture locations and may help to study prognosis of injury and improve treatment strategy including operative approaches and surgical tactics.
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Fraturas Ósseas , Fraturas Intra-Articulares , Fraturas do Ombro , Humanos , Fraturas Intra-Articulares/cirurgia , Estudos Retrospectivos , Escápula/diagnóstico por imagem , Escápula/lesões , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Tomografia Computadorizada por Raios XRESUMO
Chemobrain is a condition that negatively affects cognition in cancer patients undergoing active chemotherapy, as well as following chemotherapy cessation. Chemobrain is also known as chemotherapy-induced cognitive impairment (CICI) and has emerged as a significant medical contingency. There is no therapy to ameliorate this condition, hence identification of novel therapeutic strategies to prevent CICI is of great interest to cancer survivors. Utilizing the platinum-based chemotherapy cisplatin in an investigative approach for CICI, we identified increased expression of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in the adult mouse hippocampus, and in human cortical neuron cultures derived from induced pluripotent stem cells (iPSCs). Notably, administration of NS398, a selective COX-2 inhibitor, prevented CICI in vivo without negatively affecting the antitumor efficacy of cisplatin or potentiating tumor growth. Given that dysfunctional mitochondrial bioenergetics plays a prominent role in CICI, we explored the effects of NS398 in cisplatin-induced defects in human cortical mitochondria. We found that cisplatin significantly reduces mitochondrial membrane potential (MMP), increases matrix swelling, causes loss of cristae membrane integrity, impairs ATP production, as well as decreases cell viability and dendrite outgrowth. Pretreatment with NS398 in human cortical neurons attenuated mitochondrial dysfunction caused by cisplatin, while improving cell survival and neurite morphogenesis. These results suggest that aberrant COX-2 inflammatory pathways may contribute in cisplatin-induced mitochondrial damage and cognitive impairments. Therefore, COX-2 signaling may represent a viable therapeutic approach to improve the quality of life for cancer survivors experiencing CICI.
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BACKGROUND: Rib fractures are common injuries which can be associated with acute pain and chronic disability. While most rib fractures ultimately go on to achieve bony union, a subset of patients may go on to develop non-union. Management of these nonunited rib fractures can be challenging and variability in management exists. METHODS: The Chest Wall Injury Society's Publication Committee convened to develop recommendations for use of surgical stabilization of nonunited rib fractures (SSNURF) to treat traumatic rib fracture nonunions. PubMed, Embase, and the Cochrane database were searched for pertinent studies. Using a process of iterative consensus, all committee members voted to accept or reject the recommendation. RESULTS: No identified studies compared SSNURF to alternative therapy and the overall quality of the body of evidence was rated as low. Risk of bias was identified in all studies. Despite these limitations, there is lower-quality evidence suggesting that SSNURF may be beneficial for decreasing pain, reducing opiate use, and improving patient reported outcomes among patients with symptomatic rib nonunion. However, these benefits should be balanced against risk of symptomatic hardware failure and infection. CONCLUSION: This guideline document summarizes the current CWIS recommendations regarding use of SSNURF for management of rib nonunion. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.
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Dor Aguda , Fraturas não Consolidadas , Alcaloides Opiáceos , Fraturas das Costelas , Traumatismos Torácicos , Parede Torácica , Humanos , Fraturas das Costelas/complicações , Fraturas das Costelas/cirurgia , Costelas , Fraturas não Consolidadas/cirurgiaRESUMO
Chemotherapy has a significant positive impact in cancer treatment outcomes, reducing recurrence and mortality. However, many cancer surviving children and adults suffer from aberrant chemotherapy neurotoxic effects on learning, memory, attention, executive functioning, and processing speed. This chemotherapy-induced cognitive impairment (CICI) is referred to as "chemobrain" or "chemofog". While the underlying mechanisms mediating CICI are still unclear, there is strong evidence that chemotherapy accelerates the biological aging process, manifesting as effects which include telomere shortening, epigenetic dysregulation, oxidative stress, mitochondrial defects, impaired neurogenesis, and neuroinflammation, all of which are known to contribute to increased anxiety and neurocognitive decline. Despite the increased prevalence of CICI, there exists a lack of mechanistic understanding by which chemotherapy detrimentally affects cognition in cancer survivors. Moreover, there are no approved therapeutic interventions for this condition. To address this gap in knowledge, this review attempts to identify how adenosine signaling, particularly through the adenosine A2A receptor, can be an essential tool to attenuate accelerated aging phenotypes. Importantly, the adenosine A2A receptor uniquely stands at the crossroads of cancer treatment and improved cognition, given that it is widely known to control tumor induced immunosuppression in the tumor microenvironment, while also posited to be an essential regulator of cognition in neurodegenerative disease. Consequently, we propose that the adenosine A2A receptor may provide a multifaceted therapeutic strategy to enhance anticancer activity, while combating chemotherapy induced cognitive deficits, both which are essential to provide novel therapeutic interventions against accelerated aging in cancer survivors.
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Senilidade Prematura , Antineoplásicos , Sobreviventes de Câncer , Comprometimento Cognitivo Relacionado à Quimioterapia , Neoplasias , Doenças Neurodegenerativas , Adulto , Criança , Humanos , Adenosina , Comprometimento Cognitivo Relacionado à Quimioterapia/prevenção & controle , Neoplasias/tratamento farmacológico , Receptor A2A de Adenosina , Senilidade Prematura/induzido quimicamente , Antineoplásicos/efeitos adversosRESUMO
Current evidence suggests at least one-third of humeral shaft fractures initially managed nonoperatively will fail closed treatment, and this review highlights surgical considerations in those circumstances. Although operative indications are well-defined, certain fracture patterns and patient cohorts are at greater risk of failure. When operative intervention is necessary, internal fixation through an anterolateral approach is a safe and sensible alternative. Determining which patients will benefit most involves shared decision-making and careful patient selection. The fracture characteristics, bone quality, and adequacy of the reduction need to be carefully evaluated for the specific operative risks for individuals with certain comorbid conditions, inevitably balancing the patient's expectations and demands against the probability of infection, nerve injury, or nonunion. As our understanding of the etiology and risk of nonunion and symptomatic malunion of the humeral diaphysis matures, adhering to the principles of diagnosis and treatment becomes increasingly important. In the event of nonunion, respect for the various contributing biological and mechanical factors enhances the likelihood that all aspects will be addressed successfully through a comprehensive solution. This review further explores specific strategies to definitively restore function of the upper extremity with the ultimate objective of an uninfected, stable union.
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CASE: We report on a 35-year-old man presenting with disabling pain secondary to multiple rib nonunions and a costochondral dislocation 5 months after sustaining a chest wall crush injury. He underwent surgical reconstruction of the chest and was followed for 2 years. Surgical exposure to the heart was necessary during open reduction of the flail segment, followed by costochondral joint fixation with plates and screws. Although he was a workers' compensation patient, he returned to full gainful employment. CONCLUSION: Open reduction and internal fixation of a symptomatic, chronically displaced, precordial, flail segment can relieve pain and promote return to baseline function.
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Tórax Fundido , Fraturas das Costelas , Parede Torácica , Masculino , Humanos , Adulto , Tórax Fundido/etiologia , Tórax Fundido/cirurgia , Fraturas das Costelas/diagnóstico por imagem , Fraturas das Costelas/cirurgia , Fraturas das Costelas/complicações , Fixação Interna de Fraturas/efeitos adversos , Costelas/lesõesRESUMO
BACKGROUND: Rarely, traumatic sternum fractures may result in nonunion, which can have drastic, negative implications. Literature on traumatic sternal nonunion reconstruction outcomes is limited to case reports. We present the surgical principles and report clinical outcomes for seven patients following surgical reconstruction of a traumatic sternal body nonunion. METHODS: Consecutive adult patients with a nonunion after a traumatic sternum fracture who underwent reconstruction using locking plate technology and iliac crest bone graft at a Level I trauma center from 2013 to 2021 were identified. Demographic, injury, and surgery data was collected, and postoperative patient-reported outcome (PRO) scores were obtained. Patient-reported outcome scores included the one-question single assessment numeric evaluation (SANE), and the combined 10-question global physical health and global mental health values. Injuries were classified and all fractures were mapped onto a sternum template. Postoperative radiographs were reviewed for union. RESULTS: Of the study's seven patients, five were female, and the mean age was 58 years. Mechanism of injury included motor vehicle collision (5) and blunt object chest trauma (2). The mean time from initial fracture to nonunion fixation was 9 months. Four of the seven patients achieved in-clinic follow-up at ≥12 months (mean = 14.3 months), while the other three achieved ≥6 months of in-clinic follow-up. Six patients completed outcomes surveys ≥12 months after surgery (mean = 28.9 months). Mean PRO scores at final follow-up included: SANE of 75 (out of 100), and global physical health and global mental health of 44 and 47, respectively (US population mean = 50).Six of seven patients achieved known radiographic union. CONCLUSION: We describe an effective and practical method of achieving stable fixation in traumatic sternal body nonunions as evidenced by the positive clinical outcomes of a seven-patient series. Despite the variation in presentation and fracture morphology of this rare injury, the surgical technique and principles outlined can serve as a useful tool for chest wall surgeons. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.
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Fraturas Ósseas , Traumatismos Torácicos , Parede Torácica , Ferimentos não Penetrantes , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Esterno/cirurgia , Traumatismos Torácicos/cirurgiaRESUMO
OBJECTIVE: Orthopaedics is becoming increasingly competitive. Approximately 25% of applicants to orthopaedic surgery go unmatched each year. The mean US Medical Licensing Examination step scores and average publication numbers have increased markedly in recent years. Reapplicants have a match rate of <60%. This study describes the results of an orthopaedic trauma research fellowship and its effectiveness in obtaining a successful orthopaedic match. METHODS: A 1 to 2-year research fellowship was established at a level 1 academic trauma center. Prefellowship and fellowship metrics of 11 fellows were recorded, including undergraduate and medical schools; step-1 + step-2 scores; Alpha Omega Alpha appointment; and publication, podium, poster, and chapter accomplishments. RESULTS: The average step-1 score of the fellows was 218 (range, 192 to 252) and 232 (range, 212 to 254) for step-2. Seven of 11 fellows were reapplicants. Prefellowship, the average number of journal publications was 1, one podium, two posters, and zero textbook chapters. During fellowship, the average publications was 5, five podiums, six posters, and 1.5 textbook chapters. Ten of 11 fellows successfully matched into an orthopaedic residency, with six of seven being reapplicants. CONCLUSIONS: Six of 7 reapplying fellows (86%) successfully matched highlighting the effectiveness of this fellowship. Research fellowships should be considered as an excellent choice for applicants who may be less than ideal candidates or reapplicants.
Assuntos
Internato e Residência , Ortopedia , Humanos , Ortopedia/educação , Bolsas de EstudoRESUMO
BACKGROUND: Parent psychological distress during childhood cancer treatment has short- and long-term implications for parent, child, and family well-being. Identifying targetable predictors of parental distress is essential to inform interventions. We investigated the association between household material hardship (HMH), a modifiable poverty-exposure defined as housing, food, or utility insecurity, and severe psychological distress among parents of children aged 1-17 years with acute lymphoblastic leukemia (ALL) enrolled on the multicenter Dana-Farber ALL Consortium Trial 16-001. METHODS: This was a secondary analysis of parent-reported data. Parents completed an HMH survey within 32 days of clinical trial enrollment (T0) and again at 6 months into therapy (T1). The primary exposure was HMH at T0 and primary outcome was severe parental distress at T0 and T1, defined as a score greater than or equal to 13 on the Kessler-6 Psychological Distress Scale. Multivariable models were adjusted for ALL risk group and single parent status. RESULTS: Among 375 evaluable parents, one-third (32%; n = 120/375) reported HMH at T0. In multivariable analyses, T0 HMH was associated with over twice the odds of severe psychological distress at T0 and T1 HMH was associated with over 5 times the odds of severe distress at T1. CONCLUSIONS: Despite uniform clinical trial treatment of their children at well-resourced pediatric centers, HMH-exposed parents-compared with unexposed parents-experienced statistically significantly increased odds of severe psychological distress at the time of their child's leukemia diagnosis, which worsened 6 months into therapy. These data identify a high-risk parental population who may benefit from early psychosocial and HMH-targeted interventions to mitigate disparities in well-being.