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OBJECTIVE: A multi-national high-volume center study was undertaken to evaluate outcomes after primary surgery (PS) or neoadjuvant treatment followed by surgery (NAT/S) in cT2 staged adenocarcinomas of the esophagus (EAC) and gastroesophageal junction (GEJ). BACKGROUND: Optimal treatment approach with either NAT/S or PS for clinically staged cT2cNany or cT2N0 EAC and GEJ remains unknown due to the lack of randomized controlled trials. METHODS: Retrospective analysis of prospectively maintained databases from ten centers was performed. Between 01/2012-08/2023 645 patients who fulfilled inclusion criteria of GEJ Siewert type I, II or EAC with cT2 status at diagnosis underwent PS or NAT/S with curative intent. Primary endpoint was overall survival (OS). RESULTS: In the cT2cNany cohort 192 patients (29.8%) underwent PS and 453 (70.2%) underwent NAT/S. In all cT2cN0 patients (n=333), NAT/s remained the more frequent treatment (56.2%). Patients undergoing PS were in both cT2 cohorts older (P<0.001) and had a higher ASA classification (P<0.05). R0 resection showed no differences between NAT/S and PS in both cT2 cohorts (P>0.4).Median OS was 51.0 months in the PS group (95% CI 31.6-70.4) versus 114.0 months (95% CI 53.9-174.1) in the NAT/S group (P=0.003) of cT2cNany patients. For cT2cN0 patients NAT/S was associated with longer OS (P=0.002) and disease-free survival (DFS) (P=0.001). After propensity score matching of cT2N0 patients, survival benefit for NAT/S remained (P=0.004). Histopathology showed that 38.1% of cT2cNany and 34.2% of cT2cN0 patients were understaged. CONCLUSIONS: Due to unreliable identification of cT2N0 disease, all patients should be offered a multimodal therapeutic approach.
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BACKGROUND: There are limited published data on population estimates of survival after spinal surgery for metastatic disease. We performed a population-based study to evaluate survival and complications among patients with cancer who underwent surgery for spinal metastases in Ontario, Canada, between 2006 and 2016. METHODS: We used health administrative databases to identify all patients who underwent surgery for spinal metastases in Ontario between Jan. 1, 2006, and Dec. 31, 2016. We assessed overall survival, mortality rates according to primary cancer lesion and complications after surgery. We contrast the results to those for a comparable cohort from 1991 to 1998. RESULTS: A total of 2646 patients (1194 women [45.1%]; mean age 62.5 yr [standard deviation 12.2 yr]) were identified. The median survival time was 236 (interquartile range 84-740) days. Mortality was highest for patients with melanoma, upper gastrointestinal cancer and lung cancer, with 50% dying within 90 days of surgery. The longest median survival times were observed for primary cancers of the thyroid (906 d) and breast (644 d), and myeloma (830 d). Overall 90-day and 1-year mortality rates were 29% and 59%, respectively. CONCLUSION: We identified differential survivorship based on primary tumour type and a shift in the distribution of operations performed for specific primary cancers over the past 2 decades in Ontario. Overall reductions in mortality associated with this shift in treatment may reflect the use of adjuvant therapies and more personalized treatment approaches.
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Neoplasias Pulmonares , Neoplasias da Coluna Vertebral , Estudos de Coortes , Terapia Combinada , Feminino , Humanos , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Ontário/epidemiologia , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/secundário , Taxa de SobrevidaRESUMO
Background: Patients with lumbar disc herniation may greatly benefit from microdiscectomy. Although spine surgeons performing microdiscectomy routinely obtain informed consent, the potential adverse events they disclose often vary. Moreover, little is known about what disclosures are deemed most valuable by patients. The aim of this mixed-methods study was to determine practice variations among spine surgeons in regard to the disclosure of potential adverse events during informed consent discussions for lumbar microdiscectomy and to determine which topics patients perceived to be valuable in the consent discussion. Methods: A survey evaluating the frequency with which spine surgeons disclose 15 potential adverse events related to lumbar microdiscectomy during informed consent discussions was distributed among Canadian Spine Society members. Additionally, semistructured interviews were conducted with preoperative patients, postoperative patients, attending spine surgeons, spine fellows and orthopedic residents. Interview transcripts were analyzed using thematic analysis with open coding. Results: Fifty-one Canadian Spine Society members completed the survey. The number of potential adverse events not routinely discussed was greater among orthopedic surgeons than among neurosurgeons (relative risk 1.83; 95% confidence interval 1.22-2.73; p = 0.003). Three preoperative patients, 7 postoperative patients, 6 attending spine surgeons, 3 spine fellows and 5 orthopedic residents participated in the semistructured interviews. The interviews identified gaps in information provided to patients, particularly on topics relating to postoperative care such as expected recovery time, activity restrictions and need for a caregiver. Conclusion: There is variation in the disclosure of potential adverse events during informed consent discussions for lumbar microdiscectomy among Canadian spine surgeons. Patients desire more information regarding their postoperative care. Further research should focus on developing guidelines to reduce practice variation and optimize the effectiveness of consent discussions.
Contexte: Les patients atteints d'une hernie discale lombaire pourraient profiter grandement d'une microdiscectomie. Bien que les chirurgiens spécialistes de la colonne vertébrale réalisant des microdiscectomies obtiennent toujours le consentement éclairé du patient, les événements indésirables potentiels présentés varient souvent. De plus, on en connaît peu sur les informations les plus importantes du point de vue des patients. L'objectif de cette étude à méthodes mixtes était de déterminer les différentes pratiques des chirurgiens en ce qui a trait à la présentation des événements indésirables potentiels pendant les discussions sur le consentement éclairé pour les microdiscectomies lombaires et de déterminer les sujets les plus importants pour les patients pendant ces discussions. Méthodes: Un sondage sur la fréquence à laquelle les chirurgiens présentent 15 événements indésirables potentiels associés à la microdiscectomie lombaire pendant les discussions sur le consentement éclairé a été distribué aux membres de la Société canadienne du rachis. De plus, des entretiens semi-dirigés ont été réalisés auprès de patients en période préopératoire, de patients en période postopératoire, de chirurgiens spécialistes de la colonne vertébrale, de fellows en chirurgie spinale et de résidents en chirurgie orthopédique. Des analyses thématiques utilisant un code ouvert ont été réalisées sur les transcriptions des entretiens. Résultats: Cinquante-et-un membres de la Société canadienne du rachis ont répondu au sondage. Le nombre d'événements indésirables potentiels non systématiquement mentionnés était plus élevé chez les chirurgiens orthopédiques que chez les neurochirurgiens (risque relatif 1,83; intervalle de confiance de 95 % 1,222,73; p = 0,003). Dans les entretiens semi-dirigés, on a recueilli les commentaires de 3 patients en période préopératoire, de 7 patients en période postopératoire, de 6 chirurgiens spécialistes de la colonne vertébrale, de 3 fellows en chirurgie spinale et de 5 résidents en chirurgie orthopédique. Les entretiens ont révélé des lacunes dans l'information transmise aux patients, particulièrement sur les soins postopératoires, comme le temps de récupération attendu, les restrictions quant aux activités et la nécessité d'un soignant. Conclusion: On a trouvé une variation dans la présentation des événements indésirables potentiels pendant les discussions sur le consentement éclairé pour les microdiscectomies lombaires chez les chirurgiens spécialistes de la colonne vertébrale au Canada. Les patients veulent en savoir plus sur les soins postopératoires. Des lignes directrices devraient être établies pour réduire les différences entre les pratiques et optimiser l'efficacité des discussions sur le consentement.
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Discotomia/ética , Consentimento Livre e Esclarecido , Degeneração do Disco Intervertebral/cirurgia , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares , Cirurgiões Ortopédicos/ética , Preferência do Paciente , Adulto , Idoso , Canadá , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
CONTEXT: Dynamic balance is a measure of core stability. Deficits in the dynamic balance have been related to injuries in the athletic populations. The Star Excursion Balance Test (SEBT) is suggested to measure and improve dynamic balance when used as a rehabilitative tool. OBJECTIVE: To determine the electromyographic activity of the hip and the trunk muscles during the SEBT. DESIGN: Descriptive. SETTING: University campus. PARTICIPANTS: Twenty-two healthy adults (11 males and 11 females; 23.3 [3.8] y, 170.3 [7.6] cm, 67.8 [10.3] kg, and 15.1% [5.0%] body fat). INTERVENTION: Surface electromyographic data were collected on 22 healthy adults of the erector spinae, external oblique, and rectus abdominis bilaterally, and gluteus medius and gluteus maximus muscle of the stance leg. A 2-way repeated measures analysis of variance was used to determine the interaction between the percentage maximal voluntary isometric contraction (%MVIC) and the reach directions. The %MVIC for each muscle was compared across the 8 reach directions using the Sidak post hoc test with α at .05. MAIN OUTCOME MEASURES: %MVIC. RESULTS: Significant differences were observed for all the 8 muscles. Highest electromyographic activity was found for the tested muscles in the following reach directions-ipsilateral external oblique (44.5% [38.4%]): anterolateral; contralateral external oblique (52.3% [40.8%]): medial; ipsilateral rectus abdominis (8% [6.6%]): anterior; contralateral rectus abdominis (8% [5.3%]): anteromedial; ipsilateral erector spinae (46.4% [20.2%]): posterolateral; contralateral erector spinae (33.5% [11.3%]): posteromedial; gluteus maximus (27.4% [11.7%]): posterior; and gluteus medius (54.6% [26.1%]): medial direction. CONCLUSIONS: Trunk and hip muscle activation was direction dependent during the SEBT. This information can be used during rehabilitation of the hip and the trunk muscles.
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Quadril , Músculo Esquelético/fisiologia , Equilíbrio Postural , Tronco , Adulto , Nádegas , Eletromiografia , Feminino , Humanos , Contração Isométrica , Masculino , Coxa da Perna , Adulto JovemRESUMO
A newly identified lethal form of hereditary sensory and autonomic neuropathy (HSAN), designated HSAN-VI, is caused by a homozygous mutation in the bullous pemphigoid antigen 1 (BPAG1)/dystonin gene (DST). The HSAN-VI mutation impacts all major neuronal BPAG1/dystonin protein isoforms: dystonin-a1, -a2 and -a3. Homozygous mutations in the murine Dst gene cause a severe sensory neuropathy termed dystonia musculorum (dt). Phenotypically, dt mice are similar to HSAN-VI patients, manifesting progressive limb contractures, dystonia, dysautonomia and early postnatal death. To obtain a better molecular understanding of disease pathogenesis in HSAN-VI patients and the dt disorder, we generated transgenic mice expressing a myc-tagged dystonin-a2 protein under the regulation of the neuronal prion protein promoter on the dt(Tg4/Tg4) background, which is devoid of endogenous dystonin-a1 and -a2, but does express dystonin-a3. Restoring dystonin-a2 expression in the nervous system, particularly within sensory neurons, prevented the disorganization of organelle membranes and microtubule networks, attenuated the degeneration of sensory neuron subtypes and ameliorated the phenotype and increased life span in these mice. Despite these improvements, complete rescue was not observed likely because of inadequate expression of the transgene. Taken together, this study provides needed insight into the molecular basis of the dt disorder and other peripheral neuropathies including HSAN-VI.
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Proteínas de Transporte/genética , Proteínas do Citoesqueleto/genética , Neuropatias Hereditárias Sensoriais e Autônomas/genética , Proteínas do Tecido Nervoso/genética , Animais , Proteínas de Transporte/metabolismo , Células Cultivadas , Proteínas do Citoesqueleto/metabolismo , Modelos Animais de Doenças , Distonia Muscular Deformante/genética , Distonina , Gânglios Espinais/patologia , Neuropatias Hereditárias Sensoriais e Autônomas/patologia , Humanos , Membranas Intracelulares/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microtúbulos/metabolismo , Fusos Musculares/metabolismo , Fusos Musculares/patologia , Fibras Nervosas Mielinizadas/metabolismo , Fibras Nervosas Mielinizadas/patologia , Proteínas do Tecido Nervoso/metabolismo , Junção Neuromuscular/metabolismo , Junção Neuromuscular/patologia , Fenótipo , Propriocepção , Células Receptoras Sensoriais/patologia , TransgenesRESUMO
BACKGROUND: Given the large number of publications in all fields of practice, it is essential that clinicians focus on the resources that provide the highest level of evidence (LOE). We sought to determine the LOE that exists in the field of pediatrics, present in the general pediatric as well as high impact clinical literature. METHODS: Clinical pediatric literature, published between April 2011 and March 2012 inclusive in high-impact clinical journals (HICJ) (New England Journal of Medicine, Journal of the American Medical Association, & The Lancet) and the highest-impact general pediatric journals (GPJ) (Pediatrics, Journal of Pediatrics, & Archives of Pediatrics & Adolescent Medicine), was assessed. In addition to the LOE, articles were evaluated on criteria including subspecialty within pediatrics, number of authors, number of centers, and other parameters. Eligible level I randomized control trials were appraised using the Consolidated Standards of Reporting Trials (CONSORT) guidelines. RESULTS: Of 6511 articles screened, 804 met inclusion criteria (68 in HICJ and 736 in GPJ). On average, LOE in pediatrics-focused articles within The Lancet were significantly higher than all GPJ (p < 0.05). Average CONSORT scores were significantly higher in HICJ vs. GPJ (15.2 vs. 13.6, respectively, p < 0.001). CONCLUSIONS: LOE and quality of randomized control trials within the pediatric field is highest within HICJ, however, only represent a small proportion of data published. Following CONSORT criteria, and promoting studies of high LOE may allow authors and readers to turn to journals and articles of greater clinical impact.
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Medicina Baseada em Evidências/normas , Pediatria/normas , Publicações Periódicas como Assunto/normas , Fator de Impacto de Revistas , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Estados UnidosRESUMO
Integrin-linked kinase (ILK) is a major structural adaptor protein governing signaling complex formation and cytoskeletal dynamics. Here, through the use of conditional knock-out mice, we demonstrate a requirement for ILK in oligodendrocyte differentiation and axonal myelination in vivo. In conjunction, ILK-deficient primary oligodendrocytes are defined by a failure in process extension and an inability to form myelin membrane upon axonal contact. Surprisingly, phosphorylation of the canonical downstream targets Akt and GSK3ß is unaffected following ILK loss. Rather, the defects are due in part to actin cytoskeleton dysregulation with a correspondent increase in active RhoA levels. Morphological rescue is possible following Rho kinase inhibition in an oligodendrocyte subset. Furthermore, phenotypic severity correlates with environmental complexity; oligodendrocytes are severely malformed in vitro (a relatively simple environment), but undergo phenotypic recovery in the context of the whole animal. Together, our work demonstrates ILK as necessary for normal oligodendrocyte development, reinforces its role as a bridge between the actin cytoskeleton and cell membrane, and highlights the overarching compensatory capacity of oligodendrocytes in response to cellular milieu.
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Actinas/metabolismo , Citoesqueleto/metabolismo , Oligodendroglia/fisiologia , Proteínas Serina-Treonina Quinases/fisiologia , Animais , Diferenciação Celular/fisiologia , Células Cultivadas , Feminino , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Simulação de Dinâmica MolecularRESUMO
PURPOSE: An efficient physics-informed deep learning approach for extracting spinopelvic measures from X-ray images is introduced and its performance is evaluated against manual annotations. METHODS: Two datasets, comprising a total of 1470 images, were collected to evaluate the model's performance. We propose a novel method of detecting landmarks as objects, incorporating their relationships as constraints (LanDet). Using this approach, we trained our deep learning model to extract five spine and pelvis measures: Sacrum Slope (SS), Pelvic Tilt (PT), Pelvic Incidence (PI), Lumbar Lordosis (LL), and Sagittal Vertical Axis (SVA). The results were compared to manually labelled test dataset (GT) as well as measures annotated separately by three surgeons. RESULTS: The LanDet model was evaluated on the two datasets separately and on an extended dataset combining both. The final accuracy for each measure is reported in terms of Mean Absolute Error (MAE), Standard Deviation (SD), and R Pearson correlation coefficient as follows: [ S S ∘ : 3.7 ( 2.7 ) , R = 0.89 ] , [ P T ∘ : 1.3 ( 1.1 ) , R = 0.98 ] , [ P I ∘ : 4.2 ( 3.1 ) , R = 0.93 ] , [ L L ∘ : 5.1 ( 6.4 ) , R = 0.83 ] , [ S V A ( m m ) : 2.1 ( 1.9 ) , R = 0.96 ] . To assess model reliability and compare it against surgeons, the intraclass correlation coefficient (ICC) metric is used. The model demonstrated better consistency with surgeons with all values over 0.88 compared to what was previously reported in the literature. CONCLUSION: The LanDet model exhibits competitive performance compared to existing literature. The effectiveness of the physics-informed constraint method, utilized in our landmark detection as object algorithm, is highlighted. Furthermore, we addressed the limitations of heatmap-based methods for anatomical landmark detection and tackled issues related to mis-identifying of similar or adjacent landmarks instead of intended landmark using this novel approach.
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Aprendizado Profundo , Lordose , Humanos , Reprodutibilidade dos Testes , Sacro/diagnóstico por imagem , Pelve/diagnóstico por imagem , Vértebras Lombares/cirurgiaRESUMO
Spinal muscular atrophy (SMA) is a devastating childhood motor neuron disease caused by mutations and deletions within the survival motor neuron 1 (SMN1) gene. Although other tissues may be involved, motor neurons remain primary pathological targets, with loss of neuromuscular junctions (NMJs) representing an early and significant event in pathogenesis. Although defects in axonal outgrowth and pathfinding have been observed in cell culture and in lower organisms upon Smn depletion, developmental defects in mouse models have been less obvious. Here, we have employed the Smn(2B/-) mouse model to investigate NMJ remodelling during SMA pathology, induced reinnervation, and paralysis. We show that whilst NMJs are capable of remodelling during pathogenesis, there is a marked reduction in paralysis-induced remodelling and in the nerve-directed re-organisation of acetylcholine receptors. This reduction in remodelling potential could not be attributed to a decreased rate of axonal growth. Finally, we have identified a loss of terminal Schwann cells which could contribute to the defects in remodelling/maintenance observed. Our work demonstrates that there are specific defects in NMJ remodelling in an intermediate SMA mouse model, which could contribute to or underlie pathogenesis in SMA. The development of strategies that can promote the remodelling potential of NMJs may therefore be of significant benefit to SMA patients.
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Atrofia Muscular Espinal/patologia , Atrofia Muscular Espinal/fisiopatologia , Junção Neuromuscular/patologia , Junção Neuromuscular/fisiopatologia , Proteína 1 de Sobrevivência do Neurônio Motor/metabolismo , Acetilcolina/metabolismo , Animais , Axônios/patologia , Axônios/fisiologia , Toxinas Botulínicas Tipo A , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Regeneração Nervosa/fisiologia , Plasticidade Neuronal/fisiologia , Paralisia/patologia , Paralisia/fisiopatologia , Células de Schwann/patologia , Células de Schwann/fisiologia , Proteína 1 de Sobrevivência do Neurônio Motor/genética , Nervo Tibial/lesões , Nervo Tibial/patologia , Nervo Tibial/fisiopatologiaRESUMO
INTRODUCTION: Military service personnel are required to deploy to austere environments where they are exposed to harsh conditions. Many service personnel continue to wear contact lenses when deployed as they are an effective alternative to spectacles by affording superior ergonomic functionality, although they are associated with significant complications. We aimed to explore the prevalence and type of contact lens-related complications among deployed service personnel worldwide. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement. PubMed, Medline, CINAHL and EMBASE databases were searched for relevant articles published between 1950 and 2023. The keywords 'contact lens' and 'military' or 'army' or 'navy' or 'air force' and 'austere' or 'deployed' or 'adverse' were used. RESULTS: Five eligible articles were included. Excluded articles reported contact lens wear in the firm base, were not related to military personnel or did not involve the deployed setting. Major complications associated with contact lens wear included microbial keratitis and contact lens-related discomfort. Excluding case reports, the overall incidence of contact lens-related complications ranged from 0.35% to 25.4%. The three case reports included in this systematic review described Acanthamoeba keratitis, Nocardia keratitis and contact lens-related discomfort as significant complications. These case reports also detailed time to initial presentation and type of contact lens worn when complications were encountered. Types of deployed conditions service personnel were exposed to included desert, temperate and underwater environments. CONCLUSIONS: We highlight a scarcity of recent data regarding contact lens-related complications in the deployed setting. While contact lens-wearing service personnel are at risk of infectious keratitis and contact lens-related discomfort, we recommend good-quality data collection on contact lens wearing schedules and complication rates to steer guidance on contact lens wear in service personnel.
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Background: The Star Excursion Balance Test (SEBT) has been used as a rehabilitation exercise. To improve its efficacy, efficiency, and method variations, the Y-Balance Test (YBT) with anterior (A), posterolateral (PL), and posteromedial (PM) directions of the SEBT has been recommended. Electromyographic activity has been reported to change when the same task is performed on various surfaces. Hypothesis/Purpose: To compare the EMG activity of trunk and LE muscles during the performance of the YBT on stable and unstable surfaces. Study Design: Cross-Sectional study. Methods: Healthy adults with no history of chronic ankle instability were recruited for the study. Surface electromyography was collected for bilateral (ipsilateral [i] and contralateral [c]) rectus abdominis (RA), external oblique (EOB), erector spinae (ES). While, gluteus maximus (GMAX), gluteus medius (GMED), medial hamstrings (MH), biceps femoris (BF), vastus medialis (VM), rectus femoris (RF), vastus lateralis (VL), anterior tibialis (AT), and medial gastrocnemius (MG) on the stance leg (ipsilateral side), during the performance of the YBT. The unstable surface was introduced using a Thera-Band stability trainer. Differences in electromyography were examined for each reach direction and muscle between the stable and unstable surfaces (p≤ 0.05). Results: Twenty (10 male, 10 female) subjects participated (age: 27.5 ± 4.0 years, height:167 ± 1.0 cm, weight: 66.5 ± 13.0 kg, body fat: 14.1 ± 6.2%). Significantly higher muscle activity for the unstable surface (p<0.05) with moderate to large effect sizes were observed for the following muscles in the A direction: GMED, GMAX, VM, RF, and MG; PL direction: iEOB, iES, cES, GMED, BF, VM, RF, and MG; and PM direction iEOB, iES, GMED, BF, VM, and RF. Significantly higher muscle activity for the stable surface (p = 0.007) was observed in MH muscle in the A direction. No significant differences (p>0.05) between the stable and unstable surfaces were observed in iRA, cRA, cEOB, VL, and AT for any of the directions of the YBT. Conclusion: An increase in muscle activity was observed during YBT on unstable versus stable surfaces for some muscles. Level of Evidence: 2B.
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STUDY DESIGN: Systematic review. OBJECTIVES: Review the surgical techniques and construct options aimed at improving the biomechanical strength of cervical constructs. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search of the MEDLINE, Embase, and Cochrane Library databases was performed to identify all studies examining biomechanical strategies utilized in the osteoporotic cervical spine. Screening was performed in duplicate for all stages of the review process. RESULTS: An initial search returned 3887 articles. After deletion of duplications and review of abstracts and full text, 39 articles met inclusion criteria. Overall, the surgical techniques reviewed aimed at obtaining rigid fixation in the setting of poor bone quality, or dispersing the forces at the bone-implant interface. We identified 6 key techniques to improve biomechanical fixation. These include bicortical fixation, appropriate screw selection (size and trajectory), PMMA augmentation, load sharing techniques, consideration of ancillary fixation around the occipitocervical junction, and supplementing the construct with post-operative collar or halo. CONCLUSION: The summation of the literature highlights a framework of modalities available to surgeons to improve biomechanical fixation in the cervical spine. While these may improve construct strength in the setting of osteoporosis, there is a paucity of evidence available to make recommendations in this patient population.
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CASE: The global reach of coronavirus disease 2019 has led to the rollout of new generation messenger ribonucleic acid (mRNA) vaccines. As populations are vaccinated, some side effects will become more apparent. We present a case of unilateral lymphadenopathy resulting in a transient plexopathy presenting as neuralgic pain, paresthesia, and numbness in the hand. CONCLUSION: Multiple image modalities and electrodiagnostic studies were used to infer the diagnosis. This condition was expectantly managed, and the patient's symptoms resolved within weeks.
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Vacinas contra COVID-19 , COVID-19 , Linfadenopatia , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Mãos , Hipestesia , Linfadenopatia/diagnóstico por imagem , Linfadenopatia/etiologiaRESUMO
Amyloid light-chain (AL) amyloidosis is a multisystem disease with obstructive jaundice and gastrointestinal (GI) involvement being uncommon initial presentations. Patients with AL amyloidosis seldom have jaundice and advanced GI tract involvement as their presenting symptoms. This case report describes an 82-year-old lady who presented with a 6-month history of early satiety, weight loss, xerostomia and progressive jaundice. Imaging did not suggest a biliary cause but demonstrated hepatomegaly and ascites. Oesophagogastroduodenoscopy revealed a duodenal stricture. Duodenal and liver biopsies were consistent with amyloid deposition. Multiple myeloma was confirmed to be the underlying cause. Significant cholestatic liver dysfunction and a duodenal stricture have not been previously described as simultaneous manifestations of amyloidosis. This case also highlights the difficulty in treating multiple myeloma as the cause of AL amyloidosis in the context of liver dysfunction, given that many chemotherapy agents undergo hepatic metabolism.
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Background: Deep surgical site infections after spinal instrumentation represent a significant source of patient morbidity and poorer outcomes. Given lack of evidence or guidelines on the variety of procedural options in the management of deep spine surgical site infections, the purpose of this survey was to document and investigate the use of these techniques across Canada. Methods: A 34-question survey evaluating surgical techniques for irrigation and debridement in postoperative thoracolumbar infection was distributed to Canadian adult spine surgeons. Results were analyzed qualitatively, and comparisons by specialty, years of training, and number of cases were completed using Fischer's exact tests. We defined consensus as >70% agreement. Results: We received 53 responses (62% response rate) from a comprehensive sample of Canadian adult spine surgeons. There was a consensus to retain hardware (80%) and interbody implants (93%) in acute infection, to retain interbody implants in chronic/recurrent infection (71%), and application of topical antibiotics in recurrent infection (85%). There was consensus on the use of absorbable suture to close fascia in acute (83%) and chronic (87%) infection. Eighty-five percent of surgeons used nonabsorbable materials such as Nylon or staples for skin closure in chronic infection, however, there was no consensus in acute infection. Surgeons varied significantly in type, volume and pressure of fluids, adjuvant solvents, graft management, use of topical antibiotics acutely, and the use of negative pressure wound therapy. Partial hardware exchange was controversial. Additionally, specialty or surgeon experience had no impact on management strategy. Conclusions: This survey demonstrates significant heterogeneity amongst Canadian adult spine surgeons regarding key steps in the surgical management of deep instrumented spine infection, concordant with scarce literature addressing these steps.
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Dystonin is a large multidomain cytoskeletal-associated protein that plays an essential role in the nervous system. Loss of dystonin results in neuromuscular dysfunction and early death in a mouse mutant called dystonia musculorum. Conserved among related proteins, the plakin domain is a defining feature of all major dystonin isoforms, yet its interactions have not been explored in detail. The purpose of the present study was to identify novel interacting partners of the plakin domain of the neuronal isoform of dystonin (dystonin-a). Newly identified interacting proteins discovered through a pull-down assay were validated using coimmunoprecipitation, coimmunofluorescence, and proximity ligation assays. Microtubule associated protein 1B (MAP1B), a microtubule stabilizing protein, and clathrin heavy chain, the major component of the clathrin triskelion, were identified as interaction partners for dystonin-a. Increased levels of phosphorylated MAP1B suggest a misregulation of MAP1B and a potentially novel component of the dt pathology. This work will further facilitate our understanding of how cytoskeletal proteins can affect and regulate neurodegenerative disorders.
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Proteínas de Transporte/metabolismo , Cadeias Pesadas de Clatrina/metabolismo , Proteínas do Citoesqueleto/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Animais , Encéfalo/metabolismo , Células COS , Proteínas de Transporte/química , Linhagem Celular , Chlorocebus aethiops , Cadeias Pesadas de Clatrina/genética , Proteínas do Citoesqueleto/química , Distonina , Técnica Indireta de Fluorescência para Anticorpo , Expressão Gênica , Camundongos , Proteínas Associadas aos Microtúbulos/genética , Proteínas do Tecido Nervoso/química , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Mapeamento de Interação de Proteínas , RatosRESUMO
Mutations in the survival motor neuron (SMN) gene cause spinal muscular atrophy (SMA), a neuromuscular disease associated with muscle weakness that progresses to paralysis, respiratory distress, and ultimately death. Both neurons and muscle are severely affected in this disease. Tandem affinity purification (TAP) has emerged as a useful tool for studying protein complexes in vitro. We have used this purification system to discover novel SMN interacting partners in C2C12 muscle and PC12 neuronal cells. To do so, we fused a TAP-tag, consisting of a HIS hexamer and FLAG epitope separated by the tobacco etch virus (TEV) protease cleavage site, to either the N- or C-terminal region of SMN. Interestingly, the profile of SMN interacting proteins varies depending on the cell type and stage. We have identified a number of novel SMN interacting proteins in both C2C12 and PC12 cells, and from among these we have validated Annexin II and myosin regulatory light chain (MRLC). The discovery of these proteins will lead to a better understanding of the mechanisms underlying the pathophysiology of SMA.
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Cromatografia de Afinidade/métodos , Mapeamento de Interação de Proteínas/métodos , Proteínas do Complexo SMN/metabolismo , Animais , Anexina A2/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Histidina/metabolismo , Imunoprecipitação , Camundongos , Microscopia de Fluorescência , Músculo Esquelético/metabolismo , Atrofia Muscular Espinal/metabolismo , Cadeias Leves de Miosina/metabolismo , Oligopeptídeos/metabolismo , Peptídeos/metabolismo , Fosfoproteínas/metabolismo , Proteínas de Ligação a RNA/metabolismo , Reprodutibilidade dos Testes , Proteínas do Complexo SMN/genética , NucleolinaRESUMO
BACKGROUND: The stabilizing action of the serratus anterior (SA) muscle is vital in maintaining normal scapulothoracic rhythm. This warrants investigation of exercises to discern which are best to activate the SA muscle. Recruitment of the muscles in the trunk and lower extremity kinetic chain during exercises has demonstrated increased SA activation due to the myofascial connections between various segments of the body. Variation of surfaces during an exercise has also been shown to alter the muscle recruitment patterns. PURPOSE: The primary purpose was to determine the effects of trunk and lower extremity kinetic chain muscle recruitment on the SA muscle activity while on an unstable surface. The secondary purpose was to determine if the SA muscle activity would change when the surface stability during the exercises was reduced. STUDY DESIGN: Descriptive, within-subject repeated measures. METHODS: Surface electromyographic activity of the SA, latissimus dorsi (LD), external oblique (EO) on the dominant, and femoral adductor (FA) muscles on the non-dominant side and gluteus maximus bilaterally was analyzed during forward punch plus (FPP) and two of its' variations: FPP with closed chain serape (CS), FPP with open chain serape (OS) on stable and unstable surface in twenty-one healthy males. A two-way repeated measure ANOVA was used to determine the difference in the muscle activation between exercises, surfaces, and interaction between these two variables. A separate one-way repeated measures ANOVA with Sidak post hoc test was used for comparisons between stable and unstable surfaces. (p≤0.05). RESULTS: Muscle activity was statistically significantly higher for the CS and the OS exercises compared to the FPP for all the muscles except for the LD within the same surface. There was no significant difference in muscle activity for any of the muscles when compared between stable and unstable surfaces. CONCLUSIONS: Incorporating the trunk and lower extremity kinetic chain during the FPP exercise increased the SA activation on both stable and unstable surfaces. However, the type of surface did not influence the activation of any muscle across exercises. The results of this study further strengthen the benefit of the kinetic chain exercises but also caution that adding an unstable surface to an exercise does not always imply higher muscle activation. LEVEL OF EVIDENCE: 2b.
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BACKGROUND: The process of obtaining informed consent is an important and complex pursuit, especially within a paediatric setting. Medical governing bodies have stated that the role of the trainee surgeon must be explained to patients and their families during the consent process. Despite this, attitudes and practices of surgeons and their trainees regarding disclosure of the trainee's participation during the consent process has not been reported in the paediatric setting. METHODS: Nineteen face-to-face interviews were conducted with surgical trainees and staff surgeons at a tertiary-level paediatric hospital in Toronto, Canada. These were transcribed and subsequently thematically coded by three reviewers. RESULTS: Five main themes were identified from the interviews. (1) Surgeons do not consistently disclose the role of surgical trainees to parents. (2) Surgical trainees are purposefully vague in disclosing their role during the consent discussion without being misleading. (3) Surgeons and surgical trainees believe parents do not fully understand the specific role of surgical trainees. (4) Graduated responsibility is an important aspect of training surgeons. (5) Surgeons feel a responsibility towards both their patients and their trainees. Surgeons do not explicitly inform patients about trainees, believing there is a lack of understanding of the training process. Trainees believe families likely underestimate their role and keep information purposely vague to reduce anxiety. CONCLUSION: The majority of surgeons and surgical trainees do not voluntarily disclose the degree of trainee participation in surgery during the informed consent discussion with parents. An open and honest discussion should occur, allowing for parents to make an informed decision regarding their child's care. Further patient education regarding trainees' roles would help develop a more thorough and patient-centred informed consent process.
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BACKGROUND: The indications and technique for the transtrochanteric approach to the hip have evolved greatly since its initial popularization in the 1960s. The purpose of this systematic review was to assess current uses of this approach on the basis of indications, osteotomy technique, trochanteric fixation method, complications, and functional outcome. METHODS: A comprehensive search of MEDLINE and Embase databases from January 2000 to July 2017 was performed in accordance with the PRISMA guidelines. Articles were divided into 3 major categories on the basis of the type of hip surgery performed: (1) primary arthroplasty, (2) revision arthroplasty, and (3) joint-preserving procedures. Patient data were then analyzed according to these 3 categories. RESULTS: Seventy-six studies (5,028 hips), mainly of Level-IV evidence, were included. Four types of osteotomy were reported for a variety of indications. Rates of nonunion were 6.0% (303 of 5,028) across all studies, 4.2% (39 of 921) for primary arthroplasty, 6.7% (114 of 1,690) for revision arthroplasty, and 4.4% (56 of 1,278) for joint-preserving procedures. Rates of dislocation were 1.5% (14 of 921) for primary arthroplasty and 4.6% (77 of 1,690) for revision arthroplasty. The rate of osteonecrosis after joint-preserving procedures was 1.1% (14 of 1,278). Rates of deep infection were 1.1% (55 of 5,028) across all studies, 0.1% (1 of 921) for primary arthroplasty, 2.1% (36 of 1,690) for revision arthroplasty, and 0.6% (8 of 1,278) for joint-preserving procedures. CONCLUSIONS: The transtrochanteric approach remains useful in cases requiring extensile exposure of the acetabulum or femoral medullary canal. However, trochanteric complications continue to pose a clinical challenge. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.