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1.
Foot Ankle Int ; 45(4): 393-405, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38404018

RESUMO

BACKGROUND: Talar displacement is considered the main predictive factor for poor outcomes and the development of post-traumatic osteoarthritis after ankle fractures. Isolated lateral talar translation, as previously studied by Ramsey and Hamilton using carbon powder imprinting, does not fully replicate the multidirectional joint subluxations seen in ankle fractures. The purpose of this study was to analyze the influence of multiple uniplanar talar displacements on tibiotalar contact mechanics utilizing weightbearing computed tomography (WBCT) and finite element analysis (FEA). METHODS: Nineteen subjects (mean age = 37.6 years) with no history of ankle surgery or injury having undergone WBCT arthrogram (n = 1) and WBCT without arthrogram (n = 18) were included. Segmentation of the WBCT images into 3D simulated models of bone and cartilage was performed. Three-dimensional (3D) multiple uniplanar talar displacements were simulated to investigate the respective influence of various uniaxial displacements (including lateral translation, anteroposterior translation, varus-valgus angulation, and external rotation) on the tibiotalar contact mechanics using FEA. Tibiotalar peak contact stress and contact area were modeled for each displacement and its gradations. RESULTS: Our modeling demonstrated that peak contact stress of the talus and tibia increased, whereas contact area decreased, with incremental displacement in all tested directions. Contact stress maps of the talus and tibia were computed for each displacement demonstrating unique patterns of pressure derangement. One millimeter of lateral translation resulted in 14% increase of peak talar contact pressure and a 3% decrease in contact area. CONCLUSION: Our model predicted that with lateral talar translation, there is less noticeable change in tibiotalar contact area compared with prior studies whereas external rotation greater than 12 degrees had the largest effect on peak contact stress predictions. LEVEL OF EVIDENCE: Level V, computational simulation study.


Assuntos
Análise de Elementos Finitos , Tálus , Tomografia Computadorizada por Raios X , Suporte de Carga , Humanos , Tálus/diagnóstico por imagem , Suporte de Carga/fisiologia , Adulto , Masculino , Fenômenos Biomecânicos , Imageamento Tridimensional , Articulação do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/fisiopatologia , Feminino , Pessoa de Meia-Idade
2.
Arch Bone Jt Surg ; 12(1): 51-57, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38318310

RESUMO

Objectives: Majority of Lisfranc fracture-dislocations require anatomic reduction and rigid internal fixation to prevent debilitating sequelae. Current methods include solid screws and flexible fixations which have been in use for many years. Biointegrative screw is a newer option that has not yet been thoroughly investigated for its effectiveness for Lisfranc injuries. Methods: The ligaments of the Lisfranc complex were resected in eight lower-leg cadaveric specimens. This was done by eight foot and ankle surgeons individually. Distraction forces were applied from opposite sides at the joint to replicate weight bearing conditions. Three methods of fixation - flexible fixation, metal, and biointegrative screws- were evaluated. The diastasis and area at the level of the ligament were measured at four conditions (replicated injury and each type of fixation) in neutral and distraction conditions using fluoroscopy images. The Wilcoxon test and Kruskal Wallis test were used for comparison. P value <0.05 was considered statistically significant. Results: The diastasis value for the transected ligament scenario (2.47 ± 0.51 mm) was greater than those after all three fixation methods without distraction (2.02 ± 0.5 for flexible fixation, 1.72 ± 0.63 mm for metal screw fixation and 1.67 ± 0.77 mm for biointegrative screw fixation). The transected ligament diastasis was also greater than that for metal screw (1.61 ± 1.31mm) and biointegrative screws (1.69 ± 0.64 mm) with distraction (p<0.001). The area at the level of the ligament showed higher values for transected ligament (32.7 ± 13.08 mm2) than the three fixatives (30.75 ± 7.42 mm2 for flexible fixation, 30.75 ± 17.13 mm2 for metal screw fixation and 29.53 ± 9.15 mm2 for biointegrative screw fixation; p<0.05). Conclusion: Metal screws, flexible fixation and biointegrative screws showed comparable effectiveness intra-op, in the correction of diastasis created as a consequence of Lisfranc injury.

4.
Arch Bone Jt Surg ; 11(7): 453-457, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37538130

RESUMO

When obtaining surgical fixation of lateral malleolus fractures, a cortical lag screw is commonly used to obtain anatomic reduction. Subsequently, a neutralization plate is applied. Slight loss of fracture reduction after plate placement occasionally occurs. Although this is frequently attributed to poor bone quality or suboptimal initial lag screw fixation, a frequently overlooked factor is screw order when applying the neutralization plate. The purpose of this technique tip is to highlight the biomechanical rationale behind this loss of reduction and advocate a specific screw order for lateral malleolus fixation.

5.
Injury ; 53(12): 4146-4151, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36289020

RESUMO

INTRODUCTION: Ankle fractures are one of the most common injuries sustained worldwide, with the majority being isolated lateral malleolus fractures. The majority of the world's population live in Low and Middle Income Countries (LMIC), where implant cost may limit surgical treatment of ankle fractures. We investigate if Weber B ankle fractures could be effectively treated with a lower-cost technique using two screws between the fibula and the tibia to neutralize an interfragmentary lag screw. METHODS: After IRB approval, consecutive patients from January 1, 2020 to December 31, 2020 with Weber-B ankle fractures were treated using AO technique (AOT) with plate osteosynthesis neutralizing an interfragmentary screw. Syndesmotic injuries, as well as injuries to the medial malleolus or foot were treated according to the surgeon's preferences. From January 1, 2021 to December 31, 2021 these injuries were treated with a screw-only technique (SOT) with two fibula pro tibia screws to neutralize an interfragmentary screw. Patient demographics including age, sex, BMI, smoking status, associated rheumatoid arthritis, and associated diabetes mellitus were recorded. The primary outcome variable was a stable radiographic mortise at six weeks post-surgery, secondary outcome variables included clinical union, infection, hardware removal, and implant cost for lateral malleolar fixation charged to the hospital. RESULTS: Seventeen AOT and 10 SOT constructs were included. Demographic characteristics were similar between groups. All fractures maintained a stable mortise with clinical union at 6 weeks without infection. There was a statistically significant difference in hardware removal (17.6% AOT, 50% SOT, p = 0.012). The average implant cost to the hospital of the lateral malleolar fixation was significantly less in the SOT group ($592 (SD $229)), compared to the AOT group ($1,949.97 (SD $562)), (p < 0.0001). CONCLUSION: We introduce proof of concept of a novel lower-cost fixation strategy for Weber B ankle fractures that maintained a stable mortise with clinical union at six weeks post-surgery. However, there was a significantly higher rate of hardware removal following fixation with a screw-only construct.


Assuntos
Fraturas do Tornozelo , Humanos , Fraturas do Tornozelo/diagnóstico por imagem , Fraturas do Tornozelo/cirurgia , Fíbula/cirurgia , Fíbula/lesões , Estudos Retrospectivos , Parafusos Ósseos , Estudos de Viabilidade , Fixação Interna de Fraturas/métodos , Custos e Análise de Custo , Resultado do Tratamento
6.
Science ; 376(6592): eabi8175, 2022 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-35482859

RESUMO

Establishing causal relationships between genetic alterations of human cancers and specific phenotypes of malignancy remains a challenge. We sequentially introduced mutations into healthy human melanocytes in up to five genes spanning six commonly disrupted melanoma pathways, forming nine genetically distinct cellular models of melanoma. We connected mutant melanocyte genotypes to malignant cell expression programs in vitro and in vivo, replicative immortality, malignancy, rapid tumor growth, pigmentation, metastasis, and histopathology. Mutations in malignant cells also affected tumor microenvironment composition and cell states. Our melanoma models shared genotype-associated expression programs with patient melanomas, and a deep learning model showed that these models partially recapitulated genotype-associated histopathological features as well. Thus, a progressive series of genome-edited human cancer models can causally connect genotypes carrying multiple mutations to phenotype.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Melanócitos/metabolismo , Melanoma/patologia , Mutação , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Microambiente Tumoral/genética
7.
Foot Ankle Int ; 43(3): 378-388, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34677113

RESUMO

BACKGROUND: Early revision rates within 12 months after ankle fracture open reduction internal fixation (AF-ORIF) are fairly low; however, they remain relevant given the volume of ankle fractures occurring annually. Understanding these rates is complex because reoperation due to technical or mechanical complications is typically reported alongside soft tissue-related problems such as symptomatic hardware, wound dehiscence, or infection. There are limited data identifying risk factors specifically for revision of ankle fracture fixation in the absence of soft tissue complications. Understanding variables that predispose to aseptic technical and mechanical failure without this confounder may provide insight and improve patient care. METHODS: A retrospective cohort study was performed at 2 large academic medical centers. Research Patient Data Registry (RPDR) data available from 2002 to 2019 were used to identify patients who underwent aseptic revision of AF-ORIF within 12 months (n = 33). A control group (n = 100) was selected by identifying sequential patients who underwent AF-ORIF not requiring revision within 12 months. Multiple factors were recorded for all patients in both cohorts. Each fracture was also evaluated according to the Ankle Reduction Classification System (ARCS) of Chien et al,8 which categorizes biplanar talar displacement in relation to a central tibial plumb line into 1 of 3 grades: A (0-2 mm), B (3-10 mm), and C (>10 mm). Adapted from its original purpose of grading reduction quality, we applied ARCS to pre-reduction radiographs to assess initial fracture displacement. All variables collected were compared in univariate analysis. Variables that achieved significance in univariate comparisons were included as candidates for multivariable analysis. RESULTS: Final multivariable logistic regression modeling demonstrated the following factors to independently predict the need for aseptic revision surgery: documented falls in the early postoperative period (aOR, 298; 95% CI, 15.4, 5759; P < .001), movement-altering disorders (aOR, 81.7; 95% CI, 4.12, 1620; P = .004), a nonanatomic mortise (medial clear space [MCS] > superior clear space [SCS]) on immediate postoperative imaging (aOR, 38.4; 95% CI, 5.53, 267; P < .001), initial coronal plane tibiotalar displacement >10 mm and sagittal plane tibiotalar dislocation (ARCS-C) (aOR vs ARCS-A, 25.8; 95% CI, 2.81, 237; P = .004), substance abuse (aOR, 15.7; 95% CI, 2.66, 92.8; P = .002), and polytrauma (aOR, 12.3; 95% CI, 2.02, 74.8; P = .006). CONCLUSION: In this investigation we found a notable increase in risk for revision surgery after AF-ORIF for patients who had one of the following: (1) falls in the early postoperative period, (2) movement-altering disorders, (3) a nonanatomic mortise (MCS > SCS) on immediate postoperative imaging, (4) more severe initial fracture displacement, (5) substance abuse, or (6) polytrauma. Identifying these factors may allow surgeons to better understand risk and counsel patients, and may serve as future targets for intervention aimed at improving patient safety and outcomes after ankle fracture ORIF. LEVEL OF EVIDENCE: Level III, retrospective cohort study.


Assuntos
Fraturas do Tornozelo , Fraturas do Tornozelo/diagnóstico por imagem , Fraturas do Tornozelo/etiologia , Fraturas do Tornozelo/cirurgia , Fixação Interna de Fraturas/métodos , Humanos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
8.
Pharmacogenet Genomics ; 32(1): 1-9, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34380996

RESUMO

OBJECTIVES: Primary nonresponse (PNR) to antitumor necrosis factor-α (TNFα) biologics is a serious concern in patients with inflammatory bowel disease (IBD). We aimed to identify the genetic variants associated with PNR. PATIENTS AND METHODS: Patients were recruited from outpatient GI clinics and PNR was determined using both clinical and endoscopic findings. A case-control genome-wide association study was performed in 589 IBD patients and associations were replicated in an independent cohort of 293 patients. Effect of the associated variant on gene expression and TNFα secretion was assessed by cell-based assays. Pleiotropic effects were investigated by Phenome-wide association study (PheWAS). RESULTS: We identified rs34767465 as associated with PNR to anti-TNFα therapy (odds ratio: 2.07, 95% CI, 1.46-2.94, P = 2.43 × 10-7, [replication odds ratio: 1.8, 95% CI, 1.04-3.16, P = 0.03]). rs34767465 is a multiple-tissue expression quantitative trait loci for FAM114A2. Using RNA-sequencing and protein quantification from HapMap lymphoblastoid cell lines (LCLs), we found a significant decrease in FAM114A2 mRNA and protein expression in both heterozygous and homozygous genotypes when compared to wild type LCLs. TNFα secretion was significantly higher in THP-1 cells [differentiated into macrophages] with FAM114A2 knockdown versus controls. Immunoblotting experiments showed that depletion of FAM114A2 impaired autophagy-related pathway genes suggesting autophagy-mediated TNFα secretion as a potential mechanism. PheWAS showed rs34767465 was associated with comorbid conditions found in IBD patients (derangement of joints [P = 3.7 × 10-4], pigmentary iris degeneration [P = 5.9 × 10-4], diverticulum of esophagus [P = 7 × 10-4]). CONCLUSIONS: We identified a variant rs34767465 associated with PNR to anti-TNFα biologics, which increases TNFα secretion through mechanism related to autophagy. rs34767465 may also explain the comorbidities associated with IBD.


Assuntos
Estudo de Associação Genômica Ampla , Doenças Inflamatórias Intestinais , Estudos de Casos e Controles , Estudos de Coortes , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/genética , Fator de Necrose Tumoral alfa/genética
10.
J Foot Ankle Surg ; 61(1): 93-98, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34275718

RESUMO

The use of Nitinol compression staples has increased in foot and ankle procedures due to their ease of delivery and ability to offer sustained, dynamic compression. Prior biomechanical studies have predominantly examined mechanical performance in healthy bone models without investigating the effect of unicortical versus bicortical fixation. The purpose of this study was to examine the effect of bone quality and staple leg depth on the biomechanical performance of Nitinol staples in a bicortical bone model. Two-legged Nitinol staples were implanted in bicortical sawbone of 2 densities. Two different leg depths were tested to simulate unicortical versus bicortical fixation. Interfacial compressive forces, interfacial compression area, torsional strength, and shear strength were measured for each group. The effect of leg depth was minimal compared to the effect of sawbone density on the mechanical performance of Nitinol staples. Interfacial compressive force and interfacial compression areas were greater in the low density bone model, while torsional strength and shear strength were greater in the normal density bone model. Nitinol staple's mechanical performance is highly dependent upon bone quality and less dependent on whether staple legs terminate in cancellous versus cortical bone. Low density bone allows for a higher compressive interfacial area to be imparted by the staple. Staples in normal density bone are able to resist torsion and shear deformation more readily than staples in low density bone. Bone density may have a greater effect on the Nitinol staple's stability and compressive capability in vivo as compared to unicortical versus bicortical leg fixation.


Assuntos
Ligas , Perna (Membro) , Fenômenos Biomecânicos , Humanos , Suturas
11.
Orthopedics ; 44(6): e719-e723, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34618640

RESUMO

Many patients have questions about traveling by air after orthopedic surgery. The goal of this review was to provide a guide to addressing these issues to better prepare patients for air travel. A comprehensive literature review was conducted to address patient questions regarding metal detectors, as well as deep venous thrombosis risk with flying. Further, patient questions pertaining to specific airlines, airports, and Transportation Security Administration policies were answered through direct discussion with representatives, website review, and internet research. Ultimately, providers should be aware of the many challenges that orthopedic patients face during air travel, and patients should consult their providers before making travel plans. Airline passengers are likewise encouraged to equip themselves with the information presented in this article, to best advocate for themselves. This guide should be used as a reference tool, providing up-to-date information about air travel after orthopedic surgery to both patients and providers alike. [Orthopedics. 2021;44(6):e719-e723.].


Assuntos
Viagem Aérea , Procedimentos Ortopédicos , Ortopedia , Aeronaves , Humanos , Procedimentos Ortopédicos/efeitos adversos
12.
Acta Orthop Belg ; 87(2): 359-365, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34529393

RESUMO

Medial Collateral Ligament (MCL) injury may require operative treatment. Marx et al. described the latest technique for reconstruction of MCL. While good results have been reported using the Marx technique, some issues have been observed. To address the mentioned issues, a modification to the Marx technique has been devised. Eleven patients were enrolled and their ligaments were repaired by the fixation of allograft on the proximal and distal attachment footprints of the superficial MCL. For preventing loss of knee ROM, MCL and other ligaments were reconstructed in 2 separate stages. At the last follow up the ROM, knee ligament laxity and functional outcome scores, subjective (IKDC) and Lysholm score were evaluated and recorded. Knee motion was maintained in all cases. Two cases demonstrated 1+ valgus instability at 30 degrees of knee flexion. Both were treated for combined MCL and PCL tear, the rest were stable. The average IKDC-subjective score was 93 ± 4 and the average Lysholm score was 92 ± 3. All patients were satisfied and returned to their previous level of activity. In this technique, the superficial MCL was recon- structed closer to its anatomical construct. Patients didn't have any complaints of hardware under the skin and the need for a second surgery for hardware removal was avoided. Patients didn't have any complaints of hardware under the skin and the need for a second surgery for hardware removal was avoided. Also reconstructing the ligaments in 2 stages helped to preserve the knee motion. Level of Evidence : Level IV therapeutic.


Assuntos
Instabilidade Articular , Traumatismos do Joelho , Ligamento Colateral Médio do Joelho , Aloenxertos , Ligamento Cruzado Anterior , Seguimentos , Humanos , Instabilidade Articular/cirurgia , Traumatismos do Joelho/cirurgia , Ligamento Colateral Médio do Joelho/cirurgia , Resultado do Tratamento
13.
Surg Neurol Int ; 12: 77, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33767881

RESUMO

BACKGROUND: As the field of brain and spine stereotactic radiosurgery (SRS) continues to grow, so will the need for a comprehensive evidence base. However, it is unclear to what degree trainees feel properly equipped to use SRS. We assess the perceptions and comfort level reported by neurosurgery and radiation oncology residents concerning the evidence-based practice of SRS. METHODS: A continuing medical education (CME) course provided peer-reviewed updates regarding treatment with intracranial and spinal SRS. Presentations were given by neurosurgery and radiation oncology residents with mentorship by senior faculty. To gauge perceptions regarding SRS, attendees were surveyed. Responses before and after the course were analyzed using the Fisher's exact test in R statistical software. RESULTS: Participants reported the greatest knowledge improvements concerning data registries (P < 0.001) and clinical trials (P = 0.026). About 82% of all (n = 17) radiation oncology and neurosurgery residents either agreed or strongly agreed that a brain and spine SRS rotation would be beneficial in their training. However, only 47% agreed or strongly agreed that one was currently part of their training. In addition, knowledge gains in SRS indications (P = 0.084) and ability to seek collaboration with colleagues (P = 0.084) showed notable trends. CONCLUSION: There are clear knowledge gaps shared by potential future practitioners of SRS. Specifically, knowledge regarding SRS data registries, indications, and clinical trials offer potential areas for increased educational focus. Furthermore, the gap between enthusiasm for increased SRS training and the current availability of such training at medical institutions must be addressed.

14.
Foot Ankle Int ; 42(8): 994-1001, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33787360

RESUMO

BACKGROUND: Many orthopedic surgeries utilize intraoperative fluoroscopy. The mini C-arm is an advantageous device as it can be easily used without the need for a dedicated radiology technician. However, there are concerns that the mini C-arm may represent a potential source of contamination and subsequent postoperative infection. Previous investigations of standard C-arm drapes have shown high rates of contamination. Similar contamination rates would be even more concerning for the mini C-arm as it requires physically maneuvering the machine. This study aimed to determine the rate of mini C-arm drape contamination and identify high-risk areas. METHODS: Fifty foot and ankle surgeries requiring the use of mini C-arm fluoroscopy were included. Eight locations on the mini C-arm drape were sampled at the conclusion of each procedure. Culture Q-swabs were used for sampling defined locations. Swab samples were then assessed for bacterial growth on a 5% blood agar plate using a semiquantitative technique. RESULTS: In 70% of surgical cases, contamination was observed in at least 1 location. Six of the 8 evaluated locations were found to have significantly higher contamination in comparison with their corresponding negative controls (Mann-Whitney U test, P < .05). The "outer portion of the upper arm" (location 1) exhibited bacteria growth in 26% (P < .0001) of cases. The "superior portion of the x-ray source" (location 2) exhibited growth in 30% (P < .0001) of cases. These were the highest-risk areas for contamination and were both significantly more likely to be involved than the "inferior portion of the x-ray source" and "superior portion of the beam receiver," locations 4 and 5, respectively. Fourteen percent (7/50) C-arm cases and 1.72% (1/58) Achilles tendon surgery control cases developed surgical site infection (P = .0234; OR, 9.27). CONCLUSION: Bacterial contamination of the mini C-arm drape was found to be common after foot and ankle procedures. Contamination was more prevalent on the outer ring areas of the C-arm, both at the emitter and receiver. LEVEL OF EVIDENCE: Level III, prospective cohort study.


Assuntos
Tornozelo , Procedimentos Ortopédicos , Tornozelo/cirurgia , Fluoroscopia , Humanos , Estudos Prospectivos , Infecção da Ferida Cirúrgica/prevenção & controle
15.
Am J Hum Genet ; 108(3): 431-445, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33600772

RESUMO

Whether or not populations diverge with respect to the genetic contribution to risk of specific complex diseases is relevant to understanding the evolution of susceptibility and origins of health disparities. Here, we describe a large-scale whole-genome sequencing study of inflammatory bowel disease encompassing 1,774 affected individuals and 1,644 healthy control Americans with African ancestry (African Americans). Although no new loci for inflammatory bowel disease are discovered at genome-wide significance levels, we identify numerous instances of differential effect sizes in combination with divergent allele frequencies. For example, the major effect at PTGER4 fine maps to a single credible interval of 22 SNPs corresponding to one of four independent associations at the locus in European ancestry individuals but with an elevated odds ratio for Crohn disease in African Americans. A rare variant aggregate analysis implicates Ca2+-binding neuro-immunomodulator CALB2 in ulcerative colitis. Highly significant overall overlap of common variant risk for inflammatory bowel disease susceptibility between individuals with African and European ancestries was observed, with 41 of 241 previously known lead variants replicated and overall correlations in effect sizes of 0.68 for combined inflammatory bowel disease. Nevertheless, subtle differences influence the performance of polygenic risk scores, and we show that ancestry-appropriate weights significantly improve polygenic prediction in the highest percentiles of risk. The median amount of variance explained per locus remains the same in African and European cohorts, providing evidence for compensation of effect sizes as allele frequencies diverge, as expected under a highly polygenic model of disease.


Assuntos
Calbindina 2/genética , Predisposição Genética para Doença , Doenças Inflamatórias Intestinais/genética , Receptores de Prostaglandina E Subtipo EP4/genética , Negro ou Afro-Americano/genética , Idoso , Idoso de 80 Anos ou mais , Colite Ulcerativa/genética , Colite Ulcerativa/patologia , Doença de Crohn/genética , Doença de Crohn/patologia , Feminino , Frequência do Gene , Estudo de Associação Genômica Ampla , Humanos , Doenças Inflamatórias Intestinais/patologia , Masculino , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único/genética , População Branca/genética , Sequenciamento Completo do Genoma
16.
Clin Neurophysiol ; 132(2): 358-364, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33450558

RESUMO

OBJECTIVE: We aimed to define the prewarning sign of brainstem auditory evoked potentials (BAEPs) associated with cerebellar retraction (CR) during microvascular decompression surgery for hemifacial spasm. METHODS: A total of 241 patients with a latency prolongation of 1 ms or an amplitude decrement of 50% of wave V were analyzed. According to BAEPs before significant changes during CR, patients were classified into Groups A (latency prolongation of wave I [≥0.5 ms] without prolongation of the I-III interpeak interval [<0.5 ms]) and B (no latency prolongation of wave I [<0.5 ms] with prolongation of the I-III interpeak interval [≥0.5 ms]). BAEPs and postoperative hearing loss (HL) were compared between the two groups. RESULTS: Group B comprised 160 (66.4%) patients. With maximal changes in wave V, latency prolongation (≥1 ms) with amplitude decrement (≥50%) was more common in Group B (p < 0.018). At the end of the operation, wave V loss was observed in 11 patients, including 10 patients from Group B. Five patients developed postoperative HL; all were from Group B. CONCLUSIONS: Latency prolongation of wave III during CR was associated with serious BAEPs changes and postoperative HL. SIGNIFICANCE: Latency prolongation of wave III is a significant prewarning sign.


Assuntos
Potenciais Evocados Auditivos do Tronco Encefálico , Perda Auditiva/prevenção & controle , Espasmo Hemifacial/cirurgia , Monitorização Neurofisiológica Intraoperatória/métodos , Cirurgia de Descompressão Microvascular/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Adulto , Idoso , Feminino , Perda Auditiva/etiologia , Humanos , Masculino , Cirurgia de Descompressão Microvascular/métodos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Tempo de Reação
17.
Cancer Discov ; 11(5): 1212-1227, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33372007

RESUMO

Cytosolic DNA is characteristic of chromosomally unstable metastatic cancer cells, resulting in constitutive activation of the cGAS-STING innate immune pathway. How tumors co-opt inflammatory signaling while evading immune surveillance remains unknown. Here, we show that the ectonucleotidase ENPP1 promotes metastasis by selectively degrading extracellular cGAMP, an immune-stimulatory metabolite whose breakdown products include the immune suppressor adenosine. ENPP1 loss suppresses metastasis, restores tumor immune infiltration, and potentiates response to immune checkpoint blockade in a manner dependent on tumor cGAS and host STING. Conversely, overexpression of wild-type ENPP1, but not an enzymatically weakened mutant, promotes migration and metastasis, in part through the generation of extracellular adenosine, and renders otherwise sensitive tumors completely resistant to immunotherapy. In human cancers, ENPP1 expression correlates with reduced immune cell infiltration, increased metastasis, and resistance to anti-PD-1/PD-L1 treatment. Thus, cGAMP hydrolysis by ENPP1 enables chromosomally unstable tumors to transmute cGAS activation into an immune-suppressive pathway. SIGNIFICANCE: Chromosomal instability promotes metastasis by generating chronic tumor inflammation. ENPP1 facilitates metastasis and enables tumor cells to tolerate inflammation by hydrolyzing the immunotransmitter cGAMP, preventing its transfer from cancer cells to immune cells.This article is highlighted in the In This Issue feature, p. 995.


Assuntos
Metástase Neoplásica , Neoplasias/terapia , Nucleotídeos Cíclicos/metabolismo , Evasão Tumoral , Animais , Humanos , Hidrólise , Imunoterapia , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/metabolismo , Neoplasias/patologia
18.
J Bone Joint Surg Am ; 103(4): 326-334, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33369982

RESUMO

BACKGROUND: The burden of musculoskeletal trauma is increasing worldwide, especially in low-income countries such as Malawi. Ankle fractures are common in Malawi and may receive suboptimal treatment due to inadequate surgical capacity and limited provider knowledge of evidence-based treatment guidelines. METHODS: This study was conducted in 3 phases. First, we assessed Malawian orthopaedic providers' understanding of anatomy, injury identification, and treatment methods. Second, we observed Malawian providers' treatment strategies for adults with ankle fractures presenting to a central hospital. These patients' radiographs underwent blinded, post hoc review by 3 U.S.-based orthopaedic surgeons and a Malawian orthopaedic surgeon, whose treatment recommendations were compared with actual treatments rendered by Malawian providers. Third, an educational course addressing knowledge deficits was implemented. We assessed post-course knowledge and introduced a standardized management protocol, specific to the Malawian context. RESULTS: In Phase 1, deficits in injury identification, ideal treatment practices, and treatment standardization were identified. In Phase 2, 17 (35%) of 49 patients met operative criteria but did not undergo a surgical procedure, mainly because of resource limitations and provider failure to recognize unstable injuries. In Phase 3, 51 (84%) of 61 participants improved their overall performance between the pre-course and post-course assessments. Participants answered a mean of 32.4 (66%) of 49 questions correctly pre-course and 37.7 (77%) of 49 questions correctly post-course, a significant improvement of 5.2 more questions (95% confidence interval [CI], 3.8 to 6.6 questions; p < 0.001) answered correctly. Providers were able to identify 1 more injury correctly of 8 injuries (mean, 1.1 questions [95% CI, 0.6 to 1.6 questions]; p < 0.001) and to identify 1 more ideal treatment of the 7 that were tested (mean, 1.0 question [95% CI, 0.5 to 1.4 questions]; p < 0.001). CONCLUSIONS: Adult ankle fractures in Malawi were predominantly treated nonoperatively despite often meeting evidence-based criteria for surgery. This was due to resource limitations, knowledge deficits, and lack of treatment standardization. We demonstrated a comprehensive approach to examining the challenges of providing adequate orthopaedic care in a resource-limited setting and the successful implementation of an educational intervention to improve care delivery. This approach can be adapted for other conditions to improve orthopaedic care in low-resource settings.


Assuntos
Fraturas do Tornozelo/terapia , Articulação do Tornozelo/cirurgia , Conhecimentos, Atitudes e Prática em Saúde , Adulto , Fraturas do Tornozelo/diagnóstico por imagem , Fraturas do Tornozelo/cirurgia , Articulação do Tornozelo/diagnóstico por imagem , Feminino , Humanos , Malaui , Masculino , Pessoa de Meia-Idade , Radiografia
19.
Foot Ankle Surg ; 27(7): 723-729, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33087305

RESUMO

Toe hypoperfusion is a commonly encountered concern following forefoot surgery, yet there is limited clinical guidance available to surgeons to aid in management of this scenario. This work aims to review the etiology, pathophysiology and current strategies to address a perioperative ischemic toe. The authors review various interventions to approach this problem based on available evidence and clinical experience. Interventions to restore perfusion can be loosely based on the ischemic causality they intend to address. Described maneuvers to restore perfusion have, in turn, been designed to either chemically (through topical/local medication) or mechanically (bending/removing K-wires, adjusting repair tension) aid in mitigation of the offending cause. Depending upon the type of surgery performed, which may or may not include instrumentation, a surgeon can implement a series of steps to maximize restoration of toe perfusion. LEVEL OF EVIDENCE: V.


Assuntos
Fios Ortopédicos , , Humanos , Dedos do Pé/cirurgia
20.
Korean J Neurotrauma ; 16(2): 348-354, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33163449

RESUMO

In treating the ventral pathology of spine, ligating the segmental vessels is sometimes necessary. This may cause spinal cord ischemia, and concerns of neurologic injury have been presented. However, spinal cord ischemic injury after sacrificing segmental vessels during spine surgery is very rare. Reports of this have been scarce in the literature and most of these complications occur after multi-level segmental vessel ligation. Here we report a case of a patient with postoperative anterior spinal artery syndrome, which occurred after ligating one level segmental vessels during spinal surgery for a T8 vertebral pathologic fracture. Despite its rarity, the risk of spinal cord ischemic injury after segmental vessel ligation is certainly present. Surgeons must keep in mind such risk, and surgery should be planned under a careful risk-benefit consideration.

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