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1.
Cell ; 161(3): 647-660, 2015 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-25910212

RESUMO

How disease-associated mutations impair protein activities in the context of biological networks remains mostly undetermined. Although a few renowned alleles are well characterized, functional information is missing for over 100,000 disease-associated variants. Here we functionally profile several thousand missense mutations across a spectrum of Mendelian disorders using various interaction assays. The majority of disease-associated alleles exhibit wild-type chaperone binding profiles, suggesting they preserve protein folding or stability. While common variants from healthy individuals rarely affect interactions, two-thirds of disease-associated alleles perturb protein-protein interactions, with half corresponding to "edgetic" alleles affecting only a subset of interactions while leaving most other interactions unperturbed. With transcription factors, many alleles that leave protein-protein interactions intact affect DNA binding. Different mutations in the same gene leading to different interaction profiles often result in distinct disease phenotypes. Thus disease-associated alleles that perturb distinct protein activities rather than grossly affecting folding and stability are relatively widespread.


Assuntos
Doença/genética , Mutação de Sentido Incorreto , Mapas de Interação de Proteínas , Proteínas/genética , Proteínas/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Estudo de Associação Genômica Ampla , Humanos , Fases de Leitura Aberta , Dobramento de Proteína , Estabilidade Proteica
2.
Cell ; 159(5): 1212-1226, 2014 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-25416956

RESUMO

Just as reference genome sequences revolutionized human genetics, reference maps of interactome networks will be critical to fully understand genotype-phenotype relationships. Here, we describe a systematic map of ?14,000 high-quality human binary protein-protein interactions. At equal quality, this map is ?30% larger than what is available from small-scale studies published in the literature in the last few decades. While currently available information is highly biased and only covers a relatively small portion of the proteome, our systematic map appears strikingly more homogeneous, revealing a "broader" human interactome network than currently appreciated. The map also uncovers significant interconnectivity between known and candidate cancer gene products, providing unbiased evidence for an expanded functional cancer landscape, while demonstrating how high-quality interactome models will help "connect the dots" of the genomic revolution.


Assuntos
Mapas de Interação de Proteínas , Proteoma/metabolismo , Animais , Bases de Dados de Proteínas , Estudo de Associação Genômica Ampla , Humanos , Camundongos , Neoplasias/metabolismo
3.
Eur J Orthop Surg Traumatol ; 34(3): 1373-1379, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38175277

RESUMO

PURPOSE: Ankle arthrodesis is a mainstay of surgical management for ankle arthritis. Accurately risk-stratifying patients who undergo ankle arthrodesis would be of great utility. There is a paucity of accurate prediction models that can be used to pre-operatively risk-stratify patients for ankle arthrodesis. We aim to develop a predictive model for major perioperative complication or readmission after ankle arthrodesis. METHODS: This is a retrospective cohort study of adult patients who underwent ankle arthrodesis at any non-federal California hospital between 2015 and 2017. The primary outcome is readmission within 30 days or major perioperative complication. We build logistic regression and ML models spanning different classes of modeling approaches, assessing discrimination and calibration. We also rank the contribution of the included variables to model performance for prediction of adverse outcomes. RESULTS: A total of 1084 patients met inclusion criteria for this study. There were 131 patients with major complication or readmission (12.1%). The XGBoost algorithm demonstrates the highest discrimination with an area under the receiver operating characteristic curve of 0.707 and is well-calibrated. The features most important for prediction of adverse outcomes for the XGBoost model include: diabetes, peripheral vascular disease, teaching hospital status, morbid obesity, history of musculoskeletal infection, history of hip fracture, renal failure, implant complication, history of major fracture. CONCLUSION: We report a well-calibrated algorithm for prediction of major perioperative complications and 30-day readmission after ankle arthrodesis. This tool may help accurately risk-stratify patients and decrease likelihood of major complications.


Assuntos
Artroplastia de Substituição do Tornozelo , Fraturas Ósseas , Adulto , Humanos , Artroplastia de Substituição do Tornozelo/efeitos adversos , Articulação do Tornozelo/cirurgia , Readmissão do Paciente , Estudos Retrospectivos , Tornozelo/cirurgia , Artrodese/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Fraturas Ósseas/cirurgia , Algoritmos , Resultado do Tratamento
4.
Eur Radiol ; 33(9): 6582-6591, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37042979

RESUMO

OBJECTIVES: While fully supervised learning can yield high-performing segmentation models, the effort required to manually segment large training sets limits practical utility. We investigate whether data mined line annotations can facilitate brain MRI tumor segmentation model development without requiring manually segmented training data. METHODS: In this retrospective study, a tumor detection model trained using clinical line annotations mined from PACS was leveraged with unsupervised segmentation to generate pseudo-masks of enhancing tumors on T1-weighted post-contrast images (9911 image slices; 3449 adult patients). Baseline segmentation models were trained and employed within a semi-supervised learning (SSL) framework to refine the pseudo-masks. Following each self-refinement cycle, a new model was trained and tested on a held-out set of 319 manually segmented image slices (93 adult patients), with the SSL cycles continuing until Dice score coefficient (DSC) peaked. DSCs were compared using bootstrap resampling. Utilizing the best-performing models, two inference methods were compared: (1) conventional full-image segmentation, and (2) a hybrid method augmenting full-image segmentation with detection plus image patch segmentation. RESULTS: Baseline segmentation models achieved DSC of 0.768 (U-Net), 0.831 (Mask R-CNN), and 0.838 (HRNet), improving with self-refinement to 0.798, 0.871, and 0.873 (each p < 0.001), respectively. Hybrid inference outperformed full image segmentation alone: DSC 0.884 (Mask R-CNN) vs. 0.873 (HRNet), p < 0.001. CONCLUSIONS: Line annotations mined from PACS can be harnessed within an automated pipeline to produce accurate brain MRI tumor segmentation models without manually segmented training data, providing a mechanism to rapidly establish tumor segmentation capabilities across radiology modalities. KEY POINTS: • A brain MRI tumor detection model trained using clinical line measurement annotations mined from PACS was leveraged to automatically generate tumor segmentation pseudo-masks. • An iterative self-refinement process automatically improved pseudo-mask quality, with the best-performing segmentation pipeline achieving a Dice score of 0.884 on a held-out test set. • Tumor line measurement annotations generated in routine clinical radiology practice can be harnessed to develop high-performing segmentation models without manually segmented training data, providing a mechanism to rapidly establish tumor segmentation capabilities across radiology modalities.


Assuntos
Neoplasias Encefálicas , Processamento de Imagem Assistida por Computador , Adulto , Humanos , Processamento de Imagem Assistida por Computador/métodos , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Encéfalo/diagnóstico por imagem
5.
Eur Spine J ; 32(8): 2637-2646, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37079079

RESUMO

PURPOSE: Current literature suggests that biportal spinal endoscopy is safe and effective in treating lumbar spine pathology such as lumbar disc herniation, lumbar stenosis, and degenerative spondylolisthesis. No prior study has investigated the postoperative outcomes or complication profile of the technique as a whole. This study serves as the first comprehensive systematic review and meta-analysis of biportal spinal endoscopy in the lumbar spine. METHODS: A PubMed literature search provided over 100 studies. 42 papers were reviewed and 3673 cases were identified with average follow-up time of 12.5 months. Preoperative diagnoses consisted of acute disc herniation (1098), lumbar stenosis (2432), and degenerative spondylolisthesis (229). Demographics, operative details, complications, and perioperative outcome and satisfaction scores were analyzed. RESULTS: Average age was 61.32 years, 48% male. 2402 decompressions, 1056 discectomies, and 261 transforaminal lumbar Interbody fusions (TLIFs) were performed. Surgery was performed on 4376 lumbar levels, with L4-5 being most common(61.3%). 290 total complications occurred, 2.23% durotomies, 1.29% inadequate decompressions, 3.79% epidural hematomas, and < 1% transient nerve root injuries, infections, and iatrogenic instability. Significant improvement in VAS-Back, VAS-Leg, ODI, and Macnab Scores were seen across the cohort. CONCLUSION: Biportal spinal endoscopy is a novel method to address pathology in the lumbar spine with direct visualization through an endoscopic approach. Complications are comparable to previously published rates. Clinical outcomes demonstrate effectiveness. Prospective studies are required to assess the efficacy of the technique as compared to traditional techniques. This study demonstrates that the technique can be successful in the lumbar spine.


Assuntos
Deslocamento do Disco Intervertebral , Fusão Vertebral , Estenose Espinal , Espondilolistese , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Deslocamento do Disco Intervertebral/cirurgia , Espondilolistese/cirurgia , Constrição Patológica , Estenose Espinal/cirurgia , Endoscopia/efeitos adversos , Endoscopia/métodos , Vértebras Lombares/cirurgia , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos , Resultado do Tratamento , Estudos Retrospectivos
6.
Arch Orthop Trauma Surg ; 143(4): 2135-2140, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35674820

RESUMO

INTRODUCTION: Stiffness and decreased range of motion frequently lead to hindrance of activities of daily living and dissatisfaction follow total knee arthroplasty (TKA). This study aims to evaluate the effect of non-aspirin (ASA) chemoprophylaxis and determine patient-related risk factors for stiffness and need for manipulation under anesthesia (MUA) following primary TKA. MATERIALS AND METHODS: A review of all patients undergoing primary TKA from 2013 to 2019 at a single academic orthopedic hospital was conducted. The primary outcome measure was MUA performed post-operatively. Chi-square analysis and Mann-Whitney U test were used to determine statistically significant relationships between risk factors and outcomes. Significance was set at p < 0.05. Univariate logistic regression was performed to control for identified independent risk factors for MUA. RESULTS: A total of 11,550 patients undergoing primary TKA from January 2013 to September 2019 at an academic medical center were included in the study. Increasing age and Charlson Comorbidity Index were associated with statistically significant decreased odds of MUA (0.93, 95% CI: 0.92-0.94, p < 0.001, OR 0.71, 95% CI 0.63-0.79, p < 0.001). Active smokers had a 2.01 increased odds of MUA (OR 2.01, 95% CI 1.28, 3.02, p < 0.001). There was no significant difference in rates of MUA between ASA and non-ASA VTE prophylaxis (p 0.108). CONCLUSIONS: Younger age, lower CCI, and history of smoking are associated with a higher rate, while different chemical VTE prophylaxis does not influence rate of MUA after TKA. Arthroplasty surgeons should consider these risk factors when counseling patient preoperatively. Understanding each patients' risk for MUA allows surgeons to appropriately set preoperative expectations and reasonable outcome goals.


Assuntos
Anestesia , Artroplastia do Joelho , Tromboembolia Venosa , Humanos , Atividades Cotidianas , Artroplastia do Joelho/efeitos adversos , Articulação do Joelho/cirurgia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
7.
J Surg Oncol ; 126(6): 978-985, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35809223

RESUMO

BACKGROUND AND OBJECTIVES: Adequate coverage of the soft tissue defects from wide resection of sacropelvic malignancies remains challenging. The vastus lateralis flap has been described for coverage in the setting of trauma and infection. This flap has not been described for coverage of sacropelvic tumor defects. METHODS: This is a retrospective cohort study of adult patients who underwent wide resection of a primary sacropelvic malignancy with reconstruction employing a pedicled vastus lateralis flap at two tertiary care centers. Patient demographics, tumor staging, and rate of complications were assessed. RESULTS: Twenty-eight patients were included, with a median age of 51 years. The most common primary tumor was chondrosarcoma followed by chondroblastic osteosarcoma. The median follow-up was 1.1 years. There were 10 cases of wound infection requiring re-operation and three cases of flap failure. CONCLUSIONS: We describe a pedicled vastus lateralis flap for coverage of defects after wide resection of sacropelvic malignancies. A large proportion of our cohort had independent risk factors for wound complications. Even with a cohort with high baseline risk for wound complications, we show that the use of a pedicled vastus lateralis flap is a safe reconstructive option with a wound complication rate in line with the literature.


Assuntos
Retalho Miocutâneo , Procedimentos de Cirurgia Plástica , Adulto , Humanos , Pessoa de Meia-Idade , Retalho Miocutâneo/cirurgia , Músculo Quadríceps/cirurgia , Procedimentos de Cirurgia Plástica/efeitos adversos , Estudos Retrospectivos , Coxa da Perna/cirurgia
8.
Eur Spine J ; 31(8): 1952-1959, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34392418

RESUMO

PURPOSE: Posterior cervical fusion is associated with increased rates of complications and readmission when compared to anterior fusion. Machine learning (ML) models for risk stratification of patients undergoing posterior cervical fusion remain limited. We aim to develop a novel ensemble ML algorithm for prediction of major perioperative complications and readmission after posterior cervical fusion and identify factors important to model performance. METHODS: This is a retrospective cohort study of adults who underwent posterior cervical fusion at non-federal California hospitals between 2015 and 2017. The primary outcome was readmission or major complication. We developed an ensemble model predicting complication risk using an automated ML framework. We compared performance with standard ML models and logistic regression (LR), ranking contribution of included variables to model performance. RESULTS: Of the included 6822 patients, 18.8% suffered a major complication or readmission. The ensemble model demonstrated slightly superior predictive performance compared to LR and standard ML models. The most important features to performance include sex, malignancy, pneumonia, stroke, and teaching hospital status. Seven of the ten most important features for the ensemble model were markedly less important for LR. CONCLUSION: We report an ensemble ML model for prediction of major complications and readmission after posterior cervical fusion with a modest risk prediction advantage compared to LR and benchmark ML models. Notably, the features most important to the ensemble are markedly different from those for LR, suggesting that advanced ML methods may identify novel prognostic factors for adverse outcomes after posterior cervical fusion.


Assuntos
Doenças da Coluna Vertebral , Fusão Vertebral , Adulto , Vértebras Cervicais/cirurgia , Humanos , Aprendizado de Máquina , Readmissão do Paciente , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Doenças da Coluna Vertebral/cirurgia , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos
9.
Indian J Urol ; 38(3): 204-209, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35983113

RESUMO

Introduction: An opportunity for e-learning has been created by the ongoing pandemic and lockdown, along with the availability of efficient technology. Webinars have filled in the lacunae of the learning process. We conducted an online survey to evaluate the interest and opinion regarding webinars, which enables for standardization of future webinars and reap the maximum benefits. Methods: An online survey was conducted among practicing urologists and urology residents. The survey was formulated and edited by a group of urologists and uro-oncologists who had experience conducting several regional and international conferences and webinars. The survey comprised 39 questions divided into six parts. Results: A total of 328 urologists throughout the country participated in the survey, and 303 complete responses were obtained for the analysis. 67.3% subjects felt that live webinars are the preferred method of knowledge exchange during the coronavirus disease pandemic, and 58.1% felt that this concept of webinars had to be extended even after the pandemic was over. Few shortcomings in the webinars included lack of networking (41.3%), lack of personal connection (73.3%), and lack of practical skills (35%). About 85.5% felt that the duration should be <90 min, and 83.2% thought that speakers should be restricted to <5. They were comfortable attending the webinars on weekends (48.8%) or weekdays but after hospital hours (43.9%). Most of them felt (92.4%) that webinars should be focused, covering a single theme and including international and national speakers (84.2%). Conclusions: Webinars can be streamlined for the better and continued after the pandemic. A few issues in this novel learning process have to be adequately addressed to strengthen this modality of academic urology.

10.
J Arthroplasty ; 36(5): 1655-1662.e1, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33478891

RESUMO

BACKGROUND: As the prevalence of hip osteoarthritis increases, the number of total hip arthroplasty (THA) procedures performed is also projected to increase. Accurately risk-stratifying patients who undergo THA would be of great utility, given the significant cost and morbidity associated with developing perioperative complications. We aim to develop a novel machine learning (ML)-based ensemble algorithm for the prediction of major complications after THA, as well as compare its performance against standard benchmark ML methods. METHODS: This is a retrospective cohort study of 89,986 adults who underwent primary THA at any California-licensed hospital between 2015 and 2017. The primary outcome was major complications (eg infection, venous thromboembolism, cardiac complication, pulmonary complication). We developed a model predicting complication risk using AutoPrognosis, an automated ML framework that configures the optimally performing ensemble of ML-based prognostic models. We compared our model with logistic regression and standard benchmark ML models, assessing discrimination and calibration. RESULTS: There were 545 patients who had major complications (0.61%). Our novel algorithm was well-calibrated and improved risk prediction compared to logistic regression, as well as outperformed the other four standard benchmark ML algorithms. The variables most important for AutoPrognosis (eg malnutrition, dementia, cancer) differ from those that are most important for logistic regression (eg chronic atherosclerosis, renal failure, chronic obstructive pulmonary disease). CONCLUSION: We report a novel ensemble ML algorithm for the prediction of major complications after THA. It demonstrates superior risk prediction compared to logistic regression and other standard ML benchmark algorithms. By providing accurate prognostic information, this algorithm may facilitate more informed preoperative shared decision-making.


Assuntos
Artroplastia de Quadril , Osteoartrite do Quadril , Adulto , Algoritmos , Artroplastia de Quadril/efeitos adversos , Humanos , Aprendizado de Máquina , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco
11.
Int J Mol Sci ; 22(24)2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34948444

RESUMO

Alzheimer's disease is a type of dementia characterized by problems with short-term memory, cognition, and difficulties with activities of daily living. It is a progressive, neurodegenerative disorder. The complement system is an ancient part of the innate immune system and comprises of more than thirty serum and membrane-bound proteins. This system has three different activating pathways and culminates into the formation of a membrane attack complex that ultimately causes target cell lysis (usually pathogens) The complement system is involved in several important functions in the central nervous system (CNS) that include neurogenesis, synaptic pruning, apoptosis, and neuronal plasticity. Here, we discuss how the complement system is involved in the effective functioning of CNS, while also contributing to chronic neuroinflammation leading to neurodegenerative disorders such as Alzheimer's disease. We also discuss potential targets in the complement system for stopping its harmful effects via neuroinflammation and provide perspective for the direction of future research in this field.


Assuntos
Doença de Alzheimer/imunologia , Proteínas do Sistema Complemento/metabolismo , Regulação da Expressão Gênica , Humanos , Neurogênese , Plasticidade Neuronal
12.
Nucleic Acids Res ; 41(15): e152, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23814183

RESUMO

Recently, we developed an oligonucleotide-based probe, ratiometric bimolecular beacon (RBMB), which generates a detectable fluorescent signal in living cells that express the target RNA. Here, we show that RBMBs can also be used to image single RNA transcripts in living cells, when the target RNA is engineered to contain as few as four hybridization sites. Moreover, comparison with single-molecule fluorescence in situ hybridization confirmed that RBMBs could be used to accurately quantify the number of RNA transcripts within individual cells. Measurements of gene expression could be acquired within 30 min and using a wide range of RBMB concentrations. The ability to acquire accurate measurements of RNA copy number in both HT-1080 cells and CHO cells also suggests that RBMBs can be used to image and quantify single RNA transcripts in a wide range of cell lines. Overall, these findings highlight the robustness and versatility of RBMBs as a tool for imaging RNA in live cells. We envision that the unique capabilities of RBMBs will open up new avenues for RNA research.


Assuntos
Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Sondas de Oligonucleotídeos/química , RNA Mensageiro/isolamento & purificação , Animais , Sítios de Ligação , Células CHO , Cricetinae , Cricetulus , Fibrossarcoma/química , Fluorescência , Proteínas de Fluorescência Verde/química , Humanos , Hibridização de Ácido Nucleico , RNA Mensageiro/química , Sequências de Repetição em Tandem , Transcrição Gênica
13.
Stroke ; 45(2): 598-601, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24302484

RESUMO

BACKGROUND AND PURPOSE: Hyperpermeability and iron deposition are 2 central pathophysiological phenomena in human cerebral cavernous malformation (CCM) disease. Here, we used 2 novel MRI techniques to establish a relationship between these phenomena. METHODS: Subjects with CCM disease (4 sporadic and 17 familial) underwent MRI imaging using the dynamic contrast-enhanced quantitative perfusion and quantitative susceptibility mapping techniques that measure hemodynamic factors of vessel leak and iron deposition, respectively, previously demonstrated in CCM disease. Regions of interest encompassing the CCM lesions were analyzed using these techniques. RESULTS: Susceptibility measured by quantitative susceptibility mapping was positively correlated with permeability of lesions measured using dynamic contrast-enhanced quantitative perfusion (r=0.49; P≤0.0001). The correlation was not affected by factors, including lesion volume, contrast agent, and the use of statin medication. Susceptibility was correlated with lesional blood volume (r=0.4; P=0.0001) but not with lesional blood flow. CONCLUSIONS: The correlation between quantitative susceptibility mapping and dynamic contrast-enhanced quantitative perfusion suggests that the phenomena of permeability and iron deposition are related in CCM; hence, more leaky lesions also manifest a more cumulative iron burden. These techniques might be used as biomarkers to monitor the course of this disease and the effect of therapy.


Assuntos
Permeabilidade Capilar/fisiologia , Hemangioma Cavernoso do Sistema Nervoso Central/patologia , Adolescente , Adulto , Biomarcadores , Mapeamento Encefálico , Criança , Meios de Contraste , Interpretação Estatística de Dados , Feminino , Gadolínio , Humanos , Processamento de Imagem Assistida por Computador , Ferro/metabolismo , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Adulto Jovem
14.
Vasc Med ; 19(1): 67-74, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24558030

RESUMO

Recent studies have shown mitochondrial dysfunction and increased production of reactive oxygen species in peripheral blood mononuclear cells (PBMCs) and endothelial cells from patients with diabetes mellitus. Mitochondria oxygen consumption is coupled to adenosine triphosphate (ATP) production and also occurs in an uncoupled fashion during formation of reactive oxygen species by components of the electron transport chain and other enzymatic sites. We therefore hypothesized that diabetes would be associated with higher total and uncoupled oxygen consumption in PBMCs that would correlate with endothelial dysfunction. We developed a method to measure oxygen consumption in freshly isolated PBMCs and applied it to 26 patients with type 2 diabetes mellitus and 28 non-diabetic controls. Basal (192 ± 47 vs 161 ± 44 pmoles/min, p = 0.01), uncoupled (64 ± 16 vs 53 ± 13 pmoles/min, p = 0.007), and maximal (795 ± 87 vs 715 ± 128 pmoles/min, p=0.01) oxygen consumption rates were higher in diabetic patients compared to controls. There were no significant correlations between oxygen consumption rates and endothelium-dependent flow-mediated dilation measured by vascular ultrasound. Non-endothelium-dependent nitroglycerin-mediated dilation was lower in diabetics (10.1 ± 6.6 vs 15.8 ± 4.8%, p = 0.03) and correlated with maximal oxygen consumption (r = -0.64, p=0.001). In summary, we found that diabetes mellitus is associated with a pattern of mitochondrial oxygen consumption consistent with higher production of reactive oxygen species. The correlation between oxygen consumption and nitroglycerin-mediated dilation may suggest a link between mitochondrial dysfunction and vascular smooth muscle cell dysfunction that merits further study. Finally, the described method may have utility for the assessment of mitochondrial function in larger scale observational and interventional studies in humans.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Endotélio Vascular/metabolismo , Leucócitos Mononucleares/metabolismo , Mitocôndrias/metabolismo , Consumo de Oxigênio/fisiologia , Adulto , Idoso , Artéria Braquial/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nitroglicerina/metabolismo
15.
Cureus ; 16(1): e52364, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38361672

RESUMO

Hereditary hemochromatosis (HH) is an autosomal recessive disorder characterized by excess iron absorption in the body following a mutation in the HFE gene. Though prolonged iron deposition has been shown to cause clinical symptoms such as hyperpigmentation, arthralgias, and liver damage, many individuals remain asymptomatic and exhibit no signs of iron overload. Here, we present a case where a 34-year-old with a history of severe alcohol use disorder presented with high iron, ferritin and transferrin saturation levels indicative of iron overload. Further testing for HFE gene mutations revealed simple heterozygote C282Y status, confirming the diagnosis of hereditary hemochromatosis. Simple heterozygotes, however, typically do not present with any symptoms of iron overload. This patient was counseled on lifestyle modifications which included abstaining from alcohol and reducing iron and vitamin C intake. As a result, his iron panel parameters improved. Thus, our case highlights that excessive alcohol consumption can exacerbate hereditary hemochromatosis and risk for overload even among heterozygotes.

16.
Diagnostics (Basel) ; 14(9)2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38732376

RESUMO

Spinal metastasis is exceedingly common in patients with cancer and its prevalence is expected to increase. Surgical management of symptomatic spinal metastasis is indicated for pain relief, preservation or restoration of neurologic function, and mechanical stability. The overall prognosis is a major driver of treatment decisions; however, clinicians' ability to accurately predict survival is limited. In this narrative review, we first discuss the NOMS decision framework used to guide decision making in the treatment of patients with spinal metastasis. Given that decision making hinges on prognosis, multiple scoring systems have been developed over the last three decades to predict survival in patients with spinal metastasis; these systems have largely been developed using expert opinions or regression modeling. Although these tools have provided significant advances in our ability to predict prognosis, their utility is limited by the relative lack of patient-specific survival probability. Machine learning models have been developed in recent years to close this gap. Employing a greater number of features compared to models developed with conventional statistics, machine learning algorithms have been reported to predict 30-day, 6-week, 90-day, and 1-year mortality in spinal metastatic disease with excellent discrimination. These models are well calibrated and have been externally validated with domestic and international independent cohorts. Despite hypothesized and realized limitations, the role of machine learning methodology in predicting outcomes in spinal metastatic disease is likely to grow.

17.
Cureus ; 16(2): e55163, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38558605

RESUMO

Carcinoid tumors are rare neuroendocrine tumors that can be found in the gastrointestinal tract as well as other areas throughout the body. The neurosecretory nature of these tumors can have implications for other chronic diseases that patients may have, such as diabetes. Certain treatments that may be implemented for patients who have carcinoid tumors, such as somatostatin analogs and Everolimus, can also alter blood glucose control. This highlights the importance of diagnosing and treating carcinoid tumors as early as possible to avoid complications associated with metastasis and more intense treatment. With more advanced diseases, clinicians should consider the possible effects of carcinoid tumors and their treatments on other chronic conditions as they manage the patient. For gastrointestinal carcinoid tumors, colonoscopy screening guidelines are incredibly important to counsel patients on, as resection can yield a complete cure for carcinoid tumors when they are found at an early stage. Here, we describe the case of an incidentally diagnosed rectal carcinoid tumor in a 46-year-old female patient with a history of type 2 diabetes mellitus and hypertension.

18.
Indian J Surg Oncol ; 15(1): 44-52, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38511030

RESUMO

Neoadjuvant chemotherapy (NACT) is routinely offered to operable locally advanced breast cancer (LABC) patients desirous of breast conservation surgery and inoperable LABC patients. Pathological complete response (pCR) following chemotherapy is recognized as a surrogate for survival outcomes in high grade tumour subtypes. Many biological and tumor characters have been shown to predict pCR. The current study was performed with the aim of investigating the ability of Ki-67 in predicting pCR with NACT in breast cancer patients. A total of 105 patients with locally advanced breast cancer who completed NACT followed by surgery were included in this study from January 2020 till December 2022. Patients with advanced metastatic breast carcinoma, who did not give consent for NACT, who did not complete NACT and who did not undergo surgery were excluded. All patients were assessed for Ki-67 score on core-needle biopsy samples and response rate was assessed clinically and by histopathological examination of resected specimen. Quantitative variables were compared using unpaired t-test or Mann-Whitney 'U' test and for categorical variables Chi-square or Fisher's exact test were used. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive potential of Ki-67 expression levels in predicting pCR. To identify the predictive factors associated with pCR, univariate analysis was performed. The P value < 0.05 was considered as statistically significant. Mean age was 51.57 ± 10.8 years. 51 patients achieved clinical complete response (cCR) and 33 achieved pCR after NACT. Mean Ki-67 index in overall study population, in pCR group and no pCR group was 46.44 ± 22.92%, 51.60 ± 22.3% and 44.06 ± 22.7%, respectively. On univariate analysis, ER negativity, PR negativity and Her 2neu positivity were found predictive of pCR. On subgroup analysis, TNBC and Her 2neu positive sub groups were associated with higher cCR and pCR rate. We found no significant association between Ki-67 and pCR. This result may be confounded by the fact that a significant duration of the study was in the COVID-19 pandemic. Validation of this data is required in a large prospective study.

19.
J Spine Surg ; 10(1): 68-79, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38567010

RESUMO

Background: Biportal endoscopic spine surgery is an effective minimally invasive technique for treating common lumbar pathologies. We aim to evaluate the impact of intraoperative tranexamic acid (TXA) use on postoperative blood loss in biportal endoscopic decompression surgery. Methods: Patients undergoing biportal endoscopic lumbar discectomies and decompressions either by same day surgery or overnight stay at a single institution beginning in October 2021 were prospectively enrolled. This study was non-randomized, non-blinded with the first cohort of consecutive patients receiving 1 g of intravenous TXA intra-operatively before closure and the second cohort of consecutive patients receiving no TXA. Exclusion criteria included any revision surgery, any surgery for the diagnosis of spinal instability, infection, tumor, or trauma, any contraindication for TXA. Results: Eighty-four patients were included in the study, with 45 (54%) receiving TXA and 39 (46%) not receiving TXA. Median follow-up was 168 days [interquartile range (IQR), 85-368 days]. There were no differences in patient or surgical characteristics between cohorts. Estimated blood loss (EBL) was similar (P=0.20), while post-operative drain output was significantly lower in the TXA cohort (P=0.0028). Single level discectomies had significantly less drain output as compared to 2 level unilateral laminotomy, bilateral decompression (ULBD) cases (P<0.005). Post-operative complications were similar, with low rates of wound complication (1.2%) and transient postoperative weakness (2.4%, P>0.99 for both). Oswestry disability index (ODI), visual analog scale (VAS) back and VAS leg scores decreased significantly; the absolute decrease in scores did not differ between groups (P=0.71, 0.22, 0.86, respectively). Conclusions: Systemic intraoperative TXA administration is associated with a significant decrease in post-operative blood loss in biportal spinal endoscopy, with no impact on the improvement in patient-reported outcomes (PROs) or rate of post-operative complications. Single level biportal discectomies had significantly less postoperative drainage with TXA and may not need drains postoperatively. Larger, randomized studies are necessary to evaluate the cost-effectiveness of TXA use in biportal spinal endoscopy.

20.
J Am Acad Orthop Surg ; 32(12): 550-557, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38595147

RESUMO

BACKGROUND: The management of elderly acetabular fractures is complex, with high rates of conversion total hip arthroplasty (THA) after open reduction and internal fixation (ORIF), but potentially higher rates of complications after acute THA. METHODS: The California Office of Statewide Health Planning and Development database was queried between 2010 and 2017 for all patients aged 60 years or older who sustained a closed, isolated acetabular fracture and underwent ORIF, THA, or a combination. Chi-square tests and Student t tests were used to identify demographic differences between groups. Multivariate regression was used to evaluate predictors of 30-day readmission and 90-day complications. Kaplan-Meier (KM) survival analysis and Cox proportional hazards model were used to estimate the revision surgery-free survival (revision-free survival [RFS]), with revision surgery defined as conversion THA, revision ORIF, or revision THA. RESULTS: A total of 2,184 surgically managed acetabular fractures in elderly patients were identified, with 1,637 (75.0%) undergoing ORIF and 547 (25.0%) undergoing THA with or without ORIF. Median follow-up was 295 days (interquartile range, 13 to 1720 days). 99.4% of revisions following ORIF were for conversion arthroplasty. Unadjusted KM analysis showed no difference in RFS between ORIF and THA (log-rank test P = 0.27). RFS for ORIF patients was 95.1%, 85.8%, 78.3%, and 71.4% at 6, 12, 24 and 60 months, respectively. RFS for THA patients was 91.6%, 88.9%, 87.2%, and 78.8% at 6, 12, 24 and 60 months, respectively. Roughly 50% of revisions occurred within the first year postoperatively (49% for ORIF, 52% for THA). In propensity score-matched analysis, there was no difference between RFS on KM analysis ( P = 0.22). CONCLUSIONS: No difference was observed in medium-term RFS between acute THA and ORIF for elderly acetabular fractures in California. Revision surgeries for either conversion or revision THA were relatively common in both groups, with roughly half of all revisions occurring within the first year postoperatively. LEVEL OF EVIDENCE: III.


Assuntos
Acetábulo , Artroplastia de Quadril , Fixação Interna de Fraturas , Fraturas Ósseas , Redução Aberta , Reoperação , Humanos , Reoperação/estatística & dados numéricos , Idoso , Artroplastia de Quadril/efeitos adversos , Acetábulo/lesões , Acetábulo/cirurgia , Feminino , Masculino , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/efeitos adversos , Fraturas Ósseas/cirurgia , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
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