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1.
Toxins (Basel) ; 13(4)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807196

RESUMO

Ultrasound (US)-guided botulinum neurotoxin (BoNT) injections are becoming a mainstay in the treatment of muscle spasticity in upper motor neuron syndromes. As a result, there has been a commensurate increase in US-guided BoNT injection for spasticity training courses. However, many of these courses do not emphasize the importance of ergonomics. This paper aims to highlight the importance of ultrasound ergonomics and presents ergonomic recommendations to optimize US-guided BoNT injection techniques in spasticity management. Expert consensus opinion of 11 physicians (4 different continents; representing 8 countries, with an average of 12.6 years of practice using US guidance for BoNT chemodenervation (range 3 to 22 years)). A search using PubMed, College of Physicians and Surgeons of British Columbia database, EMbase was conducted and found no publications relating the importance of ergonomics in US-guided chemodenervation. Therefore, recommendations and consensus discussions were generated from the distribution of a 20-question survey to a panel of 11 ultrasound experts. All 11 surveyed physicians considered ergonomics to be important in reducing physician injury. There was complete agreement that physician positioning was important; 91% agreement that patient positioning was important; and 82% that ultrasound machine positioning was important. Factors that did not reach our 80% threshold for consensus were further discussed. Four categories were identified as being important when implementing ultrasound ergonomics for BoNT chemodenervation for spasticity; workstation, physician, patient and visual ergonomics. Optimizing ergonomics is paramount when performing US-guided BoNT chemodenervation for spasticity management. This includes proper preparation of the workspace and allowing for sufficient pre-injection time to optimally position both the patient and the physician. Lack of awareness of ergonomics for US-guided BoNT chemodenervation for spasticity may lead to suboptimal patient outcomes, increase work-related injuries, and patient discomfort. We propose key elements for optimal positioning of physicians and patients, as well as the optimal setup of the workspace and provide clinical pearls in visual identification of spastic muscles for chemodenervation.

2.
Nat Commun ; 12(1): 2043, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33824312

RESUMO

The tumour suppressor FBW7 is a substrate adaptor for the E3 ubiquitin ligase complex SKP1-CUL1-F-box (SCF), that targets several oncoproteins for proteasomal degradation. FBW7 is widely mutated and FBW7 protein levels are commonly downregulated in cancer. Here, using an shRNA library screen, we identify the HECT-domain E3 ubiquitin ligase TRIP12 as a negative regulator of FBW7 stability. We find that SCFFBW7-mediated ubiquitylation of FBW7 occurs preferentially on K404 and K412, but is not sufficient for its proteasomal degradation, and in addition requires TRIP12-mediated branched K11-linked ubiquitylation. TRIP12 inactivation causes FBW7 protein accumulation and increased proteasomal degradation of the SCFFBW7 substrate Myeloid Leukemia 1 (MCL1), and sensitizes cancer cells to anti-tubulin chemotherapy. Concomitant FBW7 inactivation rescues the effects of TRIP12 deficiency, confirming FBW7 as an essential mediator of TRIP12 function. This work reveals an unexpected complexity of FBW7 ubiquitylation, and highlights branched ubiquitylation as an important signalling mechanism regulating protein stability.


Assuntos
Proteínas de Transporte/metabolismo , Proteína 7 com Repetições F-Box-WD/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Biocatálise , Resistencia a Medicamentos Antineoplásicos , Células HCT116 , Células HEK293 , Humanos , Lisina/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Ligação Proteica , Processamento de Proteína Pós-Traducional , Estabilidade Proteica , RNA Interferente Pequeno/metabolismo , Especificidade por Substrato , Enzimas de Conjugação de Ubiquitina/metabolismo
3.
Can J Surg ; 64(2): E218-E227, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33769006

RESUMO

Background: Timeliness can have a substantial effect on treatment outcomes, prognosis and quality of life for patients with lung cancer. We sought to evaluate changes in wait times for patients with non-small cell lung carcinoma (NSCLC) and to identify bottlenecks in cancer care. Methods: We included patients who received treatment with curative intent or palliative treatment for NSCLC, diagnosed through mediastinal staging by a thoracic surgeon. Data were collected from 3 cohorts over 3 time periods: before the regionalization of lung cancer care (2005-2007, C1), immediately postregionalization (2011-2013, C2) and 5 years after regionalization (2016-2017, C3). Total wait time and delays along treatment pathways were compared across cohorts using multivariate Cox proportionality models. Results: Our total sample size was 299 patients. Overall, there was no significant difference in total wait time among the 3 cohorts. However, wait time from symptom onset to first physician visit significantly increased in C3 compared with C2 (hazard ratio [HR] 0.41, p < 0.01) and C1 (HR 0.43, p < 0.01). Time from first physician visit to computed tomography (CT) scan significantly decreased in C3 compared with C2 (HR 1.54, p < 0.01). Time from abnormal CT scan to first surgeon visit also significantly decreased in C2 (HR 1.43, p < 0.01) and C3 (HR 4.47, p < 0.01) compared with C1, and between C3 and C2 (HR 2.67, p < 0.01). In contrast, time from first surgeon visit to completion of staging significantly increased in C2 (HR 0.36, p < 0.01) and C3 (HR 0.24, p < 0.01) compared with C1, as well as between C3 and C2 (HR 0.60, p < 0.01). Time to first treatment after completion of staging was significantly shorter for C3 than C1 (HR 1.58, p < 0.01). Conclusion: Trends toward a reduction in wait time are evident 5 years after the regionalization of lung cancer care, primarily led by shorter wait times for CT scans and thoracic surgeon consults. However, wait times can further be reduced by addressing delays in staging completion and patient and provider education to identify the early signs of NSCLC.

4.
Int J Qual Health Care ; 33(1)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33693752

RESUMO

BACKGROUND: There is little available data on common general surgical never events (NEs). Lack of this information may have affected our attempts to reduce the incidence of these potentially serious clinical incidents. OBJECTIVES: The purpose of this study was to identify common general surgical NEs from the data held by the National Health Service (NHS) England. METHODS: We analysed the NHS England NE data from April 2012 to February 2020 to identify common general surgical NEs. RESULTS: There was a total of 797 general surgical NEs identified under three main categories such as wrong-site surgery (n = 427; 53.58%), retained items post-procedure (n = 355; 44.54%) and wrong implant/prosthesis (n = 15; 1.88%). We identified a total of 56 common general surgical themes-25 each in the wrong-site surgery and retained foreign body categories and six in wrong implants category.Wrong skin condition surgery was the commonest wrong-site surgery (n = 117; 27.4%). There were 18 wrong-side chest drains (4.2%) and 18 (4.2%) wrong-side angioplasty/angiograms. There were seven (1.6%) instances of confusion in pilonidal/perianal/perineal surgeries and six (1.4%) instances of biopsy of the cervix rather than the colon or rectum.Retained surgical swabs were the most common retained items (n = 165; 46.5%). There were 28 (7.9%) laparoscopic retrieval bags with or without the specimen, 26 (7.3%) chest drain guide wires, 26 (7.3%) surgical needles and 9 (2.5%) surgical drains. Wrong stents were the most common (n = 9; 60%) wrong implants followed by wrong breast implants (n = 2; 13.3%). CONCLUSION: This study found 56 common general surgical NEs. This information is not available to surgeons around the world. Increased awareness of these common themes of NEs may allow for the adoption of more effective and specific safeguards and ultimately help reduce their incidence.

5.
Obes Surg ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33675021

RESUMO

BACKGROUND: Hundreds of thousands of patient-safety clinical incidents are reported to the National Reporting and Learning System (NRLS) database in England and Wales every year. The purpose of this study was to identify bariatric surgery-related learning points from these incidents. METHODS: We analysed bariatric surgery-related clinical incidents reported to the NRLS database between 01 April 2005 and 31st October 2020. The authors used their experience to identify learning themes, attribute severity, and design a safety checklist from these reported incidents. RESULTS: We identified 541 bariatric surgery-related clinical incidents in 58 different themes. Preoperative, intraoperative, and postoperative incidents represented 30.3% (N = 164), 38.1% (N = 206), and 31.6% (N = 171) incidents respectively. One hundred fifty (27.7%), 244 (45.1%), and 147 (27.2%) incidents were attributed high, medium, and low severity respectively. The most commonly reported high severity theme was the failure of thromboprophylaxis (50; 9.2%). Intraoperative high severity incidents included 17 incidents of stapling of orogastric/nasogastric tubes or temperature probes, 8 missed needles, 8 broken graspers, and 6 incidents of band parts left behind. Postoperatively, the most commonly reported high severity theme was improper management of diabetes mellitus (DM) (35; 6.5%). Medication errors represented a significant proportion of the medium severity incidents. CONCLUSION: We identified 58 specific themes of bariatric surgery-related clinical incidents. We propose specific recommendations for the prevention of each theme and a safety checklist to help improve the safety of bariatric surgery worldwide.

6.
Clin Neurol Neurosurg ; 203: 106560, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33618173

RESUMO

BACKGROUND: The proinflammatory state and metabolic changes associated with obesity contribute to cerebrovascular disease. Bariatric surgery can achieve a reliable reduction in body weight and improved metabolic profile in obese patients. However, its impact on cerebrovascular morbidity remains unexplored. This study investigates the effect of bariatric surgery on long-term risk of major cerebrovascular events. METHODS: A retrospective cohort study was designed. Data was extracted from the Clinical Practice Research Datalink. 4212 bariatric surgery patients were compared to 4212 age, sex, and BMI-matched controls. The primary composite endpoint was occurrence of any major adverse cerebrovascular event. Secondary endpoints included composite endpoints of ischaemic events, haemorrhagic events, individual components of the primary endpoint alone and all-cause mortality. An adjusted Cox proportional hazards model was implemented to analyse time to event data. RESULTS: Mean follow-up length was 11.4 years. The primary endpoint occurred in 73 patients. The bariatric surgery group had significantly lower adjusted major cerebrovascular event rates (HR 0.352, 95 %CI 0.195-0.637). Bariatric surgery was associated with lower rates of ischaemic events (HR 0.315, 95 %CI 0.156-0.635), particularly from transient ischaemic attacks (HR 0.364, 95 %CI 0.171-0.775). There was no difference in the rate of haemorrhagic events (HR 0.442, 95 %CI 0.147-1.330) or acute ischaemic stroke (HR 0.221, 95 %CI 0.046-1.054). In total 229 patients died during follow-up. Overall, all-cause mortality was significantly lower in the bariatric surgery group (HR 0.352, 95 %CI 0.195-0.637). CONCLUSIONS: This study identifies an association between bariatric surgery and lower long-term risk of major adverse cerebrovascular events in patients with obesity.

7.
Cell ; 184(5): 1262-1280.e22, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33636129

RESUMO

Improving effector activity of antigen-specific T cells is a major goal in cancer immunotherapy. Despite the identification of several effector T cell (TEFF)-driving transcription factors (TFs), the transcriptional coordination of TEFF biology remains poorly understood. We developed an in vivo T cell CRISPR screening platform and identified a key mechanism restraining TEFF biology through the ETS family TF, Fli1. Genetic deletion of Fli1 enhanced TEFF responses without compromising memory or exhaustion precursors. Fli1 restrained TEFF lineage differentiation by binding to cis-regulatory elements of effector-associated genes. Loss of Fli1 increased chromatin accessibility at ETS:RUNX motifs, allowing more efficient Runx3-driven TEFF biology. CD8+ T cells lacking Fli1 provided substantially better protection against multiple infections and tumors. These data indicate that Fli1 safeguards the developing CD8+ T cell transcriptional landscape from excessive ETS:RUNX-driven TEFF cell differentiation. Moreover, genetic deletion of Fli1 improves TEFF differentiation and protective immunity in infections and cancer.

8.
BMC Gastroenterol ; 21(1): 65, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579203

RESUMO

BACKGROUND: Single nucleotide polymorphism (SNP)-based polygenic risk scoring is predictive of colorectal cancer (CRC) risk. However, few studies have investigated the association of genetic risk score (GRS) with detection of adenomatous polyps at screening colonoscopy. METHODS: We randomly selected 1769 Caucasian subjects who underwent screening colonoscopy from the Genomic Health Initiative (GHI), a biobank of NorthShore University HealthSystem. Outcomes from initial screening colonoscopy were recorded. Twenty-two CRC risk-associated SNPs were obtained from the Affymetrix™ SNP array and used to calculate an odds ratio (OR)-weighted and population-standardized GRS. Subjects with GRS of < 0.5, 0.5-1.5, and > 1.5 were categorized as low, average and elevated risk. RESULTS: Among 1,769 subjects, 520 (29%) had 1 or more adenomatous polyps. GRS was significantly higher in subjects with adenomatous polyps than those without; mean (95% confidence interval) was 1.02 (1.00-1.05) and 0.97 (0.95-0.99), respectively, p < 0.001. The association remained significant after adjusting for age, gender, body mass index, and family history, p < 0.001. The detection rate of adenomatous polyps was 10.8%, 29.0% and 39.7% in subjects with low, average and elevated GRS, respectively, p-trend < 0.001. Higher GRS was also associated with early age diagnosis of adenomatous polyps, p < 0.001. In contrast, positive family history was not associated with risk and age of adenomatous polyps. CONCLUSIONS: GRS was significantly associated with adenomatous polyps in subjects undergoing screening colonoscopy. This result may help in stratifying average risk patients and facilitating personalized colonoscopy screening strategies.

9.
Am J Physiol Endocrinol Metab ; 320(4): E671-E679, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33459181

RESUMO

Bile acids (BA) regulate postprandial metabolism directly and indirectly by affecting the secretion of gut hormones like glucagon-like peptide-1 (GLP-1). The postprandial effects of BA on the secretion of other metabolically active hormones are not well understood. The objective of this study was to investigate the effects of oral ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) on postprandial secretion of GLP-1, oxyntomodulin (OXM), peptide YY (PYY), glucose-dependent insulinotropic peptide (GIP), glucagon, and ghrelin. Twelve healthy volunteers underwent a mixed meal test 60 min after ingestion of UDCA (12-16 mg/kg), CDCA (13-16 mg/kg), or no BA in a randomized crossover study. Glucose, insulin, GLP-1, OXM, PYY, GIP, glucagon, ghrelin, and fibroblast growth factor 19 were measured prior to BA administration at -60 and 0 min (just prior to mixed meal) and 15, 30, 60, 120, 180, and 240 min after the meal. UDCA and CDCA provoked differential gut hormone responses; UDCA did not have any significant effects, but CDCA provoked significant increases in GLP-1 and OXM and a profound reduction in GIP. CDCA increased fasting GLP-1 and OXM secretion in parallel with an increase in insulin. On the other hand, CDCA reduced postprandial secretion of GIP, with an associated reduction in postprandial insulin secretion. Exogenous CDCA can exert multiple salutary effects on the secretion of gut hormones; if these effects are confirmed in obesity and type 2 diabetes, CDCA may be a potential therapy for these conditions.NEW & NOTEWORTHY Oral CDCA and UDCA have different effects on gut and pancreatic hormone secretion. A single dose of CDCA increased fasting secretion of the hormones GLP-1 and OXM with an accompanying increase in insulin secretion. CDCA also reduced postprandial GIP secretion, which was associated with reduced insulin. In contrast, UDCA did not change gut hormone secretion fasting or postprandially. Oral CDCA could be beneficial to patients with obesity and diabetes.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33433660

RESUMO

BACKGROUND AND AIMS: Patients with obesity are at high risk of suffering from arterial and venous peripheral vascular disease (PVD). Bariatric surgery is an effective strategy to achieve weight reduction for patients with obesity. The long-term impact of bariatric surgery on obesity-related morbidity is subject to increasing research interest. This study aimed to ascertain the impact of bariatric surgery on the long-term occurrence of PVD in patients with obesity. METHODS: The study population was extracted from the Clinical Practice Research Datalink, a nation-wide database containing primary and secondary care records of consenting patients. The intervention cohort was 2959 patients who had undergone bariatric surgery during follow-up; their controls were 2959 propensity-score-matched counterparts. The primary endpoint was development of any PVD: arterial or venous. Secondary endpoints were incident peripheral arterial disease alone, incident peripheral venous disease alone. RESULTS: Three hundred forty-six patients suffered a primary endpoint during follow-up. Bariatric surgery did not improve peripheral vascular disease rates as a whole, but it was associated with significantly lower event rates of arterial disease (HR = 0.560, 95%CI 0.327-0.959, p = 0.035) but higher event rates of venous disease (HR = 1.685, 95%CI 1.256-2.262, p < 0.001). CONCLUSIONS: Bariatric surgery was associated with significantly reduced long-term occurrence of arterial disease but increased occurrence of venous disease in patients with obesity.

11.
PLoS Med ; 17(12): e1003228, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33285553

RESUMO

BACKGROUND: Although bariatric surgery is well established as an effective treatment for patients with obesity and type 2 diabetes mellitus (T2DM), there exists reluctance to increase its availability for patients with severe T2DM. The aims of this study were to examine the impact of bariatric surgery on T2DM resolution in patients with obesity and T2DM requiring insulin (T2DM-Ins) using data from a national database and to develop a health economic model to evaluate the cost-effectiveness of surgery in this cohort when compared to best medical treatment (BMT). METHODS AND FINDINGS: Clinical data from the National Bariatric Surgical Registry (NBSR), a comprehensive database of bariatric surgery in the United Kingdom, were extracted to analyse outcomes of patients with obesity and T2DM-Ins who underwent primary bariatric surgery between 2009 and 2017. Outcomes for this group were combined with data sourced from a comprehensive literature review in order to develop a state-transition microsimulation model to evaluate cost-effectiveness of bariatric surgery versus BMT for patients over a 5-year time horizon. The main outcome measure for the clinical study was insulin cessation at 1-year post-surgery: relative risks (RR) summarising predictive factors were determined, unadjusted, and after adjusting for variables including age, initial body mass index (BMI), duration of T2DM, and weight loss. Main outcome measures for the economic evaluation were total costs, total quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) at willingness-to-pay threshold of GBP£20,000. A total of 2,484 patients were eligible for inclusion, of which 1,847 had 1-year follow-up data (mean age of 51 years, mean initial BMI 47.2 kg/m2, and 64% female). 67% of patients no longer required insulin at 1-year postoperatively: these rates persisted for 4 years. Roux-en-Y gastric bypass (RYGB) was associated with a higher rate of insulin cessation (71.7%) than sleeve gastrectomy (SG; 64.5%; RR 0.92, confidence interval (CI) 0.86-0.99) and adjustable gastric band (AGB; 33.6%; RR 0.45, CI 0.34-0.60; p < 0.001). When adjusted for percentage total weight loss and demographic variables, insulin cessation following surgery was comparable for RYGB and SG (RR 0.97, CI 0.90-1.04), with AGB having the lowest cessation rates (RR 0.55, CI 0.40-0.74; p < 0.001). Over 5 years, bariatric surgery was cost saving compared to BMT (total cost GBP£22,057 versus GBP£26,286 respectively, incremental difference GBP£4,229). This was due to lower treatment costs as well as reduced diabetes-related complications costs and increased health benefits. Limitations of this study include loss to follow-up of patients within the NBSR dataset and that the time horizon for the economic analysis is limited to 5 years. In addition, the study reflects current medical and surgical treatment regimens for this cohort of patients, which may change. CONCLUSIONS: In this study, we observed that in patients with obesity and T2DM-Ins, bariatric surgery was associated with high rates of postoperative cessation of insulin therapy, which is, in turn, a major driver of overall reductions in direct healthcare cost. Our findings suggest that a strategy utilising bariatric surgery for patients with obesity and T2DM-Ins is cost saving to the national healthcare provider (National Health Service (NHS)) over a 5-year time horizon.

12.
Neurosurgery ; 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33289519

RESUMO

BACKGROUND: Surgical decompression for degenerative cervical myelopathy (DCM) is one of the mainstays of treatment, with generally positive outcomes. However, some patients who undergo surgery for DCM continue to show functional decline. OBJECTIVE: To use machine learning (ML) algorithms to determine predictors of worsening functional status after surgical intervention for DCM. METHODS: This is a retrospective analysis of prospectively collected data. A total of 757 patients enrolled in 2 prospective AO Spine clinical studies, who underwent surgical decompression for DCM, were analyzed. The modified Japanese Orthopedic Association (mJOA) score, a marker of functional status, was obtained before and 1 yr postsurgery. The primary outcome measure was the dichotomized change in mJOA at 1 yr according to whether it was negative (worse functional status) or non-negative. After applying an 80:20 training-testing split of the dataset, we trained, optimized, and tested multiple ML algorithms to evaluate algorithm performance and determine predictors of worse mJOA at 1 yr. RESULTS: The highest-performing ML algorithm was a polynomial support vector machine. This model showed good calibration and discrimination on the testing data, with an area under the receiver operating characteristic curve of 0.834 (accuracy: 74.3%, sensitivity: 88.2%, specificity: 72.4%). Important predictors of functional decline at 1 yr included initial mJOA, male gender, duration of myelopathy, and the presence of comorbidities. CONCLUSION: The reasons for worse mJOA are frequently multifactorial (eg, adjacent segment degeneration, tandem lumbar stenosis, ongoing neuroinflammatory processes in the cord). This study successfully used ML to predict worse functional status after surgery for DCM and to determine associated predictors.

13.
Obes Surg ; 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33151519

RESUMO

PURPOSE: To prospectively evaluate the feasibility of single-stage bariatric surgery in patients with super-super obesity and compare their outcomes with patients undergoing intra-gastric balloon insertion as a bridging device prior to definitive surgery. MATERIALS AND METHODS: Data from 42 patients with BMI 60-75 kg/m2 who underwent either intra-gastric balloon insertion followed by sleeve gastrectomy (two-stage group); or attempted bariatric surgery as a single-stage procedure were compared. RESULTS: All patients in the single-stage group underwent successful bariatric surgery. Length of hospital stay after definitive bariatric surgery (3.3 ± 1.9 vs 2.2 ± 0.6 days, p = 0.005) and overall complication rates were significantly higher in the two-stage group. CONCLUSIONS: Routine use of an intra-gastric balloon in super-super obese patients is not required and may be associated with poorer peri-operative outcomes and delayed weight loss.

14.
Sci Rep ; 10(1): 16132, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32999299

RESUMO

Previous studies aimed at identifying predictors of clinical outcomes following surgical decompression for degenerative cervical myelopathy (DCM) are limited by multicollinearity among predictors, whereby the high degree of correlation between covariates precludes detection of potentially significant findings. We apply partial least squares (PLS), a data-driven approach, to model multi-dimensional variance and dissociate patient phenotypes associated with functional, disability, and quality of life (QOL) outcomes in DCM. This was a post-hoc analysis of DCM patients enrolled in the prospective, multi-center AOSpine CSM-NA/CSM-I studies. Baseline clinical covariates evaluated as predictors included demographic (e.g., age, sex), clinical presentation (e.g., signs and symptoms), and treatment (e.g., surgical approach) characteristics. Outcomes evaluated included change in functional status (∆mJOA), disability (∆NDI), and QOL (∆SF-36) at 2 years. PLS was used to derive latent variables (LVs) relating specific clinical covariates with specific outcomes. Statistical significance was estimated using bootstrapping. Four hundred and seventy-eight patients met eligibility criteria. PLS identified 3 significant LVs. LV1 indicated an association between presentation with hand muscle atrophy, treatment by an approach other than laminectomy alone, and greater improvement in physical health-related QOL outcomes (e.g., SF-36 Physical Component Summary). LV2 suggested the presence of comorbidities (respiratory, rheumatologic, psychological) was associated with lesser improvements in functional status post-operatively (i.e., mJOA score). Finally, LV3 reflected an association between more severe myelopathy presenting with gait impairment and poorer mental health-related QOL outcomes (e.g., SF-36 Mental Component Summary). Using PLS, this analysis uncovered several novel insights pertaining to patients undergoing surgical decompression for DCM that warrant further investigation: (1) comorbid status and frailty heavily impact functional outcome; (2) presentation with hand muscle atrophy is associated with better physical QOL outcomes; and (3) more severe myelopathy with gait impairment is associated with poorer mental QOL outcomes.

15.
Obes Surg ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064260

RESUMO

Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) have been shown to improve metabolic comorbidities as well as quality of life (QoL) in the obese population. The vast majority of previous studies have investigated the metabolic effects of bariatric surgery and there is a dearth of studies examining long-term QoL outcomes post bariatric surgery. The outcomes of 43 patients who underwent bariatric surgery were prospectively assessed, using BAROS questionnaires to quantify QoL and metabolic status pre-operatively, at 1 year and at 8 years. Total weight loss and comorbidity resolution were similar between RYGB and SG. The RYGB cohort experienced greater QoL improvement from baseline and had higher BAROS scores at 8 years. RYGB may provide more substantial and durable long-term benefits as compared to SG.

16.
Nat Biomed Eng ; 4(11): 1076-1089, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33020600

RESUMO

Bone-marrow endothelial cells in the haematopoietic stem-cell niche form a network of blood vessels that regulates blood-cell traffic as well as the maintenance and function of haematopoietic stem and progenitor cells. Here, we report the design and in vivo performance of systemically injected lipid-polymer nanoparticles encapsulating small interfering RNA (siRNA), for the silencing of genes in bone-marrow endothelial cells. In mice, nanoparticles encapsulating siRNA sequences targeting the proteins stromal-derived factor 1 (Sdf1) or monocyte chemotactic protein 1 (Mcp1) enhanced (when silencing Sdf1) or inhibited (when silencing Mcp1) the release of stem and progenitor cells and of leukocytes from the bone marrow. In a mouse model of myocardial infarction, nanoparticle-mediated inhibition of cell release from the haematopoietic niche via Mcp1 silencing reduced leukocytes in the diseased heart, improved healing after infarction and attenuated heart failure. Nanoparticle-mediated RNA interference in the haematopoietic niche could be used to investigate haematopoietic processes for therapeutic applications in cancer, infection and cardiovascular disease.

17.
Pain Physician ; 23(4S): S439-S448, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32942799

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has drastically altered daily living and medical care for Ohio residents and the practice of medicine for the interventional pain management physician. As a state, Ohio tends to be demographically representative of the broader US population. OBJECTIVE: Reviewing the efforts deployed by Ohio to flatten the COVID-19 infection curve and reduce the spread of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important component of determining optimal procedures for mitigating the effects of the COVID-19 pandemic. METHODS: Over the course of several announcements and orders during the months of March and April, new policies were put into place to prevent COVID-19 transmission, which included efforts to facilitate social distancing and ensure the health care system could manage the number of COVID-19 cases at peak infection rate. Efforts directed toward medical providers included delay of elective procedures, expansion of telehealth options, and new temporary guidance for prescribing controlled substances. RESULTS: The Ohio COVID-19 containment approach resulted in a substantial reduction in COVID-19 cases compared with early models of disease spread, and the state has begun a phased reopening. Continued vigilance in applying social distancing and infection control measures will be a critical component of preventing or reducing the impact of a second wave of COVID-19 in Ohio. LIMITATIONS: A narrative review with paucity of literature.


Assuntos
Controle de Doenças Transmissíveis/métodos , Infecções por Coronavirus/prevenção & controle , Manejo da Dor , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Betacoronavirus , Infecções por Coronavirus/transmissão , Humanos , Ohio , Pneumonia Viral/transmissão
18.
Spinal Cord ; 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963361

RESUMO

STUDY DESIGN: Retrospective analysis of prospectively collected data. OBJECTIVES: Recently, logistic regression models were developed to predict independence in bowel function 1 year after spinal cord injury (SCI) on a multicenter European SCI (EMSCI) dataset. Here, we evaluated the external validity of these models against a prospectively accrued North American SCI dataset. SETTING: Twenty-five SCI centers in the United States and Canada. METHODS: Two logistic regression models developed by the EMSCI group were applied to data for 277 patients derived from three prospective multicenter SCI studies based in North America. External validation was evaluated for both models by assessing their discrimination, calibration, and clinical utility. Discrimination and calibration were assessed using ROC curves and calibration curves, respectively, while clinical utility was assessed using decision curve analysis. RESULTS: The simplified logistic regression model, which used baseline total motor score as the predictor, demonstrated the best performance, with an area under the ROC curve of 0.869 (95% confidence interval: 0.826-0.911), a sensitivity of 75.5%, and a specificity of 88.5%. Moreover, the model was well calibrated across the full range of observed probabilities and displayed superior clinical benefit on the decision curve. CONCLUSIONS: A logistic regression model using baseline total motor score as a predictor of independent bowel function 1 year after SCI was successfully validated against an external dataset. These findings provide evidence supporting the use of this model to enhance the care for individuals with SCI.

19.
Front Neurol ; 11: 644, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32793094

RESUMO

The success of devices delivering functional electrical stimulation (FES) has been hindered by complications related to implants including skin breakdown and subsequent wound dehiscence. Our hypothesis was that a vascularized muscle flap along the dorsal surface of an epimysial electrode would prevent skin breakdown during FES therapy to treat atrophy of the gastrocnemius muscle during peripheral nerve injury. Resection of a tibial nerve segment with subsequent electrode implantation on the dorsal surfaces of the gastrocnemius muscle was performed on ten Lewis rats. In five rats, the biceps femoris (BF) muscle was dissected and placed along the dorsal surface of the electrode (Flap group). The other five animals did not undergo flap placement (No Flap group). All animals were treated with daily FES therapy for 2 weeks and degree of immune response and skin breakdown were evaluated. The postoperative course of one animal in the No Flap group was complicated by complete wound dehiscence requiring euthanasia of the animal on postoperative day 4. The remaining 4 No Flap animals showed evidence of ulceration at the implant by postoperative day 7. The 5 animals in the Flap group did not have ulcerative lesions. Excised tissue at postoperative day 14 examined by histology and in vivo Imaging System (IVIS) showed decreased implant-induced inflammation in the Flap group. Expression of specific markers for local foreign body response were also decreased in the Flap group.

20.
World Neurosurg ; 140: 512-518, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32797983

RESUMO

Personalized medicine is a new paradigm of healthcare in which interventions are based on individual patient characteristics rather than on "one-size-fits-all" guidelines. As epidemiological datasets continue to burgeon in size and complexity, powerful methods such as statistical machine learning and artificial intelligence (AI) become necessary to interpret and develop prognostic models from underlying data. Through such analysis, machine learning can be used to facilitate personalized medicine via its precise predictions. Additionally, other AI tools, such as natural language processing and computer vision, can play an instrumental part in personalizing the care provided to patients with spine disease. In the present report, we discuss the current strides made in incorporating AI into research on spine disease, especially traumatic spinal cord injury and degenerative spine disease. We describe studies using AI to build accurate prognostic models, extract important information from medical reports via natural language processing, and evaluate functional status in a granular manner using computer vision. Through a case illustration, we have demonstrated how these breakthroughs can facilitate an increased role for more personalized medicine and, thus, change the landscape of spine care.

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