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1.
Clin Nutr ESPEN ; 36: 99-105, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32220375

RESUMO

BACKGROUND AND AIMS: Early post-operative feeding is recommended within enhanced recovery after surgery programmes. This study aimed to describe post-operative feeding patterns and associated factors among patients following colorectal surgery, using a post-hoc analysis of observational data from a previous RCT on chewing gum after surgery. METHODS: Data from 301 participants (59% male, median age 67 years) were included. Amounts of meals consumed on post-operative days (POD) 1-5 were recorded as: none, a quarter, half, three-quarters, all. 'Early' consumers were those who ate ≥a quarter of a meal on POD1. 'Early' tolerance was the consumption of at least half of three meals on POD1 or 2 without vomiting. Exploration of selected peri-operative factors with early feeding and tolerance were assessed using logistic regression. RESULTS: 222 people (73.8%) consumed solid food early, and 109 people (36.2%) tolerated solid food early. Several factors were associated with postoperative feeding: provision of pre-operative bowel preparation was associated with delayed consumption [odds ratio (OR) 0.34, 95% confidence interval (CI) 0.14-0.83] and tolerance (OR 0.35, 95% CI 0.16-0.81) of food; and laparoscopic/laparoscopic assisted (vs. open/converted to open surgery) was associated with early tolerance of food (OR 1.99, 95% CI 1.17-3.39). CONCLUSIONS: While three-quarters of the study population ate solid food early, only one-third tolerated solid food early. Findings suggest that bowel preparation and surgery type are factors warranting further investigation in future studies to improve uptake of early post-operative feeding.

2.
J Clin Neurosci ; 72: 102-107, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31926661

RESUMO

This study aimed to show that a more distal insertion of S2-alar-iliac screws (S2AI) towards the S2 foramen facilitates a more natural trajectory and results in fewer breaches of the iliac wing due to the anteroposterior relationship of the sacrum and pelvis. Thirty-six consecutive patients who had received S2AI and postoperative computed tomography (CT) imaging were retrospectively reviewed. A freehand technique was used to insert all screws. Screws were stratified into two groups (Zone A and Zone B) based on the insertion point within the sacrum. Zone A was defined as screw insertion proximal to the second sacral foramen. Zone B was defined as screw insertion at or distal to the level of the second sacral foramen. CT imaging was reviewed to identify passage of the screw through either the fibrous or bony sacroiliac joint, and to check for instrumentation breach of the iliac wing. Sixty-two S2AI in 36 patients were identified. Twenty-six screws (42%) were inserted into Zone A and 36 (58%) into Zone B. There were 11 instrumentation breaches of the iliac wing in Zone A (42%) and 0 in Zone B (p < 0.0001). In Zone A, 24 screws (92%) passed through the upper, fibrous portion of the sacroiliac joint. In Zone B, no screws passed through this region (p < 0.0001). In conclusion, insertion of S2AI at or distal to the second sacral foramen facilitates improved screw placement due to the anteroposterior relationship of the sacrum and pelvis at this level.

3.
Bioinformatics ; 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31971579

RESUMO

MOTIVATION: Systematic identification of molecular targets among known drugs plays an essential role in drug repurposing and understanding of their unexpected side effects. Computational approaches for prediction of drug-target interactions (DTIs) are highly desired in comparison to traditional experimental assays. Furthermore, recent advances of multi-omics technologies and systems biology approaches have generated large-scale heterogeneous, biological networks, which offer unexpected opportunities for network-based identification of new molecular targets among known drugs. RESULTS: In this study, we present a network-based computational framework, termed AOPEDF, an Arbitrary-Order Proximity Embedded Deep Forest approach, for prediction of DTIs. AOPEDF learns a low-dimensional vector representation of features that preserve arbitrary-order proximity from a highly integrated, heterogeneous biological network connecting drugs, targets (proteins), and diseases. In total, we construct a heterogeneous network by uniquely integrating 15 networks covering chemical, genomic, phenotypic, and network profiles among drugs, proteins/targets, and diseases. Then, we build a cascade deep forest classifier to infer new DTIs. Via systematic performance evaluation, AOPEDF achieves high accuracy in identifying molecular targets among known drugs on two external validation sets collected from DrugCentral (area under receiver operating characteristic curve [AUROC] = 0.868) and ChEMBL (AUROC = 0.768) databases, outperforming several state-of-the-art methods. In a case study, we showcase that multiple molecular targets predicted by AOPEDF are associated with mechanism-of-action of substance abuse disorder for several marketed drugs (such as aripiprazole, risperidone, and haloperidol). AVAILABILITY: Source code and data can be downloaded from https://github.com/ChengF-Lab/AOPEDF. SUPPLEMENTARY INFORMATION: Supplementary data are available online at Bioinformatics.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31931555

RESUMO

Objective: To analyze the accuracy of iliac screws using freehand technique performed by the same surgeon. We also analyzed how the breach of iliac screws was related to the clinical symptoms resulting in revision surgery. Methods: From January 2009 to November 2015, 100 patients (193 iliac screws) were analyzed using postoperative computed tomography scans. The breaches were classified based on the superior, inferior, lateral, and medial iliac wall violation by the screw. According to the length of screw extrusion, the classification grades were as follows : grade 1, screw extrusion <1 cm; grade II, 1 cm ≤ screw extrusion <2 cm; grade III, 2 cm ≤ screw extrusion <3 cm; and grade IV, 3 cm ≤ screw extrusion. We also reviewed the revision surgery associated with iliac screw misplacement. Results: Of the 193 inserted screws, 169 were correctly located and 24 were misplaced screws. There were eight grade I, six grade II, six grade III, and four grade IV screw breaches, and 11, 8, 2, and 3 screws violated the medial, lateral, superior, and inferior walls, respectively. Four revision surgeries were performed for the grade III or IV iliac screw breaches in the lateral or inferior direction with respect to its related symptoms. Conclusion: In iliac screw placement, 12.4% breaches developed. Although most breaches were not problematic, symptomatic violations (2.1%) could result in revision surgery. Notably, the surgeon should keep in mind that lateral or inferior wall breaches longer than 2 cm can be risky and should be avoided.

5.
Spine (Phila Pa 1976) ; 45(1): 32-37, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31415459

RESUMO

STUDY DESIGN: Post-hoc analysis of a prospective, multicenter cohort study. OBJECTIVE: To analyze the impact of smoking on rates of postoperative adverse events (AEs) in patients undergoing high-risk adult spine deformity surgery. SUMMARY OF BACKGROUND DATA: Smoking is a known predictor of medical complications after adult deformity surgery, but the effect on complications, implant failure and other AEs has not been adequately described in prospective studies. METHODS: Twenty-six patients with a history of current smoking were identified out of the 272 patients enrolled in the SCOLI-RISK-1 study who underwent complex adult spinal deformity surgery at 15 centers, with 2-year follow-up. The outcomes and incidence of AEs in these patients were compared to the nonsmoking cohort (n = 244) using univariate analysis, with additional multivariate regression to adjust for the effect of patient demographics, complexity of surgery, and other confounders. RESULTS: The number of levels and complexity of surgery in both cohorts were comparable. In the univariate analysis, the rates of implant failure were almost double (odds ratio 2.28 [0.75-6.18]) in smoking group (n = 7; 26.9%)) that observed in the nonsmoking group (n = 34; 13.9%), but this was not statistically significant (P = 0.088). Surgery-related excessive bleeding (>4 L) was significantly higher in the smoking group (n = 5 vs. n = 9; 19.2% vs. 3.7%; OR 6.22[1.48 - 22.75]; P = 0.006). Wound infection rates and respiratory complications were similar in both groups. In the multivariate analysis, the smoking group demonstrated a higher incidence of any surgery-related AEs over 2 years (n = 13 vs. n = 95; 50.0% vs. 38.9%; OR 2.12 [0.88-5.09]) (P = 0.094). CONCLUSION: In this secondary analysis of patients from the SCOLI-RISK-1 study, a history of smoking significantly increased the risk of excessive intraoperative bleeding and nonsignificantly increased the rate of implant failure or surgery-related AEs over 2 years. The authors therefore advocate a smoking cessation program in patients undergoing complex adult spine deformity surgery. LEVEL OF EVIDENCE: 2.

6.
Nat Biotechnol ; 37(12): 1446-1451, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31712773

RESUMO

Vagus nerve stimulation can ameliorate autoimmune diseases such as rheumatoid arthritis by modulation of the immune system. Its efficacy for the treatment of type 1 diabetes has not been explored, in part because the nerves projecting to the pancreatic lymph nodes (pLNs) in mice are unmapped. Here, we map the nerve projecting to the pancreas and pLNs in mice and use a minimally invasive surgical procedure to implant micro-cuff electrodes onto the nerve. Pancreatic nerve electrical stimulation (PNES) resulted in ß-adrenergic receptor-mediated-accumulation of B and T cells in pLNs and reduced production of pro-inflammatory cytokines following lipopolysaccharide stimulation. Autoreactive T cells showed reduced proliferation in pLNs of mice receiving PNES as compared to sham controls. In a spontaneous mouse model of autoimmune diabetes, PNES inhibited disease progression in diabetic mice.


Assuntos
Diabetes Mellitus Tipo 1 , Terapia por Estimulação Elétrica , Pâncreas , Animais , Linfócitos B/imunologia , Glicemia/metabolismo , Citocinas/metabolismo , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/terapia , Feminino , Insulina/metabolismo , Linfonodos/citologia , Linfonodos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos SCID , Pâncreas/imunologia , Pâncreas/inervação , Pâncreas/metabolismo , Linfócitos T/imunologia
7.
Am J Respir Cell Mol Biol ; 61(6): 765-775, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31596601

RESUMO

S-nitrosothiols (SNOs) are endogenous signaling molecules that have numerous beneficial effects on the airway via cyclic guanosine monophosphate-dependent and -independent processes. Healthy human airways contain SNOs, but SNO levels are lower in the airways of patients with cystic fibrosis (CF). In this study, we examined the interaction between SNOs and the molecular cochaperone C-terminus Hsc70 interacting protein (CHIP), which is an E3 ubiquitin ligase that targets improperly folded CF transmembrane conductance regulator (CFTR) for subsequent degradation. Both CFBE41o- cells expressing either wild-type or F508del-CFTR and primary human bronchial epithelial cells express CHIP. Confocal microscopy and IP studies showed the cellular colocalization of CFTR and CHIP, and showed that S-nitrosoglutathione inhibits the CHIP-CFTR interaction. SNOs significantly reduced both the expression and activity of CHIP, leading to higher levels of both the mature and immature forms of F508del-CFTR. In fact, SNO inhibition of the function and expression of CHIP not only improved the maturation of CFTR but also increased CFTR's stability at the cell membrane. S-nitrosoglutathione-treated cells also had more S-nitrosylated CHIP and less ubiquitinated CFTR than cells that were not treated, suggesting that the S-nitrosylation of CHIP prevents the ubiquitination of CFTR by inhibiting CHIP's E3 ubiquitin ligase function. Furthermore, the exogenous SNOs S-nitrosoglutathione diethyl ester and S-nitro-N-acetylcysteine increased the expression of CFTR at the cell surface. After CHIP knockdown with siRNA duplexes specific for CHIP, F508del-CFTR expression increased at the cell surface. We conclude that SNOs effectively reduce CHIP-mediated degradation of CFTR, resulting in increased F508del-CFTR expression on airway epithelial cell surfaces. Together, these findings indicate that S-nitrosylation of CHIP is a novel mechanism of CFTR correction, and we anticipate that these insights will allow different SNOs to be optimized as agents for CF therapy.

8.
Pediatr Pulmonol ; 54(12): 1989-1996, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31486289

RESUMO

BACKGROUND: Bronchopulmonary dysplasia (BPD) with airway hyperreactivity is a long-term pulmonary complication of prematurity. The endogenous nonadrenergic, noncholinergic signaling molecule, S-nitrosoglutathione (GSNO) and its catabolism by GSNO reductase (GSNOR) modulate airway reactivity. Tracheomalacia is a major, underinvestigated complication of BPD. We studied trachealis, left main bronchus (LB), and intrapulmonary bronchiolar (IPB) relaxant responses to GSNO in a murine hyperoxic BPD model. METHODS: Wild-type (WT) or GSNOR knockout (KO) newborn mice were raised in 60% (BPD) or 21% (control) oxygen during the first 3 weeks of life. After room air recovery, adult trachealis, LB, and IPB smooth muscle relaxant responses to GSNO (after methacholine preconstriction) were studied using wire myographs. Studies were repeated after GSNOR inhibitor (GSNORi) pretreatment and in KO mice. RESULTS: GSNO relaxed all airway preparations. GSNO relaxed WT BPD trachealis substantially more than WT controls (P < .05). Pharmacologic or genetic ablation of GSNOR abolished the exaggerated BPD tracheal relaxation to GSNO and also augmented BPD IPB relaxation to GSNO. LB ring contractility was not significantly different between groups or conditions. Additionally, GSNORi treatment induced relaxation of WT IPBs but not trachealis or LB. CONCLUSION: GSNO dramatically relaxed the trachealis in our BPD model, an effect paradoxically reversed by loss of GSNOR. Conversely, GSNOR inhibition augmented IBP relaxation. These data suggest that GSNOR inhibition could benefit both the BPD trachealis and distal airways, restoring relaxant responses to those of room air controls. Because therapeutic options are limited in this high-risk population, future studies of GSNOR inhibition are needed.

9.
Cochrane Database Syst Rev ; 7: CD004080, 2019 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-31329285

RESUMO

BACKGROUND: This is an update of the review last published in 2011. It focuses on early postoperative enteral nutrition after lower gastrointestinal surgery. Traditional management consisted of 'nil by mouth', where patients receive fluids followed by solids after bowel function has returned. Although several trials have reported lower incidence of infectious complications and faster wound healing upon early feeding, other trials have shown no effect. The immediate advantage of energy intake (carbohydrates, protein or fat) could enhance recovery with fewer complications, and this warrants a systematic evaluation. OBJECTIVES: To evaluate whether early commencement of postoperative enteral nutrition (within 24 hours), oral intake and any kind of tube feeding (gastric, duodenal or jejunal), compared with traditional management (delayed nutritional supply) is associated with a shorter length of hospital stay (LoS), fewer complications, mortality and adverse events in patients undergoing lower gastrointestinal surgery (distal to the ligament of Treitz). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library 2017, issue 10), Ovid MEDLINE (1950 to 15 November 2017), Ovid Embase (1974 to 15 November 2017). We also searched for ongoing trials in ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform (15 November 2017). We handsearched reference lists of identified studies and previous systematic reviews. SELECTION CRITERIA: We included randomised controlled trials (RCT) comparing early commencement of enteral nutrition (within 24 hours) with no feeding in adult participants undergoing lower gastrointestinal surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study quality using the Cochrane 'Risk of bias' tool tailored to this review and extracted data. Data analyses were conducted according to the Cochrane recommendations.We rated the quality of evidence according to GRADE.Primary outcomes were LoS and postoperative complications (wound infections, intraabdominal abscesses, anastomotic dehiscence, pneumonia).Secondary outcomes were: mortality, adverse events (nausea, vomiting), and quality of life (QoL).LoS was estimated using mean difference (MD (presented as mean +/- SD). For other outcomes we estimated the common risk ratio (RR) and calculated the associated 95% confidence intervals. For analysis, we used an inverse-variance random-effects model for the primary outcome (LoS) and Mantel-Haenszel random-effects models for the secondary outcomes. We also performed Trial Sequential Analyses (TSA). MAIN RESULTS: We identified 17 RCTs with 1437 participants undergoing lower gastrointestinal surgery. Most studies were at high or unclear risk of bias in two or more domains. Six studies were judged as having low risk of selection bias for random sequence generation and insufficient details were provided for judgement on allocation concealment in all 17 studies. With regards to performance and deception bias; 14 studies reported no attempt to blind participants and blinding of personnel was not discussed either. Only one study was judged as low risk of bias for blinding of outcome assessor. With regards to incomplete outcome data, three studies were judged to be at high risk because they had more than 10% difference in missing data between groups. For selective reporting, nine studies were judged as unclear as protocols were not provided and eight studies had issues with either missing data or incomplete reporting of results.LOS was reported in 16 studies (1346 participants). The mean LoS ranged from four days to 16 days in the early feeding groups and from 6.6 days to 23.5 days in the control groups. Mean difference (MD) in LoS was 1.95 (95% CI, -2.99 to -0.91, P < 0.001) days shorter in the early feeding group. However, there was substantial heterogeneity between included studies (I2 = 81, %, Chi2 = 78.98, P < 0.00001), thus the overall quality of evidence for LoS is low. These results were confirmed by the TSA showing that the cumulative Z-curve crossed the trial sequential monitoring boundary for benefit.We found no differences in the incidence of postoperative complications: wound infection (12 studies, 1181 participants, RR 0.99, 95%CI 0.64 to 1.52, very low-quality evidence), intraabdominal abscesses (6 studies, 554 participants, RR 1.00, 95%CI 0.26 to 3.80, low-quality evidence), anastomotic leakage/dehiscence (13 studies, 1232 participants, RR 0.78, 95%CI 0.38 to 1.61, low-quality evidence; number needed to treat for an additional beneficial outcome (NNTB) = 100), and pneumonia (10 studies, 954 participants, RR 0.88, 95%CI 0.32 to 2.42, low-quality evidence; NNTB = 333).Mortality was reported in 12 studies (1179 participants), and showed no between-group differences (RR = 0.56, 95%CI, 0.21 to 1.52, P = 0.26, I2 = 0%, Chi2 = 3.08, P = 0.96, low-quality evidence). The most commonly reported cause of death was anastomotic leakage, sepsis and acute myocardial infarction.Seven studies (613 participants) reported vomiting (RR 1.23, 95%CI, 0.96 to 1.58, P = 0.10, I2 = 0%, Chi2 = 4.98, P = 0.55, low-quality evidence; number needed to treat for an additional harmful outcome (NNTH) = 19), and two studies (118 participants) reported nausea (RR 0.95, 0.71 to 1.26, low-quality evidence). Four studies reported combined nausea and vomiting (RR 0.94, 95%CI 0.51 to 1.74, very low-quality evidence). One study reported QoL assessment; the scores did not differ between groups at 30 days after discharge on either QoL scale EORTC QLQ-C30 or EORTC QlQ-OV28 (very low-quality evidence). AUTHORS' CONCLUSIONS: This review suggests that early enteral feeding may lead to a reduced postoperative LoS, however cautious interpretation must be taken due to substantial heterogeneity and low-quality evidence. For all other outcomes (postoperative complications, mortality, adverse events, and QoL) the findings are inconclusive, and further trials are justified to enhance the understanding of early feeding for these. In this updated review, only a few additional studies have been included, and these were small and of poor quality.To improve the evidence, future trials should address quality issues and focus on clearly defining and measuring postoperative complications to allow for better comparison between studies. However due to the introduction of fast track protocols which already include an early feeding component, future trials may be challenging. A more feasible trial may be to investigate the effect of differing postoperative energy intake regimens on relevant outcomes.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Nutrição Enteral/métodos , Tempo de Internação , Complicações Pós-Operatórias/prevenção & controle , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo
10.
Global Spine J ; 9(1 Suppl): 15S-21S, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31157143

RESUMO

Study Design: Retrospective case study on prospectively collected data. Objectives: The purpose of this explorative study was: 1) to determine if patterns of spinal cord injury could be detected through intra-operative neuromonitoring (IONM) changes in pediatric patients undergoing spinal deformity corrections, 2) to identify if perfusion based or direct trauma causes of IONM changes could be distinguished, 3) to observe the effects of the interventions performed in response to these events, and 4) to attempt to identify different treatment algorithms for the different causes of IONM alerts. Methods: Prospectively collected neuromonitoring data in pre-established forms on consecutive pediatric patients undergoing coronal spinal deformity surgery at a single center was reviewed. Real-time data was collected on IONM alerts with >50% loss in signal. Patients with alerts were divided into 2 groups: unilateral changes (direct cord trauma), and bilateral MEP changes (cord perfusion deficits). Results: A total of 97 pediatric patients involving 71 females and 26 males with a mean age of 14.9 (11-18) years were included in this study. There were 39 alerts in 27 patients (27.8% overall incidence). All bilateral changes responded to a combination of transfusion, increasing blood pressure, and rod removal. Unilateral changes as a result of direct trauma, mainly during laminotomies for osteotomies, improved with removal of the causative agent. Following corrective actions in response to the alerts, all cases were completed as planned. Signal returned to near baseline in 20/27 patients at closure, with no new neurological deficits in this series. Conclusion: A high incidence of alerts occurred in this series of cases. Dividing IONM changes into perfusion-based vs direct trauma directed treatment to the offending cause, allowing for safe corrections of the deformities. Patients did not need to recover IONM signal to baseline to have a normal neurological examination.

11.
Spine (Phila Pa 1976) ; 44(17): 1211-1219, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30921297

RESUMO

STUDY DESIGN: Secondary analysis of prospective multicenter cohort. OBJECTIVE: To assess effect of serious adverse events (SAEs) on 2- and 4-year patient-reported outcomes measures (PROMs) in patients surgically treated for adult symptomatic lumbar scoliosis (ASLS). SUMMARY OF BACKGROUND DATA: Operative treatment for ASLS can improve health-related quality of life, but has high rates of SAEs. How these SAEs effect health-related quality of life remain unclear. METHODS: The ASLS study assessed operative versus nonoperative ASLS treatment, with randomized and observational arms. Patients were 40- to 80-years-old with ASLS, defined as lumbar coronal Cobb ≥30° and Oswestry Disability Index (ODI) ≥20 or Scoliosis Research Society-22 (SRS-22) ≤4.0 in pain, function, and/or self-image domains. SRS-22 subscore and ODI were compared between operative patients with and without a related SAE and nonoperative patients using an as-treated analysis combining randomized and observational cohorts. RESULTS: Two hundred eighty-six patients were enrolled, and 2- and 4-year follow-up rates were 90% and 81%, respectively, although at the time of data extraction not all patients were eligible for 4-year follow-up. A total of 97 SAEs were reported among 173 operatively treated patients. The most common were implant failure/pseudarthrosis (n = 25), proximal junctional kyphosis/failure (n = 10), and minor motor deficit (n = 8). At 2 years patients with an SAE improved less than those without an SAE based on SRS-22 (0.52 vs. 0.79, P = 0.004) and ODI (-11.59 vs. -17.34, P = 0.021). These differences were maintained at 4-years for both SRS-22 (0.51 vs. 0.86, P = 0.001) and ODI (-10.73 vs. -16.69, P = 0.012). Despite this effect, patients sustaining an operative SAE had greater PROM improvement than nonoperative patients (P<0.001). CONCLUSION: Patients affected by SAEs following surgery for ASLS had significantly less improvement of PROMs at 2- and 4-year follow-ups versus those without an SAE. Regardless of SAE occurrence, operatively treated patients had significantly greater improvement in PROMs than those treated nonoperatively. LEVEL OF EVIDENCE: 2.


Assuntos
Região Lombossacral/cirurgia , Complicações Pós-Operatórias/epidemiologia , Qualidade de Vida , Escoliose/cirurgia , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Pessoa de Meia-Idade , Pseudoartrose/epidemiologia
12.
Br J Haematol ; 185(2): 311-316, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30714125

RESUMO

Iron deficiency anaemia (IDA) is the most common cause of anaemia and a frequent indication for colonoscopy, although the prevalence of colorectal cancer (CRC) in IDA is low. Measurement of faecal haemoglobin by immunochemical techniques (FIT) is used to detect symptomatic patients. We studied FIT in patients with anaemia attending a gastroenterology clinic in Plymouth and looked at an artificial intelligence (AI) learning algorithm (ColonFlag™) in these patients, together with a cohort who had undergone colonoscopy for IDA in London. Of 592 patients referred on the basis of haemoglobin concentration, 21 (3.5%) had CRC. Using ColonFlag™, rather than haemoglobin concentration, in combination with symptoms, would have resulted in prioritisation of 304 patients for urgent referral rather than 592. One CRC would have been missed but might have been detected by FIT, which was not available in this case. In patients aged <55 years in whom the incidence of CRC is low, 15 rather than 109 patients would have been prioritised for urgent referral with no cancers missed. FIT has a high negative predictive value in IDA so its use may enable some patients to avoid investigation and AI learning may be a more useful trigger than haemoglobin concentration for urgent referral for colonoscopy.

13.
J Bone Joint Surg Am ; 101(4): 338-352, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30801373

RESUMO

BACKGROUND: The effectiveness of operative compared with nonoperative treatment at initial presentation (no prior fusion) for adult lumbar scoliosis has not, to our knowledge, been evaluated in controlled trials. The goals of this study were to evaluate the effects of operative and nonoperative treatment and to assess the benefits of these treatments to help treating physicians determine whether patients are better managed operatively or nonoperatively. METHODS: Patients with adult symptomatic lumbar scoliosis (aged 40 to 80 years, with a coronal Cobb angle measurement of ≥30° and an Oswestry Disability Index [ODI] score of ≥20 or Scoliosis Research Society [SRS]-22 score of ≤4.0) from 9 North American centers were enrolled in concurrent randomized or observational cohorts to evaluate operative versus nonoperative treatment. The primary outcomes were differences in the mean change from baseline in the SRS-22 subscore and ODI at 2-year follow-up. For the randomized cohort, the initial sample-size calculation estimated that 41 patients per group (82 total) would provide 80% power with alpha equal to 0.05, anticipating 10% loss to follow-up and 20% nonadherence in the nonoperative arm. However, an interim sample-size calculation estimated that 18 patients per group would be sufficient. RESULTS: Sixty-three patients were enrolled in the randomized cohort: 30 in the operative group and 33 in the nonoperative group. Two hundred and twenty-three patients were enrolled in the observational cohort: 112 in the operative group and 111 in the nonoperative group. The intention-to-treat analysis of the randomized cohort found that, at 2 years of follow-up, outcomes did not differ between the groups. Nonadherence was high in the randomized cohort (64% nonoperative-to-operative crossover). In the as-treated analysis of the randomized cohort, operative treatment was associated with greater improvement at the 2-year follow-up in the SRS-22 subscore (adjusted mean difference, 0.7 [95% confidence interval (CI), 0.5 to 1.0]) and in the ODI (adjusted mean difference, -16 [95% CI, -22 to -10]) (p < 0.001 for both). Surgery was also superior to nonoperative care in the observational cohort at 2 years after treatment on the basis of SRS-22 subscore and ODI outcomes (p < 0.001). In an overall responder analysis, more operative patients achieved improvement meeting or exceeding the minimal clinically important difference (MCID) in the SRS-22 subscore (85.7% versus 38.7%; p < 0.001) and the ODI (77.4% versus 38.3%; p < 0.001). Thirty-four revision surgeries were performed in 24 (14%) of the operative patients. CONCLUSIONS: On the basis of as-treated and MCID analyses, if a patient with adult symptomatic lumbar scoliosis is satisfied with current spine-related health, nonoperative treatment is advised, with the understanding that improvement is unlikely. If a patient is not satisfied with current spine health and expects improvement, surgery is preferred. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Vértebras Lombares , Escoliose/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Procedimentos Ortopédicos/estatística & dados numéricos , Resultado do Tratamento , Conduta Expectante/estatística & dados numéricos
14.
Arthritis Care Res (Hoboken) ; 71(9): 1178-1185, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30629338

RESUMO

OBJECTIVE: To evaluate rates of prescription opioid use among patients with presurgical knee, hip, and spine osteoarthritis (OA) and associations between use and sociodemographic and health status characteristics. METHODS: Participants were patients with presurgical, end-stage OA of the knee (n = 77), hip (n = 459), and spine (n = 168). Data were collected on current use of opioids and other pain medications, as well as measures of sociodemographic and health status variables and depression and pain (0-10 numeric rating scale). Rates of opioid use were calculated by sex, age, and surgical site. Multivariable logistic regression was used to examine associations between opioid use (sometimes/daily versus never) and other study variables. RESULTS: The mean age of participants was 65.6 years; 55.5% were women, 15% of patients reported "sometimes" using opioids, and 15% reported "daily use." Use of opioids was highest among patients with spine OA (40%) and similar among patients with knee and hip OA (28% and 30%, respectively). Younger women (ages <65 years) reported the greatest use of opioids overall, particularly among patients with spine OA. From multivariable logistic regression, greater likelihood of opioid use was significantly associated with spine OA (versus knee OA), obesity, being a current or former smoker, higher symptomatic joint count, greater depressive symptoms, greater pain, and current use of other prescription pain medication. CONCLUSION: Nearly one-third of patients with presurgical OA used prescription opioid medication. Given the questionable efficacy of opioids in OA and risk of adverse effects, higher opioid use among younger individuals and those with depressive symptoms is of concern and warrants further investigation.

15.
Spine J ; 19(3): 395-402, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30118851

RESUMO

BACKGROUND CONTEXT: Scoli-RISK-1 is a multicenter prospective cohort designed to study neurologic outcomes following complex adult spinal deformity (ASD). The effect of unilateral versus bilateral postoperative motor deficits on the likelihood of long-term recovery has not been previously studied in this population. PURPOSE: To evaluate whether bilateral postoperative neurologic deficits have a worse recovery than unilateral deficits. STUDY DESIGN: Secondary analysis of a prospective, multicenter, international cohort study. METHODS: In a cohort of 272 patients, neurologic decline was defined as deterioration of the American Spinal Injury Association Lower Extremity Motor Scores (LEMS) following surgery. Patients with lower extremity neurologic decline were grouped into unilateral and bilateral cohorts. Differences in demographics, surgical variables, and patient outcome measures between the two cohorts were analyzed. RESULTS: A total of 265 patients had LEMS completed at discharge. Unilateral decline was seen in 32 patients (12%), while 29 (11%) had bilateral symptoms. At 2 years, there was no significant difference in either median LEMS (unilateral 50.0, interquartile range [IQR] 47.5-50.0; bilateral 50.0, IQR 48.0-50.0, p=.939) or change in LEMS from baseline (unilateral 0.0, IQR -1.0 to 0.0; bilateral 0.0, IQR -1.0 to 0.0, p=.920). In both groups, approximately two-thirds of patients saw recovery to at least their preoperative baseline by 2 years postoperatively (unilateral n=15, 63%; bilateral n=14, 67%). The mean Scoliosis Research Society-22R (SRS-22R) score at 2 years was 3.7±0.6 versus 3.2±0.6 (p=.009) for unilateral and bilateral groups, respectively. CONCLUSIONS: The prognosis for neurologic recovery of new motor deficits following complex adult spinal deformity is similar with both unilateral and bilateral weaknesses. Despite similar rates of neurologic recovery, patient reported outcomes for those with bilateral motor decline measured by SRS-22R are worse at 2 years after surgery.


Assuntos
Extremidade Inferior/fisiopatologia , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Escoliose/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escoliose/patologia , Coluna Vertebral/fisiopatologia , Caminhada
16.
Drug Test Anal ; 11(3): 403-410, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30242972

RESUMO

CONTEXT: Sudaxine is a novel respiratory stimulant that increases ventilatory drive via NO+ -thiolate signaling and is under development for reversal of opioid-induced respiratory depression and other critical care indications. OBJECTIVE: This study investigates the pharmacokinetic characteristics after intravenous administration of Sudaxine by using a simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. MATERIALS AND METHODS: A sensitive LC-MS/MS method was validated to determine the concentration of Sudaxine in beagle dog plasma after intravenous administration of Sudaxine at (3, 10, 30, and 100 mg/kg). Blood samples (1 mL) were collected at designated time points and SDX concentration was measured for pharmacokinetic study. RESULTS: The calibration curve was linear within the range of 50-5,000 ng/mL with the lower limit of quantification at 50 ng/mL. The CTmax for all doses was reached at 10 minutes (Tmax ). Over the dose range studied, average concentration - time curves and systemic exposure (CTmax and AUC0-t ) increased to Sudaxine dose. The terminal half-life of Sudaxine in dogs ranged from 10 to 30 minutes and about 17.3 ± 1.0% of Sudaxine was protein-bound in dog plasma. DISCUSSION AND CONCLUSIONS: We developed a novel LC-MS/MS method of Sudaxine detection and quantification and determined its pharmacokinetic profiles after intravenous administration in canine subjects. Sudaxine followed first-order kinetics with rapid dose-dependent clearance rates and short half-life making it an ideal candidate for use in a critical care setting with intramuscular or IV administration.


Assuntos
Cromatografia Líquida/métodos , Cistina/análogos & derivados , Cistina/farmacologia , Fármacos do Sistema Respiratório/farmacocinética , Espectrometria de Massas em Tandem/métodos , Administração Intravenosa , Animais , Cistina/sangue , Cães , Meia-Vida , Masculino , Ensaio Radioligante , Fármacos do Sistema Respiratório/sangue , Fármacos do Sistema Respiratório/química
17.
Eur Spine J ; 28(1): 170-179, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30327909

RESUMO

PURPOSE: Accurate information regarding the expected complications of complex adult spinal deformity (ASD) is important for shared decision making and informed consent. The purpose of the present study was to investigate the rate and types of non-neurologic adverse events after complex ASD surgeries, and to identify risk factors that affect their occurrence. METHODS: The details and occurrence of all non-neurologic adverse events were reviewed in a prospective cohort of 272 patients after complex ASD surgical correction in a mulitcentre database of the Scoli-RISK-1 study with a planned follow-up of 2 years. Logistic regression analyses were used to identify potential risk factors for non-neurologic adverse events. RESULTS: Of the 272 patients, 184 experienced a total of 515 non-neurologic adverse events for an incidence of 67.6%. 121 (44.5%) patients suffered from more than one adverse event. The most frequent non-neurologic adverse events were surgically related (27.6%), of which implant failure and dural tear were most common. In the unadjusted analyses, significant factors for non-neurologic adverse events were age, previous spine surgery performed, number of documented non-neurologic comorbidities and ASA grade. On multivariable logistic regression analysis, previous spine surgery was the only independent risk factor for non-neurologic adverse events. CONCLUSIONS: The incidence of non-neurologic adverse events for patients undergoing corrective surgeries for ASD was 67.6%. Previous spinal surgery was the only independent risk factor predicting the occurrence of non-neurologic adverse events. These findings complement the earlier report of neurologic complications after ASD surgeries from the Scoli-RISK-1 study. These slides can be retrieved under Electronic Supplementary Material.

18.
Bioorg Med Chem Lett ; 29(4): 668-673, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30554956

RESUMO

Parkinson's disease is a relatively common neurological disorder with incidence increasing with age. Present treatments merely alleviate the symptoms and do not alter the course of the disease, thus identification of disease modifying therapies represents a significant unmet medical need. Mutations in the LRRK2 gene are risk-factors for developing PD and it has been hypothesized that the increased kinase activity of certain LRRK2 mutants are responsible for the damage of the dopaminergic neurons, thus LRRK2 inhibitors offer the potential to target an underlying cause of the disease. In this communication, we describe hit-to-lead medicinal chemistry program on a novel series of 5-azaindazoles. Compound 1, obtained from high-throughput screening was optimized to a highly potent, selective series of molecules with promising DMPK properties. Introduction of heterocycles at the 3-position were found to significantly increase the potency and kinase selectivity, whilst changes to the 4-chlorobenzyl group improved the physicochemical properties. Our series was licensed to a major pharmaceutical company for further development.

19.
Global Spine J ; 8(7): 690-697, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30443478

RESUMO

Study Design: A retrospective case-control study. Objectives: To determine factors influencing the ability to achieve coronal balance following spinal deformity surgery. Methods: Following institutional ethics approval, the radiographs of 47 patients treated for spinal deformity surgery with long fusions to the pelvis, were retrospectively reviewed. The postoperative measurements included coronal balance, L4 tilt, and L5 tilt, levels fused, apical vertebral translation and maximum Cobb angle. L4 and L5 tilt angles were measured between the superior endplate and the horizontal. Sagittal parameters including thoracic kyphosis, lumbar lordosis, pelvic incidence, and sagittal vertical axis were recorded. Coronal balance was defined as the distance between the central sacral line and the mid body of C7 being ≤40 mm. Surgical factors, including levels fused, use of iliac fixation with and without connectors, use of S2A1 screws, interbody devices, and osteotomies. Statistical tests were performed to determine factors that contribute to postoperative coronal imbalance. Results: Of the 47 patients reviewed, 32 were balanced after surgery and 14 were imbalanced. Coronal balance was 1.30 cm from center in the balanced group compared to 4.83 cm in the imbalanced group (P < .01). Both L4 and L5 tilt were statistically different between the groups. Gender and the use of transverse connectors differed between the groups but not statistically. Conclusions: In adult spinal deformity patients undergoing primary fusions to the pelvis, the ability to level the coronal tilt of L4 and L5 had the greatest impact on the ability to achieve coronal balance in this small series. A larger prospective series can help validate this important finding.

20.
Cochrane Database Syst Rev ; 10: CD004080, 2018 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-30353940

RESUMO

BACKGROUND: This is an update of the review last published in 2011. It focuses on early postoperative enteral nutrition after lower gastrointestinal surgery. Traditional management consisted of 'nil by mouth', where patients receive fluids followed by solids after bowel function has returned. Although several trials have reported lower incidence of infectious complications and faster wound healing upon early feeding, other trials have shown no effect. The immediate advantage of energy intake (carbohydrates, protein or fat) could enhance recovery with fewer complications, and this warrants a systematic evaluation. OBJECTIVES: To evaluate whether early commencement of postoperative enteral nutrition (within 24 hours), oral intake and any kind of tube feeding (gastric, duodenal or jejunal), compared with traditional management (delayed nutritional supply) is associated with a shorter length of hospital stay (LoS), fewer complications, mortality and adverse events in patients undergoing lower gastrointestinal surgery (distal to the ligament of Treitz). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library 2017, issue 10), Ovid MEDLINE (1950 to 15 November 2017), Ovid Embase (1974 to 15 November 2017). We also searched for ongoing trials in ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform (15 November 2017). We handsearched reference lists of identified studies and previous systematic reviews. SELECTION CRITERIA: We included randomised controlled trials (RCT) comparing early commencement of enteral nutrition (within 24 hours) with no feeding in adult participants undergoing lower gastrointestinal surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study quality using the Cochrane 'Risk of bias' tool tailored to this review and extracted data. Data analyses were conducted according to the Cochrane recommendations.We rated the quality of evidence according to GRADE.Primary outcomes were LoS and postoperative complications (wound infections, intraabdominal abscesses, anastomotic dehiscence, pneumonia).Secondary outcomes were: mortality, adverse events (nausea, vomiting), and quality of life (QoL).LoS was estimated using mean difference (MD (presented as mean +/- SD). For other outcomes we estimated the common risk ratio (RR) and calculated the associated 95% confidence intervals. For analysis, we used an inverse-variance random-effects model for the primary outcome (LoS) and Mantel-Haenszel random-effects models for the secondary outcomes. We also performed Trial Sequential Analyses (TSA). MAIN RESULTS: We identified 17 RCTs with 1437 participants undergoing lower gastrointestinal surgery. Most studies were at high or unclear risk of bias in two or more domains. Six studies were judged as having low risk of selection bias for random sequence generation and insufficient details were provided for judgement on allocation concealment in all 17 studies. With regards to performance and deception bias; 14 studies reported no attempt to blind participants and blinding of personnel was not discussed either. Only one study was judged as low risk of bias for blinding of outcome assessor. With regards to incomplete outcome data, three studies were judged to be at high risk because they had more than 10% difference in missing data between groups. For selective reporting, nine studies were judged as unclear as protocols were not provided and eight studies had issues with either missing data or incomplete reporting of results.LOS was reported in 16 studies (1346 participants). The mean LoS ranged from four days to 16 days in the early feeding groups and from 6.6 days to 23.5 days in the control groups. Mean difference (MD) in LoS was 1.95 (95% CI, -2.99 to -0.91, P < 0.001) days shorter in the early feeding group. However, there was substantial heterogeneity between included studies (I2 = 81, %, Chi2 = 78.98, P < 0.00001), thus the overall quality of evidence for LoS is low. These results were confirmed by the TSA showing that the cumulative Z-curve crossed the trial sequential monitoring boundary for benefit.We found no differences in the incidence of postoperative complications: wound infection (12 studies, 1181 participants, RR 0.99, 95%CI 0.64 to 1.52, very low-quality evidence), intraabdominal abscesses (6 studies, 554 participants, RR 1.00, 95%CI 0.26 to 3.80, low-quality evidence), anastomotic leakage/dehiscence (13 studies, 1232 participants, RR 0.78, 95%CI 0.38 to 1.61, low-quality evidence; number needed to treat for an additional beneficial outcome (NNTB) = 100), and pneumonia (10 studies, 954 participants, RR 0.88, 95%CI 0.32 to 2.42, low-quality evidence; NNTB = 333).Mortality was reported in 12 studies (1179 participants), and showed no between-group differences (RR = 0.56, 95%CI, 0.21 to 1.52, P = 0.26, I2 = 0%, Chi2 = 3.08, P = 0.96, low-quality evidence). The most commonly reported cause of death was anastomotic leakage, sepsis and acute myocardial infarction.Seven studies (613 participants) reported vomiting (RR 1.23, 95%CI, 0.96 to 1.58, P = 0.10, I2 = 0%, Chi2 = 4.98, P = 0.55, low-quality evidence; number needed to treat for an additional harmful outcome (NNTH) = 19), and two studies (118 participants) reported nausea (RR 0.95, 0.71 to 1.26, low-quality evidence). Four studies reported combined nausea and vomiting (RR 0.94, 95%CI 0.51 to 1.74, very low-quality evidence). One study reported QoL assessment; the scores did not differ between groups at 30 days after discharge on either QoL scale EORTC QLQ-C30 or EORTC QlQ-OV28 (very low-quality evidence). AUTHORS' CONCLUSIONS: This review suggests that early enteral feeding may lead to a reduced postoperative LoS, however cautious interpretation must be taken due to substantial heterogeneity and low-quality evidence. For all other outcomes (postoperative complications, mortality, adverse events, and QoL) the findings are inconclusive, and further trials are justified to enhance the understanding of early feeding for these. In this updated review, only a few additional studies have been included, and these were small and of poor quality.To improve the evidence, future trials should address quality issues and focus on clearly defining and measuring postoperative complications to allow for better comparison between studies. However due to the introduction of fast track protocols which already include an early feeding component, future trials may be challenging. A more feasible trial may be to investigate the effect of differing postoperative energy intake regimens on relevant outcomes.


Assuntos
Colo/cirurgia , Nutrição Enteral , Tempo de Internação , Complicações Pós-Operatórias/terapia , Reto/cirurgia , Ingestão de Alimentos , Humanos , Complicações Pós-Operatórias/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo
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