Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 127
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Ann Surg ; 279(6): 973-984, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38258573

RESUMO

OBJECTIVE: To evaluate the current evidence for surgical sabermetrics: digital methods of assessing surgical nontechnical skills and investigate the implications for enhancing surgical performance. BACKGROUND: Surgeons need high-quality, objective, and timely feedback to optimize performance and patient safety. Digital tools to assess nontechnical skills have the potential to reduce human bias and aid scalability. However, we do not fully understand which of the myriad of digital metrics of performance assessment have efficacy for surgeons. METHODS: A systematic review was conducted by searching PubMed, EMBASE, CINAHL, and PSYCINFO databases following PRISMA-ScR guidelines. MeSH terms and keywords included "Assessment," "Surgeons," and "Technology". Eligible studies included a digital assessment of nontechnical skills for surgeons, residents, and/or medical students within an operative context. RESULTS: From 19,229 articles screened, 81 articles met the inclusion criteria. The studies varied in surgical specialties, settings, and outcome measurements. A total of 122 distinct objective, digital metrics were utilized. Studies digitally measured at least 1 category of surgical nontechnical skill using a single (n=54) or multiple objective measures (n=27). The majority of studies utilized simulation (n=48) over live operative settings (n=32). Surgical Sabermetrics has been demonstrated to be beneficial in measuring cognitive load (n=57), situation awareness (n=24), communication (n=3), teamwork (n=13), and leadership (n=2). No studies measured intraoperative decision-making. CONCLUSIONS: The literature detailing the intersection between surgical data science and operative nontechnical skills is diverse and growing rapidly. Surgical Sabermetrics may provide a promising modifiable technique to achieve desirable outcomes for both the surgeon and the patient. This study identifies a diverse array of measurements possible with sensor devices and highlights research gaps, including the need for objective assessment of decision-making. Future studies may advance the integration of physiological sensors to provide a holistic assessment of surgical performance.


Assuntos
Competência Clínica , Salas Cirúrgicas , Humanos , Cirurgiões
2.
Crit Care Med ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38912884

RESUMO

OBJECTIVES: International guidelines recommend IV crystalloid as the primary fluid for sepsis resuscitation, with 5% human albumin solution (HAS) as the second line. However, it is unclear which fluid has superior clinical effectiveness. We conducted a trial to assess the feasibility of delivering a randomized controlled trial comparing balanced crystalloid against 5% HAS as sole early resuscitation fluid in patients with sepsis presenting to hospital. DESIGN: Multicenter, open, parallel-group randomized feasibility trial. SETTING: Emergency departments (EDs) in 15 U.K. National Health Service (NHS) hospitals. PATIENTS: Adult patients with sepsis and a National Early Warning Score 2 greater than or equal to five requiring IV fluids withing one hour of randomization. INTERVENTIONS: IV fluid resuscitation with balanced crystalloid or 5% HAS for the first 6 hours following randomization. MEASUREMENTS AND MAIN RESULTS: Primary feasibility outcomes were recruitment rate and 30-day mortality. We successfully recruited 301 participants over 12 months. Mean (sd) age was 69 years (± 16 yr), and 151 (50%) were male. From 1303 participants screened; 502 participants were potentially eligible and 300 randomized to receive trial intervention with greater than 95% of participants receiving the intervention. The median number of participants per site was 19 (range, 1-63). Thirty-day mortality was 17.9% (n = 53). Thirty-one participants died (21.1%) within 30 days in the 5% HAS arm, compared with 22 participants (14.8%) in the crystalloid arm (adjusted odds ratio, 1.50; 95% CIs, 0.84-2.83). CONCLUSIONS: Our results suggest it is feasible to recruit critically ill patients to a fluid resuscitation trial in U.K. EDs using 5% HAS as a primary resuscitation fluid. There was lower mortality in the balanced crystalloid arm. Given these findings, a definitive trial is likely to be deliverable, but the point estimates suggest such a trial would be unlikely to demonstrate a significant benefit from using 5% HAS as a primary resuscitation fluid in sepsis.

3.
Br J Surg ; 111(4)2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38593042

RESUMO

BACKGROUND: Features of cancer cachexia adversely influence patient outcomes, yet few currently inform clinical decision-making. This study assessed the value of the cachexia index (CXI), a novel prognostic marker, in patients for whom neoadjuvant chemotherapy and surgery for oesophagogastric cancer is planned. METHODS: Consecutive patients newly diagnosed with locally advanced (T3-4 or at least N1) oesophagogastric cancer between 1 January 2010 and 31 December 2015 were identified through the West of Scotland and South-East Scotland Cancer Networks. CXI was calculated as (L3 skeletal muscle index) × (serum albumin)/(neutrophil lymphocyte ratio). Sex-stratified cut-off values were determined based on the area under the curve (AUC), and patients were divided into groups with low or normal CXI. Primary outcomes were disease progression during neoadjuvant chemotherapy and overall survival (at least 5 years of follow-up). RESULTS: Overall, 385 patients (72% men, median age 66 years) were treated with neoadjuvant chemotherapy for oesophageal (274) or gastric (111) cancer across the study interval. Although patients with a low CXI (men: CXI below 52 (AUC 0.707); women: CXI below 41 (AUC 0.759)) were older with more co-morbidity, disease characteristics were comparable to those in patients with a normal CXI. Rates of disease progression during neoadjuvant chemotherapy, leading to inoperability, were higher in patients with a low CXI (28 versus 12%; adjusted OR 3.07, 95% c.i. 1.67 to 5.64; P < 0.001). Low CXI was associated with worsened postoperative mortality (P = 0.019) and decreased overall survival (median 14.9 versus 56.9 months; adjusted HR 1.85, 1.42 to 2.42; P < 0.001). CONCLUSION: CXI is associated with disease progression, worse postoperative mortality, and overall survival, and could improve prognostication and decision-making in patients with locally advanced oesophagogastric cancer.


Assuntos
Neoplasias Gástricas , Masculino , Humanos , Feminino , Idoso , Neoplasias Gástricas/complicações , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/tratamento farmacológico , Caquexia/etiologia , Linfócitos , Progressão da Doença , Estudos de Coortes , Prognóstico , Estudos Retrospectivos
4.
Curr Opin Clin Nutr Metab Care ; 27(5): 393-396, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39110108

RESUMO

PURPOSE OF REVIEW: The following article examines the rationale for an inflammation-first approach for diagnosing cachexia and how the current Global Leadership Initiative on Malnutrition (GLIM) framework may be adapted to facilitate this. RECENT FINDINGS: Recently, the GLIM have published guidance on the measurement of inflammation in the context of cachexia, advocating that C-reactive protein (CRP) should be utilized for quantification. The inclusion of a systemic inflammatory biomarker for the diagnosis of cachexia questions whether it may be more aptly considered a systemic inflammatory syndrome. SUMMARY: The current consensus of the GLIM is that cachexia is 'disease-related malnutrition with inflammation'. In line with this definition, the GLIM proposed a two-step diagnostic framework: screening for malnutrition using validated screening tools and then confirming the presence of disease-related malnutrition with phenotypic (nonvolitional weight loss, low BMI, and reduced muscle mass) and aetiologic criterion reduced food intake/assimilation, and inflammation or disease burden). The GLIM are to be commended for guidance on the measurement of systemic inflammation in their current proposal, given the relative importance to clinical outcomes in patients with cancer. However, the use of CRP is somewhat rudimentary and contrasts other cancer cachexia guidelines and contemporary clinical cancer research.


Assuntos
Biomarcadores , Proteína C-Reativa , Caquexia , Inflamação , Desnutrição , Neoplasias , Humanos , Caquexia/diagnóstico , Caquexia/etiologia , Inflamação/diagnóstico , Desnutrição/diagnóstico , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Biomarcadores/sangue , Neoplasias/complicações , Avaliação Nutricional , Liderança
5.
Eur Radiol ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38526750

RESUMO

BACKGROUND: Personalising management of primary oesophageal adenocarcinoma requires better risk stratification. Lack of independent validation of proposed imaging biomarkers has hampered clinical translation. We aimed to prospectively validate previously identified prognostic grey-level co-occurrence matrix (GLCM) CT features for 3-year overall survival. METHODS: Following ethical approval, clinical and contrast-enhanced CT data were acquired from participants from five institutions. Data from three institutions were used for training and two for testing. Survival classifiers were modelled on prespecified variables ('Clinical' model: age, clinical T-stage, clinical N-stage; 'ClinVol' model: clinical features + CT tumour volume; 'ClinRad' model: ClinVol features + GLCM_Correlation and GLCM_Contrast). To reflect current clinical practice, baseline stage was also modelled as a univariate predictor ('Stage'). Discrimination was assessed by area under the receiver operating curve (AUC) analysis; calibration by Brier scores; and clinical relevance by thresholding risk scores to achieve 90% sensitivity for 3-year mortality. RESULTS: A total of 162 participants were included (144 male; median 67 years [IQR 59, 72]; training, 95 participants; testing, 67 participants). Median survival was 998 days [IQR 486, 1594]. The ClinRad model yielded the greatest test discrimination (AUC, 0.68 [95% CI 0.54, 0.81]) that outperformed Stage (ΔAUC, 0.12 [95% CI 0.01, 0.23]; p = .04). The Clinical and ClinVol models yielded comparable test discrimination (AUC, 0.66 [95% CI 0.51, 0.80] vs. 0.65 [95% CI 0.50, 0.79]; p > .05). Test sensitivity of 90% was achieved by ClinRad and Stage models only. CONCLUSIONS: Compared to Stage, multivariable models of prespecified clinical and radiomic variables yielded improved prediction of 3-year overall survival. CLINICAL RELEVANCE STATEMENT: Previously identified radiomic features are prognostic but may not substantially improve risk stratification on their own. KEY POINTS: • Better risk stratification is needed in primary oesophageal cancer to personalise management. • Previously identified CT features-GLCM_Correlation and GLCM_Contrast-contain incremental prognostic information to age and clinical stage. • Compared to staging, multivariable clinicoradiomic models improve discrimination of 3-year overall survival.

6.
J Surg Res ; 302: 222-231, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39106733

RESUMO

INTRODUCTION: Cognitive load (CogL) is increasingly recognized as an important resource underlying operative performance. Current innovations in surgery aim to develop objective performance metrics via physiological monitoring from wearable digital sensors. Surgeons have access to consumer technology that could measure CogL but need guidance regarding device selection and implementation. To realize the benefits of surgical performance improvement these methods must be feasible, incorporating human factors usability and design principles. This paper aims to evaluate the feasibility of using wearable sensors to assess CogL, identify the benefits and challenges of implementing devices, and develop guidance for surgeons planning to implement wearable devices in their research or practice. METHODS: We examined the feasibility of wearable sensors from a series of empirical studies that measured aspects of clinical performance relating to CogL. Across four studies, 84 participants and five sensors were involved in the following clinical settings: (i) real intraoperative surgery; (ii) simulated laparoscopic surgery; and (iii) medical team performance outside the hospital. RESULTS: Wearable devices worn on the wrist and chest were found to be comfortable. After a learning curve, electrodermal activity data were easily and reliably collected. Devices using photoplethysmography to determine heart rate variability were significantly limited by movement artifact. There was variable success with electroencephalography devices regarding connectivity, comfort, and usability. CONCLUSIONS: It is feasible to use wearable sensors across various clinical settings, including surgery. There are some limitations, and their implementation is context and device dependent. To scale sensor use in clinical research, surgeons must embrace human factors principles to optimize wearability, usability, reliability, and data security.

7.
Br J Surg ; 110(12): 1703-1711, 2023 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-37527401

RESUMO

BACKGROUND: Cancer cachexia is not purely an end-stage phenomenon and can influence the outcomes of patients with potentially curable disease. This review examines the effect of pre-treatment cachexia on overall survival, in patients undergoing surgical resection of oesophagogastric cancer. METHODS: A systematic literature search of MEDLINE, EMBASE and Cochrane Library databases was conducted, from January 2000 to May 2022, to identify studies reporting the influence of cachexia on patients undergoing an oesophagogastric resection for cancer with curative intent. Meta-analyses of the primary (overall survival) and secondary (disease-free survival and postoperative mortality) outcomes were performed using random-effects modelling. Meta-regression was used to examine disease stage as a potential confounder. RESULTS: Ten non-randomized studies, comprising 7186 patients, were eligible for inclusion. The prevalence of pre-treatment cachexia was 35 per cent (95 per cent c.i.: 24-47 per cent). Pooled adjusted hazard ratios showed that cachexia was adversely associated with overall survival (HR 1.46, 95 per cent c.i.: 1.31-1.60, P < 0.001). Meta-analysis of proportions identified decreased overall survival at 1-, 3- and 5-years in cachectic cohorts. Pre-treatment cachexia was not a predictor of disease-free survival and further data are required to establish its influence on postoperative mortality. The proportion of patients with stage III/IV disease was a significant moderator of between-study heterogeneity. Cachexia may have a greater influence on overall survival in studies where more patients have a locally advanced malignancy. CONCLUSION: Pre-treatment cachexia adversely influences overall survival following resection of an oesophagogastric malignancy.


Assuntos
Caquexia , Neoplasias , Humanos , Prognóstico , Caquexia/etiologia , Intervalo Livre de Doença
8.
Curr Treat Options Oncol ; 23(12): 1732-1747, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36269458

RESUMO

OPINION STATEMENT: Considerable advances in the investigation and management of oesophagogastric cancer have occurred over the last few decades. While the historically dismal prognosis associated with these diseases has improved, outcomes remain very poor. Cancer cachexia is an often neglected, yet critical, factor for this patient group. There is a persuasive argument that a lack of assessment and treatment of cachexia has limited progress in oesophagogastric cancer care. In the curative setting, the stage of the host (based on factors such as body composition, function, and inflammatory status), alongside tumour stage, has the potential to influence treatment efficacy. Phenotypical features of cachexia may decrease the survival benefit of (peri-operative) chemoradiotherapy, immunotherapy, or surgical resection in patients with potentially curative malignancy. Most patients with oesophagogastric cancer unfortunately present with disease which is not amenable, or is unlikely to respond, to these treatments. In the palliative setting, host factors can similarly impair results from systemic anti-cancer therapies, cause adverse symptoms, and reduce quality of life. To optimise treatment pathways and enhance patient outcomes, we must utilise this information during clinical decision-making. As our understanding of the genesis of cancer cachexia improves and more therapeutic options, ranging from basic (e.g. exercise and nutrition) to targeted (e.g. anti-IL1 α and anti-GDF-15), become available, there can be grounds for optimism. Cachexia can change from a hitherto neglected condition to an integral part of the oesophagogastric cancer treatment pathway.


Assuntos
Neoplasias Gastrointestinais , Neoplasias , Humanos , Caquexia/diagnóstico , Caquexia/etiologia , Caquexia/terapia , Qualidade de Vida , Neoplasias/complicações , Neoplasias Gastrointestinais/complicações , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/terapia , Prognóstico , Resultado do Tratamento
9.
Molecules ; 27(17)2022 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-36080280

RESUMO

Skeletal muscle homeostasis is essential for the maintenance of a healthy and active lifestyle. Imbalance in muscle homeostasis has significant consequences such as atrophy, loss of muscle mass, and progressive loss of functions. Aging-related muscle wasting, sarcopenia, and atrophy as a consequence of disease, such as cachexia, reduce the quality of life, increase morbidity and result in an overall poor prognosis. Investigating the muscle proteome related to muscle atrophy diseases has a great potential for diagnostic medicine to identify (i) potential protein biomarkers, and (ii) biological processes and functions common or unique to muscle wasting, cachexia, sarcopenia, and aging alone. We conducted a meta-analysis using gene ontology (GO) analysis of 24 human proteomic studies using tissue samples (skeletal muscle and adipose biopsies) and/or biofluids (serum, plasma, urine). Whilst there were few similarities in protein directionality across studies, biological processes common to conditions were identified. Here we demonstrate that the GO analysis of published human proteomics data can identify processes not revealed by single studies. We recommend the integration of proteomics data from tissue samples and biofluids to yield a comprehensive overview of the human skeletal muscle proteome. This will facilitate the identification of biomarkers and potential pathways of muscle-wasting conditions for use in clinics.


Assuntos
Caquexia , Sarcopenia , Biomarcadores/metabolismo , Ontologia Genética , Humanos , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Proteoma/genética , Proteoma/metabolismo , Proteômica , Qualidade de Vida , Sarcopenia/metabolismo
10.
Pain Pract ; 22(2): 210-221, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34634169

RESUMO

BACKGROUND: Knee pain is a major source of distress and disability, with pain progression highly variable between individuals. Previous studies defining pain trajectories have all used a single measure of pain, and these differ across studies. Different measures reflect diverse pain mechanisms. To ascertain the clinical utility of pain trajectories, we explored associations between opioid and non-steroidal anti-inflammatory drug (NSAID) use. METHODS: We model pain trajectories using two measures-Intermittent and Constant Osteoarthritis Pain (ICOAP) and the painDETECT, in 2141 participants, across 3 waves (the baseline, 1- and 3-year assessments) of the Knee Pain In the Community (KPIC) cohort. RESULTS: Latent class growth analysis identified six trajectories using ICOAP subscales (High-Stable, Low-Stable, Moderate Worsening, Moderate Recovering, Worsening, and Recovering) and four trajectories using painDETECT (High-stable, Low-stable, Moderate Worsening, and Moderate Recovering). There was a high degree of correspondence between people assigned to pain trajectories between ICOAP intermittent and constant subscales, but less so using painDETECT. Opioid use was associated with ICOAP trajectories only (e.g., High-Stable and Worsening intermittent ICOAP trajectories) and in women. CONCLUSION: Different measures of pain produce different patterns of pain progression and these are differentially related to medication use. Opioid use is linked to trajectories of pain based on the impact of pain on behavior and not pain symptoms. Thus, managing pain's behavioral impact is more central to understanding opioid use than managing pain symptoms. These findings support more in-depth questioning about the type of pain and its progression in clinical practice.


Assuntos
Dor Crônica , Osteoartrite do Joelho , Analgésicos Opioides/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Dor Crônica/tratamento farmacológico , Feminino , Humanos , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/tratamento farmacológico , Medição da Dor
11.
Colorectal Dis ; 23(5): 1233-1238, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33544433

RESUMO

BACKGROUND: The Versius surgical system, from CMR Surgical, is the first UK-based robotic platform to become commercially available. This is a prospective series in accordance with the IDEAL development framework for surgical innovation reporting the clinical implementation and initial experience using this robotic platform. METHODS: Patients with colorectal cancer were included. Exclusion criteria included T4 tumours, ultra-low rectal cancer and severe comorbidity (American Society of Anesthesiologists grade ≥ 3). Institutional ethical approval was obtained, and patients were counselled preoperatively with informed consent. Patients underwent colorectal resection using the Versius surgical system. Procedures were anticipated as hybrid operations (laparoscopic/robotic) consistent with a proof of concept/technical feasibility study. RESULTS: Main outcome measures included operative time, complication rates and pathological results. Thirty-two patients (15 men) underwent colorectal cancer resections. The mean age was 68 years (27-85 years). Estimated blood loss was 150 ml; range <100 to <500 ml. For right hemicolectomy, the average operative time was 221 min (183-323 min). The average console time was 111 min (64-213 min). For robotic anterior resection, the total operative time was on average 319 min (222-408 min) with an average console time of 204 min (85-242 min). Eight patients experienced Grade II morbidities (22%) with no serious morbidities and no mortalities. Mean return to bowel function was 2.9 days (1-6 days). The average length of stay was 5.3 days with a median of 4 days (2-20 days). All resections were R0 with an average lymph node yield of 20 nodes (8-46 nodes). CONCLUSION: Our initial experience with Versius demonstrates its safe adoption and implementation for colorectal resections.


Assuntos
Laparoscopia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Idoso , Colectomia , Humanos , Masculino , Estudos Prospectivos , Neoplasias Retais/cirurgia , Resultado do Tratamento
12.
Psychol Med ; 50(10): 1663-1671, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31387661

RESUMO

BACKGROUND: Pain and depression are common in the population and co-morbid with each other. Both are predictive of one another and are also associated with cognitive function; people who are in greater pain and more depressed respectively perform less well on tests of cognitive function. It has been argued that pain might cause deterioration in cognitive function, whereas better cognitive function earlier in life might be a protective factor against the emergence of disease. When looking at the dynamic relationship between these in chronic diseases, studying samples that already have advanced disease progression often confounds this relationship. METHODS: Using data from waves 1 to 3 of the English Longitudinal Study of Ageing (ELSA) (n = 516), we examined the interplay between pain, cognitive function and depression in a subsample of respondents reporting a diagnosis of arthritis at wave 2 of the ELSA using cross-lagged panel models. RESULTS: The models showed that pain, cognitive function and depression at wave 1, prior to diagnosis, predict pain at wave 2, and that pain at wave 1 predicts depression at wave 2. Pain and depression at wave 2 predict cognitive function at wave 3. CONCLUSIONS: The results indicate that better cognitive function might be protective against the emergence of pain prior to an arthritis diagnosis, but cognitive function is subsequently impaired by pain and depression. Furthermore, higher depression predicts lower cognitive function, but not vice versa. This is discussed in the context of the emerging importance of inflammation in depression.


Assuntos
Envelhecimento , Artrite/complicações , Depressão/epidemiologia , Modelos Psicológicos , Dor/epidemiologia , Idoso , Artrite/diagnóstico , Cognição , Comorbidade , Feminino , Humanos , Individualidade , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Reino Unido/epidemiologia
17.
Curr Opin Clin Nutr Metab Care ; 22(3): 196-204, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30946052

RESUMO

PURPOSE OF REVIEW: Cancer-associated muscle wasting affects many patients and leads to reduced patient function, decreased quality of life and poor responses to surgical and oncological treatments. Despite advancements in the understanding of its pathophysiology, no current treatment or accepted strategy for successful management exists. In this review, we provide an update on potential novel therapeutic targets in cancer cachexia. RECENT FINDINGS: Recent research has focused on molecular mechanisms underlying cancer-associated muscle wasting, allowing identification of potential therapeutic targets and the development of several promising drugs. However, due to the multifactorial and patient-specific pathogenesis of cachexia, the demonstration of a measurable and meaningful clinical effect in randomized controlled trials has proven difficult. Potential novel targets such as circulating macrophage inhibitory cytokine 1/growth differentiation factor 15 and ZRT/IRT-like protein 14 have shown relevance in animal models, but their therapeutic manipulation has yet to be translated to patients. Increasing evidence has suggested that a single therapy may not be successful and a targeted, multimodal approach is required. SUMMARY: The management of cancer-associated muscle wasting is complex. Future clinical trials should focus on early multimodal therapeutic interventions involving targeted therapies, with careful deliberation of chosen nutritional and functional outcomes.


Assuntos
Caquexia , Neoplasias/complicações , Síndrome de Emaciação , Caquexia/etiologia , Caquexia/prevenção & controle , Caquexia/terapia , Humanos , Medicina Molecular , Síndrome de Emaciação/etiologia , Síndrome de Emaciação/prevenção & controle , Síndrome de Emaciação/terapia
18.
Mol Psychiatry ; 23(5): 1157-1168, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28894301

RESUMO

Increased motivation for highly rewarding food is a major contributing factor to obesity. Most of the literature focuses on the mesolimbic nuclei as the core of reward behavior regulation. However, the lateral hypothalamus (LH) is also a key reward-control locus in the brain. Here we hypothesize that manipulating glucagon-like peptide-1 receptor (GLP-1R) activity selectively in the LH can profoundly affect food reward behavior, ultimately leading to obesity. Progressive ratio operant responding for sucrose was examined in male and female rats, following GLP-1R activation and pharmacological or genetic GLP-1R blockade in the LH. Ingestive behavior and metabolic parameters, as well as molecular and efferent targets, of the LH GLP-1R activation were also evaluated. Food motivation was reduced by activation of LH GLP-1R. Conversely, acute pharmacological blockade of LH GLP-1R increased food motivation but only in male rats. GLP-1R activation also induced a robust reduction in food intake and body weight. Chronic knockdown of LH GLP-1R induced by intraparenchymal delivery of an adeno-associated virus-short hairpin RNA construct was sufficient to markedly and persistently elevate ingestive behavior and body weight and ultimately resulted in a doubling of fat mass in males and females. Interestingly, increased food reinforcement was again found only in males. Our data identify the LH GLP-1R as an indispensable element of normal food reinforcement, food intake and body weight regulation. These findings also show, for we believe the first time, that brain GLP-1R manipulation can result in a robust and chronic body weight gain. The broader implications of these findings are that the LH differs between females and males in its ability to control motivated and ingestive behaviors.


Assuntos
Comportamento Alimentar/fisiologia , Receptor do Peptídeo Semelhante ao Glucagon 1/fisiologia , Região Hipotalâmica Lateral/metabolismo , Animais , Peso Corporal , Condicionamento Operante/efeitos dos fármacos , Dieta Hiperlipídica , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Hipotálamo/metabolismo , Masculino , Motivação/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Reforço Psicológico , Recompensa
19.
Support Care Cancer ; 27(7): 2371-2384, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30944994

RESUMO

PURPOSE: The optimal components for rehabilitation in patients with incurable cancer are unclear. However, principles of exercise and nutrition-based interventions used in cancer cachexia may be applied usefully to this population of cancer patients. This systematic review examines current evidence for rehabilitation combining exercise and nutritional support in patients with incurable cancer. METHODS: MEDLINE, EMBASE and Cochrane databases were searched. Eligible studies included patients with incurable cancer and rehabilitation programmes combining exercise and nutritional interventions. Studies of cancer survivors, curative treatments, reviews, case note reviews, protocols and abstracts were excluded. Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria were applied to patient-important outcomes. RESULTS: Of the 2424 search results, 67 abstracts were reviewed and 24 full texts examined. Eight studies (n = 685) were included comprising two randomised control trials, three prospective, one exploratory and two secondary analyses. All examined multi-modal outpatient programmes. GRADE analysis revealed moderate evidence (B) for improvements in depression and physical endurance, low-quality evidence (C) for quality of life and fatigue and very low-quality evidence (D) for overall function and nutritional status. CONCLUSION: There are limited data for multi-modal rehabilitation programmes combining exercise and nutritional interventions in patients with incurable cancer. However, studies to date report improvements in multiple domains, most notably physical endurance and depression scores. This supports the concept that multi-modal rehabilitation incorporating principles of cachexia management may be appropriate for the wider group of patients with incurable cancer. Further, high-quality studies are needed to define the optimal approach and outcome measures.


Assuntos
Terapia por Exercício/métodos , Neoplasias/reabilitação , Neoplasias/terapia , Terapia Nutricional/métodos , Qualidade de Vida/psicologia , Humanos , Pacientes Ambulatoriais , Estudos Prospectivos
20.
World J Surg ; 43(7): 1661-1668, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30788536

RESUMO

INTRODUCTION: Prehabilitation prior to major surgery has increased in popularity over recent years and aims to improve pre-operative conditioning of patients to improve post-operative outcomes. The beneficial effect of such protocols is not well established with conflicting results reported. This review aimed to assess the effect of prehabilitation on post-operative outcome after major abdominal surgery. METHODS: EMBASE, Medline, PubMed and the Cochrane database were searched in August 2018 for trials comparing outcomes of patients undergoing prehabilitation involving prescribed respiratory and exercise interventions prior to abdominal surgery. Study characteristics, overall and pulmonary morbidity, length of stay (LOS), maximum inspiratory pressure and change in six-minute walking test (6MWT) distance were obtained. The primary outcome was post-operative overall morbidity within 30 days. Dichotomous data were analysed by fixed or random effects odds ratio. Continuous data were analysed with weighted mean difference. RESULTS: Fifteen RCTs were included in the analysis with 457 prehabilitation patients and 450 control group patients. A significant reduction in overall (OR 0.63 95% CI 0.46-0.87 I2 34%, p = 0.005) and pulmonary morbidity (OR 0.4 95% CI 0.23-0.68, I2 = 0%, p = 0.0007) was observed in the prehabilitation group. No significant difference in LOS (WMD -2.39 95% CI -4.86 to 0.08 I2 = 0%, p = 0.06) or change in 6MWT distance (WMD 9.06 95% CI -35.68, 53.81 I2 = 88%, p = 0.69) was observed. CONCLUSIONS: Prehabilitation can reduce overall and pulmonary morbidity following surgery and could be utilised routinely. The precise protocol of prehabilitation has not been completely established. Further work is required to tailor optimal prehabilitation protocols for specific operative procedures.


Assuntos
Abdome/cirurgia , Complicações Pós-Operatórias/etiologia , Cuidados Pré-Operatórios/métodos , Humanos , Tempo de Internação , Condicionamento Físico Humano , Período Pós-Operatório , Ensaios Clínicos Controlados Aleatórios como Assunto , Teste de Caminhada
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA