Ultra-fast track extubation protocol following cardiovascular surgery: Predictors of failure and outcomes.

OBJECTIVES: Identifying independent predictor factors of failure of ultra-fast track (UFT) extubation and to compare in-hospital outcomes with UFT extubation versus fast track (FT) extubation after cardiovascular surgery in adults. MATERIAL AND METHODS: Retrospective analysis of 1498 consecutive patients aged over 18 years-old undergoing cardiovascular surgery at a single institution. Between December 2014 and December 2016, FT extubation was used (N = 713) while, between December 2016 and December 2018, all patients were preoperatively considered suitable for UFT extubation (N = 785). In this instance, a standardized anaesthetic protocol was applied in all cases. The decision to not extubate in the operating room (OR) was based on intraoperative haemodynamic and ventilation. RESULTS: Extubation in the OR was possible in 699 (89%) patients. Significant independent predictors factors of UFT extubation failure were: preoperative NYHA class III-IV, myocardial infarction within two days prior to surgery, preoperative intra-aortic balloon counterpulsation, urgent/emergent surgery, intraoperative transfusion of platelets and intraoperative inotropic and vasopressor support. UFT extubation was associated with lower rates of cardiovascular complications such as congestive cardiac insufficiency (OR: 1,57; 95% CI: 1,13-2,19; p = 0,008) and new-onset postoperatory atrial fibrillation (OR: 1,40; 95% CI: 1,06-1,86; p = 0,020). Patient extubated in the OR presented lower risk of overall complications, shorter intensive care unit stay and higher short-term survival, although, no statistically significance was found when performing the multivariate adjustment. CONCLUSIONS: A routine immediate extubation in the OR following adult cardiovascular surgery is a feasible and safe practice, associated with low cardiovascular morbidity.

Influence of nitric oxide signaling mechanisms in cancer.

Nitric oxide (NO) is a molecule with multiple biological functions that is involved in various pathophysiological processes such as neurotransmission and blood vessel relaxation as well as the endocrine system, immune system, growth factors, and cancer. However, in the carcinogenesis process, it has a dual behavior; at low doses, NO regulates homeostatic functions, while at high concentrations, it promotes tissue damage or acts as an agent for immune defense against microorganisms. Thus, its participation in the carcinogenic process is controversial. Cancer is a multifactorial disease that presents complex behavior. A better understanding of the molecular mechanisms associated with the initiation, promotion, and progression of neoplastic processes is required. Some hypotheses have been proposed regarding the influence of NO in activating oncogenic pathways that trigger carcinogenic processes, because NO might regulate some signaling pathways thought to promote cancer development and more aggressive tumor growth. Additionally, NO inhibits apoptosis of tumor cells, together with the deregulation of proteins that are involved in tissue homeostasis, promoting spreading to other organs and initiating metastatic processes. This paper describes the signaling pathways that are associated with cancer, and how the concentration of NO can serve a beneficial or pathological function in the initiation and promotion of neoplastic events.

Radical Resection in Entero-Pancreatic Neuroendocrine Tumors: Recurrence-Free Survival Rate and Definition of a Risk Score for Recurrence.

BACKGROUND: Surgery with radical intent is the only potentially curative option for entero-pancreatic neuroendocrine tumors (EP-NETs) but many patients develop recurrence even after many years. The subset of patients at high risk of disease recurrence has not been clearly defined to date. OBJECTIVE: The aim of this retrospective study was to define, in a series of completely resected EP-NETs, the recurrence-free survival (RFS) rate and a risk score for disease recurrence. PATIENTS AND METHODS: This was a multicenter retrospective analysis of sporadic pancreatic NETs (PanNETs) or small intestine NETs (SiNETs) [G1/G2] that underwent R0/R1 surgery (years 2000-2016) with at least a 24-month follow-up. Survival analysis was performed using the Kaplan-Meier method and risk factor analysis was performed using the Cox regression model. RESULTS: Overall, 441 patients (224 PanNETs and 217 SiNETs) were included, with a median Ki67 of 2% in tumor tissue and 8.2% stage IV disease. Median RFS was 101 months (5-year rate 67.9%). The derived prognostic score defined by multivariable analysis included prognostic parameters, such as TNM stage, lymph node ratio, margin status, and grading. The score distinguished three risk categories with a significantly different RFS (p < 0.01). CONCLUSIONS: Approximately 30% of patients with EP-NETs recurred within 5 years after radical surgery. Risk factors for recurrence were disease stage, lymph node ratio, margin status, and grading. The definition of risk categories may help in selecting patients who might benefit from adjuvant treatments and more intensive follow-up programs.

Plasma Tie2 trajectories identify vascular response criteria for VEGF inhibitors across advanced biliary tract, colorectal and ovarian cancers.

BACKGROUND: Vascular endothelial growth factor inhibitors (VEGFi) are compromised by a lack of validated biomarkers. Previously we showed that changes in the concentration of plasma Tie2 (pTie2) was a response biomarker for bevacizumab. Here, we investigated whether pTie2 can predict response and progression cross-tumour for generic VEGFi treatment. PATIENTS AND METHODS: Patients (n = 124) with advanced biliary tract cancer (ABC) received cisplatin/gemcitabine with cediranib or placebo (ABC-03 trial). Concentrations of pTie2 were measured longitudinally from before treatment until disease progression. Data from patients with ovarian cancer (n = 92, ICON7 trial) and patients with colorectal cancer (CRC) (n = 70, Travastin trial) were also included. RESULTS: Cediranib-treated ABC patients were deconvoluted into distinct groups where in one group pTie2 trajectories resembled those seen in placebo-treated patients and in another pTie2 significantly reduced (t-test P = 2.7 × 10-14). Using the 95% confidence interval for these two groups, we defined a vascular complete response (vCR) as a 24% reduction in pTie2 within 9 weeks; vascular no response (vNR) as a 7% increase in pTie2, and a vascular partial response (between these limits). vCR cediranib-treated patients had significantly improved progression-free survival (8.8 versus 7.5 months, restricted mean ratio 0.73, P = 0.012) and overall survival (18.8 versus 12.1 months, hazard ratio 0.49, P = 0.02). By integrating data across ovarian cancer, CRC and ABC, we show that (i) patients with vNR do not benefit from VEGFi and (ii) Tie2-defined vascular progression occurs sufficiently in advance of radiological progressive disease that changes in treatment could be offered to prevent clinical deterioration. CONCLUSION: pTie2 is the first cross-tumour, generic VEGFi, vascular response biomarker to guide optimum use of VEGFi in clinical practice.

ESMO Congress 2021: highlights from the EORTC gastrointestinal tract cancer group's perspective.

There has been no major change of practice in gastrointestinal oncology at the European Society for Medical Oncology (ESMO) symposium 2021, but confirmation that immunotherapy in combination with chemotherapy has become standard of care in several indications. The European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Track Cancer Group has selected important phase II and III trials presented during the symposium across all gastrointestinal cancers as well as early reports on new drugs or new combinations that may change practice in the future.

Machine Learning for Auto-Segmentation in Radiotherapy Planning.

Manual segmentation of target structures and organs at risk is a crucial step in the radiotherapy workflow. It has the disadvantages that it can require several hours of clinician time per patient and is prone to inter- and intra-observer variability. Automatic segmentation (auto-segmentation), using computer algorithms, seeks to address these issues. Advances in machine learning and computer vision have led to the development of methods for accurate and efficient auto-segmentation. This review surveys auto-segmentation techniques and applications in radiotherapy planning. It provides an overview of traditional approaches to auto-segmentation, including intensity analysis, shape modelling and atlas-based methods. The focus, though, is on uses of machine learning and deep learning, including convolutional neural networks. Finally, the future of machine-learning-driven auto-segmentation in clinical settings is considered, and the barriers that must be overcome for it to be widely accepted into routine practice are highlighted.

Setup of multidisciplinary team discussions for patients with cholangiocarcinoma: current practice and recommendations from the European Network for the Study of Cholangiocarcinoma (ENS-CCA).

BACKGROUND: Cholangiocarcinomas (CCAs) are a rare group of malignancies characterized by dismal prognosis. There are currently no standardized guidelines for multidisciplinary teams (MDTs) in CCAs. MATERIAL AND METHODS: An online survey was built with the aim of defining the current practice of MDTs in CCAs and identifying possible areas of improvement, providing minimum standards of practice for an ideal CCA MDT. Analysis of the replies regarding current and ideal MDT practice was carried out by calculating weighted average (WA) of likelihood of every item. The survey was shared with members of the European Network for the Study of Cholangiocarcinoma and other medical centers with expertise in biliary tract cancer part of the EURO-CHOLANGIO-NET (European Cholangiocarcinoma Network: https://eurocholangionet.eu/) COST Action CA18122 initiative. RESULTS: The role of the MDT coordinator was a recognized priority in an ideal well-functioning MDT (WA 3.31/4), together with providing minimum clinical information before the meeting to secure adequate case preparation (WA 3.54/4). Optimal frequency of MDT meetings was weekly according to 76.92% of the participants; 73.06% believed that ideally all newly diagnosed patients and each new treatment should be discussed, although that happened only in less than half of the MDTs (46.15%) in current practice. Most participants stated that they always (46.15%) or often (50.00%) used guidelines, mainly international (61.00%) (European and American), followed by national/local (39.00%). We defined the ideal setup of a CCA MDT, identifying specialists whose presence is mandatory with WA >3.0 (oncologist, clinician responsible for patient's care, surgeon, diagnostic and interventional radiologist, hepatologist, pathologist, endoscopist and gastroenterologist) and those whose presence would be recommended with a WA <3.0 (palliative care, nurse, dietitian, basic researcher, psychologist and social worker). CONCLUSIONS: Our identified minimum requirements should be taken into account at the time of CCA MDT setup and quality assessment.

Expression of BAFF and BAFF receptors in primary Sjögren's syndrome patients with ectopic germinal center-like structures.

B cell-activating factor (BAFF) is an essential cytokine in primary Sjögren's syndrome (pSS) physiopathology. It has been reported that pSS patients develop germinal center-like (GC-like) structures in their minor salivary glands (MSGs). BAFF, BAFF-R, TACI, and BCMA expression was analyzed in MSGs from 29 subjects (nonspecific chronic sialadenitis and focal lymphocytic sialadenitis with the presence [pSS-GC(+)] or absence [pSS-GC(-)] of GC-like structures). Twenty-four percent of patients showed ectopic GC-like structures and a high focus score [p < 0.001 vs pSS-GC(-)]. BAFF serum levels (sBAFF) were high in pSS patients (p = 0.025 vs healthy subjects). However, the pSS-GC(-) group showed higher sBAFF levels than pSS-GC(+) patients. BAFF and BAFF-R glandular expression levels were higher in pSS-GC(+) patients, without significant differences compared to pSS-GC(-) patients. Soluble levels of BAFF correlated with anti-La/SSB antibodies and disease duration. Our results showed that BAFF could contribute to focal lymphocytic infiltration. The role of BAFF-binding receptors in MSGs is proposed as a mechanism for the possible establishment of ectopic GC-like structures and disease progression in some patients. In conclusion, this study supports previous evidence that considers the active BAFF system role in the pathogenesis of pSS and the need for strong biomarkers in this disease.

Scheduling nab-paclitaxel combined with gemcitabine as first-line treatment for metastatic pancreatic adenocarcinoma.

BACKGROUND: Nab-paclitaxel plus gemcitabine (nabP+gemcitabine) offers modest survival gains for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Sequential scheduling of nabP+gemcitabine in a PDAC mouse model improved efficacy; this hypothesis was tested in a clinical trial. METHODS: Patients with previously untreated metastatic PDAC were randomised to receive nabP+gemcitabine administered either concomitantly on the same day, or sequentially, with gemcitabine administered 24 h after nabP. The primary outcome measure was progression-free survival (PFS). Secondary outcome measures were objective response rate (ORR), overall survival (OS), safety, quality of life (QoL) and predictive biomarkers. RESULTS: In total, 71 patients received sequential (SEQ) and 75 concomitant (CON) treatment. Six-month PFS was 46% with SEQ and 32% with CON scheduling. Median PFS (5.6 versus 4.0 months, hazard ratio [HR] 0.67, 95% confidence interval [95% CI] 0.47-0.95, p = 0.022) and ORR (52% versus 31%, p = 0.023) favoured the SEQ arm; median OS was 10.2 versus 8.2 months (HR 0.93, 95% CI 0.65-1.33, p = 0.70). CTCAE Grade ≥3 neutropaenia incidence doubled with SEQ therapy but was not detrimental to QoL. Strongly positive tumour epithelial cytidine deaminase (CDA) expression favoured benefit from SEQ therapy (PFS HR 0.31, 95% CI 0.13-0.70). CONCLUSIONS: SEQ delivery of nabP+gemcitabine improved PFS and ORR, with manageable toxicity, but did not significantly improve OS. CLINICAL TRIAL REGISTRATION: ISRCTN71070888; ClinialTrials.gov (NCT03529175).

Consecutive strabismus after infantile nystagmus syndrome surgery and potential risk factors.

PURPOSE: The aim of this study is to evaluate the incidence of consecutive strabismus after infantile nystagmus surgery and its potential risk factors. METHODS: A retrospective study including 89 patients was conducted. Patients presented infantile nystagmus (idiopathic or ocular disease-associated nystagmus) without previous or coincidental strabismus. Sex, age at surgery, amblyopia, botulinum toxin (BT) injection before surgery, spherical equivalent, anisometropia, surgery procedure (Anderson's or retroequatorial recessions of four horizontal recti), and follow-up were analyzed. Kaplan-Meier and univariate Cox regression were performed. RESULTS: The median age at surgery was 5 years. The median follow-up was 36 months. The incidence of consecutive strabismus was 11.2%. There were eight patients with exotropia and two patients with esotropia. Consecutive strabismus was associated with severe bilateral amblyopia (p = 0.036), previous treatment with BT injection (p = 0.025), and large recessions of the four horizontal muscles (p = 0.001). The hazard ratio for patients with severe bilateral amblyopia was 5.4 (95% CI 1.1-25.8), and for patients previously treated with BT was 6.1 (1.3-29.3). The survival rate was 95.4% at 6 months and 88.5% at 3 years. CONCLUSION: Severe bilateral amblyopia, previous BT treatment, and type of surgery seem to be associated with consecutive strabismus after infantile nystagmus surgery. Most cases appear within the first months after surgery.

A potential inflammatory role of IL-31 in psoriatic arthritis: A correlation with Th17 cytokine profile.

The goals of our study were to determine the possible association of interleukin (IL)-31 with Th17 cytokine profile in serum and to quantify retinoic acid-related orphan receptor C (RORC) mRNA expression in psoriatic arthritis (PsA) patients. This cross-sectional study was conducted in 50 patients with PsA and 30 control subjects (CS) matched by age and gender. The cytokine serum levels were quantified by magnetic bead-based assay using the Bio-Plex MAGPIX system, and RORC mRNA expression was determined by quantitative polymerase chain reaction (qPCR). As a result, significant differences in IL-31 were observed between study groups (77.23 pg/mL in PsA vs 64.4 pg/mL in CS, P < 0.001) and Th17 cytokine profile serum levels (IL-17A: 6.36 pg/mL in PsA vs 2.97 pg/mL in CS, P = 0.02; IL-17F: 44.15 pg/mL in PsA vs 23.36 pg/mL in PsA, P = 0.01; IL-17E: 3.03 pg/mL in PsA vs 0.82 pg/mL in CS, P < 0.001; IL-21: 36.45 pg/mL in PsA vs 12.44 pg/mL in CS, P = 0.02); however, significant differences were not observed for IL-23 (31.2 pg/mL in PsA vs 53.26 pg/mL in CS, P = 0.58). Furthermore, positive correlations between IL-31 and Th17 cytokine profile serum levels were found (IL-17A: rs = 0.64, P < 0.001; IL-17F: rs = 0.73, P < 0.001; IL-17E: rs = 0.70, P < 0.001; IL-21: rs = 0.54, P = 0.002; IL-23: rs = 0.5, P < 0.01). Regarding RORC gene expression, the PsA group showed an increase of 6.85-fold compared to the CS group. We did not find any association between the serum levels of cytokines and RORC gene expression. In conclusion, in PsA, there are increased serum levels of IL-31, IL-17A, IL-17F, IL-17E, and IL-21, but not IL-23. Moreover, there was a positive correlation of IL-31 with the Th17 cytokine profile and a high RORC gene expression. Altogether, these findings suggest a proinflammatory contribution of IL-31 in close association with the Th17 cytokine profile in PsA.

[Comparative study of the treatment of subtrochanteric fractures in elderly patients: reconstruction nail T2 vs long Gamma nail]. / Estudio comparativo del tratamiento de las fracturas subtrocantéreas en pacientes ancianos: clavo de reconstrucción T2 vs clavo Gamma largo.

INTRODUCTION: Subtrochanteric fractures are associated with a high rate of complications. Intramedullary nails have proven to be the best choice for treatment, but no implant has been shown to be superior to another. We want to study the differences between treating subtrochanteric fractures in the elderly with two different types of nails: T2 Recon vs Gamma3 long. MATERIAL AND METHODS: Comparative retrospective study between 2013 and 2015 with 54 patients with subtrochanteric fractures and more than 65 years. The average follow-up is 12 months; 26 patients were treated with T2 Recon, and 28 with Gamma3. The duration of surgery, need for transfusion, evolution and complications of fractures were compared in both groups. RESULTS: The duration of surgery was significantly longer for T2 Recon (p = 0.035), while the need for transfusion and fracture evolution were similar in both groups. Three cases required another surgery to achieve the final consolidation of the fracture. Two of them due to a failure of the T2 Recon implant, which represents 7.69% of the patients in this group, while the other case belonged to the Gamma3 group and it was sufficient to perform a nail dynamization. CONCLUSIONS: We found no statistically significant differences, except for a longer surgical time in the T2 Recon group, being a surgeon-dependent variable that is not enough to prove that one nail is better than another.

INTRODUCCIÓN: Las fracturas subtrocantéreas se asocian a una alta tasa de complicaciones. Los clavos intramedulares han demostrado ser la mejor opción para su tratamiento, pero ningún implante ha demostrado ser superior a otro. El objetivo es estudiar las diferencias entre tratar las fracturas subtrocantéreas en el anciano con dos tipos de clavos diferentes: T2 Recon vs Gamma3 largo. MATERIAL Y MÉTODOS: Estudio retrospectivo comparativo entre los años 2013 y 2015, con 54 pacientes con fracturas subtrocantéreas y más de 65 años. El seguimiento medio es de 12 meses; 26 pacientes fueron tratados mediante T2 Recon y 28 con Gamma3. La duración de la cirugía, necesidad de transfusión, evolución y complicaciones de las fracturas fueron comparadas en ambos grupos. RESULTADOS: La duración de la cirugía fue significativamente mayor para los T2 Recon (p = 0.035), mientras que la necesidad de transfusión y evolución de las fracturas fueron similares en ambos grupos. Tres casos fueron reintervenidos para conseguir la consolidación final de la fractura. Dos de ellos debido a un fallo del implante T2 Recon, lo cual representa 7.69% de los pacientes de este grupo, mientras que el otro caso pertenecía al grupo de los Gamma3 y fue suficiente con realizar una dinamización del clavo. CONCLUSIONES: No encontramos diferencias estadísticamente significativas, exceptuando un mayor tiempo quirúrgico en el grupo de los T2 Recon, siendo una variable cirujano-dependiente que no es suficiente para demostrar que un clavo sea mejor que otro.

Outcomes in patients ≥ 80 years with a diagnosis of a hepatopancreaticobiliary (HPB) malignancy.

Older patients are underrepresented in oncological clinical trials. The incidence of hepatopancreaticobiliary (HPB) malignancies is higher in older patients, but data on outcomes are lacking. This study assessed patient outcomes in those < 80 and ≥ 80 years with a HPB malignancy seen at a tertiary referral centre, The Christie NHS Foundation Trust. Data on patients with a HPB malignancy were collected retrospectively between 2012 and 2017 via on-line case-note review. Survival was calculated using the Kaplan-Meier method and prognostic factors using log-rank analysis. Of 1421 patients, 10% were ≥ 80 years. Of patients < 80 and ≥ 80 years, 56% and 57% had pancreas cancer, 39% and 36% biliary tract cancer, and 5% and 7% had hepatocellular carcinoma, respectively. Amongst patients ≥ 80 years, 75% had an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2. Patients ≥ 80 years had higher rates of comorbidity; 28% received systemic anti-cancer therapy (SACT), compared with 62% of patients < 80 years. Best supportive care (BSC) was instituted in 44% of older patients, compared with 13% in those < 80 years. Of patients ≥ 80 years who received SACT, 82% received monotherapy. Median overall survival (OS) for patients receiving palliative SACT was 10.07 months (95% CI 8.89-11.08) and 10.10 months (95% CI 6.30-12.30) in patients < 80 and ≥ 80 years, respectively, p 0.41; ECOG PS (p < 0.001) was prognostic for OS in older patients but Adult Comorbidity Evaluation-27 comorbidity score (p = 0.07, when comparing groups of ACE score ≤ 1 and > 1) was not. Baseline factors were similar in both age cohorts, but more comorbidities were present in older patients. Older patients were less likely to receive SACT, but when they did, they had an equivalent benefit in OS to younger patients.