Dry or wet? Fluid therapy in upper gastrointestinal surgery patients.

A correct perioperative fluid administration represents one of the most important items proposed by the Enhanced Recovery After Surgery Society. Upper gastrointestinal (UGI) surgery patients undergoing major oncological procedures are often elderly and frail. Should we prefer a wet or a dry patient? Both conditions should probably be avoided in this surgical setting. We present a narrative review on perioperative fluid administration in UGI patients undergoing major surgery, also analyzing the role of Goal Directed therapy.

Fatty Acid and Carnitine Metabolism Are Dysregulated in Systemic Sclerosis Patients.

Systemic sclerosis (SSc) is a rare chronic disease of unknown pathogenesis characterized by fibrosis of the skin and internal organs, vascular alteration, and dysregulation of the immune system. In order to better understand the immune system and its perturbations leading to diseases, the study of the mechanisms regulating cellular metabolism has gained a widespread interest. Here, we have assessed the metabolic status of plasma and dendritic cells (DCs) in patients with SSc. We identified a dysregulated metabolomic signature in carnitine in circulation (plasma) and intracellularly in DCs of SSc patients. In addition, we confirmed carnitine alteration in the circulation of SSc patients in three independent plasma measurements from two different cohorts and identified dysregulation of fatty acids. We hypothesized that fatty acid and carnitine alterations contribute to potentiation of inflammation in SSc. Incubation of healthy and SSc dendritic cells with etoposide, a carnitine transporter inhibitor, inhibited the production of pro-inflammatory cytokines such as IL-6 through inhibition of fatty acid oxidation. These findings shed light on the altered metabolic status of the immune system in SSc patients and opens up for potential novel avenues to reduce inflammation.

Enhanced recovery pathways in colorectal surgery: a consensus paper by the Associazione Chirurghi Ospedalieri Italiani (ACOI) and the PeriOperative Italian Society (POIS).

Enhanced Recovery After Surgery (ERAS) pathway is a multi-disciplinary, patient-centered protocol relying on the implementation of the best evidence-based perioperative practice. In the field of colorectal surgery, the application of ERAS programs is associated with up to 50% reduction of morbidity rates and up to 2.5 days reduction of postoperative hospital stay. However, widespread adoption of ERAS pathways is still yet to come, mainly because of the lack of proper information and communication. Purpose of this paper is to support the diffusion of ERAS pathways through a critical review of the existing evidence by members of the two national societies dealing with ERAS pathways in Italy, the PeriOperative Italian Society (POIS) and the Associazione Italiana Chirurghi Ospedalieri (ACOI), showing the results of a consensus development conference held at Matera, Italy, during the national ACOI Congress on June 10, 2019.

Enhanced recovery program (ERP) in major laryngeal surgery: building a protocol and testing its feasibility.

Enhanced recovery programs (ERP) represent a multimodal approach to perioperative patient care. The benefits of ERP are well demonstrated in colorectal surgery and Enhanced Recovery After Surgery (ERAS®) programs, that epitomise the ERP concept, have being introduced in different specialties, including vascular, gastric, pancreatic, urogynecologic and orthopaedic surgery. However, no ERP has been proposed for head and neck surgery. We developed an expert-opinion-based ERP for laryngeal surgery based on the key principles of colorectal surgery ERAS®. Twenty-four patients undergoing major laryngeal surgery (total and partial laryngectomies or surgical removal of oropharyngeal tumour with muscle flap reconstruction) were treated according to such an ERP protocol, which differed under several respects from our previous standard practice (described in 70 consecutive patients who underwent major laryngeal surgery before ERP implementation. The adherence rate to the different ERP items is reported. Adherence to ERP items was high. Nutritional assessment, antibiotic prophylaxis, postoperative nausea and vomit (PONV) prophylaxis and postoperative speech therapy targets were applied as required in 100% of cases. Some ERP items (antibiotic prophylaxis, intraoperative infusion rate, and postoperative speech therapy) were already frequently implemented before ERP adoption. Postoperative medical complications occurred in 8.3% of patients. Our expert opinion-based ERP protocol for major laryngeal surgery proved feasible. The degree of benefit deriving from its implementation has yet to be assessed.

An Ocular Protein Triad Can Classify Four Complex Retinal Diseases.

Retinal diseases generally are vision-threatening conditions that warrant appropriate clinical decision-making which currently solely dependents upon extensive clinical screening by specialized ophthalmologists. In the era where molecular assessment has improved dramatically, we aimed at the identification of biomarkers in 175 ocular fluids to classify four archetypical ocular conditions affecting the retina (age-related macular degeneration, idiopathic non-infectious uveitis, primary vitreoretinal lymphoma, and rhegmatogenous retinal detachment) with one single test. Unsupervised clustering of ocular proteins revealed a classification strikingly similar to the clinical phenotypes of each disease group studied. We developed and independently validated a parsimonious model based merely on three proteins; interleukin (IL)-10, IL-21, and angiotensin converting enzyme (ACE) that could correctly classify patients with an overall accuracy, sensitivity and specificity of respectively, 86.7%, 79.4% and 92.5%. Here, we provide proof-of-concept for molecular profiling as a diagnostic aid for ophthalmologists in the care for patients with retinal conditions.

Effect of sarcopenia and visceral obesity on mortality and pancreatic fistula following pancreatic cancer surgery.

BACKGROUND: Analytical morphometric assessment has recently been proposed to improve preoperative risk stratification. However, the relationship between body composition and outcomes following pancreaticoduodenectomy is still unclear. The aim of this study was to assess the impact of body composition on outcomes in patients undergoing pancreaticoduodenectomy for cancer. METHODS: Body composition parameters including total abdominal muscle area (TAMA) and visceral fat area (VFA) were assessed by preoperative staging CT in patients undergoing pancreaticoduodenectomy for cancer. Perioperative variables and postoperative outcomes (mortality or postoperative pancreatic fistula) were collected prospectively in the institutional pancreatic surgery database. Optimal stratification was used to determine the best cut-off values for anthropometric measures. Multivariable analysis was performed to identify independent predictors of 60-day mortality and pancreatic fistula. RESULTS: Of 202 included patients, 132 (65·3 per cent) were classified as sarcopenic. There were 12 postoperative deaths (5·9 per cent), major complications developed in 40 patients (19·8 per cent) and pancreatic fistula in 48 (23·8 per cent). In multivariable analysis, a VFA/TAMA ratio exceeding 3·2 and American Society of Anesthesiologists grade III were the strongest predictors of mortality (odds ratio (OR) 6·76 and 6·10 respectively; both P < 0·001). Among patients who developed major complications, survivors had a significantly lower VFA/TAMA ratio than non-survivors (P = 0·017). VFA was an independent predictor of pancreatic fistula (optimal cut-off 167 cm(2) : OR 4·05; P < 0·001). CONCLUSION: Sarcopenia is common among patients undergoing pancreaticoduodenectomy. The combination of visceral obesity and sarcopenia was the best predictor of postoperative death, whereas VFA was an independent predictor of pancreatic fistula.

Hepatitis C virus in Mexican Americans: a population-based study reveals relatively high prevalence and negative association with diabetes.

This study aimed to estimate the prevalence and risk factors for hepatitis C virus (HCV) infection in Mexican Americans living in South Texas. We tested plasma for the presence of HCV antibody from the Cameron County Hispanic Cohort (CCHC), a randomized, population-based cohort in an economically disadvantaged Mexican American community on the United States/Mexico border with high rates of chronic disease. A weighted prevalence of HCV antibody of 2·3% [n = 1131, 95% confidence interval (CI) 1·2-3·4] was found. Participants with diabetes had low rates of HCV antibody (0·4%, 95% CI 0·0-0·9) and logistic regression revealed a statistically significant negative association between HCV and diabetes (OR 0·20, 95% CI 0·05-0·77) after adjusting for sociodemographic and clinical factors. This conflicts with reported positive associations of diabetes and HCV infection. No classic risk factors were identified, but important differences between genders emerged in analysis. This population-based study of HCV in Mexican Americans suggests that national studies do not adequately describe the epidemiology of HCV in this border community and that unique risk factors may be involved.

Influence of the IL17A locus in giant cell arteritis susceptibility.

OBJECTIVE: Different lines of evidence have highlighted the role of IL-17A in the inflammatory process occurring in giant cell arteritis (GCA). The aim of the present study was to assess whether the IL17A locus influences GCA susceptibility and its clinical subphenotypes. METHODS: We carried out a large meta-analysis including a total of 1266 biopsy-proven GCA patients and 3779 healthy controls from four European populations (Spain, Italy, Germany and Norway). Five IL17A polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909) were selected by tagging and genotyped using TaqMan assays. Allelic combination and dependency tests were also performed. RESULTS: In the pooled analysis, two of the five analysed polymorphisms showed evidence of association with GCA (rs2275913: PMH=1.85E-03, OR=1.17 (1.06-1.29); rs7747909: PMH=8.49E-03, OR=1.15 (1.04-1.27)). A clear trend of association was also found for the rs4711998 variant (PMH=0.059, OR=1.11 (1.00-1.23)). An independent effect of rs2275913 and rs4711998 was evident by conditional regression analysis. In addition, the haplotype harbouring the risk alleles better explained the observed association than the polymorphisms independently (likelihood p value <10(-05)). CONCLUSIONS: Polymorphisms within the IL17A locus show a novel association with GCA. This finding supports the relevant role of the Th17 cells in this vasculitis pathophysiology.

Non-invasive ventilation in cardiac surgery: a concise review.

Mild to severe respiratory dysfunction is still a common issue after cardiac surgery. Postoperative respiratory complications are associated with prolonged hospitalization and worse survival. In this high-risk surgery, non-invasive ventilation could have relevant positive effects. The present narrative concise review aims to summarize available data on the role of non-invasive ventilation before and after cardiac surgery. Non-invasive ventilation exerts its main effects on the pulmonary and on the cardiovascular systems.  Non-invasive ventilation can be applied to prevent acute respiratory failure; it can also be prescribed as a curative tool to treat an established postoperative acute respiratory failure. Non-invasive ventilation could also be applied to wean patients from mechanical ventilation. When applied as a preventive tool, the main scope is the prevention of pneumonia by resolving or preventing atelectasis. So far, limited (but encouraging) data are available: its routine use in all patients to prevent postoperative acute respiratory failure cannot be recommended. Non-invasive ventilation to treat postoperative acute respiratory failure has been evaluated more extensively. A failure rate from 10 to 55% was reported. Safety appears preserved, with no relevant hemodynamic complication reported. Non-invasive ventilation has also been applied during percutaneous aortic valve implant in patients unable to lie supine due to severe respiratory limitation and orthopnea. In conclusion, non-invasive ventilation has the potential to be very useful before and after cardiac surgery. So far, results are promising but available data are limited. Training and experience are essential to obtain positive results and to avoid complications.

Do we need to use sugammadex at the end of a general anesthesia to reverse the action of neuromuscular bloking agents? Position Paper on Sugammadex use.

Sugammadex, the first selective relaxant-binding agent indicated to reverse the neuromuscular blockade induced during general anesthesia, was recently introduced into clinical practice. In the present report, the following issues pertinent to the use of sugammadex in anesthesia practice are discussed: the intraoperative use of NMBAs and the incidence of postoperative residual curarization (PORC); the efficacy and safety of rocuronium plus sugammadex compared to succinylcholine for rapid sequence induction; the availability of sugammadex in hospitals; and, finally, some relevant legal medical aspects. Sugammadex is considerably more expensive than neostigmine, but its use can be advocated based on its safety and efficacy profile as a reversal agent of steroidal neuro muscular blocking agents (NMBAs), and as a mean to prevent PORC. The availability of sugammadex in Italian hospitals may have a beneficial impact on patient safety. This is due to the fact that PORC is a common and dangerous condition that may lead to postoperative inhalational events, hypoxemia, and pneumonia; and at the moment, it is not completely preventable even when advanced neuro-muscolar monitoring techniques are applied". In the case of rapid sequence intubation (RSI), rocuronium (1.2 mg/kg) administration followed by sugammadex represents a better choice in terms of efficacy and safety than succinylcholine. If a new drug is proven to be safer and more efficient than the one it is replacing, hospitals should consider the new drug and make it available, at least for selected patients or in situations at risk of severe complications. It is reasonable to hypothesize that, when discussing informed consent for elective procedures, patients and families may want to know if the admitting facilities have the superior agent available, and that the absence of such agent could create concerns and complains.

Intensive care for pediatric traumatic brain injury.

PURPOSES: The aims of this study are to describe a cohort of head-injured pediatric patients, focusing on current practice for intracranial pressure (ICP) monitoring and treatment and to verify the relationship between clinical and radiological parameters and the six-month outcome in a multivariable statistical model. METHODS: A retrospective review was done of a prospectively collected database considering patients younger than 19 years admitted to three neuro-intensive care units (ICU). Patients were divided into four age groups: 0-5 (infant), 6-12 (children), 13-16 (pre-adolescent) and 17-18 years (adolescent). The ICP and cerebral perfusion pressure (CPP) were analyzed calculating average data and values exceeding thresholds for more than 5 min. Outcome was assessed 6 months after trauma using the Glasgow Outcome Score. RESULTS: There were 199 patients, 155 male, included. Sixty percent had extracranial injuries. Pupils were abnormal in 38 %. Emergency evacuation of intracranial hematomas was necessary in 81 cases. The ICP was monitored in 117 patients; in 87 cases ICP was higher than 20 mmHg, with no differences among age groups. All but six patients received therapy to prevent raised ICP; barbiturates, deep hyperventilation or surgical decompression were used in 31 cases. At 6 months, mortality was 21 % and favorable outcome was achieved by 72 %. Significant predictors of outcome in the multivariable model were the Glasgow Coma Scale (GCS) motor score, pupils and ICP. CONCLUSIONS: Pediatric head injury is associated with a high incidence of intracranial hypertension. Early surgical treatment and intensive care may achieve favorable outcome in the majority of cases.

Evidence that deletion at FCGR3B is a risk factor for systemic sclerosis.

There is increasing evidence that gene copy number (CN) variation influences clinical phenotype. The low-affinity Fc receptor 3B (FCGR3B) located in the FCGR gene cluster is a CN polymorphic gene involved in the recruitment of polymorphonuclear neutrophils to sites of inflammation and their activation. Given the genetic overlap between systemic lupus erythematosus and systemic sclerosis (SSc) and the strong evidence for FCGR3B CN in the pathology of SLE, we hypothesised that FCGR3B gene dosage influences susceptibility to SSc. We obtained FCGR3B deletion status in 777 European Caucasian cases and 1000 controls. There was an inverse relationship between FCGR3B CN and disease susceptibility. CN of ≤ 1 was a significant risk factor for SSc (OR=1.55 (1.13-2.14), P=0.007) relative to CN ≥ 2. Although requiring replication, these results suggest that impaired immune complex clearance arising from FCGR3B deficiency contributes to the pathology of SSc, and FCGR3B CN variation is a common risk factor for systemic autoimmunity.

A rare polymorphism in the gene for Toll-like receptor 2 is associated with systemic sclerosis phenotype and increases the production of inflammatory mediators.

OBJECTIVE: To investigate whether polymorphisms in Toll-like receptor (TLR) genes, previously reported to be associated with immune-mediated diseases, are involved in systemic sclerosis (SSc). METHODS: We genotyped 14 polymorphisms in the genes for TLRs 2, 4, 7, 8, and 9 in a discovery cohort comprising 452 SSc patients and 537 controls and a replication cohort consisting of 1,170 SSc patients and 925 controls. In addition, we analyzed 15-year followup data on 964 patients to assess the potential association of TLR variants with the development of disease complications. We analyzed the functional impact of the associated polymorphism on monocyte-derived dendritic cells. RESULTS: In the discovery cohort, we observed that a rare functional polymorphism in TLR2 (Pro631His) was associated with antitopoisomerase (antitopo) positivity (odds ratio 2.24 [95% confidence interval 1.24-4.04], P=0.003). This observation was validated in the replication cohort (odds ratio 2.73 [95% confidence interval 1.85-4.04], P=0.0001). In addition, in the replication cohort the TLR2 variant was associated with the diffuse subtype of the disease (P=0.02) and with the development of pulmonary arterial hypertension (PAH) (Cox proportional hazards ratio 5.61 [95% confidence interval 1.53-20.58], P=0.003 by log rank test). Functional analysis revealed that monocyte-derived dendritic cells carrying the Pro63His variant produced increased levels of inflammatory mediators (tumor necrosis factor α and interleukin-6) upon TLR-2-mediated stimulation (both P<0.0001). CONCLUSION: Among patients with SSc, the rare TLR2 Pro631His variant is robustly associated with antitopoisomerase positivity, the diffuse form of the disease, and the development of PAH. In addition, this variant influences TLR-2-mediated cell responses. Further research is needed to elucidate the precise role of TLR-2 in the pathogenesis of SSc.

Systemic adverse events during 2005 phacoemulsifications under monitored anesthesia care: a prospective evaluation.

BACKGROUND: The aim of the study was to evaluate the systemic adverse events triggering on-call anesthesiologist's intervention during 2005 phacoemulsification under topical anesthesia on a day-surgery monitored anesthesia care regimen. METHODS: Adverse events triggering an anesthesiologist call by the attending nurse were registered. Comorbidities (7 categories), age, gender, body mass index, ASA status, length of surgery, time of the day of surgery and operated eye (first/second) were analyzed as potentially predictive factors. Odds Ratios are expressed as OR (95% CI). RESULTS: The anesthesiologist was called in 433 (21.6%) cases: age (5-yr-OR 0.95 [0.91-0.99]), ASA status 3-4 (OR 1.37 [1.02-1.85]), positive neurological history (OR 1.60 [1.06-2.40]), positive psychiatric history (OR 2.56 [1.34-4.93]) and length of surgery (OR 1.03 [1.01-1.06]) were predictive of the anesthesiologist call. Arterial hypertension (10.3%) and agitation (9.5%) were the most frequent adverse events. Age (5-yr-OR 1.27 [1.16-1.38]) and ASA status 3-4 (OR 1.83 [1.30-2.56]) were predictive of arterial hypertension. Age (5-yr-OR 0.80 [0.76-0.85]), positive neurological history (OR 1.86 [1.10-3.14]) and positive psychiatric history (OR 4.48 [2.26-8.88]) were predictive of agitation. Interruption of surgery was never required. CONCLUSION: One-day cataract surgery performed under topical anesthesia with monitored anesthesia care required anesthesiologist intervention in 21.6% of cases, mainly because of agitation or hypertension. Agitation occurred more often in younger patients with neurological or psychiatric comorbidities. Hypertension occurred more often in older patients with higher ASA scores.

Sedation in neurocritical patients: is it useful?

Anesthetics are widely used in the management of neurocritical patients, although has never been proved that the use of these drugs can contribute to positive outcome. The aim of this review was to evaluate the expected benefit of anesthetics use in relation to the altered physiology of the damaged brain while considering possible related complications.

Clinical prediction of 5-year survival in systemic sclerosis: validation of a simple prognostic model in EUSTAR centres.

OBJECTIVE: Systemic sclerosis (SSc) is associated with a significant reduction in life expectancy. A simple prognostic model to predict 5-year survival in SSc was developed in 1999 in 280 patients, but it has not been validated in other patients. The predictions of a prognostic model are usually less accurate in other patients, especially from other centres or countries. A study was undertaken to validate the prognostic model to predict 5-year survival in SSc in other centres throughout Europe. METHODS: A European multicentre cohort of patients with SSc diagnosed before 2002 was established. Patients with SSc according to the preliminary American College of Rheumatology classification criteria were eligible for the study when they were followed for at least 5 years or shorter if they died. The primary outcome was 5-year survival after diagnosis of SSc. The predefined prognostic model uses the following baseline variables: age, gender, presence of urine protein, erythrocyte sedimentation rate (ESR) and carbon monoxide diffusing capacity (DLCO). RESULTS: Data were available for 1049 patients, 119 (11%) of whom died within 5 years after diagnosis. Of the patients, 85% were female, the mean (SD) age at diagnosis was 50 (14) years and 30% were classified as having diffuse cutaneous SSc. The prognostic model with age (OR 1.03), male gender (OR 1.93), urine protein (OR 2.29), elevated ESR (1.89) and low DLCO (OR 1.94) had an area under the receiver operating characteristic curve of 0.78. Death occurred in 12 (2.2%) of 509 patients with no risk factors, 45 (13%) of 349 patients with one risk factor, 55 (33%) of 168 patients with two risk factors and 7 (30%) of 23 patients with three risk factors. CONCLUSION: A simple prognostic model using three disease factors to predict 5-year survival at diagnosis in SSc showed reasonable performance upon validation in a European multicentre study.

Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis.

OBJECTIVE: Two functional single nucleotide polymorphisms (SNP) in the PTPN22 gene (rs24746601 and rs33996649) have been associated with autoimmunity. The aim of this study was to investigate the role of the R263Q SNP for the first time and to re-evaluate the role of the R620W SNP in the genetic predisposition to systemic sclerosis (SSc) susceptibility and clinical phenotypes. METHODS: 3422 SSc patients (2020 with limited cutaneous SSc and 1208 with diffuse cutaneous SSc) and 3638 healthy controls of Caucasian ancestry from an initial case--control set of Spain and seven additional independent replication cohorts were included in our study. Both rs33996649 and rs2476601 PTPN22 polymorphisms were genotyped by TaqMan allelic discrimination assay. A meta-analysis was performed to test the overall effect of these PTPN22 polymorphisms in SSc. RESULTS: The meta-analysis revealed evidence of association of the rs2476601 T allele with SSc susceptibility (p(FDRcorrected)=0.03 pooled, OR 1.15, 95% CI 1.03 to 1.28). In addition, the rs2476601 T allele was significantly associated with anticentromere-positive status (p(FDRcorrected)=0.02 pooled, OR 1.22, 95% CI 1.05 to 1.42). Although the rs33996649 A allele was significantly associated with SSc in the Spanish population (p(FDRcorrected)=0.04, OR 0.58, 95% CI 0.36 to 0.92), this association was not confirmed in the meta-analysis (p=0.36 pooled, OR 0.89, 95% CI 0.72 to 1.1). CONCLUSION: The study suggests that the PTPN22 R620W polymorphism influences SSc genetic susceptibility but the novel R263Q genetic variant does not. These data strengthen evidence that the R620W mutation is a common risk factor in autoimmune diseases.