Diagnostic and Prognostic Utility of Procalcitonin in Patients Presenting to the Emergency Department with Dyspnea

Background Among patients in the emergency department, dyspnea is a common complaint and can pose a diagnostic challenge. Biomarkers are used increasingly to improve diagnostic accuracy and aid with prognostication in dyspneic patients. The purpose of this study was to examine the clinical utility of serum procalcitonin (PCT) for the diagnosis of pneumonia in patients presenting to the emergency department with dyspnea. A secondary objective was to evaluate the prognostic value of PCT for death to 1 year. Methods This study pooled the patient populations of 2 prospective cohorts that previously enrolled patients presenting to 2 urban emergency departments with dyspnea. A total of 453 patients had serum samples available for biomarker analysis. Clinician certainty for the diagnosis of acutely decompensated heart failure was reviewed. Discrimination, calibration, and net reclassification improvement for the diagnosis of pneumonia as well as fatal outcomes were considered. The main outcome was accuracy of PCT for diagnostic categorization of pneumonia. The prognostic value of PCT for survival to 1 year was a secondary outcome. Results Pneumonia alone was diagnosed in 30 patients (6.6%), heart failure without pneumonia in 212 patients (47%), and both diagnoses in 30 patients (6.6%). Procalcitonin concentrations were higher in subjects with pneumonia (0.38 vs 0.06 ng/mL; P < .001). Area under the receiver operating characteristic curve for the diagnosis of pneumonia based on PCT was 0.84 (95% confidence interval [CI], 0.77-0.91; P < .001). Across all levels of clinician-based estimates of heart failure, PCT was sensitive and specific; notably, in patients judged with diagnostic uncertainty (n = 70), a PCT value of 0.10 ng/mL had the optimal balance of sensitivity and specificity (80% and 77%, respectively) for pneumonia. Adding PCT results to variables predictive of pneumonia resulted in a net reclassification improvement of 0.54 (95% CI, 0.24-0.83; P < .001) for both up- and down-reclassifying events. In adjusted analyses, elevated PCT was a predictor of 1-year mortality (hazard ratio 1.8; 95% CI, 1.4-2.3; P < .001) and was additive when elevated in conjunction with natriuretic peptides for this application. Conclusion In emergency department patients with acute dyspnea, PCT is an accurate diagnostic marker for pneumonia and adds independent prognostic information for 1-year mortality

The role of primary tumor resection in colorectal cancer patients with asymptomatic, synchronous unresectable metastasis: Study protocol for a randomized controlled trial

BACKGROUND: Approximately 20 % of all patients with colorectal cancer are diagnosed as having Stage IV cancer; 80 % of these present with unresectable metastatic lesions. It is controversial whether chemotherapy with or without primary tumor resection (PTR) is effective for the treatment of patients with colorectal cancer with unresectable metastasis. Primary tumor resection could prevent tumor-related complications such as intestinal obstruction, perforation, bleeding, or fistula. Moreover, it may be associated with an increase in overall survival. However, surgery delays the use of systemic chemotherapy and affects the systemic spread of malignancy. METHODS/DESIGN: Patients with colon and upper rectal cancer patients with asymptomatic, synchronous, unresectable metastasis will be included after screening. They will be randomized and assigned to receive chemotherapy with or without PTR. The primary endpoint measure is 2-year overall survival rate and the secondary endpoint measures are primary tumor-related complications, quality of life, surgery-related morbidity and mortality, interventions with curative intent, chemotherapy-related toxicity, and total cost until death or study closing day. The authors hypothesize that the group receiving PTR following chemotherapy would show a 10 % improvement in 2-year overall survival, compared with the group receiving chemotherapy alone. The accrual period is 3 years and the follow-up period is 2 years. Based on the inequality design, a two-sided log-rank test with α-error of 0.05 and a power of 80 % was conducted. Allowing for a drop-out rate of 10 %, 480 patients (240 per group) will need to be recruited. Patients will be followed up at every 3 months for 3 years and then every 6 months for 2 years after the last patient has been randomized. DISCUSSION: This randomized controlled trial aims to investigate whether PTR with chemotherapy shows better overall survival than chemotherapy alone for patients with asymptomatic, synchronous unresectable metastasis. This trial is expected to provide evidence so support clear treatment guidelines for patients with colorectal cancer with asymptomatic, synchronous unresectable metastasis. TRIAL REGISTRATION: Clinicaltrials.gov NCT01978249

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

Spontaneous Breathing in Early Acute Respiratory Distress Syndrome: Insights From the Large Observational Study to UNderstand the Global Impact of Severe Acute Respiratory FailurE Study

OBJECTIVES: To describe the characteristics and outcomes of patients with acute respiratory distress syndrome with or without spontaneous breathing and to investigate whether the effects of spontaneous breathing on outcome depend on acute respiratory distress syndrome severity. DESIGN: Planned secondary analysis of a prospective, observational, multicentre cohort study. SETTING: International sample of 459 ICUs from 50 countries. PATIENTS: Patients with acute respiratory distress syndrome and at least 2 days of invasive mechanical ventilation and available data for the mode of mechanical ventilation and respiratory rate for the 2 first days. INTERVENTIONS: Analysis of patients with and without spontaneous breathing, defined by the mode of mechanical ventilation and by actual respiratory rate compared with set respiratory rate during the first 48 hours of mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Spontaneous breathing was present in 67% of patients with mild acute respiratory distress syndrome, 58% of patients with moderate acute respiratory distress syndrome, and 46% of patients with severe acute respiratory distress syndrome. Patients with spontaneous breathing were older and had lower acute respiratory distress syndrome severity, Sequential Organ Failure Assessment scores, ICU and hospital mortality, and were less likely to be diagnosed with acute respiratory distress syndrome by clinicians. In adjusted analysis, spontaneous breathing during the first 2 days was not associated with an effect on ICU or hospital mortality (33% vs 37%; odds ratio, 1.18 [0.92-1.51]; p = 0.19 and 37% vs 41%; odds ratio, 1.18 [0.93-1.50]; p = 0.196, respectively ). Spontaneous breathing was associated with increased ventilator-free days (13 [0-22] vs 8 [0-20]; p = 0.014) and shorter duration of ICU stay (11 [6-20] vs 12 [7-22]; p = 0.04). CONCLUSIONS: Spontaneous breathing is common in patients with acute respiratory distress syndrome during the first 48 hours of mechanical ventilation. Spontaneous breathing is not associated with worse outcomes and may hasten liberation from the ventilator and from ICU. Although these results support the use of spontaneous breathing in patients with acute respiratory distress syndrome independent of acute respiratory distress syndrome severity, the use of controlled ventilation indicates a bias toward use in patients with higher disease severity. In addition, because the lack of reliable data on inspiratory effort in our study, prospective studies incorporating the magnitude of inspiratory effort and adjusting for all potential severity confounders are required

Identifying associations between diabetes and acute respiratory distress syndrome in patients with acute hypoxemic respiratory failure: an analysis of the LUNG SAFE database

Background: Diabetes mellitus is a common co-existing disease in the critically ill. Diabetes mellitus may reduce the risk of acute respiratory distress syndrome (ARDS), but data from previous studies are conflicting. The objective of this study was to evaluate associations between pre-existing diabetes mellitus and ARDS in critically ill patients with acute hypoxemic respiratory failure (AHRF). Methods: An ancillary analysis of a global, multi-centre prospective observational study (LUNG SAFE) was undertaken. LUNG SAFE evaluated all patients admitted to an intensive care unit (ICU) over a 4-week period, that required mechanical ventilation and met AHRF criteria. Patients who had their AHRF fully explained by cardiac failure were excluded. Important clinical characteristics were included in a stepwise selection approach (forward and backward selection combined with a significance level of 0.05) to identify a set of independent variables associated with having ARDS at any time, developing ARDS (defined as ARDS occurring after day 2 from meeting AHRF criteria) and with hospital mortality. Furthermore, propensity score analysis was undertaken to account for the differences in baseline characteristics between patients with and without diabetes mellitus, and the association between diabetes mellitus and outcomes of interest was assessed on matched samples. Results: Of the 4107 patients with AHRF included in this study, 3022 (73.6%) patients fulfilled ARDS criteria at admission or developed ARDS during their ICU stay. Diabetes mellitus was a pre-existing co-morbidity in 913 patients (22.2% of patients with AHRF). In multivariable analysis, there was no association between diabetes mellitus and having ARDS (OR 0.93 (0.78-1.11); p = 0.39), developing ARDS late (OR 0.79 (0.54-1.15); p = 0.22), or hospital mortality in patients with ARDS (1.15 (0.93-1.42); p = 0.19). In a matched sample of patients, there was no association between diabetes mellitus and outcomes of interest. Conclusions: In a large, global observational study of patients with AHRF, no association was found between diabetes mellitus and having ARDS, developing ARDS, or outcomes from ARDS. Trial registration: NCT02010073. Registered on 12 December 2013

Epidemiology and patterns of tracheostomy practice in patients with acute respiratory distress syndrome in ICUs across 50 countries

Background: To better understand the epidemiology and patterns of tracheostomy practice for patients with acute respiratory distress syndrome (ARDS), we investigated the current usage of tracheostomy in patients with ARDS recruited into the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG-SAFE) study. Methods: This is a secondary analysis of LUNG-SAFE, an international, multicenter, prospective cohort study of patients receiving invasive or noninvasive ventilation in 50 countries spanning 5 continents. The study was carried out over 4 weeks consecutively in the winter of 2014, and 459 ICUs participated. We evaluated the clinical characteristics, management and outcomes of patients that received tracheostomy, in the cohort of patients that developed ARDS on day 1-2 of acute hypoxemic respiratory failure, and in a subsequent propensity-matched cohort. Results: Of the 2377 patients with ARDS that fulfilled the inclusion criteria, 309 (13.0%) underwent tracheostomy during their ICU stay. Patients from high-income European countries (n = 198/1263) more frequently underwent tracheostomy compared to patients from non-European high-income countries (n = 63/649) or patients from middle-income countries (n = 48/465). Only 86/309 (27.8%) underwent tracheostomy on or before day 7, while the median timing of tracheostomy was 14 (Q1-Q3, 7-21) days after onset of ARDS. In the subsample matched by propensity score, ICU and hospital stay were longer in patients with tracheostomy. While patients with tracheostomy had the highest survival probability, there was no difference in 60-day or 90-day mortality in either the patient subgroup that survived for at least 5 days in ICU, or in the propensity-matched subsample. Conclusions: Most patients that receive tracheostomy do so after the first week of critical illness. Tracheostomy may prolong patient survival but does not reduce 60-day or 90-day mortality. Trial registration: ClinicalTrials.gov, NCT02010073. Registered on 12 December 2013