Limited Value of Bladder Wash Cytology During Follow-Up of Patients With Non-muscle Invasive Bladder Cancer.

Aims We aimed to assess the performance of bladder wash cytology (BWC) in daily clinical practice in a pure follow-up cohort of patients previously diagnosed with non-muscle invasive bladder cancer (NMIBC). Materials and methods We analyzed 2064 BWCs derived from 314 patients followed for NMIBC (2003-2016). Follow-up investigations were performed using cystoscopy (CS) in combination with BWC. Patients with suspicious CS and/or positive BWC underwent bladder biopsy or transurethral resection. BWC was considered positive if malignant or suspicious cells were reported. Sensitivity (Sn) and specificity (Sp) were calculated for the entire cohort and separately for low-grade (LG) and high-grade (HG) tumors, and carcinoma in situ (CIS) subgroups. Results A total of 95 recurrences were detected, of which only three were detected by BWC alone. Overall, Sn and Sp of BWC were 17.9% and 99.5%, respectively. For LG disease, these numbers were 14.0% and 100%, and for HG disease, these were 22.2% and 99.1%, respectively. For patients with CIS at initial diagnosis, Sn and Sp were 11.0% and 71.4%, respectively. For isolated primary CIS, Sn was 50.0%, and Sp was 98.2%. Conclusion Routine use of BWC in the follow-up for NMIBC is of limited value even in HG tumors. In the presence of isolated primary CIS, adjunct BWC might be justified.

Effectiveness of radiation protection systems in the cardiac catheterization laboratory: a comparative study.

BACKGROUND: As numbers and complexity of percutaneous coronary interventions are constantly increasing, optimal radiation protection is required to ensure operator safety. Suspended radiation protection systems (SRPS) and protective scatter-radiation absorbing drapes (PAD) are novel methods to mitigate fluoroscopic scattered radiation exposure. The aim of the study was to investigate the effectiveness regarding radiation protection of a SRPS and a PAD in comparison with conventional protection. METHODS: A total of 229 cardiac catheterization procedures with SRPS (N = 73), PAD (N = 82) and standard radiation protection (N = 74) were prospectively included. Real-time dosimeter data were collected from the first operator and the assistant. Endpoints were the cumulative operator exposure relative to the dose area product [standardized operator exposure (SOE)] for the first operator and the assistant. RESULTS: For the first operator, the SRPS and the PAD significantly decreased the overall SOE compared to conventional shielding by 93.9% and 66.4%, respectively (P < 0.001). The protective effect of the SRPS was significantly higher compared to the PAD (P < 0.001). For the assistant, the SRPS and the PAD provided a not statistically significant reduction compared to conventional shielding in the overall SOE by 38.0% and 30.6%, respectively. CONCLUSIONS: The SRPS and the PAD enhance radiation protection significantly compared to conventional protection. In most clinical scenarios, the protective effect of SRPS is significantly higher than the additional protection provided by the PAD. Comparison of the additional radiation protection provided by protective scatter-radiation absorbing drapes (PAD) and the suspended radiation protection system (SRPS) system over standard protection with lead aprons.

Judging Urgency in 343 Ectopic Pregnancies Prior to Surgery - The Importance of Transvaginal Sonographic Diagnosis of Intraabdominal Free Blood.

OBJECTIVES: Assessing urgency in ectopic pregnancies (ECP) remains controversial since the disorder covers a large clinical spectrum. Severe conditions such as acute abdomen or hemodynamic instability are mostly related to intra-abdominal blood loss diagnosed as free fluid (FF) on transvaginal sonography (TVS). The aims of the current study were to investigate the value of FF and to assess other potentially predictive parameters for judging urgency. METHODS: Retrospective cohort analysis on prospectively collected cases of proven ECP (n = 343). Demographics, clinical and laboratory parameters, and findings on TVS and laparoscopy (LSC) were extracted from the digital patient file. FF on TVS and free blood (FB) in LSC were evaluated. Low urgency was defined as FB (LSC) < 100 ml and high urgency as FB (LSC) ≥ 300 ml. The best subset of variables for the prediction of FB was selected and predictors of urgency were evaluated using receiver operator characteristic (ROC) curves. RESULTS: Clinical symptoms, age, ß-HCG, hemoglobin (HB) preoperative, and FF were examined in multivariate analysis for the cutoff values of 100 ml and 300 ml. FF was the only independent predictor for low and high urgency; HB preoperative was only significant for high urgency offering marginal improvement. ROC analysis revealed FF as an excellent discriminatory parameter for defining low (AUC 0.837, 95% CI 0.794-0.879) and high urgency (AUC 0.902, 95 % CI 0.860-0.945). CONCLUSION: Single assessment of FF on TVS is most valuable for judging urgency. However, the exact cutoff values for a low- and high-risk situation must still be defined.

Is Regular Radiographic Upper Urinary Tract Imaging for Surveillance of Non-Muscle Invasive Bladder Cancer Justified?

Patients with non-muscle invasive (NMI) urothelial bladder cancer (BC) are at increased risk for the development of a secondary upper-urinary-tract urothelial carcinoma (UTUC). We aimed to assess the usefulness of routine upper-tract imaging surveillance during NMIBC follow-up in a patient cohort of a tertiary academic center. All routine upper-tract-imaging scans using computerized tomography urography (CTU) between 2003 and 2016 were assessed for UTUC detection. A total of 315 patients were analyzed. Initial tumor stage was Ta in 207 patients (65.7%), T1 in 98 patients (31.1%) and pure CIS in 10 patients (3.2%). A total of 149 (47.3%) presented with low-grade (LG), and 166 (52.7%) with high-grade (HG) disease. Median follow-up was 48 months (IQR: 55). Four patients (1.2%) were diagnosed with UTUC during follow-up. All four patients presented with initial Ta HG BC. Two of the patients (50%) were diagnosed by routine upper tract imaging. The other two patients were diagnosed after development of symptoms. The 5- and 10-year UTUC-free survival was 98.5% (standard error (SE) 0.9) and 97.6% (SE 1.3), respectively. UTUCs were detected exclusively in patients with initial HG disease, indicating that upper-tract surveillance might only be necessary in these patients.

Are the rib fracture score and different computed tomography measures of obesity predictors for mortality in patients with rib fractures? A retrospective cohort study.

BACKGROUND: There is missing knowledge about the association of obesity and mortality in patients with rib fractures. Since the global measure of obesity (body mass index [BMI]) is often unknown in trauma patients, it would be convenient to use local computed tomography (CT)-based measures (e.g., umbilical outer abdominal fat) as a surrogate. The purpose of this study was to assess (1) whether local measures of obesity and rib fractures are associated with mortality and abdominal injuries and to evaluate (2) the correlation between local and global measures of obesity. MATERIALS AND METHODS: A retrospective cohort study included all inpatients with rib fractures in 2013. The main exposure variable was the rib fracture score (RFS) (number of rib fractures, uni- or bilateral, age). Other exposure variables were CT-based measures of obesity and BMI. The primary outcome (endpoint) was in-hospital mortality. The secondary outcome consisted of abdominal injuries. Sex and comorbidities were adjusted for with logistic regression. RESULTS: Two hundred and fifty-nine patients (median age 55.0 [IQR 44.0-72.0] years) were analyzed. Mortality was 8.5%. RFS > 4 was associated with 490% increased mortality (ORadjusted = 5.9, 95% CI 1.9-16.6, p = 0.002). CT-based measures and BMI were not associated with mortality, rib fractures or injury of the liver. CT-based measures of obesity showed moderate correlations with BMI (e.g., umbilical outer abdominal fat: r = 0.59, p < 0.001). CONCLUSIONS: RFS > 4 was an independent risk factors for increased mortality. Local and global measures of obesity were not associated with mortality, rib fractures or liver injuries. If the BMI is not available in trauma patients, CT-based measures of obesity may be considered as a surrogate.

Prevalence and outcome of contrast-induced nephropathy in major trauma patients.

BACKGROUND: Contrast-induced nephropathy (CIN) has been well investigated in patients undergoing coronary angiography, but not in trauma patients. The main aim of this study was to determine the prevalence and to investigate independent risk factors for the development of CIN. METHODS: Between 2008 and 2014, all pre-hospital intubated major trauma patients with documented serum creatinine levels (SCr) undergoing a contrast-enhanced whole-body CT at admission were retrospectively analyzed. CIN was defined as a relative increase in SCr > 25% over the baseline value or an absolute SCr increase of > 44 µmol/l within 72 h. Univariate and multivariable regression analyses were performed to identify significant risk factors. A p value of < 0.01 was considered statistically significant and a p value of 0.01-0.049 suggested evidence. RESULTS: Of 284 analyzed patients, 41 (14%) met the criteria for CIN. There is suggestive evidence that age and lactate level influenced the development of CIN. Six patients (15%) had hemodialysis in the CIN-group and eight (3.3%) in the group without CIN. Complication and mortality rate was higher in patients with CIN (71% vs. 56% and 32% vs. 23%, respectively). CIN was not an independent risk factor for complications or mortality while controlling for age, gender, injury severity score, and lactate level. The length of stay was not affected by CIN. CONCLUSION: CIN occurs frequently in trauma patients, but is not an independent risk factor for complications or mortality. Therefore, contrast enhanced whole-body CT can safely be performed in trauma patients.

Effect of Collaborative Review of Electronic Patient-Reported Outcomes for Shared Reporting in Breast Cancer Patients: Descriptive Comparative Study.

BACKGROUND: Digital monitoring of treatment-related symptoms and self-reported patient outcomes is important for the quality of care among cancer patients. As mobile devices are ubiquitous nowadays, the collection of electronic patient-reported outcomes (ePROs) is gaining momentum. So far, data are lacking on the modalities that contribute to the quantity and quality of ePROs. OBJECTIVE: The objective of our study was to compare the utilization of two versions of a subsequently employed mobile app for electronic monitoring of PROs and to test our hypothesis that a shared review of symptoms in patient-physician collaboration has an impact on the number of data entries. METHODS: The Consilium Care app engages cancer patients to standardize reporting of well-being and treatment-related symptoms in outpatient settings. For descriptive comparison of the utilization of two slightly different app versions, data were obtained from an early breast cancer trial (version 1 of the app, n=86) and an ongoing study including patients with advanced disease (version 2 of the app, n=106). In both app versions, patients and doctors were allowed to share the information from data entries during consultations. Version 2 of the app, however, randomly selected symptoms that required a detailed and shared regular patient-doctor review in order to focus on the collection and appropriate interpretation regarding awareness and guidance for severity grading. The numbers and types of symptom entries, satisfaction with both app versions, and patients' perceived effects during consultations were included for analysis. RESULTS: Symptom severity grading was performed according to the Common Terminology Criteria for Adverse Events (CTCAE) using a horizontal slider and was indicated in descriptive terminology in both apps, while a graphical display facilitated the illustration of symptom history charts. In total, 192 patients electronically reported 11,437 data entries on well-being and 33,380 data entries on individual symptoms. Overall, 628 (of 872 intended) requested patient-doctor symptom reviews were performed in version 2 of the app. Both the amount of data entries per patient and day for well-being (version 1 vs version 2: 0.3 vs 1.0; P<.001) and symptoms (version 1 vs version 2: 1.3 vs 1.9; P=.04) appeared significantly increased in version 2 of the app. Overall satisfaction with both app versions was high, although version 2 of the app was perceived to be more helpful in general. CONCLUSIONS: Version 2 of the app showed much better results than version 1 of the app. A request for collaborative patient-doctor symptom review is likely to affect the number of digital symptom data entries. This app shows high potential to improve the patient-doctor experience. TRIAL REGISTRATION: ClinicalTrials.gov NCT02004496; https://clinicaltrials.gov/ct2/show/NCT02004496 and ClinicalTrials.gov NCT03578731; https://clinicaltrials.gov/ct2/show/NCT03578731.

The Mechanisms Responsible for Improved Information Transfer in Avatar-Based Patient Monitoring: Multicenter Comparative Eye-Tracking Study.

BACKGROUND: Patient monitoring is central to perioperative and intensive care patient safety. Current state-of-the-art monitors display vital signs as numbers and waveforms. Visual Patient technology creates an easy-to-interpret virtual patient avatar model that displays vital sign information as it would look in a real-life patient (eg, avatar changes skin color from healthy to cyanotic depending on oxygen saturation). In previous studies, anesthesia providers using Visual Patient perceived more vital signs during short glances than with conventional monitoring. OBJECTIVE: We aimed to study the deeper mechanisms underlying information perception in conventional and avatar-based monitoring. METHODS: In this prospective, multicenter study with a within-subject design, we showed 32 anesthesia providers four 3- and 10-second monitoring scenarios alternatingly as either routine conventional or avatar-based in random sequence. All participants observed the same scenarios with both technologies and reported the vital sign status after each scenario. Using eye-tracking, we evaluated which vital signs the participants had visually fixated (ie, could have potentially read and perceived) during a scenario. We compared the frequencies and durations of participants' visual fixations of vital signs between the two technologies. RESULTS: Participants visually fixated more vital signs per scenario in avatar-based monitoring (median 10, IQR 9-11 versus median 6, IQR 4-8, P<.001; median of differences=3, 95% CI 3-4). In multivariable linear regression, monitoring technology (conventional versus avatar-based monitoring, difference=-3.3, P<.001) was an independent predictor of the number of visually fixated vital signs. The difference was less prominent in the longer (10-second) scenarios (difference=-1.5, P=.04). Study center, profession, gender, and scenario order did not influence the differences between methods. In all four scenarios, the participants visually fixated 9 of 11 vital signs statistically significantly longer using the avatar (all P<.001). Four critical vital signs (pulse rate, blood pressure, oxygen saturation, and respiratory rate) were visible almost the entire time of a scenario with the avatar; these were only visible for fractions of the observations with conventional monitoring. Visual fixation of a certain vital sign was associated with the correct perception of that vital sign in both technologies (avatar: phi coefficient=0.358; conventional monitoring: phi coefficient=0.515, both P<.001). CONCLUSIONS: This eye-tracking study uncovered that the way the avatar-based technology integrates the vital sign information into a virtual patient model enabled parallel perception of multiple vital signs and was responsible for the improved information transfer. For example, a single look at the avatar's body can provide information about: pulse rate (pulsation frequency), blood pressure (pulsation intensity), oxygen saturation (skin color), neuromuscular relaxation (extremities limp or stiff), and body temperature (heatwaves or ice crystals). This study adds a new and higher level of empirical evidence about why avatar-based monitoring improves vital sign perception compared with conventional monitoring.

Intracavitary cisplatin-fibrin chemotherapy after surgery for malignant pleural mesothelioma: A phase I trial.

OBJECTIVES: Intracavitary chemotherapy is a promising concept to improve local tumor control for malignant pleural mesothelioma with reported high morbidity rates. We have demonstrated that administration of cisplatin loaded to fibrin increased local drug concentration and reduced systemic toxicity in preclinical models. We present a phase I trial of intracavitary cisplatin-fibrin after surgical tumor resection. METHODS: A total of 12 patients (75% International Mesothelioma Interest Group stage III-IV) were treated with 4 dose levels of intracavitary cisplatin-fibrin (11-44 mg/m2 body surface area) in a dose-escalating design. Cisplatin-fibrin was sprayed on the resected surfaces after pleurectomy/decortication. Blood and tissue samples were taken to assess toxicity and pharmacokinetics. Patients were regularly followed up. RESULTS: No dose-limiting toxicity was observed. Major morbidity occurred in 4 patients (33%). The 30-day and 90-day mortality were both 0%. Of 80 adverse events, 9 were classified serious, but none of these were related to study treatment. Local cisplatin concentration in the chest wall tissue was high at all dose levels (median, 46.3 µg/g [12-133 µg/g]). In serum, median cisplatin area under the concentration time curve values were always below renal toxicity levels. The median overall survival with 95% confidence interval was 21 months (10-31 months). In 1 patient with epithelioid malignant pleural mesothelioma (International Mesothelioma Interest Group stage I), there was no sign of relapse 48 months after treatment (44 mg/m2 body surface area). CONCLUSIONS: The administration of intracavitary cisplatin-fibrin is safe with favorable pharmacokinetics. Although most patients had advanced disease, long-term outcomes are comparable to other multimodal concepts. A confirmation phase II trial is ongoing.

Iron deficiency is associated with higher mortality in patients undergoing cardiac surgery: a prospective study.

BACKGROUND: Iron deficiency is frequent in patients undergoing cardiac surgery. The relevance of iron deficiency, however, is ill defined. Therefore, our study aimed to investigate the impact of iron deficiency (ferritin <100 µg L-1) with or without concomitant anaemia on clinical outcome after cardiac surgery. METHODS: In this prospective observational study, 730 patients undergoing elective cardiac surgery were assigned into four groups according to their iron status and anaemia. Mortality, serious adverse events (SAEs), major cardiac and cerebrovascular events (MACCEs), allogenic blood transfusion requirements, and length of hospital stay were assessed during a 90-day follow-up period. The effect of iron deficiency on these outcomes was first calculated in models adjusting for anaemia only, followed by two multivariate models adjusting for anaemia and either the EuroSCORE II or any possible confounders. RESULTS: The presence of iron deficiency (ferritin <100 µg L-1) was associated with an increase in 90-day mortality from 2% to 5% in patients without anaemia, and from 4% to 14% in patients with anaemia. Logistic regression resulted in an odds ratio of 3.5 (95% confidence interval: 1.5-8.4); P=0.004. The effect persisted in both multivariate models. Moreover, iron deficiency was associated with an increased incidence of SAEs, MACCEs, transfusion, and prolonged hospital stay. CONCLUSIONS: Preoperative iron deficiency (ferritin <100 µg L-1) was independently associated with increased mortality, more SAEs, and prolonged hospital stay after cardiac surgery. These findings underline the importance of preoperative iron deficiency screening in the context of a comprehensive patient blood management programme, and highlight its importance as a research topic in cardiac surgery. CLINICAL TRIAL REGISTRATION: NCT02031289.

Standard coagulation assays alone are not sufficient to exclude surgically relevant rivaroxaban plasma concentrations.

BACKGROUND: While mainly larger hospitals have introduced routine anti-Xa assays for rivaroxaban (RXA), these are not readily available to smaller hospitals often relying on routine coagulation tests such as prothrombin time (PT) and activated partial thromboplastin time (aPTT).The aim of our study was to investigate the effect of RXA plasma concentration on the standard coagulation tests PT (Quick test and INR) and aPTT in a large group of real-life patients. We further assessed whether normal results of these standard coagulation assays are sufficient to exclude surgically relevant RXA plasma concentration, defined as > 50 mcg/l. METHODS: This retrospective study included all patients between 2012 and 2016 where anti-Xa (calibrated for RXA), PT (Quick test and INR), and/or aPTT were determined from the same sample. PT is expressed as Quick value (% of normal plasma pool). In total, 1027 measurements in 622 patients were eligible for analysis: 752 measurements of 505 patients for Quick/INR and 594 measurements of 417 patients for aPTT. RESULTS: A moderate correlation of PT/Quick (Pearson's correlation coefficient - 0.59; p < 0.001), INR (Pearson's correlation coefficient 0.5; p < 0.001), and aPTT (Pearson's correlation coefficient 0.53; p < 0.001) with RXA plasma concentration was observed. However, in 50% of all samples with a normal PT/Quick, in 25% of all samples with a normal INR and in 80% of all samples with a normal aPTT residual RXA plasma concentration was surgically relevant. CONCLUSION: Although a moderate correlation of RXA plasma concentration with PT/Quick, INR, and aPTT was observed, standard coagulation assays are not sufficient to exclude surgically relevant RXA plasma concentrations.

Implementation of new standard operating procedures for geriatric trauma patients with multiple injuries: a single level I trauma centre study.

BACKGROUND: The demographic changes towards ageing of the populations in developed countries impose a challenge to trauma centres, as geriatric trauma patients require specific diagnostic and therapeutic procedures. This study investigated whether the integration of new standard operating procedures (SOPs) for the resuscitation room (ER) has an impact on the clinical course in geriatric patients. The new SOPs were designed for severely injured adult trauma patients, based on the Advanced Trauma Life Support (ATLS) and imply early whole-body computed tomography (CT), damage control surgery, and the use of goal-directed coagulation management. METHODS: Single-centre cohort study. We included all patients ≥65 years of age with an Injury Severity Score (ISS) ≥ 9 who were admitted to our hospital primarily via ER. A historic cohort was compared to a cohort after the implementation of the new SOPs. RESULTS: We enrolled 311 patients who met the inclusion criteria between 2000 and 2006 (group PreSOP) and 2010-2012 (group SOP). There was a significant reduction in the mortality rate after the implementation of the new SOPs (P = .001). This benefit was seen only for severely injured patients (ISS ≥ 16), but not for moderately injured patients (ISS 9-15). There were no differences with regard to infection rates or rate of palliative care. CONCLUSIONS: We found an association between implementation of new ER SOPs, and a lower mortality rate in severely injured geriatric trauma patients, whereas moderately injured patients did not obtain the same benefit. TRIAL REGISTRATION: Clinicaltrials.gov NCT03319381, retrospectively registered 24 October 2017.

Clinical Features and Outcomes of Patients With Malignancy and Takotsubo Syndrome: Observations From the International Takotsubo Registry.

Background Clinical characteristics and outcomes of takotsubo syndrome (TTS) patients with malignancy have not been fully elucidated. This study sought to explore differences in clinical characteristics and to investigate short- and long-term outcomes in TTS patients with or without malignancy. Methods and Results TTS patients were enrolled from the International Takotsubo Registry. The TTS cohort was divided into patients with and without malignancy to investigate differences in clinical characteristics and to assess short- and long-term mortality. A subanalysis was performed comparing long-term mortality between a subset of TTS patients with or without malignancy and acute coronary syndrome (ACS) patients with or without malignancy. Malignancy was observed in 16.6% of 1604 TTS patients. Patients with malignancy were older and more likely to have physical triggers, but less likely to have emotional triggers compared with those without malignancy. Long-term mortality was higher in patients with malignancy (P<0.001), while short-term outcome was comparable (P=0.17). In a subanalysis, long-term mortality was comparable between TTS patients with malignancies and ACS patients with malignancies (P=0.13). Malignancy emerged as an independent predictor of long-term mortality. Conclusions A substantial number of TTS patients show an association with malignancy. History of malignancy might increase the risk for TTS, and therefore, appropriate screening for malignancy should be considered in these patients. Clinical Trial Registration URL: http://www.clinicaltrial.gov. Unique identifier: NCT01947621.

Detrusor overactivity is missed by stopping urodynamic investigation at a bladder volume of 500 mL.

OBJECTIVES: To investigate whether detrusor overactivity (DO) is missed in a relevant percentage of patients if the urodynamic investigation (UDI) is stopped at a filling volume of 500 mL due to the fear of bladder overdistention, in patients with lower urinary tract symptoms and high bladder capacity. PATIENTS AND METHODS: A consecutive series of 1598 patients with a bladder capacity of >500 mL in the bladder diary undergoing UDI due to lower urinary tract dysfunction (LUTD) was prospectively investigated. UDI was performed according to Good Urodynamic Practices recommended by the International Continence Society. UDI was stopped at strong desire to void or in case of autonomic dysreflexia, vesico-uretero-renal reflux, bladder pain or discomfort. RESULTS: Of the 1598 patients (594 women, 1004 men), 1282 (80%) and 316 (20%) had neurogenic and non-neurogenic LUTD, respectively. Overall, DO was detected in 66% (1048/1598), in 71% (910/1282) with neurogenic and in 44% (138/316) with non-neurogenic LUTD. DO occurred in 16% (263/1598, 95% confidence interval [CI] 14.7-18.4%) only at a bladder volume >500 mL. This phenomenon was significantly (P < 0.001) more frequent in patients with neurogenic (18% [236/1282], 95% CI 16.4-20.6%) compared with non-neurogenic (9% [27/316], 95% CI 5.9-12.1%) LUTD. CONCLUSIONS: In both neurological and non-neurological patients with high bladder capacity, we strongly recommend not to stop UDI at a bladder volume of 500 mL, as DO might be missed in a relevant percentage leading to inappropriate patient treatment.

Effect of ultra-short-term treatment of patients with iron deficiency or anaemia undergoing cardiac surgery: a prospective randomised trial.

BACKGROUND: Anaemia and iron deficiency are frequent in patients scheduled for cardiac surgery. This study assessed whether immediate preoperative treatment could result in reduced perioperative red blood cell (RBC) transfusions and improved outcome. METHODS: In this single-centre, randomised, double-blind, parallel-group controlled study, patients undergoing elective cardiac surgery with anaemia (n=253; haemoglobin concentration (Hb) <120 g/L in women and Hb <130 g/L in men) or isolated iron deficiency (n=252; ferritin <100 mcg/L, no anaemia) were enrolled. Participants were randomly assigned (1:1) with the use of a computer-generated range minimisation (allocation probability 0·8) to receive either placebo or combination treatment consisting of a slow infusion of 20 mg/kg ferric carboxymaltose, 40 000 U subcutaneous erythropoietin alpha, 1 mg subcutaneous vitamin B12, and 5 mg oral folic acid or placebo on the day before surgery. Primary outcome was the number of RBC transfusions during the first 7 days. This trial is registered with ClinicalTrials.gov, number NCT02031289. FINDINGS: Between Jan 9, 2014, and July 19, 2017, 1006 patients were enrolled; 505 with anaemia or isolated iron deficiency and 501 in the registry. The combination treatment significantly reduced RBC transfusions from a median of one unit in the placebo group (IQR 0-3) to zero units in the treatment group (0-2, during the first 7 days (odds ratio 0·70 [95% CI 0·50-0·98] for each threshold of number of RBC transfusions, p=0·036) and until postoperative day 90 (p=0·018). Despite fewer RBC units transfused, patients in the treatment group had a higher haemoglobin concentration, higher reticulocyte count, and a higher reticulocyte haemoglobin content during the first 7 days (p≤0·001). Combined allogeneic transfusions were less in the treatment group (0 [IQR 0-2]) versus the placebo group (1 [0-3]) during the first 7 days (p=0·038) and until postoperative day 90 (p=0·019). 73 (30%) serious adverse events were reported in the treatment group group versus 79 (33%) in the placebo group. INTERPRETATION: An ultra-short-term combination treatment with intravenous iron, subcutaneous erythropoietin alpha, vitamin B12, and oral folic acid reduced RBC and total allogeneic blood product transfusions in patients with preoperative anaemia or isolated iron deficiency undergoing elective cardiac surgery. FUNDING: Vifor Pharma and Swiss Foundation for Anaesthesia Research.

Does Coffee Intake Reduce Postoperative Ileus After Laparoscopic Elective Colorectal Surgery? A Prospective, Randomized Controlled Study: The Coffee Study.

BACKGROUND: Postoperative ileus after colorectal surgery is a frequent problem that significantly prolongs hospital stay and increases perioperative costs. OBJECTIVE: The aim was to evaluate the effect of standardized coffee intake on postoperative bowel movement after elective laparoscopic colorectal resection. DESIGN: This is a prospective randomized controlled trial that was conducted between September 2014 and December 2016. SETTINGS: This study was performed in a public cantonal hospital in Switzerland with accreditation for colon and rectum cancer surgery. PATIENTS: Patients who underwent elective colorectal surgery were included. INTERVENTIONS: Patients were randomly assigned either to the intervention group receiving coffee or the control group receiving tea. A total of 150 mL of the respective beverage was drunk 3 times per day every postoperative day until discharge. MAIN OUTCOME MEASURES: The primary end point was time to first bowel movement. Secondary end points included the use of laxative, insertion of a nasogastric tube, length of hospital stay, and postoperative complications. RESULTS: A total of 115 patients were randomly assigned: 56 were allocated to the coffee group and 59 to the tea group. After coffee intake, the first bowel movement occurred after a median of 65.2 hours versus 74.1 hours in the control group (intention-to-treat analysis; p = 0.008). The HR for earlier first bowel movement after coffee intake was 1.67 (p = 0.009). In the per-protocol analysis, hospital stay was shorter in the coffee group (6 d in the coffee group vs 7 d in the tea group; p = 0.043). LIMITATIONS: The rate of protocol violation, mostly coffee consumption in the tea arm, was relatively high, even if patients were clearly instructed not to consume coffee if they were in the tea arm. CONCLUSIONS: Coffee intake after elective laparoscopic colorectal resection leads to faster recovery of bowel function. Therefore, coffee intake represents a simple and effective strategy to prevent postoperative ileus. See Video Abstract at http://links.lww.com/DCR/A955. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT02469441.

Phenotype, treatment practice and outcome in the cobalamin-dependent remethylation disorders and MTHFR deficiency: Data from the E-HOD registry.

AIM: To explore the clinical presentation, course, treatment and impact of early treatment in patients with remethylation disorders from the European Network and Registry for Homocystinurias and Methylation Defects (E-HOD) international web-based registry. RESULTS: This review comprises 238 patients (cobalamin C defect n = 161; methylenetetrahydrofolate reductase deficiency n = 50; cobalamin G defect n = 11; cobalamin E defect n = 10; cobalamin D defect n = 5; and cobalamin J defect n = 1) from 47 centres for whom the E-HOD registry includes, as a minimum, data on medical history and enrolment visit. The duration of observation was 127 patient years. In 181 clinically diagnosed patients, the median age at presentation was 30 days (range 1 day to 42 years) and the median age at diagnosis was 3.7 months (range 3 days to 56 years). Seventy-five percent of pre-clinically diagnosed patients with cobalamin C disease became symptomatic within the first 15 days of life. Total homocysteine (tHcy), amino acids and urinary methylmalonic acid (MMA) were the most frequently assessed disease markers; confirmatory diagnostics were mainly molecular genetic studies. Remethylation disorders are multisystem diseases dominated by neurological and eye disease and failure to thrive. In this cohort, mortality, thromboembolic, psychiatric and renal disease were rarer than reported elsewhere. Early treatment correlates with lower overall morbidity but is less effective in preventing eye disease and cognitive impairment. The wide variation in treatment hampers the evaluation of particular therapeutic modalities. CONCLUSION: Treatment improves the clinical course of remethylation disorders and reduces morbidity, especially if started early, but neurocognitive and eye symptoms are less responsive. Current treatment is highly variable. This study has the inevitable limitations of a retrospective, registry-based design.

Intraoperative unfolding and postoperative pruning of the pituitary gland after transsphenoidal surgery for pituitary adenoma: A volumetric and endocrinological evaluation.

PURPOSE: To describe the volumetric changes that the pituitary gland (PG) undergoes during and after transsphenoidal surgery (TSS), and to evaluate if unfolding and/or pruning are related to endocrinological outcome measures. METHODS: Retrospective evaluation of data prospectively collected of a cohort of patients undergoing TSS for a pituitary adenoma with the adjunctive use of high field 3 Tesla intraoperative MRI. All patients underwent a full endocrinological workup preoperatively, as well as at 6 weeks and 1 year postoperatively. A decrease in PG volume ≥15% between the intraoperative and 3-month, or between the 3-month and 12-month measurements, was considered early and late pruning, respectively. RESULTS: The PG unfolds significantly during TSS, and subsequently undergoes pruning up until 1 year postoperatively, in most cases returning to the preoperatively measured PG volume. A smaller baseline PG volume predicts intraoperative unfolding. Early pruning of the PG after surgery was associated with new functional deficits. Baseline pituitary compression also correlated to newly occurring deficits after surgery. A larger 1-year pituitary volume was associated with biochemical remission in secreting adenomas. CONCLUSIONS: The PG shows dynamic change during and after TSS for pituitary adenoma. Small baseline and 3-month PG volumes, as well as early pruning were independently associated with new deficits. Our findings warrant prospective validation in a larger cohort with higher statistical power.

Efficacy of selective digestive decontamination in patients with multiple myeloma undergoing high-dose chemotherapy and autologous stem cell transplantation.

Selective digestive decontamination (SDD) with the oral, non-absorbable antimicrobial substances gentamicin, vancomycin and amphotericin B was optionally used at our institution to reduce the risk of gastrointestinal tract derived infections in multiple myeloma (MM) patients undergoing high-dose chemotherapy with subsequent autologous stem cell transplantation (HDCT/ASCT). The majority of patients received sulfamethoxazole-trimethoprim as pneumocystis pneumonia prophylaxis. From 203 patients receiving their first HDCT/ASCT between 2009 and 2015, we compared retrospectively 90 patients receiving SDD to 113 patients not receiving SDD. The administration of SDD was associated with a reduction of bacterial infections after HDCT/ASCT (overall: 8% versus 24%, p = .002; gram-negative pathogens: 1% versus 11%, p = .006) and less use of systemic antibiotics (62% versus 77%, p = .022). Omission of SDD was an independent risk factor for developing neutropenic fever and bloodstream infections. SDD could be an option to reduce bacterial infections in patients undergoing HDCT/ASCT that needs to be tested in prospective trials.

Predictors of blood loss in lung transplant surgery-a single center retrospective cohort analysis.

BACKGROUND: This retrospective study aims to identify clinical predictors of intraoperative blood loss during lung transplantation. While for other surgical specialties predictors of blood loss have been identified such as previous likewise located surgery, poor preoperative health status of patients, blood coagulation status, and use of extra corporeal circulation, predictors of blood loss during lung transplantation are not yet established. METHODS: A total of 326 lung transplants were performed between January 2000 and February 2014 at a tertiary hospital. The primary aim was to associate blood loss with the following potential predictors: pulmonary arterial hypertension, pre- or intraoperative extracorporeal life support (ECLS), previous thoracic surgery, previous lung transplant, and Charlson Comorbidity Index (CCI). Postoperative complications and 30-day mortality were secondary endpoints of the study. RESULTS: Median estimated blood loss during lung transplant was 1,500 mL (IQR, 1,000-2,875 mL). Pre- and intraoperative ECLS (P=0.02, P<0.001) independently increased blood loss by 59% and 107%, respectively. The higher blood loss during re-transplant marginally missed the significance level (P=0.05). Pulmonary arterial hypertension, previous thoracic surgery and high CCI were not associated with increased blood loss. As secondary outcomes, postoperative complications were more common in patients with a higher blood loss (P=0.04) but was not associated with higher 30-day mortality (P=0.18). CONCLUSIONS: Pre- and intraoperative ECLS were significant risk factors for higher blood loss during lung transplantation. Higher blood loss was associated with higher incidence of postoperative complications but not with a higher 30-day mortality.