Anticoagulation with Edoxaban in Patients with Atrial High-Rate Episodes.

BACKGROUND: Device-detected atrial high-rate episodes (AHREs) are atrial arrhythmias detected by implanted cardiac devices. AHREs resemble atrial fibrillation but are rare and brief. Whether the occurrence of AHREs in patients without atrial fibrillation (as documented on a conventional electrocardiogram [ECG]) justifies the initiation of anticoagulants is not known. METHODS: We conducted an event-driven, double-blind, double-dummy, randomized trial involving patients 65 years of age or older who had AHREs lasting for at least 6 minutes and who had at least one additional risk factor for stroke. Patients were randomly assigned in a 1:1 ratio to receive edoxaban or placebo. The primary efficacy outcome was a composite of cardiovascular death, stroke, or systemic embolism, evaluated in a time-to-event analysis. The safety outcome was a composite of death from any cause or major bleeding. RESULTS: The analysis population consisted of 2536 patients (1270 in the edoxaban group and 1266 in the placebo group). The mean age was 78 years, 37.4% were women, and the median duration of AHREs was 2.8 hours. The trial was terminated early, at a median follow-up of 21 months, on the basis of safety concerns and the results of an independent, informal assessment of futility for the efficacy of edoxaban; at termination, the planned enrollment had been completed. A primary efficacy outcome event occurred in 83 patients (3.2% per patient-year) in the edoxaban group and in 101 patients (4.0% per patient-year) in the placebo group (hazard ratio, 0.81; 95% confidence interval [CI], 0.60 to 1.08; P = 0.15). The incidence of stroke was approximately 1% per patient-year in both groups. A safety outcome event occurred in 149 patients (5.9% per patient-year) in the edoxaban group and in 114 patients (4.5% per patient-year) in the placebo group (hazard ratio, 1.31; 95% CI, 1.02 to 1.67; P = 0.03). ECG-diagnosed atrial fibrillation developed in 462 of 2536 patients (18.2% total, 8.7% per patient-year). CONCLUSIONS: Among patients with AHREs detected by implantable devices, anticoagulation with edoxaban did not significantly reduce the incidence of a composite of cardiovascular death, stroke, or systemic embolism as compared with placebo, but it led to a higher incidence of a composite of death or major bleeding. The incidence of stroke was low in both groups. (Funded by the German Center for Cardiovascular Research and others; NOAH-AFNET 6 ClinicalTrials.gov number, NCT02618577; ISRCTN number, ISRCTN17309850.).

Anticoagulation with edoxaban in patients with long atrial high-rate episodes ≥24†h.

BACKGROUND AND AIMS: Patients with long atrial high-rate episodes (AHREs) ≥24 h and stroke risk factors are often treated with anticoagulation for stroke prevention. Anticoagulation has never been compared with no anticoagulation in these patients. METHODS: This secondary pre-specified analysis of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High-rate episodes (NOAH-AFNET 6) trial examined interactions between AHRE duration at baseline and anticoagulation with edoxaban compared with placebo in patients with AHRE and stroke risk factors. The primary efficacy outcome was a composite of stroke, systemic embolism, or cardiovascular death. The safety outcome was a composite of major bleeding and death. Key secondary outcomes were components of these outcomes and electrocardiogram (ECG)-diagnosed atrial fibrillation. RESULTS: Median follow-up of 2389 patients with core lab-verified AHRE was 1.8 years. AHRE ≥24 h were present at baseline in 259/2389 patients (11%, 78 ± 7 years old, 28% women, CHA2DS2-VASc 4). Clinical characteristics were not different from patients with shorter AHRE. The primary outcome occurred in 9/132 patients with AHRE ≥24 h (4.3%/patient-year, 2 strokes) treated with anticoagulation and in 14/127 patients treated with placebo (6.9%/patient-year, 2 strokes). Atrial high-rate episode duration did not interact with the efficacy (P-interaction = .65) or safety (P-interaction = .98) of anticoagulation. Analyses including AHRE as a continuous parameter confirmed this. Patients with AHRE ≥24 h developed more ECG-diagnosed atrial fibrillation (17.0%/patient-year) than patients with shorter AHRE (8.2%/patient-year; P < .001). CONCLUSIONS: This hypothesis-generating analysis does not find an interaction between AHRE duration and anticoagulation therapy in patients with device-detected AHRE and stroke risk factors. Further research is needed to identify patients with long AHRE at high stroke risk.

Second-generation distal attachment cuff for adenoma detection in screening colonoscopy: a randomized multicenter study.

BACKGROUND AND AIMS: Randomized studies have demonstrated that a distal attachment cap with rubber side arms, the Endocuff Vision (ECV; Olympus America, Center Valley, Pa, USA), increased colonoscopic adenoma detection rate (ADR) in various mixed patient collectives. This is the first study to evaluate its use in a primary colonoscopic screening program. METHODS: Patients over age 55 years undergoing screening colonoscopy in 9 German private offices in Berlin and Hamburg were randomized to either the study group using ECV or the control group using high-definition colonoscopies (standard of care). The main outcome parameter was ADR, whereas secondary outcomes were detection rates of all adenomas per colonoscopy (APCs), of adenoma subgroups, and of hyperplastic polyps. RESULTS: Of 1416 patients (mean age, 61.1 years; 51.8% women), with a median of 41 examinations per examiner (n = 23; interquartile range, 12-81), 700 were examined with ECV and 716 without. Adjusting for the effects of the colonoscopies, ADR was 39.5% (95% confidence interval [CI], 32.6%-46.3%) in the ECV group versus 32.2% (95% CI, 25.9%-38.6%) in the control group, which resulted in an increase of 7.2% (95% CI, 2.3%-12.2%; P = .004). The increase in ADR was mainly because of small polyps, with adjusted ADRs for adenomas <10 mm of 33.3% (95% CI, 26.5%-40.2%) for study patients versus 24.0% (95% CI, 18.2%-29.8%) for control patients (P < .001). APC was also significantly increased (.57 ECV vs .51 control subjects, P = .045). CONCLUSIONS: A distal attachment cap with side arms significantly increased the ADR in patients undergoing primary colonoscopic screening. Because of the correlation of ADR and interval cancer, its use should be encouraged, especially in this setting. (Clinical trial registration number: NCT03442738.).

Assessment of aortic diameter in Marfan patients: intraindividual comparison of 3D-Dixon and 2D-SSFP magnetic resonance imaging.

OBJECTIVES: To compare the accuracy and precision of 3D-Dixon and 2D-SSFP MR-imaging for assessment of aortic diameter in Marfan patients. METHODS: This prospective single-center study investigated respiratory-gated 3D-Dixon and breath-hold 2D-SSFP non-contrast MR-imaging at 3 T in 47 Marfan patients (36.0 ± 13.2 years, 28♀,19♂). Two radiologists performed individual diameter measurements at five levels of the thoracic aorta and evaluated image quality on a four-grade scale (1 = poor, 4 = excellent) and artifacts (1 = severe, 4 = none). Aortic root diameters acquired by echocardiography served as a reference standard. Intraclass correlation coefficient, Bland-Altman analyses, F-test, t-test, and regression analyses were used to assess agreement between observers and methods. RESULTS: Greatest aortic diameters were observed at the level of the sinuses of Valsalva (SOV) for 3D-Dixon (38.2 ± 6.8 mm) and 2D-SSFP (38.3 ± 7.1 mm) (p = 0.53). Intra- and interobserver correlation of diameter measurements was excellent at all aortic levels for both 3D-Dixon (r = 0.94-0.99 and r = 0.94-0.98) and 2D-SSFP (r = 0.96-1.00 and r = 0.95-0.99). 3D-Dixon-derived and 2D-SSFP-derived diameter measurements at the level of the SOV revealed a strong correlation with echocardiographic measurements (r = 0.92, p < 0.001 and r = 0.93, p < 0.001, respectively). The estimated mean image quality at the level of SOV was higher for 2D-SSFP compared to that for 3D-Dixon (3.3 (95%-CI: 3.1-3.5) vs. 2.9 (95%-CI: 2.7-3.1)) (p < 0.001). Imaging artifacts were less at all aortic levels for 3D-Dixon compared to 2D-SSFP (3.4-3.8 vs. 2.8-3.1) (all p < 0.002). CONCLUSION: Respiratory-gated 3D-Dixon and breath-hold 2D-SSFP MR-imaging provide accurate and precise aortic diameter measurements. We recommend 3D-Dixon imaging for monitoring of aortic diameter in Marfan patients due to fewer imaging artifacts and the possibility of orthogonal multiplanar reformations of the aortic root. KEY POINTS: • Respiratory-gated 3D-Dixon and breath-hold 2D-SSFP imaging provide accurate and precise aortic diameter measurements in patients suffering from Marfan syndrome. • Imaging artifacts are stronger in 2D-SFFP imaging than in 3D-Dixon imaging. • We recommend 3D-Dixon imaging for monitoring of aortic diameter in Marfan patients due to fewer imaging artifacts and the possibility of orthogonal multiplanar reformations.

Preoperative Spirometry in Patients With Known or Suspected Chronic Obstructive Pulmonary Disease Undergoing Major Surgery: The Prospective Observational PREDICT Study.

BACKGROUND: Pulmonary function tests (PFTs) such as spirometry and blood gas analysis have been claimed to improve preoperative pulmonary risk assessment, but the scientific literature is conflicting. The Preoperative Diagnostic Tests for Pulmonary Risk Assessment in Chronic Obstructive Pulmonary Disease (PREDICT) study aimed to determine whether preoperative PFTs improve the prediction of postoperative pulmonary complications (PPCs) in patients with known or suspected chronic obstructive pulmonary disease (COPD) undergoing major surgery. A secondary aim was to determine whether the Global Initiative for Chronic Obstructive Lung Diseases (GOLD) classification of airflow limitation severity (grades I-IV) is associated with PPC. METHODS: In this prospective, single-center study, patients with GOLD key indicators for COPD scheduled for major surgery received PFTs. Patients with confirmed COPD (forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC] ≤0.7) were included in the COPD cohort and compared with a reference cohort without COPD. We developed 3 multivariable risk prediction models and compared their ability to predict PPC: the "standard model" (medical preconditions, and sociodemographic and surgical data), the "COPD assessment model" (additional GOLD key indicators, pack-years, and poor exercise capacity), and the "PFT model" (additional PFT parameters selected by adaptive least absolute shrinkage and selection operator [LASSO] regression). Multiple LASSO regressions were used for cross-validation. RESULTS: A total of 31,714 patients were assessed for eligibility; 1271 individuals received PFTs. Three hundred twenty patients (240 with confirmed COPD: 78 GOLD I, 125 GOLD II, 28 GOLD III, 9 GOLD IV, and 80 without COPD) completed follow-up. The diagnostic performance was similar among the standard model (cross-validated area under the curve [cvAUC], 0.723; bias-corrected bootstrapped [bc-b] 95% confidence interval [CI], 0.663-0.775), COPD assessment model (cvAUC, 0.724; bc-b 95% CI, 0.662-0.777), and PFT model (cvAUC, 0.729; bc-b 95% CI, 0.668-0.782). Previously known COPD was an independent predictor in the standard and COPD assessment model. %FEV1 PRED was the only PFT parameter selected by LASSO regression and was an independent predictor in the PFT model (adjusted odds ratios [OR], 0.98; 95% CI, 0.967-.0.998; P = .030). The risk for PPC significantly increased with GOLD grades ( P < .001). COPD was newly diagnosed in 53.8% of the patients with confirmed COPD; however, these individuals were not at increased risk for PPC ( P = .338). CONCLUSIONS: COPD is underdiagnosed in surgical patients. Patients with newly diagnosed COPD commonly presented with low GOLD severity grades and were not at higher risk for PPC. Neither a structured COPD-specific assessment nor preoperative PFTs added incremental diagnostic value to the standard clinical preassessment in patients with known or suspected COPD. Unnecessary postponement of surgery and undue health care costs can be avoided.

Transnasal Videoendoscopy for Preoperative Airway Risk Stratification: Development and Validation of a Multivariable Risk Prediction Model.

BACKGROUND: Transnasal flexible videoendoscopy (TVE) of the larynx is a standard of care for the detection and staging of pharyngolaryngeal lesions in otorhinolaryngology. Patients frequently present with existing TVE examinations before anesthesia. Although these patients are considered high risk, the diagnostic value of TVE for airway risk stratification is currently unknown. How can captured images or videos be used for anesthesia planning, and which lesions are most concerning? This study aimed to develop and validate a multivariable risk prediction model for difficult airway management based on TVE findings and to determine whether the discrimination of the Mallampati score can be improved by adding this new TVE model. METHODS: This retrospective single-center development and validation study assessed 4021 patients who underwent 4524 otorhinolaryngologic surgeries at the University Medical Centre Hamburg-Eppendorf between January 1, 2011, and April 30, 2018, with electronically stored TVE videos and included 1099 patients who underwent 1231 surgeries. TVE videos and anesthesia charts were systematically reviewed in a blinded fashion. The Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was used for variable selection, model development, and cross validation. RESULTS: The prevalence of difficult airway management was 24.7% (304/1231). Lesions at the vocal cords, epiglottis, or hypopharynx were not selected by the LASSO regression, while lesions at the vestibular folds (ß-coefficient 0.123), supraglottic region (ß-coefficient 0.161), arytenoids (ß-coefficient 0.063), and viewing restrictions on the rima glottidis that cover ≥50% of the glottis area (ß-coefficient 0.485) and pharyngeal secretion retention (ß-coefficient 0.372) were relevant risk factors for difficult airway management. The model was adjusted for sex, age, and body mass index. The area under the receiver operating characteristic curve (95% confidence interval) of the Mallampati score was 0.61 (0.57-0.65) and 0.74 (0.71-0.78) of the TVE model combined with Mallampati ( P < .001). CONCLUSIONS: Stored images and videos from TVE examinations can be reused for the purpose of predicting risk associated with airway management. Vestibular fold, supraglottic, and arytenoid lesions are most concerning, especially if they are accompanied by secretion retention or restrict the glottic view. Our data indicate that the TVE model improves discrimination of the Mallampati score and might, therefore, be a useful addition to traditional bedside airway risk examinations.

Attaining sinus rhythm mediates improved outcome with early rhythm control therapy of atrial fibrillation: the EAST-AFNET 4 trial.

AIMS: A strategy of systematic, early rhythm control (ERC) improves cardiovascular outcomes in patients with atrial fibrillation (AF). It is not known how this outcome-reducing effect is mediated. METHODS AND RESULTS: Using the Early treatment of Atrial Fibrillation for Stroke prevention Trial (EAST-AFNET 4) data set, potential mediators of the effect of ERC were identified in the total study population at 12-month follow up and further interrogated by use of a four-way decomposition of the treatment effect in an exponential model predicting future primary outcome events. Fourteen potential mediators of ERC were identified at the 12-month visit. Of these, sinus rhythm at 12 months explained 81% of the treatment effect of ERC compared with usual care during the remainder of follow up (4.1 years). In patients not in sinus rhythm at 12 months, ERC did not reduce future cardiovascular outcomes (hazard ratio 0.94, 95% confidence interval 0.65-1.67). Inclusion of AF recurrence in the model only explained 31% of the treatment effect, and inclusion of systolic blood pressure at 12 months only 10%. There was no difference in outcomes in patients who underwent AF ablation compared with those who did not undergo AF ablation. CONCLUSION: The effectiveness of early rhythm control is mediated by the presence of sinus rhythm at 12 months in the EAST-AFNET 4 trial. Clinicians implementing ERC should aim for rapid and sustained restoration of sinus rhythm in patients with recently diagnosed AF and cardiovascular comorbidities.

[Study section "From Symptom to Disease"-steps towards an integrated dentistry program]. / Studienabschnitt "Vom Symptom zur Erkrankung" ­ Schritte in ein integriertes Zahnmedizincurriculum.

Based on the integrated medicine program (iMED) at the University Medical Center Hamburg-Eppendorf, the dental education concept was fundamentally revised and an integrated dentistry program (iMED DENT) was developed. During this process, reform goals such as interdisciplinarity between dentistry and medicine, early patient contact, and psychosocial and communicative competencies as well as a scientific orientation were defined. The second study section "From Symptom to Disease" during the second and third years of study form a link between "Normal Function" in the first year and the final training section "Therapy". The modular structure of the integrated dentistry program allows topics to be taken up repetitively and deepened as well as strengthen dental skills during the preclinical practical training in preparation for patient treatment. Here, the implementation of dental prophylaxis, assisting in the clinic, and the assessment of patients' findings create an early link to the practice. Newly integrated are the science and communication tracks, which are also modular and closely interlinked with dentistry. So far, the results of the first three cohorts indicate a successful implementation of the new concept, but it should be continuously developed and improved.

Hybrid APC in Combination With Resection for the Endoscopic Treatment of Neoplastic Barrett's Esophagus: A Prospective, Multicenter Study.

INTRODUCTION: The current therapy of neoplastic Barrett's esophagus (BE) consists of endoscopic resection plus ablation, with radiofrequency ablation as the best studied technique. This prospective trial assesses a potential alternative, namely hybrid argon plasma ablation. METHODS: Consecutive patients with neoplastic BE undergoing ablation after curative endoscopic resection (89.6%) or primarily were included into this prospective trial in 9 European centers. Up to 5 ablation sessions were allowed for complete eradication of BE (initial complete eradication of intestinal metaplasia [CE-IM]), by definition including BE-associated neoplasia, documented by 1 negative endoscopy with biopsies. The main outcome was the rate of initial CE-IM in intention-to-treat (ITT) and per-protocol (PP) samples at 2 years. The secondary end points were the rate of recurrence-free cases (sustained CE-IM) documented by negative follow-up endoscopies with biopsies and immediate/delayed adverse events. RESULTS: One hundred fifty-four patients (133 men and 21 women, mean age 64 years) received a mean of 1.2 resection and 2.7 ablation sessions (range 1-5). Initial CE-IM was achieved in 87.2% of 148 cases in the PP analysis (ITT 88.4%); initial BE-associated neoplasia was 98.0%. On 2-year follow-up of the 129 successfully treated cases, 70.8% (PP) or 65.9% (ITT) showed sustained CE-IM; recurrences were mostly endoscopy-negative biopsy-proven BE epithelium and neoplasia in 3 cases. Adverse events were seen in 6.1%. DISCUSSION: Eradication and recurrence rates of Barrett's intestinal metaplasia and neoplasia by means of hybrid argon plasma coagulation at 2 years seem to be within expected ranges. Final evidence in comparison to radiofrequency ablation can only be provided by a randomized comparative trial.

Quantitative analysis of submucosal excision depth in endoscopic resection for early Barrett's cancer.

BACKGROUND : Following endoscopic resection of early-stage Barrett's esophageal adenocarcinoma (BEA), further oncologic management then fundamentally relies upon the accurate assessment of histopathologic risk criteria, which requires there to be sufficient amounts of submucosal tissue in the resection specimens. METHODS : In 1685 digitized tissue sections from endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) performed for 76 early BEA cases from three experienced centers, the submucosal thickness was determined, using software developed in-house. Neoplastic lesions were manually annotated. RESULTS : No submucosa was seen in about a third of the entire resection area (mean 33.8 % [SD 17.2 %]), as well as underneath cancers (33.3 % [28.3 %]), with similar results for both resection methods and with respect to submucosal thickness. ESD results showed a greater variability between centers than EMR. In T1b cancers, a higher rate of submucosal defects tended to correlate with R1 resections. CONCLUSION : The absence of submucosa underneath about one third of the tissue of endoscopically resected BEAs should be improved. Results were more center-dependent for ESD than for EMR. Submucosal defects can potentially serve as a parameter for standardized reports.

Incidence and risk factors of mental disorders in the elderly: The European MentDis_ICF65+ study.

OBJECTIVE: While incidence rates of depression and anxiety disorders in the elderly have been comprehensively investigated, the incidence rates of other mental disorders have rarely been researched. The incidence rate and predictors of various mental disorders in the elderly were evaluated in different European and associated countries. METHODS: A cross-sectional and longitudinal multi-centre survey of Diagnostic and Statistical Manual of Mental Disorders (4th ed.) diagnoses was conducted in different European and associated countries (Germany, Italy, Spain, Switzerland, the United Kingdom and Israel) to collect data on the prevalence and incidence of mental disorders in the elderly. The sample size of the longitudinal wave was N = 2592 elderly. RESULTS: The overall 1-year incidence rate for any mental disorder in the elderly is 8.65%. At 5.18%, any anxiety disorder had the highest incidence rate across all diagnostic groups. The incidence rate for any affective disorder was 2.97%. The lowest incidence rates were found for agoraphobia (1.37%) and panic disorder (1.30%). Risk factors for the development of any mental disorder were never having been married, no religious affiliation, a higher number of physical illnesses and a lower quality of life. CONCLUSION: In comparison to other studies, lower incidence rates for any affective disorder and middle-range incidence for any anxiety disorder were found. To the authors' knowledge, no prior studies have reported 1-year incidence rates for somatoform disorder, bipolar disorder and substance misuse in community-dwelling elderly. These findings indicate the need to raise awareness of psychosocial problems in the elderly and to ensure adequate availability of mental health services.

The baroreceptor reflex brought to life outside the classroom - an e-learning based asynchronous laboratory class using a non-supervised modified Active Standing Test.

BACKGROUND: E-learning based laboratory classes can replace or enhance in-classroom laboratories. They typically offer temporal flexibility, self-determined learning speed, repeatability and do not require supervision or face-to-face contact. The aim of this feasibility study was to investigate whether the established in-classroom laboratory class on the baroreceptor reflex (BRR) can be transformed into a new e-learning based asynchronous laboratory class for untrained, non-supervised students without medical equipment. The BRR is a fundamental cardiovascular process which is regularly visualized in physiology during in-classroom laboratories by a student-performed Active Standing Test (AST). During this voluntary provocation of orthostatic stress, the BRR reliably causes a solid rise in heart rate (HR) and a stabilization or even increase in blood pressure (BP). METHODS: The conventional AST was modified by omission of BP measurements which would require medical devices and was embedded into a framework of interactive digital material allowing independent student performance. With specific adaptions, this instrument was implemented to 1st and 2nd year curricula of human medicine, dental medicine, midwifery and pharmacy. An audience response system was used to collect the students' data on HR, epidemiology, technical problems, satisfaction and orthostatic symptoms. As primary outcome, we investigated the students' correct performance of the modified AST regarding textbook conformity of the HR data. Secondary outcomes included technical feasibility, the students' satisfaction and consistency of HR data within predefined subgroups (e.g., gender, curricula). Descriptive statistics are reported. RESULTS: The class was completed by 217 students (mean age: 23 ± 8 [SD], 81% female, 19% male). Mean reported rise of HR during standing was ~ 20 bpm (~ 30%) which is highly concordant to textbooks. Reported feasibility (~ 80% negated any technical issues) and students' satisfaction (4.4 on 5-point Likert-scale) were high. The HR data were consistent within the subgroups. CONCLUSION: This study demonstrates that the highly relevant BRR can be successfully addressed in an e-learning based asynchronous laboratory class implementing a non-supervised AST restricted to HR measurements embedded in digital material. The robust HR response and the adjustable complexity allow an application to different healthcare-related curricula. This class, therefore, provides a broad audience access to a fundamental concept of cardiovascular physiology.

Success and patient satisfaction of immediately loaded zirconia implants with fixed restorations one year after loading.

BACKGROUND: There is limited evidence for the use of zirconium dioxide implants in immediate implant placement as well as for related immediate loading protocols. The aim of this retrospective study was to investigate the survival rate, success and patient satisfaction of immediately placed zirconia implants compared to delayed placed implants. METHODS: The study included 58 partially edentulous patients who were treated between 2013 and 2015 with immediate and delayed transgingival healing zirconium dioxide implants (SDS, Kreuzlingen/ Switzerland). In addition to survival and success rate, marginal bone loss was assessed using radiographs and soft tissue was evaluated using Pink Esthetic Score. Oral health-related quality of life was investigated prospectively using a modified OHIP questionnaire. RESULTS: The cumulative survival rate of all implants included was 92% with 88% classified as full success. No significant difference was found between the bone levels of immediately and delayed placed and immediately and delayed loaded implants. The mean Pink Esthetic Score after final prosthetic rehabilitation was 12.2/14 points indicating excellent esthetic clinical results. Analysis of the OHIP questionnaire showed a mean value of 0.54/100 points reflecting a high patient satisfaction. CONCLUSIONS: Immediate and delayed placed as well as loaded zirconium dioxide implants showed excellent results regarding implant success and survival in this study. Zirconium dioxide implants may ensure excellent esthetic results and high patient satisfaction.

Prior Resection of the Primary Tumor Prolongs Survival After Peptide Receptor Radionuclide Therapy of Advanced Neuroendocrine Neoplasms.

OBJECTIVE: The aim of the study was to compare impact on survival after resection of primary tumors (PTs) after peptide receptor radionuclide therapy (PRRT). BACKGROUND: PRRT is a highly effective therapeutic option to treat locally advanced or metastatic neuroendocrine neoplasms (NENs). METHODS: We retrospectively analyzed the data of 889 patients with advanced NEN (G1-G3, stage IV) treated with at least 1 cycle of PRRT. In 486 of 889 patients (55%, group 1), PT had been removed before PRRT. Group 2 constituted 403 patients (45%) with no prior PT resection. Progression-free survival (PFS) and overall survival (OS) was determined by 68Ga SSTR-PET/CT in all patients applying RECIST and EORTC. RESULTS: Most patients had their PT in pancreas (n = 335; 38%) and small intestine (n = 284; 32%). Both groups received a mean of 4 cycles of PRRT (P = 0.835) with a mean cumulative administered radioactivity of 21.6 ±â€Š11.7 versus 22.2 ±â€Š11.2 GBq (P = 0.407). Median OS in group 1 was 134.0 months [confidence interval (CI): 118-147], whereas OS in group 2 was 67.0 months (CI: 60-80; hazard ratio 2.79); P < 0.001. Likewise, the median progression-free survival after first PRRT was longer in group 1 with 18.0 (CI: 15-20) months as compared to group 2 with 14.0 (CI: 15-18; hazard ratio 1.21) months; P = 0.012. CONCLUSIONS: A previous resection of the PT before PRRT provides a significant survival benefit in patients with NENs stage IV.

Effect of intravenous alteplase on post-stroke depression in the WAKE UP trial.

BACKGROUND AND PURPOSE: The aim was to study the effect of intravenous alteplase on the development of post-stroke depression (PSD) in acute stroke patients, and to identify predictors of PSD. METHODS: This post hoc analysis included patients with unknown onset stroke randomized to treatment with alteplase or placebo in the WAKE-UP trial (ClinicalTrials.gov number, NCT01525290), in whom a composite end-point of PSD was defined as a Beck Depression Inventory ≥10, medication with an antidepressant, or depression recorded as an adverse event. Multiple logistic regression was used to identify predictors of PSD at 90 days. Structural equation modelling was applied to assess the indirect effect of thrombolysis on PSD mediated by the modified Rankin Scale. RESULTS: Information on the composite end-point was available for 438 of 503 randomized patients. PSD was present in 96 of 224 (42.9%) patients in the alteplase group and 115 of 214 (53.7%) in the placebo group (odds ratio 0.63; 95% confidence interval 0.43-0.94; p = 0.022; adjusted for age and National Institutes of Health Stroke Scale at baseline). Prognostic factors associated with PSD included baseline medication with antidepressants, higher lesion volume, history of depression and assignment to placebo. While 65% of the effect of thrombolysis on PSD were caused directly, 35% were mediated by an improvement of the mRS. CONCLUSIONS: Treatment with alteplase in patients with acute stroke resulted in lower rates of depression at 90 days, which were only partially explained by reduced functional disability. Predictors of PSD including history and clinical characteristics may help in identifying patients at risk of PSD.

Predictors of attendance in outpatient group treatment for women with posttraumatic stress disorder and substance use disorder.

Objective: The present study investigated predictors of treatment attendance among 226 women with posttraumatic stress disorder (PTSD) and substance use disorder (SUD). Participants received either an integrated intervention for PTSD and SUD ("Seeking Safety") or a relapse prevention training (RPT) as part of a multicenter randomized controlled trial. Method: Beta-binomial regression was conducted to investigate baseline sociodemographic, motivational, mental health and substance use predictors of session attendance. Treatment by predictor interactions were included to identify treatment-specific predictors. Results: Session attendance was predicted by employment status, drug use severity and abstinence status. Higher drug use severity and unemployment were associated with less session attendance. The effect of abstinence status was treatment-specific, with abstinent participants in RPT attending most sessions. Conclusions: Considering individual characteristics could enhance session attendance in outpatient treatment for women with PTSD and SUD. This might include matching treatment concepts to abstinence status, the identification of attendance barriers in unemployed women and more intensive treatment settings for those with severe drug use.

Right-Sided Location Not Associated With Missed Colorectal Adenomas in an Individual-Level Reanalysis of Tandem Colonoscopy Studies.

BACKGROUND & AIMS: Interval cancers occur more frequently in the right colon. One reason could be that right-sided adenomas are frequently missed in colonoscopy examinations. We reanalyzed data from tandem colonoscopies to assess adenoma miss rates in relation to location and other factors. METHODS: We pooled data from 8 randomized tandem trials comprising 2218 patients who had diagnostic or screening colonoscopies (adenomas detected in 49.8% of patients). We performed a mixed-effects logistic regression with patients as cluster effects with different independent parameters. Factors analyzed included location (left vs right, splenic flexure as cutoff), adenoma size, form, and histologic features. Analyses were controlled for potential confounding factors such as patient sex and age, colonoscopy indication, and bowel cleanliness. RESULTS: Right-side location was not an independent risk factor for missed adenomas (odds ratio [OR] compared with the left side, 0.94; 95% CI, 0.75-1.17). However, compared with adenomas ≤5 mm, the OR for missing adenomas of 6-9 mm was 0.62 (95% CI, 0.44-0.87), and the OR for missing adenomas of ≥10 mm was 0.51 (95% CI, 0.33-0.77). Compared with pedunculated adenomas, sessile (OR, 1.82; 95% CI, 1.16-2.85) and flat adenomas (OR, 2.47; 95% CI, 1.49-4.10) were more likely to be missed. Histologic features were not significant risk factors for missed adenomas (OR for adenomas with high-grade intraepithelial neoplasia, 0.68; 95% CI, 0.34-1.37 and OR for sessile serrated adenomas, 0.87; 95% CI, 0.47-1.64 compared with low-grade adenomas). Men had a higher number of adenomas per colonoscopy (1.27; 95% CI, 1.21-1.33) than women (0.86; 95% CI, 0.80-0.93). Men were less likely to have missed adenomas than women (OR for missed adenomas in men, 0.73; 95% CI, 0.57-0.94). CONCLUSIONS: In an analysis of data from 8 randomized trials, we found that right-side location of an adenoma does not increase its odds for being missed during colonoscopy but that adenoma size and histologic features do increase risk. Further studies are needed to determine why adenomas are more frequently missed during colonoscopies in women than men.

CD44 is a RAS/STAT5-regulated invasion receptor that triggers disease expansion in advanced mastocytosis.

The Hermes receptor CD44 is a multifunctional adhesion molecule that plays an essential role in the homing and invasion of neoplastic stem cells in various myeloid malignancies. Although mast cells (MCs) reportedly express CD44, little is known about the regulation and function of this receptor in neoplastic cells in systemic mastocytosis (SM). We found that clonal CD34+/CD38- stem cells, CD34+/CD38+ progenitor cells, and CD117++/CD34- MCs invariably express CD44 in patients with indolent SM (ISM), SM with an associated hematologic neoplasm, aggressive SM, and MC leukemia (MCL). In addition, all human MCL-like cell lines examined (HMC-1, ROSA, and MCPV-1) displayed cytoplasmic and cell-surface CD44. We also found that expression of CD44 in neoplastic MCs depends on RAS-MEK and STAT5 signaling and increases with the aggressiveness of SM. Correspondingly, higher levels of soluble CD44 were measured in the sera of patients with advanced SM compared with ISM or cutaneous mastocytosis and were found to correlate with overall and progression-free survival. To investigate the functional role of CD44, a xenotransplantation model was employed using severe combined immunodeficient (SCID) mice, HMC-1.2 cells, and a short hairpin RNA (shRNA) against CD44. In this model, the shRNA-mediated knockdown of CD44 resulted in reduced MC expansion and tumor formation and prolonged survival in SCID mice compared with HMC-1.2 cells transduced with control shRNA. Together, our data show that CD44 is a RAS-MEK/STAT5-driven MC invasion receptor that correlates with the aggressiveness of SM. Whether CD44 can serve as therapeutic target in advanced SM remains to be determined in forthcoming studies.

Quality of life, level of functioning, and its relationship with mental and physical disorders in the elderly: results from the MentDis_ICF65+ study.

BACKGROUND: An ageing population worldwide needs to investigate quality of life (QoL) and level of functioning (LoF) in the elderly and its associated variables. We aimed to study the relationship between Quality of Life (QoL) and Level of Functioning (LoF) in an elderly population in Europe. METHOD: As part of the Ment_Dis65+ European Project, 3142 community-dwelling adults aged 65-84 years in six countries were assessed by using the adaptation for the elderly of the Composite International Diagnostic Interview (CIDI65+) to provide psychiatric diagnosis according to the International Classification of Diseases (10th edition) (ICD-10 Classification of Mental and Behavioural Disorders). Socio-demographic and clinical interviews, and two self-report tools, the World Health Organization QoL assessment (WHO QoL BREF), to assess QoL, and the WHO Disability Assessment Schedule -II (WHODAS-II), to assess LoF, were also administered. RESULTS: Most subjects reported good levels of QoL (56.6%) and self-rated health (62%), with no or mild disability (58.8%). There was a linear decrease of the QoL and the LoF by increase of age. Elderly with ICD-10 mental disorder (e.g. somatoform, affective and anxiety disorders) had poorer QoL and lower LoF. There were a number of predictors of lower levels of QoL and disability, including both socio-demographic variables (e.g. male gender, increase in age, poor financial situation, retirement, reduced number of close significant others), ICD-10 psychiatric diagnosis (mainly anxiety, somatoform disorders) and presence of medical disorders (mainly heart and respiratory diseases). CONCLUSIONS: The study indicates that QoL and LoF were quite acceptable in European elderly people. A series of variables, including psychiatric and somatic disorders, as well as socio-demographic factor influenced in a negative way both QoL and LoF. More specific links between mental health, social and health services dedicated to this segment of the population, should be implemented in order to provide better care for elderly people with conditions impacting their QoL and functioning.

Feasibility of extremely reduced-dose CT of the thoracic spine in human cadavers.

BACKGROUND: According to the as low as reasonably achievable (ALARA) principle, radiation exposure in computed tomography (CT) should be minimized while maintaining adequate image quality. Dedicated CT protocols combined with iterative reconstruction (IR) can reduce radiation dose and/or improve image quality. PURPOSE: To investigate the feasibility of extremely reduced-dose (RD) CT of the thoracic spine in human cadavers using a standard-dose (SD) and three different RDCT protocols reconstructed with filtered back projection (FBP) and IR. MATERIAL AND METHODS: The thoracic spines of 11 cadavers were examined using different RDCT protocols with decreasing reference tube currents (RDCT-1: 50 mAs; RDCT-2: 30 mAs; RDCT-3: 10 mAs) at 140 kV. A clinical SDCT (70 mAs, 140 kV) served as reference. Raw data were reconstructed using FBP and two increasing levels of IR (IRL4 and IRL6). Images were evaluated for image quality, diagnostic acceptability, and visibility of anatomical structures according to a 5-point-scale. RESULTS: Regardless of the reconstruction technique, image quality was rated as diagnostically acceptable for all cadavers in SDCT and RDCT-1. Image quality of reconstructions with FBP were generally rated lower. Application of IR improved image quality ratings in SDCT and RDCT. RDCT-2 with IR was the most reduced-dose CT protocol which enabled diagnostically acceptable image quality in all cadavers. Compared to SDCT, RDCT protocols resulted in significantly reduced effective radiation doses (SDCT: 4.1 ± 1.5 mSv; RDCT-1: 2.9 ± 1.1 mSv; 2:1.7 ± 0.6 mSv; 3:0.6 ± 0.1 mSv; P = 0.001). CONCLUSION: Diagnostically acceptable RDCT of the thoracic spine with 1.7 mSv is feasible using IR.