Expert assessment of infiltration depth and recommendation of endoscopic resection technique in early Barrett cancer.

BACKGROUND: Early Barrett cancer can be curatively treated by endoscopic resection. The choice of the resection technique, however-endoscopic mucosal resection (EMR) or submucosal dissection (ESD)-largely depends on the assumed infiltration depth as judged by the endoscopist. However, the accuracy of endoscopic diagnosis of the degree of cancer infiltration is not known. METHODS: Three to four high-quality images (both in overview and close-up) from 202 of early Barrett esophagus cancer cases (82% men, mean age 66.9 years) were selected from our endoscopy database (73.3% stage T1a and 26.7% in stage T1b). Images were shown to 9 Barrett esophagus experts, with patients' clinical data (age, sex, Barrett esophagus length) and biopsy results. The experts were asked to predict infiltration depth (T1b vs. T1a), and to suggest the appropriate endoscopic resection technique (EMR or ESD, or surgery). Interobserver variability (kappa values) was also determined for these parameters. RESULTS: Overall positive (PPV) and negative predictive values (NPV) to diagnose T1b versus T1a infiltration were 40.7% (95% CI: 36.7, 44.8) and 79.8% (95% CI: 77.5, 81.9), respectively; kappa value was 0.41. Paris classification (kappa 0.51) and suggested treatment also varied between experts. In a post hoc analysis, only the correlation between lesions classified as invisible or flat according to the Paris classification (IIB; 25% of all cases) and the suggested resection technique was better: In this subgroup, EMR was recommended in >80% of cases, with a high complete (basal R0) resection rate (mean of 88.1%). CONCLUSIONS: Precise endoscopic distinction between mucosal and submucosal involvement of Barrett esophagus cancer by experts as a basis for choosing the resection technique has limited predictive values and high interobserver variability. It seems that mainly invisible/flat lesions may result in good resection outcomes when treated by EMR, but this stratification strategy has to be assessed in further studies.

Stair-Climbing Tests or Self-Reported Functional Capacity for Preoperative Pulmonary Risk Assessment in Patients with Known or Suspected COPD-A Prospective Observational Study.

BACKGROUND: This prospective study aims to determine whether preoperative stair-climbing tests (SCT) predict postoperative pulmonary complications (PPC) better than self-reported poor functional capacity (SRPFC) in patients with known or suspected COPD. METHODS: A total of 320 patients undergoing scheduled for major non-cardiac surgery, 240 with verified COPD and 80 with GOLD key indicators but disproved COPD, underwent preoperative SRPFC and SCT and were analyzed. Least absolute shrinkage and selection operator (LASSO) regression was used for variable selection. Two multivariable regression models were fitted, the SRPFC model (baseline variables such as sociodemographic, surgical and procedural characteristics, medical preconditions, and GOLD key indicators plus SRPFC) and the SCT model (baseline variables plus SCTPFC). RESULTS: Within all stair-climbing variables, LASSO exclusively selected self-reported poor functional capacity. The cross-validated area under the receiver operating characteristic curve with bias-corrected bootstrapping 95% confidence interval (95% CI) did not differ between the SRPFC and SCT models (0.71; 0.65-0.77 for both models). SRPFC was an independent risk factor (adjusted odds ratio (OR) 5.45; 95% CI 1.04-28.60; p = 0.045 in the SRPFC model) but SCTPFC was not (adjusted OR 3.78; 95% CI 0.87-16.34; p = 0.075 in the SCT model). CONCLUSIONS: Our findings indicate that preoperative SRPFC adequately predicts PPC while additional preoperative SCTs are dispensable in patients with known or suspected COPD.

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.

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.).

Prevalence and prognostic impact of chronic kidney disease and anaemia across ACC/AHA precursor and symptomatic heart failure stages.

BACKGROUND: The importance of chronic kidney disease (CKD) and anaemia has not been comprehensively studied in asymptomatic patients at risk for heart failure (HF) versus those with symptomatic HF. We analysed the prevalence, characteristics and prognostic impact of both conditions across American College of Cardiology/American Heart Association (ACC/AHA) precursor and HF stages A-D. METHODS AND RESULTS: 2496 participants from three non-pharmacological German Competence Network HF studies were categorized by ACC/AHA stage; stage C patients were subdivided into C1 and C2 (corresponding to NYHA classes I/II and III, respectively). Overall, patient distribution was 8.1%/35.3%/32.9% and 23.7% in ACC/AHA stages A/B/C1 and C2/D, respectively. These subgroups were stratified by the absence ( - ) or presence ( +) of CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73m2) and anaemia (haemoglobin in women/men < 12/ < 13 g/dL). The primary outcome was all-cause mortality at 5-year follow-up. Prevalence increased across stages A/B/C1 and C2/D (CKD: 22.3%/23.6%/31.6%/54.7%; anaemia: 3.0%/7.9%/21.7%/33.2%, respectively), with concordant decreases in median eGFR and haemoglobin (all p < 0.001). Across all stages, hazard ratios [95% confidence intervals] for all-cause mortality were 2.1 [1.8-2.6] for CKD + , 1.7 [1.4-2.0] for anaemia, and 3.6 [2.9-4.6] for CKD + /anaemia + (all p < 0.001). Population attributable fractions (PAFs) for 5-year mortality related to CKD and/or anaemia were similar across stages A/B, C1 and C2/D (up to 33.4%, 30.8% and 34.7%, respectively). CONCLUSIONS: Prevalence and severity of CKD and anaemia increased across ACC/AHA stages. Both conditions were individually and additively associated with increased 5-year mortality risk, with similar PAFs in asymptomatic patients and those with symptomatic HF.

Empagliflozin effects on iron metabolism as a possible mechanism for improved clinical outcomes in non-diabetic patients with systolic heart failure.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors improve clinical outcomes in patients with heart failure (HF), but mechanisms of action are incompletely understood. In the EMPA-TROPISM trial, empagliflozin reversed cardiac remodeling and increased physical capacity in stable non-diabetic patients with systolic HF. Here we explore, post hoc, whether treatment effects in this cohort, comprising patients who had a high prevalence of iron deficiency, were related to iron metabolism. Myocardial iron content estimated by cardiac magnetic resonance T2* quantification increased after initiation of empagliflozin but not placebo (treatment effect: P = 0.01). T2* changes significantly correlated with changes in left ventricular volumes, mass and ejection fraction, peak oxygen consumption and 6-minute walking distance; concomitant changes in red blood cell indices were consistent with augmented hematopoiesis. Exploratory causal mediation analysis findings indicated that changes in myocardial iron content after treatment with empagliflozin may be an important mechanism to explain its beneficial clinical effects in patients with HF.ClinicalTrials.gov: NCT03485222 .

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.

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.

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.

Patient-reported outcomes predict return to work and health-related quality of life six months after cardiac rehabilitation: Results from a German multi-centre registry (OutCaRe).

BACKGROUND: Multi-component cardiac rehabilitation (CR) is performed to achieve an improved prognosis, superior health-related quality of life (HRQL) and occupational resumption through the management of cardiovascular risk factors, as well as improvement of physical performance and patients' subjective health. Out of a multitude of variables gathered at CR admission and discharge, we aimed to identify predictors of returning to work (RTW) and HRQL 6 months after CR. DESIGN: Prospective observational multi-centre study, enrolment in CR between 05/2017 and 05/2018. METHOD: Besides general data (e.g. age, sex, diagnoses), parameters of risk factor management (e.g. smoking, hypertension), physical performance (e.g. maximum exercise capacity, endurance training load, 6-min walking distance) and patient-reported outcome measures (e.g. depression, anxiety, HRQL, subjective well-being, somatic and mental health, pain, lifestyle change motivation, general self-efficacy, pension desire and self-assessment of the occupational prognosis using several questionnaires) were documented at CR admission and discharge. These variables (at both measurement times and as changes during CR) were analysed using multiple linear regression models regarding their predictive value for RTW status and HRQL (SF-12) six months after CR. RESULTS: Out of 1262 patients (54±7 years, 77% men), 864 patients (69%) returned to work. Predictors of failed RTW were primarily the desire to receive pension (OR = 0.33, 95% CI: 0.22-0.50) and negative self-assessed occupational prognosis (OR = 0.34, 95% CI: 0.24-0.48) at CR discharge, acute coronary syndrome (OR = 0.64, 95% CI: 0.47-0.88) and comorbid heart failure (OR = 0.51, 95% CI: 0.30-0.87). High educational level, stress at work and physical and mental HRQL were associated with successful RTW. HRQL was determined predominantly by patient-reported outcome measures (e.g. pension desire, self-assessed health prognosis, anxiety, physical/mental HRQL/health, stress, well-being and self-efficacy) rather than by clinical parameters or physical performance. CONCLUSION: Patient-reported outcome measures predominantly influenced return to work and HRQL in patients with heart disease. Therefore, the multi-component CR approach focussing on psychosocial support is crucial for subjective health prognosis and occupational resumption. TRIAL REGISTRATION: The study was registered at the German Clinical Trial Registry and the International Clinical Trials Registry Platform (ICTRP) of the World Health Organization (DRKS00011418; http://www.drks.de/DRKS00011418, http://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00011418).

Analysis of outcome for elderly patients after microvascular flap surgery: a monocentric retrospective cohort study.

OBJECTIVES: Increasingly, aging societies pose a challenge, particularly in the most developed countries. This trend leads to an increasing group of old and very old patients presenting unique requirements and challenges. One of these challenges consists in reassessment and adaption of established treatment strategies for the elderly patients. There is an ongoing discussion taking place among cranio-maxillo-facial surgeons about the appropriate extent of reconstructive flap surgery for old patients. MATERIALS AND METHODS: This monocentric retrospective cohort study investigated 281 reconstructions with microvascular flaps by comparing the risk for a negative outcome, which was defined as revision, flap loss, and patient death, between three subgroups of elderly patients and younger patients. The three subgroups of elderly patients were defined as-1: young old (65-74 years), 2: old (75-84 years), and 3: oldest old (≥ 85 years). The group of the younger patients was defined by age between 50 and 64 years. Data were obtained within a defined period of 42 months. RESULTS: Significant correlations with a negative outcome were found for the variables stay on IMC/ICU, multiple flaps, and radiotherapy prior surgery. Our data showed no significant correlation between age and a higher risk for a negative outcome. CONCLUSION: Defect reconstruction with microvascular flaps in old patients is not related with a higher risk for a negative outcome. CLINICAL RELEVANCE: Independently of age, treatment with microvascular flaps is an option for all operable patients, with an indication for oncologic surgery. For optimal therapy planning, individual patient resources and preferences should be considered instead of chronologic age.

Exploring sociodemographic subgroup differences in multiple mini-interview (MMI) performance based on MMI station type and the implications for the predictive fairness of the Hamburg MMI.

BACKGROUND: Sociodemographic subgroup differences in multiple mini-interview (MMI) performance have been extensively studied within the MMI research literature, but heterogeneous findings demand a closer look at how specific aspects of MMI design (such as station type) affect these differences. So far, it has not been investigated whether sociodemographic subgroup differences imply that an MMI is biased, particularly in terms of its predictive validity. METHODS: Between 2010 and 2017, the University Medical Centre Hamburg-Eppendorf (UKE) tested 1438 candidates in an MMI who also provided sociodemographic data and agreed to participate in this study. Out of these, 400 candidates were admitted and underwent a first objective structured clinical examination (OSCE) after one and a half years, including one station assessing communication skills. First, we analyzed the relationship between gender, age, native language and medical family background and MMI station performance including interaction terms with MMI station type (simulation, interview, and group) in a hierarchical linear model. Second, we tested whether the prediction of OSCE overall and communication station performance in particular differed depending on sociodemographic background by adding interaction terms between MMI performance and gender, age and medical family background in a linear regression model. RESULTS: Young female candidates performed better than young male candidates both at interview and simulation stations. The gender difference was smaller (simulation) or non-significant (interview) in older candidates. There were no gender or age effects in MMI group station performance. All effects were very small, with the overall model explaining only 0.6% of the variance. MMI performance was not related to OSCE overall performance but significantly predicted OSCE communication station performance with no differences in the prediction for sociodemographic subgroups. CONCLUSIONS: The Hamburg MMI is fair in its prediction of OSCE communication scores. Differences in MMI station performance for gender and age and their interaction with MMI station type can be related to the dimensions assessed at different station types and thus support the validity of the MMI. Rather than being threats to fairness, these differences could be useful for decisions relating to the design and use of an MMI.

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.

Hemadsorption during cardiopulmonary bypass reduces interleukin 8 and tumor necrosis factor α serum levels in cardiac surgery: a randomized controlled trial.

BACKGROUND: Surgical trauma and cardiopulmonary bypass (CPB) are associated with the liberation of pro-inflammatory cytokines. With hemadsorption (Cytosorb®) during CPB, pro-inflammatory cytokines may be reduced and the inflammatory response may be decreased. METHODS: In this prospective, randomized single center study, serum cytokine levels of interleukin 8 (Il-8), interleukin 6 (Il-6) and tumor-necrosis-factor α (TNFα) were assessed in elective on-pump cardiac surgery patients with hemadsorption on CPB (study group [SG], N.=20) and without (control group [CG], N.=20). Cytokine levels were assessed prior to CPB, at the end of CPB, and 6 hours (h) and 24 h after the end of CPB, together with a hemodynamic assessment. Cardiac-Index (CI) was assessed with transcardiopulmonary thermodilution. RESULTS: For Il-8, significantly lower serum levels were observed in the SG compared to the CG at the end of CPB (P=0.008). In the SG, TNFα levels were also below those in the CG at both the end of and 6h after CPB (P=0.034). After 24 hours, TNFα levels were at baseline in both groups. No significant differences were found for Il-6. The CI was significantly higher in the SG at the end of CPB (P=0.025). However, there was no difference between both groups 6 h after CPB. CONCLUSIONS: This prospective study shows a significant reduction in pro-inflammatory cytokine levels of Il-8 and TNFα with hemadsorption in on-pump cardiac surgery whilst also demonstrating safety in its applications. However, the differences in cytokine levels and CI between patients treated with hemadsorption and those without were minor and of short duration.

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.

Effects of two instrument-generation changes on adenoma detection rate during screening colonoscopy: results from a prospective randomized comparative study.

BACKGROUND: Previous studies have shown that multiple colonoscope features have to be changed before an improvement in adenoma detection rate (ADR) becomes obvious, such as with changing from one instrument generation to the next but one. We wanted to evaluate whether such an effect can also be observed in a private-practice screening setting. METHODS: In a randomized study, we compared the latest generation colonoscopes from one company (Olympus Exera III, 190) with the next to last one (Olympus 165), including only patients presenting for screening colonoscopy. The primary outcome was ADR achieved with 190 colonoscopes (190-C) in comparison with 165 colonoscopes (165-C). RESULTS: 1221 patients (46.1 % men; mean age 62.2 years, standard deviation 6.6) were included (599 screened with the Olympus Exera III, 190). The ADR difference in favor of the 190-C instrument (32 % [95 % confidence interval (CI) 26 % to 39 %] vs. 28 % [95 %CI 22 % to 34 %] in the 165-C group) failed to reach statistical significance (P = 0.10); only the rate of small (< 5 mm) adenomas was significantly increased at 22.5 % (95 %CI 19 % to 26 %) vs. 15.6 % (95 %CI 13 % to 18 %; P = 0.002). Furthermore, significantly more adenomas were found in the 190-C group, with an adenoma rate (all adenomas/all patients) of 0.57 (95 %CI 0.53 to 0.61) vs. 0.47 (95 %CI 0.43 to 0.51; P < 0.001). CONCLUSIONS: This randomized comparative trial in a private-practice screening setting only partially confirmed the results of prior studies that, with multiple imaging improvements achieved over two instrument generations, an increase in overall adenoma number becomes measurable.

Immediate loading of subcrestally placed dental implants in anterior and premolar sites.

PURPOSE: Immediate loading of dental implants has been evolving into an appropriate procedure for the treatment of partially edentulous jaws. The purpose of this study was to evaluate the clinical success and radiological outcome of immediately and delayed loaded dental implants in anterior and premolar sites. MATERIALS AND METHODS: In this retrospective study, data of 163 individuals requiring tooth removal with subsequent implant placement in anterior and premolar sites were analyzed. Implants were immediately loaded by provisional acrylic resin bridges or loaded with delay. Implants were followed up annually for up to 9 years including intraoral radiographs. RESULTS: A total of 285 implants in 163 patients were placed. 218 implants were immediately loaded and 67 implants with delay. Fifteen implants failed during the follow-up period resulting in survival rates of 94.5% for immediate loading and 95.5% for delayed loading. After an initial decrease of 0.3 mm in the first 12 months the marginal bone level remained stable. No statistically significant differences were found in marginal bone loss between immediately and delayed loaded implants (P = 0.518, 95% CI). CONCLUSION: Within the limits of this study, immediate loading of immediately subcrestally placed dental implants in anterior and premolar sites is a reliable treatment option for dental rehabilitation.

Unmet needs for information and psychosocial support in relation to quality of life and emotional distress: A comparison between gynecological and breast cancer patients.

OBJECTIVE: We compared gynecological and breast cancer patients regarding their needs for information and psychosocial support, quality of life (QoL), and emotional distress and the relationship among these constructs. METHODS: In a multicenter, cross-sectional study in Germany, we evaluated 1214 female cancer patients (317 with gynecological cancer, 897 with breast cancer). We obtained self-reports of unmet needs, using a self-developed measure. We measured QoL with the EORTC QLQ-C30, symptoms of depression with the Patient Health Questionnaire (PHQ-9), and symptoms of anxiety with the Generalized Anxiety Disorder Scale (GAD-7). RESULTS: Compared to breast cancer patients, gynecological cancer patients felt less informed about several aspects of their disease, particularly regarding psychological support (p<0.001), tended to have more unmet information needs, and reported lower QoL levels. Lower emotional functioning, but higher physical functioning were independent correlates of the level of unmet information needs. Depressive symptoms and higher physical functioning (only in breast cancer) were independent correlates of higher needs for psychosocial support. CONCLUSION: Compared to breast cancer, gynecological cancer patients were less satisfied with the information received and reported lower levels of QoL. PRACTICE IMPLICATIONS: Both clinicians and policy makers should take efforts to address the higher needs of gynecological cancer patients.

Survival analysis of 287 oropharyngeal squamous cell carcinoma patients in a single institution: a retrospective comparison of two consecutive time intervals with surgical and conservative treatment approaches.

This study is a retrospective analysis of clinico-pathological data to investigate survival rates of patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with different modalities in a single academic head and neck cancer center in different time intervals. Altogether, 287 patients with OPSCC were included in this comparison. Patients were analysed during two different treatment periods: Group 1 included patients treated mainly with primary surgery ± adjuvant radio(chemo)therapy between 2002 and 2007, while Group 2 included patients treated with organ/function-preservation protocols if indicated. Main outcome measures were overall survival (OS) and recurrence-free survival (RFS). Between 2002 and 2007, early-stage OPSCC showed a 5-year OS of 75% compared to that of 86% between 2008 and 2013. Locally advanced OPSCC showed a 5-year OS of 66% between 2002 and 2007 compared to that of 74% between 2008 and 2013. RFS in early-stage OPSCC was 48% between 2002 and 2007 in contrast to that of 77% between 2008 and 2013. With locally advanced OPSCC, RFS was 55% between 2002 and 2007 compared to that of 56% between 2008 and 2013. These differences were statistically not significant. The OS and RFS remained generally unchanged over the analysed time period. There was no significant difference in the outcomes with regards to HPV status and to their treatment modality.

Utilization of professional psychological care in a large German sample of cancer patients.

OBJECTIVE: Although one-third of cancer patients are perceived to have a need for psychological support based on the percentage of mental disorders, little is known about the actual utilization of psychological care in cancer. We aimed to assess cancer patients' reported use of psychological care and its correlates in a large, representative sample. METHODS: In a multicenter, cross-sectional study in Germany, 4020 cancer patients (mean age 58 years, 51% women) were evaluated. We obtained self-reports of use of psychotherapy and psychological counseling. We measured distress with the Distress Thermometer, symptoms of depression with the Patient Health Questionnaire, anxiety with the Generalized Anxiety Disorder Scale, and social support with the Illness-specific Social Support Scale. In a subsample of 2141, we evaluated the presence of a mental disorder using the Composite International Diagnostic Interview. RESULTS: In total, 28.9% (95% confidence interval 27.4%-30.4%) reported having used psychotherapy or psychological counseling or both because of distress due to cancer. Independent correlates of utilization included age (odds ratio [OR] = 0.97 per year], sex (male, OR = 0.55), social support (OR = 0.96), symptoms of depression (OR = 1.04) and anxiety (OR = 1.08), the diagnosis of a mental disorder (OR = 1.68), and a positive attitude toward psychosocial support (OR = 1.27). Less than half of those currently diagnosed with a mental disorder reported having taken up psychological support offers. CONCLUSION: Special efforts should be made to reach populations that report low utilization of psychological care in spite of having a need for support.