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Word learning plays a central role in language development and is a key predictor for later academic success. The underlying neural basis of successful word learning in children is still unknown. Here, we took advantage of the opportunity afforded by diffusion-weighted magnetic resonance imaging to investigate neural plasticity in the white matter of typically developing preschool children as they learn words. We demonstrate that after 3 weeks of word learning, children showed significantly larger increases of fractional anisotropy (FA) in the left precentral white matter compared to two control groups. Average training accuracy was correlated with FA change in the white matter underlying the left dorsal postcentral gyrus, with children who learned more slowly showing larger FA increases in this region. Moreover, we found that the status of white matter in the left middle temporal gyrus, assumed to support semantic processes, is predictive for early stages of word learning. Our findings provide the first evidence for white matter plasticity following word learning in preschool children. The present results on learning novel words in children point to a key involvement of the left fronto-parietal fiber connection, known to be implicated in top-down attention as well as working memory. While working memory and attention have been discussed to participate in word learning in children, our training study provides evidence that the neural structure supporting these cognitive processes plays a direct role in word learning.

Background Despite the progress of research and treatment for breast cancer, still up to 30% of the patients afflicted will develop distant disease. Elongation of survival and maintaining the quality of life (QoL) become pivotal issues guiding the treatment decisions. One possible approach to optimise survival and QoL is the use of patient-reported outcomes (PROs) to timely identify acute disease-related burden. We present the protocol of a trial that investigates the effect of real-time PRO data captured with electronic mobile devices on QoL in female breast cancer patients with metastatic disease. Methods This study is a randomised, controlled trial with 1:1 randomisation between two arms. A total of 1000 patients will be recruited in 40 selected breast cancer centres. Patients in the intervention arm receive a weekly request via an app to complete the PRO survey. Symptoms will be assessed by study-specific optimised short forms based on the EORTC QLQ-C30 domains using items from the EORTC CAT item banks. In case of deteriorating PRO scores, an alarm is sent to the treating study centre as well as to the PRO B study office. Following the alarm, the treating breast cancer centre is required to contact the patient to inquire about the reported symptoms and to intervene, if necessary. The intervention is not specified and depends on the clinical need determined by the treating physician. Patients in the control arm are prompted by the app every 3 months to participate in the PRO survey, but their response will not trigger an alarm. The primary outcome is the fatigue level 6 months after enrolment. Secondary endpoints include among others hospitalisations, use of rescue services and overall QoL. Discussion Within the PRO B intervention group, we expect lower fatigue levels 6 months after intervention start, higher levels of QoL, less unplanned hospitalisations and less emergency room visits compared to controls. In case of positive results, our approach would allow a fast and easy transfer into clinical practice due to the use of the already nationwide existing IT infrastructure of the German Cancer Society and the independent certification institute OnkoZert. Trial registration DRKS (German Clinical Trials Register) DRKS00024015 . Registered on 15 February 2021

Drug addiction is a neuropsychiatric disorder with grave personal consequences that has an extraordinary global economic impact. Despite decades of research, the options available to treat addiction are often ineffective because our rudimentary understanding of drug-induced pathology in brain circuits and synaptic physiology inhibits the rational design of successful therapies. This understanding will arise first from animal models of addiction where experimentation at the level of circuits and molecular biology is possible. We will review the most common preclinical models of addictive behavior and discuss the advantages and disadvantages of each. This includes non-contingent models in which animals are passively exposed to rewarding substances, as well as widely used contingent models such as drug self-administration and relapse. For the latter, we elaborate on the different ways of mimicking craving and relapse, which include using acute stress, drug administration or exposure to cues and contexts previously paired with drug self-administration. We further describe paradigms where drug-taking is challenged by alternative rewards, such as appetitive foods or social interaction. In an attempt to better model the individual vulnerability to drug abuse that characterizes human addiction, the field has also established preclinical paradigms in which drug-induced behaviors are ranked by various criteria of drug use in the presence of negative consequences. Separation of more vulnerable animals according to these criteria, along with other innate predispositions including goal- or sign-tracking, sensation-seeking behavior or impulsivity, has established individual genetic susceptibilities to developing drug addiction and relapse vulnerability. We further examine current models of behavioral addictions such as gambling, a disorder included in the DSM-5, and exercise, mentioned in the DSM-5 but not included yet due to insufficient peer-reviewed evidence. Finally, after reviewing the face validity of the aforementioned models, we consider the most common standardized tests used by pharmaceutical companies to assess the addictive potential of a drug during clinical trials.

BackgroundThe patient-reported outcomes (PRO) version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and the computerized adaptive testing (CAT) version of the EORTC quality-of-life questionnaire QLQ-C30 have been proposed as new PRO measures in oncology; however, their implementation in patients undergoing cancer surgery has not yet been evaluated.MethodsPatients undergoing elective abdominal cancer surgery were enrolled in a prospective multicenter study, and postoperative complications were recorded according to the Dindo–Clavien classification. Patients reported PRO data using the CAT EORTC QLQ-C30 and the PRO-CTCAE to measure 12 core cancer symptoms. Patients were followed-up for 6 months postoperatively. The study was carried out by medical students of the CHIR-Net SIGMA study network.ResultsData of 303 patients were obtained and analyzed across 15 sites. PRO-CTCAE symptoms ‘poor appetite’, ‘fatigue’, ‘exhaustion’ and ‘sleeping problems’ increased after surgery and climaxed 10–30 days postoperatively. At 3–6 months postoperatively, no PRO-CTCAE symptom differed significantly to baseline. Patients reported higher ‘social functioning’ (p = 0.021) and overall quality-of-life scores (p < 0.05) 6 months after cancer surgery compared with the baseline level. There was a lack of correlation between postoperative complications or death and any of the PRO items evaluated. Feasibility endpoints for student-led research were met.ConclusionThe two novel PRO questionnaires were successfully applied in surgical oncology. Postoperative complications do not affect health-reported quality-of-life or common cancer symptoms following major cancer surgery. The feasibility of student-led multicenter clinical research was demonstrated, but might be enhanced by improved student training.

Background: Fatigue thresholds such as the gas exchange threshold (GET) and respiratory compensation point (RCP) describe unique physiological responses. This study investigated the reliability of, and sex-dependent responses for, the GET and RCP across absolute, relative, and normalized expressions of volume of oxygen consumption (V˙O2), power output (PO), heart rate (HR), and rating of perceived exertion (RPE). Methods: A test–retest graded exercise test (GXT) protocol was conducted on healthy, recreationally trained males (n = 9) and females (n = 9) to determine the GET and RCP (V˙O2). Linear regression was used to identify the PO, HR, and RPE at the GET and RCP. Separate 2 [test (1, 2)] × 2 [sex (male, female)] mixed-model analysis of variance (ANOVA) examined systematic error across test and sex (p > 0.05). Separate reliability analyses were conducted for each variable for males and females using intraclass correlation coefficients (ICC2,1), minimal differences (MDs), standard errors of measure (SEMs), and coefficients of variation (CVs). Results: Absolute and relative expression of PO and V˙O2 at the GET and RCP reflected “excellent” relative reliability (R = 0.816–0.978) across sex. Absolute and normalized expression of HR and RPE at the GET and RCP demonstrated “good” to “poor” relative reliability (R= −0.093–0.886) across sex. The SEMs and MDs were relatively small with CVs at or below 10% across thresholds. Absolute PO and V˙O2 for the GET and RCP were greater for males than females, while females demonstrated greater normalized RCP as well as absolute and normalized HR and RPE at the RCP. Conclusions: Although the relative reliability for HR and RPE at the GET and RCP was, in some cases, limited, these variables demonstrated acceptable absolute reliability and, therefore, have applicability to monitor and prescribe exercise intensities. Current exercise prescription techniques may neglect the unique sex-dependent perceptual and cardiovascular responses at the GET and RCP.

The use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for cardiogenic shock is rising. Acute limb ischaemia remains one of the main complications after ECMO initiation. We analysed 104 patients from our databank from January 2015 to December 2021 who were supported with mobile ECMO therapy. We aimed to identify the impact of acute limb ischaemia on short-term outcomes in patients placed on ECMO in our institution. The main indication for ECMO therapy was left ventricular (LV) failure with cardiogenic shock (57.7%). Diameters of arterial cannulas (p = 0.365) showed no significant differences between both groups. Furthermore, concomitant intra-aortic balloon pump (IABP, p = 0.589) and Impella (p = 0.385) implantation did not differ significantly between both groups. Distal leg perfusion was established in approximately 70% of patients in two groups with no statistically significant difference (p = 0.960). Acute limb ischaemia occurred in 18.3% of cases (n = 19). In-hospital mortality was not significantly different (p = 0.799) in both groups. However, the bleeding rate was significantly higher (p = 0.005) in the limb ischaemia group compared to the no-limb ischaemia group. Therefore, early diagnosis and prevention of acute limb ischaemia might decrease haemorrhage complications in patients during ECMO therapy.

Transcatheter aortic valve replacement (TAVR) has become an established alternative to surgical aortic valve replacement (AVR) for patients with moderate-to-high perioperative risk. Periprocedural TAVR complications decrease with growing expertise of implanters. Nevertheless, TAVR can still be accompanied by life-threatening adverse events such as intraprocedural cardiopulmonary resuscitation (CPR). This study analyzed the role of a reduced left-ventricular ejection fraction (LVEF) in intraprocedural complications during TAVR. Perioperative and postoperative outcomes from patients undergoing TAVR in a high-volume center (600 cases per year) were analyzed retrospectively with regard to their left-ventricular ejection fraction. Patients with a reduced left-ventricular ejection fraction (EF ≤ 40%) faced a significantly higher risk of perioperative adverse events. Within this cohort, patients were significantly more often in need of mechanical ventilation (35% vs. 19%). These patients also underwent CPR (17% vs. 5.8%), defibrillation due to ventricular fibrillation (13% vs. 5.4%), and heart–lung circulatory support (6.1% vs. 2.5%) more often. However, these intraprocedural adverse events showed no significant impact on postoperative outcomes regarding in-hospital mortality, stroke, or in-hospital stay. A reduced preprocedural LVEF is a risk factor for intraprocedural adverse events. With respect to this finding, the identified patient cohort should be treated with more caution to prevent intraprocedural incidents.

Background. Patients with simultaneous relevant internal carotid artery stenosis and coronary artery heart or valve disease represent a high-risk collective with respect to cerebral or cardiovascular severe events when undergoing surgery. There exist several concepts regarding the timing and modality of carotid revascularization, which are controversially discussed in patients with heart disease. More data regarding outcome predictors and measures are needed to gain a better understanding of the best treatment option of the discussed patient collective. Methods. This single-center study retrospectively analyzed n = 111 patients undergoing heart surgery with coronary artery bypass grafting or heart-valve surgery and concomitant carotid surgery due to significant internal carotid artery stenosis. In order to do so, patients were divided into two groups with respect to postoperative major adverse cardiac and cerebrovascular events (MACCE) with thirty-day all-cause mortality, valve related mortality, myocardial infarction, stroke and transitory ischemic attack. Results. Preoperative patient’s characteristic in the no-MACCE and MACCE group were mainly balanced, other than higher rates of chronic obstructive pulmonary disease, chronic kidney disease, instable angina pectoris and prior transitory ischemic attack in the MACCE cohort. The analysis of intraoperative characteristics revealed a higher number of intra-aortic balloon pump implantation, which is in line for a higher number of postoperative supports. Besides MACCE, patients suffered significantly more often from postoperative bleeding events and re-thoracotomy, cardiopulmonary reanimation, new onset postoperative dialysis and prolonged intensive care unit stay related complications. Conclusions. Within the reported patient population suffering from MACCE after a simultaneous carotid endarterectomy and heart surgery, a preoperative history of transitory ischemic attack and kidney disease might account for worse outcomes, as severe events were not only neurologically driven but also associated with postoperative cardiovascular complications following heart surgical procedures.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used for patients with cardiogenic shock or cardiac arrest. However, survival rates remain low. It is unclear to what extent ECMO patients benefit from the ECMO team learning curve. Therefore, we aimed to analyze our mobile ECMO program patients from the past seven years to evaluate if a learning curve benefits patients’ outcomes. We analyzed 111 patients from our databank who were supported with a VA-ECMO and brought to our hospital from January 2015 to December 2021. Patients were divided into two groups: survival (n = 70) and non-survival (n = 41). As expected, complications after ECMO implantation were more severe in the non-survivor group. The incidence of thromboembolic events (p = 0.002), hepatic failure (p < 0.001), renal failure (p = 0.002), dialysis (p = 0.002) and systemic inflammatory response syndrome (SIRS, p = 0.044) occurred significantly more often compared with the survivor group. We were able to show that despite our extensive experience in terms of ECMO retrieval program the high mortality and morbidity rates stay fairly the same over the years. This displays that we have to focus even more on patient selection and ECMO indication.

Recent advances in perioperative care have considerably improved outcomes after coronary artery bypass graft (CABG) surgery. However, obesity can increase postoperative complication rates and can lead to increased morbidity and mortality. Between June 2011 and October 2019, a total of 1375 patients with acute coronary syndrome (ACS) underwent cardiac surgery and were retrospectively analyzed. Patients were divided into 2 groups: non-obese (body mass index (BMI) < 30 kg/m2, n = 967) and obese (BMI ≥ 30 kg/m2, n = 379). Underweight patients (n = 29) were excluded from the analysis. To compare the unequal patient groups, a propensity score-based matching (PSM) was applied (non-obese group (n = 372) vs. obese group (n = 372)). The mean age of the mentioned groups was 67 ± 10 (non-obese group) vs. 66 ± 10 (obese group) years, p = 0.724. All-cause in-hospital mortality did not significantly differ between the groups before PSM (p = 0.566) and after PSM (p = 0.780). The median length of ICU (p = 0.306 before PSM and p = 0.538 after PSM) and hospital stay (p = 0.795 before PSM and p = 0.131 after PSM) was not significantly higher in the obese group compared with the non-obese group. No significant differences regarding further postoperative parameters were observed between the unadjusted and the adjusted group. Obesity does not predict increased all-cause in-hospital mortality in patients undergoing CABG procedure. Therefore, CABG is a safe procedure for overweight patients.