Angst, Depressivität und Allgemeinbeschwerden bei Patienten mit Reizdarmsyndrom im Vergleich zu Patienten mit chronisch entzündlichen Darmerkrankungen und psychosomatischen Patienten

1.1. Zusammenfassung Hintergrund: Das Reizdarmsyndrom wird als eine chronisch funktionelle Darmerkrankung angesehen und kann entsprechend der S3-Leitlinie wie auch nach den ROME-Kriterien definiert werden. Unklar ist, wie nah das RDS den somatoformen Störungen steht und wie stark psychische Faktoren eine Rolle bei der Krankheitsentstehung, dem Krankheitsempfinden sowie dem Krankheitsverlauf spielen. Die Patienten unterliegen einem hohen Leidensdruck aufgrund eines häufig langwierigen diagnostischen Prozesses sowie der meist chronischen und belastenden Symptomatik. Daher ist das Reizdarmsyndrom mit erheblichen Kosten für das Gesundheitssystem und die Gesellschaft verbunden. Vorliegende Daten zeigen, dass die Erkrankung oft mit psychopathologischen Störungen, insbesondere Depression, Angst und Somatisierung, korreliert. Die Patienten profitieren daher von einer frühzeitigen Diagnose sowie Therapie. Bislang liegen nur wenige Daten hinsichtlich des Vergleichs von organspezifischen Beschwerden, Allgemeinbeschwerden sowie Angst und Depressivität zwischen RDS-Patienten und weiteren psychisch bzw. somatisch erkrankten Patienten vor. Methodik: Es wurden insgesamt 372 Patienten/ Probanden eingeschlossen. Untersucht wurden 4 Patientenstichproben, RDS-Patienten (n=65), Patienten, die an einer chronisch entzündlichen Darmerkrankung (CED) leiden (n=74), Patienten mit muskuloskelettalen Beschwerden (n=72) und Patienten mit einer psychosomatischen Erkrankung (n=45) sowie eine Probandengruppe aus Medizinstudenten (n=116). Zur Beurteilung der organspezifischen Beschwerden in Bezug auf den Gastrointestinaltrakt wurde sowohl die Skala Magenbeschwerden der Kurzversion des Gießener Beschwerdebogens (GBB-24) als auch der Reizdarmfragebogen (RDF) genutzt. Die Symptomausprägung von Angst und Depressivität wurde mit Hilfe des HADS-D und die Allgemeinbeschwerden wurden mit Hilfe des GBB-24 erfasst. Es wurde der Mittelwert der jeweiligen Patienten- bzw. Probandengruppe in den jeweiligen Fragebögen miteinander verglichen. Die statistische Auswertung erfolgte mit SPSS Version 20 für Windows. Ergebnisse: Das erste wichtige Ergebnis unserer Studie ist die Bestätigung der höheren Belastung der RDS-Patienten durch Angst und Depressivität im Vergleich zu den CED-Patienten, den Patienten mit muskuloskelettalen Schmerzen und der studentischen Kontrollgruppe. RDS-Patienten zeigten eine vergleichbare Ausprägung von Angst und Depressivität wie psychosomatische Patienten. Ein weiteres wichtiges Ergebnis ist, dass RDS-Patienten stärker an organspezifischen Beschwerden leiden als CED-Patienten. Es bestand keine Korrelation zwischen organspezifischen Beschwerden und Angst sowie Depressivität bei den RDS-Patienten. Es zeigte sich jedoch eine bedeutsame Korrelation zwischen organspezifischen Beschwerden und Angst sowie Depressivität in der Gruppe der CED-Patienten und der Gruppe der psychosomatischen Patienten. Zu erkennen war ebenfalls eine signifikante Korrelation zwischen den Allgemeinbeschwerden und Angst sowie Depressivität in sämtlichen Gruppen. Schlussfolgerung: Zusammenfassend bestätigt diese Arbeit zum Großteil die Ergebnisse bereits vorgestellter Studien, dass Patienten mit einem RDS an Angst und Depressivität leiden und sogar eine ähnliche Symptomausprägung dieser beider Krankheitsbilder zeigen wie Patienten, die an einer Angststörung und Depression erkrankt sind. Die Ergebnisse unterstreichen die Notwendigkeit der Diagnose und Behandlung von Angst und Depressivität bei RDS-Patienten um den Krankheitsverlauf sowie das Krankheitsempfinden positiv zu beeinflussen.1.2. Summary Background: Irritable bowel syndrome (IBS) is a chronic functional bowel disease and counts among the somatoform disorders. It can be defined according to the S3 guidelines in Germany as well as according to the ROME criteria. It is associated with significantly high costs for patients, for the healthcare system and for society. Numerous studies about IBS have shown that IBS is associated with significant psychopathological disorders especially depression, anxiety and somatization. An analysis regarding the direct comparison in relation to the organ-specific complaints, general complaints as well as anxiety and depression between IBS patients and other physically or mentally ill patients does not exist to our knowledge. Methods: A total of 372 patients / subjects were enrolled. The study included 3 patient groups, IBS patients (n = 65), patients with chronic inflammatory bowel disease (IBD) (n = 74), patients with musculoskeletal complaints (n = 72), and patients with psychosomatic disorders (n = 45), as well as a healthy study population consisting of medical student (n=116). To assess the organ-specific complaints with respect to the gastrointestinal tract, both the scale gastric disorder of the short version of the Gießener Beschwerdefragebogen (GBB-24) and the German version of the Gastrointestinal Symptom Rating Scale – Irritable Bowel Syndrome (GSRS–IBS), the Reizdarmfragebogen (RDF), were used. The symptoms of anxiety and depression were recorded using the German version of the Hospital Anxiety and Depression Scale (HADS-D) and general complaints using the GBB-24. The middle value of the subject group in the respective questionnaires was compared. Statistical evaluation was done with SPSS version 20 for Windows. Results: The first important result of our study is the confirmation of the higher burden of anxiety and depression in IBS patients in comparison to IBD patients, patients with musculoskeletal pain and the student control group. Moreover, the results show that the level of anxiety and depression in the IBS patients and the psychosomatic patients is comparable. Another important finding is that IBS patients suffer from higher organspecific complaint than IBD patients. There is no correlation between organ-specific symptoms and anxiety and depression in IBS patients. However, there was a significant correlation between organ-specific symptoms and anxiety as well as depression in the group of IBD patients and the group of psychosomatic patients. A significant correlation between general complaints and anxiety as well as depression in all groups is also recognized. Conclusion: This work largely confirms the results of previous studies that IBS patients suffer from anxiety and depression and shows that in IBS patients the severity of these two conditions is even similar to those patients who suffer from anxiety and depression. The results underline the need to search and treat anxiety and depression in IBS patients

Design and validation of a German version of the GSRS-IBS - an analysis of its psychometric quality and factorial structure

Background: Currently, a suitable questionnaire in German language is not available to monitor the progression and evaluate the severity of irritable bowel syndrome (IBS). Therefore, this study aimed to translate the Gastrointestinal Symptom Rating Scale for Irritable Bowel Syndrome (GSRS-IBS) into German and to evaluate its psychometric qualities and factorial structure. Methods: This study is based on a total sample of 372 participants [62.6% female, mean age = 41 years (SD = 17 years)]. 17.5% of the participants had a diagnosis of IBS, 19.9% were receiving treatment for chronic inflammatory bowel disease, 12.1% of the participants were recruited from a psychosomatic clinic, and 50.5% belonged to a control group. All participants completed the German version of GSRS-IBS (called Reizdarm-Fragebogen, RDF), as well as the Gießen Subjective Complaints List (GBB-24) and the Hospital Anxiety and Depression Scale - German version (HADS-D). Results: The internal consistency of the RDF total scale was at least satisfactory in all subsamples (Cronbach’s Alpha between .77 and .92), and for all subscales (Cronbach’s Alpha between .79 and .91). The item difficulties (between .25 and .73) and the item-total correlations (between .48 and .83) were equally satisfactory. Principal axis analysis revealed a four-factorial structure of the RDF items, which mainly resembled the structure of the English original. Convergent validity was established based on substantial and significant correlations with the stomach-complaint scale of the GBB-24 (r = .71; p < .01) and the anxiety (r = .42; p < .01) and depression scales (r = .43; p < .01) of the HADS-D. Conclusion: The German version of the GSRS-IBS RDF proves to be an effective, reliable, and valid questionnaire for the assessment of symptom severity in IBS, which can be used in clinical practice as well as in clinical studies

Static and dynamic 68Ga-FAPI PET/CT for the detection of malignant transformation of intraductal papillary mucinous neoplasia of the pancreas.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) may arise from intraductal papillary-mucinous neoplasms (IPMN) with malignant transformation, but a significant portion of IPMN remains to show benign behavior. Therefore, it is important to differentiate between benign IPMN and IPMN lesions undergoing malignant transformation. However, non-operative differentiation by ultrasound, CT, MRI and carbohydrate antigen 19-9 (CA19-9) is still unsatisfactory. Here, we assessed the clinical feasibility of additional assessment of malignancy by positron emission tomography using 68Gallium-labeled Fibroblast Activation Protein Inhibitors (68Ga-FAPI-PET) in 25 patients with magnetic resonance imaging (MRI) - or computed tomography (CT) - proven cystic pancreatic lesions. Methods: 25 patients with cystic pancreatic lesions who were followed up in the European Pancreas Center of Heidelberg University hospital and who were led to surgical resection or fine needle aspiration (FNA) due to suspicious clinical, laboratory chemistry or radiological findings were examined by static (all patients) and dynamic (20 patients) 68Ga-FAPI-PET. Cystic pancreatic lesions were delineated and maximum and mean standardized uptake values (SUVmax / SUVmean) were determined. Time activity curves and dynamic parameters (time to peak, K1, k2, K3, k4) were extracted from dynamic PET data. Receiver operating curves (ROC) of static and dynamic PET parameters were calculated. Results: 11 of the patients suffered from menacing IPMN (high grade IPMN with (6 cases) or without (5 cases) progression into PDAC) and 11 from low grade IPMN, 3 patients from other benign entities. Menacing IMPN showed significantly elevated 68Ga-FAPI uptake compared to low grade IPMN and other benign cystic lesions. In dynamic imaging, menacing IPMN showed increasing time activity curves (TAC) followed by slow decrease afterwards, TAC of low grade IPMN showed an immediate peak followed by rapid decrease for about 10 minutes and slower decrease for the rest of the time. ROC curves showed high sensitivity and specificity (area under the curve (AUC) greater than 80%) of static and dynamic PET parameters for the differentiation of IPMN subtypes. Conclusion: 68Ga-FAPI-PET is a helpful new tool for the differentiation of menacing and low grade IPMN and shows the potential to avoid unnecessary surgery for non-malignant pancreatic IPMN

Risk factor paradox: No prognostic impact of arterial hypertension and smoking in patients with ventricular tachyarrhythmias

Background: Data regarding the outcome of patients with ventricular tachyarrhythmias related to arterial hypertension (AHT) and smoking is limited. The study sought to assess the prognostic impact of AHT and smoking on survival in patients presenting with ventricular tachyarrhythmias. Methods: All consecutive patients surviving ventricular tachycardia (VT) and ventricular fibrillation (VF) upon admission to the University Medical Center Mannheim (UMM), Germany from 2002 to 2016 were included and stratified according to AHT and smoking by propensity score matching. The primary prognostic endpoint was all-cause mortality at 30 months.Results: A total of 988 AHT-matched patients (494 each, with and without AHT) and a total of 872 smoking-matched patients (436 each, with and without smoking) were included. The rates of VT and VF were similar in both groups (VT: AHT 60% vs. no AHT 60%; smokers 61% vs. non-smokers 62%; VF: AHT 35% vs. no AHT 38%; smokers 39% vs. non-smokers 38%). Neither AHT nor smoking were associated with the primary endpoint of long-term all-cause mortality at 30 months (long-term mortality rates: AHT/no AHT, 26% vs. 28%; log-rank p = 0.525; smoking/non-smoking, 22% vs. 25%; log-rank p = 0.683).Conclusions: Paradoxically, neither AHT nor smoking were associated with differences of long-term all-cause mortality in patients presenting with ventricular tachyarrhythmias

Type 2 diabetes is independently associated with all-cause mortality secondary to ventricular tachyarrhythmias

Objectives: The study sought to assess the prognostic impact of type 2 diabetes in patients presenting with ventricular tachyarrhythmias on admission. Background: Data regarding the prognostic outcome of diabetics presenting with ventricular tachyarrhythmias is limited. Methods: A large retrospective registry was used including all consecutive patients presenting with ventricular tachycardia (VT) and fibrillation (VF) on admission from 2002 to 2016. Patients with type 2 diabetes (diabetics) were compared to non-diabetics applying multivariable Cox regression models and propensity-score matching for evaluation of the primary prognostic endpoint of long-term all-cause mortality at 2 years. Secondary prognostic endpoints were cardiac death at 24 h, in-hospital death at index, all-cause mortality at 30 days, all-cause mortality in patients surviving index hospitalization at 2 years (i.e. “after discharge”) and rehospitalization due to recurrent ventricular tachyarrhythmias at 2 years. Results: In 2411 unmatched high-risk patients with ventricular tachyarrhythmias, diabetes was present in 25% compared to non-diabetics (75%). Rates of VT (57% vs. 56%) and VF (43% vs. 44%) were comparable in both groups. Multivariable Cox regression models revealed diabetics associated with the primary endpoint of long-term all-cause mortality at 2 years (HR = 1.513; p = 0.001), which was still proven after propensity score matching (46% vs. 33%, log rank p = 0.001; HR = 1.525; p = 0.001). The rates of secondary endpoints were higher for in-hospital death at index, all-cause mortality at 30 days, as well as after discharge, but not for cardiac death at 24 h or rehospitalization due to recurrent ventricular tachyarrhythmias. Conclusion: Presence of type 2 diabetes is independently associated with an increase of all-cause mortality in patients presenting with ventricular tachyarrhythmias on admission

Prognostic impact of age and gender on patients with electrical storm

Background: Electrical storm (ES) is a severe and life-threatening heart rhythm disorder. Age and male gender have been identified as independent risk factors for cardiovascular diseases. However, data regarding the prognostic impact of age and gender on ES patients is limited. Methods: The present study included retrospectively consecutive patients presenting with ES from 2002 to 2016. Patients 67 years old or older were compared to patients younger than 67, males were also compared to females. Receiver operating characteristic analyses were performed to find the optimum age cut-off value. The primary endpoint was all-cause mortality at 3 years. The secondary endpoints were in-hospital mortality, rehospitalization rates, electrical storm recurrences (ES-R), and major adverse cardiac events (MACE) at 3 years. Results: Eighty-seven ES patients with implantable cardioverter-defibrillators were included. Age ≥ 67 years was associated with increased all-cause mortality at 3 years (48% vs. 20%, hazard ratio = 3.046; 95% confidence interval 1.316–7.051; p = 0.008; log-rank p = 0.006). MACE, in-hospital mortality, rehospitalization rates, and ES-R were not affected by age. Even after multivariate adjustment, age ≥ 67 years was associated with increased long-term mortality at 3 years, besides left ventricular ejection fraction < 35%. In contrast, gender was not associated with the primary and secondary endpoints. Conclusions: Patients 67 years old and older presenting with ES are associated with poor long-term prognosis at 3 years. Increased long-term mortality was still evident after multivariate adjustment. In contrast, gender was not associated with the primary and secondary endpoints

Placebo Response of Non-Pharmacological and Pharmacological Trials in Major Depression: A Systematic Review and Meta-Analysis

Background: Although meta-analyses have shown that placebo responses are large in Major Depressive Disorder (MDD) trials; the placebo response of devices such as repetitive transcranial magnetic stimulation (rTMS) has not been systematically assessed. We proposed to assess placebo responses in two categories of MDD trials: pharmacological (antidepressant drugs) and non-pharmacological (device- rTMS) trials. Methodology/Principal Findings: We performed a systematic review and meta-analysis of the literature from April 2002 to April 2008, searching MEDLINE, Cochrane, Scielo and CRISP electronic databases and reference lists from retrieved studies and conference abstracts. We used the keywords placebo and depression and escitalopram for pharmacological studies; and transcranial magnetic stimulation and depression and sham for non-pharmacological studies. All randomized, double-blinded, placebo-controlled, parallel articles on major depressive disorder were included. Forty-one studies met our inclusion criteria - 29 in the rTMS arm and 12 in the escitalopram arm. We extracted the mean and standard values of depression scores in the placebo group of each study. Then, we calculated the pooled effect size for escitalopram and rTMS arm separately, using Cohen's d as the measure of effect size. We found that placebo response are large for both escitalopram (Cohen's d - random-effects model - 1.48; 95%C.I. 1.26 to 1.6) and rTMS studies (0.82; 95%C.I. 0.63 to 1). Exploratory analyses show that sham response is associated with refractoriness and with the use of rTMS as an add-on therapy, but not with age, gender and sham method utilized. Conclusions/Significance: We confirmed that placebo response in MDD is large regardless of the intervention and is associated with depression refractoriness and treatment combination (add-on rTMS studies). The magnitude of the placebo response seems to be related with study population and study design rather than the intervention itself

Subclass Analysis of Malignant, Inflammatory and Degenerative Pathologies Based on Multiple Timepoint FAPI-PET Acquisitions Using FAPI-02, FAPI-46 and FAPI-74

Purpose: FAPI-PET is a promising imaging technique for various malignant as well as non-malignant pathologies. In a recent retrospective analysis, we evaluated the diagnostic value of repetitive early FAPI-PET-imaging with FAPI-02, FAPI-46 and FAPI-74 for malignant, inflammatory/reactive and degenerative pathologies. Here, we apply a subgroup analysis to that dataset and describe the tracer-wise uptake kinetic behavior of multiple types of FAPI-positive lesions, which are encountered frequently during clinical routine. Methods: A total of 24 cancer patients underwent whole-body FAPI-PET scans, and images were acquired at 10, 22, 34, 46 and 58 min after the administration of 150–250 MBq of 68Ga-FAPI tracer molecules (eight patients each regarding FAPI-02, FAPI-46 and FAPI-74). Standardized uptake values (SUVmax and SUVmean) of healthy tissues, cancer manifestations and non-malignant lesions were measured and target-to-background ratios (TBR) versus blood and fat were calculated for all acquisition timepoints. Results: Differential uptake behavior over time was observed in several subclasses of malignant lesions, inflammatory/reactive lesions and degenerative lesions. These differences over time were particularly manifested in the direct comparison between the uptakes associated with pancreatic carcinoma (stable or increasing over time) and inflammatory lesions of the pancreas (markedly decreasing over time). Furthermore, marked differences were found between the three tracer variants regarding their time-dependent uptake and TBRs within different subclasses of malignant, inflammatory/reactive and degenerative pathologies. Conclusion: Multiple timepoint FAPI-PET/CT is a promising innovative imaging technique that provides additional imaging information compared to single timepoint imaging. Differences in the kinetic behavior of malignant and benign pathologies can facilitate the interpretation of FAPI-positive lesions

Diagnóstico e tratamento clínico curativo da leptospirose canina: relato de caso.

O objetivo do presente trabalho foi relatar um caso de leptospirose em um canino atendido no Hospital de Clínicas Veterinárias da Universidade Federal de Pelotas