To date, there is insufficient insight into inflammatory bowel disease (IBD)-associated stress, recognized disability, and contact with the social care system. We aimed to assess these parameters in ...IBD patients and a non-IBD control group, who were invited to participate in an online survey developed specifically for this study (www.soscisurvey.de) with the help of IBD patients. 505 IBD patients and 166 volunteers (i.e., control group) participated in the survey. IBD patients reported significantly increased levels of stress within the last six months and five years (p<0.0001) and were more likely to have a recognized disability (p<0.0001). A low academic status was the strongest indicator of a disability (p = 0.006). Only 153 IBD patients (30.3%) reported contact with the social care system, and a disability was the strongest indicator for this (p<0.0001). Our study provides data on stress and disability in a large unselected German IBD cohort. We showed that patients with IBD suffer more often from emotional stress and more often have a recognized disability. As only about 1/3 of the patients had come into contact with the social care system and the corresponding support, this patient group is undersupplied in this area.
Objectives
To prospectively evaluate the therapy response of third-line TACE with DSM or lipiodol in the treatment of CRLM using MRI.
Methods
In this prospective, randomized, single-center trial, ...patients were randomly assigned to receive TACE therapy with either lipiodol or DSM as the embolization agent. Therapy response was evaluated using MRI. Local tumor response was determined according to RECIST 1.1, and survival data was analyzed using the Kaplan-Meier estimator.
Results
Fifty patients (35 male, 15 female) were randomized and included in the survival analysis, whereas 31 patients completed therapy and were considered for evaluation of tumor responses (cTACE:
n
= 13, DSM-TACE:
n
= 18). In the cTACE group, PR was observed in 23%, SD in 15%, and PD in 62%. In the DSM-TACE-group, PR was observed in 22% of patients, SD in 56%, and PD in 22% (
p
= 0.047). In addition, the DSM-TACE group showed statistically significant tumor volume reduction (
p
= 0.006). Median apparent diffusion coefficient values were not significantly different between both groups at baseline (
p
= 0.26) and study endpoint (
p
= 0.83). Median survival in the cTACE group was 13 months (95% confidence interval, range 5–40 months) compared to 16 months (95% confidence interval, range 1–48 months) in the DSM-TACE group, exhibiting no statistically significant difference (
p
= 0.75).
Conclusion
DSM-TACE showed a significant difference reducing tumor volume and in tumor response according to RECIST 1.1 compared to cTACE. Thus, patients with CRLM might not only benefit from short embolization effect of DSM-TACE but also from better tumor responses. Apparent diffusion coefficients were not significantly different between both groups and cannot be used as a biomarker for monitoring for therapeutic effect of TACE.
Key Points
• To our knowledge, this is the first prospective study that directly compared cTACE and DSM-TACE in patients with CRLM.
• DSM-TACE showed a significant difference reducing tumor volume (p = 0.006) and in tumor response according to RECIST 1.1 (p = 0.047) compared to cTACE.
• Survival analysis showed a median survival of 13 months in the cTACE group compared to 16 months in the DSM-TACE group (p = 0.75).
Background and Aims The continually increasing life expectancy in man comes along with an increasing number of endoscopic interventions performed in patients with advanced or even very advanced age. ...Data on the feasibility and safety of ERCP in elderly patients are relatively scarce. Methods By a systematic query of the University Hospital Frankfurt clinical database, patients undergoing their first ERCP procedure at our center were retrospectively identified. Patients were grouped according to age at the day of the intervention (>80 years, 61-80 years, 40-60 years, and <40 years). Demographic data, indication, outcome, and risk factors were compared among the indicated groups. Results A total of 758 patients who underwent ERCP procedures at our center were identified and included in the study. Main indications for ERCP were intraductal gallstones in 345 patients (45%) and tumor obstruction of the bile ducts (distal common bile duct: n = 126 16.5%, hilar cholangiocarcinoma: n = 89 11.7%, tumor of papilla of Vater: n = 16 2.1%). Gallstones were the most common cause for ERCP in patients aged >80 years (53.8%), and normal findings indicating exclusion of relevant disease were more frequent in patients <80 years (13.4%) compared with older patients (4.3%) ( P < .01). Sedation adverse events were significantly more common in individuals aged >80 years compared with younger patients (3.4% vs 0.5%; P < .01). However, post-ERCP pancreatitis was significantly less frequent in the older patients (>80 years) (0.9% vs 5.3%; P < .05). Other adverse events were equally distributed in all age groups. The ERCP success rate (>80%) was not different among age groups. Conclusions ERCP is safe and efficient in patients aged 80 years or older. However, conscious sedation must be carefully monitored in older patients because risk of sedation adverse events is increased. The incidence of post-ERCP pancreatitis is lower in older patients compared with younger ones.
Rising prevalence of multidrug-resistant organisms (MDRO) is a major health problem in patients with liver cirrhosis. The impact of MDRO colonization in liver transplantation (LT) candidates and ...recipients on mortality has not been determined in detail.
Patients consecutively evaluated and listed for LT in a tertiary German liver transplant center from 2008 to 2018 underwent screening for MDRO colonization including methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant gram-negative bacteria (MDRGN), and vancomycin-resistant enterococci (VRE). MDRO colonization and infection status were obtained at LT evaluation, planned and unplanned hospitalization, three months upon graft allocation, or at last follow-up on the waiting list.
In total, 351 patients were listed for LT, of whom 164 (47%) underwent LT after a median of 249 (range 0-1662) days. Incidence of MDRO colonization increased during waiting time for LT, and MRDO colonization was associated with increased mortality on the waiting list (HR = 2.57, p<0.0001. One patients was colonized with a carbapenem-resistant strain at listing, 9 patients acquired carbapenem-resistant gram-negative bacteria (CRGN) on the waiting list, and 4 more after LT. In total, 10 of these 14 patients died.
Colonization with MDRO is associated with increased mortality on the waiting list, but not in short-term follow-up after LT. Moreover, colonization with CRGN seems associated with high mortality in liver transplant candidates and recipients.
Purpose
Colorectal cancer (CRC) is the second most common cancer in Germany. Around 60,000 people were diagnosed CRC in 2016 in Germany. Since 2019, screening colonoscopies are offered in Germany for ...men by the age of 50 and for women by the age of 55. It is recently discussed if women should also undergo a screening colonoscopy by the age of 50 and if there are any predictors for getting CRC.
Methods
Colonoscopies of 1553 symptomatic patients younger than 55 years were compared with colonoscopies of 1075 symptomatic patients older than 55 years. We analyzed if there are any significant differences between those two groups in the prevalence of CRC and its precursor lesions or between symptomatic men and women. We evaluated if there is a correlation between abdominal symptoms and the prevalence of CRC.
Results
In 164/1553 symptomatic patients, 194 (12.5%) polyps were detected. In total, six colorectal carcinomas (0.4%) were detected. There were no significant differences between men and women. In symptomatic patients ≥ 55 years, significantly more polyps were found (
p
<0.0001; 26.6% vs. 12.5%). Totally, 286 polyps (26.6%) were removed in 1075 symptomatic patients older than 55 years. Anorectal bleeding was the only abdominal symptom being a significant indicator for the prevalence of the occurrence of colon and rectum cancer in both groups (
p
=0.03, OR=2.73 95%-CI 1.11;6.70), but with only low sensitivity (44%).
Conclusion
Due to no significant differences in men and women, we recommend screening colonoscopies also for women by the age of 50.
Loss of intestinal barrier functions is a hallmark of inflammatory bowel disease like ulcerative colitis. The molecular mechanisms are not well understood, but likely involve dysregulation of ...membrane composition, fluidity, and permeability, which are all essentially regulated by sphingolipids, including ceramides of different chain length and saturation. Here, we used a loss-of-function model (CerS2
+/+
and CerS2
−/−
mice) to investigate the impact of ceramide synthase 2, a key enzyme in the generation of very long-chain ceramides, in the dextran sodium salt (DSS) evoked model of UC. CerS2
−/−
mice developed more severe disease than CerS2
+/+
mice in acute DSS and chronic AOM/DSS colitis. Deletion of CerS2 strongly reduced very long-chain ceramides (Cer24:0, 24:1) but concomitantly increased long-chain ceramides and sphinganine in plasma and colon tissue. In naive CerS2
−/−
mice, the expression of tight junction proteins including ZO-1 was almost completely lost in the colon epithelium, leading to increased membrane permeability. This could also be observed in vitro in CerS2 depleted Caco-2 cells. The increase in membrane permeability in CerS2
−/−
mice did not manifest with apparent clinical symptoms in naive mice, but with slight inflammatory signs such as an increase in monocytes and IL-10. AOM/DSS and DSS treatment alone led to a further deterioration of membrane integrity and to severe clinical symptoms of the disease. This was associated with stronger upregulation of cytokines in CerS2
−/−
mice and increased infiltration of the colon wall by immune cells, particularly monocytes, CD4
+
and Th17
+
T-cells, and an increase in tumor burden. In conclusion, CerS2 is crucial for the maintenance of colon barrier function and epithelial integrity. CerS2 knockdown, and associated changes in several sphingolipids such as a drop in very long-chain ceramides/(dh)-ceramides, an increase in long-chain ceramides/(dh)-ceramides, and sphinganine in the colon, may weaken endogenous defense against the endogenous microbiome.
Hepatocellular carcinoma (HCC) is a leading indication for liver transplantation (LT) worldwide. Early identification of patients at risk for HCC recurrence is of paramount importance since early ...treatment of recurrent HCC after LT may be associated with increased survival. We evaluated incidence of and predictors for HCC recurrence, with a focus on the course of AFP levels. We performed a retrospective, single-center study of 99 HCC patients who underwent LT between January 28.sup.th, 1997 and May 11.sup.th, 2016. A multi-stage proportional hazards model with three stages was used to evaluate potential predictive markers, both by univariate and multivariable analysis, for influences on 1) recurrence after transplantation, 2) mortality without HCC recurrence, and 3) mortality after recurrence. 19/99 HCC patients showed recurrence after LT. Waiting time was not associated with overall HCC recurrence (HR = 1, p = 0.979). Similarly, waiting time did not affect mortality in LT recipients both with (HR = 0.97, p = 0.282) or without (HR = 0.99, p = 0.685) HCC recurrence. Log.sub.10 -transformed AFP values at the time of LT (HR 1.75, p = 0.023) as well as after LT (HR 2.07, p = 0.037) were significantly associated with recurrence. Median survival in patients with a ratio (AFP at recurrence divided by AFP 3 months before recurrence) of 0.5 was greater than 70 months, as compared to a median of only 8 months in patients with a ratio of 5. A rise in AFP levels rather than an absolute threshold could help to identify patients at short-term risk for HCC recurrence post LT, which may allow intensification of the surveillance strategy on an individualized basis.
Patients with gastric cancer often show signs of malnutrition. We sought to evaluate the influence of sarcopenia in patients with locally advanced, not metastasized, gastric or gastro-esophageal ...junction (GEJ) cancer undergoing curative treatment (perioperative chemotherapy and surgery) on morbidity and mortality in order to identify patients in need for nutritional intervention.
Two-centre study, conducted in the Frankfurt University Clinic and Krankenhaus Nordwest (Frankfurt) as part of the University Cancer Center Frankfurt (UCT). 47/83 patients were treated in the FLOT trial (NCT01216644). Patients´ charts were reviewed for clinical data. Two consecutive CT scans were retrospectively analyzed to determine the degree of sarcopenia. Survival was calculated using the Kaplan-Meier method, multivariate analysis was performed using the Cox regression.
60 patients (72.3%) were male and 23 (27.7%) female. 45 patients (54.2%) had GEJ type 1-3 and 38 (45.8%) gastric tumors, respectively. Sarcopenic patients were significantly older than non-sarcopenic patients (mean age 65.1 years vs. 59.5 years, p = 0.042), terminated the chemotherapy significantly earlier (50% vs. 22.6%, p = 0.037) and showed higher Clavien-Dindo scores, indicating more severe perioperative complications (score ≥3 43.3 vs. 17.0%, p = 0.019). Sarcopenic patients had a significantly shorter survival than non-sarcopenic patients (139.6 ± 19.5 95% CI, 101.3-177.9 vs. 206.7 ± 13.8 95% CI, 179.5-233.8 weeks, p = 0.004). Multivariate Cox regression analysis showed that, besides UICC stage, sarcopenia significantly influenced survival.
Sarcopenia is present in a large proportion of patients with locally advanced gastric or GEJ cancer and significantly influences tolerability of chemotherapy, surgical complications and survival.
Vitamin K antagonists (VKAs) have been used in 1% of the world's population for prophylaxis or treatment of thromboembolic events for 64 years. Impairment of osteoblast function and osteoporosis has ...been described in patients receiving VKAs. Given the involvement of cells of the bone marrow microenvironment (BMM), such as mesenchymal stem cells (MSCs) and macrophages, as well as other factors such as the extracellular matrix for the maintenance of normal hematopoietic stem cells (HSCs), we investigated a possible effect of VKAs on hematopoiesis via the BMM. Using various transplantation and in vitro assays, we show here that VKAs alter parameters of bone physiology and reduce functional HSCs 8-fold. We implicate impairment of the functional, secreted, vitamin K-dependent, γ-carboxylated form of periostin by macrophages and, to a lesser extent, MSCs of the BMM and integrin β3-AKT signaling in HSCs as at least partly causative of this effect, with VKAs not being directly toxic to HSCs. In patients, VKA use associates with modestly reduced leukocyte and monocyte counts, albeit within the normal reference range. VKAs decrease human HSC engraftment in immunosuppressed mice. Following published examples that alteration of the BMM can lead to hematological malignancies in mice, we describe, without providing a causal link, that the odds of VKA use are higher in patients with vs without a diagnosis of myelodysplastic syndrome (MDS). These results demonstrate that VKA treatment impairs HSC function via impairment of the BMM and the periostin/integrin β3 axis, possibly associating with increased MDS risk.
•Warfarin impairs murine hematopoiesis via reduction of macrophagic secretion of functional periostin binding to integrin β3 on HSC.•Vitamin K antagonism impairs human HSC engraftment and, in humans, associates with modestly reduced leukocyte counts and MDS.
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Vitamin D has an inhibitory role in the inflammatory signaling pathways and supports the integrity of the intestinal barrier. Due to its immunomodulatory effect, vitamin D plays a role in chronic ...inflammatory bowel disease (IBD) and a deficiency is associated with an increased risk for a flare. We aimed to investigate to what extent the 25-hydroxyvitamin D (25(OH)D3) level correlates with disease activity and whether a cut-off value can be defined that discriminates between active disease and remission.
Patients with IBD, treated at the University Hospital Frankfurt were analyzed retrospectively. The 25(OH)D3 levels were correlated with clinical activity indices and laboratory chemical activity parameters. A deficiency was defined as 25(OH)D3 levels <30 ng/mL.
A total of 470 (257 female) patients with IBD were included, 272 (57.9%) with Crohn's disease (CD), 198 (42.1%) with ulcerative colitis (UC). The median age of the patients was 41 (18-84). In 283 patients (60.2%), a vitamin D deficiency was detected. 245 (53.6%) patients received oral vitamin D supplementation, and supplemented patients had significantly higher vitamin D levels (p < 0.0001). Remission, vitamin D substitution, and male gender were independently associated with the 25(OH)D3 serum concentration in our cohort in regression analysis. A 25(OH)D3 serum concentration of 27.5 ng/mL was the optimal cut-off value.
Vitamin D deficiency is common in IBD patients and appears to be associated with increased disease activity. In our study, vitamin D levels were inversely associated with disease activity. Thus, close monitoring should be established, and optimized supplementation should take place.
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