[Development and Implementation of a Nutrition Medicine Strategy to optimize Medical Service for Malnourished Patients at a Tertiary Referral Centre]. / Entwicklung und Implementierung einer ernährungsmedizinischen Strategie zur optimierten Versorgung von Patienten mit Mangelernährung in einem Großklinikum.

BACKGROUND: Malnutrition in hospitalised patients is an important and underestimated problem, with a negative impact on outcome and survival - not only in surgical patients. There is a discrepancy between optimal treatment as defined in relevant guidelines on clinical nutrition and the clinical reality. The Main reason for this discrepancy is the lack of established structures for nutrition medicine as an integral part of clinical routines. The necessary structural development is impaired mainly by the lack of resources, but in isolated cases also by the lack of appreciation of the problem. Therefore, practicability and feasibility with regard to local conditions are pivotal for sustainable improvement in a nutrition strategy in hospitalised patients. METHODS: We describe the institutional and procedural measures taken at a tertiary referral centre to implement a nutrition medicine strategy. The underlying nutrition medicine methodology and definitions are introduced and practical implementation at our centre is illustrated by four examples of ongoing projects. RESULTS: Using the described systematics, structural changes were implemented at our centre within one year that allowed malnutrition screening, the treatment of patients with complex nutritional care and improvements in the nutritive status of hospitalised patients by ongoing and future project initiatives. SUMMARY: The successfully implemented structural change at the University Hospital of Bonn described here may serve as a modular example for other hospitals striving to improve clinical nutrition and outcome in hospitalised patients.

[Inderdisciplinary care of patients with short-bowel-syndrome in Germany: A comparative Cost-of-Illness analysis of in- and outpatient care]. / Interdisziplinäre Betreuung von Patienten mit Kurzdarmsyndrom in Deutschland: Eine Cost-of-Illness-Analyse der stationären und ambulanten Behandlung im Vergleich zum erzielten DRG-Erlös.

INTRODUCTION: Short-bowel-syndrome (SBS) is an often chronic disease with high morbidity. The aim of this study was to evaluate the complexity of SBS treatment and the economic burden on a treating hospital. METHODS: Anonymized data of eleven consecutive SBS patients from the University Hospital of Bonn were included. Parameters of medical resources were considered for year of diagnosis (YOD) and a follow-up (FU) period of three years. Subsequently, costs were evaluated according to the corresponding catalogues. RESULTS: Median inpatient days were 96 days in YOD and decreased to three days in the third year of FU. Median cost of inpatient treatment decreased from approximately 84 500 € auf 3200 €. While major visceral surgery was usually required in the YOD, catheter-associated interventions dominated during further FU. Actual reimbursement according to the G-DRG covered approximately 50 % of inpatient treatment cost, for outpatient care only est. 16.5 % of costs were covered. Annual costs for medication, parenteral nutrition and GLP-2-analogon treatment added up to 6752 €, 48 485 € and 138 442 €, respectively. CONCLUSIONS: The interdisciplinary medical care of SBS-patients is resource-intensive and expensive. The required treatment shifts from the in- to the outpatient sector. Both settings are at present not adequately reimbursed. Hence, this imbalance may endanger adequate care for SBS-patients in the future in times of economic rationale. In concordance with other rare disease management programs, additional measures are needed to provide and improve interdisciplinary treatment of SBS.

Continuous low flow ascites drainage through the urinary bladder via the Alfapump system in palliative patients with malignant ascites.

BACKGROUND: Malignant Ascites (MA) is a therapeutic dilemma significantly impairing patients' quality of life (QoL). The Sequana Medical alfapump System (AP), a subcutaneous, externally rechargeable, implantable device, continually draining ascites via the urinary bladder, has been well established in liver cirrhosis, but not yet in MA. The AP-system was evaluated in cancer patients in reducing the need for large volume paracentesis (LVP). METHODS: A retrospective multicentre evaluation of all eligible patients who received an AP for MA-palliation was performed. AP was evaluated for its ability to reduce LVP and cross-correlated with adverse events (AE), survival and retrospective physician-reported QoL. RESULTS: Seventeen patients with median age of 63 years (range: 18-81), 70.6% female, across 7 primary tumour types were analysed. Median duration of AP-implantation was 60 min (range: 30-270) and median post-implantation hospital stay: 4 days (range: 2-24). Twelve protocol-defined AE occurred in 5 patients (29.4%): 4 kidney failures, 4 pump/catheter-related blockages, 3 infections/peritonitis and 1 wound dehiscence. Median ascitic volume (AV) pumped daily was 303.6 ml/day (range:5.6-989.3) and median total AV drained was 28 L (range: 1-638.6). Median patient post-AP-survival was 111 days (range:10-715) and median pump survival was 89 days (range: 0-715). Median number of paracenteses was 4 (range: 1-15) per patient pre-implant versus 1 (range: 0-1) post-implant (p = 0.005). 71% of patients were reported to have an improvement of at least one physician reported QoL-parameters. CONCLUSIONS: AP appears to be effective in palliating patients with MA by an acceptable morbidity profile. Its broader implementation in oncology services should be further explored. TRIAL REGISTRATION: NCT03200106; June 27, 2017.

Increased peripheral CD4+ regulatory T cells persist after successful direct-acting antiviral treatment of chronic hepatitis C.

BACKGROUND & AIMS: CD4+ regulatory T cells (Tregs) expand during chronic hepatitis C virus (HCV) infection, inhibit antiviral immunity and promote fibrosis. Direct-acting antiviral agents (DAA) have revolutionized HCV therapy. However, it is unclear if Tregs are normalized after DAA-induced HCV elimination. METHODS: We analyzed Tregs before (baseline), at end of therapy (EOT), 12 and 24weeks (SVR12, SVR24) and long-term (51±14weeks) after EOT in 26 genotype-1-infected patients who were successfully treated with sofosbuvir (SOF) plus interferon (IFN)/ribavirin (n=12) and IFN-free DAA regimens (SOF plus daclatasvir or simeprevir; n=14). Frequency, phenotype and suppressor function of peripheral Foxp3+ CD25+ CD4+ T cells were studied by multi-color flow cytometry and co-culture inhibition assays. RESULTS: Frequencies and activation status of Foxp3+ CD25+ CD4+ T cells remained elevated above those of normal controls in both treatment groups even long-term after HCV elimination. Co-culture assays indicated a dose-response relationship for functional inhibition of autologous CD4+ effector T cells and confirmed that activation of Tregs remained largely unchanged over the observation period. Unlike IFN-free regimens, SOF plus IFN/ribavirin induced a transiently increased frequency of Foxp3+ CD25+ CD4+ T cells at EOT (5.0% at baseline to 6.1% at EOT; p=0.001). These Foxp3+ CD25+ CD4+ T cells co-expressed the activation markers glycoprotein A repetitions predominant (GARP; p=0.012) and tumor necrosis factor receptor superfamily, member 4 (OX-40; p=0.001) but showed unchanged in vitro inhibitory activity. CONCLUSION: Although IFN-based DAA therapy induced transient expansion of activated Foxp3+ CD25+ CD4+ T cells, neither IFN-based nor IFN-free DAA regimens normalized frequencies and activation status of Tregs one year after viral elimination. Persistence of immunosuppressive Tregs may thus contribute to complications of liver disease even long-term after HCV cure. LAY SUMMARY: In chronic hepatitis C virus (HCV) infection, CD4+ regulatory T cells (Tregs) can reduce antiviral immune responses, promote liver fibrosis and may increase the risk for liver cancer, because they gradually expand during disease. Modern direct-acting antiviral agents (DAA) can "cure" hepatitis C in almost all treated patients. However, our study shows that DAA do not normalize the increased frequency and activation status of Tregs even long-term after HCV elimination. Tregs may persistently modulate functions of the immune system even after "cure" of hepatitis C.

Life on the line - Incidence and management of central venous catheter complications in intestinal failure.

BACKGROUND & AIMS: Loss of venous access is threatening for patients with intestinal failure (IF) under long-term parenteral nutrition (PN). We aimed to identify the incidence of central venous catheter (CVC) complications, compare different devices, and analyze interventional recanalizing procedures to restore the patency of occluded CVCs. METHODS: For this retrospective cohort study, patient data from a prospective IF database spanning 16 years was analyzed at a tertiary referral center. Catheter dwell times (CDTs) were distinguished by Kaplan-Meier survival analysis and subgroup analyses were performed for different CVC types (tunneled/port catheters). Specific complications (occlusion, catheter-related infection (CRI), displacement, and material defect) were analyzed. Explantation rates and CDTs were compared. RESULTS: Overall, 193 CVCs in 77 patients with IF under PN could be enrolled (62.524 "CVC-days"). Broviac type "B" was found to be significantly superior to type "A" regarding occlusion, CRI, and material defects (log-rank test: p = 0.05; p = 0.026; p = 0.005 respectively). Port catheters were displaying the highest incidence of CRI (2.13 events/1000 catheter days). Interventional catheter recanalization was performed 91 times and significantly increased the CDT from a median of 131 days (IQR: 62; 258) to 389 days (IQR: 262; 731) (Mann-Whitney-U-test: p= <0.001) without increasing complications. CONCLUSIONS: Different complication rates and CDT were seen depending on CVC type. Tunneled catheters were significantly superior concerning CRI. Interventional catheter recanalization is a viable alternative to fibrinolytics to restore CVC patency, but long-term patency data is scarce.

Assessing the Effects of a Perioperative Nutritional Support and Counseling in Gastrointestinal Cancer Patients: A Retrospective Comparative Study with Historical Controls.

The aim of this study was to investigate the effects of perioperative nutritional therapy care in gastrointestinal (esophageal, gastric, gastroesophageal) cancer patients on nutritional status and disease progression (complications, hospitalization, mortality). We considered 62 gastrointestinal cancer patients treated at the Center for Integrated Oncology (CIO), University Hospital Bonn, Germany (August 2017-July 2019). Of these, 42 patients (as intervention group: IG) received pre- and postoperative nutritional support with counseling, while 20 patients (as historical control group CG) received only postoperative nutritional therapy. Several clinical parameters, such as Body Mass Index (BMI), nutritional risk screening (NRS), phase angle, postoperative complications, length of hospital stay, and mortality, were determined. There were significantly fewer patients with gastric cancer/CDH1 gene mutation and more with esophageal cancer in IG (p = 0.001). Significantly more patients received neoadjuvant therapy in IG (p = 0.036). No significant differences were found between the groups regarding BMI, NRS, complications, length of hospital stay, and mortality. However, the comparison of post- and preoperative parameters in IG showed a tendency to lose 1.74 kg of weight (p = 0.046), a decrease in phase angle by 0.59° (p = 0.004), and an increase in NRS of 1.34 points (p < 0.001). Contrary to prior reports, we found no significant effect of perioperative nutritional therapy care in gastrointestinal cancer patients; however, the small cohort size and infrequent standardization in nutritional status may possibly account for the variance. Considering that oncological pathways and metabolic nutritional pathways are interrelated, dividing patients into subgroups to provide a personalized nutritional approach may help in improving their treatment.

Transient flare of psoriasis under direct-acting antiviral therapy of chronic hepatitis C: A case report.

Extrahepatic manifestations of chronic hepatitis C virus (HCV) infection frequently involve the skin. Here, we report the case of a woman, who experienced a psoriasis exacerbation on DAA treatment, which lead to psoriasis resolution upon HCV clearance under continued treatment with elbasvir/grazoprevir.

Transpapillary tissue sampling of biliary strictures: balloon dilatation prior to forceps biopsy improves sensitivity and accuracy.

The early and definitive diagnosis of malignant bile duct stenoses is essential for a timely and adequate therapy. However, tissue sampling with transpapillary brush cytology (BC) or forceps biopsy (FB) remains challenging. With this study, we aimed to compare the effectiveness and safety of different tissue sampling modalities (BC, FB without/after previous balloon dilatation). Standardized database research identified all patients, who underwent endoscopic retrograde cholangiography with BC and/or FB for indeterminate bile duct stenosis between January 2010 and April 2018 and with a definitive diagnosis. 218 patients were enrolled (149 cases with malignant and 69 with benign disease). FB had a significant higher sensitivity than BC (43% vs. 16%, p < 0.01). Prior balloon dilatation of the stenosis improved the sensitivity of FB from 41 to 71% (p = 0.03), the NPV from 36 to 81% (p < 0.01) and the accuracy from 55 to 87% (p < 0.01). The complication rates did not differ significantly between the modalities. In our center FB turned out to be the diagnostically more effective procedure. Balloon dilatation of the stenosis before FB had a significant diagnostic benefit and was not associated with a higher complication rate.

The role of variant alleles of the mannose-binding lectin in the inhibitor development in severe hemophilia A.

INTRODUCTION: The administration of FVIII leads to inhibitors in up to 30% of patients with hemophilia A (HA), the most severe treatment complication. FVIII-mannosylation fosters the presentation of FVIII to CD4+-T-lymphocytes. Mannose as primary ligand for the mannose-binding lectin (MBL) activates the lectin pathway of complement. MBL2 single nucleotide polymorphisms (SNPs) lead to low peripheral MBL concentrations that may hamper the removal of mannosylated FVIII. OBJECTIVE: Investigation of the association between the inhibitor development in hemophilia A and MBL2-SNPs. METHODS: In a case-control study the MBL2-SNPs in exon 1 at codons 52, 54 and 57 (C, B, D-Alleles respectively) were determined in 237 patients with severe hemophilia A with and without inhibitors to FVIII (119 vs 118). The association of MBL2-SNPs and the -308 G>A TNF-α-polymorphism with the presence of inhibitors were determined. RESULTS: In the inhibitor group higher frequencies of the B allele (codon 54) (OR: 1.77, P < 0.05) were present. Summarising the MBL2 SNPs (alleles B, C and D) as 0, the 0/0 type occurred only in the inhibitor group (frequencies: 0.08 vs 0, P = 0.003). Based on the genetic background a functional immune response phenotype was determined. 11.8% of patients with inhibitors were of the low MBL/high TNF-α phenotype vs 0.03% of the non-inhibitor patients (OR: 3.71). CONCLUSION: Data suggest an association of MBL2-SNPs alone or combined with the 308-TNF-α polymorphism in the inhibitor development. Investigations of components of all three complement pathways are required to comprehend their individual and overall contribution to the inhibitor development in HA.