Energy Metabolism in Residents in the Low- and Moderate Altitude Regions of Central Asia with MAFLD and Type 2 Diabetes Mellitus.

The knowledge about the features of energy metabolism in MAFLD in the population living at different climatic and geographic heights is lacking. The goal of this study is to explore the biochemical parameters of blood and erythrocyte energy consumption in patients with MAFLD with and without DM2 living in the low- and moderate-altitude regions of Central Asia. Our study was carried out on patients living in low-altitude mountains: Bishkek, altitude=750-800 m; n=67 (MAFLD with DM 2: n=24; MAFLD without DM2: n=25; control: n=18), and At-Bashy District, Naryn Region, altitude=2046-2300 m; n=58 (MAFLD with DM2: n=28; MAFLD without DM2: n=18; control: n=12). Non-alcoholic fatty liver disease was diagnosed according to history, laboratory tests, liver ultrasound, and exclusion of other liver diseases. The level of liver fibrosis was determined using the FIB-4 score. Blood adenosine 5'-triphosphate (ATP) was determined using the CellTiter-Glo method. Healthy residents living in moderate altitudes have significantly higher levels of cytosolic ATP in their blood (p+≤+0.05) than residents living in low mountains. MAFLD is characterized by an increase in the level of ATP concentration in their blood. ATP concentration decreased significantly in patients with MAFLD with DM2 living in moderate-altitude in comparison to those living in low-altitude mountains. The results suggest that chronic altitude hypoxia leads to a breakdown in adaptive mechanisms of energy metabolism of ATP in patients with MAFLD with type 2 DM.

[Management of persistent colitis after successful immunotherapy for non-small cell carcinoma of the lung]. / Management einer persistierenden Kolitis nach erfolgreicher Immuntherapie eines nicht-kleinzelligen Karzinoms der Lunge.

Immune checkpoint inhibitors have shown remarkable efficacy as new-generation drugs in anti-tumor therapy. However, the nonspecific activation of the immune system leads to a number of adverse side effects, so-called immune-related adverse events (irAEs), including the occurrence of diarrhea and colitis in about one third of treated patients.Endoscopically and histologically, there is significant overlap of immune-mediated colitis with classic IBD, making differentiation difficult.Therapeutically, high-dose glucocorticoids are used in grade 3 (severe) to grade 4 (life-threatening) colitis, in addition to discontinuation of ICI therapy. Steroid-refractory cases (up to 42%) benefit from the TNF inhibitor infliximab. Vedolizumab, analogous to inflammatory bowel disease, represents second-line therapy for infliximab-refractory cases. Little data exist to date on the efficacy of tofacitinib in refractory cases.We describe the case and therapeutic management of severe and persistent immune-mediated colitis after successful immunochemotherapy with pembrolizumab in an 80-year-old man with metastatic non-small cell carcinoma of the lung and pre-existing colitis unclassified and other comorbidities.

[Risk of malnutrition in elderly patients in acute hospitals - implications for nursing practice]. / Gefahr einer Mangelernährung älterer Patient_innen im Akutspital.

Risk of malnutrition in elderly patients in acute hospitals - implications for nursing practice Abstract. Background: The risk of malnutrition is increased in advanced age and acute illness, and its assessment and needs-based support are part of the responsibility of nursing. Research question / objective: The following research question aims to analyse the nutritional status and possible correlations with nursing diagnoses and other patient characteristics from persons who are 80 years old and older: Which patterns in the sense of clusters can be identified concerning calorie and protein requirements and other patient characteristics? METHODS: Explorative cross-sectional study with cluster analysis based on food intake protocols and nursing documentation. Patients from surgery, internal medicine and university acute geriatric care wards were included in this non-probability sample. RESULTS: Four groups were formed out of the data from 135 patients (protein requirement coverage): Well-nourished (116 %), sufficiently-nourished (77 %), insufficiently-nourished (59 %) and poorly-nourished (40 %). A significant correlation between calorie and protein requirement coverage and treatment area has been shown. CONCLUSIONS: The degree of coverage of protein- and energy requirement is related to the treatment area and consequently to its team culture and treatment concept. Based on the characteristics of the well-nourished, a positive effect of interprofessional cooperation and systematic recording of the risk of malnutrition, as implemented in the treatment area of acute geriatric care, might be concluded.

Functional Molecular Network Analysis Enables Prediction of Response to Vedolizumab Therapy in Anti-TNF Refractory IBD Patients.

BACKGROUND: We applied for the first time 2 label-free technologies, physiological intermolecular modulation spectroscopy (PIMS) and nematic protein organization technic (NPOT) in anti-tumor necrosis factor (TNF) refractory inflammatory bowel disease (IBD) patients to identify clinical responders to vedolizumab therapy and elucidate their underlying functional molecular network. METHODS: PIMS analysis was performed in peripheral blood taken prior to the first vedolizumab application in 20 IBD patients (Crohn disease n = 13; ulcerative colitis n = 7) refractory to at least 1 previous anti-TNF agent therapy. Peripheral blood taken from clinical responders and nonresponders at week 14 of vedolizumab therapy were additionally subjected to NPOT analysis. Response to therapy was assessed by respective clinical disease activity scores (partial Mayo Score and Harvey-Bradshaw Index). RESULTS: Clinical response to vedolizumab treatment was observed in 7 of 13 Crohn disease and 4 of 7 ulcerative colitis patients at week 14. Response to therapy was accurately predicted by PIMS blood analysis in 100% of ulcerative colitis and 77% of Crohn disease patients. Overall prediction of clinical response with PIMS blood analysis was achieved with a 89% positive predictive value and a 82% negative predictive value. NPOT analysis revealed the heightened expression of the proteins ITGB7, ITGAV, ITG3, PF4, and ASGH in the peripheral blood of vedolizumab responders compared to nonresponders. CONCLUSIONS: PIMS analysis of the blood of anti-TNF refractory IBD patients was able to stratify responders to vedolizumab therapy with high accuracy and specificity. NPOT technology could decipher underling molecular networks in the blood of responders, enabling subsequent personalized therapeutic approaches in IBD.

[Full thickness resection of a pyloric adenoma in the proximal duodenum in a 67-year-old patient with attenuated polyposis coli]. / Vollwandresektion eines Pylorusdrüsenadenoms im proximalen Duodenum bei einem 67-jährigen Patienten mit attenuierter Polyposis coli.

BACKGROUND: Pyloric gland adenomas (PGAs) are very rare and underdiagnosed, mostly be founded in the stomach. Similar to colorectal adenomas they have a high risk of malignant transformation to adenocarcinoma up to 12-47 %. Endoscopic resections in the duodenum harbor a significant risk of complications. EMR is the current standard technique for treatment of duodenal non-ampullary adenomas. Complete resection rates are considerably high at about 90 %. Adverse events as bleeding was reported up to 25 %. ESD is not recommended for resection of duodenal lesions since the perforation rate may be as high as 35 %. Use of EFTR in the duodenum are limited to a single case study of 20 patients. CASE: A 67 year old patient with attenuated polyposis coli presented for screening. Gastroscopy showed a 20 mm large, non-ampullary lesions in the proximal duodenum (pars I). The margins of the duodenal lesions were marked with a high-frequency (HF) probe. An integrated balloon dilatation (20 mm) of the upper esophageal sphincter and the pylorus was performed to facilitate advancing of the gastroduodenal FTRD® (Ovesco Endoscopy AG). After pulling the duodenal lesion into the cap with a grasper the FTRD clip was deployed and the lesion immediately resected with the preloaded snare. A single-shot antibiotic prophylaxis with 2 g ceftriaxone i. v. was administered during the intervention. Second-look endoscopy was scheduled 24 h after resection. The resectat showed histologically a gastric type adenoma of 18 mm in the proximal duodenum (immunohistochemistry positive for Mucin-1, Mucin-5, Mib 1). CONCLUSION: Herein we present the first case of duodenal EFTR in a patient with attenuated FAP and a PGA. There are currently no specific guidelines for the removal and surveillance. ASGE recommends resection and surveillance endoscopy at 3-5 years interval.

Acute sedation-associated complications in GI endoscopy (ProSed 2 Study): results from the prospective multicentre electronic registry of sedation-associated complications.

OBJECTIVES: Sedation has been established for GI endoscopic procedures in most countries, but it is also associated with an added risk of complications. Reported complication rates are variable due to different study methodologies and often limited sample size. DESIGNS: Acute sedation-associated complications were prospectively recorded in an electronic endoscopy documentation in 39 study centres between December 2011 and August 2014 (median inclusion period 24 months). The sedation regimen was decided by each study centre. RESULTS: A total of 368 206 endoscopies was recorded; 11% without sedation. Propofol was the dominant drug used (62% only, 22.5% in combination with midazolam). Of the sedated patients, 38 (0.01%) suffered a major complication, and overall mortality was 0.005% (n=15); minor complications occurred in 0.3%. Multivariate analysis showed the following independent risk factors for all complications: American Society of Anesthesiologists class >2 (OR 2.29) and type and duration of endoscopy. Of the sedation regimens, propofol monosedation had the lowest rate (OR 0.75) compared with midazolam (reference) and combinations (OR 1.0-1.5). Compared with primary care hospitals, tertiary referral centres had higher complication rates (OR 1.61). Notably, compared with sedation by a two-person endoscopy team (endoscopist/assistant; 53.5% of all procedures), adding another person for sedation (nurse, physician) was associated with higher complication rates (ORs 1.40-4.46), probably due to higher complexity of procedures not evident in the multivariate analysis. CONCLUSIONS: This large multicentre registry study confirmed that severe acute sedation-related complications are rare during GI endoscopy with a very low mortality. The data are useful for planning risk factor-adapted sedation management to further prevent sedation-associated complications in selected patients. TRIAL REGISTRATION NUMBER: DRKS00007768; Pre-results.

Physiological intermolecular modification spectroscopy for the prediction of response to anti-tumor necrosis factor therapy in patients with inflammatory bowel diseases.

BACKGROUND/AIMS: Anti-tumor necrosis factor (TNF) antibodies have clinical efficiency only in a subgroup of patients with inflammatory bowel diseases (IBD). Prediction of clinical response is a critical clinical problem. Physiological intermolecular modification spectroscopy (PIMS) is a label-free technology performed in physiological conditions. PIMS enables real-time monitoring of dynamic molecular resonance of entire proteins and macromolecules of an individual. The aim of this study was to explore the capacity of PIMS to discriminate IBD patients regarding response to anti-TNF treatment. METHODS: Protein extracts of peripheral blood mononuclear cells (PBMC) from 30 outpatients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) and treated with infliximab were subjected to PIMS analysis in a blinded transversal study. Total protein from each patient's PBMCs was challenged with infliximab. Dynamic changes in macromolecular interaction were registered while the temperature rose from -37 to 37°C. Individual macromolecular volume and molecular elasticity were determined for each patient. RESULTS: Clinical data revealed that 67% of UC and 79% of CD patients responded to infliximab therapy during the 3-month study period based on their respective clinical activity score. These results confirm that PIMS data predicted response to anti-TNF therapy with an accuracy of 96%. CONCLUSION: PIMS stratified IBD patients into two groups, responders and nonresponders, which correlated with the clinical efficacy of anti-TNF therapy. PIMS seems to be a powerful technology to adapt IBD treatment to the individual patient. Further studies with PIMS might enable to predict clinical response to biological treatment in IBD patients before the therapy is initiated.

Early recurrence of pancreatic cancer after resection and during adjuvant chemotherapy.

BACKGROUND/AIM: Adjuvant chemotherapy for 6 months is the current standard of care after potentially curative resection of pancreatic cancer and yields an overall survival of 15-20 months. Early tumor recurrence before or during adjuvant chemotherapy has not been evaluated so far. These patients may not benefit from adjuvant treatment. PATIENTS AND METHODS: Thirty-five patients with resection of ductal pancreatic carcinoma and adjuvant chemotherapy with gemcitabine were analyzed between 2005 and 2007. All patients had a computed tomography (CT) scan before and during adjuvant chemotherapy after 2-3 months, 12/35 patients had a histologically confirmed R1 resection. Recurrence of pancreatic cancer was determined by CT scan and the clinical course. RESULTS: Median survival of 35 patients with resected pancreatic cancer was 19.7 months, and the 2-year survival was 44%. Thirteen (37%) of the 35 patients analyzed with a CT scan showed tumor recurrence during adjuvant chemotherapy. Overall survival of patients with tumor recurrence was 9.3 months with a 2-year survival rate of 13%, whereas median overall survival of patients without early relapse was 26.3 months (P<0.001). Local recurrence of pancreatic cancer occurred in 38% (5/13); 46% (6/13) of patients developed distant metastasis, and 38% (5/13) developed lymph node metastasis. Early tumor recurrence during or adjuvant chemotherapy did not correlate with R status (R1 vs R0, P=0.69), whereas histologically confirmed lymph node invasion (pN0 vs pN1) and grading showed a statistically significant correlation with early relapse (P<0.05). CONCLUSION: A significant fraction of patients with resected pancreatic cancer have early relapse during adjuvant chemotherapy, especially those with lymph node metastasis. Radiologic examinations prior to and during adjuvant chemotherapy will help to identify patients with tumor recurrence who are unlikely to benefit from adjuvant treatment and will need individualized palliative chemotherapy.

Treatment of unresectable cholangiocarcinoma: conventional transarterial chemoembolization compared with drug eluting bead-transarterial chemoembolization and systemic chemotherapy.

BACKGROUND: Unresectable cholangiocarcinoma (CCC) has a poor prognosis. Patients with intrahepatic CCC have a very limited benefit from systemic chemotherapy (ChT). The aim of this prospective study was to evaluate the feasibility, safety, and efficacy of conventional transarterial chemoembolization (cTACE) with mitomycin-C and of irinotecan-eluting beads (iDEB-TACE), and to retrospectively compare them with ChT with oxaliplatin and gemcitabine. MATERIALS AND METHODS: Between June 2002 and June 2010, three independent prospective trials were carried out and compared retrospectively. Following predefined study protocols, 26 patients with histologically proven intrahepatic CCC were treated with iDEB-TACE (200 mg irinotecan), 10 patients were treated with cTACE using 15 mg mitomycin-C mixed with 5-10 ml of ionized oil (lipiodol), followed by embolization with gelfoam, and 31 patients received systemic ChT with gemcitabine and oxaliplatin. Treatment response and progression-free survival (PFS) were assessed by computer tomography or MRI every 2 months according to Response Evaluation Criteria in Solid Tumors. Clinical and laboratory data were assessed for side-effects according to National Cancer Institute-Common Toxicity Criteria. RESULTS: iDEB-TACE resulted in PFS of 3.9 months and overall survival (OS) of 11.7 months, compared with a PFS of 1.8 months and OS of 5.7 months, respectively, in patients treated with cTACE, and a PFS of 6.2 months and OS of 11.0 months, respectively, in patients treated with oxaliplatin and gemcitabine. The medium follow-up of patients treated with iDEB-TACE was 12 months; 2 months after treatment, 13 patients (50%) had progressive disease, 11 patients (42%) had stable disease, and one patient had a partial response and became eligible for secondary liver resection. Local tumor control was achieved in 66% of patients; 4% had a partial response, 62% had stable disease, and 27% progressive disease. Common Toxicity Criteria grade III or IV toxicities for iDEB-TACE were abdominal pain (n=7), hepatic abscess (n=1), pleural empyema due to biliary leakage (n=1), and one death due to cholangitis with hepatic failure in a patient with liver cirrhosis. No hematological side-effects were observed. Almost every patient experienced a 'postembolization syndrome' with low-grade fever, nausea, and abdominal pain for up to 2 weeks. CONCLUSION: This is the first study demonstrating that treatment of patients suffering from intrahepatic CCC with iDEB-TACE is safe in patients with normal liver function, and results in a prolongation of PFS and OS. Local tumor control, PFS and OS seem similar to systemic ChT with oxaliplatin and gemcitabine, but superior to cTACE.

Acute hepatitis after autologous stem cell transplantation and rapid progression to liver cirrhosis.

A 51-year-old woman was diagnosed with a diffuse cerebral large cell lymphoma. During the period of a combined chemotherapy followed by autologous stem cell transplantation with multiple blood donations, an acute hepatitis without hepatitis C antibodies was diagnosed. Liver biopsy showed steatohepatitis, initially thought to be related to chemotherapy. Sixteen months after the transplantation, liver cirrhosis appeared with circulatory bypass. Retrospectively, testing of serum samples showed a hepatitis C infection. Infection with the hepatitis C virus (HCV) from a blood donation was excluded through retrospective testing for HCV-RNA of blood donors. Finally, the cause of infection remained elusive. Hepatitis serology is not a reliable test under immunosuppressive therapy. The course of progression to liver cirrhosis in the presented short period of 22 months after HCV infection is remarkable and has - to our knowledge - not been reported in literature before.