Ischemic Duodenal Ulceration after Transarterial Chemoembolization for Hepatocellular Carcinoma: A Case Report

Drug-eluting bead transarterial chemoembolization (DEB-TACE) is a well-established, minimally invasive interventional treatment for nonresectable hepatocellular carcinoma (HCC). Generally, TACE is regarded as safe and effective with a low complication rate. However, remote gastrointestinal ischemia due to the carryover of embolic material into visceral arteries is a rare but serious complication of TACE. In this report, we present a case of duodenal ulceration with contained perforation and severe necrotizing pancreatitis after TACE in a patient with nonresectable HCC and underlying hepatitis C virus associated with Child-Pugh stage B liver cirrhosis. This patient showed, for the first time, complete endoscopic and clinical recovery within 2 months of conservative treatment. Considering the high mortality rate from surgical intervention in all previously reported patients, the significant recovery potential demonstrated by our case suggests conservative treatment with antibiotics and parenteral nutrition combined with close clinical, radiological, and endoscopic monitoring should be considered in all clinically stable patients without signs of peritonism or septic sequelae

Signalling and proinsulin gene regulation by Leptin in pancreatic beta-cells

Das Fettgewebshormon Leptin hemmt in Beta-Zellen des endokrinen Pankreas die Insulinbiosynthese und –sekretion. Insulin dagegen als adipogenes Hormon fördert die Leptinproduktion, so dass ein Regelkreis, die so genannte “Adipoinsuläre Achse“ entsteht. Fehlregulationen dieser Achse werden vor allem bei übergewichtigen Menschen mit einer Hyperleptinämie im Rahmen der Pathogenese des Diabetes mellitus Typ 2 diskutiert. Die genauen molekularen Mechanismen über die die transkriptionellen Effekte von Leptin auf die Proinsulingen Expression erfolgen sind bis dato nicht ausreichend verstanden. Die Signalübertragung von Leptin erfolgt über den JAK-STAT-Signalübertragungsweg. Dieser Signalübertragungsweg kann durch Moleküle aus der Familie der Suppressors of Cytokine Signalling (SOCS) gehemmt werden. Ziel dieser Arbeit war die Leptin vermittelte Signaltransduktion in Beta-Zellen des endokrinen Pankreas sowie die Insulingen Expression näher zu charakterisieren. Stimulation mit Leptin führt zu einer JAK2 abhängigen Phosphorylierung und zeitabhängigen nukleären Translokation von STAT3 und STAT5b in INS-1 Zellen. Sowohl STAT3 als auch STAT5b aktivieren den Proinsulingen Promotor in INS-1 Zellen. Für STAT5b konnte in INS-1 Zellen gezeigt werden, dass diese Aktivierung durch Interaktion mit PDX-1, dem zentralen Regulator der -Zelldifferenzierung und –funktion, und Koaktivator CBP/p300 erfolgt. Diese synergistische Aktivierung ist abhängig von der PDX-1 Bindungsstelle, dem A3/A4 Element im Ratten-Insulingenpromotor 1. Weiterhin konnte in INS-1 Zellen in vitro gezeigt werden, dass Leptin die mRNA Expression von SOCS3 induziert. Eine Aktivierung des Ratten SOCS3 Promotors konnte sowohl durch Leptin, als auch durch STAT3 und STAT5b nachgewiesen werden. Diese Aktivierung erfolgt über spezifische Bindung von STAT3 und STAT5b an bekannte STAT-Bindungsstellen im SOCS3 Promotor, was durch EMSAs mit Kernextrakten von INS-1 Zellen demonstriert werden konnte. SOCS3 wiederum hemmt sowohl die basale als auch die STAT3 und STAT5b vermittelte Aktivierung des Ratten-Insulinpromotors 1 in INS-1 Zellen. Zusammenfassend zeigen diese Ergebnisse, dass SOCS3 ein Leptin induzierter Inhibitor der Proinsulingen Expression in pankreatischen Beta-Zellen ist, im Sinne einer negativen Rückkoppelung. SOCS3 ist somit ein direkter Vermittler der Leptin Signalübertragung distal von JAK-STAT in Beta-Zellen des endokrinen Pankreas.Leptin is an adipocyte-derived hormone that inhibits insulin secretion and proinsulin gene expression in pancreatic beta cells. Insulin, in contrast, is adipogenic and stimulates leptin secretion from the adipose tissue thereby establishing an adipoinsular feedback loop, the so called adipoinsular axis. Dysregulation of this adiposinsular axis with the establishment of leptin resistance in pancreatic beta cells may lead to hyperinsulinemia, which could contribute to obesity and insulin resistance. The molecular mechanism by which leptin exerts transcriptional effects on proinsulin gene expression has yet to be shown. Leptin signal transduction through the leptin receptor is intracellularly coupled to the JAK-STAT signalling pathway. This pathway can be inhibited by a family of molecules, named suppressors of cytokine signalling (SOCS). Aim of this study was to analyse leptin mediated signal transduction and proinsulin gene regulation at the molecular level in pancreatic beta cells. Leptin stimulation lead to JAK2-dependent phosphorylation and time-dependent nuclear translocation of the transcription factors STAT3 and STAT5b in INS-1 beta cells. Both STAT3 and STAT5b activate the rat proinsulin promoter 1 in INS-1 beta cells. Furthermore STAT5b activates the rat proinsuin promoter 1 via interaction with PDX-1, a central regulator of beta cell differentiation and function, and the cofactor CBP/p300 in synergism. This synergism is dependent of the A3/A4 element in the rat insulin 1 promoter. The A3/A4 element is a PDX-1 binding site. In addition, leptin induced mRNA expression of the JAK-STAT inhibitor SOCS3 in vitro in INS-1 beta cells. Transcriptional activation of the rat SOCS3 promoter was observed with leptin, STAT3 and STAT5b. In EMSA´s Leptin induced STAT3 and STAT5b DNA binding to specific STAT responsive binding sites in the SOCS3 promoter was demonstrated. Finally, SOCS3 inhibited basal and both STAT3 and STAT5b-dependent rat insulin 1 gene promoter activity in INS-1 cells. These results suggest that SOCS3 is a leptin-induced inhibitor of proinsulin gene expression in pancreatic beta cells. SOCS3 is a mediator of leptin signalling distal of JAK-STAT in pancreatic beta cells. Leptin-mediated SOCS3 expression in pancreatic beta cells may contribute to the inhibitory effects of leptin on proinsulin gene expression and insulin biosynthesis that has been demonstrated previously

Zobu autotransplantācija ortodontijā

ZobārstniecībaVeselības aprūpeDentistryHealth CareKopsavilkums Mērķis: Šī zinātniskā darba mērķis ir novērtēt autotransplantācijas zobu efektivitāti, ilgtermiņa veiksmes rādītājus un komplikācijas, kas rodas šādas procedūras laikā, kā arī nepieciešamos kritērijus pacientiem, lai varētu veikt veiksmīgu autotransplantāciju. Uzdevumi: Lai novērtētu šo mērķi, šajā zinātniskajā darbā tika pētīta: 1) zobu autotransplantācijas efektivitāte pusaudžiem frontālā rajonā, īpaši tās nozīme gadījumos, kad priekšzobu var izmantot, lai aizstātu iedzimti trūkstošu vai traumatiski zaudētu priekšējo zobu; 2) novērtēta zobu autotransplantācijas efektivitāte, veiksmes rādītāji un to noteicošie faktori; 3) novērtēti estētiskie rezultāti, ko sniedz zobu autotransplantācija augšžokļa priekšējā rajonā; 4) komplikācijas, kas rodas šādas procedūras laikā. Materiāli un metodes: Zinātniskie raksti tika identificēti un atlasīti analīzei saskaņā ar vairākiem iekļaušanas kritērijiem: ne vecāki par 10-15 gadiem, angļu un vācu valodā, sistemātiski pārskati, primārie pētījumi, retrospektīvie pētījumi, ietverti tēmai atbilstoši atslēgvārdi. Darbā tika piemēroti šādi izslēgšanas kritēriji: gadījumu apraksti un raksti, kas vecāki par 15 gadiem, pētījumi, kas neietver vismaz vienu no turpmāk uzskaitītajiem atslēgvārdiem, nav angļu vai vācu valodā. Meklēšana tika veikta no 2021. gada decembra līdz 2022. gada martam, izmantojot vairākas datubāzes, proti, BMJ, Clinical Key, EBSCOhost, ProQuest, PubMed, ScienceDirect (Elsevier), SAGE journals un Wiley Online Library. Secinājumi: Augstā panākumu rādītāja dēļ zobu autotransplantācija ir efektīva ārstēšanas iespēja pusaudžiem un bērniem, kuriem ir iedzimti trūkstoši vai traumatiski zaudēti priekšējie zobi.Abstract Aim: The intention of this scientific thesis is to evaluate the effectiveness of auto transplanted teeth, the long-term success rate and the complications that arise with such a procedure as well as the required criteria of the patients so that successful auto- transplantation can be performed. Objectives: To assess this aim, this scientific paper will explore: 1) the effectiveness of tooth auto-transplantation in the anterior region of adolescents, especially its importance in cases where a premolar can be used to replace a congenitally absent or traumatically lost anterior tooth; 2) evaluate the success rate of tooth auto- transplantation, its survival rate and determining factors which contribute to this; 3) evaluate the aesthetic outcomes of tooth auto-transplantation in the anterior maxilla; 4) the complications that arise with such a procedure. Materials and methods: Studies were identified and selected for analysis according to following inclusion criteria; not older than 10 – 15 years, English and German language, systematic reviews, primary studies, retrospective studies and inclusive of keywords relevant to subject matter as listed below. To ensure accuracies with studies used, the following exclusion criteria were applied: case reports, articles older than 15 years, studies not including at least one of the below listed keywords, not in English or German language. The search was carried out between the months of December 2021 and March 2022, utilizing a range of databases, notably; BMJ, Clinical Key, EBSCOhost, ProQuest, PubMed, ScienceDirect (Elsevier), SAGE journals and Wiley Online Library. Conclusions: Due to its high success rate, tooth auto-transplantation is a highly viable treatment option in adolescents and children who have congenitally absent or traumatically lost anterior teeth

Longitudinal evaluation of efficacy, safety and nutritional status during one-year treatment with the duodenal-jejunal bypass liner

Abstract Background: The endoscopic duodenal-jejunal bypass liner (DJBL) represents a novel temporary endoscopic approach for treatment of obesity-associated type 2 diabetes. Recent results from the German DJBL registry confirmed substantial positive metabolic effects of the DJBL in type 2 diabetes. However, the last Food and Drug Administration trial was stopped due to a high occurrence of hepatic abscesses (3.5%). Objectives: Here, we analyzed time courses of development of co-morbidities, nutritive changes, and occurrence of adverse events during the 1-year treatment phase with the DJBL in the German DJBL registry. Methods: Sixty-six patients from the registry were analyzed for efficacy, safety, and nutritional status. Patient data sets were analyzed at implantation, 3 and 6 months after implantation, and at explantation visits. Results: Weight, body mass index, glycated hemoglobin, and low-density lipoprotein cholesterol primarily declined during the first 3 months after implantation, whereas systolic and diastolic blood pressure were predominantly reduced during the second half of the treatment phase. Severe DJBL-associated side effects were mainly documented at the explantation visit (intestinal obstruction [1.7%], dislocation [1.7%], and liver abscess [1.7%]). Measurements of serum concentrations of ferritin, albumin, vitamin B12, folic acid, 25-hydroxyvitamin D3 (25 OH-Vit-D3), and calcium provided suggestive evidence of a possible decrease of nutritional absorption of vitamins and trace elements by the DJBL. Conclusions: The DJBL demonstrates high efficacy with substantial improvement of all parameters of the metabolic syndrome and the potential for reduction of comedications in overweight patients with type 2 diabetes. These registry results are important to optimize recommendations for adaptation of concomitant medication, surveillance of adverse events, nutritional status and supplementation, and adaptation of the implantation period of the DJBL. [Epub 2018 Mar 9

Trends in BMI, Glycemic Control and Obesity-Associated Comorbidities After Explantation of the Duodenal-Jejunal Bypass Liner (DJBL)

Background A novel-approach for treatment of obesity and diabetes mellitus type 2 (T2DM) is represented by the endoscopic duodenal-jejunal bypass liner (DJBL). Recent data from the German DJBL registry provide evidence for substantial efficacy of the DJBL during the implantation period in obese patients with T2DM. However, little is known about the trends of glycemic control, BMI, and comorbidities after explantation of the DJBL, which have been investigated in the registry in this report. Methods Patients were selected from the registry if they had a dataset at implantation, explantation, and at least one time point after explantation of the DJBL (n =?77). We also investigated a subgroup of patients with available data at least 1 year (–2 weeks) after explantation of the DJBL (n =?32). Results For a mean BMI at implantation and a mean follow-up period, an increase of BMI of 2.1 kg/m2 (CI 0.8–3.2; p =?0.013) had to be expected (for HbA1c 0.3% (CI ??0.0–0.7; p =?n.s.), respectively). In the subgroup analysis, HbA1c and BMI increased after explantation of the DJBL but stayed significantly below baseline levels. Meanwhile, the mean number of antidiabetic drugs slightly increased. There was deterioration seen for blood pressure and LDL cholesterol over the postexplantation period to approximately baseline levels (or higher). Conclusion With this data, we show that improvement of HbA1c and BMI can be partly maintained over a time of nearly 1-year postexplantation of the DJBL. However, for HbA1c, this may be biased by intensified medical treatment and effects deteriorated with time after explantation. These results suggest that implantation of the DJBL needs to be integrated in a long-term weight management program as most of other interventions in obese patients with T2DM

Characteristics of cystic fibrosis-related diabetes: Data from two different sources the European cystic fibrosis society patient registry and German/Austrian diabetes prospective follow-up registry

BACKGROUND Standardized patient registries provide a unique basis to get insight into cystic fibrosis (CF)-related diabetes (CFRD), the most common comorbidity in CF. METHODS A total of 3853 CFRD patients from the European CF Society Patient Registry (ECFSPR) and 752 from the German/Austrian diabetes prospective follow-up (diabetes patienten verlaufsdokumentation [DPV]) were studied. To adjust for age and sex, multivariable regression was used (SAS 9.4). RESULTS DPV subjects were younger (26.5 [20.2-32.6] vs 28.3 [21.7-36.0] years, P < 0.001) and more often female (59.6 vs 50.9%, P < 0.001). In both registries, F508del homozygotes were most frequent, with higher proportion in DPV (80.9 vs 57.8%, P = 0.003). After adjustment, lung-transplantation (LTX) was more common in ECFSPR (18.9 vs 4.9%, P < 0.001), although duration since LTX (4.8 ± 0.2 vs 5.5 ± 0.7 years, P = 0.33) did not differ. In DPV patients without LTX, a lower BMI (19.6 ± 0.1 vs 21.0 ± 0.1 kg/m$^{2}$ , P < 0.001), higher proportion of underweight (41.2 vs 20.2%, P < 0.001) and a tendency towards worse lung function (%FEV$_{1}$ : 42.3 ± 4.2 vs 48.3 ± 0.5%, P = 0.16) were observed. CONCLUSIONS Between both registries, demographic and clinical differences of CFRD were present. Besides different kind of data sources, diverse treatment structures between countries may play a role. The results may further indicate a more serious illness in patients treated in specialized diabetes clinics, documenting their data in DPV

Comparative efficacy and safety of the duodenal-jejunal bypass liner in obese patients with type 2 diabetes mellitus – a case control study

Abstract Aims: The duodenal-jejunal bypass liner (DJBL) is an endoscopic device mimicking surgical duodenal-jejunal bypass, and is indicated for the treatment of obesity-associated type 2 diabetes mellitus. This analysis was conducted to evaluate the efficacy and safety of the DJBL in comparison to lifestyle changes and antidiabetic drugs. Materials and methods: To determine the efficacy and long-term safety of the DJBL, data concerning 235 obese patients with type 2 diabetes mellitus from the German DJBL registry were analysed. For comparison with standard treatment, propensity-score-matching with patients from the German DPV registry, including the matching parameters sex, age, diabetes duration, baseline BMI and baseline HbA1c, was applied. The final matched cohort consisted of 111 patients in the DJBL group and 222 matched control DPV patients. Results: Mean treatment time with the DJBL was 47.5 ± 12.2 weeks, mean BMI reduction was 5.0 kg/m2 (P < .001) and mean HbA1c reduction was 1.3% (11.9 mmol/mol) (P < .001). Reduction of antidiabetic medications and improvements in other metabolic and cardiovascular risk parameters was observed. In comparison to the matched control group, mean reductions in HbA1c (-1.37% vs -0.51% [12.6 vs 3.2 mmol/mol]; P < .0001) and BMI (-3.02 kg/m2 vs -0.39 kg/m2 ; P < .0001) were significantly higher. Total cholesterol, LDL cholesterol and blood pressure were also significantly better. Conclusion: This study provides the largest, so far, hypothesis-generating evidence for a putative positive risk/benefit ratio for treatment of obese patients with type 2 diabetes mellitus with the DJBL as an alternative treatment option for this patient population