[Iron supplementation in patients with chronic inflammatory bowel disease: recommendations for a practical approach]. / Eisensupplementation bei Patienten mit chronisch-entzündlicher Darmerkrankung: Empfehlungen zur praxisnahen Vorgehensweise.

Iron deficiency is the predominant cause of anemia. Iron deficiency anemia plays a major role, especially in patients with inflammatory bowel disease (IBD), and is the most common extraintestinal manifestation and IBD-associated systemic complication. The presence of anemia leads to a reduction in quality of life in patients with IBD associated with limitations in physical, emotional, and cognitive function. In addition, it is associated with an increased hospitalization rate. For this reason, iron supplementation is of particular importance. Oral and intravenous iron supplements are used to treat iron deficiency. Due to the lack of absorption and gastrointestinal side effects of oral substitution, intravenous supplementation is becoming increasingly important. However, there are still certain concerns about intravenous administration.With the help of this review, we want to address the topic of iron substitution in patients with IBD, summarize current guideline recommendations, and provide a practical approach.

A Systematic Evaluation of the SARS-CoV-2 Vaccine-Induced Anti-S-RBD-Ig Response in a Population of Health Care Workers.

In the wake of the COVID-19 pandemic, the novel class of mRNA vaccines has been granted first-time approval for active immunization against SARS-CoV-2 alongside the already established viral vector-based vaccines. In this prospective single-center study, we set out to determine the vaccine-induced humoral immune response in a population of 1512 health care employees after the second and third vaccination, respectively. Anti-SARS-CoV-2 receptor-binding domain (RBD) and nucleocapsid antigen antibody concentrations were assessed using commercially available immunoassays. We could show that, in particular, young study subjects aged below 30 years, as well as those with a prior SARS-CoV-2 infection, developed significantly higher antibody concentrations. Our data further suggest that being in physically close contact with formerly SARS-CoV-2-positive people positively affects the post-vaccination response. Surprisingly, study subjects with a BMI > 30 produced the highest anti-S-RBD Ig antibody levels if they had recently received their third vaccination. Also, heterologous dual vaccine regimens consisting of a BNT162b2 and ChAdOx1 n-CoV-19, a homologous triple combination of BNT162b2, and an application of mRNA-1273 as the third vaccine, were most efficient at eliciting a humoral immune response. Our study substantiates existing evidence, but beyond that, scrutinizes the impact of vaccine agents and their respective combinations, as well as different time intervals on humoral immunogenicity.

A Systematic Comparative Study on the Diagnostic Value of Transabdominal Ultrasound in Patients with Pancreatic Cystic Lesions.

Pancreatic cystic lesions are a frequent incidental finding in abdominal imaging. Despite its usually benign background, a small fraction exhibiting features suspicious for cancerous development demands continuous follow-up or surgical removal. Current guidelines advocate magnetic resonance imaging and endoscopic ultrasound to evaluate the risk of malignancy, whereas transabdominal ultrasound is perceived as subordinate imaging. The objective of this study was to analyze cyst detection rates of latest-generation ultrasound machines compared to magnetic resonance imaging, computed tomography, and endosonographic ultrasound and to determine inter-rater reliability. The results showed that large cysts facilitate their visualization by transabdominal ultrasound while detection rates are independent of the anatomical part of the pancreas in which they were sited. Changes in the pancreatic duct width, a connection to the pancreatic duct system, and the architectural characteristics of cysts are poorly recognized by transabdominal ultrasound compared to magnetic resonance imaging and endoscopic ultrasound. Computed tomography imaging is preferred over transabdominal ultrasound to detect calcifications and regional lymphadenopathy. Even if conducted by experienced investigators, transabdominal ultrasound examinations fail to agree with magnetic resonance imaging scans regarding cyst detection rates (κ = 0.093).

Microbial Spectra and Clinical Outcomes from Endoscopically Drained Pancreatic Fluid Collections: A Descriptive Cohort Study.

Pancreatic pseudocyst (PC) and walled-off necrosis (WON) are dreaded complications of acute pancreatitis. Standard therapy consists of endoscopic ultrasound-guided transmural placement of stents to expedite resolution through internal drainage of fluids or necrotic material. Either double pigtail plastic stents (DPPS) or lumen-apposing metal stents (LAMS), or a combination of both, are available for this purpose. The objective of this study was to examine the impact of different stent types on infection rates in addition to clinical outcome measures such as periprocedural adverse events. We conducted a retrospective study comprising 77 patients who had undergone endoscopic drainage for PC or WON in a pancreatitis tertiary referral center. Analysis revealed that both bacterial and fungal infections occurred more frequently in patients treated with LAMS with or without DPPS compared to DPPS only. The use of antibiotics and antimycotics followed the same pattern. Furthermore, a prolonged length of hospital stay and a higher likelihood of transfer to an intermediate care unit were observed in patients with LAMS with or without DPPS. These differences were eliminated if only WON patients were analyzed. Our data imply that the clinical course is primarily influenced by the complexity of the pancreatic fluid collection (PFC) itself rather than the stent type. Prospective large-scale cohort studies are mandatory to underpin these findings.

Intestinal organoids in coculture: redefining the boundaries of gut mucosa ex vivo modeling.

All-time preservation of an intact mucosal barrier is crucial to ensuring intestinal homeostasis and, hence, the organism's overall health maintenance. This complex process relies on an equilibrated signaling system between the intestinal epithelium and numerous cell populations inhabiting the gut mucosa. Any perturbations of this delicate cross talk, particularly regarding the immune cell compartment and microbiota, may sustainably debilitate the intestinal barrier function. As a final joint event, a critical rise in epithelial permeability facilitates the exposure of submucosal immunity to microbial antigens, resulting in uncontrolled inflammation, collateral tissue destruction, and dysbiosis. Organoid-derived intestinal coculture models have established themselves as convenient tools to reenact such pathophysiological events, explore interactions between selected cell populations, and assess their roles with a central focus on intestinal barrier recovery and stabilization.

[SARS-CoV-2 and the digestive tract - Organoids to model gastrointestinal infection]. / SARS-CoV-2-Infektion des Verdauungstrakts ­ Experimentelle Ansätze einer Organoid-basierten in vitro Modellierung.

SARS-CoV-2 is a novel human pathogenic coronavirus whose predilection for the respiratory tract has given rise to a rapid pandemic spread via airborne particles. Organ-specific susceptibility is substantially determined by the density of cell surface expression of ACE2, which is exploited by viral spike protein as a receptor molecule to mediate adhesion and, thus, to permit internalization of the viral genome into the host cell. Based on an ample data set derived from clinical studies and case reports, evidence suggests that distinct cell populations of the digestive and olfactory-gustatory system are equally equipped with membrane-bound ACE2, rendering them "vulnerable" to SARS-CoV-2. Numerous reports on concomitant gastrointestinal complaints and laboratory abnormalities are thought to reflect a relevant degree of organ dysfunction and underscore the tropism of SARS-CoV-2 for the digestive tract. Organoids are three-dimensional in vitro replicas of organ tissue which, owing to their organotypic complex cellular composition and functional resemblance to primary cells, are particularly appreciated for basic research in the field of infectious diseases. This review specifically addresses the involvement of digestive organs by SARS-CoV-2 and outlines the significant contribution of organoid- and primary-cell culture-based models to gaining a deeper understanding of the underlying pathophysiological processes.

Enteropathogenic Infections: Organoids Go Bacterial.

Enteric infections represent a major health care challenge which is particularly prevalent in countries with restricted access to clean water and sanitation and lacking personal hygiene precautions, altogether facilitating fecal-oral transmission of a heterogeneous spectrum of enteropathogenic microorganisms. Among these, bacterial species are responsible for a considerable proportion of illnesses, hospitalizations, and fatal cases, all of which have been continuously contributing to ignite researchers' interest in further exploring their individual pathogenicity. Beyond the universally accepted animal models, intestinal organoids are increasingly valued for their ability to mimic key architectural and physiologic features of the native intestinal mucosa. As a consequence, they are regarded as the most versatile and naturalistic in vitro model of the gut, allowing monitoring of adherence, invasion, intracellular trafficking, and propagation as well as repurposing components of the host cell equipment. At the same time, infected intestinal organoids allow close characterization of the host epithelium's immune response to enteropathogens. In this review, (i) we provide a profound update on intestinal organoid-based tissue engineering, (ii) we report the latest pathophysiological findings defining the infected intestinal organoids, and (iii) we discuss the advantages and limitations of this in vitro model.

Antibiotics regulate the immune response in both presence and absence of lipopolysaccharide through modulation of Toll-like receptors, cytokine production and phagocytosis in vitro.

The inflammatory response to pathogen-associated molecular patterns such as lipopolysaccharide (LPS) in sepsis is mediated via Toll-like receptors (TLRs). Since TLRs also trigger various immune functions, including phagocytosis, their modulation is a promising strategy in the treatment of sepsis. As antibiotics have immunomodulatory properties, this study examined the effect of commonly used classes of antibiotics on i) the expression of TLRs and cytokines and ii) the phagocytic activity under sepsis-like conditions in vitro. This was achieved by incubating THP-1 monocytes and peripheral blood mononuclear cells (PBMCs) obtained from patients after open-heart surgery with the addition of LPS and six key antibiotics (piperacillin, doxycycline, erythromycin, moxifloxacin or gentamicin). After 24h, mRNA levels of both cytokines (IL-1ß, IL-6) and TLRs (1, 2, 4, and 6) were monitored and phagocytosis was determined following coincubation with Escherichia coli. Each antibiotic differentially regulated the gene expression of the investigated TLRs and cytokines in monocytes. Erythromycin, moxifloxacin and doxycyclin displayed the strongest effects and changed mRNA-levels of the investigated genes up to 5.6-fold. Consistent with this, antibiotics and, in particular, moxifloxacin, regulated the TLR-and cytokine expression in activated PBMCs obtained from patients after open-heart surgery. Furthermore, piperacillin, doxycyclin and moxifloxacin inhibited the phagocytic activity of monocytes. Our results suggest that antibiotics regulate the immune response by modulating TLR- and cytokine expression as well as phagocytosis under septic conditions. Moxifloxacin, doxycycline and erythromycin were shown to possess the strongest immunomodulatory effects and these antibiotic classes should be considered for future immunomodulatory studies in sepsis.

Repair of aortic root in patients with aneurysm or dissection: comparing the outcomes of valve-sparing root replacement with those from the Bentall procedure / Reparação de raiz aórtica em pacientes com aneurisma ou dissecção: comparando os resultados da técnica de substituição valve-sparing com os da operação de Bentall

INTRODUCTION: Management of aortic root aneurysm or dissection has been the subject of much discussion that has led to some modifications. The current trend is a valve-sparing root replacement. We compared the outcome following valve sparing root repair with Bentall procedure. METHODS: We retrospectively evaluated 70 patients who underwent root replacement for aneurysm or dissection and compared the outcomes of valve-sparing root replacement with those of the Bentall procedure from January 2007 to December 2011 at our institution. RESULTS: Twenty-five patients had valve-sparing aortic root replacement (VSR, including reimplantation or remodeling) (23 males and 2 females), and 45 patients had the Bentall procedure (34 males and 11 females). Patients who underwent a VSR were younger with a mean age of 55.4 ± 14.8 years compared to those who underwent the Bentall procedure with a mean age of 60.6 ± 12.7 (P=ns). The preoperative aortic insufficiency (AI) in the VSR group was moderate in 8 (32%) patients, and severe in 6 (24%). Preoperative creatinine was 1 ± 0.35 mg/dl in the VSR group and 1.1 ± 0.87 mg/dl in the Bentall group. In the VSR group, 3 (12%) patients had emergency surgery; by contrast, in the Bentall group, 8 (17%) patients had emergent surgery. Concomitant coronary artery bypass grafting (excluding coronary reimplantation) was performed in 8 (32%) patients in the VSR group and in 12 (26.6%) patients in the Bentall group (P=0.78); additional valve procedures were performed in 2 (8%) patients in the VSR group and in 11 (24.4%) patients in the Bentall group. The perioperative mortality was 8% (n=2) and 13.3% (n=6), for the VSR and Bentall procedures, respectively (P=0.7, ns). The total duration of intensive care unit stay was 116.6 ± 106 hours for VSR patients and 152.5 ± 218.2 hours for Bentall patients (P=0.5). The overall length of stay in the hospital was 10 ± 8.1 days for VSR and 11 ± 9.52 days for Bentall (P=0.89). The one-year survival was 92% for the VSR group and 79.0% for the Bentall group. The seven-year survival for the VSR group was 92% and 79% for the Bentall group (95% CI [1.215 to 0.1275], P=0.1). CONCLUSION: Aortic valve-sparing root replacement can be performed with acceptable morbidity and mortality with a comparable long-term survival to the Bentall procedure.

INTRODUÇÃO: Manejo de aneurisma da aorta ou dissecção da raiz tem sido objeto de muita discussão que levou a algumas modificações. A tendência atual é o uso da técnica de substituição valve-sparing (VSR). Nós comparamos o resultado da reparação da raiz utilizando a técnica de substituição valve-sparing com o procedimento de Bentall. MÉTODOS: Foram avaliados, retrospectivamente, 70 pacientes submetidos à substituição da raiz de aneurisma ou dissecção, comparando os resultados da técnica de substituição valve-sparing com os do procedimento Bentall de janeiro de 2007 a dezembro de 2011 em nossa instituição. RESULTADOS: Vinte e cinco pacientes foram submetidos à substituição da valva aórtica com o uso da técnica valve-sparing (VSR, incluindo o reimplante ou remodelação) (23 homens e duas mulheres), e 45 pacientes pelo procedimento de Bentall (34 homens e 11 mulheres). Pacientes que se submeteram à VSR eram mais jovens, com idade média de 55,4 ± 14,8 anos em comparação àqueles que foram submetidos ao procedimento Bentall, idade média de 60,6 ± 12,7 anos (P = ns). A insuficiência aórtica pré-operatória no grupo VSR foi moderada em oito (32%) pacientes e grave em seis (24%). Creatinina pré-operatória foi 1 ± 0,35 mg/dl, no grupo do VSR, e 1,1 ± 0,87 mg/dl, no grupo de Bentall. No grupo VSR, três (12%) pacientes foram operados em caráter de emergência e, no grupo de Bentall, oito (17%). Revascularização do miocárdio concomitante (excluindo reimplante coronariano) foi realizada em oito (32%) pacientes no grupo VSR e, em 12 (26,6%), no grupo de Bentall (P=0,78); procedimentos valvares adicionais foram realizados em 2 (8%) pacientes no grupo do VSR e em 11 (24,4%) no grupo de Bentall. A mortalidade perioperatória foi de 8% (n = 2) e 13,3% (n = 6), para os procedimentos de VSR e Bentall, respectivamente (P=0,7, ns). O tempo de internação na unidade de terapia intensiva foi de 116,6 ± 106,0 horas para pacientes VSR e 152,5 ± 218,2 horas para pacientes Bentall (P=0,5). O tempo de permanência no hospital foi de 10 ± 8,1 dias para VSR e 11 ± 9,52 dias para Bentall (P=0,89). A sobrevida em um ano foi de 92,0 % para o grupo VSR e 79,0% para o grupo de Bentall. A sobrevivência de sete anos para o grupo VSR foi de 92% e 79% para o grupo de Bentall (IC95% [1,215 a 0,1275], P=0,1). CONCLUSÃO: A técnica valve-sparing substituição da raiz aórtica pode ser realizada com a morbidade e mortalidade aceitáveis, e sobrevivência aceitável a longo prazo comparável com o procedimento de Bentall.

Repair of aortic root in patients with aneurysm or dissection: comparing the outcomes of valve-sparing root replacement with those from the Bentall procedure.

INTRODUCTION: Management of aortic root aneurysm or dissection has been the subject of much discussion that has led to some modifications. The current trend is a valve-sparing root replacement. We compared the outcome following valve sparing root repair with Bentall procedure. METHODS: We retrospectively evaluated 70 patients who underwent root replacement for aneurysm or dissection and compared the outcomes of valve-sparing root replacement with those of the Bentall procedure from January 2007 to December 2011 at our institution. RESULTS: Twenty-five patients had valve-sparing aortic root replacement (VSR, including reimplantation or remodeling) (23 males and 2 females), and 45 patients had the Bentall procedure (34 males and 11 females). Patients who underwent a VSR were younger with a mean age of 55.4 ± 14.8 years compared to those who underwent the Bentall procedure with a mean age of 60.6 ± 12.7 (P=ns). The preoperative aortic insufficiency (AI) in the VSR group was moderate in 8 (32%) patients, and severe in 6 (24%). Preoperative creatinine was 1 ± 0.35 mg/dl in the VSR group and 1.1 ± 0.87 mg/dl in the Bentall group. In the VSR group, 3 (12%) patients had emergency surgery; by contrast, in the Bentall group, 8 (17%) patients had emergent surgery. Concomitant coronary artery bypass grafting (excluding coronary reimplantation) was performed in 8 (32%) patients in the VSR group and in 12 (26.6%) patients in the Bentall group (P=0.78); additional valve procedures were performed in 2 (8%) patients in the VSR group and in 11 (24.4%) patients in the Bentall group. The perioperative mortality was 8% (n=2) and 13.3% (n=6), for the VSR and Bentall procedures, respectively (P=0.7, ns). The total duration of intensive care unit stay was 116.6 ± 106 hours for VSR patients and 152.5 ± 218.2 hours for Bentall patients (P=0.5). The overall length of stay in the hospital was 10 ± 8.1 days for VSR and 11 ± 9.52 days for Bentall (P=0.89). The one-year survival was 92% for the VSR group and 79.0% for the Bentall group. The seven-year survival for the VSR group was 92% and 79% for the Bentall group (95% CI [1.215 to 0.1275], P=0.1). CONCLUSION: Aortic valve-sparing root replacement can be performed with acceptable morbidity and mortality with a comparable long-term survival to the Bentall procedure.