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1.
Exp Clin Endocrinol Diabetes ; 132(4): 223-226, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38458229

RESUMO

BACKGROUND: Due to a multicenter study early in the coronavirus disease (COVID)-pandemic that revealed an increased risk for postoperative mortality, thromboembolic and pulmonary complications in case of surgery shortly after a COVID infection, current recommendations for planning elective surgeries suggest postponing surgery for at least 7 weeks after COVID infection. However, virus variants have evolved throughout the pandemic, leading to less severe symptoms. Besides, laparoscopic adrenal gland surgery itself is a safe procedure with low morbidity rates. Therefore, this study aimed to compare the perioperative course of patients undergoing laparoscopic adrenalectomy shortly after a COVID-19 infection with those who had not had a recent SARS-CoV-2 infection in 2022. PATIENTS, MATERIAL, AND METHODS: All patients who underwent laparoscopic adrenalectomy at the Department for General, Visceral and Transplantation Surgery at Ludwig-Maximilian University between January and December 2022 were included. RESULTS: There was no event of thromboembolic or pulmonary complications in the study population. Duration of surgery did not differ between the two groups; neither did the need for postoperative ICU-admittance nor the duration of ICU-stay. Intraoperative FiO2 did not differ, nor did the SpO2 or the number of different catecholamines. There was a slight trend towards higher noradrenaline dosage among patients after COVID-19 infection. Previous COVID infection did not lead to prolonged hospital stays. CONCLUSION: The results demonstrate that in case of well-standardized surgical procedures, with a limited surgical trauma and the possibility for patients to be mobilized early, surgery shortly after a mild COVID infection seems safe and reasonable.


Assuntos
COVID-19 , Laparoscopia , Humanos , SARS-CoV-2 , Estudos Retrospectivos , Laparoscopia/efeitos adversos , Glândulas Suprarrenais , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
2.
Int J Colorectal Dis ; 39(1): 36, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38456914

RESUMO

INTRODUCTION: Crohn's disease (CD) is a chronic inflammatory bowel disease of a multifactorial pathogenesis. Recently numerous genetic variants linked to an aggressive phenotype were identified, leading to a progress in therapeutic options, resulting in a decreased necessity for surgery. Nevertheless, surgery is often inevitable. The aim of the study was to evaluate possible risk factors for postoperative complications and disease recurrence specifically after colonic resections for CD. PATIENTS AND METHODS: A total of 241 patients who underwent colonic and ileocaecal resections for CD at our instiution between 2008 and 2018 were included. All data was extracted from clinical charts. RESULTS: Major complications occurred in 23.8% of all patients. Patients after colonic resections showed a significantly higher rate of major postoperative complications compared to patients after ICR (p = < 0.0001). The most common complications after colonic resections were postoperative bleeding (22.2%), the need for revision surgery (27.4%) and ICU (17.2%) or hospital readmission (15%). As risk factors for the latter, we identified time interval between admission and surgery (p = 0.015) and the duration of the surgery (p = 0.001). Isolated distal resections had a higher risk for revision surgery and a secondary stoma (p = 0.019). Within the total study population, previous bowel resections (p = 0.037) were identified as independent risk factors for major perioperative complications. CONCLUSION: The results indicate that both a complex surgical site and a complex surgical procedure lead to a higher perioperative morbidity in colonic resections for Crohn's colitis.


Assuntos
Colite , Doença de Crohn , Humanos , Doença de Crohn/complicações , Doença de Crohn/cirurgia , Doença de Crohn/patologia , Colectomia/efeitos adversos , Colectomia/métodos , Recidiva Local de Neoplasia/cirurgia , Complicações Pós-Operatórias/epidemiologia , Colite/cirurgia , Colite/complicações , Morbidade
3.
Stat Methods Med Res ; 33(3): 433-448, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38327081

RESUMO

The development process of medical devices can be streamlined by combining different study phases. Here, for a diagnostic medical device, we present the combination of confirmation of diagnostic accuracy (phase III) and evaluation of clinical effectiveness regarding patient-relevant endpoints (phase IV) using a seamless design. This approach is used in the Thyroid HEmorrhage DetectOr Study (HEDOS & HEDOS II) investigating a post-operative hemorrhage detector named ISAR-M THYRO® in patients after thyroid surgery. Data from the phase III trial are reused as external controls in the control group of the phase IV trial. An unblinded interim analysis is planned between the two study stages which includes a recalculation of the sample size for the phase IV part after completion of the first stage of the seamless design. The study concept presented here is the first seamless design proposed in the field of diagnostic studies. Hence, the aim of this work is to emphasize the statistical methodology as well as feasibility of the proposed design in relation to the planning and implementation of the seamless design. Seamless designs can accelerate the overall trial duration and increase its efficiency in terms of sample size and recruitment. However, careful planning addressing numerous methodological and procedural challenges is necessary for successful implementation as well as agreement with regulatory bodies.


Assuntos
Hemorragia , Projetos de Pesquisa , Humanos , Grupos Controle , Tamanho da Amostra , Resultado do Tratamento
4.
Ann Surg ; 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38275104

RESUMO

BACKGROUND: Recent retrospective studies suggest a role for distinct microbiota in the perioperative morbidity and mortality of pancreatic head resections. OBJECTIVE: We aimed to prospectively investigate the microbial colonization of critical operative sites of pancreatic head resections to identify microbial stratification factors for surgical and long-term oncologic outcomes. METHODS: Prospective biomarker study applying 16S rRNA sequencing and microbial culturing to samples collected from various sites of the GI tract and surgical sites of patients during pancreatic head resections at a German single high-volume pancreatic center. RESULTS: A total of 101 patients were included (38 non-cancer, 63 cancer patients [50 PDAC patients]) in the study. In a first data analysis series, 16S rRNA sequencing data were utilized from 96 patients to assess associations of microbiome profiles with clinical parameters and outcomes. In general, microbiome composition varied according to sampling site, cancer, age or preoperative ERCP intervention, notably for the bile microbiome. In the PDAC subcohort, compositional variance of the bile or periampullary microbiome was significantly associated with postoperative complications such as ICU admission; on a taxonomic level we observed Enterococcus spp. to be significantly more abundant in patients developing deep or organ-space surgical site infections (SSI). Elevated Enterococcus relative abundances in the upper GI tract, in turn, were associated with 6-months mortality rates. In a second step, we focused on microbiological cultures collected from bile aspirates during surgery and investigated associations with perioperative complications and long-term survival. Notably, Enterococcus spp. were among the most prevalent pathobiont isolates observed in cancer patient bile specimens that were associated with severe SSIs, and thereby elevated mortality rates up to 24 months. Clinically relevant postoperative pancreatic fistulas or severe SSI were found as other major variables determining short-term mortality in this cancer patient cohort. In the context of adverse microbiological factors, a preoperative ERCP was also observed to segregate long-term survival, and it appeared to interact with the presence of Enterococcus spp. as highest mortality rates were observed in PDAC patients with both preoperative ERCP and presence of E. faecalis in bile aspirates. CONCLUSIONS: The presence of Enterococcus spp. in bile ducts of PDAC patients undergoing pancreatic surgery represents a significant risk factor for perioperative infections and, thereby, elevated postoperative and long-term mortality. This finding supports previous data on the use of the antibiotic drug piperacillin-tazobactam as appropriate perioperative antibiotic prophylaxis for preventing adverse outcomes after pancreatoduodenectomy.

5.
J Am Coll Surg ; 238(1): 70-80, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37870235

RESUMO

BACKGROUND: Intestinal homeostasis is a crucial factor for complication-free short- and long-term postoperative recovery. The brush border enzyme intestinal alkaline phosphatase (IAP) is an important regulator of gut barrier function and intestinal homeostasis and prevents endotoxemia by detoxifying lipopolysaccharides (LPSs). As IAP is predominantly secreted by enterocytes in the duodenum, we hypothesized that pancreaticoduodenectomy (PD) leads to a significantly stronger decrease in IAP than other major abdominal surgery. STUDY DESIGN: Pre- and postoperative blood, stool, and intestinal samples were collected from patients undergoing PD, as well as other major surgical procedures without duodenectomy. The samples were analyzed using enzyme histochemistry, the para -nitrophenyl phosphate method for IAP, and the limulus amebocyte lysate assay for LPS. RESULTS: Overall, 88 patients were prospectively enrolled in the study. Fecal IAP activity negatively correlated with serum LPS (r = -0.3603, p = 0.0006). PD led to a significant decline in IAP compared to preoperative baseline levels (p < 0.0001). The decline in IAP correlated with the length of proximal small intestinal resection (r = 0.4271, p = 0.0034). Compared to controls, PD was associated with a much more pronounced reduction in IAP-also after adjusting for surgical trauma (operative time, blood loss; r = 0.4598, p = 0.0086). Simultaneously, PD triggered a clearly more prominent increase in serum LPS compared to controls (p = 0.0001). Increased postoperative LPS was associated with an elongated hospitalization (r = 0.7534, p = 0.0062) and more prominent in pancreatic cancer (p = 0.0009). CONCLUSIONS: Based upon the functional roles for IAP, supplementation with exogenous IAP might be a new treatment option to improve short- and long-term outcome after PD.


Assuntos
Fosfatase Alcalina , Lipopolissacarídeos , Pancreaticoduodenectomia , Humanos , Fosfatase Alcalina/metabolismo , Fosfatase Alcalina/fisiologia , Homeostase , Mucosa Intestinal , Período Pós-Operatório , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/reabilitação
6.
BMC Surg ; 23(1): 303, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37794384

RESUMO

PURPOSES: Postoperative bleeding remains a life-threatening complication in thyroid surgery. The aim was to assess the efficacy of four different hemostatic agents, Collagen-Fibrinogen-Thrombin Patch (CFTP) in two sizes (3 × 2.5 cm and 9.5 × 4.8 cm), polysaccharide particles (1 g) and Cellulose Gauze (2.5 × 5 cm) on postoperative drainage volume (DV) compared to a control group. METHODS: We included from October 2007 until Mai 2011, 150 patients (30 per group) for this monocentric, retrospective case-controlled study. Patients were scheduled for a hemithyroidectomy or thyroidectomy. The primary endpoint was the postoperative DV within the first 24 h, secondary the incidence of adverse events. RESULTS: There were no difference in demographic parameters. The mean DV (± SD) was 51.15 (± 36.86) ml in the control, 50.65 (± 42.79) ml in small (3 × 2.5 cm), 25.38 (± 23.99) ml in large CFTP (9.5 × 4.8 cm), 53.11 (± 39.48) ml in the polysaccharide particles and 48.94 (± 30.59) ml in the cellulose gauze group. DV was significantly reduced with the large CFTP (p < 0.05) compared to all other groups. There were no adverse events. CONCLUSIONS: We were able to demonstrate a significant reduction in the DV for the large CFTP group compared to the other collectives. Although this as being associated with not inconsiderable costs and we would only recommend its use for high-risk patients only.


Assuntos
Hemostáticos , Glândula Tireoide , Humanos , Glândula Tireoide/cirurgia , Estudos Retrospectivos , Hemostáticos/uso terapêutico , Trombina , Fibrinogênio/uso terapêutico , Celulose/uso terapêutico , Polissacarídeos
7.
Cancers (Basel) ; 15(19)2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37835436

RESUMO

BACKGROUND: Chronic inflammation is a significant factor in colorectal cancer (CRC) development, especially in colitis-associated CRC (CAC). T-cell exhaustion is known to influence inflammatory bowel disease (IBD) progression and antitumor immunity in IBD patients. This study aimed to identify unique immune infiltration characteristics in CAC patients. METHODS: We studied 20 CAC and 20 sporadic CRC (sCRC) patients, who were matched by tumor stage, grade, and location. Immunohistochemical staining targeted various T-cell markers (CD3, CD4, CD8, and FOXP3), T-cell exhaustion markers (TOX and TIGIT), a B-cell marker (CD20), and a neutrophil marker (CD66b) in tumor and tumor-free mucosa from both groups. The quantification of the tumor immune stroma algorithm assessed immune-infiltrating cells. RESULTS: CAC patients had significantly lower TOX+ cell infiltration than sCRC in tumors (p = 0.02) and paracancerous tissues (p < 0.01). Right-sided CAC showed increased infiltration of TOX+ cells (p = 0.01), FOXP3+ regulatory T-cells (p < 0.01), and CD20+ B-cells (p < 0.01) compared to left-sided CAC. In sCRC, higher tumor stages (III and IV) had significantly lower TIGIT+ infiltrate than stages I and II. In CAC, high CD3+ (p < 0.01) and CD20+ (p < 0.01) infiltrates correlated with improved overall survival. In sCRC, better survival was associated with decreased TIGIT+ cells (p < 0.038) and reduced CD8+ infiltrates (p = 0.02). CONCLUSION: In CAC, high CD3+ and CD20+ infiltrates relate to improved survival, while this association is absent in sCRC. The study revealed marked differences in TIGIT and TOX expression, emphasizing distinctions between CAC and sCRC. T-cell exhaustion appears to have a different role in CAC development.

8.
NPJ Precis Oncol ; 7(1): 63, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37393364

RESUMO

The incidence of early-onset colorectal cancer (EO-CRC, in patients younger than 50) is increasing worldwide. The specific gene signatures in EO-CRC patients are largely unknown. Since EO-CRC with microsatellite instability is frequently associated with Lynch syndrome, we aimed to comprehensively characterize the tumor microenvironment (TME) and gene expression profiles of EO-CRC with microsatellite stable (MSS-EO-CRC). Here, we demonstrated that MSS-EO-CRC has a similar pattern of tumor-infiltrating immune cells, immunotherapeutic responses, consensus molecular subtypes, and prognosis as late-onset CRC with MSS (MSS-LO-CRC). 133 differential expressed genes were identified as unique gene signatures of MSS-EO-CRC. Moreover, we established a risk score, which was positively associated with PD-L1 expression and could reflect both the level of tumor-infiltrating immune cells and the prognosis of MSS-EO-CRC patients. Application of this score on the anti-PD-L1 treatment cohort demonstrated that the low-risk score group has significant therapeutic advantages and clinical benefits. In addition, candidate driver genes were identified in the different-sidedness of MSS-EO-CRC patients. Altogether, MSS-EO-CRC exhibits distinct molecular profiles that differ from MSS-LO-CRC even though they have a similar TME characterization and survival pattern. Our risk score appears to be robust enough to predict prognosis and immunotherapeutic response and therefore could help to optimize the treatment of MSS-EO-CRC.

9.
Front Immunol ; 14: 1156488, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37483596

RESUMO

Background: Colorectal cancer (CRC) is one of the most common solid malignant burdens worldwide. Cancer immunology and immunotherapy have become fundamental areas in CRC research and treatment. Currently, the method of generating Immune-Related Gene Prognostic Indices (IRGPIs) has been found to predict patient prognosis as an immune-related prognostic biomarker in a variety of tumors. However, their role in patients with CRC remains mostly unknown. Therefore, we aimed to establish an IRGPI for prognosis evaluation in CRC. Methods: RNA-sequencing data and clinical information of CRC patients were retrieved from The Cancer Genome Atlas (TCGA) and The Gene Expression Omnibus (GEO) databases as training and validation sets, respectively. Immune-related gene data was obtained from the ImmPort and InnateDB databases. The weighted gene co-expression network analysis (WGCNA) was used to identify hub immune-related genes. An IRGPI was then constructed using Cox regression methods. Based on the median risk score of IRGPI, patients could be divided into high-risk and low-risk groups. To further investigate the immunologic differences, Gene set variation analysis (GSVA) studies were conducted. In addition, immune cell infiltration and related functional analysis were used to identify the differential immune cell subsets and related functional pathways. Results: We identified 49 immune-related genes associated with the prognosis of CRC, 17 of which were selected for an IRGPI. The IRGPI model significantly differentiates the survival rates of CRC patients in the different groups. The IRGPI as an independent prognostic factor significantly correlates with clinico-pathological factors such as age and tumor stage. Furthermore, we developed a nomogram to improve the clinical utility of the IRGPI score. Immuno-correlation analysis in different IRGPI groups revealed distinct immune cell infiltration (CD4+ T cells resting memory) and associated pathways (macrophages, Type I IFNs responses, iDCs.), providing new insights into the tumor microenvironment. At last, drug sensitivity analysis revealed that the high-risk IRGPI group was sensitive to 11 and resistant to 15 drugs. Conclusion: Our study established a promising immune-related risk model for predicting survival in CRC patients. This could help to better understand the correlation between immunity and the prognosis of CRC providing a new perspective for personalized treatment of CRC.


Assuntos
Cardiomiopatia Dilatada , Neoplasias Colorretais , Humanos , Prognóstico , Nomogramas , Bases de Dados Factuais , Neoplasias Colorretais/genética , Microambiente Tumoral/genética
10.
Int J Colorectal Dis ; 38(1): 187, 2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37420132

RESUMO

BACKGROUND: Enterovaginal fistulas represent a serious complication of various diseases and therapeutic procedures, often associated with complicated clinical courses and massive impairment of quality of life. As underlying conditions and procedures are multifarious, therapeutic approaches are challenging and have to be tailored individually. As the therapeutic management is complex and individualized, multiple surgical interventions might be necessary. METHODS: The aim of this study was to identify possible predictors for outcome in the treatment enterovaginal fistula patients. The study was realized as a retrospective analysis. Ninety-two patients treated with enterovaginal fistulas between 2004 and 2016 were analyzed. Patient characteristics, therapeutic data, and endoscopic findings were stratified according to etiology, closure rate and time, as well as recurrence of fistula. Main outcome measure was the overall rate of fistula closure. RESULTS: Overall therapeutic success rate was 67.4%. Postoperatively derived fistulas were most frequent (40.2%), mainly after rectal surgery (59.5%). Postoperative and non-IBD-inflammation associated fistulas had better outcome than IBD-, radiotherapy-, and tumor-related fistulas (p = 0.001). Successful fistula closure was observed more frequently after radical surgical interventions, best results observed after transabdominal surgery (p < 0.001). Fistula recurrence was also less frequently observed after radical surgical therapies (p = 0.029). A temporary stoma was associated with higher incidence of fistula closure (p = 0.013) and lower incidence of fistula recurrence (p = 0.042) in the postoperative subgroup, as well as shortened therapy period in all groups (p = 0.031). CONCLUSION: Enterovaginal fistulas are a result of various etiologies, and treatment should be adjusted accordingly. A very sustainable, rapid, and persistent therapeutic success can be expected after radical surgical approaches with temporary diverting stoma. This is especially true for postoperatively derived fistulas.


Assuntos
Fístula Retal , Fístula Retovaginal , Feminino , Humanos , Fístula Retovaginal/etiologia , Fístula Retovaginal/cirurgia , Estudos Retrospectivos , Qualidade de Vida , Resultado do Tratamento , Fístula Retal/etiologia
12.
Int J Colorectal Dis ; 38(1): 114, 2023 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-37147435

RESUMO

BACKGROUND AND AIMS: Early-onset colorectal neoplasms (EoCRN) include both benign and malign colorectal tumors, which occur before the age of 50. The incidence of EoCRN is rising worldwide. Tobacco smoking has previously been proven to be related to the development of various tumor types. However, its relationship with EoCRN is not clearly defined. Hence, we carried out a systematic review and a meta-analysis to evaluate the relationship between smoking status and the risk of EoCRN. METHODS: A systematic search of PubMed, EMBASE, and Web of Science up to September 7, 2022, was performed for studies that evaluated the association of smoking status with EoCRN. The quality of the case-control study was evaluated with the Newcastle‒Ottawa Scale. The quality of the cross-sectional studies was evaluated with the American Health Care Research and Quality checklist. Fixed-effects models were used to pool odds ratios (ORs) to evaluate the relationship between the risk of developing EoCRN and smoking status. The meta-analyses were performed with Review Manager version 5.4, and funnel plots and publication bias tests were produced by STATA software. RESULTS: A total of six studies were included in this meta-analysis. After pooling the results of these six studies, we found that current smokers carry a relatively high risk of developing EoCRN (OR, 1.33; 95% confidence interval [CI], 1.17-1.52) compared to never-smokers. Ex-smokers were not at a significantly increased risk for developing EoCRN (OR, 1.00; 95% CI, 0.86-1.18). DISCUSSION: Smoking behavior is significantly associated with an increased risk for developing EoCRN and might be one of the reasons for the increasing incidence. Ex-smokers who quit are not at significant risk of developing EoCRN.


Assuntos
Neoplasias , Fumar , Humanos , Estudos de Casos e Controles , Estudos Transversais , Fumar/efeitos adversos , Fumar/epidemiologia , Fatores de Risco , Fumar Tabaco
13.
J Gastrointest Surg ; 27(7): 1466-1472, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36973501

RESUMO

BACKGROUND: Inflammation is known to be an essential driver of various types of cancer. An increasing number of studies have suggested that the occurrence and development of colorectal cancer (CRC) are linked to the inflammatory microenvironment of the intestine. This assumption is further supported by the fact that patients with inflammatory bowel disease (IBD) are more likely to develop CRC. Multiple studies in mice and humans have shown that preoperative systemic inflammatory response is predictive of cancer recurrence after potentially curative resection. Lipopolysaccharides (LPS) are membrane surface markers of gram-negative bacteria, which induce gut barrier dysfunction and inflammation and might be significantly involved in the occurrence and development of CRC. METHODS: A selective literature search was conducted in Medline and PubMed, using the terms "Colorectal Cancer", "Gut Barrier", "Lipopolysaccharides", and "Inflammation". RESULTS: Disruption of intestinal homeostasis, including gut barrier dysfunction, is linked to increased LPS levels and is a critical factor for chronic inflammation. LPS can activate the diverse nuclear factor-κB (NF-κB) pathway via Toll-like receptors 4 (TLR4) to promote the inflammatory response, which aggravates gut barrier dysfunction and encourages CRC development. An intact gut barrier prevents antigens and bacteria from crossing the intestinal endothelial layer and entering circulation. In contrast, a damaged gut barrier triggers inflammatory responses and increases susceptibility to CRC. Thus, targeting LPS and the gut barrier might be a promising novel therapeutic approach for additional treatment of CRC. CONCLUSION: Gut barrier dysfuction and bacterial LPS seem to play an important role in the pathogenesis and disease progression of colorectal cancer and therefore require further investigation.


Assuntos
Neoplasias Colorretais , Lipopolissacarídeos , Humanos , Camundongos , Animais , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Neoplasias Colorretais/patologia , Recidiva Local de Neoplasia , NF-kappa B/metabolismo , Inflamação , Bactérias/metabolismo , Microambiente Tumoral
14.
Int J Mol Sci ; 24(5)2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36902269

RESUMO

Liver transplantation as a treatment option for end-stage liver diseases is associated with a relevant risk for complications. On the one hand, immunological factors and associated chronic graft rejection are major causes of morbidity and carry an increased risk of mortality due to liver graft failure. On the other hand, infectious complications have a major impact on patient outcomes. In addition, abdominal or pulmonary infections, and biliary complications, including cholangitis, are common complications in patients after liver transplantation and can also be associated with a risk for mortality. Thereby, these patients already suffer from gut dysbiosis at the time of liver transplantation due to their severe underlying disease, causing end-stage liver failure. Despite an impaired gut-liver axis, repeated antibiotic therapies can cause major changes in the gut microbiome. Due to repeated biliary interventions, the biliary tract is often colonized by several bacteria with a high risk for multi-drug resistant germs causing local and systemic infections before and after liver transplantation. Growing evidence about the role of gut microbiota in the perioperative course and their impact on patient outcomes in liver transplantation is available. However, data about biliary microbiota and their impact on infectious and biliary complications are still sparse. In this comprehensive review, we compile the current evidence for the role of microbiome research in liver transplantation with a focus on biliary complications and infections due to multi-drug resistant germs.


Assuntos
Sistema Biliar , Doença Hepática Terminal , Microbioma Gastrointestinal , Transplante de Fígado , Microbiota , Humanos , Transplante de Fígado/efeitos adversos , Doença Hepática Terminal/microbiologia
15.
Metabolites ; 13(1)2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36677026

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disease, ranging from simple steatosis to hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Liver fibrosis, which portends a poor prognosis in NAFLD, is characterized by the excessive accumulation of extracellular matrix (ECM) proteins resulting from abnormal wound repair response and metabolic disorders. Various metabolic factors play crucial roles in the progression of NAFLD, including abnormal lipid, bile acid, and endotoxin metabolism, leading to chronic inflammation and hepatic stellate cell (HSC) activation. Autophagy is a conserved process within cells that removes unnecessary or dysfunctional components through a lysosome-dependent regulated mechanism. Accumulating evidence has shown the importance of autophagy in NAFLD and its close relation to NAFLD progression. Thus, regulation of autophagy appears to be beneficial in treating NAFLD and could become an important therapeutic target.

16.
Transpl Immunol ; 77: 101782, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36608832

RESUMO

BACKGROUND: Cathepsin S (CatS) and proteinase-activated receptor (PAR)-2 are involved in the remodelling of vascular walls and neointima formation as well as in alloantigen presentation and T-cell priming. Therefore, we hypothesized that CatS/PAR-2 inhibition/deficiency would attenuate chronic allograft vasculopathy. METHODS: Heterotopic aortic murine transplantation was performed from C57BL/6J donors to C57BL/6J recipients (syngeneic control group), Balb/c to C57BL/6J without treatment (allogenic control group), Balb/c to C57BL/6J with twice daily oral CatS inhibitor (allogenic treatment group) and Balb/c to Par2-/- C57BL/6J (allogenic knockout group). The recipients were sacrificed on day 28 and the grafts were harvested for histological analysis and RT-qPCR. RESULTS: After 28 days, mice of the allogenic control group exhibited significant neointima formation and massive CD8 T-cell infiltration into the neointima while the syngeneic control group showed negligible allograft vasculopathy. The mRNA expression level of CatS in allografts was 5-fold of those in syngeneic grafts. Neointima formation and therefore intima/media-ratio were significantly decreased in the treatment and knockout group in comparison to the allogenic control group. Mice in treatment group also displayed significantly fewer CD8 T cells in the neointima compared with allogeneic controls. Additionally, treatment with the CatS inhibitor and PAR2-deficiency decreased mRNA-levels of interleukins and cytokines. CONCLUSION: In conclusion, our data indicate that inhibiting CatS and PAR-2 deficiency led to a marked reduction of neointima formation and associated inflammation in a murine heterotopic model for allograft vasculopathy.


Assuntos
Neointima , Receptor PAR-2 , Animais , Camundongos , Receptor PAR-2/genética , Camundongos Endogâmicos C57BL , Catepsinas , Aloenxertos , RNA Mensageiro , Rejeição de Enxerto , Camundongos Endogâmicos BALB C
18.
Chirurgie (Heidelb) ; 94(2): 155-163, 2023 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-36260140

RESUMO

INTRODUCTION: The new competency-based continuing education regulations for surgical training (WBO) came into effect in Bavaria in August 2022. METHODS: From May to July 2022, we conducted an anonymized online survey among Bavarian general and visceral surgeons and surgical residents (ÄiW). The aim was to survey expectations of the effects of the new WBO. RESULTS: The response rate was 35%. In total data could be collected from 80 persons, 36 ÄiW (45%), 30 specialists and senior physicians (37.5%) and 14 chief physicians (17.5%). The majority of respondents worked at a university hospital (38.8%) or a regular provider (35%). A strengthening of the competence to act through implementation of the new WBO is seen by 41.3% and 55.7% see independent operating under partial supervision by the instructor as a goal. Of the respondents 50% see the required case numbers as not achievable and 55.1% deny reaching them in the expected period of 6 years. About 60% do not expect to be able to train the same number of ÄiWs in the same amount of time. Almost 75% of the respondents state that from their point of view, a good continuing education with the achievement of a solid competence to act would not work without overtime hours. About 44% of the respondents expect that a full surgical training would continue to be possible at their institution. CONCLUSION: Both among the instructors and among the trainees there is a tendency to fear that realistic training, in particular the achievement of the guideline figures, will no longer be possible in the usual further training time. This necessitates the consistent implementation of structured continuing education with a high degree of transparency in training.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Internato e Residência , Cirurgiões , Humanos , Inquéritos e Questionários , Educação Continuada
19.
Cancers (Basel) ; 14(24)2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36551592

RESUMO

The development and progression of colorectal cancer (CRC) are known to be affected by the interplay between tumor and immune cells. However, the impact of CRC cells on the systemic immunity has yet to be elucidated. We aimed to comprehensively evaluate the circulating immune subsets and transcriptional profiles of CRC patients. In contrast to healthy controls (HCs), CRC patients had a lower percentage of B and T lymphocytes, T helper (Th) cells, non-classical monocytes, dendritic cells, and a higher proportion of polymorphonuclear myeloid-derived suppressor cells, as well as a reduced expression of CD69 on NK cells. Therefore, CRC patients exhibit a more evident systemic immune suppression than HCs. A diagnostic model integrating seven immune subsets was constructed to distinguish CRC patients from HCs with an AUC of 1.000. Moreover, NR3C2, CAMK4, and TRAT1 were identified as candidate genes regulating the number of Th cells in CRC patients. The altered composition of circulating immune cells in CRC could complement the regional immune status of the tumor microenvironment and contribute to the discovery of immune-related biomarkers for the diagnosis of CRC.

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