Objective
This study was performed to identify risk factors for acute cellular rejection after liver transplantation (LT).
Methods
Consecutive LT recipients who underwent surgery in our institution ...from 2002 to 2015 were retrospectively evaluated.
Results
In total, 176 patients were eligible for statistical analysis. During a mean observation period of 61.1 ± 36.3 months, 43 episodes of acute rejection were evident. Of these, 34 (79.0%) were responsive to methylprednisolone, 3 (7.0%) were treated by adjusting the dosage of immunosuppressive agents, and 6 (14.0%) were methylprednisolone-resistant and treated using anti-thymocyte globulin. Biliary complications (odds ratio OR = 4.89, 95% confidence interval CI = 2.00–11.98); donor-negative, recipient-positive CMV mismatch (OR = 9.88, 95% CI = 1.18–82.36); sex mismatch (OR = 3.16, 95% CI = 1.31–8.10); and sex mismatch with a female donor (OR = 3.00, 95% CI = 1.10–7.58) were identified as significant risk factors for acute graft rejection after LT.
Conclusion
In patients who develop acute cellular rejection after LT, biliary complications should be evaluated as a potential cause. Most acute rejections after LT respond to bolus corticosteroid therapy.
COVID-19 is a pandemic disease that causes severe pulmonary damage and hyperinflammation. Vitamin A is a crucial factor in the development of immune functions and is known to be reduced in cases of ...acute inflammation. This prospective, multicenter observational cross-sectional study analyzed vitamin A plasma levels in SARS-CoV-2 infected individuals, and 40 hospitalized patients were included. Of these, 22 developed critical disease (Acute Respiratory Distress Syndrome ARDS/Extracorporeal membrane oxygenation ECMO), 9 developed severe disease (oxygen supplementation), and 9 developed moderate disease (no oxygen supplementation). A total of 47 age-matched convalescent persons that had been earlier infected with SARS-CoV-2 were included as the control group. Vitamin A plasma levels were determined by high-performance liquid chromatography. Reduced vitamin A plasma levels correlated significantly with increased levels of inflammatory markers (CRP, ferritin) and with markers of acute SARS-CoV-2 infection (reduced lymphocyte count, LDH). Vitamin A levels were significantly lower in hospitalized patients than in convalescent persons (p < 0.01). Of the hospitalized patients, those who were critically ill showed significantly lower vitamin A levels than those who were moderately ill (p < 0.05). Vitamin A plasma levels below 0.2 mg/L were significantly associated with the development of ARDS (OR = 5.54 1.01–30.26; p = 0.048) and mortality (OR 5.21 1.06–25.5, p = 0.042). Taken together, we conclude that vitamin A plasma levels in COVID-19 patients are reduced during acute inflammation and that severely reduced plasma levels of vitamin A are significantly associated with ARDS and mortality.
Limited information is available on the clinical course of outpatients with mild coronavirus disease (COVID-19). This information is critically important to inform public health prevention strategies ...and to provide anticipatory guidance to patients, primary care providers, and employers. We retrospectively assessed the daily prevalence of symptoms in 313 COVID-19 outpatients for the first 20 days of illness. Generalized estimating equations were used to assess the probability of symptom occurrence over time. Fatigue (91%), cough (85%), and headache (78%) were the most common symptoms and occurred a median of 1 day from symptom onset. Neurologic symptoms, such as loss of taste (66%) and anosmia (62%), and dyspnea (51%) occurred considerably later (median 3-4 days after symptom onset). Symptoms of COVID-19 are similar to those of other respiratory pathogens, so symptomatic patients should be tested more frequently for severe acute respiratory syndrome coronavirus 2 during influenza season to prevent further spread of COVID-19.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background & Aims Oncogene polycomb group protein enhancer of zeste homolog 2 ( EZH 2) has been proposed to be a target gene of putative tumor suppressor microRNA-101 (miR-101). The aim of our study ...was to investigate the functional role of both miR-101 and EZH 2 in human hepatocellular carcinoma (HCC). Methods MiR-101 and EZH 2 expressions were evaluated in tumor tissues of 99 HCC patients and 7 liver cancer cell lines by real-time PCR. Luciferase reporter assay was employed to validate whether EZH 2 represents a target gene of miR-101. The effect of miR-101 on HCC growth as well as programmed cell death was studied in vitro and in vivo. Results MiR-101 expression was significantly downregulated in most of HCC tissues and all cell lines, whereas EZH 2 was significantly overexpressed in most of HCC tissues and all cell lines. There was a negative correlation between expression levels of miR-101 and EZH 2. Luciferase assay results confirmed EZH 2 as a direct target gene of miR-101, which negatively regulates EZH 2 expression in HCC. Ectopic overexpression of miR-101 dramatically repressed proliferation, invasion, colony formation as well as cell cycle progression in vitro and suppressed tumorigenicity in vivo . Furthermore, miR-101 inhibited autophagy and synergized with either doxorubicin or fluorouracil to induce apoptosis in tumor cells. Conclusion Tumor suppressor miR-101 represses HCC progression through directly targeting EZH 2 oncogene and sensitizes liver cancer cells to chemotherapeutic treatment. Our findings provide significant insights into molecular mechanisms of hepatocarcinogenesis and may have clinical relevance for the development of novel targeted therapies for HCC.
SEC61A1 encodes a central protein of the mammalian translocon and dysfunction results in severe disease. Recently, mutation R236C was identified in patients having autosomal dominant polycystic liver ...disease (ADPLD). The molecular phenotype of R236C was assessed in two cellular platforms. Cells were immortalized by retroviral transduction of an oncogene (UCi) or reprogrammed to induced pluripotent stem cells (iPSC) that were differentiated to cholangiocyte progenitor-like cells (CPLC). UCi and CPLC were subjected to analyses of molecular pathways that were associated with development of disease. UCi displayed markers of epithelial cells, while CPLCs expressed typical markers of both cholangiocytes and hepatocytes. Cells encoding R236C showed a stable, continuous proliferation in both platforms, however growth rates were reduced as compared to wildtype control. Autophagy, cAMP synthesis, and secretion of important marker proteins were reduced in R236C-expressing cells. In addition, R236C induced increased calcium leakiness from the ER to the cytoplasm. Upon oxidative stress, R236C led to a high induction of apoptosis and necrosis. Although the grade of aberrant cellular functions differed between the two platforms, the molecular phenotype of R236C was shared suggesting that the mutation, regardless of the cell type, has a dominant impact on disease-associated pathways.
Background
Standard endoscopic treatment might fail to treat biliary stone disease. Here, we investigated the efficacy and safety of recently introduced digital single-operator video cholangioscopy ...(SOVC) for the treatment of difficult biliary stones.
Methods
Digital SOVC procedures, performed in two tertiary referral centers between 2015 and 2018, were retrospectively analyzed. Only patients with a previous failure of endoscopic standard treatment and a SOVC-based biliary stone treatment using electrohydraulic lithotripsy (EHL) or laser lithotripsy (LL) were included. The primary endpoint was to evaluate the stone removal rate per procedure and per patient.
Results
In total, 75 examinations with a digital SOVC-assisted biliary stone treatment, performed in 60 patients, were identified. Biliary stones were mainly located extrahepatic (64%) and less frequently intrahepatic (36%). The median stone size was 20 mm (interquartile range IQR: 10–25 mm) and the median stone number was 1 (IQR: 1–2). Digital SOVC-based treatment of biliary stone disease was successful in 95% of patients and 15% needed at least two treatment sessions. Evaluated per procedure, a complete stone removal was accomplished in 67% of all examinations (including initial and repeated procedures), while an incomplete stone removal was observed in 33% of cases. The per procedure analyzes revealed that the success rates for a complete stone removal were similar between LL and EHL (66% vs. 68%;
p
= 0.87). Complications, such as postinterventional cholangitis and pancreatitis occurred in 16% of examinations; however, except from one case, all were mild or moderate and no procedure-associated mortality occurred.
Conclusions
Digital SOVC-assisted biliary stone treatment is highly effective even in cases with difficult biliary stones and might be considered the new standard of care for these patients. Furthermore, mild up to moderate complications were intermittently observed which might document the complexity of our included cases.
Purpose Postoperative pancreatic fistula (POPF) with reported incidence rates up to 45% contributes substantially to overall morbidity. In this study, we conducted a retrospective evaluation of POPF ...along with its potential perioperative clinical risk factors and its effect on tumor recurrence. Methods Clinical data on patients who had received pancreatoduodenectomy (PD), distal pancreatectomy (DP), or duodenum-preserving pancreatic head resection (DPPHR) were prospectively collected between 2007 and 2016. A Picrosirius red staining score was developed to enable morphological classification of the resection margin of the pancreatic stump. The primary end point was the development of major complications. The secondary end points were overall and recurrence-free survival. Results 340 patients underwent pancreatic resection including 222 (65.3%) PD, 87 (25.6%) DP, and 31 (9.1%) DPPHR. Postoperative major complications were observed in 74 patients (21.8%). In multivariable logistic regression analysis, POPF correlated with body mass index (BMI) (p = 0.025), prolonged stay in hospital (p<0.001), high Picrosirius red staining score (p = 0.049), and elevated postoperative levels of amylase or lipase in drain fluid (pless than or equal to0.001). Multivariable Cox regression analysis identified UICC stage (p<0.001), tumor differentiation (p<0.001), depth of invasion (p = 0.001), nodal invasion (p = 0.001), and the incidence of POPF grades B and C (p = 0.006) as independent prognostic markers of recurrence-free survival. Conclusion Besides the known clinicopathological risk factors BMI and amylase in the drain fluid, the incidence of POPF correlates with high Picrosirius red staining score in the resection margins of the pancreatic stumps of curatively resected pancreatic ductal adenocarcinoma (PDAC). Furthermore, clinically relevant POPF seems to be a prognostic factor for tumor recurrence in PDAC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The COVID-19 pandemic is caused by the SARS CoV-2 virus and can lead to severe lung damage and hyperinflammation. In the context of COVID-19 infection, inflammation-induced degradation of the ...glycocalyx layer in endothelial cells has been demonstrated. Syndecan-1 (SDC-1) is an established parameter for measuring glycocalyx injury. This prospective, multicenter, observational, cross-sectional study analyzed SDC-1 levels in 24 convalescent patients that had been infected with SARS-CoV-2 with mild disease course without need of hospitalization. We included 13 age-matched healthy individuals and 10 age-matched hospitalized COVID-19 patients with acute mild disease course as controls. In convalescent COVID-19 patients, significantly elevated SDC-1 levels were detected after a median of 88 days after symptom onset compared to healthy controls, whereas no difference was found when compared to SDC-1 levels of hospitalized patients undergoing acute disease. This study is the first to demonstrate signs of endothelial damage in non-pre-diseased, convalescent COVID-19 patients after mild disease progression without hospitalization. The data are consistent with studies showing evidence of persistent endothelial damage after severe or critical disease progression. Further work to investigate endothelial damage in convalescent COVID-19 patients should follow.
The effective calcineurin inhibitor (CNI) tacrolimus (Tac) is an integral part of the standard immunosuppressive regimen after renal transplantation (RTx). However, as a potent CNI it has nephrotoxic ...potential leading to impaired renal function in some cases. Therefore, it is of high clinical impact to identify factors which can predict who is endangered to develop CNI toxicity. We hypothesized that the Tac metabolism rate expressed as the blood concentration normalized by the dose (C/D ratio) is such a simple predictor. Therefore, we analyzed the impact of the C/D ratio on kidney function after RTx. Renal function was analyzed 1, 2, 3, 6, 12 and 24 months after RTx in 248 patients with an immunosuppressive regimen including basiliximab, tacrolimus, mycophenolate mofetil and prednisolone. According to keep the approach simple, patients were split into three C/D groups: fast, intermediate and slow metabolizers. Notably, compared with slow metabolizers fast metabolizers of Tac showed significantly lower estimated glomerular filtration rate (eGFR) values at all the time points analyzed. Moreover, fast metabolizers underwent more indication renal biopsies (p = 0.006) which revealed a higher incidence of CNI nephrotoxicity (p = 0.015) and BK nephropathy (p = 0.024) in this group. We herein identified the C/D ratio as an easy calculable risk factor for the development of CNI nephrotoxicity and BK nephropathy after RTx. We propose that the simple C/D ratio should be taken into account early in patient's risk management strategies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Lipids in liver transplant recipients Hüsing, Anna; Kabar, Iyad; Schmidt, Hartmut H
World journal of gastroenterology : WJG,
03/2016, Letnik:
22, Številka:
12
Journal Article
Odprti dostop
Hyperlipidemia is very common after liver transplantation and can be observed in up to 71% of patients. The etiology of lipid disorders in these patients is multifactorial, with different lipid ...profiles observed depending on the immunosuppressive agents administered and the presence of additional risk factors, such as obesity, diabetes mellitus and nutrition. Due to recent improvements in survival of liver transplant recipients, the prevention of cardiovascular events has become more important, especially as approximately 64% of liver transplant recipients present with an increased risk of cardiovascular events. Management of dyslipidemia and of other modifiable cardiovascular risk factors, such as hypertension, diabetes and smoking, has therefore become essential in these patients. Treatment of hyperlipidemia after liver transplantation consists of life style modification, modifying the dose or type of immunosuppressive agents and use of lipid lowering agents. At the start of administration of lipid lowering medications, it is important to monitor drugdrug interactions, especially between lipid lowering agents and immunosuppressive drugs. Furthermore, as combinations of various lipid lowering drugs can lead to severe side effects, such as myopathies and rhabdomyolysis, these combinations should therefore be avoided. To our knowledge, there are no current guidelines targeting the management of lipid metabolism disorders in liver transplant recipients. This paper therefore recommends an approach of managing lipid abnormalities occurring after liver transplantation.
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