Differentiation between small hepatocellular carcinoma (<3 cm) and benign hepatocellular lesions in patients with Budd-Chiari syndrome: the role of multiparametric MR imaging

ObjectiveTo investigate the value of multiparametric MR imaging to differentiate between small hepatocellular carcinoma (s-HCC) versus benign liver lesions in patients with Budd-Chiari syndrome.Methods12 patients with benign hepatocellular lesions and 32 patients with small (&lt;3 cm) HCCs were assessed. MRI images were reviewed by two radiologists blinded to the patient background information; lesion T1 and T2 signal intensities and ADC values were compared with the background liver. Enhancement of lesion relative to hepatic parenchyma [(T1Enh-T1liver)/T1liver] in the arterial, venous, and delayed phases was also compared between the two groups. A multivariable logistic model was developed using these categorical measures; the predictive value of the model was tested using the Area Under the Receiver operating characteristic (AU-ROC) curve for logistic models. P-values &lt;0.05 were considered statistically significant.ResultsThere were consistent differences in T1lesion/T1liver, and T2lesion/T2liver, and ADClesion/ADCliver between benign hepatocellular lesions versus the sHCC group (p&lt;0.001, p&lt;0.001, p = 0.045, respectively). Lesion-to-background liver enhancement in the portal venous and delayed phases was different between the benign lesions versus sHCC (p=0.001). ROC analysis for the logistic model that included the T1 ratio, T2 ratio, and portal venous enhancement ratio demonstrated excellent discriminatory power with the area under the curve of 0.94.ConclusionMultiparametric MR imaging is a useful method to help differentiate benign liver lesions from sHCC in patients with Budd-Chiari syndrome

Global, regional, and national burden of colorectal cancer and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Funding: F Carvalho and E Fernandes acknowledge support from Fundação para a Ciência e a Tecnologia, I.P. (FCT), in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy i4HB; FCT/MCTES through the project UIDB/50006/2020. J Conde acknowledges the European Research Council Starting Grant (ERC-StG-2019-848325). V M Costa acknowledges the grant SFRH/BHD/110001/2015, received by Portuguese national funds through Fundação para a Ciência e Tecnologia (FCT), IP, under the Norma Transitória DL57/2016/CP1334/CT0006.proofepub_ahead_of_prin

A Review of Applications of Nanoceria in Cancer

Cancer is one of the most difficult diseases to treat in modern medicine. Annually, many articles are published that propose various ways for preventing carcinogenesis. Furthermore, research into cancer treatments is carried out with minimal side effects. The most common non-invasive cancer treatments include chemotherapy, targeted therapy, radiotherapy, and immunotherapy. Low effectiveness of chemo-radiation therapy and normal tissue toxicity caused by these treatments are two of the most difficult challenges. Some medicines have been recommended as adjuvants to increase tumor responses while also reducing normal tissue damage. Cerium oxide as a nanoparticle (nanoceria, CNPs) has recieved a lot of interest as a way to control tumor and normal tissue responses to various cancer treatment regimens. In vitro and in vivo studies demonstrate that it can reduce chemo-radiation toxicity in normal tissues as an antioxidant and anti-inflammatory agent. Furthermore, it has the ability to make cancer cells more sensitive to both chemotherapy and radiotherapy. In this paper, we reviewed the potential role of nanoceria for preserving normal tissues and sensitization of cancer cells in combination with different cancer treatment modalities

Alteration in Frequency and Function of CD4+CD25+ FOXP3+ Regulatory T cells in Patients with Immune Thrombocytopenic Purpura

Immune thrombocytopenic  purpura (ITP) is an autoimmune bleeding disorder characterized by production  of auto-antibodies against platelet antigens. It is obvious that regulatory T cells (Tregs) have a major role in controlling immune homeostasis and preventing autoimmunity. To investigate the frequency and functions of Tregs, twenty ITP patients and twenty age- and sex- matched healthy controls were recruited. The peripheral blood mononuclear cells were isolated and the proportion of Tregs was defined by flow cytometry method. The expression of immune-regulatory markers, cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and glucocorticoid induced tumor necrosis  factor  receptor  (GITR)  were  also  assessed by  quantitative  Real-time polymerase chain reaction TaqMan method. For evaluation of Treg function, Tregs were enriched and their ability to inhibit proliferation of T cells was measured and levels of immune-regulatory cytokines IL-10 and Transforming growth factor beta (TGF-β) were also measured.Results showed that the frequency of Tregs  and  the  mean  fluorescence  intensity  of  forkhead  box  P3  (FOXP3)  protein  significantly decreased in ITP patients compared to those in healthy controls. In addition, there was a significant reduction  in relative expression of both  CTLA-4 and GITR  mRNA  in ITP  patients (p=0.02 and p=0.006, respectively). The suppressive function of Tregs also diminished in ITP patients compared to controls. Both  IL-10 and TGF-β  cytokines were produced  in lower amounts  in ITP  patients than controls. It  could  be  concluded  that  alteration  in  Treg  frequency and  functional  characteristics might  be responsible for loss of self-tolerance and subsequently destructive immune responses observed in ITP patients

New insights into physiopathology of immunodeficiency-associated vaccine-derived poliovirus infection; systematic review of over 5 decades of data.

International audienceWidespread administration of oral poliovirus vaccine (OPV) has decreased global incidence of poliomyelitis by ≈99.9%. However, the emergence of vaccine-derived polioviruses (VDPVs) is threatening polio-eradication program. Primary immunodeficiency (PID) patients are at higher risks of vaccine-associated paralytic poliomyelitis (VAPP) and prolonged excretion of immunodeficiency-associated VDPV (iVDPV). We searched Embase, Medline, Science direct, Scopus, Web of Science, and CDC and WHO databases by 30 September 2016, for all reports of iVDPV cases. Patient-level data were extracted form eligible studies. Data on immunization coverage and income-level of countries were extracted from WHO/UNICEF and the WORLD BANK databases, respectively. We assessed bivariate associations between immunological, clinical, and virological parameters, and exploited multivariable modeling to identify independent determinants of poliovirus evolution and patients' outcomes. Study protocol was registered with PROSPERO (CRD42016052931). 4329 duplicate-removed titles were screened. A total of 107 iVDPV cases were identified from 68 eligible articles. The majority of cases were from higher income countries with high polio-immunization coverage. 74 (69.81%) patients developed VAPP. Combined immunodeficiency patients showed lower rates of VAPP (p \textless .001) and infection clearance (p = .02), compared to humoral immunodeficiency patients. The rate of poliovirus genomic evolution was higher at early stages of replication, decreasing over time until reaching a steady state. Independent of replication duration, higher extent (p = .04) and rates (p = .03) of genome divergence contributed to a less likelihood of virus clearance. PID type (p \textless .001), VAPP occurrence (p = .008), and income-level of country (p = .04) independently influenced patients' survival. With the use of OPV, new iVDPVs will emerge independent of the rate of immunization coverage. Inherent features of PIDs contribute to the clinical course of iVDPV infection and virus evolution. This finding could shed further light on poliomyelitis pathogenesis and iVDPV evolution pattern. It also has implications for public health, the polio eradication effort and the development of effective antiviral interventions

Characterization of an Enzyme-Catalyzed Crosslinkable Hydrogel as a Wound Dressing in Skin Tissue Engineering: Enzyme-Catalyzed Crosslinkable Hydrogels for Skin Tissue Engineering

Introduction: Wound healing can have a very important impact on the patients’ quality of life. For its treatment, wound dressings have vital and effective uses. Indeed, the use of a proper wound dressing can improve the healing process and duration. Recently, wound dressings with unique properties have been prepared using natural hydrogels. In addition to the general wound characteristics, new generations of wound dressings, such as those lasting longer on the wound, can have specific properties such as transferring allogeneic cells to enhance the healing effect and speed up the healing process. The present study aimed to prepare a gelatin-based hydrogel and to characterize it for therapeutic purposes.Methods: In this experimental-laboratory study, a gelatin hydrogel was made using a microbial transglutaminase (mTG) enzyme. The prepared hydrogel was evaluated in terms of appearance, physical, and chemical properties. To investigate the biological properties of the hydrogel, cells were cultured on it and the toxicity of the hydrogel for the cells was investigated. The location of the cells on the hydrogel was imaged via an electron microscope. The absorption and reflectance characteristics of the hydrogel were recorded by optical spectroscopy. Data were collected and statistical analysis was performed.Results: The results showed that the mTG gelatin hydrogel had a uniform pore size and good physical, chemical, and mechanical properties for use in wound healing. Cell experiments showed evident cell proliferation and high viability. The results also revealed that the cells grew vigorously and adhered tightly to the hydrogel.Conclusion: The preparation of a gelatin hydrogel under GMP conditions can be considered in the healing of diabetic wounds and burns. Doi:10.34172/jlms.2021.77

Role of MRI-Derived Radiomics Features in Determining Degree of Tumor Differentiation of Hepatocellular Carcinoma

Background: To investigate radiomics ability in predicting hepatocellular carcinoma histological degree of differentiation by using volumetric MR imaging parameters. Methods: Volumetric venous enhancement and apparent diffusion coefficient were calculated on baseline MRI of 171 lesions. Ninety-five radiomics features were extracted, then random forest classification identified the performance of the texture features in classifying tumor degree of differentiation based on their histopathological features. The Gini index was used for split criterion, and the random forest was optimized to have a minimum of nine participants per leaf node. Predictor importance was estimated based on the minimal depth of the maximal subtree. Results: Out of 95 radiomics features, four top performers were apparent diffusion coefficient (ADC) features. The mean ADC and venous enhancement map alone had an overall error rate of 39.8%. The error decreased to 32.8% with the addition of the radiomics features in the multi-class model. The area under the receiver-operator curve (AUC) improved from 75.2% to 83.2% with the addition of the radiomics features for distinguishing well- from moderately/poorly differentiated HCCs in the multi-class model. Conclusions: The addition of radiomics-based texture analysis improved classification over that of ADC or venous enhancement values alone. Radiomics help us move closer to non-invasive histologic tumor grading of HCC

Polyautoimmunity in Patients with LPS-Responsive Beige-Like Anchor (LRBA) Deficiency

<p><b>Background</b>: Polyautoimmunity is defined as the presence of more than one autoimmune disorder in a single patient. Lipopolysaccharide (LPS)-responsive beige-like anchor (LRBA) deficiency is one of the monogenic causes of polyautoimmunity. The aim of this study was to report the characteristics of polyautoimmunity in patients with LRBA deficiency.</p> <p><b>Methods</b>: A total of 14 LRBA deficiency patients with confirmed autoimmunity were enrolled in this study. For those patients with polyautoimmunity, demographic information, clinical records, laboratory, and molecular data were collected. We also compared our results with the currently reported patients with LRBA deficiency associated with polyautoimmunity.</p> <p><b>Results</b>: In 64.2% (9 out of 14) of patients, autoimmunity presented as polyautoimmunity. In these patients, autoimmune cytopenias were the most frequent complication, observed in seven patients. Three patients presented with four different types of autoimmune conditions. The review of the literature showed that 41 of 72 reported LRBA deficient patients (74.5%) had also polyautoimmunity, with a wide spectrum of autoimmune diseases described. Hematopoietic stem cell transplantation is increasingly used as the treatment for patients with severe polyautoimmunity associated to LRBA deficiency.</p> <p><b>Conclusions</b>: Mutation in LRBA gene is one of the causes of monogenic polyautoimmunity. Awareness of this association is important in order to make an early diagnosis and prompt treatment.</p