Anti-ganglioside antibodies and celiac disease

We describe our own experience on the prevalence of a wider range of anti-ganglioside antibodies and their clinical significance in CD patients. Using a commercially available ELISA kit (IMMCO Diagnostics, Buffalo, NY, USA), we studied anti-GM1, anti-GD1b, and anti-GQ1b serum IgG and IgM antibodies in 22 adult patients (median age 35, range: 19–56 years; three males, 19 females) with CD and neurological manifestations, including eight cases of idiopathic cerebellar ataxia, seven cases with epilepsy (without cerebral calcifications), two with multiple sclerosis, three with attention/memory impairment, and two with peripheral neuropathies. In all cases, diagnosis of CD was confirmed by endoscopic duodenal biopsy, revealing different grades of villous atrophy (from 3a to 3c, according to the modified Marsh classification). In all CD patients, intestinal villous atrophy was associated with a positivity for serological CD markers (anti-endomysial and/or anti-tissue transglutaminase antibodies) further supporting the diagnosis of CD. All available data, regarding CD diagnosis, diagnostic work-up, histopathology and treatment were obtained from the hospital digital database

Antinuclear antibodies in COVID 19

We appreciated very much the interesting study by Chang et al. on the presence of antinuclear antibodies (ANAs) in patients with moderate/critical coronavirus disease 2019 (COVID 19). Both we and Chang and collaborators described the presence and significance of ANAs in patients with COVID‐19. The two experiences can be compared because Chang et al. studied a number of cases only slightly larger than us. In our opinion, the most important finding is represented by the presence of the nucleolar ANA reactivity, which, in the study by Chang et al., as in ours, is the most frequently detected among the different ANA patterns. In this regard, it is worth mentioning that the nucleolar ANA pattern is one of the several ANA pattern detectable by Indirect immunofluorescence, together with other patterns, such as speckled, homogenous, multiple nuclear dots, and rim like membranous; this pattern can be the serological marker of systemic sclerosis and its antigenic target is the topoisomerase I protein (or scl70). Interestingly, it is of major relevance to note that among the clinical manifestations of systemic sclerosis, it includes pulmonary involvement in the form of a restrictive syndrome secondary to interstitial pneumopathy resembling COVID‐19 interstitial pneumonia

Hepatic Steatosis in Patients with Celiac Disease: The Role of Packaged Gluten-Free Foods

Background: An increased risk of nonalcoholic fatty liver disease (NAFLD) in patients with celiac disease (CD) adhering to a gluten-free diet (GFD) was recently reported. The nutritional composition of packaged gluten-free foods (PGFF) has been proposed as a possible cause. This hypothesis has not been investigated further, since a systematic structural nutritional interview for all patients would be problematic in clinical practice. Methods: We administered a simple questionnaire based on a Recency, Frequency, and Monetary value (RFM) analysis (a cornerstone of direct marketing segmentation) to consecutive CD patients on a GFD for >6 months and verified its association with NAFLD. Subgroup analyses were performed to understand whether specific patterns of PGFF consumption were significantly associated with NAFLD. Results: Amongst 147 patients (female 82%, median age 42 years), 45 (30.6%) had NAFLD. Total RFM score (adjusted odds ratio = 1.223, 95% CI: 1.059–1.413, p = 0.006), body mass index, and total cholesterol and triglycerides were independently related to NAFLD, and “Bread and bakery” (p = 0.002), “salty convenience” (p = 0.005), and “sweet convenience” (p = 0.049) products were significantly related with NAFLD. Also, questions about the number of purchased PGFF in the last month (monetary value) and different categories of PGFF consumed in the last week (recency) were particularly able to identify NAFLD patients. Conclusions: The specific GFD dietary habits of CD patients were correlated with the degree of risk of NAFLD. Information was obtained through a questionnaire which could be used in clinical practice to favor a patient-tailored approach and in future studies to verify the reproducibility of our results in different geographical areas

Risk of Drop-Out from Follow-Up Evaluations for Celiac Disease: Is It Similar for All Patients?

Background: Celiac disease (CD) follow-up is a relatively underevaluated topic. However, correct adherence to follow-up procedures is central to the early recognition of complicated CD and other conditions typically associated with CD. Establishing whether patients at increased risk of complications follow clinicians’ recommendations has multiple repercussions. Methods: We retrospectively analyzed the records of patients consecutively diagnosed with CD in our outpatient clinic between January 2004 and October 2017 to investigate the factors associated with drop-out from follow-up procedures. Results: Among the 578 patients analyzed, 40 (6.9%) dropped out during the first six months and 272 (50.6%) during the observation period. The median time to drop-out was 7.4 years (95% confidence interval: 6.8–8.0). No factors were associated with early drop-out. Instead, age at diagnosis >40 years (40–59 years, p < 0.001; ≥60 years, p = 0.048) and classical clinical presentation (p = 0.016) were significantly associated with a lower risk of later drop-out. Conclusions: Patients at increased risk of complicated CD are more compliant with follow-up procedures than patients at lower risk, despite being prescribed the same controls. These results indirectly support the hypothesis of tailored follow-up strategies, differentiated according to the risk of complications

Alternative acceptor materials for organic photovoltaic cells

Synthesis and spectroscopic characterization of perylene derivatives (perylene monoimides and diimides) are reported. The aim of the present work is to investigate the synthesis of these compounds in detail in order to highlight the crucial factors for obtaining a specific class of molecules. The final compounds of the synthetic pathway would be able to mimic the peculiar properties of fullerene derivatives, up to now the best candidates as accepting materials

Prognosis of Single Early-Stage Hepatocellular Carcinoma (HCC) with CEUS Inconclusive Imaging (LI-RADS LR-3 and LR-4) Is No Better than Typical HCC (LR-5)

The American College of Radiology (ACR) released the Liver Imaging Report and Data System (LI-RADS) scheme, which categorizes hepatic nodules in risk classes from LR-1 to LR-5 (according to the degree of risk to be HCC) and LR-M (probable malignancy not specific for HCC). The aim of this study was to test whether HCC with different LR patterns on CEUS have different overall survival (OS) and recurrence-free survival (RFS). We retrospectively enrolled 167 patients with the first definitive diagnosis of single HCC (by using CT/MRI or histological techniques if CT/MRI were inconclusive) for whom CEUS examination was available. The median size of HCC lesions was 2.2 cm (range 1.0–7.2 cm). According to CEUS LI-RADS classification, 28 patients were in LR-3, 48 in LR-4, 83 in LR-5, and 8 in LR-M. Patient liver function and nodule characteristics were not statistically different between CEUS LI-RADS classes. Using univariate analysis, CEUS LI-RADS class was not found to be a predictor of survival (p = 0.347). In conclusion, HCC showing the CEUS LI-RADS classes LR-3 and LR-4 have no better clinical outcome than typical HCC. Such data support the EASL policy, aimed at conclusive diagnostic investigations of indeterminate nodules up to obtaining histological proof to avoid leaving aggressive HCC not timely treated

Experience with regorafenib in the treatment of hepatocellular carcinoma

Regorafenib is a diphenylurea oral multikinase inhibitor, structurally comparable to sorafenib, which targets a variety of kinases implicated in angiogenic and tumor growth-promoting pathways. Regorafenib was the first agent to positively show significant survival advantage as a second-line therapy in patients with unresectable hepatocellular carcinoma (HCC) who had previously failed first-line treatment with sorafenib. Recent evidence has shown that its antitumor efficacy is due to a comprehensive spectrum of tumor neo-angiogenesis and proliferation inhibition and immunomodulatory effects on the tumor microenvironment, which plays a crucial role in tumor development. This review addresses the rationale and supporting evidence for regorafenib’s efficacy in HCC that led to regorafenib’s approval as a second-line therapy. In addition, we review proof from clinical practice studies that validate the RESORCE trial results. We discuss regorafenib’s potential role in the newly emerging therapeutic strategy based on combination with immune checkpoint blockade and its possible extensibility to patient categories not enrolled in the registrative study

Radiological Features of Microvascular Invasion of Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease

Background: The aim of the present study was to evaluate the presence and the prognostic value of the radiological signs of microvascular invasion (MVI) of hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD). Methods: Between January 2015 and December 2017, all patients (91 patients) with de novo HCC or HCC recurrence occurring at least 2 years after the last treatment in NAFLD (36 patients) or with hepatitis C virus (HCV) liver disease (55 patients) were included. Each HCC was treated with liver resection and transplantation to obtain the anatomopathological confirmation of MVI. All patients had at least one available computed tomography (CT) scan or magnetic resonance imaging (MRI) performed no more than one month prior to the treatment. The clinical data of each patient, tumor burden (diameter, margins, two-trait predictor of venous invasion (TTPVI), and peritumoral enhancement), the recurrence rate (RR) after a 1-year follow-up, and the time to recurrence (TTR) were collected. Results: The NAFLD–HCC nodules were larger as compared to HCV–HCC (51 mm vs. 36 mm, p = 0.004) and showed a higher prevalence of TTPVI (38.9 vs. 20.0%, p = 0.058). At multivariate analysis, nodule diameter >50 mm was found to be the only independent prognostic factor of TTPVI (hazard ratio: 21.3, 95% confidence interval: 4.2–107.7, p < 0.001), and the presence of TTPVI was confirmed to be the only independent prognostic factors of recurrence (hazard ratio: 2.349, 95% confidence interval: 1.369–4.032, p = 0.002). No correlations were found between TTR and irregular tumor margins or peritumoral enhancement. Conclusion: The NAFLD–HCC patients had larger tumors at diagnosis and showed a more frequent presence of radiological signs of MVI as compared to the HCV–HCC patients. The MVI was related to a more rapid recurrence after curative treatments, demonstrating the prognostic value of this radiological diagnosis

Paraneoplastic Anti-Tif1-gamma Autoantibody-positive Dermatomyositis as Clinical Presentation of Hepatocellular Carcinoma Recurrence

Hepatocellular carcinoma (HCC) is rarely associated with autoimmune paraneoplastic syndromes. We report a case of anti-transcriptional intermediary factor-1 gamma (TIF1-??)-positive dermatomyositis (DM) as clinical presentation of HCC recurrence in a 72-year-old male patient admitted to our hospital due to fatigue, myalgia, and typical skin rash. His medical history was notable for hepatitis C-related cir-rhosis, successful treatment with direct-acting antiviral agents, and previously efficacious treatment of HCC. Labo-ratory testing showed significant rhabdomyolysis with anti-TIF1-?? antibodies at high titer, and DM was diagnosed. After a careful diagnostic workup, HCC recurrence was diagnosed. After first-line corticosteroid treatment, azathioprine and in-travenous immunoglobulin treatments were administered; unfortunately, he mounted only partial response. Owing to the compromised performance status, no HCC treatment was feasible, and, according to international guidelines, he received only best supportive care. Here, we discuss the diagnostic, prognostic, and pathogenic roles of anti-TIF1-?? antibodies associated with paraneoplastic DM and the scant literature data on its occurrence in HCC patients. Consider-ing the TIF1 gene family???s established role in oncogenesis, we also review the role of TIF1-?? as a tumor-related neo-antigen, leading to the development of clinically overt anti-TIF1-?? antibodies-positive DM

Segmental Distribution of Hepatocellular Carcinoma in Cirrhotic Livers

Background: To evaluate the segmental distribution of hepatocellular carcinoma (HCC) according to Couinaud’s anatomical division in cirrhotic patients. Methods: Between 2020 and 2021, a total of 322 HCC nodules were diagnosed in 217 cirrhotic patients who underwent computed tomography (CT) or magnetic resonance imaging (MRI) for the evaluation of suspicious nodules (>1 cm) detected during ultrasound surveillance. For each patient, the segmental position of the HCC nodule was recorded according to Couinaud’s description. The clinical data and nodule characteristics were collected. Results: A total of 234 (72.7%) HCC nodules were situated in the right lobe whereas 79 (24.5%) were detected in the left lobe (p < 0.0001) and only 9 nodules were in the caudate lobe (2.8%). HCC was most common in segment 8 (n = 88, 27.4%) and least common in segment 1 (n = 9, 2.8%). No significant differences were found in the frequencies of segmental or lobar involvement considering patient demographic and clinical characteristics, nodule dimension, or disease appearance. Conclusions: The intrahepatic distribution of HCC differs among Couinaud’s segments, with segment 8 being the most common location and segment 1 being the least common. The segmental distribution of tumour location was similar to the normal liver volume distribution, supporting a possible correlation between HCC location and the volume of hepatic segments and/or the volumetric distribution of the portal blood flow