The anatomic variant of common celiacomesenteric trunk.

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The GH-IGF-SST system in hepatocellular carcinoma: biological and molecular pathogenetic mechanisms and therapeutic targets

Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide. Different signalling pathways have been identified to be implicated in the pathogenesis of HCC; among these, GH, IGF and somatostatin (SST) pathways have emerged as some of the major pathways implicated in the development of HCC. Physiologically, GH-IGF-SST system plays a crucial role in liver growth and development since GH induces IGF1 and IGF2 secretion and the expression of their receptors, involved in hepatocytes cell proliferation, differentiation and metabolism. On the other hand, somatostatin receptors (SSTRs) are exclusively present on the biliary tract. Importantly, the GH-IGF-SST system components have been indicated as regulators of hepatocarcinogenesis. Reduction of GH binding affinity to GH receptor, decreased serum IGF1 and increased serum IGF2 production, overexpression of IGF1 receptor, loss of function of IGF2 receptor and appearance of SSTRs are frequently observed in human HCC. In particular, recently, many studies have evaluated the correlation between increased levels of IGF1 receptors and liver diseases and the oncogenic role of IGF2 and its involvement in angiogenesis, migration and, consequently, in tumour progression. SST directly or indirectly influences tumour growth and development through the inhibition of cell proliferation and secretion and induction of apoptosis, even though SST role in hepatocarcinogenesis is still opened to argument. This review addresses the present evidences suggesting a role of the GH-IGF-SST system in the development and progression of HCC, and describes the therapeutic perspectives, based on the targeting of GH-IGF-SST system, which have been hypothesised and experimented in HCC

Role of Electrostatic Interactions in Calcitonin Prefibrillar Oligomer-Induced Amyloid Neurotoxicity and Protective Effect of Neuraminidase

Salmon calcitonin is a good model for studying amyloid behavior and neurotoxicity. Its slow aggregation rate allows the purification of low molecular weight prefibrillar oligomers, which are the most toxic species. It has been proposed that these species may cause amyloid pore formation in neuronal membranes through contact with negatively charged sialic acid residues of the ganglioside GM1. In particular, it has been proposed that an electrostatic interaction may be responsible for the initial contact between prefibrillar oligomers and GM1 contained in lipid rafts. Based on this evidence, the aim of our work was to investigate whether the neurotoxic action induced by calcitonin prefibrillar oligomers could be counteracted by treatment with neuraminidase, an enzyme that removes sialic acid residues from gangliosides. Therefore, we studied cell viability in HT22 cell lines and evaluated the effects on synaptic transmission and long-term potentiation by in vitro extracellular recordings in mouse hippocampal slices. Our results showed that treatment with neuraminidase alters the surface charges of lipid rafts, preventing interaction between the calcitonin prefibrillar oligomers and GM1, and suggesting that the enzyme, depending on the concentration used, may have a partial or total protective action in terms of cell survival and modulation of synaptic transmission

Botulinum toxin injection for the treatment of chronic anal fissure: uni- and multivariate analysis of the factors that promote healing

Purpose Anal fissure is caused by a pathological contraction of the internal anal sphincter. Lateral internal sphincterotomy remains the gold standard for the treatment of fissure. Botulinum toxin injections have been proposed to treat this condition without any risk of permanent injury of the internal sphincter. We investigate clinical and pathological variables and the effects of different dosage regimens of botulinum toxin to induce healing in patients with idiopathic anal fissure. Methods This is a retrospective study at a single center. The patients underwent a pre-treatment evaluation that included clinical inspection of the fissure and anorectal manometry. We collected and analyzed demographic data, pathological variables, associated pathological conditions, and treatment variables. Success was defined as healing of the fissure, and improvement of symptoms was defined as asymptomatic persistent fissure. Results The findings of 1003 patients treated with botulinum toxin injections were reported. At 2 months evaluation, complete healing was evident in 780 patients (77.7%). Resting anal tone (77.1 +/- 18.9 mmHg) was significantly lower from baseline (P < 0.0001) and from 1-month value (P = 0.0008). Thirty-nine not healed patients underwent lateral internal sphincterotomy, and 184 were re-treated with 50 UI of botulinum toxin. In these patients, the healing rate was 93.9% (171 patients). Dose and injection site of toxin correlates with healing rate. There were no relapses during an average of about 71 months. Conclusion Our data show that injection of botulinum toxin into the internal anal sphincter is a safe and effective alternative to surgery in patients with chronic anal fissure

Bone Marrow Edema: Overview of Etiology and Treatment Strategies

➤: Bone marrow edema (BME) is a nonspecific but relevant finding, usually indicating the presence of an underlying pathology. ➤: The gold standard technique for detecting BME is magnetic resonance imaging (MRI), as it allows for a correct diagnosis to be made, which is extremely important given the heterogeneity of BME-related diseases. ➤: Depending on the severity of painful symptomatology and the MRI evidence, different treatment strategies can be followed: physical modalities, pharmacological options, and surgical therapy

Endometrial microbiota profile in in-vitro fertilization (IVF) patients by culturomics-based analysis

IntroductionIt is well recognized that the human uterus and adjoining tissues of the female reproductive tract exist in a non-sterile state where dysbiosis can impact reproductive outcomes. The endometrial microbiota is a part of this greater milieu. To date, it has largely been studied using 16S rRNA or metagenomics-based methodologies. Despite the known advantages of sequencing analysis, several difficulties have been noted including sample contamination and standardization of DNA extraction or sequencing. The aim of this study was to use a culturomics-based method to analyze the endometrial microbiota and correlate the results with ongoing pregnancy rates.MethodsA prospective cohort study was performed at the University of Naples from June 2022 to December 2022. Ninety-three patients undergoing an IVF cycle with single embryo transfer (ET) (fresh or frozen) were enrolled in the study. Following ET, the catheter tip was inserted into brain heart infusion (BHI) medium under sterile conditions for culture. After 24h and 48h of incubation the microorganisms in the colonies were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).ResultsOverall, 68 (73,92%) patients resulted positive for one or more microbes and 25 patients (26,08%) had no microbial growth. Across all participants, the four most important phyla were Firmicutes (87,76%), Proteobacteria (27,94%), Actinobacteria (10,29%) and Ascomycota (8,82%). Lactobacillus species, in particular, was significantly correlated with ongoing pregnancy rate (p=0,05). On the other hand, Staphylococcus subspecies (spp.) (p<0,05) and Enterobacteriaceae (p<0,001) were found to have a negative impact on the implantation rate.DiscussionDetection of bacteria by culturomics from catheter tips used for embryo transfer has been shown to be a reliable method to detect pathogen growth. Endometrial microbiota testing in clinical practice could certainly offer a means to further improve diagnosis and treatment strategies in IVF patients

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

Aberrant right hepatic duct and cystic duct both draining into the common hepatic duct

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