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Introduction/Background*Endometrial cancer (EC) patients have a good prognosis at early stages, but for recurrent or metastatic EC the prognosis remains poor. EC treatments are related to known prognostic factors included in ESMO-ESGO-ESTRO risk classes classification, but they are not sufficient to predict outcomes or recurrence rate of early stages. To improve patient clinical management and allow personalized therapy a better characterization of risk classes in EC is needed. To fill this gap, we investigated EC immune escape processes, customized on the knowledge of maternal-fetal interface immune mechanisms, since the two processes share common pathways.MethodologyThis has been addressed by the identification of potential shared immune-based signatures between maternal-fetal interface and EC, such as those linked to lectin-type oxidized LDL receptor 1 (LOX-1) and NALP3 inflammasome, in order to achieve a potential immune score implementation to better characterize EC risk classes. The immunohistochemical assessment of LOX-1 and NALP3 was performed on formalin-fixed paraffin-embedded (FFPE) endometrial tissues.Result(s)*41 patients divided in 3 groups were enrolled: healthy endometrial tissue, endometrial hyperplasia and EC. We detected an increased expression of LOX-1, by immunohistochemistry (IHC), within the endometrial carcinoma tissues, a lower expression in cases of hyperplasia, to arrive to an absent staining in the healthy endometrial tissue (*p< 0.05, *Kruskal-Wallis followed by Mann-Whitney test). This grading is inverted in NALP3, which expression appears to be lower in EC (*p< 0.05). A proportional relationship between LOX-1 and NALP3 expression was demonstrated (p=0.006, Spearman test, confirmed through a linear regression test): increasing the expression of LOX-1, NALP3 decreases.Abstract 501 Figure 1Immunohistochemical staining on formalin-fixed paraffin-embedded samples of endometrical tissue showing expression of LOX-1 and NALP3 markersAbstract 501 Table 1Clinical and pathologic features of enrolled featuresConclusion*An increased LOX-1 and a decreased NALP3 expression seems be associated with EC progression. To identify patients at risk of developing EC from pre-cancerous lesions, by searching potential immune prognostic factors, such as LOX-1 and NALP3 on endometrial biopsy, could re-defy the actual EC risk classes through a potential ’immune score’ creation. Nevertheless, further studies are needed to define EC transcriptome immune-based signature. Furthermore, pathways detected by deciphering the immune changes linked to EC progression, could be potential target for immunotherapy.

Beginning in December 2019, the 2019 novel coronavirus disease (COVID-19) has caused a pneumonia epidemic that began in Wuhan, China, and is rapidly spreading throughout the whole world. Italy is the hardest hit country after China. Considering the deleterious consequences of malnutrition, which certainly can affect patients with COVID-19, the aim of this article is to present a pragmatic protocol for early nutritional supplementation of non-critically ill patients hospitalized for COVID-19 disease. It is based on the observation that most patients present at admission with severe inflammation and anorexia leading to a drastic reduction of food intake, and that a substantial percentage develops respiratory failure requiring non-invasive ventilation or even continuous positive airway pressure. High-calorie dense diets in a variety of different consistencies with highly digestible foods and snacks are available for all patients. Oral supplementation of whey proteins as well as intravenous infusion of multivitamin, multimineral trace elements solutions are implemented at admission. In the presence of 25-hydroxyvitamin D deficit, cholecalciferol is promptly supplied. If nutritional risk is detected, two to three bottles of protein-calorie oral nutritional supplements (ONS) are provided. If <2 bottles/d of ONS are consumed for 2 consecutive days and/or respiratory conditions are worsening, supplemental/total parenteral nutrition is prescribed. We are aware that our straight approach may be debatable. However, to cope with the current emergency crisis, its aim is to promptly and pragmatically implement nutritional care in patients with COVID-19, which might be overlooked despite being potentially beneficial to clinical outcomes and effective in preventing the consequences of malnutrition in this patient population. •Novel coronavirus disease (COVID-19) is spreading throughout the world and if nutritional care is not promptly implemented, malnutrition will affect also patients with the disease.•Most infected patients present with severe inflammation and anorexia leading to a drastic reduction of food intake; a large percentage develop respiratory failure.•A pragmatic protocol for early nutritional supplementation of patients with COVID-19 not in the intensive care unit was implemented.•Every effort should be made to avoid or limit underfeeding in patients with COVID-19, even if it means struggling against insurmountable difficulties due to the emergency scenario.

•Vitamin D has antiinflammatory and immunoregulatory functions.•The involvement of vitamin D in the pathophysiology of coronavirus disease 2019 (COVID-19) is still not clear.•Some studies support a link between vitamin D deficiency and worse COVID-19 outcomes.•Vitamin D may also enhance macrophage activation and aberrant immune response.•In our study, vitamin D supplementation was associated with a trend toward higher mortality.•Supplementation trials are crucial to clarify the role of vitamin D in COVID-19.

Background Understanding the molecular interactions between cells, tissues or organs is key to understanding the functioning of a biological system as a whole. Results Here, we propose crossWGCNA : a co-expression-based method that identifies highly interacting genes unbiasedly and that we employ to study stroma-epithelium communication in breast cancer. CrossWGCNA can be applied to bulk, single cell and spatial transcriptomics data. We validate it both in silico and experimentally, and we provide a fully documented R package allowing users to employ it. Conclusions The wide applicability and agnostic nature of our tool make it complementary to existing methods overcoming the limitations arising from strong baseline assumptions. Graphical Abstract

Background Chronic anal fissures (CAFs) are the second most common anorectal disease. Non-surgical treatment includes several options with controversial efficacy. The aim of this study was to evaluate the efficacy and safety of a new ointment based on methylene blue in addition to glyceryl trinitrate. Methods A phase II randomized single-centre triple-blinded study was carried out in a tertiary proctology unit on patients with CAF. The enrollment started after local ethics committee approval (study n. 6461, protocol approval n. 0045085). Eligible consecutive patients were randomized to one of three different groups, each receiving a different ointment. The efficacy of the treatment was evaluated with the REALISE score. Results Nine patients were treated with cream A (median age 47 years, IQR 40–56, 22% female), nine with cream B (median age 52 years, IQR 49–57, 33% female), and nine with cream C (median age 58 years, IQR 46–62, 55% female). In group A, REALISE scores decreased significantly from a median of 22 (IQR 12–25) to 6 (IQR 4–8) ( p  < 0.05) after 40 days. In group B, REALISE scores improved significantly from a median of 20 (IQR 17–22) to 5 (IQR 4–9) ( p  < 0.05). In group C, REALISE scores decreased significantly from a median of 19 (IQR 19–20) to 4 (4–5) ( p  < 0.05). No statistically differences were recorded. The healing rate was 77% with creams A and C, while it was 44% with cream B. Conclusion Methylene blue-based ointments could be a new and innovative treatment for the non-operative management and healing of CAFs.

Background Cancer mortality is mainly caused by organ failure and thrombotic events. It has been demonstrated that NETosis, a chromatin release mechanism implemented by neutrophils, may contribute to these lethal systemic effects. Our aim was to investigate NETosis biomarkers in endometrial cancer (EC). Methods The experiments were conducted on 21 healthy subjects (HS) with no gynecological conditions, and on 63 EC patients. To assess the presence of NETosis features, IHC and IF was performed using antibodies against citrullinated histone H3 (citH3), neutrophil elastase (NE) and histone 2B. Serum levels of cell free DNA (cfDNA), cell free mitochondrial DNA (cfmtDNA) and citH3 were measured by qPCR using one microliter of deactivated serum, and by ELISA assay respectively. Fragmentation pattern of serum cfDNA was analyzed using the Agilent 2100 Bioanalyzer and High Sensitivity DNA Chips. Receiver operating characteristic (ROC) analysis was used to identify a cut off for cfDNA and cfmtDNA values able to discriminate between ECs and HSs. Correlation analysis and multiple correspondence analysis (MCA) between cfDNA, mtcfDNA, citH3 and blood parameters were used to identify the potential association among serum parameters in EC grades. Results We demonstrated the presence of NETosis features in tissues from all EC grades. Serum cfDNA and cfmtDNA levels discriminate ECs from HSs and a direct correlation between citH3 and cfDNA content and an inverse correlation between cfmtDNA and citH3 in EC sera was observed, not detectable in HSs. MCA indicates cfDNA, cfmtDNA and citH3 as features associated to G1 and G2 grades. A correlation between increased levels of cfDNA, citH3 and inflammation features was found. Finally, serum nucleosomal cfDNA fragmentation pattern varies in EC sera and correlates with increased levels of cfDNA, citH3, lymphocytes and fibrinogen. Conclusion Our data highlight the occurrence of NETosis in EC and indicate serum cfDNA and citH3 as noninvasive biomarkers of tumor-induced systemic effects in endometrial cancer.

In the tumor microenvironment, Cancer Associated Fibroblasts (CAFs) become activated by cancer cells and increase their secretory activity to produce soluble factors that contribute to tumor cells proliferation, invasion and dissemination to distant organs. The pro-tumorigenic transcription factor STAT3 and its canonical inducer, the pro-inflammatory cytokine IL-6, act conjunctly in a positive feedback loop that maintains high levels of IL-6 secretion and STAT3 activation in both tumor and stromal cells. Here, we demonstrate that STAT3 is essential for the pro-tumorigenic functions of murine breast cancer CAFs both in vitro and in vivo, and identify a STAT3 signature significantly enriched for genes encoding for secreted proteins. Among these, ANGPTL4, MMP13 and STC-1 were functionally validated as STAT3-dependent mediators of CAF pro-tumorigenic functions by different approaches. Both in vitro and in vivo CAFs activities were moreover impaired by MMP13 inhibition, supporting the feasibility of a therapeutic approach based on inhibiting STAT3-induced CAF-secreted proteins. The clinical potential of such an approach is supported by the observation that an equivalent CAF-STAT3 signature in humans is expressed at high levels in breast cancer stromal cells and characterizes patients with a shorter disease specific survival, including those with basal-like disease.

With regard to vitamin D supplementation, several epidemiologic and observational studies seem to support the hypothesis of its protective role [3], but most of these are based on retrospective data or small case series, and whether vitamin D25OH adequacy may prevent the infection or improve clinical outcomes still needs to be assessed by adequately sized and designed population-based studies and intervention trials. Other nutrients (vitamins A, B6, B12, C, E, and folate; trace elements, including zinc, iron, selenium, magnesium, and copper; and omega-3 fatty acids) are known to play important and complementary roles in supporting the immune system and could be useful in improving clinical outcomes of patients with COVID-19 in the presence of nutritional derangements [4]. [...]we are happy that our article stimulated the development and adoption of several protocols aimed at promptly implementing nutritional care in patients with COVID-19, and it is our hope that early appropriate nutritional management will be systematically considered in this fragile patient population, as it is potentially beneficial to clinical outcomes and effective in preventing the consequences of malnutrition.

Injection sclerotherapy is an effective and safe treatment in selected cases. It might be used as the first treatment for I-III degree hemorrhoidal disease (HD), but also as a bridge therapy for more severe cases not amenable to invasive treatments. However, concerning the long-term recurrence rate, open excisional hemorrhoidectomy remains the gold standard in cases of III- and IV-degree HD. In this context, it is recommended to perform the excision of no more than three piles and to preserve the muco-cutaneous bridges to avoid post-operative anal stenosis. The aim of this study is to evaluate surgical outcomes and efficacy of the combined treatment of open excisional hemorrhoidectomy and the use of ST on the remnant muco-cutaneous bridges/residual piles. This was a single-center retrospective study and a total of 18 patients with IV-degree HD, aged between 18 and 75 years with symptomatic HD according to the Goligher classification, were enrolled between January 2023 and June 2023 and their follow-up continued until October 2023 after reaching 3 months of follow-up. The Hemorrhoidal Disease Symptom Score (HDSS), the Short Health Scale for HD (SHS-HD) score and the Vaizey Incontinence Score were used to assess symptoms and their impact on quality of life and continence. A total of 77.8% (14/18) of the patients were symptom-free (hemorrhoidal disease symptom score (HDSS) score = 0) after 3 months. Moreover, a statistically significant decrease in the median HDSS and short health scale for HD (SHS-HD) score was registered from 16 preoperatively (T0) to 2 at 3-month follow-up (T3). Neither post-operative bleeding nor any type of complications occurred. The use of sclerotherapy in combination with the traditional open excisional hemorrhoidectomy has shown promising results. Further structured studies are needed and greater dissemination and education of the general surgeon on the subject is necessary.