Poorly differentiated clusters (PDC) in colorectal cancer: Does their localization in tumor matter?

Poorly differentiated clusters (PDC) are aggregates of at least five neoplastic cells lacking evidence of glandular differentiation. By definition, they can be present at the invasive front (peripheral PDC or pPDC) and within the tumor stroma (central PDC or cPDC). In colorectal cancer (CRC), PDC are considered adverse prognosticators and seem to reflect epithelial mesenchymal transition (EMT). In this study, we have investigated the immuno-expression of two EMT-related proteins, E-cadherin and β-catenin, in PDC of primary CRCs and matched liver metastases. pPDC always showed nuclear β-catenin staining and diffusely reduced/absence of E-cadherin expression as opposed cPDC which showed nuclear β-catenin immunoreactivity and E-cadherin expression in about 50% of cases. In addition, the pattern of β-catenin and E-cadherin expression differed between PDC and the main tumor, and between primary CRC and liver metastasis (LM), in a percentage of cases. A discordant pattern of β-catenin and E-cadherin expression between pPDC and cPDC, between main tumor and cPDC, and between primary CRC and LM, confirms that EMT is a dynamic and reversible process in CRC. On the overall, this suggests that pPDC and cPDC are biologically different. We may advocate that PDC develop at the tumor center (cPDC) and then some of them migrate towards the tumor periphery while progressively completing EMT process (pPDC). Based on these results, PDC presence and counting may have different prognostic relevance if the assessment is done at the invasive front of the tumor or in the intratumor stroma

Constitutive psgl-1 correlates with cd30 and tcr pathways and represents a potential target for immunotherapy in anaplastic large t-cell lymphoma

Due to the high expression of P-selectin glycoprotein ligand-1 (PSGL-1) in lymphoprolif-erative disorders and in multiple myeloma, it has been considered as a potential target for humoral immunotherapy, as well as an immune checkpoint inhibitor in T-cells. By investigating the expression of SELPLG in 678 T-and B-cell samples by gene expression profiling (GEP), further supported by tissue microarray and immunohistochemical analysis, we identified anaplastic large T-cell lymphoma (ALCL) as constitutively expressing SELPLG at high levels. Moreover, GEP analysis in CD30+ ALCLs highlighted a positive correlation of SELPLG with TNFRSF8 (CD30-coding gene) and T-cell receptor (TCR)-signaling genes (LCK, LAT, SYK and JUN), suggesting that the common dysreg-ulation of TCR expression in ALCLs may be bypassed by the involvement of PSGL-1 in T-cell activation and survival. Finally, we evaluated the effects elicited by in vitro treatment with two anti-PSGL-1 antibodies (KPL-1 and TB5) on the activation of the complement system and induction of apoptosis in human ALCL cell lines. In conclusion, our data demonstrated that PSGL-1 is specifically enriched in ALCLs, altering cell motility and viability due to its involvement in CD30 and TCR signaling, and it might be considered as a promising candidate for novel immunotherapeutic approaches in ALCLs

SARS-CoV-2 modulates virus receptor expression in placenta and can induce trophoblast fusion, inflammation and endothelial permeability

SARS-CoV-2 is a devastating virus that induces a range of immunopathological mechanisms including cytokine storm, apoptosis, inflammation and complement and coagulation pathway hyperactivation. However, how the infection impacts pregnant mothers is still being worked out due to evidence of vertical transmission of the SARS-CoV-2, and higher incidence of preeclampsia, preterm birth, caesarian section, and fetal mortality. In this study, we assessed the levels of the three main receptors of SARS-CoV-2 (ACE2, TMPRSS2 and CD147) in placentae derived from SARS-CoV-2 positive and negative mothers. Moreover, we measured the effects of Spike protein on placental cell lines, in addition to their susceptibility to infection. SARS-CoV-2 negative placentae showed elevated levels of CD147 and considerably low amount of TMPRSS2, making them non-permissive to infection. SARS-CoV-2 presence upregulated TMPRSS2 expression in syncytiotrophoblast and cytotrophoblast cells, thereby rendering them amenable to infection. The non-permissiveness of placental cells can be due to their less fusogenicity due to infection. We also found that Spike protein was capable of inducing proinflammatory cytokine production, syncytiotrophoblast apoptosis and increased vascular permeability. These events can elicit pre-eclampsia-like syndrome that marks a high percentage of pregnancies when mothers areinfected with SARS-CoV-2. Our study raises important points relevant to SARSCoV- 2 mediated adverse pregnancy outcomes

A Agroecologia na Escola Família Agrícola de Itaquiraí, em Mato Grosso do Sul.

bitstream/item/66246/1/31208.pdfOrganizado por: Alberto Feiden, Milton Parron Padovan, Adalgiza Inês Campolim, Aurélio Vinícius Borsato, Ivo de Sá Motta, João Batista Catto, Tércio Jacques Fehlauer

Retrospective analysis of risk factors and gaps in prevention strategies for mother-to-child HIV transmission in Rio de Janeiro, Brazil

Background Despite great progress made in methods to prevent mother-to-child transmission of HIV (MTCT), delivery and uptake of these measures remains a challenge in many countries. Although the Brazilian Ministry of Health aimed to eliminate MTCT by 2015, infection still occured in 15–24% of infants born to HIV-infected mothers. We sought to identify remaining factors that constrain MTCT elimination. Methods We conducted a retrospective, matched case-control study by reviewing hospital charts of infants born to HIV-infected mothers between 1997 and 2014 at three MTCT reference hospitals in the Rio de Janeiro metropolitan area. Cases were defined as HIV-exposed children with two positive HIV tests before 18 months of age; controls were defined as HIV-exposed children with two negative HIV tests before 18 months of age. We performed bivariate and MTCT cascade analyses to identify risk factors for MTCT and gaps in prevention services. Results We included 435 infants and their mothers (145 cases, 290 controls). Bivariate analyses of MTCT preventative care (PMTCT) indicated that cases were less likely to complete all individual measures in the antenatal, delivery, and postnatal period (p < 0.05). Assessing completion of the PMTCT cascade, the sequential steps of PMTCT interventions, we found inadequate retention in care among both cases and controls, and cases were significantly less likely than controls to continue receiving care throughout the cascade (p < 0.05). Motives for incompletion of PMTCT measures included infrastructural issues, such as HIV test results not being returned, but were most often due to lack of care-seeking. Over the course of the study period, PMTCT completion improved, although it remained below the 95% target for antenatal care, HIV testing, and antenatal ART set by the WHO. Adding concern, evaluation of co-infections indicated that case infants were also more likely to have congenital syphilis (OR: 4.29; 95% CI: 1.66 to 11.11). Conclusions While PMTCT coverage has improved over the years, completion of services remains insufficient. Along with interventions to promote care-seeking behaviour, increased infrastructural support for PMTCT services is needed to meet the HIV MTCT elimination goal in Brazil as well as address rising national rates of congenital syphilis

Occurrence and identification of risk areas of Ixodes ricinus-borne pathogens: a cost-effectiveness analysis in north-eastern Italy

<p>Abstract</p> <p>Background</p> <p><it>Ixodes ricinus</it>, a competent vector of several pathogens, is the tick species most frequently reported to bite humans in Europe. The majority of human cases of Lyme borreliosis (LB) and tick-borne encephalitis (TBE) occur in the north-eastern region of Italy. The aims of this study were to detect the occurrence of endemic and emergent pathogens in north-eastern Italy using adult tick screening, and to identify areas at risk of pathogen transmission. Based on our results, different strategies for tick collection and pathogen screening and their relative costs were evaluated and discussed.</p> <p>Methods</p> <p>From 2006 to 2008 adult ticks were collected in 31 sites and molecularly screened for the detection of pathogens previously reported in the same area (i.e., LB agents, TBE virus, <it>Anaplasma phagocytophilum, Rickettsia </it>spp., <it>Babesia </it>spp., "<it>Candidatus Neoehrlichia mikurensis</it>"). Based on the results of this survey, three sampling strategies were evaluated <it>a</it>-<it>posteriori</it>, and the impact of each strategy on the final results and the overall cost reductions were analyzed. The strategies were as follows: tick collection throughout the year and testing of female ticks only (strategy A); collection from April to June and testing of all adult ticks (strategy B); collection from April to June and testing of female ticks only (strategy C).</p> <p>Results</p> <p>Eleven pathogens were detected in 77 out of 193 ticks collected in 14 sites. The most common microorganisms detected were <it>Borrelia burgdorferi </it>sensu lato (17.6%), <it>Rickettsia helvetica </it>(13.1%), and "<it>Ca. N. mikurensis</it>" (10.5%). Within the <it>B. burgdorferi </it>complex, four genotypes (i.e., <it>B. valaisiana, B. garinii, B. afzelii</it>, and <it>B. burgdorferi </it>sensu stricto) were found. Less prevalent pathogens included <it>R. monacensis </it>(3.7%), TBE virus (2.1%), <it>A. phagocytophilum </it>(1.5%), <it>Bartonella </it>spp. (1%), and <it>Babesia </it>EU1 (0.5%). Co-infections by more than one pathogen were diagnosed in 22% of infected ticks. The prevalences of infection assessed using the three alternative strategies were in accordance with the initial results, with 13, 11, and 10 out of 14 sites showing occurrence of at least one pathogen, respectively. The strategies A, B, and C proposed herein would allow to reduce the original costs of sampling and laboratory analyses by one third, half, and two thirds, respectively. Strategy B was demonstrated to represent the most cost-effective choice, offering a substantial reduction of costs, as well as reliable results.</p> <p>Conclusions</p> <p>Monitoring of tick-borne diseases is expensive, particularly in areas where several zoonotic pathogens co-occur. Cost-effectiveness studies can support the choice of the best monitoring strategy, which should take into account the ecology of the area under investigation, as well as the available budget.</p

Prevention of congenital malformations and other adverse pregnancy outcomes with 4.0 mg of folic acid : community-based randomized clinical trial in Italy and the Netherlands

Background: In 2010 a Cochrane review confirmed that folic acid (FA) supplementation prevents the first- and second-time occurrence of neural tube defects (NTDs). At present some evidence from observational studies supports the hypothesis that FA supplementation can reduce the risk of all congenital malformations (CMs) or the risk of a specific and selected group of them, namely cardiac defects and oral clefts. Furthermore, the effects on the prevention of prematurity, foetal growth retardation and pre-eclampsia are unclear.Although the most common recommendation is to take 0.4 mg/day, the problem of the most appropriate dose of FA is still open.The aim of this project is to assess the effect a higher dose of peri-conceptional FA supplementation on reducing the occurrence of all CMs. Other aims include the promotion of pre-conceptional counselling, comparing rates of selected CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age, abruptio placentae.Methods/Design: This project is a joint effort by research groups in Italy and the Netherlands. Women of childbearing age, who intend to become pregnant within 12 months are eligible for the studies. Women are randomly assigned to receive 4 mg of FA (treatment in study) or 0.4 mg of FA (referent treatment) daily. Information on pregnancy outcomes are derived from women-and-physician information.We foresee to analyze the data considering all the adverse outcomes of pregnancy taken together in a global end point (e.g.: CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age). A total of about 1,000 pregnancies need to be evaluated to detect an absolute reduction of the frequency of 8%. Since the sample size needed for studying outcomes separately is large, this project also promotes an international prospective meta-analysis.Discussion: The rationale of these randomized clinical trials (RCTs) is the hypothesis that a higher intake of FA is related to a higher risk reduction of NTDs, other CMs and other adverse pregnancy outcomes. Our hope is that these trials will act as catalysers, and lead to other large RCTs studying the effects of this supplementation on CMs and other infant and maternal outcomes.Trial registration: Italian trial: ClinicalTrials.gov Identifier: NCT01244347.Dutch trial: Dutch Trial Register ID: NTR3161

Pitfalls in the embolisation of a thyrocervical trunk bleeding: A case report

none6noIntroduction: An intrathoracic bleeding from the thyrocervical branch is not common in blunt trauma, but an interventional radiologist should be aware of the risks in order to prevent complications. Case presentation: A 30-year-old male presented with a right pneumo-haemothorax due to active bleeding revealed at contrast-enhanced CT, as a consequence of a fall occurred in the previous week. The patient was treated with endovascular embolisation in an angiographic room with coils placement, since the right thyrocervical artery was found to be supplying the pneumo-haemothorax. A radiculo-medullary branch rose from the thyrocervical trunk, impeding the proximal embolization with microparticles and needing selective isolation of the bleeding artery with the catheter to avoid spinal cord injuries. The treatment had a successful result and the following CT control showed signs of recovering, without any complication. Conclusion: Our paper presents a rare contingency, warning the operator to bear in mind the presence of arteries feeding the spinal cord. This crucial detail precludes the use of microparticles embolisation to prevent neurologic sequelae, whereas the use of endovascular coils for embolization should be mandatory. Moreover, this case reminds that the post-traumatic bleeding deriving from a cervical trauma may also occur later.openPerrucci L.; Graziano M.; Ferrante Z.; Salviato E.; Carnevale A.; Galeotti R.Perrucci, L.; Graziano, M.; Ferrante, Z.; Salviato, E.; Carnevale, A.; Galeotti, R

Gastrointestinal bleeding from Dieulafoy’s lesion: endovascular management with gelfoam and coil

Clinical History/Pre-treatment Imaging: A 56-year-old man was admitted to our hospital for some day of asthenia. He reported aspirin intake for a mouth. His past medical history included splenectomy for trauma. Laboratory tests showed hemoglobin of 9.1 g/dL and digital rectal examination revealed melena. Esophagogastroduodenoscopy showed, in proximal gastric body, active arterial spurting from two close minute mucosal defect. These lesions were successfully treated with combined mechanical hemostasis and injection therapy. However, a following laboratory test revealed hemoglobin drop. Treatment Options/Results: Patient performed endovascular angiography but no active source of gastrointestinal (GI) bleeding were found. After celiac trunk catheterization, images revealed distal left gastric artery branches maintaining constant arterial caliber and tortuous appearance (Fig.1), finding suspected of Dieulafoy’s lesion. To minimize risk of premature rebleeding, embolization with gelfoam and coil was performed demonstrating reduce flow towards the proximal stomach (Fig.2). Discussion: Although often misdiagnosed, Dieulafoy’s lesion represents an important etiology of acute, life-threatening and recurrent GI bleeding. Hemostasis with angiographic embolization has been reported in sporadic case reports. To minimize the risk of bowel infarction, the super-selective catheterization technique and a temporary agent such as gelfoam slurry is mandatory. In our patient, despite active bleeding was no seen, we have decided to release also a proximal single coil. To our knowledge, it allows to reduce recurrent bleeding risk decreasing perfusion pressure but to maintain sufficient tissue blood flow avoiding ischemia. Take-home points: The embolization strategy is essential in the endovascular management of Dieulafoy’s lesion to balance the risk of rebleeding and the risk of bowel ischemia

Massive rectal bleeding treated with transcatheter artery embolization: an unusual presentation of the solitary rectal ulcer syndrome

Clinical History/Pre-treatment Imaging: A 35-year-old paraplegic man because of a thoracic spinal cord injury and, history of constipation and self-digitation maneuver to evacuate, complained rectal bleeding and maroon-colored stools from some days. Laboratory findings revealed hemoglobin of 8.3 g/dL and a hematocrit of 25% requiring the transfusion of 3 units of packed blood cells. Esophagogastroscopy was negative and colonoscopy was inconclusive showing blood and clots. Abdominal contrast enhanced CT showed endorectal active contrast extravasation from left superior hemorrhoidal artery (SHA). Endovascular angiography and embolization was performed for controlling acute bleeding. Treatment Options/Results: Selective catheter angiography at the inferior mesenteric artery demonstrated active extravasation from a peripheral posterior branch of the left SHA (Fig.1). It was subsequently super-selective embolized with coils. Post-embolization images demonstrated resolved bleeding (Fig.2). Two days later endoscopy revealed a single shallow longitudinal ulcerating lesion covered by white slough on a hyperemic surrounding mucosa. Combination of symptomatology, patient history and endoscopy prompted the diagnosis of Solitary Rectal Ulcer Syndrome (SRUS). Discussion: SRUS is a rare benign disorder supposed to be secondary to straining, self-inducted trauma, paradoxical contraction of puborectal muscle, rectal prolapse and intussusception. Although rectal bleeding is one of the most common clinical features, massive hemorrhage is extremely rare. Patients with a massively bleeding rectal ulcer that does not stabilize with endoscopic or supportive therapy must be considered for operative treatment, including endovascular embolization. Take-home points: -SRUS is an extremely rare cause of massive lower gastrointestinal bleeding. -Embolization is a safe and effective alternative to endoscopic treatment and surgery for the rapid clinical stabilization