Pancreatic cancer molecular classifications: From bulk genomics to single cell analysis

Pancreatic cancer represents one of the most lethal disease worldwide but still orphan of a molecularly driven therapeutic approach, although many genomic and transcriptomic classifications have been proposed over the years. Clinical heterogeneity is a hallmark of this disease, as different patients show different responses to the same therapeutic regimens. However, genomic analyses revealed quite a homogeneous disease picture, with very common mutations in four genes only (KRAS, TP53, CDKN2A, and SMAD4) and a long tail of other mutated genes, with doubtful pathogenic meaning. Even bulk transcriptomic classifications could not resolve this great heterogeneity, as many informations related to small cell populations within cancer tissue could be lost. At the same time, single cell analysis has emerged as a powerful tool to dissect intratumoral heterogeneity like never before, with possibility of generating a new disease taxonomy at unprecedented molecular resolution. In this review, we summarize the most relevant genomic, bulk and single-cell transcriptomic classifications of pancreatic cancer, and try to understand how novel technologies, like single cell analysis, could lead to novel therapeutic strategies for this highly lethal disease

Children at risk of domestic accidents when are locked up at home: the other side of COVID-19 outbreak lockdown

Background We proposed to analyze thoroughly the impact of the COVID-19 lockdown (CL) in changes of profiles and in trend of the domestic accidents (DAs) in children. Methods This was a single experience, cross-sectional study conducted at the emergency department (ED) of III trauma center. We enrolled children under 18 years admitted to ED with a diagnosis of DAs comparing the CL period from 10(th) March 2020 to 4(th) May 2020 with the same period of the previous year,10(th) March 2019 to 4(th) May 2019. Results In CL period, the cumulative incidence of ED visits for DAs increased from 86.88 to 272.13 per 1,000 children and the cumulative incidence of hospitalizations for DAs increased from 409.72 to 534.48 per 1,000 children. We reported in CL a decrease in the severity of ED presentation assessed by proxy measures: the level of priority ED visits reduced by 67% in CL period (OR: 0.33; 95%CI 0.22-0.48; p < 0.001); the likelihood of delayed time of presentation to ED increased by 65% in case of domestic injuries occurring in CL period (OR: 1.65; 95% CI: 1.17-2.34; p = 0.004); the odds of transfer from other hospital decreased by 78% in CL (OR: 0.15-0.33; p < 0.001). Children were more at risk of poisoning (OR:3.35-106.11; p = 0.001), of body foreign ingestion (OR: 1.83-14.39; p = 0.002) and less at risk of animal bite trauma (OR:0.05-0.35; p < 0.001). Conclusion Although the need to stay home has made a decisive breakthrough on the spread of COVID-19, the experience from this study underlines how this preventive measure has also had a downside in term of increased cumulative incidence of ED visits and of hospitalizations for DA

Spesolimab in patients with flare of generalized pustular psoriasis: A multicentre case-series

Dear Editor,Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening, chronic inf lammatory disease character-ized by acute f lares of pustular eruptions that can be accom-panied by systemic inf lammation. GPP can be associated with chronic plaque psoriasi

Assessing the experience of using synthetic cannabinoids by means of interpretative phenomenological analysis

BACKGROUND: New psychoactive substances (NPS) have been increasingly consumed by people who use drugs in recent years, which pose a new challenge for treatment services. One of the largest groups of NPS is synthetic cannabinoids (SCs), which are intended as a replacement to cannabis. While there is an increasing body of research on the motivation and the effects associated with SC use, little is known about the subjective interpretation of SC use by the people who use drugs themselves. The aim of this study was to examine the experiences and personal interpretations of SC use of users who were heavily dependent on SC and are in treatment. METHODS: A qualitative research method was applied in order to explore unknown and personal aspects of SC use. Semi-structured interviews were conducted with six participants who had problematic SC use and entered treatment. The research was conducted in Hungary in 2015. We analyzed data using interpretative phenomenological analysis (IPA). RESULTS: Participants perceived SCs to be unpredictable: their initial positive experiences quickly turned negative. They also reported that SCs took over their lives both interpersonally and intrapersonally: the drug took their old friends away, and while initially it gave them new ones, in the end it not only made them asocial but the drug became their only friend, it hijacked their personalities and made them addicted. CONCLUSIONS: Participants experienced rapid development of effects and they had difficulties interpreting or integrating these experiences. The rapid alteration of effects and experiences may explain the severe psychopathological symptoms, which may be important information for harm reduction and treatment services. Since, these experiences are mostly unknown and unpredictable for people who use SCs, a forum where they could share their experiences could have a harm reducing role. For a harm reduction point of view of SCs, which are underrepresented in literature, it is important to emphasize the impossibility of knowing the quantity, purity, or even the number of different SC compounds in a particular SC product. Our study findings suggest that despite the adverse effects, including a rapid turn of experiences to negative, rapid development of addiction and withdrawal symptoms of SCs, participants continued using the drug because this drug was mostly available and cheap. Therefore, a harm reduction approach would be to make available and legal certain drugs that have less adverse effects and could cause less serious dependence and withdrawal symptoms, with controlled production and distribution (similarly to cannabis legalization in the Netherlands)

Enhancing Preparedness for Arbovirus Infections with a One Health Approach: The Development and Implementation of Multisectoral Risk Assessment Exercises

10 Pág.One Health is receiving attention for arbovirus infection prevention and control and for defining national "intersectoral" priorities. Increasing awareness of intersectoral priorities through multisectorial risk assessments (MRA) is promising, where data are not systematically shared between sectors. Towards this aim, the MediLabSecure project organized three MRA exercises (hereby called exercises): one on West Nile virus, one on Crimean-Congo haemorrhagic fever, and one on Rift Valley fever, assessing the added value of this approach.The authors acknowledge the active participation of the members of MediLabSecure network to the MRA exercises. The MediLabSecure project was supported by the European Commission (DEVCO: IFS/21010/23/_194 & IFS/2018/402-247). The funding body was not involved in the design of the study, in collection, analysis, and interpretation of data, and in writing the manuscript.Peer reviewe

Parathyroidectomy and survival in a cohort of Italian dialysis patients: results of a multicenter, observational, prospective study

Background: Severe secondary hyperparathyroidism (SHPT) is associated with mortality in end stage kidney disease (ESKD). Parathyroidectomy (PTX) becomes necessary when medical therapy fails, thus highlighting the interest to compare biochemical and clinical outcomes of patients receiving either medical treatment or surgery. Methods: We aimed to compare overall survival and biochemical control of hemodialysis patients with severe hyperparathyroidism, treated by surgery or medical therapy followed-up for 36 months. Inclusion criteria were age older than 18 years, renal failure requiring dialysis treatment (hemodialysis or peritoneal dialysis) and ability to sign the consent form. A control group of 418 patients treated in the same centers, who did not undergo parathyroidectomy was selected after matching for age, sex, and dialysis vintage. Results: From 82 Dialysis units in Italy, we prospectively collected data of 257 prevalent patients who underwent parathyroidectomy (age 58.2 ± 12.8 years; M/F: 44%/56%, dialysis vintage: 15.5 ± 8.4 years) and of 418 control patients who did not undergo parathyroidectomy (age 60.3 ± 14.4 years; M/F 44%/56%; dialysis vintage 11.2 ± 7.6 y). The survival rate was higher in the group that underwent parathyroidectomy (Kaplan–Meier log rank test = 0.002). Univariable analysis (HR 0.556, CI: 0.387–0.800, p = 0.002) and multivariable analysis (HR 0.671, CI:0.465–0.970, p = 0.034), identified parathyroidectomy as a protective factor of overall survival. The prevalence of patients at KDOQI targets for PTH was lower in patients who underwent parathyroidectomy compared to controls (PTX vs non-PTX: PTH < 150 pg/ml: 59% vs 21%, p = 0.001; PTH at target: 18% vs 37% p = 0.001; PTH > 300 pg/ml 23% vs 42% p = 0.001). The control group received more intensive medical treatment with higher prevalence of vitamin D (65% vs 41%, p = 0.0001), calcimimetics (34% vs 14%, p = 0.0001) and phosphate binders (77% vs 66%, p = 0.002). Conclusions: Our data suggest that parathyroidectomy is associated with survival rate at 36 months, independently of biochemical control. Lower exposure to high PTH levels could represent an advantage in the long term. Graphical abstract: [Figure not available: see fulltext.]

Opportunistic metastatic porocarcinoma after saphenous venectomy for coronary bypass surgery

Immunocompromised areas of the skin, caused by chronic lymphoedema, paraplegia, infections or traumas, represent a site of regional neuroimmunocutaneous destabilization, termed the immunocompromised cutaneous district (ICD), in which malignancies and other opportunistic disorders are more likely to occur. We report the case of a metastatic porocarcinoma (PC) occurring on a lymphoedematous limb in a 72-year-old man. We reviewed the literature to better understand the potential pathogenetic mechanisms behind this condition. It has been reported that removal of the leg vein destroys the medial group of the superficial lymphatic vessels and alters the normal lymph drainage of the leg, predisposing to recurrent cellulitis. Our observations suggest that saphenous venectomy can induce development of an ICD. We suggest that PC, a rare cutaneous tumour, should be included in the growing list of tumours arising in the ICD. © 2013 British Association of Dermatologists

Opportunistic metastatic porocarcinoma after saphenous venectomy for coronary bypass surgery

Immunocompromised areas of the skin, caused by chronic lymphoedema, paraplegia, infections or traumas, represent a site of regional neuroimmunocutaneous destabilization, termed the immunocompromised cutaneous district (ICD), in which malignancies and other opportunistic disorders are more likely to occur. We report the case of a metastatic porocarcinoma (PC) occurring on a lymphoedematous limb in a 72-year-old man. We reviewed the literature to better understand the potential pathogenetic mechanisms behind this condition. It has been reported that removal of the leg vein destroys the medial group of the superficial lymphatic vessels and alters the normal lymph drainage of the leg, predisposing to recurrent cellulitis. Our observations suggest that saphenous venectomy can induce development of an ICD. We suggest that PC, a rare cutaneous tumour, should be included in the growing list of tumours arising in the ICD. © 2013 British Association of Dermatologists

Gas exchange and leaf metabolism of irrigated maize at different growth stages

Net ecosystem exchange (NEE), leaf gas exchange and biochemical traits were investigated in an irrigated maize crop grown under Mediterranean conditions. Sub-optimal irrigation water supply determined a drought stress during the early vegetative growth stage (45–49 days after swing) that decreased NEE. Drought, in the late vegetative stage, also caused a reduction of leaf gas exchange. In the latter period, proline, glycine and serine, as well as sucrose leaf contents increased, while starch, proteins and glucose contents decreased. In the early reproductive stage, the crop experienced a longer dry spell that induced a reduction in canopy as well as in leaf gas exchanges, while protein and free amino acid contents decreased with respect to the late vegetative stage. Both ecophysiological and biochemical data demonstrate a good capacity of cultivar Pioneer PR32D99 to endure the environmental stress, related to Mediterranean summer drought, leading to an elevated dry matter yield at harvest. Photosynthetic apparatus appeared fairly resistant to soil water shortage due likely to the increased leaf content of organic solutes, such as amino acids and soluble sugars