Cardiovascular risk markers in patients with primary aldosteronism: A systematic review and meta-analysis of literature studies

Background/objectives: Several studies reported an increased cardiovascular (CV) morbidity and mortality in patients with primary aldosteronism (PA). We performed a meta-analysis on the impact of PA on major markers of CV risk. Methods: Studies on the relationship between PA and common carotid artery intima-media thickness (CCA-IMT), prevalence of carotid plaques, flow-mediated dilation (FMD), nitrate-mediated dilation (NMD), pulse-wave velocity (PWV), augmentation index (AIx), and ankle-brachial index (ABI) were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. Results: 12 case-control studies (445 cases, 472 controls) were included. Compared to subjects with essential hypertension (EH), PA patients showed a higher CCA-IMT (MD: 0.12 mm; 95% CI: 0.09, 0.16; P<0.00001), and a higher aortic-PWV (272 cases and 240 controls, MD: 1.39 m/s; 95% CI: 0.90, 1.87; P<0.00001). In contrast, non-significant differences were found in AIx and AIx normalized to a heart rate of 75 beats per minute (AIx@75). When compared to normotensive subjects, PA patients showed significantly higher CCA-IMT (MD: 0.16 mm; 95% CI: 0.05, 0.27; P=0.004), aortic-PWV (MD: 3.74 m/s; 95% CI: 3.43, 4.05; P<0.00001), AIx@75 (MD: 8.59%; 95% CI: 0.69, 16.50; P=0.03), and a significantly lower FMD (MD: -2.52%; 95% CI: -3.64, -1.40; P<0.0001). Sensitivity and subgroup analyses substantially confirmed our results. Metaregression models showed that male gender, diabetes, and smoking habit impact on the observed results. Conclusions: PA appears significantly associated with markers of subclinical atherosclerosis and CV risk. These findings could help establish more specific CV prevention strategies in this clinical setting

Pancreatic ductal adenocarcinoma and distal cholangiocarcinoma: a proposal of preoperative diagnostic score for differential diagnosis

Purpose:The differential diagnosis between primary adenocarcinoma of the pancreas head and distalcholangiocarcinoma remains a clinical challenge. Recent studies have shown important differences in terms ofsurvival between these tumors. Therefore, different treatments should be considered, but the preoperativehistological diagnosis is still difficult. Aim of this study is to create a preoperative diagnostic score for differentialdiagnosis between primary pancreatic adenocarcinoma and primary distal cholangiocarcinoma.Methods:One hundred eighty consecutive patients who underwent pancreaticoduodenectomy at SapienzaUniversity of Rome from January 2010 to December 2019 were retrospectively analyzed. Inclusion criteria werepancreatic or biliary histologic origin obtained by definitive postoperative histological examination. Exclusion criteriawere diagnosis of ampullary carcinoma, non-ampullary duodenal adenocarcinoma, pancreatic metastasis, andbenign disease. One hundred one patients were considered eligible for the retrospective study. Preoperativebiological, clinical, and radiological parameters were considered.Results:CRP &gt; 10 mg/dL (p= 0.001), modified Glasgow Prognostic Score 2 (p= 0.002), albumin &lt; 35 g/L (p= 0.05),CA 19-9 &gt; 230 U/mL (p= 0.001), and Wirsung diameter &gt; 3 mm (p&lt; 0.001) were significant at univariate logisticanalysis. Multivariate logistic analysis has shown that parameters independently associated with primary pancreaticadenocarcinoma were CRP &gt; 10 mg/dL (p= 0.012), CA 19-9 &gt; 230 U/mL (p= 0.043), and diameter of the Wirsung&gt; 3 mm (p= 0.005). Through these parameters, a diagnostic score has been developed to predict a primarypancreatic adenocarcinoma when &gt; 1 and a primary distal cholangiocarcinoma when &lt; 1.Conclusion:This feasible and low-cost diagnostic score could have a potential impact to differentiate pancreaticcancer histologic origin and to improve target therapeutic strategy

A prognostic score for predicting survival in patients with pancreatic head adenocarcinoma and distal cholangiocarcinoma

Background/aim: Survival of patients with pancreatic cancer remains poor despite improvements in therapeutic strategies. This study aims to create a novel preoperative score to predict prognosis in patients with tumors of the pancreaticobiliary head. Patients and methods: Data on 190 patients who underwent to pancreaticoduodenectomy at Sapienza University of Rome from January 2010 to December 2018 were retrospectively analyzed. After exclusion criteria, 101 patients were considered eligible for retrospective study. Preoperative biological, clinical and radiological parameters were considered. Results: Pancreatic ductal adenocarcinoma [hazard ratio (HR)=1.995, 95% confidence intervaI (CI)=1.1-3.3; p=0.01], carbohydrate antigen 19.9 (CA 19.9) &gt;230 U/ml (HR=2.414, 95% CI=2.4-1.5, p&lt;0.0001) and Wirsung duct diameter &gt;3 mm (HR=1.592, 95% CI=1.5-0.9; p=0.08) were the only parameters associated with poor prognosis. Through these parameters, a prognostic score (PHT score) was developed which predicted worst survival when exceeding 2 and better survival when ≤2. Conclusion: The PHT score may have a potential impact on predicting overall survival and consequently modulate the timing and type of treatment (up-front surgery vs. neoadjuvant therapy) patients are offered

Immunological backbone of uveal melanoma: is there a rationale for immunotherapy?

No standard treatment has been established for metastatic uveal melanoma (mUM). Immunotherapy is commonly used for this disease even though UM has not been included in phase III clinical trials with checkpoint inhibitors. Unfortunately, only a minority of patients obtain a clinical benefit with immunotherapy. The immunological features of mUM were reviewed in order to understand if immunotherapy could still play a role for this disease

Microchemical Investigation of Long-Term Buried Gilded and Silvered Artifacts From Ancient Peru

A large number of metal artifacts with exceptional artistic value of the Moche culture have been found in the tombs of the Lords of Sipán (Lambayeque, Peru) and of the Lady of Cao (El Brujo, Peru) characterized by different burial conditions. Some of the objects, dated around 300–400 AD, are constituted by substrates of Cu- or Ag-based alloys coated by uniformly distributed thin films of precious metal (1–4 microns) that create also polymetallic bicolored surfaces with "gold" and "silver" areas. In order to investigate the corrosion product structure and composition as well as to identify the techniques used to give the gold or silver appearance, an integrated analytical approach has been adopted. The selected complementary methodologies were scanning electron microscopy (SEM) coupled with energy-dispersive spectroscopy (EDS), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and optical microscopy (OM). The findings reveal that the substrates are mainly composed of Cu-Ag-Au alloys that at the site of Sipán have been almost completely corroded during the burial. Furthermore, the results show that the main aggressive agent is Cl– coming from the soil and that the degradation phenomena were likely enhanced by the galvanic coupling between the precious metal layer and the less noble substrate. The degradation products have formed mainly layered structures containing chloroargyrite (AgCl), cuprite (Cu2O), nantokite (CuCl), and atacamite [CuCl2.3Cu(OH)2] polymorphs. These latter species warn that dangerous copper cyclic corrosion is occurring, a harmful phenomenon, commonly defined as "bronze disease," which must be firmly mitigated. Finally, the findings reveal that the Moche metal workers used the depletion gilding to selectively modify the surface chemical composition of the artifacts to produce the Ag or Au thin films. According to this subtractive method, the surface of the Cu-Au-Ag alloys was enriched with a layer of precious metal by means of cycles of thermal treatments and removal of Cu or both Cu and Ag from the outermost region by using pickling solutions

A network approach to define the predictive role of immune profile on tumor response and toxicity of anti PD-1 single agent immunotherapy in patients with solid tumors

Background: The immune profile of each patient could be considered as a portrait of the fitness of his/her own immune system. The predictive role of the immune profile in immune-related toxicities (irAEs) development and tumour response to treatment was investigated. Methods: A prospective, multicenter study evaluating, through a multiplex assay, the soluble immune profile at the baseline of 53 patients with advanced cancer, treated with immunotherapy as single agent was performed. Four connectivity heat maps and networks were obtained by calculating the Spearman correlation coefficients for each group: responder patients who developed cumulative toxicity (R-T), responders who did not develop cumulative toxicity (R-NT), non-responders who developed cumulative toxicity (NR-T), non-responders who did not develop cumulative toxicity (NR-NT). Results: A statistically significant up-regulation of IL-17A, sCTLA4, sCD80, I-CAM-1, sP-Selectin and sEselectin in NR-T was detected. A clear loss of connectivity of most of the soluble immune checkpoints and cytokines characterized the immune profile of patients with toxicity, while an inversion of the correlation for ICAM-1 and sP-selectin was observed in NR-T. Four connectivity networks were built for each group. The highest number of connections characterized the NR-T. Conclusions: A connectivity network of immune dysregulation was defined for each subgroup of patients, regardless of tumor type. In patients with the worst prognosis (NR-T) the peculiar connectivity model could facilitate their early and timely identification, as well as the design of a personalized treatment approach to improve outcomes or prevent irAEs

Immune-related toxicity and soluble profile in patients affected by solid tumors: a network approach

Background: Immune checkpoint inhibitors (ICIs) have particular, immune-related adverse events (irAEs), as a consequence of interfering with self-tolerance mechanisms. The incidence of irAEs varies depending on ICI class, administered dose and treatment schedule. The aim of this study was to define a baseline (T0) immune profile (IP) predictive of irAE development. Methods: A prospective, multicenter study evaluating the immune profile (IP) of 79 patients with advanced cancer and treated with anti-programmed cell death protein 1 (anti-PD-1) drugs as a first- or second-line setting was performed. The results were then correlated with irAEs onset. The IP was studied by means of multiplex assay, evaluating circulating concentration of 12 cytokines, 5 chemokines, 13 soluble immune checkpoints and 3 adhesion molecules. Indoleamine 2, 3-dioxygenase (IDO) activity was measured through a modified liquid chromatography-tandem mass spectrometry using the high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method. A connectivity heatmap was obtained by calculating Spearman correlation coefficients. Two different networks of connectivity were constructed, based on the toxicity profile. Results: Toxicity was predominantly of low/moderate grade. High-grade irAEs were relatively rare, while cumulative toxicity was high (35%). Positive and statistically significant correlations between the cumulative toxicity and IP10 and IL8, sLAG3, sPD-L2, sHVEM, sCD137, sCD27 and sICAM-1 serum concentration were found. Moreover, patients who experienced irAEs had a markedly different connectivity pattern, characterized by disruption of most of the paired connections between cytokines, chemokines and connections of sCD137, sCD27 and sCD28, while sPDL-2 pair-wise connectivity values seemed to be intensified. Network connectivity analysis identified a total of 187 statistically significant interactions in patients without toxicity and a total of 126 statistically significant interactions in patients with toxicity. Ninety-eight interactions were common to both networks, while 29 were specifically observed in patients who experienced toxicity. Conclusions: A particular, common pattern of immune dysregulation was defined in patients developing irAEs. This immune serological profile, if confirmed in a larger patient population, could lead to the design of a personalized therapeutic strategy in order to prevent, monitor and treat irAEs at an early stage

Management of Germ Cell Tumors During the Outbreak of the Novel Coronavirus Disease-19 Pandemic:A Survey of International Expertise Centers

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has become a public health emergency affecting frail populations, including patients with cancer. This poses the question of whether cancer treatments can be postponed or modified without compromising their efficacy, especially for highly curable cancers such as germ cell tumors (GCTs). MATERIALS AND METHODS: To depict the state-of-the-art management of GCTs during the COVID-19 pandemic, a survey including 26 questions was circulated by e-mail among the physicians belonging to three cooperative groups: (a) Italian Germ Cell Cancer Group; (b) European Reference Network-Rare Adult Solid Cancers, Domain G3 (rare male genitourinary cancers); and (c) Genitourinary Medical Oncologists of Canada. Percentages of agreement between Italian respondents (I) versus Canadian respondents (C), I versus European respondents (E), and E versus C were compared by using Fisher's exact tests for dichotomous answers and chi square test for trends for the questions with three or more options. RESULTS: Fifty-three GCT experts responded to the survey: 20 Italian, 6 in other European countries, and 27 from Canada. Telemedicine was broadly used; there was high consensus to interrupt chemotherapy in COVID-19-positive patients (I = 75%, C = 55%, and E = 83.3%) and for use of granulocyte colony-stimulating factor primary prophylaxis for neutropenia (I = 65%, C = 62.9%, and E = 50%). The main differences emerged regarding the management of stage I and stage IIA disease, likely because of cultural and geographical differences. CONCLUSION: Our study highlights the common efforts of GCT experts in Europe and Canada to maintain high standards of treatment for patients with GCT with few changes in their management during the COVID-19 pandemic. IMPLICATIONS FOR PRACTICE: Despite the chaos, disruptions, and fears fomented by the COVID-19 illness, oncology care teams in Italy, other European countries, and Canada are delivering the enormous promise of curative management strategies for patients with testicular cancer and other germ cell tumors. At the same time, these teams are applying safe and innovative solutions and sharing best practices to minimize frequency and intensity of patient contacts with thinly stretched health care capacity

Spontaneous abortion: the importance of nursing and care aspects

non