A MSFD complementary approach for the assessment of pressures, knowledge and data gaps in Southern European Seas : the PERSEUS experience

PERSEUS project aims to identify the most relevant pressures exerted on the ecosystems of the Southern European Seas (SES), highlighting knowledge and data gaps that endanger the achievement of SES Good Environmental Status (GES) as mandated by the Marine Strategy Framework Directive (MSFD). A complementary approach has been adopted, by a meta-analysis of existing literature on pressure/impact/knowledge gaps summarized in tables related to the MSFD descriptors, discriminating open waters from coastal areas. A comparative assessment of the Initial Assessments (IAs) for five SES countries has been also independently performed. The comparison between meta-analysis results and IAs shows similarities for coastal areas only. Major knowledge gaps have been detected for the biodiversity, marine food web, marine litter and underwater noise descriptors. The meta-analysis also allowed the identification of additional research themes targeting research topics that are requested to the achievement of GES. 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license.peer-reviewe

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Η έκφραση της Survivin στο ηπατοκυτταρικό καρκίνωμα και η σχέση της με τα κλινικοπαθολογοανατομικά χαρακτηριστικά και την κλινική έκβαση

Η έκφραση της Survivin αποτελεί έναν δυνητικό προγνωστικό δείκτη σε πολλά καρκινώματα. Ωστόσο, η προγνωστική αξία της για την επιβίωση στο ηπατοκυτταρικό καρκίνωμα (ΗΚΚ) παραμένει αμφιλεγόμενη. Σκοπός της μελέτης είναι να εξετάσει την έκφραση του αναστολέα της απόπτωσης Survivin στο ΗΚΚ και να διερευνήσει την συσχέτιση της με τα κλινικο-παθολογοανατομικά χαρακτηριστικά και την συνολική επιβίωση μετά την ηπατεκτομή. Εξήντα ασθενείς συμπεριλήφθηκαν στην μελέτη. Θετική έκφραση της Survivin διαπιστώθηκε σε 26 ασθενείς (43,3%). Η έκφραση της Survivin εμφάνιζε θετική στατιστικά σημαντική συσχέτιση με το βαθμό διαφοροποίησης του όγκου (p=0,000), την ύπαρξη δορυφόρων εστιών καρκινώματος (p=0,033) και την αγγειακή διήθηση (p=0,003). Στατιστικά σημαντική αρνητική συσχέτιση διαπιστώθηκε μεταξύ της έκφρασης της Survivin και του Bcl-2 (p=0,000) στους ασθενείς με θετική την έκφραση της Survivin. Δεν διαπιστώθηκε στατιστικώς σημαντική συσχέτιση της έκφρασης της Survivin με τους υπόλοιπους παράγοντες που εξετάσθηκαν (φύλο, F-score, μέγεθος του όγκου, μη διηθημένα χειρουργικά όρια, τύπος ηπατεκτομής, επιπλοκές επέμβασης, προϋπάρχουσα Ηπατίτιδα Β/C και ηλικία). Όσον αφορά την επιβίωση, ο συσχετισμός μεταξύ της επιβίωσης και των 16 ανεξάρτητων μεταβλητών κατέδειξε στατιστικά σημαντική αρνητική συσχέτιση με τους θετικούς στην Survivin ασθενείς (p=0,007), τους ασθενείς που έχουν υποβληθεί σε μείζονα (4 τμήματα και άνω) ηπατεκτομή (p=0,05) και στις περιπτώσεις των ασθενών με αγγειακή διήθηση (p=0,03). Αντίθετα, στατιστικά σημαντική θετική συσχέτιση καταγράφηκε με τα αρνητικά χειρουργικά όρια (> 1 εκ.) (p=0,000). Δεν διαπιστώθηκε στατιστικά σημαντική συσχέτιση μεταξύ της επιβίωσης και των υπόλοιπων ανεξάρτητων μεταβλητών (μέγεθος όγκου, Bcl-2 έκφραση, φύλο, διαφοροποίηση του όγκου, δορυφόρες εστίες, επιπλοκές, ιστορικό ηπατίτιδων, μεταγγίσεις και ηλικία). Κατά την πολυπαραγοντική ανάλυση της επιβίωσης (Cox regression), η συνολική επιβίωση συσχετιζόταν σημαντικά με την θετική ανοσοέκφραση της Survivin (p=0,007) και τον χαμηλό βαθμό διαφοροποίησης (p=0,000), με τις δυο αυτές μεταβλητές να αντιπροσωπεύουν αρνητικούς προγνωστικούς παράγοντες για τους ασθενείς με ΗΚΚ. Στην πολυπαραγοντική ανάλυση της επιβίωσης, η ανοσοέκφραση της Bcl-2 δεν φάνηκε να επηρεάζει στατιστικώς την επιβίωση στους ασθενείς με θετική έκφραση survivin, ακόμα και αν διαπιστώθηκε στατιστικά αρνητικός συσχετισμός στην έκφραση της survivin και του Bcl-2. Από την μελέτη προκύπτει ότι η έκφραση της Survivin αντανακλά περιπτώσεις ΗΚΚ με επιθετική ιστολογική και κλινική συμπεριφορά και συσχετίζεται με φτωχότερη συνολική επιβίωση. Κατ΄αυτό τον τρόπο καταδεικνύεται η προγνωστική σημασία της Survivin στο ΗΚΚ. Περαιτέρω μελέτες είναι απαραίτητες για να επιβεβαιωθεί εάν η Survivin μπορεί να χρησιμοποιηθεί ως προγνωστικός βιοδείκτης και κατ’ επέκταση την μελλοντική δυνατότητα αξιοποίησης της Survivin σε στοχευμένη θεραπεία στο ΗΚΚ.Survivin expression is a potential prognostic indicator in various carcinomas. The prognostic value of Survivin for survival in hepatocellular carcinoma, (HCC) however, remains controversial. The aim of the study is to examine the expression of the inhibitor of apoptosis Survivin in HCC, and investigate the correlation with the clinic-pathologic characteristics and overall survival (OS) following surgical resection. Sixty patients were included in the study. Survivin was expressed in 26 patients (43.3%). Survivin expression was significantly correlated to OS (p=0.014). Survivin expression was found to have statistically more frequent positive expression in patients with advanced tumor grade (p<0.001), in the cases with satellite nodules (p=0.033) and when microvascular and major vascular invasion was present (p=0.003). A statistically significant negative correlation between Survivin and BCL-2 was also noted (p=0.000). No significant correlation with sex, F-score, tumor size, clear surgical margins, extent of hepatectomy, complications, viral infection and patient age was noted. Regarding OS, in univariate unifactorial analysis using the Kaplan-Meier curves, survival was found to be significantly higher in patients with negative margins (p=0.000), negative Survivin expression (p=0.007), less extensive operations (p=0.05) and no vascular invasion (p-0,03). No significant correlation was noted between survival outcomes and the other independent variables (tumor size, BCL-2 staining, sex, grading, F-score, complications, HBV history, transfusion blood units and age). In multivariate analysis of survival (Cox Regression), using variables with differences in survival in univariate analysis (margin status, Survivin expression, vascular invasion, extent of surgery,) no variable was found to be an independent predictor of survival. Survivin expression reflects aggressive histological and clinical behavior of HCC and correlates with poorer OS. Further studies are required to confirm if Survivin can be used as a predictive biomarker to evaluate prognosis and target treatments for HCC

Expression of Survivin in hepatocellular carcinoma and correlation with clinicopathological characteristics and survival

Survivin expression is a potential prognostic indicator in various carcinomas. The prognostic value of Survivin for survival in hepatocellular carcinoma, (HCC) however, remains controversial. The aim of the study is to examine the expression of the inhibitor of apoptosis Survivin in HCC, and investigate the correlation with the clinic-pathologic characteristics and overall survival (OS) following surgical resection. Sixty patients were included in the study. Survivin was expressed in 26 patients (43.3%). Survivin expression was significantly correlated to OS (p=0.014). Survivin expression was found to have statistically more frequent positive expression in patients with advanced tumor grade (p 1 εκ.) (p=0,000). Δεν διαπιστώθηκε στατιστικά σημαντική συσχέτιση μεταξύ της επιβίωσης και των υπόλοιπων ανεξάρτητων μεταβλητών (μέγεθος όγκου, Bcl-2 έκφραση, φύλο, διαφοροποίηση του όγκου, δορυφόρες εστίες, επιπλοκές, ιστορικό ηπατίτιδων, μεταγγίσεις και ηλικία). Κατά την πολυπαραγοντική ανάλυση της επιβίωσης (Cox regression), η συνολική επιβίωση συσχετιζόταν σημαντικά με την θετική ανοσοέκφραση της Survivin (p=0,007) και τον χαμηλό βαθμό διαφοροποίησης (p=0,000), με τις δυο αυτές μεταβλητές να αντιπροσωπεύουν αρνητικούς προγνωστικούς παράγοντες για τους ασθενείς με ΗΚΚ. Στην πολυπαραγοντική ανάλυση της επιβίωσης, η ανοσοέκφραση της Bcl-2 δεν φάνηκε να επηρεάζει στατιστικώς την επιβίωση στους ασθενείς με θετική έκφραση survivin, ακόμα και αν διαπιστώθηκε στατιστικά αρνητικός συσχετισμός στην έκφραση της survivin και του Bcl-2. Από την μελέτη προκύπτει ότι η έκφραση της Survivin αντανακλά περιπτώσεις ΗΚΚ με επιθετική ιστολογική και κλινική συμπεριφορά και συσχετίζεται με φτωχότερη συνολική επιβίωση. Κατ΄αυτό τον τρόπο καταδεικνύεται η προγνωστική σημασία της Survivin στο ΗΚΚ. Περαιτέρω μελέτες είναι απαραίτητες για να επιβεβαιωθεί εάν η Survivin μπορεί να χρησιμοποιηθεί ως προγνωστικός βιοδείκτης και κατ’ επέκταση την μελλοντική δυνατότητα αξιοποίησης της Survivin σε στοχευμένη θεραπεία στο ΗΚΚ

Cancer therapy and cardiovascular risk: focus on bevacizumab

Recognition and management of treatment-related cardiovascular toxicity, defined as either an acute cardiac event or a chronic condition, has been tightly integrated into routine cancer care and has become an important component in treatment selection. Several chemotherapeutic agents, such as anthracyclines, are traditionally characterized as cardiotoxic, but cardiovascular adverse events are also associated with commonly used molecular targeted therapies. In the past decade, bevacizumab, a monoclonal humanized antibody against vascular endothelial growth factor, has been introduced in the treatment of a variety of metastatic malignancies. Despite its efficacy, bevacizumab has been associated with significant risk of cardiovascular complications, such as hypertension, cardiac ischemia, and congestive heart failure. This review will focus on the cardiovascular toxicity of bevacizumab, providing the latest evidence on the incidence, clinical spectrum, risk factors, and responsible mechanisms

Adrenal Incidentalomas in Cancer Patients Are Not Always “Innocent”: A Case Report and Review of the Literature

Herein, we report an unusual case of a 78-year-old woman with synchronous presentation of sigmoid cancer and a nonfunctioning primary adrenal cortex carcinoma, who developed superior vena cava syndrome due to metastatic lymphadenopathy from the latter malignancy. Our case suggests that adrenal incidentalomas during initial staging evaluation after cancer diagnosis are not always “innocent” and should not be “a priori” considered incidental findings attributed to hyperplasia, adenoma or even a non life-threatening metastasis from the primary tumor. It also emphasizes the importance of a continuous assessment of patients with synchronous primary malignancies, in order to timely evaluate changes in clinical or biological behavior and administrate the appropriate treatment

The ChoCO-W prospective observational global study: Does COVID-19 increase gangrenous cholecystitis?

BACKGROUND: The incidence of the highly morbid and potentially lethal gangrenous cholecystitis was reportedly increased during the COVID-19 pandemic. The aim of the ChoCO-W study was to compare the clinical findings and outcomes of acute cholecystitis in patients who had COVID-19 disease with those who did not. METHODS: Data were prospectively collected over 6 months (October 1, 2020, to April 30, 2021) with 1-month follow-up. In October 2020, Delta variant of SARS CoV-2 was isolated for the first time. Demographic and clinical data were analyzed and reported according to the STROBE guidelines. Baseline characteristics and clinical outcomes of patients who had COVID-19 were compared with those who did not. RESULTS: A total of 2893 patients, from 42 countries, 218 centers, involved, with a median age of 61.3 (SD: 17.39) years were prospectively enrolled in this study; 1481 (51%) patients were males. One hundred and eighty (6.9%) patients were COVID-19 positive, while 2412 (93.1%) were negative. Concomitant preexisting diseases including cardiovascular diseases (p < 0.0001), diabetes (p < 0.0001), and severe chronic obstructive airway disease (p = 0.005) were significantly more frequent in the COVID-19 group. Markers of sepsis severity including ARDS (p < 0.0001), PIPAS score (p < 0.0001), WSES sepsis score (p < 0.0001), qSOFA (p < 0.0001), and Tokyo classification of severity of acute cholecystitis (p < 0.0001) were significantly higher in the COVID-19 group. The COVID-19 group had significantly higher postoperative complications (32.2% compared with 11.7%, p < 0.0001), longer mean hospital stay (13.21 compared with 6.51 days, p < 0.0001), and mortality rate (13.4% compared with 1.7%, p < 0.0001). The incidence of gangrenous cholecystitis was doubled in the COVID-19 group (40.7% compared with 22.3%). The mean wall thickness of the gallbladder was significantly higher in the COVID-19 group [6.32 (SD: 2.44) mm compared with 5.4 (SD: 3.45) mm; p < 0.0001]. CONCLUSIONS: The incidence of gangrenous cholecystitis is higher in COVID patients compared with non-COVID patients admitted to the emergency department with acute cholecystitis. Gangrenous cholecystitis in COVID patients is associated with high-grade Clavien-Dindo postoperative complications, longer hospital stay and higher mortality rate. The open cholecystectomy rate is higher in COVID compared with non -COVID patients. It is recommended to delay the surgical treatment in COVID patients, when it is possible, to decrease morbidity and mortality rates. COVID-19 infection and gangrenous cholecystistis are not absolute contraindications to perform laparoscopic cholecystectomy, in a case by case evaluation, in expert hands

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P &lt; 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)