Aryl–Cl vs heteroatom–Si bond cleavage on the route to the photochemical generation of σ,π-heterodiradicals

The photochemistry of aryl chlorides having a X-SiMe3 group (X = O, NR, S, SiMe2) tethered to the aromatic ring has been investigated in detail, with the aim to generate valuable ϭ,π-heterodiradicals. Two competitive pathways arising from the excited triplet state of the aromatics have been observed, namely heterolysis of the aryl–chlorine bond and homolysis of the X–silicon bond. The former path is found in chlorinated phenols and anilines, whereas the latter is exclusive in the case of silylated thiophenols and aryl silanes. A combined experimental/computational approach was pursued to explain such a photochemical behavior. Graphical abstract[Figure not available: see fulltext.

High Risk of Secondary Infections Following Thrombotic Complications in Patients With COVID-19

Background. This study’s primary aim was to evaluate the impact of thrombotic complications on the development of secondary infections. The secondary aim was to compare the etiology of secondary infections in patients with and without thrombotic complications. Methods. This was a cohort study (NCT04318366) of coronavirus disease 2019 (COVID-19) patients hospitalized at IRCCS San Raffaele Hospital between February 25 and June 30, 2020. Incidence rates (IRs) were calculated by univariable Poisson regression as the number of cases per 1000 person-days of follow-up (PDFU) with 95% confidence intervals. The cumulative incidence functions of secondary infections according to thrombotic complications were compared with Gray’s method accounting for competing risk of death. A multivariable Fine-Gray model was applied to assess factors associated with risk of secondary infections. Results. Overall, 109/904 patients had 176 secondary infections (IR, 10.0; 95% CI, 8.8–11.5; per 1000-PDFU). The IRs of secondary infections among patients with or without thrombotic complications were 15.0 (95% CI, 10.7–21.0) and 9.3 (95% CI, 7.9–11.0) per 1000-PDFU, respectively (P = .017). At multivariable analysis, thrombotic complications were associated with the development of secondary infections (subdistribution hazard ratio, 1.788; 95% CI, 1.018–3.140; P = .043). The etiology of secondary infections was similar in patients with and without thrombotic complications. Conclusions. In patients with COVID-19, thrombotic complications were associated with a high risk of secondary infections

Visible-Light-Mediated Divergent and Regioselective Vicinal Difunctionalization of Styrenes with Arylazo Sulfones

Activated by visible light, arylazo sulfones can serve as multifaceted reactants and are employed in diazenylation, sulfonylation, and arylation reactions under (photo)catalyst-free conditions. Such versatile reactivity enabled us to develop an operationally simple, regioselective, and tunable difunctionalization of styrenes with arylazo sulfones to produce α-sulfonyl arylhydrazones and 1,2-alkoxyarylated products in moderate to excellent yields. Furthermore, such difunctionalized products have been exploited as key building blocks for the synthesis of various heterocycles

Effect of Diabetes on Survival after Resection of Pancreatic Adenocarcinoma. A Prospective, Observational Study

<div><p>Aim</p><p>To investigate the effect of diabetes mellitus (DM) on disease-free and overall post-resection survival of patients with pancreatic ductal adenocarcinoma (PDAC)</p><p>Methods</p><p>Prospective observational study on patients admitted for pancreatic disease from January 2008 to October 2012. DM was classified as recent-onset (<48 months before PDAC diagnosis), longstanding (≥48 months before PDAC) or new onset (after surgery).</p><p>Results</p><p>Of 296 patients, 140 had a diagnosis of DM prior to surgery (26 longstanding, 99 recent-onset, 15 with unknown duration). Median follow-up time was 5.4 ± 0.22 years. Patients with recent onset DM had poorer postoperative survival than patients without DM: disease-free survival and overall survival were 1.14±0.13 years and 1.52±0.12 years in recent onset DM, versus 1.3±0.15 years and 1.87±0.15 years in non-diabetic patients (p = 0.013 and p = 0.025, respectively). Longstanding DM and postoperative new onset DM had no impact on prognosis. Compared to cases without DM, patients with recent onset DM were more likely to have residual disease after surgery and to develop liver metastases during follow-up. Multivariate analysis confirmed recent onset DM was independently associated with PDAC relapse (hazard ratio 1.45 [1.06–1.99]).</p><p>Conclusion</p><p>Preoperative recent onset DM has an impact on survival after the resection of PDAC.</p></div

Patients characteristics by postoperative diabetic status.

<p>Patients characteristics by postoperative diabetic status.</p

Effect of pre-operative recent onset DM on PDAC relapse.

<p>Kaplan-Meier estimates of disease free survival and stratified according to seven main recurrence sites for 255 patients (156 no diabetes; 99 recent onset diabetes) with a diagnosis of pancreatic ductal carcinoma submitted to pancreatectomy with radical intent from the Pancreatic Surgery Unit of the S. Raffaele Scientific Institute (2008–2012). The <i>X-axis</i> shows the time since pancreatectomy and the <i>y-axis</i> the PDAC recurrence-free probability. P value of <i>log</i>-<i>rank test</i> vs no diabetes are reported.</p

Effect of pre-operative DM on PDAC outcome.

<p>Kaplan-Meier estimates of disease-free (left) and overall (right) survival stratified according to pre-operative DM for 281 patients with a diagnosis of pancreatic ductal carcinoma submitted to pancreatectomy with radical intent from the Pancreatic Surgery Unit of the S. Raffaele Scientific Institute (2008–2012). At the time of PDAC diagnosis participants were classified as having: long-standing diabetes if they had a documented diagnosis of DM for ≥48 months; recent onset DM if participants were diagnosed with DM at the time of the diagnosis of PDAC or had a documented diagnosis of DM for <48 months. The <i>X-axis</i> shows the time since pancreatectomy. P value of <i>log</i>-<i>rank test</i> vs no diabetes are reported.</p

Patient characteristics by types of preoperative diabetes.

<p>Patient characteristics by types of preoperative diabetes.</p

How good is your marine protected area at curbing threats?

Marine protected areas (MPAs) are key tools to mitigate human impacts in coastal environments, promoting sustainable activities to conserve biodiversity. The designation of MPAs alone may not result in the lessening of some human threats, which is highly dependent on management goals and the related specific regulations that are adopted. Here, we develop and operationalize a local threat assessment framework. We develop indices to quantify the effectiveness of MPAs (or individual zones within MPAs in the case of multiple-use MPAs) in reducing anthropogenic extractive and non-extractive threats operating at local scale, focusing specifically on threats that can be managed through MPAs. We apply this framework in 15 Mediterranean MPAs to assess their threat reduction capacity. We show that fully protected areas effectively eliminate extractive activities, whereas the intensity of artisanal and recreational fishing within partially protected areas, paradoxically, is higher than that found outside MPAs, questioning their ability at reaching conservation targets. In addition, both fully and partially protected areas attract non-extractive activities that are potential threats. Overall, only three of the 15 MPAs had lower intensities for the entire set of eight threats considered, in respect to adjacent control unprotected areas. Understanding the intensity and occurrence of human threats operating at the local scale inside and around MPAs is important for assessing MPAs effectiveness in achieving the goals they have been designed for, informing management strategies, and prioritizing specific actionsVersión del editor4,11

European e-Delphi process to define expert consensus on electrochemotherapy treatment indications, procedural aspects, and quality indicators in melanoma

The application of electrochemotherapy in patients with melanoma lacks consensus regarding treatment indications, procedural aspects, and quality indicators. A large European expert panel engaged in a Delphi process, and provided consensus recommendations on patient selection criteria, procedural aspects of electrochemotherapy, and quality indicators with benchmarks to improve future research and current clinical practice.Lay summary Electrochemotherapy is an effective locoregional therapy for skin metastases from melanoma, a problem faced by almost half of patients with metastatic disease. The lack of comparative studies and the heterogeneity of its clinical application among centres make it challenging to support consistent, evidence-based recommendations. To address this unmet need, a three-round online survey was conducted to establish a consensus on treatment indications, standard operating procedures, and quality indicators. In the survey, a panel of 100 European melanoma experts agreed on 56 statements that can be used to improve patient selection, homogenize treatment application, and monitor outcomes.Background Skin metastases are an important co-morbidity in melanoma. Despite broad adoption, electrochemotherapy implementation is hindered by a lack of treatment indications, uncertainty regarding procedural aspects, and the absence of quality indicators. An expert consensus may harmonize the approach among centres and facilitate comparison with other therapies. Methods An interdisciplinary panel was recruited for a three-round e-Delphi survey. A literature-based 113-item questionnaire was proposed to 160 professionals from 53 European centres. Participants rated each item for relevance and degree of agreement on a five-point Likert scale, and received anonymous controlled feedback to allow revision. The items that reached concordant agreement in two successive iterations were included in the final consensus list. In the third round, quality indicator benchmarks were defined using a real-time Delphi method. Results The initial working group included 122 respondents, of whom 100 (82 per cent) completed the first round, thus qualifying for inclusion in the expert panel (49 surgeons, 29 dermatologists, 15 medical oncologists, three radiotherapists, two nurse specialists, two clinician scientists). The completion rate was 97 per cent (97 of 100) and 93 per cent (90 of 97) in the second and third rounds respectively. The final consensus list included 54 statements with benchmarks (treatment indications, (37); procedural aspects, (1); quality indicators, (16)). Conclusion An expert panel achieved consensus on the use of electrochemotherapy in melanoma, with a core set of statements providing general direction to electrochemotherapy users to refine indications, align clinical practices, and promote quality assurance programmes and local audits. The residual controversial topics set future research priorities to improve patient care