Effects of naringenin and its phase II metabolites on in vitro human macrophage gene expression.

Naringenin, together with its glycosidic forms, is a flavanone abundant in grapefruit and orange. It has been detected in human plasma, following citrus juice intake, at sub-µmolar concentrations, and its main phase II conjugated metabolites (naringenin-7-O-glucuronide and narigenin-4’-O-glucuronide) have been identified in urine. Recent evidence suggests a potential active anti-inflammatory role of flavonoids on macrophages, cells actively involved in atherogenesis. The aim of this study was to evaluate the effects of naringenin and its phase II metabolites on the expression of specific genes in differently activated macrophages at concentrations coherent with dietary exposure. Results suggest that phase II metabolites, as well as the aglyconic form of naringenin, were able to perturb macrophage gene expression in directions that are not always consistent with anti-inflammatory effects. Moreover, the effects of metabolites were not always consistent with each other and with those of their aglycone, underlining the paramount importance of testing physiological forms of phytochemicals within in vitro experimental models. In vivo studies are needed to further explore these observations and investigate their practical consequences

Transcriptome profiling in lympho-monocytes of healthy subjects identifies a biomarker of early insulin resistance with potential implications in chronic heart failure

Background and aims: Gene expression profile (GEP) of peripheral blood mononuclear cells (PBMCs) is significantly affected by various diseases and may serve as biomarker of pathological changes occurring in other tissues. The aim of our study was to investigate whether insulin resistance (IR) per se is characterized by a specific pattern of GEP. Materials and methods: 150 healthy young adults, were recruited in a cardiovascular risk assessment study (Multi-Knowledge project).Two groups of 10 subjects with extreme HOMAIR indices (High HOMA:4.0\ub12.8; Low HOMA:0.5\ub10.1), but with normal, similar BMI (22.2\ub12.6 vs 22.5\ub12.2 kg/m2), and comparable age (33.9\ub16.2 vs 40.2\ub1 11.3 years) and gender (7 M and 3 F in both groups) were selected. Standard anthropometric, hemodynamic, and metabolic variables were assessed. GEP of PBMCs from all subjects was evaluated using Agilent whole genome oligonucleotide mRNA microarrays. Data were analyzed with a novel ad-hoc rank-based classification method, optimized to extract a gene expression signature with highest power and statistical significance (p at least<0.005) to discriminate the two groups. Gene enrichment analysis was applied on the significant differentially expressed list of genes. All analyses were performed with R and Matlab. Results:We identified a set of 512 probes corresponding to 321 annotated genes which summarize the characteristics of each sample and allow distinguishing Low HOMA and High HOMA subjects with an accuracy of 100%, according to a 5-fold cross-validation approach. Gene enrichment analysis of the 321 genes showed significant enrichment for the KEGG pathway \u201cAdrenergic signaling in cardiomyocytes\u201d, in which differentially expressed genes were compatible with a cluster of alterations, including increased intracellular cAMP and Ca2+ and accelerated apoptosis in the High HOMA group. We hypothesized that this pathway should biomark chronic heart failure (CHF), of which IR is a known risk factor. In two publicly available gene expression data sets (GSE21125 and GSE9128) we investigated whether the genes in the pathway of interest could differentiate between patients with CHF and controls. Two biomarkers (length 41 and 22, respectively) were found with high discriminant accuracy (95%), at a significant p value (p<0.02), overlapping with the \u201cadrenergic signaling in cardiomyocytes\u201d pathway. Conclusion: GEP of the \u201cadrenergic signaling pathway in cardiomyocytes\u201d in lymphomocytes is a fingerprint of IR and is implicated also as a biomarker of patients with CHF. This may be a major molecular platform linking IR to CHF

Effects of naringenin and its phase II metabolites on in vitro human macrophage gene expression

Naringenin, together with its glycosidic forms, is a flavanone abundant in grapefruit and orange. It has been detected in human plasma, following citrus juice intake, at sub-\u3bcmolar concentrations, and its main phase II conjugated metabolites (naringenin-7-O-glucuronide and narigenin-4'-O-glucuronide) have been identified in urine. Recent evidence suggests a potential active anti-inflammatory role of flavonoids on macrophages, cells actively involved in atherogenesis. The aim of this study was to evaluate the effects of naringenin and its phase II metabolites on the expression of specific genes in differently activated macrophages at concentrations coherent with dietary exposure. Results suggest that phase II metabolites, as well as the aglyconic form of naringenin, were able to perturb macrophage gene expression in directions that are not always consistent with anti-inflammatory effects. Moreover, the effects of metabolites were not always consistent with each other and with those of their aglycone, underlining the paramount importance of testing physiological forms of phytochemicals within in vitro experimental models. In vivo studies are needed to further explore these observations and investigate their practical consequences. \ua9 2013 Informa UK Ltd. All rights reserved

Correction: Evolving Trends in the Management of Acute Appendicitis During COVID-19 Waves: The ACIE Appy II Study

Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide

Evolving Trends in the Management of Acute Appendicitis During COVID-19 Waves: The ACIE Appy II Study

Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide

Correction: Evolving Trends in the Management of Acute Appendicitis During COVID-19 Waves: The ACIE Appy II Study (World Journal of Surgery, (2022), 46, 9, (2021-2035), 10.1007/s00268-022-06649-z)

In the original online version of this article Oreste Claudio Buonomo’s family name was misspelled. The original article was corrected

Global attitudes in the management of acute appendicitis during COVID-19 pandemic: ACIE Appy Study

676sinoneBackground: Surgical strategies are being adapted to face the COVID-19 pandemic. Recommendations on the management of acute appendicitis have been based on expert opinion, but very little evidence is available. This study addressed that dearth with a snapshot of worldwide approaches to appendicitis. Methods: The Association of Italian Surgeons in Europe designed an online survey to assess the current attitude of surgeons globally regarding the management of patients with acute appendicitis during the pandemic. Questions were divided into baseline information, hospital organization and screening, personal protective equipment, management and surgical approach, and patient presentation before versus during the pandemic. Results: Of 744 answers, 709 (from 66 countries) were complete and were included in the analysis. Most hospitals were treating both patients with and those without COVID. There was variation in screening indications and modality used, with chest X-ray plus molecular testing (PCR) being the commonest (19·8 per cent). Conservative management of complicated and uncomplicated appendicitis was used by 6·6 and 2·4 per cent respectively before, but 23·7 and 5·3 per cent, during the pandemic (both P &lt; 0·001). One-third changed their approach from laparoscopic to open surgery owing to the popular (but evidence-lacking) advice from expert groups during the initial phase of the pandemic. No agreement on how to filter surgical smoke plume during laparoscopy was identified. There was an overall reduction in the number of patients admitted with appendicitis and one-third felt that patients who did present had more severe appendicitis than they usually observe. Conclusion: Conservative management of mild appendicitis has been possible during the pandemic. 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E.; Moro-Valdezate, D.; Pertile, D.; Giusti, D. M.; Keller, D. S.; Tarik, D.; Kalivaci, D.; Mazingi, D.; Maldonado-Pintado, D. G.; Sasia, D.; Linardoutsos, D.; Osilli, D.; Murrone, D.; Russello, D.; Rodas, E.; Roa, E. A. A.; Ricciardi, E.; Rosso, E.; Saladino, E.; Flores-Villalba, E.; Ajs, E. R.; Smith-Singares, E.; Baili, E.; Kouroumpas, E.; Bourmpouteli, E.; Douka, E.; Martin-Perez, E.; Guaitoli, E.; Samadov, E.; Francone, E.; Vaterlini, E.; Morales, E.; Pena, E.; Zhao, E.; Andres, E. D. P.; Benzoni, E.; Erdas, E.; Pinotti, E.; Colas-Ruiz, E.; Aytac, E.; Laterza, E.; Agastra, E.; Foianini, E.; Moscoso, E.; Laviano, E.; Marra, E.; Cardamone, E.; Licardie, E.; Mpaili, E.; Pinna, E.; Varo, E.; Navarro, F. M.; Marino, F.; Medas, F.; Romano, F.; Maraska, F.; Saliu, F.; Madrid, F.; Rosa, F.; Mastella, F.; Gheza, F.; Luvisetto, F.; Alconchel, F.; Vieira, F. M.; Pareja, F.; Agresta, F.; Luna, F.; Bonilla, F.; Cordera, F.; Burdio, F.; Mendoza-Moreno, F.; Flores, F. M.; Aranda, F. P.; Taylor, F.; Ramos, F. L.; Fernandes, F.; Tropeano, F. P.; Balestra, F.; Bianco, F.; Ceci, F.; Colombo, F.; Di Marzo, F.; Ferrara, F.; Lancellotti, F.; Lazzarin, F.; Litta, F.; Martini, F.; Pizza, F.; Roscio, F.; Virdis, F.; Antona, F. B.; Ramirez, F. C.; Fernandez, F. M.; Llinares, F. O.; Quezada, F.; Schlottmann, F.; Quezada, F.; Herrera-Almario, G.; Massaferro, G.; Bislenghi, G.; van Ramshorst, G.; Gallo, G.; Luglio, G.; Bointas, G.; Kampouroglou, G.; Papadopoulos, G.; Manrique, G. A.; Calini, G.; Nastri, G.; Formisano, G.; Galiffa, G.; Palini, G. M.; Colucci, G.; Pagano, G.; Pellino, G.; Vanni, G.; Pattacini, G. C.; Gravante, G.; De Paola, G.; Lisi, G.; Partida, G.; Bellanova, G.; De Nobili, G.; Necchi, G. S.; Sinibaldi, G.; Tebala, G.; Bagaglini, G.; Izzo, G.; Argenio, G.; Brisinda, G.; Candilio, G.; Di Grezia, G.; Esposito, G.; Faillace, G.; Frazzetta, G.; La Gumina, G.; Nigri, G.; Romeo, G.; Amatriain, G. C.; Ortega, G.; Martin-Martin, G.; Stavrou, G. A.; Gunadi, ; Ugon, G. A.; Machain, G.; Marcucci, G.; Martinez-Mier, G.; Machain, G. M.; Nari, G.; Calvo, H.; Fathy, H.; Hamilto, ; Ahmed, H.; Faraj, H.; Nava, H.; Macias, H. O.; Nikaj, H.; Solano, H.; Khan, H. A.; Alarcon, H. S.; Ebied, H.; Giani, I.; Ateca, I. V.; Neri, I.; Roman, I. A. S.; Fidoshev, I.; Rodriguez, I. M.; Negoi, I.; Ortega, I.; Bernescu, I.; Russo, I. S.; Rodriguez, I. V.; Palomares, I.; Baltazar, I.; Torrejimeno, I. J.; Jurado, I. M. C.; Reccia, I.; Hussain, I.; Toledo, I. B.; Mora-Guzman, I.; Dogaru, I.; Romic, I.; Balciscueta, I.; Kenington, J. C.; Sagolsem, J.; Jang, J. Y.; Olivier, J.; Lammel-Lindemann, J.; Dziakova, J.; Villavicencio, J. I. R.; Salinas, J.; Parreira, J. P. J. G.; Jovanovic, ; Perez, J. R.; Reyes, J. A. S.; Luque, J. A. M.; Mak, J.; Rodriguez, J. S.; Kok, J. H. H.; Krook, J.; Diaz-Elizondo, J. A.; Castell, J.; Garcia-Flores, J. E.; Navalon, J. M. J.; Rodrigues, J. M. S.; Pereira, J.; Gomez, J. T. C.; Luque, J. B.; del Olmo, J. C. M.; Salamea, J. C.; Olivier, J. F. C.; Laina, J. L. B.; Ordonez, J. M.; Gutierrez, J.; Abba, J.; Sofi, J. A.; Sherafgan, K.; Sahnan, K.; Yanaga, K.; Beatson, K.; Asim, L.; Alvarez, L.; Siragusa, L.; Farber, L.; Ong, L.; Athanasios, L.; Garcia-Bruna, L.; De Martino, L.; Ferrario, L.; Giordano, L.; Gordini, L.; Pio, L.; Ponchietti, L.; Moletta, L.; Curella, L.; Poggi, L.; Taglietti, L.; Bonavina, L.; Conti, L.; Goffredi, L.; Ruiz, L. A. G.; Barrionuevo, L.; Fregoso, L. E.; Cabrera, L. F.; Rodriguez, L. G.; Grande, L.; Osoria, L. G.; Gonzalez, L. J. K.; Sanchez-Guillen, L.; Tallon-Aguilar, L.; Tresierra, L.; Giavarini, L.; Hasabelnabi, M.; Odovic, M.; Uemura, M.; Khan, M.; Artiles-Armas, M.; David, M.; Di Martino, M.; Spampinato, M. G.; Ribeiro, M. A. F.; Viola, M.; Angrisani, M.; Calussi, M.; Cannistra, M.; Catarci, M.; Cereda, M.; Conte, M.; Giordano, M.; Pellicciaro, M.; Marino, M. V.; Vaterlini, M. E.; Jimenez, M. F.; Lolli, M. G.; Bellini, M. I.; Lemma, M.; Chiarello, M. M.; Nicola, M.; Arrigo, M.; Mejia, M. C.; Manrique, M. M.; Rodriguez-Lopez, M.; Serradilla-Martin, M.; Lara, M. Z.; Martinez, M.; Bagnall, M.; Peter, M.; Lara, M. C.; Gomez, M. J.; Paniagua-Garcia-Senorans, M.; Gonzalez, M. P.; Rutegard, M.; Salo, M.; Franceschilli, M.; Silveri, M.; Veroux, M.; Pezzulo, M.; Nardi, M.; Rottoli, M.; Tolonen, M.; Ciro, M. P.; Zuluagua, M.; Cannavo, M.; Cervellera, M.; Iacobone, M.; Montuori, M.; Podda, M.; Dominguez, M. G.; Bingol-Kologlu, M.; Tahir, M.; Lim, M.; Wilson, M. S.; Wilson, M.; Campanelli, M.; Bisaccia, M.; De Rosa, M.; Maruccia, M.; Paterno, M.; Pisano, M.; Torre, M.; Trevino, M.; Zuolo, M.; Hernandez Bartolome, M. A.; Farina, M.; Pera, M.; Calvo, M. P.; Sotelo, M.; Thway, M. M.; Hassan, M.; Hassan, M. S. E.; Azfar, M.; Bouhuwaish, M.; Taha, M.; Zaieem, M.; Korkoman, M.; Guraieb, M.; Shalaby, M.; Raza, M. A.; Younis, M. U.; Elhadi, M.; Ali, M. Z.; Quazi, N.; Dudi-Venkata, N. N.; Alselaim, N.; Loria, N.; Ramirez, N. V.; Than, N. W.; Smart, N.; Trelles, N.; Pinto, N.; Allievi, N.; Petrucciani, N.; Antonacci, N.; Cillara, N.; Gica, N.; Cristiana, N. D.; Krystek, N.; Falco, N.; Pecorelli, N.; Tamini, N.; Dallas, N. A.; Machairas, N.; Brito, N.; Fieturi, N. A.; Ortega, N.; Mercado, O. A.; Irkorucu, O.; Alsherif, O.; Valles, O.; Ioannidis, O.; Palmas, O. H.; Palmas, O. I. H.; Guadarrama, O. S.; Bozbiyik, O.; Omelanczuk, P.; Ottolino, P.; Rodrigues, P.; Ruiz, P.; Campenni, P.; Chiarade, P.; Olivares, P. P.; Baroffio, P.; Panaccio, P.; Wintringer, P.; Di Fronzo, P.; Talento, P.; Favoriti, P.; Sendino, P.; Marsanic, P.; Mifsut, P.; Andrade, P.; Ajawin, P.; Abadia-Barno, P.; Castaneda, P. A. N.; Arevalos, P. O. S.; Bellver, P. P.; Koh, P. S.; Souza, P.; Major, P.; Bali, R. S.; Khattar, R. M.; Melo, R. B.; Ebrahiminia, R.; Azar, R.; Murga, R. L.; Caruso, R.; Pirolo, R.; Brady, R.; Davies, R. J.; Dholakia, R.; Rattan, R.; Singhal, R.; Lim, R.; Angelico, R.; Isernia, R. M.; Tutino, R.; Faccincani, R.; Peltrini, R.; Carrera-Ceron, R.; Tejos, R.; Kashyap, R.; Fajardo, R.; Lozito, R.; Pareja, R. M.; Garbarino, S.; Di Saverio, S.; Morales-Conde, S.; Benli, S.; Mansour, S.; Flores, S.; Suarez, S. L.; Ben, S. L.; Fuentes, S.; Napetti, S.; de Guzman, S. O.; Awad, S.; Weckmann Lujan, S. A.; Gentilli, S.; Grimaldi, S.; Pizarro, S. O.; Tayar, S.; Nabi, S.; Chan, S. M.; Junaid, S.; Rojas, S.; Monetti, S.; Garcia, S.; Salvans, S.; Tenconi, S.; Shaw, S.; Santoni, S.; Parra, S. A.; Cardenas, S.; Perez-Bertolez, S.; Chiappetta, S.; Dessureault, S.; Delis, S.; Bonapasta, S. A.; Rausei, S.; Scaringi, S.; Keswani, S.; Ali, S. M.; Cetinkunar, S.; Fung, T. L. D.; Rawashdeh, T.; Lopez, T. N.; De Campos, T.; Duque, T. C.; Perra, T.; Liakakos, T.; Daskalakis, T.; Liakakos, T.; Barnes, T.; Koeter, T.; Zalla, T.; Gonzalez, T. E.; Elosua, T.; Campagnaro, T.; Brown, T.; Luoto, T.; Oumar, T. A.; Giustizieri, U.; Grossi, U.; Bracale, U.; Rivas, U.; Sosa, V.; Testa, V.; Andriola, V.; Tonini, V.; Balassone, V.; Celentano, V.; Progno, V.; Raju, V.; Carroni, V.; Cavallaro, V.; Katta, V. R.; De Simone, V.; Romaguera, V. P.; Orozco, V. H. G.; Luraschi, V.; Rachkov, V.; Turrado-L, V.; Visag-Castillo, V.; Dowling, V.; Graham, V.; Papagni, V.; Vigorita, V.; Fonseca, V. C.; Carneros, V. J.; Bellato, V.; Goncalves, W.; Powers, W. F.; Grigg, W.; Bechstein, W. O.; Lim, Y. B.; Altinel, Y.; Golubovic, Z.; Balciscueta, Z