Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic

A Short and Convenient Chemical Route to Optically Pure 2-Methyl Chromanmethanols. Total Asymmetric Synthesis of β-, γ-, and δ-Tocotrienols

(Chemical Equation Presented) With use of inexpensive commercially available raw materials, chromanmethanol precursors to the natural β-, γ-, and δ-tocotrienols have been prepared in high yield. Enzymatic resolution afforded chiral chromanmethanols in high enantiomeric excess. Subsequent attachment of the farnesyl side chain was high yielding, thus allowing the preparation of asymmetric β-, γ-, and δ-tocotrienols in one final step wherein simultaneous deprotection of the phenol and removal of the sulfone group occurs. This chemistry provides the first synthesis of natural-series β-tocotrienol

Nuove oxazinine dai mitili contaminati del Mar Adriatico

L???aumento delle intossicazioni, dovute all???ingestione di molluschi contaminati, determina non solo gravi problemi sanitari, ma anche ingenti perdite economiche all???industria marina. L???avvelenamento dei molluschi è connesso alla produzione di biotossine marine da parte di microalghe. I mitili, infatti, filtrando il plancton marino, possono accumulare livelli di tossine tali da poter essere letali per l???uomo. Per minimizzare tale rischio, è nata la necessità di continui controlli dei molluschi raccolti nelle aree più a rischio. A tal scopo, il nostro gruppo di ricerca ha intrapreso da diversi anni un programma di monitoraggio dei mitili provenienti dalle coste del Mar Adriatico Settentrionale, dove si concentra il 90 % della produzione nazionale. Nel corso di queste analisi abbiamo isolato biotossine di tipo DSP (Diarrhetic Shellfish poisoning)1 e delle yessotossine, alcune delle quali sembrano essere peculiari dei nostri mari. In aggiunta a queste classiche biotossine marine, seguendo la tossicità delle frazioni isolate, sono stati trovati e caratterizzati da un punto di vista stereostrutturale anche altri composti citotossici, appartenenti alla classe dei clorosolfolipidi3 e delle oxazinine4. Il ritrovamento di queste sostanze aggrava ulteriormente i rischi sanitari collegati al consumo dei molluschi. Recentemente, l???analisi di una partita di mitili (Mytilus galloprovincialis) raccolta dalle acque di Cesenatico nel 2002 ha permesso di isolare delle nuove oxazinine citotossiche, la cui determinazione stereostrutturale è stata effettuata attraverso una dettagliata analisi spettroscopica NMR. La loro attività citotossica è stata valutata calcolando la percentuale di inibizione di crescita su linee cellulari WEHI 164 e J774. 1. Fattorusso, E.; Ciminiello, P.; Costantino, V.; Magno, S.; Mangoni, A.; Milandri, A.; Poletti, R.; Pompei, M.; Viviani, R. Mar. Poll. Bull.1992, 24, 234. 2. Ciminiello, P.; Fattorusso, E.; Forino, M.; Poletti, R.; Viviani, R. Chem. Res. in Toxicology. 2000, 13, 770. 3. Ciminiello, P.; Fattorusso, E.; Forino, M.; Di Rosa, M.; Ianaro, A.; Poletti, R. J. Org. Chem. 2001, 66, 578. 4. Ciminiello, P.; Dell???Aversano, C.; Fattorusso, E.; Forino, M.; Magno, S.; Ianaro, A.; Di Rosa, M. Eur. J. Org. Chem.2001, 1, 49

New adamantane derivatives with sigma affinity and antiproliferative activity

The synthesis of 4-(1-adamantyl)-4,4-diarylbutylamines 1, 5-(1-adamantyl)-5,5-diarylpentylamines 2 and 6-(1-adamantyl)-6,6- diarylhexylamines 3 is described and the σ1, σ2-receptors and sodium channels binding affinity of compounds 1 were investigated. The in vitro activity of compounds 1, 2 and 3 against main cancer cell lines is significant. One of the most active analogs, 1a, had an interesting in vivo anticancer profile against the ovarian cancer cell line IGROV-1, which was associated with an anagelsic activity against the neuropathic pain induced by the main anticancer drugs. © 2012 Bentham Science Publishers

New Adamantane Phenylalkylamines with σ‑Receptor Binding Affinity and Anticancer Activity, Associated with Putative Antagonism of Neuropathic Pain

The synthesis of the adamantane phenylalkylamines <b>2a</b>–<b>d</b>, <b>3a</b>–<b>c</b>, and <b>4a</b>–<b>e</b> is described. These compounds exhibited significant antiproliferative activity, in vitro, against eight cancer cell lines tested. The σ₁, σ₂, and sodium channel binding affinities of compounds <b>2a</b>, <b>3a</b>, <b>4a</b>, and <b>4c</b>–<b>e</b> were investigated. The most interesting analogue, <b>4a</b>, exhibited significant in vivo anticancer profile on pancreas, prostate, leukemia, and ovarian cancer cell line xenografts together with apoptosis and caspase-3 activation. Inhibition of the cancer cells cycle at the sub-G1 level was also obtained with <b>4a</b>. Finally, encouraging results were observed with <b>4a</b> in vivo on mice, suggesting putative antimetastatic and analgesic activities of this compound

Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic