Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

The role of the mammalian multisubunit tethering factor TRAPP in ER-to-Golgi transport

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

All-Purpose Containers? Lipid-Binding Protein – Drug Interactions

<div><p>The combined use of <i>in vitro</i> (¹⁹F-NMR) and <i>in silico</i> (molecular docking) procedures demonstrates the affinity of a number of human calycins (lipid-binding proteins from ileum, liver, heart, adipose tissue and epidermis, and retinol-binding protein from intestine) for different drugs (mainly steroids and vastatins). Comparative evaluations on the complexes outline some of the features relevant for interaction (non-polar character of the drugs; amino acids and water molecules in the protein calyx most often involved in binding). Dissociation constants (K_i) for drugs typically lie in the same range as K_i for natural ligands; in most instances (different proteins and docking conditions), vastatins are the strongest interactors, with atorvastatin ranking top in half of the cases. The affinity of some calycins for some of the vastatins is in the order of magnitude of the drug C_max after systemic administration in humans. The possible biological implications of this feature are discussed in connection with drug delivery parameters (route of administration, binding to carrier proteins, distribution to, and accumulation in, human tissues).</p></div

¹⁹F-NMR spectra recorded after the interaction of c-FABPL with increasing amounts of fluvastatin (from 0.5 to 2 equivalents; panel A traces a-c) and flurbiprofen (1 and 2 equivalents, panel B, traces e,f).

<p>The spectra of the drugs in the absence of the protein are shown in traces d (fluvastatin) and g (flurbiprofen). Operating conditions: phosphate buffer pH 7.4, 7 T, 298 K.</p

Carbonyl-carboxylic regions of the ¹³C-NMR spectra of cholic, panel A, and glycocholic acid, panel B, in the presence of c-FABPL.

<p>The spectra of the bile acids in the absence of the protein are shown in traces c and f, respectively. Operating conditions: phosphate buffer pH 7.4, 7 T, 298 K.</p

The highest affinity evaluated with any of the test calycins (Fig 9) is reported for each of the test drugs in systemic use in comparison with experimental C_max.

<p>Data from <a href="http://www.rxlist.com/script/main/hp.asp" target="_blank">http://www.rxlist.com/script/main/hp.asp</a> and [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132096#pone.0132096.ref045" target="_blank">45</a>].</p

Progressive shift of the resonance of dexamethasone (solid circles) towards the values of the free ligand (empty circle) on increasing the amount of cholate in solution.

<p>Operating conditions: phosphate buffer pH 7.4, 7 T, 298 K.</p

¹⁹F-NMR data on protein-ligand complexes.

<p>^a free ligand data in CDCl3</p><p>¹⁹F-NMR data on protein-ligand complexes.</p

Log₁₀K_i for the interaction of each of the test ligands (in Table 1) with c-FABPL.

<p>The <i>holo</i> structure of the protein (pdb code 1TW4) was taken as <i>receptor</i> and ligand atoms as <i>docking site</i>; the procedure was repeated in the presence (dark grey bars) and in the absence (light grey bars) of consensus water (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132096#pone.0132096.g001" target="_blank">Fig 1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132096#pone.0132096.s007" target="_blank">S1 Table</a>).</p

¹⁹F-NMR spectra of the c-FABPL/2-fluoropalmitic complex in the presence of increasing amounts of cholate (0–20 equivalents).

<p>Operating conditions: phosphate buffer pH 7.4, 7 T, 298 K.</p