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

Tuning Second-Order Optical Nonlinearities in Push-Pull Benzimidazoles

The synthesis and full characterization of new chromophores with second order optical nonlinearities containing the 2- phenyl-(5,6)-nitrobenzimidazole group is reported. Starting from 2-{4-[(4-N,N-dihydroxyethylamino)phenylazo]phenyl}- 5(6)-nitrobenzimidazole, a combined theoretical and experimental approach, including theoretical computations of second order nonlinear optical activity (MNDO/AM1), X-ray structural analysis and synthetic strategies, has led to a significant optimization (more than 50%) of the NLO activity of related chromophores. The results indicate that 6-nitro-substituted compounds are more active than 5-nitro-substitutedones and that a further increase of NLO activity can be achieved by insertion of a carbon−carbon double bond between the benzimidazole and 2-phenyl rings. Calculations also suggest that an additional improvement of the nonlinearity should be expected upon functionalization of the N1 atom of the 6-nitrobenzimidazole with electron-withdrawing groups. Experimental nonlinearities (EFISH technique, μβ/10−48 esu, λ = 1.907 μm, DMF solution) between 940 and 1550 were measured

Age‐dependent decline of NAD⁺- universal truth or confounded consensus?

Nicotinamide adenine dinucleotide (NAD(+)) is an essential molecule involved in various metabolic reactions, acting as an electron donor in the electron transport chain and as a co-factor for NAD(+)-dependent enzymes. In the early 2000s, reports that NAD(+) declines with aging introduced the notion that NAD(+) metabolism is globally and progressively impaired with age. Since then, NAD(+) became an attractive target for potential pharmacological therapies aiming to increase NAD(+) levels to promote vitality and protect against age-related diseases. This review summarizes and discusses a collection of studies that report the levels of NAD(+) with aging in different species (i.e., yeast, C. elegans, rat, mouse, monkey, and human), to determine whether the notion that overall NAD(+) levels decrease with aging stands true. We find that, despite systematic claims of overall changes in NAD(+) levels with aging, the evidence to support such claims is very limited and often restricted to a single tissue or cell type. This is particularly true in humans, where the development of NAD(+) levels during aging is still poorly characterized. There is a need for much larger, preferably longitudinal, studies to assess how NAD(+) levels develop with aging in various tissues. This will strengthen our conclusions on NAD metabolism during aging and should provide a foundation for better pharmacological targeting of relevant tissues

Dietary Protein Restriction Improves Metabolic Dysfunction in Patients with Metabolic Syndrome in a Randomized, Controlled Trial

Dietary restriction (DR) reduces adiposity and improves metabolism in patients with one or more symptoms of metabolic syndrome. Nonetheless, it remains elusive whether the benefits of DR in humans are mediated by calorie or nutrient restriction. This study was conducted to determine whether isocaloric dietary protein restriction is sufficient to confer the beneficial effects of dietary restriction in patients with metabolic syndrome. We performed a prospective, randomized controlled dietary intervention under constant nutritional and medical supervision. Twenty-one individuals diagnosed with metabolic syndrome were randomly assigned for caloric restriction (CR; n = 11, diet of 5941 ± 686 KJ per day) or isocaloric dietary protein restriction (PR; n = 10, diet of 8409 ± 2360 KJ per day) and followed for 27 days. Like CR, PR promoted weight loss due to a reduction in adiposity, which was associated with reductions in blood glucose, lipid levels, and blood pressure. More strikingly, both CR and PR improved insulin sensitivity by 62.3% and 93.2%, respectively, after treatment. Fecal microbiome diversity was not affected by the interventions. Adipose tissue bulk RNA-Seq data revealed minor changes elicited by the interventions. After PR, terms related to leukocyte proliferation were enriched among the upregulated genes. Protein restriction is sufficient to confer almost the same clinical outcomes as calorie restriction without the need for a reduction in calorie intake. The isocaloric characteristic of the PR intervention makes this approach a more attractive and less drastic dietary strategy in clinical settings and has more significant potential to be used as adjuvant therapy for people with metabolic syndrome

Effects of CGEN-856S and captopril administration on (A) systolic tension, (B) diastolic tension, (C) +dT/dt, (D) -dT/dt, (E) coronary flow, and (F) heart rate of rat hearts with myocardial infarction (MI).

<p>Values are expressed as mean ± SEM, n = 7−8 animals. *<i>P</i><0.05 vs. sham; ^#<i>P</i><0.05 vs. MI+vehicle; ^α<i>P</i><0.05 vs. MI+captopril.</p

Effects of CGEN-856S and losartan administration on the deposition of type I collagen (CO I), type III collagen (CO III), and fibronectin (FN) in the left ventricles of isoproterenol (ISO)-treated rats.

<p>(A) Representative confocal photomicrographs and (B) quantification of CO I, CO III, and FN in the left ventricles of animals treated with CGEN-856S. (C) Representative confocal photomicrographs and (D) quantification of CO I, CO III, and FN in the left ventricles of animals treated with losartan. Values are expressed as arbitrary units (mean gray value ± SEM, n = 4−5 animals). *<i>P</i><0.05 vs. ISO+vehicle.</p

Effects of CGEN-856S and captopril administration on left ventricular infarct area.

<p>(A) Representative photomicrographs and (B) quantification of the infarct area of animals treated with CGEN-856S or captopril. Values are expressed as mean ± SEM, n = 7−8 animals. MI: myocardial infarction. *<i>P</i><0.05 vs. sham; ^#<i>P</i><0.05 vs. MI+vehicle.</p