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Abstract Cancers of the digestive system are major contributors to global cancer-associated morbidity and mortality, accounting for 35% of annual cases of cancer deaths. The etiologies, molecular features, and therapeutic management of these cancer entities are highly heterogeneous and complex. Over the last decade, genomic and functional studies have provided unprecedented insights into the biology of digestive cancers, identifying genetic drivers of tumor progression and key interaction points of tumor cells with the immune system. This knowledge is continuously translated into novel treatment concepts and targets, which are dynamically reshaping the therapeutic landscape of these tumors. In this review, we provide a concise overview of the etiology and molecular pathology of the six most common cancers of the digestive system, including esophageal, gastric, biliary tract, pancreatic, hepatocellular, and colorectal cancers. We comprehensively describe the current stage-dependent pharmacological management of these malignancies, including chemo-, targeted, and immunotherapy. For each cancer entity, we provide an overview of recent therapeutic advancements and research progress. Finally, we describe how novel insights into tumor heterogeneity and immune evasion deepen our understanding of therapy resistance and provide an outlook on innovative therapeutic strategies that will shape the future management of digestive cancers, including CAR-T cell therapy, novel antibody-drug conjugates and targeted therapies.

The primary objectives of this study were to analyze economic feasibility of incorporating black soldier fly products in broiler feed and to compare the viability of alive (alive grown larvae (AGL)) or processed (defatted larvae meal (DLM) and insect oil) insect inclusion into the two Dutch broiler welfare systems: conventional and better life one star (BLS).An existing simulation model for insect production was adapted to build an economic model for the insect-fed broiler breast meat supply chain. Amounts, full costs, and breakeven prices of different production setups were compared and the impacts of specific input parameters were tested by sensitivity and breakeven analyses.Results indicated a hypothetical demand of 2.15 million tons wet matter of raw substrate to meet the total Dutch breast meat production (BLS broilers and 10% AGL inclusion). In case of 10% processed insect inclusion, the conventional broiler breast meat price increased from 3,947 to 6,069 €/t (53.7%) and the BLS breast meat price from 6,493 to 9,662 €/t (48.8%). Alive insect inclusion resulted in a smaller cost increase (42.2%) by skipping the costly processing step. To become price competitive, DLM or AGL must cost 618 or 801 €/ton dry matter (tDM), respectively, requiring a raw substrate mix price of −109 €/tDM.High input amounts and costs currently hinder the widespread adoption of insect products in Dutch mass poultry feed. However, in the long run, using negative value substrates or targeting niche markets for broiler welfare with low AGL inclusion levels could become viable business models.Research is needed on the impact of negative value substrates on insect production performance and contamination risks. Furthermore, the impact of varying AGL composition requires special attention.

Background & aimsDespite increased risks for adverse effects in patients with cirrhosis, little is known about opioid prescriptions for this population. We aimed to assess time trends in opioid prescribing and factors associated with receiving opioids among patients with cirrhosis.MethodsAmong Veterans with cirrhosis, identified using national Veterans Health Administration data (2005-2014), we assessed characteristics of patients and their prescriptions for opioids. We calculated the annual proportion of patients receiving any opioid prescription. Among opioid recipients, we assessed prescriptions that were long-term (>90 days' supply), for high doses (>100 MME/day), or involved combinations of opioids and acetaminophen or benzodiazepine. We evaluated patient characteristics independently associated with long-term and any opioid prescriptions using mixed-effects regression models.ResultsAmong 127,239 Veterans with cirrhosis, 97,974 (77.0%) received a prescription for an opioid. Annual opioid prescriptions increased from 36% in 2005 to 47% in 2014 (P < .01). Among recipients of opioids, the proportions of those receiving long-term prescriptions increased from 47% in 2005 to 54% in 2014 (P < .01), and19%-21% received prescriptions for high-dose opioids. Prescriptions for combinations of opioids and acetaminophen decreased from 68% in 2005 to 50% in 2014 (P < .01) and for combinations of opioids and benzodiazepines decreased from 24% to 19% over this time (P < .01). Greater probability of long-term opioid prescriptions was independently associated with younger age, female sex, white race, hepatitis C, prior hepatic decompensation, hepatocellular carcinoma, mental health disorders, nicotine use disorders, medical comorbidities, surgery, and pain-related conditions.ConclusionAmong Veterans with cirrhosis, 36%-47% were prescribed opioids in each year. Mental health disorders and hepatic decompensation were independently associated with long-term opioid prescriptions.

Background Mycoplasma genitalium (MG) is on the CDC Watch List of Antimicrobial Resistance Threats, yet there is no systematic surveillance to monitor change. Methods We initiated surveillance in sexual health clinics in 6 cities, selecting a quota sample of urogenital specimens tested for gonorrhea and/or chlamydia. We abstracted patient data from medical records and detected MG and macrolide-resistance mutations (MRMs) by nucleic acid amplification testing. We used Poisson regression to estimate adjusted prevalence ratios (aPRs) and 95% CIs, adjusting for sampling criteria (site, birth sex, symptom status). Results From October–December 2020 we tested 1743 urogenital specimens: 57.0% from males, 46.1% from non-Hispanic Black persons, and 43.8% from symptomatic patients. MG prevalence was 16.6% (95% CI: 14.9–18.5%; site-specific range: 9.9–23.5%) and higher in St Louis (aPR: 1.9; 1.27–2.85), Greensboro (aPR: 1.8; 1.18–2.79), and Denver (aPR: 1.7; 1.12–2.44) than Seattle. Prevalence was highest in persons <18 years (30.4%) and declined 3% per each additional year of age (aPR:.97;.955–.982). MG was detected in 26.8%, 21.1%, 11.8%, and 15.4% of urethritis, vaginitis, cervicitis, and pelvic inflammatory disease (PID), respectively. It was present in 9% of asymptomatic males and 15.4% of asymptomatic females, and associated with male urethritis (aPR: 1.7; 1.22–2.50) and chlamydia (aPR: 1.7; 1.13–2.53). MRM prevalence was 59.1% (95% CI: 53.1–64.8%; site-specific range: 51.3–70.6%). MRMs were associated with vaginitis (aPR: 1.8; 1.14–2.85), cervicitis (aPR: 3.5; 1.69–7.30), and PID cervicitis (aPR: 1.8; 1.09–3.08). Conclusions MG infection is common in persons at high risk of sexually transmitted infections; testing symptomatic patients would facilitate appropriate therapy. Macrolide resistance is high and azithromycin should not be used without resistance testing. [ABSTRACT FROM AUTHOR]