Hepatocellular carcinoma surveillance may be associated with potential psychological harms in patients with cirrhosis.

BACKGROUND AND AIMS: The value of HCC surveillance is determined by the balance between benefits and harms; however, no studies have enumerated psychological harms. APPROACH AND RESULTS: We fielded surveys measuring psychological harms to patients with cirrhosis in a multicenter randomized trial of HCC surveillance outreach. All patients with positive or indeterminate surveillance results and matched patients with negative results were invited to complete surveys measuring (1) depression through the Patient Health Questionnaire-ninth version, (2) anxiety through State-Trait Anxiety Inventory, (3) HCC-specific worry through Psychological Consequences Questionnaire, and (4) decisional regret. Patients were classified into 4 groups: true positive (TP), false positive (FP), indeterminate, and true negative (TN). Multivariable longitudinal regression analysis using the generalized estimating equation method was performed to compare the means of measures across groups. We conducted 89 semistructured interviews in a subset of patients stratified by health system and test results. Of 2872 patients in the trial, 311 completed 1+ follow-up survey (63 FP, 77 indeterminate, 38 TP, and 133 TN). Moderate depression decreased in TN patients, increased in TP, and had intermittent but mild increases in those with FP and indeterminate results. High anxiety temporarily increased in patients with TP results but resolved over time and was stable in those with FP and indeterminate results. Decisional regret was low and did not differ across groups. In semistructured interviews, patients reported apprehension, anxiety, emotional distress, and coping related to HCC surveillance. CONCLUSIONS: Psychological harms of HCC surveillance appear mild but differ by test result. Future research should determine the impact of psychological harms on the value of HCC surveillance programs.

Effectiveness of mailed outreach and patient navigation to promote HCC screening process completion: a multicentre pragmatic randomised clinical trial.

BACKGROUND: Hepatocellular carcinoma (HCC) is plagued by failures across the cancer care continuum, leading to frequent late-stage diagnoses and high mortality. We evaluated the effectiveness of mailed outreach invitations plus patient navigation to promote HCC screening process completion in patients with cirrhosis. METHODS: Between April 2018 and September 2021, we conducted a multicentre pragmatic randomised clinical trial comparing mailed outreach plus patient navigation for HCC screening (n=1436) versus usual care with visit-based screening (n=1436) among patients with cirrhosis at three US health systems. Our primary outcome was screening process completion over a 36-month period, and our secondary outcome was the proportion of time covered (PTC) by screening. All patients were included in intention-to-screen analyses. RESULTS: All 2872 participants (median age 61.3 years; 32.3% women) were included in intention-to-screen analyses. Screening process completion was observed in 6.6% (95% CI: 5.3% to 7.9%) of patients randomised to outreach and 3.3% (95% CI: 2.4% to 4.3%) of those randomised to usual care (OR 2.05, 95% CI: 1.44 to 2.92). The intervention increased HCC screening process completion across most subgroups including age, sex, race and ethnicity, Child-Turcotte-Pugh class and health system. PTC was also significantly higher in the outreach arm than usual care (mean 37.5% vs 28.2%; RR 1.33, 95% CI: 1.31 to 1.35). Despite screening underuse, most HCC in both arms were detected at an early stage. CONCLUSION: Mailed outreach plus navigation significantly increased HCC screening process completion versus usual care in patients with cirrhosis, with a consistent effect across most examined subgroups. However, screening completion remained suboptimal in both arms, underscoring a need for more intensive interventions. TRIAL REGISTRATION NUMBER: NCT02582918.

Racialized inequities in live birth after cancer: A population-based study of 63,000 female adolescents and young adults with cancer.

INTRODUCTION: Fertility after cancer is a top concern for adolescents and young adults with cancer (AYAs) (15-39 years old at diagnosis). The authors characterized live births after cancer by race and ethnicity ("race/ethnicity") in a population-based sample of female AYAs. METHODS: This study used Texas Cancer Registry data linked to birth certificates (1995-2016) to estimate cumulative incidence of live birth, based on first live birth after cancer, and compared differences by race/ethnicity. Proportional subdistribution hazards models were used to estimate associations between race/ethnicity and live birth, adjusted for diagnosis age, cancer type, stage, year, and prior live birth, overall and for each cancer type. RESULTS: Among 65,804 AYAs, 10-year cumulative incidence of live birth was lower among non-Hispanic Black AYAs than other racial/ethnic groups: 10.2% (95% confidence interval [CI], 9.4-10.9) compared to 15.9% (95% CI, 14.1-17.9) among Asian or Pacific Islander, 14.7% (95% CI, 14.2-15.3) among Hispanic, and 15.2% (95% CI, 14.8-15.6) among non-Hispanic White AYAs (p < .01). In the adjusted overall model, Black AYAs were less likely to have a live birth after cancer than all other groups. In adjusted models for each cancer type, live birth was significantly less likely for Black AYAs with gynecologic cancers or lymphomas (compared to White AYAs) or thyroid cancers (compared to Hispanic AYAs). CONCLUSION: Black AYAs are less likely than AYAs of other races/ethnicities to have a live birth after cancer, in contrast to patterns of live birth in the general population. Research and action to promote childbearing equity after cancer are imperative.

Birth Cohort Colorectal Cancer (CRC): Implications for Research and Practice.

Colorectal cancer (CRC) epidemiology is changing due to a birth cohort effect, first recognized by increasing incidence of early onset CRC (EOCRC, age <50 years). In this paper, we define "birth cohort CRC" as the observed phenomenon, among individuals born 1960 and later, of increasing CRC risk across successive birth cohorts, rising EOCRC incidence, increasing incidence among individuals aged 50 to 54 years, and flattening of prior decreasing incidence among individuals aged 55 to 74 years. We demonstrate birth cohort CRC is associated with unique features, including increasing rectal cancer (greater than colon) and distant (greater than local) stage CRC diagnosis, and increasing EOCRC across all racial/ethnic groups. We review potential risk factors, etiologies, and mechanisms for birth cohort CRC, using EOCRC as a starting point and describing importance of viewing these through the lens of birth cohort. We also outline implications of birth cohort CRC for epidemiologic and translational research, as well as current clinical practice. We postulate that recognition of birth cohort CRC as an entity-including and extending beyond rising EOCRC-can advance understanding of risk factors, etiologies, and mechanisms, and address the public health consequences of changing CRC epidemiology.

Financial Burden of Hepatocellular Carcinoma Screening in Patients With Cirrhosis.

BACKGROUND: The overall value of hepatocellular carcinoma screening is defined by the balance of benefits and harms. Studies have only reported physical harms with none describing financial harms. METHODS: We conducted a multicenter pragmatic randomized clinical trial of hepatocellular carcinoma screening outreach among 2872 patients with cirrhosis from March 2018 to April 2021. Patients with positive or indeterminate results and matched patients with negative results completed surveys at baseline and at follow-up measuring financial harms via Cancer Self-Administered Questionnaire and financial burden via Comprehensive Score for Financial Toxicity Functional Assessment of Chronic Illness Therapy. Univariable and multivariable longitudinal regression analyses were performed to compare changes in financial harms across groups: true positive, true negative, false positive, and indeterminate. Semistructured interviews were conducted in a subset of patients, sampled by center and test result. RESULTS: Of 311 patients who completed at least 1 follow-up survey (75% response rate), 37 had true positive, 133 true negative, 64 false positive, and 77 indeterminate results. Financial harms increased in true positive and false positive patients with no significant changes noted among those with true negative or indeterminate results. At follow-up, 21.8% of patients reported moderate-severe financial burden, which was not significantly associated with test results. Semistructured interviews revealed variation in the frequency and severity of financial harms based on test results, with increased harm in those with false positive results. CONCLUSIONS: Financial harms of hepatocellular carcinoma screening vary by test result and can pose a barrier that must be considered when determining the optimal screening program.

Colorectal Cancer Screening Receipt Does Not Differ by 10-Year Mortality Risk Among Older Adults.

BACKGROUND: Health status and life expectancy are important considerations for assessing potential benefits and harms of colorectal cancer (CRC) screening programs, particularly among older adults. METHODS: We examined receipt of past-year CRC screening according to predicted 10-year mortality risk among 25,888 community-dwelling adults aged 65-84 years who were not up-to-date with screening in the nationwide National Health Interview Survey. Ten-year mortality risk was estimated using a validated index; from the lowest to highest quintiles of the index, risk was 12%, 24%, 39%, 58%, and 79%, respectively. We also examined the proportion of screening performed among adults with life expectancy <10 years. RESULTS: The prevalence of past-year CRC screening was 39.5%, 40.6%, 38.7%, 36.4%, and 35.4%, from the lowest to highest quintile of 10-year mortality risk. Odds of CRC screening did not differ between adults in the lowest vs highest quintile (adjusted odds ratio 1.05, 95% confidence interval: 0.93-1.20). One-quarter (27.9%) of past-year CRC screening occurred in adults with life expectancy <10 years, and more than half (50.7%) of adults aged 75-84 years had 10-year mortality risk ≥50% at the time of screening. In an exploratory analysis, invasive but not noninvasive screening increased as 10-year mortality risk increased ( P < 0.05) among adults aged 70-79 years. DISCUSSION: Past-year CRC screening does not differ by predicted 10-year mortality risk. An age-based approach to CRC screening results in underscreening of older, healthier adults and overscreening of younger adults with chronic conditions. Personalized screening with incorporation of individual life expectancy may increase the value of CRC screening programs.

Pandemic-Related Changes in Incidence and Mortality Rates of Gastrointestinal Cancers During 2020.

INTRODUCTION: Coronavirus Disease 2019 disrupted cancer-related care in early 2020. METHODS: We used population-based cancer registry data to estimate incidence and mortality rates of gastrointestinal cancers between 2016 and 2020. RESULTS: Incidence rates were unchanged from 2016 to 2019 but decreased in 2020, with the largest declines for colorectal cancer (rate ratio [RR] 0.88; 95% confidence interval [CI] 0.87-0.90) and hepatocellular carcinoma (RR 0.85; 95% CI 0.82-0.88). Mortality rates of colorectal cancer (RR 1.06; 95% CI 1.04-1.08) and esophageal adenocarcinoma (RR 1.06; 95% CI 1.00-1.13) increased in 2020. DISCUSSION: Incidence and mortality rates of gastrointestinal cancers may increase in the future given pandemic-related delays in 2020.

Proportion of Time Covered by Hepatocellular Carcinoma Surveillance in Patients With Cirrhosis.

INTRODUCTION: Hepatocellular carcinoma (HCC) surveillance is associated with improved early tumor detection, but effectiveness is limited by underuse. We characterized adherence to HCC surveillance using proportion of time covered (PTC) and estimated its association with clinical outcomes among patients with cirrhosis. METHODS: We conducted a retrospective cohort study of patients diagnosed with HCC between January 2008 and December 2022 at 2 large US health systems. We characterized PTC by imaging in the 12 and 24 months before HCC diagnosis. We used multivariable logistic and Cox regression analyses to assess the association between PTC and early HCC detection, receipt of curative treatment, and overall survival. RESULTS: Among 2,027 patients with HCC, 331 (51.4% Barcelona Clinic Liver Cancer 0/A) had been followed up for at least 12 months before diagnosis. The median PTC was 24.9% (interquartile range 1.1%-50.7%), with only 16.0% having semiannual imaging and 42.0% having annual surveillance. Semiannual and annual surveillance decreased to 6.3% and 29.6% when assessed over 24 months, although the median PTC remained unchanged at 24.9%. Receipt of gastroenterology/hepatology care had the strongest association with PTC, with median PTC of 36.7% and 3.8% for those with and without gastroenterology/hepatology care, respectively. PTC was independently associated with improved early HCC detection, curative treatment receipt, and overall survival. The median survival was 15.7, 26.8, and 32.7 months among those with PTC of <25% (n = 168 patients), PTC 25%-50% (n = 69 patients), and PTC >50% (n = 94 patients), respectively. DISCUSSION: The proportion of time covered by HCC surveillance in patients with cirrhosis remains low, highlighting a need for multilevel interventions.

The Spectrum of State Approaches to Medicaid Maternity Care Contracting.

Policy Points Maternal health is influenced by the quality and accessibility of care before, during, and after pregnancy. Nationwide, Medicaid covers nearly one in two births and uses managed care as a central means for carrying out these responsibilities. Thus, managed care plays a fundamental role in assuring timely, equitable, quality care and improving maternal health outcomes. A close review of managed care contracts makes evident that the absence of a national set of maternal health standards has caused challenges in setting expectations for managed care performance. State Medicaid agencies adopt a variety of approaches and underlying philosophies for contracting. CONTEXT: Managed care is how Medicaid agencies principally furnish maternity care. For this reason, the contracts that Medicaid agencies enter into with managed care organizations have attracted strong interest as a means of improving maternal health access, quality, and equity. However, limited research has documented the extent to which states use these agreements to set binding expectations across the maternal health continuum and how states approach the task of maternal health contracting. METHODS: To explore maternal health contracting within Medicaid Managed Care, this study took a three-phase, sequential approach: (1) an extensive literature review to identify clinical guidelines and expert recommendations regarding maternal health "best practices" for people with elevated health and social needs, (2) a review of the managed care contracts in use across 40 states and Washington, DC, to determine the extent to which they incorporate these best practices, and (3) interviews conducted with four state Medicaid agencies to better understand how states approach maternal health when developing their contracts. FINDINGS: The evidence on maternal health best practices reveals nearly 60 "best practices," although the literature review also underscored the extent to which these recommendations are fragmented across numerous professional bodies and government agencies and are thus difficult for Medicaid agencies to ascertain. The contracts themselves reflect an approach to the maternal health continuum in a fragmented and incomplete way. Thematic analysis of interviews with state Medicaid agencies revealed three key approaches to contracting for maternity care: an "organic" approach, an "intentional" approach, and an approach "grounded" in state strategy. CONCLUSIONS: The absence of comprehensive, integrated guidelines reflecting the full maternal health continuum likely complicates the contracting task and contributes to incomplete, ambiguous contracts. A major step would be the development of a "best practices tool" that helps state Medicaid agencies translate evidence into comprehensive, clear contracting expectations.

Increasing Access to Cardiac Rehabilitation Services Among Disadvantaged Populations.

The Prince George's County Health Department encountered several challenges to increasing access to cardiac rehabilitation (CR) services among disadvantaged populations. They include excessive patient out-of-pocket costs; requirements that CR orders must be signed by a physician; provider reluctance to refer patients to CR, with most primary care providers preferring to refer clients to cardiologists for the latter to determine whether the patient needs CR referral; limited availability of CR programs; and difficulty identifying patients eligible for CR services. Discussions with other local health departments and public health practitioners indicate that these challenges are not unique to Maryland but are indicative of policy and system barriers that prevent the optimal delivery of cardiovascular health services. This case study documents the challenges and the Prince George's County Health Department's efforts to resolve them and provides recommendations for decision-makers seeking to make CR programs more accessible to disadvantaged populations.

Racial and Ethnic Disparities in Early-Onset Colorectal Cancer Survival.

BACKGROUND: Young adults diagnosed with colorectal cancer (CRC) comprise a growing, yet understudied, patient population. We estimated 5-year relative survival of early-onset CRC and examined disparities in survival by race-ethnicity in a population-based sample. METHODS: We used the National Cancer Institute's Surveillance, Epidemiology, and End Results program of cancer registries to identify patients diagnosed with early-onset CRC (20-49 years of age) between January 1, 1992, and December 31, 2013. For each racial-ethnic group, we estimated 5-year relative survival, overall and by sex, tumor site, and stage at diagnosis. To illustrate temporal trends, we compared 5-year relative survival in 1992-2002 vs 2003-2013. We also used Cox proportional hazards regression models to examine the association of race-ethnicity and all-cause mortality, adjusting for age at diagnosis, sex, county type (urban vs rural), county-level median household income, tumor site, and stage at diagnosis. RESULTS: We identified 33,777 patients diagnosed with early-onset CRC (58.5% White, 14.0% Black, 13.0% Asian, 14.5% Hispanic). Five-year relative survival ranged from 57.6% (Black patients) to 69.1% (White patients). Relative survival improved from 1992-2002 to 2003-2013 for White patients only; there was no improvement for Black, Asian, or Hispanic patients. This pattern was similar by sex, tumor site, and stage at diagnosis. In adjusted analysis, Black (adjusted hazard ratio [aHR], 1.42; 95% confidence interval [CI], 1.36-1.49), Asian (aHR, 1.06; 95% CI, 1.01-1.12), and Hispanic (aHR, 1.16; 95% CI, 1.10-1.21) race-ethnicity were associated with all-cause mortality. CONCLUSION: Our study adds to the well-documented disparities in CRC in older adults by demonstrating persistent racial-ethnic disparities in relative survival and all-cause mortality in patients with early-onset CRC.

Burden and Cost of Gastrointestinal, Liver, and Pancreatic Diseases in the United States: Update 2021.

BACKGROUND & AIMS: Gastrointestinal diseases account for considerable health care use and expenditures. We estimated the annual burden, costs, and research funding associated with gastrointestinal, liver, and pancreatic diseases in the United States. METHODS: We generated estimates using data from the National Ambulatory Medical Care Survey; National Hospital Ambulatory Medical Care Survey; Nationwide Emergency Department Sample; National Inpatient Sample; Kids' Inpatient Database; Nationwide Readmissions Database; Surveillance, Epidemiology, and End Results program; National Vital Statistics System; Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research; MarketScan Commercial Claims and Encounters data; MarketScan Medicare Supplemental data; United Network for Organ Sharing registry; Medical Expenditure Panel Survey; and National Institutes of Health (NIH). RESULTS: Gastrointestinal health care expenditures totaled $119.6 billion in 2018. Annually, there were more than 36.8 million ambulatory visits for gastrointestinal symptoms and 43.4 million ambulatory visits with a primary gastrointestinal diagnosis. Hospitalizations for a principal gastrointestinal diagnosis accounted for more than 3.8 million admissions, with 403,699 readmissions. A total of 22.2 million gastrointestinal endoscopies were performed, and 284,844 new gastrointestinal cancers were diagnosed. Gastrointestinal diseases and cancers caused 255,407 deaths. The NIH supported $3.1 billion (7.5% of the NIH budget) for gastrointestinal research in 2020. CONCLUSIONS: Gastrointestinal diseases are responsible for millions of health care encounters and hundreds of thousands of deaths that annually costs billions of dollars in the United States. To reduce the high burden of gastrointestinal diseases, focused clinical and public health efforts, supported by additional research funding, are warranted.

Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines.

BACKGROUND & AIMS: Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC. METHODS: After reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%. RESULTS: The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. On the basis of current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later-onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors. The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients. CONCLUSIONS: The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC.

Disparities in the use of assisted reproductive technologies after breast cancer: a population-based study.

PURPOSE: Equitable access to oncofertility services is a key component of cancer survivorship care, but factors affecting access and use remain understudied. METHODS: To describe disparities in assisted reproductive technology (ART) use among women with breast cancer in California, we conducted a population-based cohort study using linked oncology, ART, and demographic data. We identified women age 18-45 years diagnosed with invasive breast cancer between 2000 and 2015. The primary outcome was ART use-including oocyte/embryo cryopreservation or embryo transfer-after cancer diagnosis. We used log-binomial regression to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) to identify factors associated with ART use. RESULTS: Among 36,468 women with invasive breast cancer, 206 (0.56%) used ART. Women significantly less likely to use ART were age 36-45 years at diagnosis (vs. 18-35 years: PR = 0.17, 95% CI 0.13-0.22); non-Hispanic Black or Hispanic (vs. non-Hispanic White: PR = 0.31, 95% CI 0.21-0.46); had at least one child (vs. no children: adjusted PR [aPR] = 0.39, 95% CI 0.25-0.60); or lived in non-urban areas (vs. urban: aPR = 0.28, 95% CI 0.10-0.75), whereas women more likely to use ART lived in high-SES areas (vs. low-/middle-SES areas: aPR = 2.93, 95% CI 2.04-4.20) or had private insurance (vs. public/other insurance: aPR = 2.95, 95% CI 1.59-5.49). CONCLUSION: Women with breast cancer who are socially or economically disadvantaged, or who already had a child, are substantially less likely to use ART after diagnosis. The implementation of policies or programs targeting more equitable access to fertility services for women with cancer is warranted.

Multicenter evaluation of the BIOFIRE Joint Infection Panel for the detection of bacteria, yeast, and AMR genes in synovial fluid samples.

The bioMérieux BIOFIRE Joint Infection (JI) Panel is a multiplex in vitro diagnostic test for the simultaneous and rapid (~1 h) detection of 39 potential pathogens and antimicrobial resistance (AMR) genes directly from synovial fluid (SF) samples. Thirty-one species or groups of microorganisms are included in the kit, as well as several AMR genes. This study, performed to evaluate the BIOFIRE JI Panel for regulatory clearance, provides data from a multicenter evaluation of 1,544 prospectively collected residual SF samples with performance compared to standard-of-care (SOC) culture for organisms or polymerase chain reaction (PCR) and sequencing for AMR genes. The BIOFIRE JI Panel demonstrated a sensitivity of 90.9% or greater for all but six organisms and a positive percent agreement (PPA) of 100% for all AMR genes. The BIOFIRE JI Panel demonstrated a specificity of 98.5% or greater for detection of all organisms and a negative percent agreement (NPA) of 95.7% or greater for all AMR genes. The BIOFIRE JI Panel provides an improvement over SOC culture, with a substantially shorter time to result for both organisms and AMR genes with excellent sensitivity/PPA and specificity/NPA, and is anticipated to provide timely and actionable diagnostic information for joint infections in a variety of clinical scenarios.

Perkinsus marinus in bioreactor: growth and a cost-reduced growth medium.

Perkinsus marinus (Perkinsea) is an osmotrophic facultative intracellular marine protozoan responsible for "Dermo" disease in the eastern oyster, Crassostrea virginica. In 1993 in vitro culture of P. marinus was developed in the absence of host cells. Compared to most intracellular protozoan parasites, the availability of P. marinus to grow in the absence of host cells has provided the basis to explore its use as a heterologous expression system. As the genetic toolbox is becoming available, there is also the need for larger-scale cultivation and lower-cost media formulations. Here, we took an industrial approach to scaled-up growth from a small culture flask to bioreactors, which required developing new cultivation parameters, including aeration, mixing, pH, temperature control, and media formulation. Our approach also enabled more real-time data collection on growth. The bioreactor cultivation method showed similar or accelerated growth rates of P. marinus compared to culture in T-flasks. Redox measurements indicated sufficient oxygen availability throughout the cultivation. Replacing fetal bovine serum with chicken serum showed no differences in the growth rate and a 60% reduction in the medium cost. This study opens the door to furthering P. marinus as a valid heterologous expression system by showing the ability to grow in bioreactors. ONE-SENTENCE SUMMARY: Perkinsus marinus, a microbial parasite of oysters that could be useful for developing vaccines for humans, has been shown to grow well in laboratory equipment that can be expanded to commercial scale using a less expensive growth formula than usual laboratory practice.

Two distinct amphipathic peptide antibiotics with systemic efficacy.

Antimicrobial peptides are important candidates for developing new classes of antibiotics because of their potency against antibiotic-resistant pathogens. Current research focuses on topical applications and it is unclear how to design peptides with systemic efficacy. To address this problem, we designed two potent peptides by combining database-guided discovery with structure-based design. When bound to membranes, these two short peptides with an identical amino acid composition can adopt two distinct amphipathic structures: A classic horizontal helix (horine) and a novel vertical spiral structure (verine). Their horizontal and vertical orientations on membranes were determined by solid-state 15N NMR data. While horine was potent primarily against gram-positive pathogens, verine showed broad-spectrum antimicrobial activity. Both peptides protected greater than 80% mice from infection-caused deaths. Moreover, horine and verine also displayed significant systemic efficacy in different murine models comparable to conventional antibiotics. In addition, they could eliminate resistant pathogens and preformed biofilms. Significantly, the peptides showed no nephrotoxicity to mice after intraperitoneal or intravenous administration for 1 wk. Our study underscores the significance of horine and verine in fighting drug-resistant pathogens.

Maternal obesity, pregnancy weight gain, and birth weight and risk of colorectal cancer.

OBJECTIVE: Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. Obesity is a well-established risk factor for CRC, and fetal or developmental origins of obesity may underlie its effect on cancer in adulthood. We examined associations of maternal obesity, pregnancy weight gain, and birth weight and CRC in adult offspring. DESIGN: The Child Health and Development Studies is a prospective cohort of women receiving prenatal care between 1959 and 1966 in Oakland, California (N=18 751 live births among 14 507 mothers). Clinical information was abstracted from mothers' medical records 6 months prior to pregnancy through delivery. Diagnoses of CRC in adult (age ≥18 years) offspring were ascertained through 2019 by linkage with the California Cancer Registry. We used Cox proportional hazards models to estimate adjusted HR (aHR); we examined effect measure modification using single-referent models to estimate the relative excess risk due to interaction (RERI). RESULTS: 68 offspring were diagnosed with CRC over 738 048 person-years of follow-up, and half (48.5%) were diagnosed younger than age 50 years. Maternal obesity (≥30 kg/m2) increased the risk of CRC in offspring (aHR 2.51, 95% CI 1.05 to 6.02). Total weight gain modified the association of rate of early weight gain (RERI -4.37, 95% CI -9.49 to 0.76), suggesting discordant growth from early to late pregnancy increases risk. There was an elevated association with birth weight (≥4000 g: aHR 1.95, 95% CI 0.8 to 4.38). CONCLUSION: Our results suggest that in utero events are important risk factors for CRC and may contribute to increasing incidence rates in younger adults.

Hepatocellular carcinoma recurrence after direct-acting antiviral therapy: an individual patient data meta-analysis.

OBJECTIVE: The benefit of direct-acting antivirals (DAAs) against HCV following successful treatment of hepatocellular carcinoma (HCC) remains controversial. This meta-analysis of individual patient data assessed HCC recurrence risk following DAA administration. DESIGN: We pooled the data of 977 consecutive patients from 21 studies of HCV-related cirrhosis and HCC, who achieved complete radiological response after surgical/locoregional treatments and received DAAs (DAA group). Recurrence or death risk was expressed as HCC recurrence or death per 100 person-years (100PY). Propensity score-matched patients from the ITA.LI.CA. cohort (n=328) served as DAA-unexposed controls (no-DAA group). Risk factors for HCC recurrence were identified using random-effects Poisson. RESULTS: Recurrence rate and death risk per 100PY in DAA-treated patients were 20 (95% CI 13.9 to 29.8, I2=74.6%) and 5.7 (2.5 to 15.3, I2=54.3), respectively. Predictive factors for recurrence were alpha-fetoprotein logarithm (relative risk (RR)=1.11, 95% CI 1.03 to 1.19; p=0.01, per 1 log of ng/mL), HCC recurrence history pre-DAA initiation (RR=1.11, 95% CI 1.07 to 1.16; p<0.001), performance status (2 vs 0, RR=4.35, 95% CI 1.54 to 11.11; 2 vs 1, RR=3.7, 95% CI 1.3 to 11.11; p=0.01) and tumour burden pre-HCC treatment (multifocal vs solitary nodule, RR=1.75, 95% CI 1.25 to 2.43; p<0.001). No significant difference was observed in RR between the DAA-exposed and DAA-unexposed groups in propensity score-matched patients (RR=0.64, 95% CI 0.37 to 1.1; p=0.1). CONCLUSION: Effects of DAA exposure on HCC recurrence risk remain inconclusive. Active clinical and radiological follow-up of patients with HCC after HCV eradication with DAA is justified.

Prevalence of Forceps Polypectomy of Nondiminutive Polyps Is Substantial But Modifiable.

BACKGROUND AND AIMS: The use of forceps for removal of nondiminutive polyps is associated with incomplete resection compared with snare polypectomy. However, few studies have characterized the frequency of forceps polypectomy for nondiminutive polyps or identified strategies to improve this practice. To address this gap, we estimated the prevalence and predictors of forceps polypectomy in clinical practice and examined the effectiveness of a multicomponent intervention to reduce inappropriate forceps polypectomy. METHODS: We retrospectively reviewed all colonoscopies with polypectomies performed at 2 U.S. health systems between October 1, 2017, and September 30, 2019. We used a mixed-effects logistic regression model to examine the effect of a multicomponent intervention, including provider education and a financial incentive, to reduce inappropriate forceps polypectomy, defined as use of forceps polypectomy for polyps ≥5 mm. RESULTS: A total of 9968 colonoscopies with 25,534 polypectomies were performed by 42 gastroenterologists during the study period. Overall, 8.5% (n = 2176) of polyps were removed with inappropriate forceps polypectomy. Inappropriate forceps polypectomy significantly decreased after the intervention (odds ratio [OR], 0.34, 95% confidence interval [CI], 0.30-0.39), from 11.4% (n = 1539) to 5.3% (n = 637). Predictors of inappropriate forceps polypectomy included inadequate bowel prep (OR, 1.25; 95% CI, 1.06-1.47), polyps in the right colon (vs left: OR, 1.29; 95% CI, 1.09-1.51), and number of polyps removed (OR, 0.96; 95% CI, 0.94-0.97). Inappropriate forceps polypectomy also varied by gastroenterologist (median OR, 3.43). In a post hoc analysis, the proportion of polyps >2 mm removed with forceps decreased from 50.0% before the intervention to 43.0% after it (OR, 0.62; 95% CI, 0.58-0.68). CONCLUSIONS: Inappropriate forceps polypectomy is common but modifiable. The proportion of nondiminutive polyps removed with forceps polypectomy should be considered as a quality measure.