Neoplasia Diagnosis After Multi-target Stool DNA Is Enhanced Among Lowest Baseline Detectors.

BACKGROUND AND AIMS: Variation in colorectal neoplasia detection limits the effectiveness of screening colonoscopy. By evaluating neoplasia detection rates of individual colonoscopists, we aimed to quantify the effects of pre-procedural knowledge of a positive (+) multi-target stool DNA (mt-sDNA) on colonoscopy quality metrics. METHODS: We retrospectively identified physicians who performed a high volume of + mt-sDNA colonoscopies; colorectal neoplasia at post-mt-sDNA colonoscopy was recorded. These colonoscopists were stratified into quartiles based on baseline adenoma detection rates. Baseline colonoscopy adenoma detection rates and sessile serrated lesion detection rates were compared to post-mt-sDNA colonoscopy neoplasia diagnosis rates among each quartile. Withdrawal times were measured from negative exams. RESULTS: During the study period (2014-17) the highest quartile of physicians by volume of post-mt-sDNA colonoscopies were evaluated. Among thirty-five gastroenterologists, their median screening colonoscopy adenoma detection rate was 32% (IQR, 28-39%) and serrated lesion detection rate was 13% (8-15%). After + mt-sDNA, adenoma diagnosis increased to 47% (36-56%) and serrated lesion diagnosis increased to 31% (17-42%) (both p < 0.0001). Median withdrawal time increased from 10 (7-13) to 12 (10-17) minutes (p < 0.0001) and was proportionate across quartiles. After + mt-sDNA, lower baseline detectors had disproportionately higher rates of adenoma diagnosis in female versus male patients (p = 0.048) and higher serrated neoplasia diagnosis rates among all patients (p = 0.0092). CONCLUSIONS: Knowledge of + mt-sDNA enriches neoplasia diagnosis compared to average risk screening exams. Adenomatous and serrated lesion diagnosis was magnified among those with lower adenoma detection rates. Awareness of the mt-sDNA result may increase physician attention during colonoscopy. Pre-procedure knowledge of a positive mt-sDNA test improves neoplasia diagnosis rates among colonoscopists with lower baseline adenoma detection rates, independent of withdrawal time.

Clinical Outcomes of Portosystemic Shunts on the Outcome of Liver Transplantation.

Spontaneous portosystemic shunts (SPSSs) have been associated with worse clinical outcomes in the pre-liver transplantation (LT) setting, but little is known about their post-LT impacts. Our aim was to compare LT candidates with and without SPSSs and assess the impact of SPSSs on patient mortality and graft survival in the post-LT setting. Patients 18 years or older with abdominal imaging done prior to LT were included. Exclusion criteria were the presence of pre-LT surgical shunts, LT indications other than cirrhosis, and combined solid organ transplantations. SPSSs were classified as absent, small, or large according to their maximum diameter (8 mm). Multiple variables that could influence the post-LT course were extracted for analysis. Patient and graft survival were estimated using the Kaplan-Meier method and were compared between groups using a log-rank test. The project received institutional review board approval. We extracted data from 326 patients. After comparing patients without SPSS or with small or large SPSSs, no statistical difference was found for overall patient survival: no SPSS (n = 8/63), reference; small SPSS (n = 18/150), hazard ratio (HR), 1.05 (95% confidence interval [CI], 0.45-2.46); and large SPSS (n = 6/113), HR, 0.60 (95% CI, 0.20-1.78); P = 0.20. Also, no difference was found for graft survival: no SPSS (n = 11/63), reference; small SPSS (n = 21/150), HR, 0.80 (95% CI, 0.38-1.70); large SPSS (n = 11/113), HR, 0.59 (95% CI, 0.25-1.40); P = 0.48. Similarly, no statistical significance was found for these variables when comparing if the graft used was procured from a donation after circulatory death donor versus a donation after brain death donor. In conclusion, the previously described association between SPSSs and worse clinical outcomes in pre-LT patients seems not to persist once patients undergo LT. This study suggests that no steps to correct SPSS intraoperatively are necessary.

When free-ranging dogs threaten wildlife: Public attitudes toward management strategies in southern Chile.

Free-ranging dogs (Canis familiaris) significantly threaten wildlife, including endangered species. Although this problem resembles threats from other invasive animals, managing roaming dogs is even more fraught due to their close association with humans. Here we use interviews (n = 166) to document patterns of dog ownership and care and to measure public attitudes toward management strategies to control free-roaming dogs that threaten wildlife in rural areas of southern Chile. We compare attitudes toward lethal control and fines in scenarios where dogs attack livestock, children or wild animals or enter protected areas. We also test for variation in attitudes according to gender, age, education and proximity to urban areas. Most respondents (98.1%) opposed lethal control for at least one scenario and they were more likely to accept killing dogs that attacked sheep than those attacking wildlife. Similarly, support for fines was higher when dogs attacked livestock or people versus wild animals. Respondents consistently favored fining the owner over eliminating the problem dog. When asked about their management preferences, many respondents indicated that the movement of problem dogs-including to a lesser extent those threatening wildlife-should be restricted. However, in practice most dog-owners allowed one or more of their dogs to move freely at least part of the time. Finally, the wildlife species of concern mattered, e.g. 40% thought no action was necessary when dogs attack foxes, but this dropped to 12% for pudu (a small deer). In sum, participants had significantly more concern for livestock and human safety than for wildlife protection. We close by discussing management and policy implications.

Racial Disparities in the Presentation and Treatment of Colorectal Cancer: A Statewide Cross-sectional Study.

BACKGROUND: Non-Hispanic blacks (NHB) and Hispanics often present with advanced colorectal cancer (CRC). The aim of the study was to characterize CRC differences among Hispanics, NHB, and non-Hispanic whites (NHW). METHODS: A cross-sectional analysis and logistic regression of 2009 Florida Agency for Healthcare Administration Hospital Admission Database data for CRC using the International Classification of Diseases, 9th Revision, Clinical Modification codes was performed. Outcomes included CRC location, frequency of metastasis and colectomy rates. Each minority group was compared with NHW. RESULTS: A total of 34,577 patients were NHW, 5190 were NHB, and 5033 were Hispanic. NHB had more proximal CRC [odds ratio (OR), 1.17; 95% confidence interval (CI), 1.09-1.25; P<0.0001]; Hispanics had more distal CRC (OR, 0.90; 95% CI, 0.83-0.96; P=0.0024). Hispanics had increased metastases (OR, 1.11; 95% CI, 1.02-1.22; P=0.04). NHB and Hispanics underwent fewer colectomies [(OR, 0.93; 95% CI, 0.86-0.99; P=0.03) and (OR, 0.9; 95% CI, 0.84-0.97; P=0.001), respectively]. CONCLUSIONS: Disparities in CRC metastases and colectomy rates exist among these racial groups in Florida. This work should serve as a foundation to study potential causes and to design culture-specific interventions.

An update on cancer risk and surveillance in primary sclerosing cholangitis.

Malignancy represents substantial morbidity and mortality in patients with primary sclerosing cholangitis (PSC). This subset of patients has been proven to be at increased risk for developing cholangiocarcinoma, gallbladder carcinoma and colorectal cancer in those with overlapping inflammatory bowel disease. Herein, we review the prevalence of these malignancies and recommend screening tools and current knowledge to reduce the disease burden in this population. Cholangiocarcinoma is the most dominant malignancy affecting PSC patients, with a lifetime risk ranging from 5% to 20%. We advocate for serial US or MRI/MRCP and CA 19-9 to screen for cholangiocarcinoma. Gallbladder cancer has a lifetime risk around 2% in this population and we agree with annual imaging for lesions as recommended by national guidelines. Patients with PSC and concomitant IBD are at increased risk of colorectal carcinoma from time of diagnosis and therefore should likely undergo annual surveillance. The low rates of hepatocellular cancer and pancreatic cancer indicate surveillance for these malignancies is less advantageous.

Value of Oral Proton Pump Inhibitors in Acute, Nonvariceal Upper Gastrointestinal Bleeding: A Network Meta-Analysis.

BACKGROUND: Intravenous (IV) proton pump inhibitors (PPI) are the standard medical treatment in acute nonvariceal upper gastrointestinal bleeding (ANVGIB). Optimal route of PPI delivery has been questioned. AIM: The aim was to perform a systematic review and network meta-analysis for the endpoints of risk of rebleeding, length of stay (LOS), surgery (ROS), mortality, and total units of blood transfused (UBT) among trials evaluating acid suppressive medications in ANVGIB. METHODS: A total of 39 studies using IV PPI drip, IV scheduled PPI, oral PPI, H2-receptor antagonists, and placebo were identified. Network meta-analysis was used for indirect comparisons and Bayesian Markov Chain Monte Carlo methods for calculation of probability superiority. RESULTS: No difference was observed between IV PPI drip and scheduled IV PPI for mortality (relative risk=1.11; 95% credibility interval, 0.56-2.21), LOS (0.04, -0.49 to 0.44), ROS (1.27, 0.64-2.35) and risk of rebleeding within 72 hours, 1 week, and 1 month [(0.98, 0.48-1.95), (0.59, 0.13-2.03), (0.82, 0.28-2.16)]. Oral PPIs were as effective as IV scheduled PPIs and IV PPI drip for LOS (0.22, -0.61 to 0.79 and 0.16, -0.56 to 0.80) and UBT (-0.25, -1.23 to 0.65 and -0.06, -0.71 to 0.65) and superior to IV PPI drip for ROS (0.30, 0.10 to 0.78). CONCLUSION: Scheduled IV PPIs were as effective as IV PPI drip for most outcomes. Oral PPIs were comparable to scheduled IV for LOS and UBT and superior to IV PPI drip for ROS. Conclusions should be tempered by low frequency endpoints such as ROS, but question the need for IV PPI drip in ANVGIB.

On the causes and consequences of the free-roaming dog problem in southern Chile.

Free-roaming dogs are an important concern for public health, livestock production and the environment. Human behaviors-such as allowing pets to roam, abandoning dogs, or feeding stray animals-could influence free-roaming dog abundance and the frequency of occurrence of dog-caused problems. Here we aim to determine patterns of free-roaming dog abundance in urban and rural areas, to reveal spatial variation in human behaviors underlying the free-roaming dog problem, and to test for associations between free-roaming dog abundance and related problems. We conducted our study in Chile, where dogs are a major environmental issue. In Chile, as in many other Global South countries, many people leave their dogs to roam, partly due to norms and to lax enforcement of dog control laws. To address our objectives, we counted dogs in 213 transects in urban and rural areas to model dog abundance using N-mixture models. Then we conducted interviews in 553 properties around the transects to determine people's dog management, their behavior towards free-roaming dogs and the prevalence of dog-caused problems. Dog abundance was higher in transects where a higher number of owned dogs was allowed to roam, as well as in lower-income neighborhoods (based on property tax valuation). Meanwhile, rural citizens were more likely to let their dogs' roam. Dog abandonment was reported more frequently in lower-income urban neighborhoods and rural areas. Not surprisingly, we found that several problems-such as dog bites-were more frequent where we detected more free-roaming dogs. Our results highlight that the owned dog population is a central component of the free-roaming dog problem, and that human behavior is the key driver underlying the problem. Dog management programs should promote responsible dog-ownership, with a strong message focused on keeping dogs inside properties and preventing abandonment.

Field experimental evidence of sandy beach community changes in response to artificial light at night (ALAN).

Artificial light at night (ALAN) is a pervasive but still under-recognized driver of global change. In coastal settings, a large majority of the studies assessing ALAN impacts has focused on individual species, even though it is unclear whether results gathered from single species can be used to predict community-wide responses. Similarly, these studies often treat species as single life-stage entities, ignoring the variation associated with distinct life stages. This study addresses both limitations by focusing on the effects of ALAN on a sandy beach community consisting of species with distinct early- and late-life stages. Our hypothesis was that ALAN alters community structure and these changes are mediated by individual species and also by their ontogenetic stages. A field experiment was conducted in a sandy beach of north-central Chile using an artificial LED system. Samples were collected at different night hours (8-levels in total) across the intertidal (9-levels) over several days in November and January (austral spring and summer seasons). The abundance of adults of all species was significantly lower in ALAN treatments. Early stages of isopods showed the same pattern, but the opposite was observed for the early stages of the other two species. Clear differences were detected in the zonation of these species during natural darkness versus those exposed to ALAN, with some adult-juvenile differences in this response. These results support our hypothesis and document a series of changes affecting differentially both early and late life stages of these species, and ultimately, the structure of the entire community. Although the effects described correspond to short-term responses, more persistent effects are likely to occur if ALAN sources become established as permanent features in sandy beaches. The worldwide growth of ALAN suggests that the scope of its effect will continue to grow and represents a concern for sandy beach systems.

Influence of care of domestic carnivores on their predation on vertebrates.

Domestic dogs (Canis familiaris) and cats (Felis catus) are the most abundant mammalian carnivores worldwide. Given that domestic carnivores rely on human-provided food, their densities are usually independent of prey densities. Nevertheless, underfed pets may need to hunt to meet their energetic and nutritional requirements. We explored the effects of different levels of care (provision of food) of dogs and cats on their predation rates on wild vertebrates in 2 areas of southern Chile. We interviewed cat and dog owners and analyzed prey remains in scats of pets to examine how domestic dogs and cats were managed and to gather information on the wild vertebrates killed and harassed by pets. We used logistic regression to examine the association between pet care and the frequency of wild vertebrate remains in scats. The probability of a dog preying on vertebrates was higher for poorly fed than for adequately fed dogs (odds ratio = 3.7) and for poorly fed than for adequately fed cats (odds ratio = 4.7). Domestic dogs and cats preyed on most endemic and threatened mammals present in the study sites. Our results provide support for the hypothesis that the less care domestic animals receive from owners the higher the probability those animals will prey on wild vertebrates.

Widespread Presence of Domestic Dogs on Sandy Beaches of Southern Chile.

Dogs on sandy beaches are a threat to shorebirds. Managing this problem requires understanding the factors that influence the abundance of dogs in these ecosystems. We aimed to determine the proportion of beaches used by dogs and the effects of human presence on dog abundance on sandy beaches of southern Chile. We conducted dog counts and recorded the presence of tracks on 14 beaches. We used zero-inflated generalized linear mixed models to determine if the number of people, number of households, and other covariates were associated with dog abundance. We detected dog tracks on all the beaches, and dog sightings on most of them. Dogs were frequently not supervised (45%) and only 13% of them were leashed. The number of people on the beach and the number of houses near the beach were positively associated with the number of dogs on beaches. Finally, when dogs co-occurred with whimbrels (Numenius phaeopus), the probability of dog harassment was high (59%). Our work reveals that human presence determines the abundance of dogs on sandy beaches. Therefore, our study suggests that any strategy aiming at reducing dog harassment of shorebirds requires changes in those human behaviors that favor the presence of free-ranging dogs at beaches.

Urban wildlife in times of COVID-19: What can we infer from novel carnivore records in urban areas?

The onset of the COVID-19 pandemic brought an unusual decrease in human activity associated with partial and total lockdowns. Simultaneously, a series of wildlife sightings-mainly in urban areas-have been brought to public attention and often attributed to lockdown measures. Here we report on a series of wild carnivore records, including threatened species, obtained through camera traps set in urban forests, campuses, suburbs, and peri-urban areas of two cities in Chile, during partial lockdown measures. Our records are novel for Chile, a country where urban carnivore ecology is mostly unknown, and include the detection of four native carnivores, including the vulnerable güiña (Leopardus guigna) and the endangered southern river otter (Lontra provocax). These records also constitute a valuable baseline collected during partial lockdown measures in two cities of the Global South. We emphasize, however, that these findings cannot be used to argue for or against an effect of lockdown measures on wildlife. More generally, we call for caution in the interpretation of seemingly novel carnivore records during periods of lockdown and stress the value of international collaboration in evaluating the effects of the Anthropause on wildlife.

Detection of Postcolonoscopy Colorectal Neoplasia by Multi-target Stool DNA.

INTRODUCTION: Significant variability between colonoscopy operators contributes to postcolonoscopy colorectal cancers (CRCs). We aimed to estimate postcolonoscopy colorectal neoplasia (CRN) detection by multi-target stool DNA (mt-sDNA), which has not previously been studied for this purpose. METHODS: In a retrospective cohort of patients with +mt-sDNA and completed follow-up colonoscopy, positive predictive value (PPV) for endpoints of any CRN, advanced adenoma, right-sided neoplasia, sessile serrated polyps (SSP), and CRC were stratified by the time since previous colonoscopy (0-9, 10, and ≥11 years). mt-sDNA PPV at ≤9 years from previous average-risk screening colonoscopy was used to estimate CRN missed at previous screening colonoscopy. RESULTS: Among the 850 studied patients with +mt-sDNA after a previous negative screening colonoscopy, any CRN was found in 535 (PPV 63%). Among 107 average-risk patients having +mt-sDNA ≤9 years after last negative colonoscopy, any CRN was found in 67 (PPV 63%), advanced neoplasia in 16 (PPV 15%), right-sided CRN in 48 (PPV 46%), and SSP in 20 (PPV 19%). These rates were similar to those in 47 additional average risk persons with previous incomplete colonoscopy and in an additional 68 persons at increased CRC risk. One CRC (stage I) was found in an average risk patient who was mt-sDNA positive 6 years after negative screening colonoscopy. DISCUSSION: The high PPV of mt-sDNA 0-9 years after a negative screening colonoscopy suggests that lesions were likely missed on previous examination or may have arisen de novo. mt-sDNA as an interval test after negative screening colonoscopy warrants further study.

Comparison of Universal Genetic Testing vs Guideline-Directed Targeted Testing for Patients With Hereditary Cancer Syndrome.

IMPORTANCE: Hereditary factors play a key role in the risk of developing several cancers. Identification of a germline predisposition can have important implications for treatment decisions, risk-reducing interventions, cancer screening, and germline testing. OBJECTIVE: To examine the prevalence of pathogenic germline variants (PGVs) in patients with cancer using a universal testing approach compared with targeted testing based on clinical guidelines and the uptake of cascade family variant testing (FVT). DESIGN, SETTING, AND PARTICIPANTS: This prospective, multicenter cohort study assessed germline genetic alterations among patients with solid tumor cancer receiving care at Mayo Clinic cancer centers and a community practice between April 1, 2018, and March 31, 2020. Patients were not selected based on cancer type, disease stage, family history of cancer, ethnicity, or age. EXPOSURES: Germline sequencing using a greater than 80-gene next-generation sequencing platform. MAIN OUTCOMES AND MEASURES: Proportion of PGVs detected with a universal strategy compared with a guideline-directed approach and uptake of cascade FVT in families. RESULTS: A total of 2984 patients (mean [SD] age, 61.4 [12.2] years; 1582 [53.0%] male) were studied. Pathogenic germline variants were found in 397 patients (13.3%), including 282 moderate- and high-penetrance cancer susceptibility genes. Variants of uncertain significance were found in 1415 patients (47.4%). A total of 192 patients (6.4%) had incremental clinically actionable findings that would not have been detected by phenotype or family history-based testing criteria. Of those with a high-penetrance PGV, 42 patients (28.2%) had modifications in their treatment based on the finding. Only younger age of diagnosis was associated with presence of PGV. Only 70 patients (17.6%) with PGVs had family members undergoing no-cost cascade FVT. CONCLUSIONS AND RELEVANCE: This prospective, multicenter cohort study found that universal multigene panel testing among patients with solid tumor cancer was associated with an increased detection of heritable variants over the predicted yield of targeted testing based on guidelines. Nearly 30% of patients with high-penetrance variants had modifications in their treatment. Uptake of cascade FVT was low despite being offered at no cost.

Cytomegalovirus infection after liver transplantation.

Human cytomegalovirus (CMV) represents the most common opportunistic infection in liver transplant recipients. CMV infections in post liver transplant patients cause significant morbidity and mortality, directly affecting post-transplant outcomes. This review will provide the framework for the surveillance, diagnosis, prophylaxis and treatment of CMV in the liver transplant population.

Review: Pathogenesis of cholestatic liver diseases.

Cholestatic liver diseases (CLD) begin to develop after an impairment of bile flow start to affect the biliary tree. Cholangiocytes actively participate in the liver response to injury and repair and the intensity of this reaction is a determinant factor for the development of CLD. Progressive cholangiopathies may ultimately lead to end-stage liver disease requiring at the end orthotopic liver transplantation. This narrative review will discuss cholangiocyte biology and pathogenesis mechanisms involved in four intrahepatic CLD: Primary biliary cholangitis, primary sclerosing cholangitis, cystic fibrosis involving the liver, and polycystic liver disease.

A forest-specialist carnivore in the middle of the desert?Comments on https://onlinelibrary.wiley.com/doi/full/10.1002/ece3.5230.

We present comments on an article recently published in Ecology and Evolution ("High-resolution melting of the cytochrome B gene in fecal DNA: A powerful approach for fox species identification of the Lycalopex genus in Chile") by Anabalon et al. that reported the presence of Darwin's fox (Lycalopex fulvipes), a temperate forest specialist, in the hyperarid Atacama Desert of northern Chile. We argue that this putative record lacks ecological support in light of ongoing research on this endangered species, and contains numerous methodological flaws and omissions related to the molecular identification of the species. Based on these issues, we suggest the scientific community and conservation decision-makers disregard the alleged presence of the Darwin's fox in the Atacama Desert.

Acute Hepatitis Secondary to the Use of Ilex paraguariensis (Mate Tea): A Case Report and Review of Literature.

Drug induced liver injury is a very frequent cause of hepatotoxicity and within that group, herbal and dietary supplements are a well described subcategory. The following clinical vignette describes the case of a young man with acute hepatitis secondary to the use of Ilex paraguariensis, also known as yerba mate, which is a herbal product commonly drunk in South America. This is the first written case of mate tea induced hepatotoxicity.

Artificial light pollution at night (ALAN) disrupts the distribution and circadian rhythm of a sandy beach isopod.

Coastal habitats, in particular sandy beaches, are becoming increasingly exposed to artificial light pollution at night (ALAN). Yet, only a few studies have this far assessed the effects of ALAN on the species inhabiting these ecosystems. In this study we assessed the effects of ALAN on Tylos spinulosus, a prominent wrack-consumer isopod living in sandy beaches of north-central Chile. This species burrows in the sand during daylight and emerges at night to migrate down-shore, so we argue it can be used as a model species for the study of ALAN effects on coastal nocturnal species. We assessed whether ALAN alters the distribution and locomotor activity of this isopod using a light system placed in upper shore sediments close to the edge of the dunes, mimicking light intensities measured near public lighting. The response of the isopods was compared to control transects located farther away and not exposed to artificial light. In parallel, we measured the isopods' locomotor activity in the laboratory using actographs that recorded their movement within mesocosms simulating the beach surface. Measurements in the field indicated a clear reduction in isopod abundance near the source of the light and a restriction of their tidal distribution range, as compared to control transects. Meanwhile, the laboratory experiments showed that in mesocosms exposed to ALAN, isopods exhibited reduced activity and a circadian rhythm that was altered and even lost after a few days. Such changes with respect to control mesocosms with a natural day/night cycle suggest that the changes observed in the field were directly related to a disruption in the locomotor activity of the isopods. All together these results provide causal evidence of negative ALAN effects on this species, and call for further research on other nocturnal sandy beach species that might become increasingly affected by ALAN.

Primary Nonbacterial Thrombotic Endocarditis Presenting with Bowel Infarction Secondary to Superior Mesenteric Artery Embolism.

Nonbacterial thrombotic endocarditis (NBTE) is a rare antemortem diagnosis that is commonly associated with hypercoagulable states such as advanced malignancies, disseminated intravascular coagulation, and autoimmune diseases such as antiphospholipid syndrome and systemic lupus erythematosus. We present a case of a previously healthy 42-year-old man who presented with small bowel infarction caused by embolic occlusion of the superior mesenteric artery and was subsequently diagnosed with NBTE. Despite thorough investigation, efforts to find an underlying cause failed to reveal any associated systemic illnesses. This case report emphasizes the importance of further investigation into the possible underlying causes of NBTE, as it can manifest without any apparent systemic factors.