Seroprevalence of five parasitic pathogens in pregnant women in ten Caribbean countries.

To date, published epidemiological studies of parasitic infections in humans in the Caribbean region are very limited. Here, we report the seroprevalence of five parasitic pathogens, including Ascaris lumbricoides, Entamoeba histolytica, Giardia lamblia, Schistosoma mansoni, and Toxocara canis in 435 serum samples collected between 2008 and 2011 from pregnant women in ten Caribbean islands. We tested the serum samples for IgG antibodies against the five parasites by enzyme-linked immunosorbent assay (ELISA). Among them, 66.2 % were serologically positive for at least one parasite. The most prevalent parasite was G. lamblia (40.5 %), followed by A. lumbricoides (37.9 %), T. canis (14.5 %), E. histolytica (6.7 %), and S. mansoni (3.0 %). Evidence of infections of G. lamblia and A. lumbricoides were detected in all ten Caribbean countries. Seroprevalence estimates significantly differed between countries for A. lumbricoides, E. histolytica, and T. canis (p values <0.001). For S. mansoni, significance was observed by Fisher's exact test (p = 0.013) but not by multiple comparisons. The prevalence of G. lamblia was not significantly different between countries (p = 0.089). A significant negative correlation between the gross domestic product (GDP) per capita and overall seroprevalence by country was also observed (Pearson's r = -0.9202, p = 0.0002). The data strongly indicates that neglected parasitic infections remain a significant health burden on people in these countries. Thus, justification has been provided to regional health planners to enhance existing public health surveillance programs on parasitic diseases and to heighten the public's awareness through education and outreach programs on how they can minimize the occurrence of parasitic infections.

Public health response and lessons learned from the 2014 chikungunya epidemic in Grenada.

In June 2014, the first cases of chikungunya virus (CHIKV) were diagnosed on the island of Carriacou, part of the tri-island state of Grenada. In the three months that followed, CHIKV spread rapidly, with conservative estimates of the population infected of at least 60%. Multiple challenges were encountered in the battle to manage the spread and impact of this high-attack rate virus, including 1) limited indigenous laboratory diagnostic capabilities; 2) an under-resourced health care system; 3) a skeptical general public, hesitant to accept facts about the origin and mode of transmission of the new virus; and 4) resistance to the vector control strategies used. Lessons learned from the outbreak included the need for 1) a robust and reliable epidemiological surveillance system; 2) effective strategies for communicating with the general population; 3) exploration of other methods of mosquito vector control; and 4) a careful review of all health care policies and protocols to ensure that effective, organized responses are triggered when an infectious outbreak occurs.

Toxoplasmosis in the Caribbean islands: literature review, seroprevalence in pregnant women in ten countries, isolation of viable Toxoplasma gondii from dogs from St. Kitts, West Indies with report of new T. gondii genetic types.

Little is currently known of clinical toxoplasmosis in humans and animals in the Caribbean. We investigated the prevalence of IgG and IgM antibodies in 437 pregnant women from 10 English speaking Caribbean countries. Overall, antibodies (IgG) to Toxoplasma gondii (modified agglutination test, MAT, cut-off 1:6) were found in 174 (39.8 %) of 437 human sera; specifically 12 of 38 from Antigua-Barbuda, 26 of 52 from Belize, 9 of 50 from Bermuda, 29 of 49 from Dominica, 18 of 49 from Grenada, 16 of 47 from Jamaica, 5 of 15 from Montserrat, 8 of 44 from St. Kitts/Nevis, 24 of 45 from St. Lucia, and 27 of 50 from St. Vincent/Grenadines were seropositive. All IgG-positive sera were tested for IgM antibodies using the immunocapture method; all sera were negative for IgM antibodies. Additionally, tissues and sera of 45 dogs from St. Kitts were examined for T. gondii infection. Antibodies (IgG, MAT, 1:≥25) were found in 19 (42.2 %) of 45 dogs. Muscle samples (tongue, leg) of 19 seropositive dogs were digested in pepsin, and homogenates were bioassayed in mice. Viable T. gondii were isolated from 6 dogs. T. gondii isolates were further propagated in cell culture. PCR-RFLP genotyping of cell culture derived tachyzoites using 10 genetic markers, SAG1, SAG2 (5' and 3' SAG2, and alt.SAG2) SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico revealed that 4 isolates were ToxoDB PCR-RFLP genotype #2, and 2 were new genotypes #264 and #265. Review of 22 viable T. gondii isolates from chickens, dogs, and cats from Grenada and St. Kitts revealed that 1 isolate was type II, 13 were type III, and 8 were atypical. Thus, type III strains were predominant. Overall, the study revealed high prevalence of T. gondii in the Caribbean islands.

Prenatal exposure to persistent organic pollutants and polybrominated diphenyl ethers in 10 Caribbean countries.

Prenatal exposures to legacy persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) and dioxin-like compounds (DLC), as well as polybrominated diphenyl ethers (PBDE), were analyzed in pregnant women from 10 Caribbean countries. A total of 438 samples were collected and descriptive statistics calculated and compared to comparable Canadian Health Measure Survey (CHMS) and U.S. National Health and Nutritional Examination Survey (NHANES) datasets. Maternal POPs blood concentrations were found to be generally relatively low in the Caribbean samples compared with the U.S. and Canada datasets. Evidence of exposure to DLC and PBDE was established. DLC levels ranged from a geometric mean low of 3.96 pg/g lipids in Antigua and Barbuda to a high of 11.4 pg/g lipids in St. Lucia. Several of the PBDEs (15, 17, 25, 28, 33, 100) were detected in less than 60% of the country' samples. For PBDE-47, significantly higher levels were found in Bermuda, while Jamaica recorded a significantly low level. The overall calculated concentration of PBDE-47 for the Caribbean (5.33 µg/kg lipids) was significantly lower than the concentrations measured for the U.S. (10.83 µg/kg lipids) and Canada (23.90 µg/kg lipids). This study confirms that prenatal expose to multiple environmental chemicals is taking place in the Caribbean and highlights the need to implement surveillance programs that continuously monitor, intervene, and evaluate the levels of these toxic environmental contaminants to ensure that they are reduced as much as possible and that the health risk to humans, in particular the unborn child, are minimized.

Estimating the burden of acute gastrointestinal illness in Grenada.

This is the first study conducted in Grenada, with a population of approximately 108,000, to quantify the magnitude, distribution, and burden of self-reported acute gastroenteritis (AGE). A retrospective population survey was conducted in October 2008 and April 2009 and a laboratory survey from October 2008 to September 2009. The estimated monthly prevalence of AGE was 10.7% (95% CI 9.0-12.6; 1.4 episodes/ person-year), with a median of 3 days of illness. Of those who reported AGE, 31% sought medical care (stool samples were requested from 12.5%); 10% took antibiotics; 45% took non-prescribed medication; and 81% reported restricted activity. Prevalence of AGE was significantly higher among children aged <5 years (23.5%, p < 0.001). Of the AGE stool samples submitted to the laboratory for analysis, 12.1% were positive for a foodborne pathogen. Salmonella enteritidis was the most common foodborne pathogen associated with AGE-related illness. The estimated percentage of underreporting of syndromic AGE to the Ministry of Health was 69%. In addition, for every laboratory-confirmed foodborne/AGE pathogen, it was estimated that there were 316 additional cases occurring in the population. The minimum estimated cost associated with treatment for AGE was US$ 703,950 each year, showing that AGE has a potentially significant economic impact in Grenada.

Temporal trends in ambient fine particulate matter and the impacts of COVID-19 on this pollutant in Grenada, West Indies.

Most Caribbean islands do not have air pollution surveillance programs. Those who live in these countries are exposed to ambient air pollution from a variety of sources including motor vehicles, ocean-going vessels, and Saharan dust. We conducted an air sampling exposure study in Grenada to describe daily changes in fine particulate matter (PM2.5) pollution, and during Saharan dust episodes. Further, we assessed the impacts of COVID-19 public health interventions on PM2.5 concentrations in 2020. Four fixed-site PurpleAir monitors were installed throughout Grenada, and one on the neighboring island of Carriacou. PM2.5 was measured between January 6 and December 31, 2020. We classified each of these days based on whether COVID-19 public health mitigation measures were in place or not. Descriptive analyses were performed to characterize fluctuations in PM2.5, and we assessed the impacts of public health restrictions on PM2.5 using multivariate regression. The mean daily PM2.5 concentration in 2020 was 4.4 µg/m3. During the study period, the minimum daily PM2.5 concentration was 0.7 µg/m3, and the maximum was 20.4 µg/m3. Daily mean PM2.5 concentrations more than doubled on Saharan dust days (8.5 vs 3.6 µg/m3; p < 0.05). The daily mean PM2.5 concentrations were estimated to be 1.2 µg/m3 lower when COVID-19 restrictions were in effect. Ambient PM2.5 concentrations in Grenada are relatively low compared to other countries; however, Saharan dust episodes represent an important source of exposure. Low-cost sensors provide an opportunity to increase surveillance of air pollution in the Caribbean, however their value could be enhanced with the development of correction algorithms that more closely approximate values from reference-grade monitors.Implications: This study describes daily fluctuations in ambient PM2.5 concentrations in Grenada in 2020. Overall, concentrations of PM2.5 were low; however, we found that Saharan dust events cause daily exceedances in PM2.5 above the current 24-hr limits of the World Health Organization. Moreover, the constructed models suggest that public health interventions to reduce the spread of COVID-19 reduced PM2.5 concentrations by 27%.

Infectious diseases genomic surveillance capacity in the Caribbean: A retrospective analysis of SARS-CoV-2.

Background: The ongoing coronavirus diseases 2019 (COVID-19) pandemic with its numerous variants of concern has shown the need to have a robust and complete global infectious diseases genomic surveillance network worldwide. Various clinical and research institutions have stepped up to perform SARS-CoV-2 sequencing thus enhancing the understanding of this virus' global evolution. However, given that genomic sequencing capacities and capabilities are not available in every region or country, significant gaps exist, which lead to geographic blind spots. One such region is the Caribbean. This paper measures the Caribbean region's SARS-CoV-2 genomic sequencing capacity and highlights the need to improve further regional genomics surveillance capacities and capabilities, which are essential for efficient health interventions for infectious diseases. Methods: A map showing SARS-CoV-2 sequences available for each Caribbean Island was constructed using SARS-CoV-2 genomic, epidemiological and populational data obtained from GISAID, the World Health Organization, the United Nations, and the World Bank. The number of reported SARS-CoV-2 cases and the proportion of cases sequenced in each Caribbean Island was then analysed by the Gross Domestic Product per capita and political status. Findings: As of August 6, 2022, the number of SARS-CoV-2 sequences from the Caribbean are underrepresented with only 40,190 (1.07%) of the over 3.76 million documented cases sequenced, which is further exacerbated by a disparity based not only on the country's income but also on its political status (sovereign country versus dependent or integrated) and accessibility to sequencing technologies. There are a limited number of sequencing centres based in the Caribbean islands with the majority located on the American and European continents. Using mobile sequencing technologies while concomitantly investing in data analysis training could lead to greater and more sustainable coverage. Interpretation: Considering the Caribbean region's dispersed heterogeneous populations, varying political regimes, and resource-constrained healthcare systems, further development of local next-generation sequencing capacity and capabilities in the Caribbean region is needed to achieve global public health goals. Funding: No funding source was required for this study.

Evaluation of Bisphenol A in Pregnant Women from 10 Caribbean Countries.

Bisphenol A (BPA), a phenolic chemical incorporated into many plastic products, has been found to act as an endocrine disruptor that potentially is linked to adverse neurodevelopmental outcomes. Prenatal BPA concentration levels were assessed in 10 English-speaking Caribbean countries by randomly selecting 15 maternal urine samples from approximately 50 pregnant women samples collected in each island and then comparing the findings with comparable data from Canada and the U.S. BPA was detected in all samples ranging from a low geometric mean of 1.46 µg/L (St. Lucia) to a high of 4.88 µg/L (St. Kitts & Nevis). All of the Caribbean islands sampled had geometric mean concentration levels that were higher than those recorded in two Canadian biomonitoring surveys (1.26 µg/L and 0.80 µg/L) and the U.S. NHANES survey (1.39 µg/L). This first biomonitoring survey of BPA concentration levels in maternal urine samples taken from Caribbean countries clearly points to the need for Caribbean governments and public health officials to first engage in legislative and regulatory efforts to ban or minimize the importation and use of BPA products used the Caribbean and, second, to continue to conduct biomonitoring surveys so as to ensure that these laws and regulations are indeed leading to a decrease of BPA concentrations in Caribbean populations.

Strengthening integrated research and capacity development within the Caribbean region.

BACKGROUND: The Caribbean region, like other developing regions of the world, faces significant challenges in conducting research, especially in the context of limited resource capacities and capabilities. Further, due to its diverse and multiple island states, research capacity is scattered and unevenly spread within the region. The Caribbean EcoHealth Programme (CEHP) is a research program that is structured to improve the capacity and capability of health professionals in the Caribbean region to respond in integrative and innovative ways to on-going and emerging environmental health challenges by means of multi-sectoral interventions. METHODS: Core parts of the CEHP's mission are to (1) conduct collaborative research in areas that the region has identified as critical; (2) build and strengthening integrated approaches to research; and (3) develop and enhance basic research capacity within the Caribbean region.Fundamental to the success of the CEHP's human and resource development mission has been its use of the Atlantis Mobile Laboratory (AML). The AML has allowed the CEHP program to move throughout the Caribbean and be able to respond to calls for specific research and capacity building opportunities. RESULTS: The CEHP's five main research projects have generated the following results: (1) the Persistent Organic Pollutants (POPs) study has evaluated human exposures to POPs, heavy metals, pesticides, and zoonotic infections; (2) the Burden of Illness (BOI) studies have developed protocols for the testing of foodborne microorganisms, strengthen laboratory analytical capabilities, and determined the prevalence and incidence of food-borne illness; (3) the Rainwater Harvesting (RWH) study has evaluated the microbial and chemical quality of rainwater harvesting systems; (4) the Ecotoxicology Water (ETW) studies have provided much needed data on the quality of recreational and drinking water supplies, and (5) the Food Safety Training Program has developed Diploma and M.Sc Agri-Food Safety and Quality Assurance programmes. CONCLUSIONS: The CEHP program provides a successful example of how a collaborative instead of researcher driven research agenda can lead to not only the generation of needed information, but also leave within the region where the research has been carried out the capacity and capabilities to continue to do so independent of outside interventions.

Preliminary Assessment of COVID-19 Implications for the Water and Sanitation Sector in Latin America and the Caribbean.

COVID-19 has had a severe impact on human health, as well as in social and economic terms, with implications for the management and governance of the water and sanitation sector. These implications are evident in Latin America and the Caribbean due to existing challenges the region faces in accessing water and sanitation services. In spite of significant advances, around 65 million people in the LAC region currently lack appropriate access to water and soap to wash their hands-one of the most basic measures to prevent the spread of disease. Furthermore, social and economic vulnerabilities have exacerbated the effects of the pandemic in the region, particularly among those living in poverty. The COVID-19 pandemic thus requires the mobilization of frameworks such as the human rights to water and sanitation, specifically considering the region's realities. This paper provides a review of some of the challenges currently faced in the region and advances a series of recommendations for enhancing access to water, sanitation and hygiene. The importance of effective governance, management and communication strategies in the water provisioning sector is highlighted in the context of the pandemic, and the role of science and research for adequate decision making is emphasized.

Knowledge, attitudes, and practices regarding rabies in Grenada.

OBJECTIVE: While Grenada attained a zero-human-rabies case status since 1970, the authors conducted the first study to assess knowledge, attitudes, and practices that may contribute to this status as well as to receive feedback on the rabies control program in Grenada. METHODOLOGY: A cross-sectional survey was conducted in July, 2017 with 996 households on the mainland. A questionnaire was administered to collect information on knowledge of rabies and prevention, vaccination practices, perception of institutional responsibilities for rabies control, and evaluation of the anti-rabies program. RESULTS: Of the 996 households, 617 (62%) had owners of animals that can be infected with rabies and were included in the analysis. Respondents were very aware of rabies as a disease that can infect animals and humans. The rate of participation in the vaccination program was 51.6% for pets and 38.0% for livestock. About 40% of respondents were knowledgeable about the extent of protection from the rabies vaccine. Respondents did not demonstrate exceptionally high levels of knowledge about animals that were likely to be infected with rabies, neither the anti-rabies programs that were conducted in Grenada. The three most frequent recommendations made to improve the rabies-control programs were: increase education programs, control the mongoose population, and expand the vaccination period each year. CONCLUSIONS: Conducting a comprehensive national rabies education program, expanding the vaccination program, and increasing the rate of animal vaccination are important steps that need to be taken to maintain the current zero-human-case status.

Antibiotic Use in Poultry Production in Grenada.

OBJECTIVE: Research is often lacking in low-income countries to substantiate the regulation of antibiotics in poultry production. Nonregulation of antibiotics in food animal industries has implications for human health. This study was conducted to provide an understanding of farmers' knowledge, attitudes, and practices regarding the use of antibiotics in poultry production in Grenada. METHOD: A cross-sectional study was conducted in August-September, 2016, surveying 30 poultry farmers each having 500 or more chickens grown for commercial purposes. RESULTS: More than 1000 birds were kept on 18 (60.0%) farms. Antibiotics were used on the majority of farms (25, 83.3%). More than half of the respondents, 19 (63.3%), stated they were only somewhat aware of issues related to the use of antibiotics and the majority, 21 (70.0%), were also unable to define antimicrobial resistance. There was inconsistency in the farmers' knowledge about how and when to use antibiotics. There was also a high level of noncompliance with manufacturers' recommendations for use of antibiotics. The respondents were not aware of local programs to monitor antibiotic use or manage antibiotic resistance in the poultry industry. CONCLUSION: Generally, the farmers' knowledge and practices were inconsistent with recommendations by the World Health Organization for antibiotic stewardship. While low-income countries, such as Grenada, are challenged with the lack of resources to undertake research and implement responsive actions, this research highlights the need for some immediate measures of remedy, such as education of farmers and monitoring procurement and use of antibiotics, to reduce risk to public health.

Comparison of fused-filament fabrication to direct compression and injection molding in the manufacture of oral tablets.

Oral tablets are a convenient form to deliver active pharmaceutical ingredients (API) and have a high level of acceptance from clinicians and patients. There is a wide range of excipients available for the fabrication of tablets thereby offering a versatile platform for the delivery of therapeutic agents to the gastrointestinal tract. However, the geometry of tablets is limited by conventional manufacturing processes. This study aimed to compare three manufacturing processes in the production of flat-faced oral tablets using the same formulation composed of a polymer blend and caffeine as a model drug: fused-filament fabrication (FFF), direct compression (DC) and injection molding (IM). Hot-melt extrusion was used to convert a powder blend into feedstock material for FFF and IM processes, while DC was performed on the powder mixture. Tablets were produced with the same dimensions and were characterized for their physical and dissolution properties. There were statistical differences in the physical properties and drug release profiles of the tablets produced by the different manufacturing processes. DC tablets displayed immediate release, IM provided sustained release over 48 h, and FFF tablets displayed both release types depending on the printing parameters. FFF continues to demonstrate high potential as a manufacturing process for the efficient production of personalized oral tablets.

DNA Methylation Controls Metastasis-Suppressive 14q32-Encoded miRNAs.

Expression of 14q32-encoded miRNAs is a favorable prognostic factor in patients with metastatic cancer. In this study, we used genomic inhibition of DNA methylation through disruption of DNA methyltransferases DNMT1 and DNMT3B and pharmacologic inhibition with 5-Aza-2'-deoxycytidine (5-Aza-dC, decitabine) to demonstrate that DNA methylation predominantly regulates expression of metastasis-suppressive miRNAs in the 14q32 cluster. DNA demethylation facilitated CCCTC-binding factor (CTCF) recruitment to the maternally expressed gene 3 differentially methylated region (MEG3-DMR), which acts as a cis-regulatory element for 14q32 miRNA expression. 5-Aza-dC activated demethylation of the MEG3-DMR and expression of 14q32 miRNAs, which suppressed adhesion, invasion, and migration (AIM) properties of metastatic tumor cells. Cancer cells with MEG3-DMR hypomethylation exhibited constitutive expression of 14q32 miRNAs and resistance to 5-Aza-dC-induced suppression of AIM. Expression of methylation-dependent 14q32 miRNAs suppressed metastatic colonization in preclinical models of lung and liver metastasis and correlated with improved clinical outcomes in patients with metastatic cancer. These findings implicate epigenetic modification via DNA methylation in the regulation of metastatic propensity through miRNA networks and identify a previously unrecognized action of decitabine on the activation of metastasis-suppressive miRNAs. SIGNIFICANCE: This study investigates epigenetic regulation of metastasis-suppressive miRNAs and the effect on metastasis.

Tumor-reprogrammed resident T cells resist radiation to control tumors.

Successful combinations of radiotherapy and immunotherapy depend on the presence of live T cells within the tumor; however, radiotherapy is believed to damage T cells. Here, based on longitudinal in vivo imaging and functional analysis, we report that a large proportion of T cells survive clinically relevant doses of radiation and show increased motility, and higher production of interferon gamma, compared with T cells from unirradiated tumors. Irradiated intratumoral T cells can mediate tumor control without newly-infiltrating T cells. Transcriptomic analysis suggests T cell reprogramming in the tumor microenvironment and similarities with tissue-resident memory T cells, which are more radio-resistant than circulating/lymphoid tissue T cells. TGFß is a key upstream regulator of T cell reprogramming and contributes to intratumoral Tcell radio-resistance. These findings have implications for the design of radio-immunotherapy trials in that local irradiation is not inherently immunosuppressive, and irradiation of multiple tumors might optimize systemic effects of radiotherapy.

Network of Ethical Relationships model for global North-South population health research.

Although a substantial body of literature exists that details how to address ethical issues and provide oversight for traditional research study designs, there currently is very little guidance available to researchers on how to deal with the unique and novel challenges that arise when conducting research that goes outside of these well-defined boundaries. One such example is North-South (N-S) team-based global population health (GPH) research. This paper presents a Network of Ethical Relationships (NER) model which can allow GPH researchers better understand and resolve ethical issues that arise in N-S collaborative research efforts. The NER model elucidates some of the core relationships involved in GPH research and sheds light on the complex milieu of moral, institutional, societal and legal processes in which it is embedded. The utility of the NER model is examined by reviewing 14 GPH research teams, looking at two relationships in more detail - Researcher-Ethics Board, and Researcher-Funder relationships. The paper argues that improved dialogue and flexibility in the application of formal ethical rules and procedures can lead to research being conducted in a more ethical manner since it better accounts for the multitude of voices and perspectives influencing researchers' choices and actions.

Material Considerations for Fused-Filament Fabrication of Solid Dosage Forms.

Material choice is a fundamental consideration when it comes to designing a solid dosage form. The matrix material will ultimately determine the rate of drug release since the physical properties (solubility, viscosity, and more) of the material control both fluid ingress and disintegration of the dosage form. The bulk properties (powder flow, concentration, and more) of the material should also be considered since these properties will influence the ability of the material to be successfully manufactured. Furthermore, there is a limited number of approved materials for the production of solid dosage forms. The present study details the complications that can arise when adopting pharmaceutical grade polymers for fused-filament fabrication in the production of oral tablets. The paper also presents ways to overcome each issue. Fused-filament fabrication is a hot-melt extrusion-based 3D printing process. The paper describes the problems encountered in fused-filament fabrication with Kollidon® VA64, which is a material that has previously been utilized in direct compression and hot-melt extrusion processes. Formulation and melt-blending strategies were employed to increase the printability of the material. The paper defines for the first time the essential parameter profile required for successful 3D printing and lists several pre-screening tools that should be employed to guide future material formulation for the fused-filament fabrication of solid dosage forms.

Author Correction: Integrated molecular subtyping defines a curable oligometastatic state in colorectal liver metastasis.

In the originally published version of this Article, the affiliation details for Kevin P. White inadvertently omitted 'Tempus Labs, Chicago, IL, 60654, USA'. This has now been corrected in both the PDF and HTML versions of the Article.

Integrated molecular subtyping defines a curable oligometastatic state in colorectal liver metastasis.

The oligometastasis hypothesis suggests a spectrum of metastatic virulence where some metastases are limited in extent and curable with focal therapies. A subset of patients with metastatic colorectal cancer achieves prolonged survival after resection of liver metastases consistent with oligometastasis. Here we define three robust subtypes of de novo colorectal liver metastasis through integrative molecular analysis. Patients with metastases exhibiting MSI-independent immune activation experience the most favorable survival. Subtypes with adverse outcomes demonstrate VEGFA amplification in concert with (i) stromal, mesenchymal, and angiogenic signatures, or (ii) exclusive NOTCH1 and PIK3C2B mutations with E2F/MYC activation. Molecular subtypes complement clinical risk stratification to distinguish low-risk, intermediate-risk, and high-risk patients with 10-year overall survivals of 94%, 45%, and 19%, respectively. Our findings provide a framework for integrated classification and treatment of metastasis and support the biological basis of curable oligometastatic colorectal cancer. These concepts may be applicable to many patients with metastatic cancer.