An in vitro platform supports generation of human innate lymphoid cells from CD34+ hematopoietic progenitors that recapitulate ex vivo identity.

Innate lymphoid cells (ILCs) are critical effectors of innate immunity and inflammation, whose development and activation pathways make for attractive therapeutic targets. However, human ILC generation has not been systematically explored, and previous in vitro investigations relied on the analysis of few markers or cytokines, which are suboptimal to assign lineage identity. Here, we developed a platform that reliably generated human ILC lineages from CD34+ hematopoietic progenitors derived from cord blood and bone marrow. We showed that one culture condition is insufficient to generate all ILC subsets, and instead, distinct combination of cytokines and Notch signaling are essential. The identity of natural killer (NK)/ILC1s, ILC2s, and ILC3s generated in vitro was validated by protein expression, functional assays, and both global and single-cell transcriptome analysis, recapitulating the signatures and functions of their ex vivo ILC counterparts. These data represent a resource to aid in clarifying ILC biology and differentiation.

In Situ Maturation and Tissue Adaptation of Type 2 Innate Lymphoid Cell Progenitors.

Innate lymphoid cells (ILCs) are generated early during ontogeny and persist predominantly as tissue-resident cells. Here, we examined how ILCs are maintained and renewed within tissues. We generated a single cell atlas of lung ILC2s and found that Il18r1+ ILCs comprise circulating and tissue-resident ILC progenitors (ILCP) and effector-cells with heterogeneous expression of the transcription factors Tcf7 and Zbtb16, and CD103. Our analyses revealed a continuous differentiation trajectory from Il18r1+ ST2- ILCPs to Il18r- ST2+ ILC2s, which was experimentally validated. Upon helminth infection, recruited and BM-derived cells generated the entire spectrum of ILC2s in parabiotic and shield chimeric mice, consistent with their potential role in the renewal of tissue ILC2s. Our findings identify local ILCPs and reveal ILCP in situ differentiation and tissue adaptation as a mechanism of ILC maintenance and phenotypic diversification. Local niches, rather than progenitor origin, or the developmental window during ontogeny, may dominantly imprint ILC phenotypes in adult tissues.

UTexas Aptamer Database: the collection and long-term preservation of aptamer sequence information.

A growing interest in aptamer research, as evidenced by the increase in aptamer publications over the years, has led to calls for a go-to site for aptamer information. A comprehensive, publicly available aptamer dataset, which may be a repository for aptamer data, standardize aptamer reporting, and generate opportunities to expand current research in the field, could meet such a demand. There have been several attempts to create aptamer databases; however, most have been abandoned or removed entirely from public view. Inspired by previous efforts, we have published the UTexas Aptamer Database, https://sites.utexas.edu/aptamerdatabase, which includes a publicly available aptamer dataset and a searchable database containing a subset of all aptamer data collected to date (1990-2022). The dataset contains aptamer sequences, binding and selection information. The information is regularly reviewed internally to ensure accuracy and consistency across all entries. To support the continued curation and review of aptamer sequence information, we have implemented sustaining mechanisms, including researcher training protocols, an aptamer submission form, data stored separately from the database platform, and a growing team of researchers committed to updating the database. Currently, the UTexas Aptamer Database is the largest in terms of the number of aptamer sequences with 1,443 internally reviewed aptamer records.

RNA-guided DNA base damage repair via DNA polymerase-mediated nick translation.

DNA repair is mediated by DNA synthesis guided by a DNA template. Recent studies have shown that DNA repair can also be accomplished by RNA-guided DNA synthesis. However, it remains unknown how RNA can guide DNA synthesis to repair DNA damage. In this study, we revealed the molecular mechanisms underlying RNA-guided DNA synthesis and base damage repair mediated by human repair DNA polymerases. We showed that pol ß, pol κ, and pol ι predominantly synthesized one nucleotide, and pol η, pol ν, and pol θ synthesized multi-nucleotides during RNA-guided DNA base damage repair. The steady-state kinetics showed that pol η exhibited more efficient RNA-guided DNA synthesis than pol ß. Using molecular dynamics simulation, we further revealed dynamic conformational changes of pol ß and pol η and their structural basis to accommodate the RNA template and misoriented triphosphates of an incoming nucleotide. We demonstrated that RNA-guided base damage repair could be accomplished by the RNA-guided DNA strand-displacement synthesis and nick translation leading to nick ligation in a double-strand DNA region. Our study revealed a novel RNA-guided base damage repair pathway during transcription and DNA replication.

Heterologous vaccination interventions to reduce pandemic morbidity and mortality: Modeling the US winter 2020 COVID-19 wave.

COVID-19 remains a stark health threat worldwide, in part because of minimal levels of targeted vaccination outside high-income countries and highly transmissible variants causing infection in vaccinated individuals. Decades of theoretical and experimental data suggest that nonspecific effects of non-COVID-19 vaccines may help bolster population immunological resilience to new pathogens. These routine vaccinations can stimulate heterologous cross-protective effects, which modulate nontargeted infections. For example, immunization with Bacillus Calmette-Guérin, inactivated influenza vaccine, oral polio vaccine, and other vaccines have been associated with some protection from SARS-CoV-2 infection and amelioration of COVID-19 disease. If heterologous vaccine interventions (HVIs) are to be seriously considered by policy makers as bridging or boosting interventions in pandemic settings to augment nonpharmaceutical interventions and specific vaccination efforts, evidence is needed to determine their optimal implementation. Using the COVID-19 International Modeling Consortium mathematical model, we show that logistically realistic HVIs with low (5 to 15%) effectiveness could have reduced COVID-19 cases, hospitalization, and mortality in the United States fall/winter 2020 wave. Similar to other mass drug administration campaigns (e.g., for malaria), HVI impact is highly dependent on both age targeting and intervention timing in relation to incidence, with maximal benefit accruing from implementation across the widest age cohort when the pandemic reproduction number is >1.0. Optimal HVI logistics therefore differ from optimal rollout parameters for specific COVID-19 immunizations. These results may be generalizable beyond COVID-19 and the US to indicate how even minimally effective heterologous immunization campaigns could reduce the burden of future viral pandemics.

The Immunologists' Guide to Pandemic Preparedness.

Immunologists are central to fighting any pandemic. From pathogenesis to disease modeling, pharmaceuticals to vaccines, immunologists play a crucial role in translating basic science into effective response strategies. This article describes our view on how lessons from the coronavirus disease 2019 (COVID-19) pandemic can be developed into an immunologists' guide for preparedness for future pandemics.

Deep Dive Into Gaps and Barriers to Implementation of Antimicrobial Stewardship Programs in Hospitals in Latin America.

BACKGROUND: Antimicrobial resistance has worsened in Latin America. There is an urgent need to understand the development of antimicrobial stewardship programs (ASPs) and the barriers to implementing effective ASPs in light of limited national action plans or policies to promote ASPs in the region. METHODS: We performed a descriptive mixed-methods study of ASPs in 5 Latin American countries in March-July 2022. An electronic questionnaire with an associated scoring system (hospital ASP self-assessment) was used, and ASP development was classified based on the scores (inadequate, 0-25; basic, 26-50; intermediate, 51-75; or advanced, 76-100). Interviews among healthcare workers (HCWs) involved in antimicrobial stewardship (AS) inquired about behavioral and organizational factors that influence AS activities. Interview data were coded into themes. Results from the ASP self-assessment and interviews were integrated to create an explanatory framework. RESULTS: Twenty hospitals completed the self-assessment, and 46 AS stakeholders from these hospitals were interviewed. ASP development was inadequate/basic in 35% of hospitals, intermediate in 50%, and advanced in 15%. For-profit hospitals had higher scores than not-for-profit hospitals. Interview data validated the self-assessment findings and provided further insight into ASP implementation challenges, which included limited formal hospital leadership support, inadequate staffing and tools to perform AS work more efficiently, limited awareness of AS principles by HCWs, and limited training opportunities. CONCLUSIONS: We identified several barriers to ASP development in Latin America, suggesting the need to create accurate business cases for ASPs to obtain the necessary funding for their effective implementation and sustainability.

A phase Ib trial of mivavotinib (TAK-659), a dual SYK/FLT3 inhibitor, in patients with relapsed/refractory acute myeloid leukemia.

Mivavotinib (TAK-659) is an investigational type 1 tyrosine kinase inhibitor with dual activity against spleen tyrosine kinase (SYK) and FMS-like tyrosine kinase 3 (FLT3). We conducted a phase Ib study to investigate the safety, tolerability, and efficacy of mivavotinib in patients with refractory and/or relapsed (R/R) acute myeloid leukemia (AML). Both daily (QD) and twice daily (BID) dosing regimens were evaluated. A total of 43 patients were enrolled, and there were 5 complete responses (4 with incomplete count recovery). In the QD dosing regimen, the maximum tolerated dose (MTD) was not reached up to 160 mg QD per protocol; 140 mg QD was identified as the recommended phase II dose. In the BID dosing regimen, the MTD was 60 mg BID. Thirty patients (70%) experienced a bleeding event on study; the majority were grades 1 or 2, were resolved without mivavotinib modification, and were not considered related to study treatment. Eleven patients (26%) experienced grade ≥3 bleeding events, which were observed most frequently with the 80 mg BID dose. We conducted platelet aggregation studies to investigate the potential role of mivavotinib-mediated SYK inhibition on platelet function. The bleeding events observed may have been the result of several confounding factors, including AML disease status, associated thrombocytopenia, and high doses of mivavotinib. Overall, these findings indicate that the activity of mivavotinib in R/R AML is modest. Furthermore, any future clinical investigation of this agent should be undertaken with caution, particularly in thrombocytopenic patients, due to the potential bleeding risk of SYK inhibition. ClinicalTrials.gov: NCT02323113.

Characterization of 554 Mexican Patients With Nonsyndromic Cleft Lip and Palate: Descriptive Study.

Orofacial clefts are one of the most common birth defects and the most common craniofacial malformation worldwide. The most common orofacial clefts (OFCs) are congenital cleft lip with or without cleft palate (CL ± P) and isolated cleft palate (CP). The incidence of OFCs varies depending on region and ethnicity; however, it affects approximately 1 in 600 newborns worldwide. In most cases, CL ± P and CP are multifactorial congenital malformations, where both exogenous and genetic factors play an important role. The objective of this study was to describe the frequency of potential risk factors associated with the development of CL ± P and CP in Mexican population. Patients were referred for multisystemic treatment, from private and public institutions in different regions of the country (center, north, and south). Sociodemographic information, prenatal and parental history were obtained through direct interviews with the patients or the patients' mothers in the case of underaged patients. Referred patients were invited to participate in the study. No interventions were applied for this study. The relationship between these factors and the prevalence of CL ± P and CP was studied. A total of 554 patients were included, the majority with CLP (30% to 7%), statistically significant differences were found for folic acid ( P = 0.02) consumption. Familial aggregation did not reach statistical significance for first-degree family members ( P = 0.34) but was significant for second-degree family members ( P = 0.007). More risk factors associated with CL ± P and CP may still be unknown, prompting more epidemiological research and research in other little-studied areas, such as; specific genetic factors in Mexican population.

Effects of storage up to 1 year on the in vitro antimicrobial activity of preformulated antibiotic-impregnated calcium sulfate beads.

OBJECTIVE: To compare antimicrobial activity as demonstrated by the zone of inhibition (ZOI) produced by antibiotic-impregnated calcium sulfate (CaSO4 ) beads after storage for 0, 3, 6, 9, and 12 months. STUDY DESIGN: Controlled laboratory study. SAMPLE POPULATION: Three-millimeter diameter CaSO4 beads impregnated with vancomycin (125 mg/mL), or amikacin (250 mg/mL), or without antibiotic (control). METHODS: Calcium sulfate beads were created at the onset of the study. Individual beads were separated in sterile containers and stored in a closed cabinet at room temperature and humidity for 0, 3, 6, 9, or 12 months until testing. The ZOI against methicillin-resistant Staphylococcus pseudintermedius, methicillin-resistant Staphylococcus aureus, and Pseudomonas aeruginosa was recorded with serial replating on a fresh lawn of bacteria every 24 h until beads failed to produce a ZOI. The ZOIs and their changes were compared with mixed-effects linear models. Eluted concentrations of vancomycin measured with high-performance liquid chromatography were reported. RESULTS: At 24 h, ZOIs were comparable regardless of time since formulation, except vancomycin against P. aeruginosa, which failed to generate a ZOI. The daily changes of ZOI and duration of activity of antibiotics did not vary between storage length (p > .05). There was no consistent change in eluted drug concentration between storage length of beads. CONCLUSION: Light protected storage at room temperature for up to 12 months did not impair the in vitro activity of antibiotic-impregnated CaSO4 beads, as demonstrated through ZOIs. CLINICAL SIGNIFICANCE: When stored correctly, antibiotic-impregnated CaSO4 beads can be used at least up to 12 months after formulation.

Does the association between smoking and mortality differ due to frailty status? A secondary analysis from the Mexican Health and Aging Study.

BACKGROUND: despite the well-known adverse health effects of smoking, evidence of these effects on frail individuals is still scarce. AIMS: to assess whether frailty influences the association between smoking and mortality. METHODS: individuals ≥50 years from the Mexican Health and Aging Study were analysed. Mortality rates from a 17-year follow-up were compared between smoking status groups (never, previous and current) and other smoking behaviour-related characteristics (pack-years, age commenced and cessation). Baseline variables were included to adjust the Cox regression models. First, models were adjusted for the whole sample, including an interaction term between the frailty index (FI) and smoking variables. A second set of models were stratified by FI levels: 0.00-0.10, 0.11-0.20, 0.21-0.30 and ≥ 0.31. RESULTS: from a total 14,025 individuals, mean age was 62.4 (95% confidence interval [95% CI]: 62.1-62.8) and 53.9% were women (95% CI: 52.4-55.6). Main results from the survival analyses showed that when including FI interaction term with smoking status, comparing current to never smoking, the hazard ratio (HR) was 2.03 (95% CI: 1.07-3.85, P = 0.029), and comparing current to previous smoking, the HR was 2.13 (95% CI: 1.06-4.26, P = 0.032). Models stratified by FI levels showed a significant HR only for the two highest level groups. Similar results were found for the smoking behaviour-related characteristics. DISCUSSION: our results suggest that frailty could modify smoking mortality risk. Other smoking characteristics were impacted by frailty, in particular, cessation. It was noteworthy that having ≥10 years of tobacco cessation was beneficial for frail individuals. CONCLUSIONS: smoking has a higher toll on frail individuals, but ceasing is still beneficial for this group.

Rheumatology Training in Latin America: A Collaborative Study by the Pan American League of Associations for Rheumatology.

BACKGROUND/OBJECTIVE: Demand for rheumatology care has steadily increased in recent years. The number of specialists in this field, however, seems insufficient. No recent studies have diagnosed the attributes of rheumatology training in Latin America. METHODS: This is a descriptive cross-sectional study. We obtained data on each country through local rheumatologists of the Pan-American League Against Rheumatism, who acted as principal investigators for participating countries. Our sample was analyzed and described through means and standard deviations or through frequencies and percentages, depending on the variable. RESULTS: Countries with the most rheumatology-training programs were Brazil (n = 50), Argentina (n = 18), and Mexico (n = 15). Ecuador, Honduras, and Nicaragua do not have rheumatology-training programs. The countries with the most available slots for rheumatology residents were Brazil (n = 126) and Argentina (n = 36). To be admitted into rheumatology training, candidates were required to have completed graduate studies in internal medicine in 42.1% of the programs. In 8 countries (42.1%), residents are not required to pay tuition; the median cost of tuition in the remaining countries is US $528 (interquartile range, US $2153). CONCLUSIONS: Conditions associated with rheumatology training in Latin America vary. Significant differences exist in income and tuition fees for residents, for example, and 4 countries in Latin America do not currently offer programs. Information collected in this study will be useful when comparing the status of rheumatology services offered in Latin America with those in other countries. Most countries require a wider offering of rheumatology-training programs, as well as more available slots.

Innate lymphoid cells in lung infection and immunity.

In recent years, innate lymphoid cells (ILCs) have emerged as key mediators of protection and repair of mucosal surfaces during infection. The lung, a dynamic mucosal tissue that is exposed to a plethora of microbes, is a playground for respiratory infection-causing pathogens which are not only a major cause of fatalities worldwide, but are also associated with comorbidities and decreased quality of life. The lung provides a rich microenvironment to study ILCs in the context of innate protection mechanisms within the airways, unraveling their distinct functions not only in health but also in disease. In this review, we discuss how pulmonary ILCs play a role in protection against viral, parasitic, bacterial, and fungal challenge, along with the mechanisms underlying this ILC-mediated immunity.

Heterologous vaccine interventions: boosting immunity against future pandemics.

While vaccines traditionally have been designed and used for protection against infection or disease caused by one specific pathogen, there are known off-target effects from vaccines that can impact infection from unrelated pathogens. The best-known non-specific effects from an unrelated or heterologous vaccine are from the use of the Bacillus Calmette-Guérin (BCG) vaccine, mediated partly through trained immunity. Other vaccines have similar heterologous effects. This review covers molecular mechanisms behind the heterologous effects, and the potential use of heterologous vaccination in the current COVID-19 pandemic. We then discuss novel pandemic response strategies based on rapidly deployed, widespread heterologous vaccination to boost population-level immunity for initial, partial protection against infection and/or clinical disease, while specific vaccines are developed.

Extreme immunotherapy: emergency immunology to defeat pandemics.

The ongoing global COVID-19 pandemic has thrown into sharp relief the gap between modern biology's ability to investigate and respond to a novel pathogen and modern medicine's ability to marshal effective front-line interventions to limit its immediate health impact. While we have witnessed the rapid development of innovative vaccines against SARS-CoV-2 using novel molecular platforms, these have yet to alter the pandemic's long-term trajectory in all but a handful of high-income countries. Health workers at the clinical front lines have little more in their clinical armamentarium than was available a century ago-chiefly oxygen and steroids-and yet advances in modern immunology and immunotherapeutics suggest an underuse of extant and effective, if unorthodox, therapies, which we now call "Extreme Immunotherapies for Pandemics (EIPs)."

A novel combination regimen of BET and FLT3 inhibition for FLT3-ITD acute myeloid leukemia.

Acute myeloid leukemia patients with FLT3-ITD mutations have a high risk of relapse and death. FLT3 tyrosine kinase inhibitors improve overall survival, but their efficacy is limited and most patients who relapse will ultimately die of the disease. Even with potent FLT3 inhibition, the disease persists within the bone marrow microenvironment, mainly due to bone marrow stroma activating parallel signaling pathways that maintain pro-survival factors. BET inhibitors suppress pro-survival factors such as MYC and BCL2, but these drugs thus far have shown only limited single-agent clinical potential. We demonstrate here, using pre-clinical and clinical correlative studies, that the novel 4-azaindole derivative, PLX51107, has BET-inhibitory activity in vitro and in vivo. The combination of BET and FLT3 inhibition induces a synergistic antileukemic effect in a murine xenograft model of FLT3-ITD AML, and against primary FLT3-ITD AML cells co-cultured with bone marrow stroma. Using suppression of MYC as a surrogate for BET inhibition, we demonstrate BET inhibition in human patients. The short plasma half-life of PLX51107 results in intermittent target inhibition to enable tolerability while overcoming the protective effect of the microenvironment. Mechanistically, the synergistic cytotoxicity is associated with suppression of key survival genes such as MYC. These data provide the scientific rationale for a clinical trial of a BET plus FLT3 inhibitor for the treatment of relapsed/refractory FLT3-ITD AML. A clinical trial of PLX51107 as monotherapy in patients with different malignancies is underway and will be reported separately.

[Clinical and microbiological characteristics of bloodstream infections in adult neutropenic patients]. / Características clínicas y microbiológicas de infecciones del torrente sanguíneo en pacientes adultos neutropénicos.

Bloodstream infections (BI) are relevant in neutropenic patients because they are associated with an increased number of complications and death. The objective was determinate the epidemiologic and microbiologic features of the BI in neutropenic patients with solid neoplasm (SN) and hematologic neoplasm (HN). Retrospective study in two third level hospitals between 2009 and 2016. They were included all the patients older than 18 years-old with active oncologic disease and neutropenia, who had BI. Patients with dermatologic cancer other than melanoma where excluded. A total of 143 BI in neutropenic were observed, of which 80.4% occurred in HN. Around 97.9% of the patients had a high-risk neutropenia without differences between both groups. The most frequent site of BI was primary bacteremia (46.9%) and catheter-associated infection (21%), without significant differences between the two groups. The gram negatives bacilli (GNB) predominated over the gram positive cocci (GPC) and they represented 74.1% of the isolated bacteria, being Escherichia coli the most frequent (32.8%). Among the gram positive cocci, Staphylococcus aureus (28.1%) was the most frequent isolated, followed by coagulase-negative Staphylococci (CNS). There were no differences in microbiological isolates between both groups. With regard to the antimicrobial susceptibility 67.5% of the CNS, 17.6% of the E. coli and 27.6% of the Klebsiella pneumoniae were multiresistant with no differences between both groups. Only 11.1% of S. aureus isolates were methicillin resistant. In conclusion BI of the neutropenic patients where most frequents within patients with HN, GNB were the main microbiological isolates. High mortality was observed in neutropenic patients with BI.

Immunology and social networks: an approach towards impact assessment.

Scientific journals have changed the mechanisms they use for distribution and dissemination of information. Different approaches towards determining impact have emerged and among these, metrics derived from activity on social media are an emerging trend. This article aims to assess whether a correlation exists between the traditional impact factor and activity on social media. We assessed journals categorized within the area of "immunology" on the SCImago Journal and Country Rank website. Variables reflecting traditional and alternative measures of impact were collected. Differences between journals with and without social networks were assessed using non-parametric Mann-Whitney U tests. Correlation was assessed through Spearman tests. 156 journals were analyzed, 17% had at least one social network. 48.2% of journals with social networks were classified within SJR's quartile 1. An almost perfect correlation was found between the SJR and the number of followers on Twitter, this correlation remained statistically significant after adjusting for time since creation of the account [Spearman's correlation (rs) = 0.83]. We propose the use of Twitter as a mechanism for dissemination of information by immunology journals, as well as other social networks for their potential to increase their audience, as well as the dissemination and impact of their publications.

Temporal and latitudinal comparisons of reproductive parameters in a heavily exploited shark, the bonnethead, Sphyrna tiburo (L. 1758), in the southern Gulf of Mexico.

In the southern Gulf of Mexico, the bonnethead shark, Sphyrna tiburo, is one of the most frequently captured species in landings of small-scale fisheries. Based on the analysis of two fishery-dependent sampling periods (1993-1994 and 2007-2014), this study aimed to determine reproductive parameters and identify temporal differences between the two time periods. In the first sampling period, 776 males and 352 females with a size range of 28.0-120.0 cm total stretched length (LT ) were analysed, and in the second sampling period, 387 males and 432 females with a size range of 28.0-122.0 cm LT were analysed. The size at 50% maturity in the second sampling period was significantly different between sexes, 82.6 cm LT for females and 73.8 cm LT for males (no estimation was possible for the first sampling period). The size at 50% maternity was not different between sampling periods, 97.3 cm LT for the first sampling period and 99.0 cm LT for the second sampling period. Litter size varied from 3 to 19 embryos and the average was not statistically different in both periods, 10.1 (S.D. = 3.8) for the first sampling period and 11.3 (S.D. = 3.5) for the second sampling period. The female reproductive cycle is asynchronous, and it seems to be annual, with a gestation period of 5-6 months, and a consecutive ovarian cycle and gestation period. Temporal (between sampling periods) and latitudinal (southern Gulf versus northern regions) variations occur in the synchronicity of the reproductive cycle, temporal variation in the relationship between maternal length and litter size, and latitudinal variation in average size of mature sharks.

Comparison of Performance of the Pediatric Index of Mortality (PIM)-2 and PIM-3 Scores in the Pediatric Intensive Care Unit of a High Complexity Institution.

OBJECTIVE: To determine the performance of each of the available pediatric index of mortality (PIM) scores, by assessing the capability for discrimination and calibration in patients admitted to a pediatric intensive care unit in Bogotá. DESIGN AND SETTING: We designed a retrospective, observational cohort study, which included all patients aged between a month and 17 years and 364 days, admitted to the pediatric intensive care unit of a high complexity university hospital between April 1, 2016 and December 31, 2018. We analyzed the standardized mortality ratio, discrimination, calibration, and net reclassification index (NRI) for each model. RESULTS: A total of 722 patients were included, the mortality rate was 3.74%, and for PIM-3, the ratio between expected and observed mortality was 0.66 [confidence interval (CI) 0.40-1.05] for PIM-2 and 1.00 (CI 0.59-1.68) for PIM-3. The Hosmer-Lemeshow (HL) test suggests inadequate calibration for PIM-2 (HL = 13.18, p = 0.11) and adequate calibration for PIM-3 (HL = 28.08, p < 0.01). The area under the diagnostic performance curves for PIM-2 and PIM-3 were 0.87 (95% CI 0.80-0.94) and 0.89 (95% CI 0.82-0.95), respectively. The NRI was -27.1%. PIM-3 classified survivors better than PIM-2, but inadequately classified nonsurvivors. CONCLUSION: Although both models show adequate discrimination ability, PIM-3 shows a better correlation between predicted risk score and observed mortality. Thus, it may be a useful tool for measuring the internal processes of intensive care units in Colombia and for making comparisons between groups of similar characteristics. HOW TO CITE THIS ARTICLE: Quiñónez-López D, Patino-Hernandez D, Zuluaga CA, García ÁA, Muñoz-Velandia OM. Comparison of Performance of the Pediatric Index of Mortality (PIM)-2 and PIM-3 Scores in the Pediatric Intensive Care Unit of a High Complexity Institution. Indian J Crit Care Med 2020;24(11):1095-1102.