Discriminant analysis and machine learning approach for evaluating and improving the performance of immunohistochemical algorithms for COO classification of DLBCL.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is classified into germinal center-like (GCB) and non-germinal center-like (non-GCB) cell-of-origin groups, entities driven by different oncogenic pathways with different clinical outcomes. DLBCL classification by immunohistochemistry (IHC)-based decision tree algorithms is a simpler reported technique than gene expression profiling (GEP). There is a significant discrepancy between IHC-decision tree algorithms when they are compared to GEP. METHODS: To address these inconsistencies, we applied the machine learning approach considering the same combinations of antibodies as in IHC-decision tree algorithms. Immunohistochemistry data from a public DLBCL database was used to perform comparisons among IHC-decision tree algorithms, and the machine learning structures based on Bayesian, Bayesian simple, Naïve Bayesian, artificial neural networks, and support vector machine to show the best diagnostic model. We implemented the linear discriminant analysis over the complete database, detecting a higher influence of BCL6 antibody for GCB classification and MUM1 for non-GCB classification. RESULTS: The classifier with the highest metrics was the four antibody-based Perfecto-Villela (PV) algorithm with 0.94 accuracy, 0.93 specificity, and 0.95 sensitivity, with a perfect agreement with GEP (κ = 0.88, P < 0.001). After training, a sample of 49 Mexican-mestizo DLBCL patient data was classified by COO for the first time in a testing trial. CONCLUSIONS: Harnessing all the available immunohistochemical data without reliance on the order of examination or cut-off value, we conclude that our PV machine learning algorithm outperforms Hans and other IHC-decision tree algorithms currently in use and represents an affordable and time-saving alternative for DLBCL cell-of-origin identification.

Cytotoxic Activity of a Black Bean (Phaseolus vulgaris L.) Extract and its Flavonoid Fraction in Both In Vitro and In Vivo Models of Lymphoma.

BACKGROUND: Black bean (Phaseolus vulgaris L.) is a very common legume seed in Mexican diet. Flavonoids and crude extracts from different plants have been reported as effective agents for chemoprevention and cytotoxicity in several cancer cell lines. We investigated the effects of black bean hulls extract (BBE) and its flavonoid fraction (FF) on lymphoma cells. METHODS: BBE and FF were characterized by high-performance liquid chromatography. Viability and flow cytometry assays were carried out. Finally, a mouse model was generated to test the in vivo effect of both fractions. RESULTS: Both BBE and FF inhibited cell proliferation in a dose-dependent way. In addition, cells underwent apoptosis, and the cellular population at S-phase increased after exposure to these fractions. Furthermore, mice treated with BBE or FF increased the overall survival by 5 or 6 days, respectively, in comparison with a placebo group (p = 0.056). DISCUSSION: BBE and FF had cytotoxic action by driving OCI-Ly7 cells into apoptosis as well as blocking progression to G2/M phase. In addition, BBE and FF treatments were effective in xenograft models.

[A decade of lead monitoring in schoolchildren in the metropolitan area of Monterrey NL, Mexico]. / Una década de monitoreo de plomo en sangre en niños escolares del área metropolitana de Monterrey, NL.

OBJECTIVE: To establish the blood lead concentration and associated risk factors in schoolchildren during 1998 and 2008. MATERIALS AND METHODS: A blood lead screening was conducted in schoolchildren of 6-12 years of age, enrolled in 17 elementary schools of the metropolitan area of Monterrey, México, during 1998 and 2008. RESULTS: The mean blood lead level were 9.6 ± 3.0 (µg/dL range of 3.18 to 20.88) in 1998 and 4.5±4.8 µg/dL (range of 3.3 to 53.7) showing a 2.1-times reduction in blood lead levels (p<0.01). CONCLUSIONS: This reduction in blood lead levels demonstrate environmental and industrial control improvements and the benefits of fading out the leaded gasoline during the 1990's.

Isolated cardiac valve involvement in smoldering adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive mature T-cell neoplasm caused by infection with the Human T-cell Lymphotropic Virus Type 1 (HTLV-1). Cardiac involvement in patients with ATLL is infrequent, and when it happens it is usually seen in aggressive ATLL subtypes. However, ATLL presenting as isolated cardiac valve involvement is extremely rare. To date, only three histologically proven cases of ATLL with isolated cardiac valve involvement have been reported. Herein, we describe a 61-year-old Peruvian man who presented heart failure symptoms secondary to progressive cardiac valve infiltration. The patient underwent mitral valve replacement with a mechanical prosthesis. Histopathological evaluation of the resected valve revealed leaflet thickening with a nodular appearance due to fibrous tissue containing atypical T-lymphocytes with Foxp3 expression, infiltrating all layers of the resected valve. Interestingly, tumor cells were distributed around an incidental venous malformation (i.e., cavernous hemangioma). Postoperative evaluation demonstrated positive serology for HTLV-1, and a diagnosis of ATLL was established. Postoperative positron emission tomography/computed tomography did not show lesions outside the heart and cell blood counts were within normal range with low level of circulating CD4+ CD25+ lymphoma cell counts (7%); therefore, patient's disease was considered as smoldering ATLL and a "watch and wait" strategy was pursued. Currently, the patient is alive with no progression of disease after 18 months from diagnosis. Isolated cardiac valve involvement by ATLL should be considered in the differential diagnosis of HTLV-1 carriers with progressive heart failure, even when systemic lymphoma involvement is absent or not apparent.

Non-Hodgkin lymphoma treatment in middle-income countries in Latin America: perspective of the Latin American Study Group of Lymphoproliferative Disorders [Grupo de Estudio de Linfoproliferativos de Latino América (GELL)].

INTRODUCTION: Non-Hodgkin lymphomas (NHL) are the most frequently recognized entities among lymphoproliferative syndromes and rank fifth among neoplasms not associated with gender. There is scarce information on the clinical characteristics of the most frequent NHL, and no data on treatment regimens and their outcomes in Latin America. Although many factors affect a patient's possibilities of receiving treatment, the annual income per person/country is pivotal in Latin America. AIM: We present the clinical characteristics, risk groups, and treatment regimens of the three most frequent lymphoma subtypes in Latin America [diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and peripheral T-cell lymphoma (PTCL)], based on the data collected by the largest study group of lymphoproliferative diseases in Latin America: The Latin American Study Group of Lymphoproliferative Disease [Grupo de Estudio de Linfoproliferativos de Latino America (GELL)]. OUTCOMES: The most frequent treatment regimen for B-cell lymphomas is immunochemotherapy (R-CHOP ≥70%), and CHOP for PTCL. Survival is similar to that reported by industrialized nations. We have no solid data on the results of treatment with salvage regimens nor stem cell transplantation in refractory/ relapsed NHL. CONCLUSION: In Latin America, the same treatment regimens are used as in highly developed countries, although we lack the necessary technology to apply CAR T-cell therapies or a network of trials sponsored by the pharmaceutical industry.

Accelerometer-Based Physical Activity, Sedentary Time, and BMI among Preschoolers in Puerto Rico.

OBJECTIVE: A minimum of 3-h/day of any intensity physical activity (PA) has been recommended for preschoolers. No previous study has documented accelerometer-based PA and sedentary time (ST) among Hispanic preschoolers in Puerto Rico, a population with high obesity and low PA prevalence. The purpose of this study was to describe and compare total, weekdays (during- and out-of-preschool) and weekend PA and ST, and test associations with body mass index (BMI). METHODS: A group of 3-5-year-old preschoolers (9 boys,13 girls) completed height and weight measurements, and wore an accelerometer during 7-days. Shapiro-Wilk, Mann-Whitney U test and Spearman correlations were used to test for normality, sex differences and associations, respectively. RESULTS: No sex differences were observed for BMI, weekdays and weekends PA and ST. Light to vigorous intensity PA (LVPA=3.2±0.6 h/day) and moderate to vigorous intensity PA (MVPA=80.4±21.7 min/day) were within guidelines only on weekdays. LVPA occupied 21.3% (15.4±3.7 min/h), MVPA 9.5% (6.6±2.3 min/h), and ST 65.3% (4.8±0.4 h/day) of preschool time. Boys had higher MVPA than girls only during-preschool time. BMI indicative of overweight-obesity was identified in 36.3%, and BMI directly correlated with total ST and inversely correlated with LVPA. CONCLUSION: Total and during-preschool LVPA and ST, and their association with BMI highlight the need for interventions to promote PA and reduce ST, particularly during-preschool time.

Analysis of IgG, IgA and IgM antibodies against SARS-CoV-2 spike protein S1 in convalescent and vaccinated patients with the Pfizer-BioNTech and CanSinoBio vaccines.

The SARS-CoV-2 virus was detected for the first time in December 2019 in Wuhan, China. Currently, this virus has spread around the world, and new variants have emerged. This new pandemic virus provoked the rapid development of diagnostic tools, therapies and vaccines to control this new disease called COVID-19. Antibody detection by ELISA has been broadly used to recognize the number of persons infected with this virus or to evaluate the response of vaccinated individuals. As the pandemic spread, new questions arose, such as the prevalence of antibodies after natural infection and the response induced by the different vaccines. In Mexico, as in other countries, mRNA and viral-vectored vaccines have been widely used among the population. In this work, we developed an indirect ELISA test to evaluate S1 antibodies in convalescent and vaccinated individuals. By using this test, we showed that IgG antibodies against the S1 protein of SARS-CoV-2 were detected up to 42 weeks after the onset of the symptoms, in contrast to IgA and IgM, which decreased 14 weeks after the onset of symptoms. The evaluation of the antibody response in individuals vaccinated with Pfizer-BioNTech and CanSinoBio vaccines showed no differences 2 weeks after vaccination. However, after completing the two doses of Pfizer-BioNTech and the one dose of CanSinoBio, a significantly higher response of IgG antibodies was observed in persons vaccinated with Pfizer-BioNTech than in those vaccinated with CanSinoBio. In conclusion, these results confirm that after natural infection with SARS-CoV-2, it is possible to detect antibodies for up to 10 months. Additionally, our results showed that one dose of the CanSinoBio vaccine induces a lower response of IgG antibodies than that induced by the complete scheme of the Pfizer-BioNTech vaccine.

An international, multicenter, retrospective study on the positive impact of cutaneous involvement on the clinical outcome of adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is a largely incurable disease. Cutaneous involvement is common and could be first symptom of the disease. We analyzed 169 patients with ATLL of whom 63 had cutaneous involvement. Cutaneous involvement was found in 48, 27, 17, and 60% of acute, lymphomatous, chronic and smoldering ATLL cases, respectively. Eight cases had primary cutaneous tumoral variant. Erythroderma (24%) and plaques (22%) were the most frequent skin lesions. The presence of cutaneous involvement was associated with better overall survival compared to non-cutaneous involvement (aHR 0.55 [95% CI: 0.37-0.82], p < 0.01; 1-year OS 53 vs. 27%, respectively, p = 0.012). Combination zidovudine and interferon-alpha (AZT-IFN) yielded high response rates (overall response, OR = 100%, n = 8; complete response 62.5%) compared to chemotherapy (OR = 33.3%, n = 12/36). In conclusion, cutaneous involvement was associated with better survival in Latin American patients with ATLL. AZT-IFN demonstrated encouraging responses in ATLL patients with cutaneous involvement.

Treatment and Survival Outcomes of Waldenstrom Macroglobulinemia in Latin American Patients: A Multinational Retrospective Cohort Study.

PURPOSE: Waldenstrom Macroglobulinemia (WM) is a rare lymphoma with distinct clinical features, and data from Latin American patients are lacking. Therefore, we aim to investigate the clinical, therapy, and outcome patterns of WM in Latin America. METHODS: We retrospectively analyzed patients with WM diagnosed between 1991 and 2019 from 24 centers in seven Latin American countries. The study outcomes were overall survival (OS) and progression-free survival (PFS). RESULTS: We identified 159 cases (median age 67 years, male 62%). Most patients (95%) were symptomatic at diagnosis. The International Prognostic Scoring System for WM (IPSSWM) at diagnosis was available in 141 (89%) patients (high-risk 40%, intermediate-risk 37%, and low-risk 23%). Twenty-seven (17%) patients were tested for MYD88L265P, with 89% (n = 24 of 27) carrying the mutation. First-line and second-line therapies were administered to 142 (89%) and 53 (33%) patients, respectively. Chemoimmunotherapy was the most commonly used first-line (66%) and second-line (45%) approach; only 18 (11%) patients received ibrutinib. With a median follow-up of 69 months, the 5-year OS rate was 81%. In treated patients, the 5-year OS and PFS rates were 78% and 59%, respectively. High-risk IPSSWM at treatment initiation was an independent risk factor for OS (adjusted hazard ratio: 4.73, 95% CI, 1.67 to 13.41, P = .003) and PFS (adjusted hazard ratio: 2.43, 95% CI, 1.31 to 4.50, P = .005). CONCLUSION: In Latin America, the management of WM is heterogeneous, with limited access to molecular testing and novel agents. However, outcomes were similar to those reported internationally. We validated the IPSSWM score as a prognostic factor for OS and PFS. There is an unmet need to improve access to recommended diagnostic approaches and therapies in Latin America.

Efficacy and safety of canakinumab in the treatment of adult-onset Still's disease: A systematic review.

BACKGROUND: Adult-onset Still's disease (AOSD) is a rare inflammatory disease, typically characterized by spiking fever, skin rash, and arthralgia or arthritis. Its conventional treatment includes NSAIDs and corticosteroids, and DMARDs as second-line therapy. Frequently, IL-1 inhibitors are also required, mainly in patients refractory to traditional therapy. Canakinumab is a monoclonal antibody that binds IL-1ß with high affinity and specificity, making it appropriate for therapeutic purposes in AOSD. OBJECTIVE: The aim of this systematic review was to identify and compile the current data on the efficacy and safety of canakinumab in the treatment of AOSD. METHODS: Following the guidelines established by the PRISMA statement, we searched Scopus, Web of Science, Pubmed, and Cochrane Library for relevant literature up to March 2021. The inclusion criteria comprised: randomized controlled trials, pooled analyses, observational studies, case series, and case reports. RESULTS: Seventeen studies published from 2012 to 2021 were evaluated; 11 of these correspond to case series or case reports, four observational studies, one placebo-controlled phase II trial, and one analysis of pooled systemic juvenile idiopathic arthritis data. In general, out of a total of 99 patients, 68.7% of these presented a complete remission of the systemic and arthritic manifestations at the end of the observation period, while 16.2% of the patients showed a partial improvement of the symptoms and the remaining (15.1%) did not show clinical improvement or were excluded. Moreover, 210 adverse events were reported in 69 patients during canakinumab treatment, of which the majority correspond to respiratory tract infections, arthralgia, disease flares, abdominal pain, nausea, and diarrhea, whereas the most common severe adverse events included macrophage activation syndrome and serious infections. Also, a corticosteroid-sparing effect was observed in a large percentage of patients. CONCLUSION: More studies with solid evidence are needed to support the efficacy of canakinumab in AOSD, although its use is encouraged by the increasing favorable results reported and the efficacy of other IL-1 inhibitors. It was also associated with an acceptable safety profile, similar to expected in IL-1 inhibitor therapy. However, future studies with well-defined endpoints are warranted to examine further the usefulness of canakinumab in AOSD.

Real-World Data on Adult T-Cell Leukemia/Lymphoma in Latin America: A Study From the Grupo de Estudio Latinoamericano de Linfoproliferativos.

PURPOSE: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive disease caused by the human T-cell leukemia virus type 1. Real-world data of ATLL in Latin America are lacking. PATIENTS AND METHODS: We analyzed patients with ATLL (acute, lymphomatous, chronic, and smoldering) encountered in 11 Latin American countries between 1995 and 2019. Treatment response was assessed according to the 2009 consensus report. Survival curves were estimated using the Kaplan-Meier method and log-rank test. RESULTS: We identified 253 patients; 226 (lymphomatous: n = 122, acute: n = 73, chronic: n = 26, and smoldering: n = 5) had sufficient data for analysis (median age 57 years). Most patients with ATLL were from Peru (63%), Chile (17%), Argentina (8%), and Colombia (7%). Hypercalcemia was positively associated with acute type (57% v lymphomatous 27%, P = .014). The median survival times (months) were 4.3, 7.9, 21.1, and not reached for acute, lymphomatous, chronic, and smoldering forms, with 4-year survival rates of 8%, 22%, 40%, and 80%, respectively. First-line zidovudine (AZT)-interferon alfa (IFN) resulted in an overall response rate of 63% (complete response [CR] 24%) for acute. First-line chemotherapy yielded an overall response rate of 41% (CR 29%) for lymphomatous. CR rate was 42% for etoposide, cyclophosphamide, vincristine, doxorubicin, and prednisone versus 12% for cyclophosphamide, vincristine, doxorubicin, and prednisone-like regimen (P < .001). Progression-free survival at 1 year for acute type patients treated with AZT-IFN was 67%, whereas 2-year progression-free survival in lymphomatous type patients who achieved CR after chemotherapy was 77%. CONCLUSION: This study confirms Latin American ATLL presents at a younger age and has a high incidence of lymphomatous type, low incidence of indolent subtypes, and worse survival rates as compared with Japanese patients. In aggressive ATLL, chemotherapy remains the preferred choice for lymphomatous favoring etoposide-based regimen (etoposide, cyclophosphamide, vincristine, doxorubicin, and prednisone), whereas AZT-IFN remains a good first-line option for acute subtype.

miRNA signature associated with R-CHOP refractoriness in patients diagnosed with diffuse large B cell lymphoma.

Refractoriness remains as one of the challenges in patients with lymphoma under chemotherapy, and among biological regulators in cells driving this type of response are microRNAs (miRNAs). Different genes are constantly turned on or off according to the miRNAs expression profiles affecting the drug response in patients and their stability in serum and plasma makes them potential prognostic biomarkers in several diseases. Here we described a profile of miRNAs in plasma of diffuse large B cell lymphoma (DLBCL) patients. miRNA expression arrays were carried using pre-treatment plasma samples of sixteen patients, followed by a comparison between the responder and the non-responders. After six cycles of R-CHOP treatment, twelve out of sixteen patients were clinically diagnosed with complete response while in four patients no clinical response was observed. Between these groups, a signature of fifteen differential expressed miRNAs was found. The circulating miRNAs in plasma of patients with no response were related to the drug resistance in other types of cancer, by targeting genes involved in cell proliferation and apoptosis, among other cell processes.

A Multi-Institutional Validation of the Prognostic Value of the Neutrophil-to-Lymphocyte Ratio in Patients With Diffuse Large B-Cell Lymphoma: A Study From The Latin American Group of Lymphoproliferative Disorders (GELL).

INTRODUCTION: We aimed at investigating the prognostic role of the neutrophil-to-lymphocyte ratio (NLR) in 2 independent cohorts of Latin American patients with diffuse large B-cell lymphoma (DLBCL) treated with chemoimmunotherapy. PATIENTS AND METHODS: The learning cohort was composed of 274 patients and the validation cohort of 323 patients, for a total of 597 patients. An optimal NLR cutoff ≥ 4 was determined using receiver operating characteristic analysis. RESULTS: In multivariate models, NLR ≥ 4 was independently associated with lower odds for complete response to chemoimmunotherapy in the learning (odds ratio, 0.46; P = .006) and the validation cohort (odds ratio, 0.49; P = .01), and independently associated with worse survival in the learning (hazard ratio, 1.55; P = .04) and the validation cohort (hazard ratio, 1.80; P = .003). CONCLUSIONS: The adverse prognostic value of NLR ≥ 4 was independent of the International Prognostic Index and the National Comprehensive Cancer Network-International Prognostic Index score. Based on the results of this multi-institutional study, NLR ≥ 4 emerges as an adverse prognostic factor in Latin American patients with DLBCL treated with chemoimmunotherapy.

Nodular regenerative hyperplasia associated to aplastic anemia: a case report and literature review.

INTRODUCTION: Nodular regenerative hyperplasia (NRH) is a rare condition is associated to immune, neoplastic, vascular disorders, and certain drugs and toxins. Portal hypertension is the main complication. AIM: To report the case of a woman with NRH and aplastic anemia, association not previously described. CASE: A 31- year-old hispanic female presented with pancitopenia and cholestasis. Bone marrow biopsy: aplastic anemia. Abdominal ultrasound revealed multiple liver nodules, without hepato-splenomegaly. No abnormalities were noted in hepatic vessels. Antimitochondrial (AMAs) were positive. Coagulation tests were normal. Liver biopsy: hepatocite nodules with central atrophy and sinusoidal dilatation in the absence of significant fibrosis. No arteritis, thrombosis or bile duct damage was found. DISCUSSION: Pathogenesis of NRH remains unclear. The most accepted theory was developed by Wanless 24 years ago, and reinforced in 1997. It states that alterations in hepatic blood flow (portal obliterative venopathy) originate a specific response, initially consisting of apoptosis secondary to acute ischemia, with ensuing parenchymal atrophy and surrounding areas of liver regeneration and chronic ischemia. The common pathologic mechanism of all the diseases associated with NRH involves liver blood-flow abnormalities secondary to microthromboses, vascular congestion, or vasculitis. In the current case we were unable to document evidence of liver flow abnormalities. Noteworthy, there are previous descriptions of the as- sociation of NRH with primary biliary cirrhosis, and this patient was AMA positive, but without bile duct damage in liver biopsy. CONCLUSIONS: We cannot sustain Wanless' theory, and this is the first description of the association of NRH with aplastic anemia.

A PER3 polymorphism is associated with better overall survival in diffuse large B-cell lymphoma in Mexican population.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of malignant lymphoma. Presently, one of the most important clinical predictors of survival in DLBCL patients is the International Prognostic Index (IPI). Circadian rhythms are the approximate 24 hour biological rhythms with more than 10 genes making up the molecular clock. OBJECTIVE: Determine if functional single nucleotide polymorphism in circadian genes may contribute to survival status in patients diagnosed with diffuse large B-cell lymphoma. METHODS: Sixteen high-risk non-synonymous polymorphisms in circadian genes (CLOCK, CRY2, CSNK1E, CSNK2A1, NPAS2, PER1, PER2, PER3, PPP2CA, and TIM) were genotyped by screening PCR. Results were visualized by agarose gel electrophoresis and confirmed by two-direction sequencing. Clinical variables were compared between mutated and non-mutated groups. LogRank survival analysis and Kaplan-Meier method were used to calculate the overall survival. RESULTS: PER3 rs10462020 variant showed significant difference in overall survival between patients containing mutated genotypes and those with non-mutated genotypes (p = 0.047). LDH levels (p = 0.021) and IPI score (p < 0.001) also showed differences in overall survival. No clinical differences were observed in mutated vs. non-mutated patients. CONCLUSIONS: This work suggests a role of PER3 rs10462020 in predicting a prognosis in DLBCL overall survival of patients.

Can sTREM-1 predict septic shock & death in late-onset neonatal sepsis? A pilot study.

BACKGROUND AND OBJECTIVES: The transmembrane glycoprotein TREM-1 triggers an inflammatory response. Its soluble fraction (sTREM-1) has been shown to have diagnostic accuracy for late-onset neonatal sepsis (LONS). Until now, the potential of sTREM-1 to predict septic shock and/or death in septic neonates has not been explored. This study obtained estimates of the incidence and prevalence of septic shock and/or death in septic neonates for future sample size calculations for confirmatory studies and evaluated the feasibility of using sTREM-1 as a predictor of septic shock and/or death in neonates with LONS criteria. STUDY DESIGN: A pilot study with a cross-sectional design was performed from May 1(st) to October 31(st), 2012. The participants were hospitalized neonates who, after three days of life, were diagnosed as having LONS. Plasma sTREM-1 was quantified by ELISA. The main outcome measurement was the development of septic shock and/or death. RESULTS: Of 71 eligible subjects, nine (12.7%) progressed to septic shock and/or death. In the LONS-Non-Shock group, the sTREM-1 median and interquartile range (IQR) plasma value were 10 (10 to 70) pg/mL. In the LONS & Shock/Death group, the values were 567 (260 to 649) pg/mL. These values were significantly different (Mann-Whitney's U test, p=0.001). A ROC curve for a proposed sTREM-1 cut-off value of 300 pg/mL exhibited an area under the curve of 0.884 (95% CI=0.73 to 1.0; p<0.0001), with a sensitivity of 0.78 (95% CI=0.46 to 0.94) and specificity of 0.97 (95% CI=0.92 to 0.99); PPV would be 0.78 (95% CI=0.46 to 0.94) and NPV 0.97 (95% CI=0.92 to 0.99). CONCLUSIONS: In neonates with LONS, sTREM-1 has the potential to provide an excellent predictive value for septic shock/death. Larger sample sizes are needed to identify the optimal cut-off value of plasma sTREM-1 for this diagnosis and to provide diagnostic accuracy measures.