Defining blood hematology reference values in female pig-tailed macaques (Macaca nemestrina) using the Isolation Forest algorithm.

BACKGROUND: Pig-tailed macaques (PTMs) are commonly used as preclinical models to assess antiretroviral drugs for HIV prevention research. Drug toxicities and disease pathologies are often preceded by changes in blood hematology. To better assess the safety profile of pharmaceuticals, we defined normal ranges of hematological values in PTMs using an Isolation Forest (iForest) algorithm. METHODS: Eighteen female PTMs were evaluated. Blood was collected 1-24 times per animal for a total of 159 samples. Complete blood counts were performed, and iForest was used to analyze the hematology data to detect outliers. RESULTS: Median, IQR, and ranges were calculated for 13 hematology parameters. From all samples, 22 outliers were detected. These outliers were excluded from the reference index. CONCLUSIONS: Using iForest, we defined a normal range for hematology parameters in female PTMs. This reference index can be a valuable tool for future studies evaluating drug toxicities in PTMs.

The genetic architecture of complete blood counts in lactating Holstein dairy cows.

Complete blood counts (CBCs) measure the abundance of individual immune cells, red blood cells, and related measures such as platelets in circulating blood. These measures can indicate the health status of an animal; thus, baseline circulating levels in a healthy animal may be related to the productive life, resilience, and production efficiency of cattle. The objective of this study is to determine the heritability of CBC traits and identify genomic regions that are associated with CBC measurements in lactating Holstein dairy cattle. The heritability of CBCs was estimated using a Bayes C0 model. The study population consisted of 388 cows with genotypes at roughly 75,000 markers and 16 different CBC phenotypes taken at one to three time points (n = 33, 131, and 224 for 1, 2, and 3 time points, respectively). Heritabilities ranged from 0.00 ± 0.00 (red cell distribution width) to 0.68 ± 0.06 (lymphocytes). A total of 96 different 1-Mb windows were identified that explained more than 1% of the genetic variance for at least one CBC trait, with 10 windows explaining more than 1% of the genetic variance for two or more traits. Multiple genes in the identified regions have functions related to immune response, cell differentiation, anemia, and disease. Positional candidate genes include RAD52 motif-containing protein 1 (RDM1), which is correlated with the degree of immune infiltration of immune cells, and C-X-C motif chemokine ligand 12 (CXCL12), which is critically involved in neutrophil bone marrow storage and release regulation and enhances neutrophil migration. Since animal health directly impacts feed intake, understanding the genetics of CBCs may be useful in identifying more disease-resilient and feed-efficient dairy cattle. Identification of genes responsible for variation in CBCs will also help identify the variability in how dairy cattle defend against illness and injury.

Hemograms and serial hemogram-derived ratios in survivors and non-survivors of COVID-19 in Campinas, Brazil

Introduction The hemogram and hemogram-derivative ratios (HDRs) are becoming markers of the severity and mortality of COVID-19. We evaluated the hemograms and serial weekly HDRs [neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), neutrophil-platelet ratio (NPR) and systemic immune-inflammatory index (SII)] in the survivors and non-survivors of COVID-19. Methods We retrospectively reviewed the medical notes and serial hemograms of real-time reverse-transcription polymerase chain reaction (RT-PCR)-confirmed COVID-19 adults hospitalized from April 2020 to March 2021 from the time of diagnosis to the 3rd week of diagnosis. Results Of the 320 adults, 257 (80.3%) were survivors and had a lower mean age than the non-survivors (57.73 vs. 64.65 years, p < 0.001). At diagnosis, the non-survivors had lower hematocrit (p = 0.021), and lymphocyte (p = 0.002) and basophil (p = 0.049) counts and the hematocrit showed a p-value (Is this what you meant???) of 0.021); higher NLR (p < 0.001), PLR (p = 0.047), NPR (p = 0.022) and SII (p = 0.022). Using general linear models, the survivors and non-survivors showed significant variations with weekly lymphocyte count (p < 0.001), neutrophil count (p = 0.005), NLR (p = 0.009), MLR (p = 0.010) and PLR (p = 0.035). All HDRs remained higher in the non-survivors in the 2nd week and 3rd week of diagnosis and the HDRs were higher in the intubated patients than in the non-intubated patients. The NLR and SII were more efficient predictors of mortality in COVID-19 patients. Conclusions This study shows that serial lymphocyte and neutrophil counts, NLR, PLR, MLR, NPR and SII could serve as good and easily accessible markers of severity and predictors of outcomes in COVID-19 patients and should be used for the monitoring of treatment response.

Age-related changes in hematological biomarkers in common marmosets.

Researchers and veterinarians often use hematology and clinical chemistry to evaluate animal health. These biomarkers are relatively easy to obtain, and understanding how they change across healthy aging is critical to clinical care and diagnostics for these animals. We aimed to evaluate how clinical biomarkers from a chemistry profile and complete blood count (CBC) change with age in common marmosets (Callithrix jacchus). We assessed blood samples collected during routine physical exams at the Southwest National Primate Research Center and the University of Texas Health San Antonio marmoset colonies from November 2020-November 2021. We found that chemistry and CBC profiles varied based on facility, sex, and age. Significant changes in albumin, phosphorus/creatinine ratio, albumin/globulin ratio, amylase, creatinine, lymphocyte percent, hematocrit, granulocytes percent, lymphocytes, hemoglobin, red cell distribution width, and platelet distribution width were all reported with advancing age. Aged individuals also demonstrated evidence for changes in liver, kidney, and immune system function compared with younger individuals. Our results suggest there may be regular changes associated with healthy aging in marmosets that are outside of the range typically considered as normal values for healthy young individuals, indicating the potential need for redefined healthy ranges for clinical biomarkers in aged animals. Identifying animals that exhibit values outside of this defined healthy aging reference will allow more accurate diagnostics and treatments for aging colonies.

A score-based method of immune status evaluation for healthy individuals with complete blood cell counts.

BACKGROUND: With the COVID-19 outbreak, an increasing number of individuals are concerned about their health, particularly their immune status. However, as of now, there is no available algorithm that effectively assesses the immune status of normal, healthy individuals. In response to this, a new score-based method is proposed that utilizes complete blood cell counts (CBC) to provide early warning of disease risks, such as COVID-19. METHODS: First, data on immune-related CBC measurements from 16,715 healthy individuals were collected. Then, a three-platform model was developed to normalize the data, and a Gaussian mixture model was optimized with expectation maximization (EM-GMM) to cluster the immune status of healthy individuals. Based on the results, Random Forest (RF), Light Gradient Boosting Machine (LightGBM) and Extreme Gradient Boosting (XGBoost) were used to determine the correlation of each CBC index with the immune status. Consequently, a weighted sum model was constructed to calculate a continuous immunity score, enabling the evaluation of immune status. RESULTS: The results demonstrated a significant negative correlation between the immunity score and the age of healthy individuals, thereby validating the effectiveness of the proposed method. In addition, a nonlinear polynomial regression model was developed to depict this trend. By comparing an individual's immune status with the reference value corresponding to their age, their immune status can be evaluated. CONCLUSION: In summary, this study has established a novel model for evaluating the immune status of healthy individuals, providing a good approach for early detection of abnormal immune status in healthy individuals. It is helpful in early warning of the risk of infectious diseases and of significant importance.

Reconstructing the cytokine view for the multi-view prediction of COVID-19 mortality.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a rapidly developing and sometimes lethal pulmonary disease. Accurately predicting COVID-19 mortality will facilitate optimal patient treatment and medical resource deployment, but the clinical practice still needs to address it. Both complete blood counts and cytokine levels were observed to be modified by COVID-19 infection. This study aimed to use inexpensive and easily accessible complete blood counts to build an accurate COVID-19 mortality prediction model. The cytokine fluctuations reflect the inflammatory storm induced by COVID-19, but their levels are not as commonly accessible as complete blood counts. Therefore, this study explored the possibility of predicting cytokine levels based on complete blood counts. METHODS: We used complete blood counts to predict cytokine levels. The predictive model includes an autoencoder, principal component analysis, and linear regression models. We used classifiers such as support vector machine and feature selection models such as adaptive boost to predict the mortality of COVID-19 patients. RESULTS: Complete blood counts and original cytokine levels reached the COVID-19 mortality classification area under the curve (AUC) values of 0.9678 and 0.9111, respectively, and the cytokine levels predicted by the feature set alone reached the classification AUC value of 0.9844. The predicted cytokine levels were more significantly associated with COVID-19 mortality than the original values. CONCLUSIONS: Integrating the predicted cytokine levels and complete blood counts improved a COVID-19 mortality prediction model using complete blood counts only. Both the cytokine level prediction models and the COVID-19 mortality prediction models are publicly available at http://www.healthinformaticslab.org/supp/resources.php .

End-of-Life transfusion support at hospice and pediatric oncology unit: Bridging the gap between benefits and therapeutic alliance.

OBJECTIVES: Although transfusion support is commonly used in oncological palliative care, there is still a paucity of literature. We examined the transfusion support provided in the terminal stage of the disease and compared the approach at a pediatric oncology unit and a pediatric hospice. CASE DESCRIPTION: This case series analyzed patients treated at the Fondazione IRCCS Istituto Nazionale dei Tumori di Milano (INT)'s pediatric oncology unit who died between January 2018 and April 2022. We compared these with those who died at the VIDAS hospice and analyzed the number of complete blood counts taken in a patient's last 14 days of life, and the number of transfusions performed in the same period.We analyzed 44 patients (22 in pediatric oncology unit; 22 in hospice) in total. Twenty-eight complete blood counts were performed (7/22 patients at the hospice; 21/22 patients at the pediatric oncology unit). Nine patients were given transfusions, three at the hospice, six at our pediatric oncology unit (24 transfusions in total): 20 transfusions at the pediatric oncology unit, four at the hospice. In total 17/44 patients were given active therapies in the last 14 days of life: 13 at the pediatric oncology unit, four at the pediatric hospice. Ongoing cancer treatments did not correlate with a greater likelihood of receiving a transfusion (p=0.91). CONCLUSIONS: The hospice's approach was more conservative than the pediatric oncology one. In the in-hospital setting, the need for a transfusion cannot always be decided on by a combination of numerical values and parameters alone. The family's emotional-relational response must be considered too.

Survival of Persons Living With HIV/AIDS: A Multicentric Study From India.

BACKGROUND: It has been more than 17 years since the introduction of free ART in India. At this point, it would be prudent to look at the factors associated with the survival of persons living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (PLHA) who are already enrolled in the ART program. METHODS: PLHAs enrolled from antiretroviral therapy (ART) centers located in three different cities in India - Delhi, Pune and Kolkata, and were followed up at six monthly intervals monitoring the WHO stage, CD4 counts, complete blood counts, and liver and kidney function tests, for a duration of three years. RESULTS AND DISCUSSION: The incidence of mortality among HIV/AIDS patients on ART was 5.0 per 1000 patient-years (21/1410, 1.4%). Age at initiation of ART, being above 35 years, was the only significant predictor of mortality (log-rank p = 0.018). Multivariable analysis showed a significant association of an unfavourable outcome (defined as mortality or development of opportunistic infection during follow-up) with male gender (adjusted odds ratio (AOR) = 5.26, p = <0.01) and being unmarried at ART initiation (AOR = 1.39, p = 0.005). CONCLUSION: The survival of PLHA with good adherence to ART is independent of the WHO stage or CD4 counts at the initiation of ART. Initiation of ART after 35 years of age was a significant predictor of mortality.

Method comparison between Alinity hq and Sysmex XT-4000i in an emergency laboratory.

Due to technological advancements, haematology analysers are becoming increasingly more complex. Before introducing new analyzers, laboratories must compare the agreement between the new and the old instruments. This study aimed to quantify the method agreement between Sysmex XT-4000i and Alinity hq analysers in order to establish whether they can be used interchangeably. A total of 415 complete blood counts (CBC) from adult patients of the Emergency Clinical County Hospital of Târgu Mureș, Romania, were analysed within 4 h from the collection on Sysmex XT-4000i (considered the reference method), then on Alinity hq. Statistical analysis consisted of outlier removal, Spearman Correlation, Bland-Altman test, and Passing-Bablok regression. For each CBC parameter, the analytical difference between methods was compared with the Reference Change Value (RCV) at medical decision levels (MDL). Despite using different technologies, the instruments have a good agreement regarding cell differentiation and counting. Cell counting and haemoglobin measurement showed a good agreement at all (Medical Decision Limits) MDLs. The analytical difference between methods surpassed the (Reference Change Value) RCV with 1.2% at the 14% MDL of HCT and with 0.2% at the 100 fL MDL of MCV. This study can not tell whether Sysmex or Alinity is superior, only if the two methods agree. The poorer agreement observed for RBC indices, especially MCHC, suggests an accumulation of differences caused by the different working principles of the two methods. However, it is reasonable to assume that such small differences will not affect clinical decision-making and patient outcome.

The Roles of IL-18 in a Realistic Partial Body Irradiation with 5% Bone Marrow Sparing (PBI/BM5) Model.

IL-18 has been shown to play important roles in response to total body irradiation. However, homogenous total body irradiation is not a realistic model to reflect the radiation exposure in a real nuclear event. To further study the roles of IL-18 in a real nuclear scenario, we developed a mouse partial body irradiation with 5% bone marrow sparing (PBI/BM5) model to mimic the inhomogeneous radiation exposure. We established the dose response curves of PBI/BM5 using different radiation doses ranging from 12 to 16 Gy. Using the PBI/BM5 model, we showed that IL-18 knockout mice were significantly more radiation resistant than the wild-type mice at 14.73 Gy. We further studied the hematopoietic changes using a complete blood count, bone marrow colony-forming assays, and serum cytokine assays on the mice exposed to PBI/BM5 with IL-18BP treatment and wild-type/IL-18 knockout mice. In conclusion, our data suggest that IL-18 plays important roles in mouse survival in a realistic nuclear exposure model, potentially through the IL-18/IFNγ pathway.

Hemograms and serial hemogram-derived ratios in survivors and non-survivors of COVID-19 in Campinas, Brazil.

Introduction: The hemogram and hemogram-derivative ratios (HDRs) are becoming markers of the severity and mortality of COVID-19. We evaluated the hemograms and serial weekly HDRs [neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), neutrophil-platelet ratio (NPR) and systemic immune-inflammatory index (SII)] in the survivors and non-survivors of COVID-19. Methods: We retrospectively reviewed the medical notes and serial hemograms of real-time reverse-transcription polymerase chain reaction (RT-PCR)-confirmed COVID-19 adults hospitalized from April 2020 to March 2021 from the time of diagnosis to the 3rd week of diagnosis. Results: Of the 320 adults, 257 (80.3%) were survivors and had a lower mean age than the non-survivors (57.73 vs. 64.65 years, p < 0.001). At diagnosis, the non-survivors had lower lymphocyte (p = 0.002) and basophil (p = 0.049) counts and the hematocrit showed a p-value (Is this what you meant???) of 0.021); higher NLR (p < 0.001), PLR (p = 0.047), NPR (p = 0.022) and SII (p = 0.022). Using general linear models, the survivors and non-survivors showed significant variations with weekly lymphocyte count (p < 0.001), neutrophil count (p = 0.005), NLR (p = 0.009), MLR (p = 0.010) and PLR (p = 0.035). All HDRs remained higher in the non-survivors in the 2nd week and 3rd week of diagnosis and the HDRs were higher in the intubated patients than in the non-intubated patients. The NLR and SII were more efficient predictors of mortality in COVID-19 patients. Conclusions: This study shows that serial lymphocyte and neutrophil counts, NLR, PLR, MLR, NPR and SII could serve as good and easily accessible markers of severity and predictors of outcomes in COVID-19 patients and should be used for the monitoring of treatment response.

Haematological Alterations Associated with Selected Vector-Borne Infections and Exposure in Dogs from Pereira, Risaralda, Colombia.

Infections due to Ehrlichia, Anaplasma, Dirofilaria, Mycoplasma, Babesia and Hepatozoon continue to be highly prevalent in dogs, especially in tropical and subtropical areas, where vectors of many of them are present. However, many clinical aspects of dogs have not been characterized in detail, including assessing the haematological alterations associated with them, particularly in Colombia and Latin America. A group of 100 dogs with Ehrlichia, Anaplasma, Dirofilaria, Mycoplasma, Babesia and Hepatozoon infections/exposure were assessed by blood smear serology (SNAP4DX) and PCR in Pereira, Colombia. We performed blood counts to evaluate anaemia, leukopenia/leukocytosis, neutropenia, neutrophilia, lymphopenia/lymphocytosis, monocytosis, eosinophilia, and thrombocytopenia, among other alterations. Bivariate analyses were performed on Stata®14, with significant p < 0.05. From the total, 85% presented ≥1 infection (past or present), 66% with coinfections (≥2 pathogens) (Ehrlichia 75%), and 89% presented clinical alterations. A total of 100% showed anaemia, 70% thrombocytopenia, 61% monocytosis, and 47% neutropenia, among other alterations. Additionally, 11% presented pancytopenia and 59% bicytopenia. The median platelet count was lower in infected dogs (126,000 cells/µL) versus non-infected (221,000 cells/µL) (p = 0.003). Thrombocytopenia was higher among infected dogs (75%) versus non-infected (40%) (p = 0.006), with a 91% positive predictive value for infection. Median neutrophil count was lower in infected dogs (6591 cells/µL) versus non-infected (8804 cells/µL) (p = 0.013). Lymphocytosis occurred only among those infected (27%) (p = 0.022). Leukopenia was only observed among infected dogs (13%). Pancytopenia was only observed among infected dogs. Ehrlichiosis and other hematic infections have led to a significant burden of haematological alterations on infected dogs, including pancytopenia in a tenth of them, most with thrombocytopenia and all anemic.

Detecting Preeclampsia Severity Using Maternal-Obstetrical Characteristics and Complete Blood Cell Counts.

Purpose: This study aimed to use the combination of maternal-obstetrical characteristics (MOCs) and complete blood cell counts (CBCs) with different red blood cell (RBC) indices as an alternative tool to detect preeclampsia (PE) severity immediately before delivery. Patients and Methods: This retrospective study included all singleton pregnancies delivered after 24 weeks of gestation from April 2016 to April 2020. Patients were divided into four different groups: non-hypertensive (NH), gestational hypertension (GH), PE, and severe PE (SPE). Univariate and forward stepwise multivariate logistic regression analysis was conducted using MOCs, CBCs, and RBC indices. The calculation was performed between SPE and other non-hypertensive and hypertensive (GH, PE) groups. Moreover, the area under the curve (AUC) for the receiver operating characteristic curve, sensitivity, and specificity were estimated. Results: The combined variables for differentiating SPE from NH were maternal age >29.5 years, weight >27.24, gestational age <272 days at the time of blood withdrawal, platelet count <217.5×103/µL, Srivastava indices <6.35, and Siradah indices <43.02 (AUC, 0.834; 95% confidence interval [CI], 0.773-0.895). The combined variables for differentiating SPE from GH were maternal age >29.5 years, body mass index >25.28, gestational age <268.5 days at the time of blood withdrawal, mean corpuscular volume <78.85 fL, and platelet count <234.5×103/µL (AUC, 0777; 95% CI, 0.703-0.852). The combined variables for differentiating SPE from PE were maternal age >32.5 years, mean corpuscular hemoglobin concentration >34.55 g/dL, and Siradah indices <40.05 (AUC, 0.745; 95% CI, 0.656-0.833). Conclusion: The combination of selected variables from MOCs and CBCs with RBC indices before delivery showed satisfactory results for detecting PE severity.

The effects of administering different metaphylactic antimicrobials on growth performance and health outcomes of high-risk, newly received feedlot steers.

Bovine respiratory disease (BRD) is the primary animal health concern facing feedlot producers. Many antimicrobial mitigation strategies are available, but few studies have compared feedlot performance during both the receiving and finishing periods following application of different antimicrobials used as metaphylaxis at arrival. The objective of this study was to compare antimicrobial metaphylaxis methods on clinical health and growth performance across both the receiving and finishing periods. A total of 238 multiple-sourced steers in two source blocks were used in a generalized complete block design. The four treatments included: 1) a negative control, 5 mL of sterile saline injected subcutaneously (CON); 2) subcutaneous administration of florfenicol at 40 mg/kg of BW (NUF); 3) subcutaneous administration of ceftiofur in the posterior aspect of the ear at 6.6 mg/kg of BW (EXC); and 4) subcutaneous administration of tulathromycin at 2.5 mg/kg of BW (DRA). The morbidity rate for the first treatment of BRD was decreased for the DRA and EXC treatments compared to CON and NUF (P < 0.01). Additionally, average daily gain (ADG), dry matter intake (DMI), and gain-to-feed (G:F) were greater (P ≤ 0.02) in the DRA treatment during the receiving period compared to all other treatments. The ADG was also greater (P < 0.05) for EXC than the CON treatment throughout the finishing period. Nonetheless, other growth performance variables did not differ among metaphylactic treatments during the finishing period (P ≥ 0.14). Likewise, no differences in carcass characteristics or liver abscess score were observed (P ≥ 0.18). All complete blood count (CBC) variables were affected by day (P ≤ 0.01) except mean corpuscular hemoglobin concentration (P = 0.29). Treatment × time interactions were observed for platelet count, white blood cell (WBC) count, monocyte count and percentage, and lymphocyte percentage (P ≤ 0.03). However, there were no observed hematological variables that differed among treatment (P ≥ 0.10). The results indicate that some commercially available antimicrobials labeled for metaphylactic use are more efficacious than others in decreasing morbidity rate.

Blood counts in children with Down syndrome.

BACKGROUND: Children with Down syndrome (DS) are more likely to have hematologic and immunologic abnormalities compared to their typically developing peers, but normal ranges have not been defined. The goal of this study was to create references for complete blood counts (CBCs) in patients with DS. METHODS: A retrospective investigation of 355 (male = 196, 55.2%; mean age = 6.49 years, SD = 5.07) healthy pediatric patients with DS who received a CBC between 2011 and 2017 as part of their medical care at a single, large, pediatric teaching hospital. Control data on 770 healthy patients without DS were included. Descriptive statistics were performed on demographic and clinical characteristics. Kruskal-Wallis H tests, nested analysis-of-variance tests, and t-tests were run to determine the significant associations. RESULTS: Age-related normative curves for healthy children with DS outlining 2.5th, 25th, 50th, 75th, and 97.5th percentiles are provided for total white blood count, hemoglobin concentration, hematocrit, mean corpuscular volume, and platelet, absolute neutrophil, absolute lymphocyte, eosinophil, monocyte, and basophil counts. Statistical differences were found between children with and without DS receiving care at the same hospital based on matched age/sex groups. CONCLUSIONS: This study demonstrates that patients with DS have different reference ranges for multiple blood counts compared to those without DS, creating a new resource for pediatricians to refer to when evaluating CBCs in this population.

A Risk Model Composed of Complete Blood Count, BRAF V600E and MAP2K1 Predicts Inferior Prognosis of Langerhans Cell Histiocytosis in Children.

BACKGROUND: In children, Langerhans cell histiocytosis (LCH), which is the most prevalent histiocytic disorder, exhibits a wide variety of manifestations and outcomes. There is no standard prognosis evaluation system for LCH. We investigated the combined predictive significance of complete blood counts (CBCs), BRAF V600E and MAP2K1 in childhood LCH. METHODS: A cohort of 71 childhood LCH patients was retrospectively studied. The prognosis predictive significance of platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), systemic inflammation response index (SIRI), systemic immune inflammation index (SII), BRAF V600E, and MAP2K1 were analyzed. RESULTS: Histiocyte Society (HS) classification of LCH patients was correlated with NLR, SIRI, and progression free survival (PFS), bone involvement was correlated with SIRI, liver involvement was correlated with NLR, SII, SIRI, and PFS, spleen involvement was correlated with SIRI, lung involvement was correlated with NLR and PFS, CNS involvement was correlated with PFS, while BRAF V600E was correlated with PLR, NLR, SIRI, SII, PFS, and OS (p <0.05). MAP2K1 was correlated with NLR, SIRI, PFS, and OS (p <0.05). Elevated NLR, PLR SIRI, and SII predicted inferior PFS and OS (p <0.05). PLR, NLE, SIRI, SII, BRAF V600E, and MAP2K1 were used to establish a risk model for stratifying the LCH patients into 3 different risk groups. Respective median PFS for low-, mediate-, and high-risk groups were not reached, 26, and 14 months (p <0.001), and all median OS were not reached (p <0.001). CONCLUSION: The risk model combined with CBCs, BRAF V600E, and MAP2K1 might be a promising prognostic system for LCH in children.

Metformin with neoadjuvant chemoradiation to improve pathologic response in rectal cancer: A pilot phase I/II trial.

PURPOSE: Neoadjuvant radiotherapy with or without chemotherapy decreases the risk of local recurrence after surgery for rectal cancer. Emerging data suggest that diabetic patients on metformin may have improved cancer outcome after radiotherapy. A single institutional pilot study was performed to determine if metformin given concurrently with long course chemoradiation (CRT) may improve pathologic complete response (pCR) in non-diabetic rectal cancer patients. The study was designed to construct a confidence interval (CI) for the pCR rate to determine the sample size for a phase 2 trial. METHODS: Non-diabetic patients with biopsy confirmed rectal cancer deemed candidates for long course neoadjuvant CRT were invited to participate. Radiation consisted of 50.4 Gy in 28 daily fractions with concurrent daily capecitabine (825 mg/m2 twice daily). Participants self-administered metformin (500 mg of twice daily) 2 weeks prior to, during and for 4 weeks after CRT. RESULTS: A total of 16 patients were accrued. One patient withdrew from the study. Only grade 1 or 2 adverse events were observed. Three patients had a clinical complete response (cCR) and did not undergo surgery. Of the 12 patients who underwent surgery, there were two pCRs. For the combined pCR/cCR rate of 33% (95% CI 19-47%), a total of 85 patients will be required to yield a 95% CI with a 10% margin of error. CONCLUSIONS: Adding metformin to neoadjuvant CRT for rectal cancer does not appear to enhance toxicities. These results will be used to refine the design and conduct of a future phase 2 trial to determine whether adding metformin to CRT improves pCR/cCR rates.

Complete Blood Count Analysis on Beef Cattle Exposed to Fescue Toxicity and Rumen-Protected Niacin Supplementation.

Offspring born to dams genetically tested for resistance to fescue toxicity were separated in groups based on their dams' resistance level (tolerant vs. susceptible). Rumen-protected niacin (RPN) is proposed as a potential alleviator for vasoconstriction produced by fescue toxicity. Complete blood count (CBC) analysis was utilized for detection of significant responses to treatments applied. Our objectives were as follows: (a) to analyze changes in CBC due to fescue toxicity, maternal resistance level, and RPN in growing offspring; and (b) to assess the effects of maternal resistance level when consuming endophyte-infected tall fescue seeds in addition to RPN in offspring performance. Body weight, average daily gain, or health status were not improved by RPN or the genetic test to detect fescue toxicity resistance. Typical signs of alkaloids intoxication and heat stress were noticed in offspring. Particularly, rectal temperature was greater for susceptible control heifers. Results showed that susceptible control offspring presented signs of anemia denoted by low mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV). High levels of white blood cells (WBC) and basophils in combination to low neutrophils to lymphocytes ratio were the signs of infection or inflammation detected in the CBC analysis, especially in tolerant niacin steers. Furthermore, offspring of control heifers had a greater percentage of reticulocytes and RDW, denoting signs of anemia.