Count Response Research Articles

Influence of zinc oxide nanoparticles (ZnO NPs) on the hemocyte count and hemocyte-mediated immune responses of the Greater Wax Moth Galleria mellonella (Lepidoptera: Pyralidae)

In this study, we examined the effects of different doses (100, 500, 1000, 3000, and 5000 ppm) of zinc oxide nanoparticles (ZnO NPs) on the total hemocyte count and hemocyte-mediated immune responses of the Greater Wax Moth Galleria mellonella (Lepidoptera: Pyralidae). The results showed that NPs caused a decrease in hemocyte count at 1000, 3000, and 5000 ppm doses. To investigate the effects of ZnO NPs on the encapsulation and melanization response of G. mellonella, the pre-dyed Sephadex chromatography beads were injected into the hemolymph of each last-instar larva. Larvae were dissected in the 4th and 24th hours after the injection. The level of the encapsulation response and melanization status around the beads were determined under microscopy. The analyses of the beads injected into the insects as encapsulation targets revealed that the number of weakly encapsulated beads increased significantly at 100, 1000, 3000, and 5000 ppm doses when compared to the control group after a short (4-h) post-injection. The number of melanized beads increased significantly at 100, 1000, and 3000 ppm doses in comparison to the control group after the short (4-h) post-injection. Finally, the number of melanized beads decreased significantly at 1000 and 5000 ppm doses when compared to the control group after the long-term (24-h) post-injection.

Superovulatory response, anti-Müllerian hormone concentration and antral follicle count in Holstein cattle with short or long anogenital distance

To understand the mechanisms underlying the inverse relationship between anogenital distance (AGD) and fertility in dairy cattle, we determined if embryo yield and quality differed between cattle of short- and long-AGD (Study 1), and whether anti-Müllerian hormone (AMH), antral follicle count (AFC) and superovulation responses differed by AGD group (Study 2). In Study 1, records of embryo yield and quality in Holstein heifers (n = 43) and cows (n = 14) from two commercial dairy herds were analyzed, retrospectively. Short- and long-AGD groups were based on the median AGD cut-points of 113 and 134 mm, for heifers and cows, respectively. The mean numbers of total (7.4 vs. 9.0; 9.4 vs.12.9), fertilized ova (5.6 vs. 6.2; 6.6 vs. 6.9), and viable embryos (4.4 vs. 4.8; 5.9 vs. 5.3) per heifer and cow did not differ between cattle of short vs. long AGD. Short-AGD cows, however, had greater proportions of fertilized ova (69.7 vs. 53.3%; P = 0.07) and viable embryos (62.1 vs. 41.1%; P = 0.03) than long-AGD cows. The odds of short-AGD cows yielding fertilized ova and viable embryos were 2.0 and 4.0 times greater, respectively, than the odds of long-AGD cows. In Study 2, lactating cows (n = 24) of a research herd had their AGD categorized as in Study 1, and AFC, AMH, and superovulation responses (i.e., no. of preovulatory follicles [≥ 10 mm] and CL) were determined. Mean AFC (27 ± 4.5 vs. 21 ± 4.0) and CL (9 ± 1.6 vs. 7 ± 1.4) per cow did not differ between short- and long-AGD groups. Serum AMH concentration (pg/mL) was lesser in short-AGD cows compared with long-AGD cows (114 ± 30.4 vs. 200 ± 26.8; P = 0.05), but the no. of preovulatory follicles was greater (15 ± 1.9 vs. 8 ± 1.7; P = 0.01) in short-AGD than in long-AGD cows. The overall proportion of follicles ≥10 mm was also greater in short-AGD cows than in long-AGD cows (56 vs 44%; P = 0.03). Preovulatory follicle number was affected by a parity x AGD group interaction (P = 0.04), with multiparous short-AGD cows accounting for the largest number of follicles. No associations were found among AGD, AFC and AMH. The associations between AFC and superovulation responses (follicles: r = 0.67, and CL: 0.58; P < 0.01) were moderate but AMH was not associated with superovulation responses. In summary, whereas AGD-associated differences in the yield and quality of embryos were not evident in heifers, the proportions of fertilized ova and viable embryos were greater in short-AGD than in long-AGD cows. In addition, the proportion of preovulatory follicles, an indicator of superovulatory response, was greater in short-AGD cows than in long-AGD cows.

Multiple inflated negative binomial regression for correlated multivariate count data

Abstract This article aims to provide a method of regression for multivariate multiple inflated count responses assuming the responses follow a negative binomial distribution. Negative binomial regression models are common in the literature for modeling univariate and multivariate count data. However, two problems commonly arise in modeling such data: choice of the multivariate form of the underlying distribution and modeling the zero-inflated structure of the data. Copula functions have become a popular solution to the former problem because they can model the response variables’ dependence structure. The latter problem is often solved by modeling an assumed latent variable Z Z generating excess zero-valued counts in addition to the underlying distribution. However, despite their flexibility, zero-inflation models do not account for the case of m m additional inflated values at k 1 , k 2 , … , k m {{\bf{k}}}_{1},{{\bf{k}}}_{2},\ldots ,{{\bf{k}}}_{m} . We propose a multivariate multiple-inflated negative binomial regression model for modeling such cases. Furthermore, we present an iterative procedure for estimating model parameters using maximum likelihood estimation. The multivariate distribution functions considering the dependence structure of the response vectors are found using copula methods. The proposed method is illustrated using simulated data and applied to real data.

The multivariate Poisson‐Generalized Inverse Gaussian claim count regression model with varying dispersion and shape parameters

AbstractWe introduce a multivariate Poisson‐Generalized Inverse Gaussian regression model with varying dispersion and shape for modeling different types of claims and their associated counts in nonlife insurance. The multivariate Poisson‐Generalized Inverse Gaussian regression model is a general class of models which, under the approach adopted herein, allows us to account for overdispersion and positive correlation between the claim count responses in a flexible manner. For expository purposes, we consider the bivariate Poisson‐Generalized Inverse Gaussian with regression structures on the mean, dispersion, and shape parameters. The model's implementation is demonstrated by using bodily injury and property damage claim count data from a European motor insurer. The parameters of the model are estimated via the Expectation‐Maximization algorithm which is computationally tractable and is shown to have a satisfactory performance.

NEUTROPHIL COUNTS RELATED TO PRESENTATION OF COVID IN AUTOIMMUNE NEUTROPENIA?

To describe 2 cases of autoimmune neutropenia (AIN) patients infected with Sars-Cov-2. Two subjects case report. Case report 1: A girl with primary AIN since 1 year and 10 months old, maintaining severe neutropenia and mild recurrent infections. Presented to the emergency department in June/2020, at 3 years and 8 months old, with flu-like symptoms, afebrile, in good general condition. Physical examination was normal. The absolute neutrophil count (ANC) was 0.279 × 10 9 /L. At hospital admission, Sars-Cov-2 (RT-PCR) tested positive and filgrastim (G-CSF) 5 μg/kg/day was initiated. Chest X-ray was also normal and blood culture resulted negative. She remained in great general condition, afebrile, and was discharged on the 2nd day of hospitalization, with clarithromycin (15 mg/kg/day). After G-CSF, ANC: 0.494 × 10 9 /L (1 st dose), 1.431 × 10 9 /L (2 nd dose). On outpatient follow-up, she had no long-term complications from Covid-19. Case Report 2: A man with chronic immune thrombocytopenia purpura (ITP) since 2008, autoimmune hemolytic anemia since 2013, evolved with AIN on May/2020, at 42 years old, with ANC lower than 0.5 × 10 9 /L. On 6/1/2020, he had ANC 0.170 × 10 9 /L. On 6/25/2020, he started flu-like symptoms, had ANC of 5.118 × 10 9 /L, and tested positive for Sars-Cov-2 (RT-PCR). He kept high fever (102,2°F) and was hospitalized for 10 days without use of G-CSF. After discharge, on outpatient follow-up, he had no long-term complications from Covid-19, and presented ANC 0.338 × 10 9 /L (Aug/2020). At beginning of Covid-19 pandemic, severity infection in children was unknown. Today is known that most of them have milder clinical course, regardless of chronic diseases. In adults, in contrast, the inflammatory response tends to exacerbation, with more severe clinical conditions. Furthermore, many case reports of patients infected by SARS-CoV-2 with comorbidities literature are published. However, to date there are no reports on the impact of COVID-19 in AIN patients. Increased neutrophil counts during infectious episodes are common in AIN, which appears to be related to the benign course of most infections. We reported 2 cases of AIN patients diagnosed with Covid-19, both with favorable clinical outcomes despite heterogenic clinical course. On the first case, she presented few symptoms and ANC increased only after using G-CSF. On the second reported patient, there was a spontaneous increase of ANC and greater inflammatory response than the first case. It could suggest a correlation between inflammatory response to COVID-19 and ANC in cases of autoimmune neutropenia. In the reported cases, clinical course of disease and neutrophil count were different between adult and pediatric patients. It is not possible to state whether this difference is due to age group, individual response to infection or other variables. It is important to assess other cases of AIN infected by COVID 19 to better understand correlation between severity of infection and neutrophil count response.

Mitigating heat stress in broilers by dietary dried tamarind (Tamarindus indica L.) pulp: Effect on growth and blood traits, oxidative status and immune response

The objective of the present study was to evaluate the effect different levels of dried pulp of tamarind (DTSP) on growth, lipid profile, oxidative status and immune response in broilers exposed to cyclic heat stress (HS). A total of 720 one-d-old male broiler chickens (Hubbard) were randomly allocated to 6 treatments (5 replicates) consisted of thermoneutral (TN) and HS. In this experiment, 4 groups of broilers under HS condition were fed four levels of dried tamarind seeds pulp (DTSP) powder at the rate of 0 (DTSP), 5 (DTSP-5), 7.5 (DTSP-7.5), 10 (DTSP-10) and 12.5 (DTSP-12.5) g/kg of feed for 35 d of age. Body weight and feed conversion ratio (FCR) increased (p < 0.05) in the TN and DTSP fed broilers. Blood concentration of paraoxonase-1 (PON1) was higher (p < 0.05) in TN and DTSP-10 and DTSP-12.5. However, antibody titer against Newcastle disease (ND) was higher (p < 0.05) in TN, DTSP-7.5, DTSP-10 and DTSP-12.5. Blood cholesterol and triglyceride were lower (p < 0.05) in TN, DTSP-7.5, DTSP-10 and DTSP-12.5. However, blood HDL was higher (p < 0.05) in DTSP-10 and DTSP-12.5. Blood LDL was significantly lower in DTSP-7.5, DTSP-10 and DTSP-12.5. Significantly higher total leucocytes count (TLC) was found in TN and DTSP-12.5; however, heterophils were significantly lower in the same group. In contrast, lymphocytes increased (p < 0.05) in TN, DTSP-7.5, DTSP-10 and DTSP-12.5, while monocytes was significantly decreased in the same group. In conclusion, DTSP improved growth, cholesterol profile, PON1 and leucocytes count and immune response against ND in broilers exposed to heat stress.

Bayesian discrete conditional transformation models

We propose a novel Bayesian model framework for discrete ordinal and count data based on conditional transformations of the responses. The conditional transformation function is estimated from the data in conjunction with an a priori chosen reference distribution. For count responses, the resulting transformation model is novel in the sense that it is a Bayesian fully parametric yet distribution-free approach that can additionally account for excess zeros with additive transformation function specifications. For ordinal categoric responses, our cumulative link transformation model allows the inclusion of linear and non-linear covariate effects that can additionally be made category-specific, resulting in (non-)proportional odds or hazards models and more, depending on the choice of the reference distribution. Inference is conducted by a generic modular Markov chain Monte Carlo algorithm where multivariate Gaussian priors enforce specific properties such as smoothness on the functional effects. To illustrate the versatility of Bayesian discrete conditional transformation models, applications to counts of patent citations in the presence of excess zeros and on treating forest health categories in a discrete partial proportional odds model are presented.

Chemo-immune cell therapy by intratumoral injection of adoptive NK cells with capecitabine in gastric cancer xenograft model.

Gastric cancer is one of the most commonly known malignancies and is the fifth cancer-related death globally. Whereas natural killer (NK) cells play a critical role in tumor elimination; therefore, adoptive NK cell therapy has become a promising approach in cancer cytotherapy. Hence, this study investigated the chemo-immune cell therapy in MKN-45 derived xenograft gastric cancer model. Three groups of animals have received the following treatments separately: activated NK cells, capecitabine, the combination of capecitabine and activated NK cells, and one was considered as the control group. Morphometric properties of tumor samples were evaluated at the end of the study. NK cells infiltration was evaluated by immunohistochemistry (IHC) of hCD56. Mitotic count and treatment response was assessed by hematoxylin and eosin (H&E) staining. The proliferation ratio to apoptosis was determined by IHC assessment of Ki67 and caspase 3. The results indicated that the NK cell therapy could effectively decrease the mitotic count in pathology assessment, but the tumor was not completely eradicated. In combination with metronomic chemotherapy (MC) of capecitabine, NK cell therapy demonstrated a significant difference in tumor morphometric properties compared to the control group. The proliferation ratio to apoptosis was also in line with pathology data. Although NK cell therapy could effectively decrease the mitotic count in vivo, the obtained findings indicated lesser potency than MC despite ex vivo activation. In order to enhance NK cell therapy effectiveness, suppressive features of the tumor microenvironment and inhibitory immune checkpoints blockade should be considered.

Biclustering via Semiparametric Bayesian Inference

Motivated by classes of problems frequently found in the analysis of gene expression data, we propose a semiparametric Bayesian model to detect biclusters, that is, subsets of individuals sharing similar patterns over a set of conditions. Our approach is based on the well-known plaid model by Lazzeroni and Owen (2002). By assuming a truncated stick-breaking prior we also find the number of biclusters present in the data as part of the inference. Evidence from a simulation study shows that the model is capable of correctly detecting biclusters and performs well compared to some competing approaches. The flexibility of the proposed prior is demonstrated with applications to the analysis of gene expression data (continuous responses) and histone modifications data (count responses).

Sufficient Dimension Reduction for Poisson Regression

Poisson regression is popular and commonly employed to analyze frequency of occurrences in a fixed amount of time. In practice, data collected from many scientific disciplines tend to grow in both volume and complexity. One characteristic of such complexity is the inherent sparsity in high-dimensional covariates space. Sufficient dimension reduction (SDR) is known to be an effective cure for its advantage of making use of all available covariates. Existing SDR techniques for a continuous or binary response do not naturally extend to count response data. It is challenging to detect the dependency between the response variable and the covariates due to the curse of dimensionality. To bridge the gap between SDR and its applications in count response models, an efficient estimating procedure is developed to recover the central subspace through estimating a finite dimensional parameter in a semiparametric model. The proposed model is flexible which does not require model assumption on the conditional mean or multivariate normality assumption on covariates. The resulting estimators achieve optimal semiparametric efficiency without imposing linearity or constant variance assumptions. The finite sample performance of the estimators is examined via simulations, and the proposed method is further demonstrated in the baseball hitter example and pathways to desistance study.

Comparison of two electromyography-based neuromuscular monitors, AF-201P and TetraGraph, in rocuronium-induced neuromuscular block: A prospective comparative study

BackgroundThe study aimed to compare the responses obtained simultaneously from the newly developed electromyography (EMG)-based neuromuscular monitors, AF-201P and TetraGraph™, during rocuronium-induced neuromuscular block. MethodsTwenty patients were enrolled in this study. During total intravenous general anesthesia, train-of-four (TOF) responses following 0.9-mg/kg-rocuronium administration were monitored at the abductor digiti minimi muscle with AF-201P and TetraGraph on the contralateral arms. Sugammadex 2 mg/kg was administered when both devices showed TOF counts (TOFC) = 2. The primary outcome was time from rocuronium administration to the first appearance of the post-tetanic count (PTC) response (first PTC). The secondary outcomes were supramaximal current, baseline compound muscle action potential, onset time, time to TOFC = 1, time to TOFC = 2, and time from sugammadex administration to TOF ratio ≥ 0.9. We used the paired t-test and Wilcoxon signed-rank test to analyze parametric and non-parametric data, respectively. P < 0.05 defined statistical significance. ResultsA total of 19 patients were analyzed. The supramaximal current was significantly lower with AF-201P than TetraGraph (31.7 ± 13.2 vs. 43.2 ± 8.2, p = .002). The time to first PTC (24.9 ± 9.4 vs. 27.3 ± 8.9 min, p = .026), time to TOFC = 1 (42.3 ± 9.0 vs. 45.1 ± 10.4 min, p = .03), and time to TOFC = 2 (52.0 ± 10.5 vs. 54.6 ± 11.7 min, p = .014) were significantly faster with AF-201P than with TetraGraph. There were no significant differences in the other outcomes between the devices. ConclusionsAF-201P showed faster recovery of rocuronium-induced neuromuscular block compared with TetraGraph.

Prognostic significance of CNSL at diagnosis of childhood B-cell acute lymphoblastic leukemia: A report from the South China Children's Leukemia Group.

ObjectivesThe prognostic significance of acute lymphoblastic leukemia (ALL) patients with central nervous system leukemia (CNSL) at diagnosis is controversial. We aimed to determine the impact of CNSL at diagnosis on the clinical outcomes of childhood B-cell ALL in the South China Children’s Leukemia Group (SCCLG).MethodsA total of 1,872 childhood patients were recruited for the study between October 2016 and July 2021. The diagnosis of CNSL depends on primary cytological examination of cerebrospinal fluid, clinical manifestations, and imaging manifestations. Patients with CNSL at diagnosis received two additional courses of intrathecal triple injections during induction.ResultsThe frequency of CNLS at the diagnosis of B-cell ALL was 3.6%. Patients with CNSL at diagnosis had a significantly higher mean presenting leukocyte count (P = 0.002) and poorer treatment response (P <0.05) compared with non-CNSL patients. Moreover, CNSL status was associated with worse 3-year event-free survival (P = 0.030) and a higher risk of 3-year cumulative incidence of relapse (P = 0.008), while no impact was observed on 3-year overall survival (P = 0.837). Multivariate analysis revealed that CNSL status at diagnosis was an independent predictor with a higher cumulative incidence of relapse (hazard ratio = 2.809, P = 0.016).ConclusionCNSL status remains an adverse prognostic factor in childhood B-cell ALL, indicating that additional augmentation of CNS-directed therapy is warranted for patients with CNSL at diagnosis.

Evaluation of CD4 count response in HIV subjects with antiretroviral treatment protocol

The present study was undertaken to evaluate the CD4 count responses in subjects who are on long term first line antiretroviral treatment (ART).A total of 200 People Living with HIV/AIDS (PLHIV), on first line ART for five years seen in the ART centre were included in the study. Patients were interviewed and details entered as per the proforma. Proforma included various details such as serial CD4 counts and Opportunistic infection pre and post ART.Mean CD4 count pre ART was 171.32 ± 65.23 per mm and one year after ART was 374.56 ± 159.12. There was significant rise in CD4 count one year after the initiation of ART (p = 0.000) The mean CD4 count at the time of collection of data was 545.23 ± 259.11 as compared to mean CD4 count pre ART of 171.32 ± 65.23 per mm. The rise was significant.National AIDS Control. OrganizationNACO) suggested first line regimens outcome in vigorous immunologic response that is continued over a mean period of over six years in a majority (84%) of the subjects and consequence in significant decline in opportunistic infections.

Development of a novel low-background noise blood loop model for testing blood-contacting biomaterials and medical devices in fresh human blood.

A novel low volume blood loop model (Ension Triad System [ETS]) incorporating pulsatile flow and a proprietary low-activation blood-contacting surface (Ension bioactive surface [EBS]) enabling high signal-to-noise performance is described. The ETS system incorporates a test chamber that allows direct comparison of material samples or finished medical devices such as catheters with varying compositions and/or surface treatments. ETS performance is presented from two independent organizations (Medtronic and MLM Labs) and includes results for hemolysis (pfHgb), platelet count, platelet activation (βTG), coagulation (TAT), inflammation (PMN Elastase, PMN CD112b, and monocyte CD112b) and immune response (SC5b-9) were made on: (1) the EBS-treated system itself without a test material (No Material, NM); (2) the EBS-treated system with an idealized untreated catheter (UC); and (3) the EBS-treated system with the prototype catheter treated with the EBS surface treatment (CC). The untreated catheter (UC) was associated with significant elevation of all activation marker levels (pfHgb excluded). The EBS-treated catheter, in direct comparison to the UC and NM catheters, appeared invisible with respect to the activation markers (all markers statistically different than the UC and equivalent to the NM control). Based on these data, we conclude that using a relatively small surface area test sample and a small volume of fresh human blood, the high signal-to-noise performance of the ETS system demonstrates comprehensive and statistically significant material differences in the major ISO 10993-4 categories of blood interaction. These data underscore the important benefit of minimal confounding of test/device responses with non-test-material/model-related responses. ETS offers a practical alternative to the common one-test-category-at-a-time approach when assessing blood/medical device interactions.

Multivariate mixed Poisson Generalized Inverse Gaussian INAR(1) regression

In this paper, we present a novel family of multivariate mixed Poisson-Generalized Inverse Gaussian INAR(1), MMPGIG-INAR(1), regression models for modelling time series of overdispersed count response variables in a versatile manner. The statistical properties associated with the proposed family of models are discussed and we derive the joint distribution of innovations across all the sequences. Finally, for illustrative purposes different members of the MMPGIG-INAR(1) class are fitted to Local Government Property Insurance Fund data from the state of Wisconsin via maximum likelihood estimation.

O-131 Progesterone Primed Ovarian Stimulation (PPOS) Vs Clomiphene Primed Ovarian Stimulation (CPOS) in high responder (HR) patients undergoing controlled ovarian stimulation - A Randomized Control Trial

Study questionIn high responder individuals, stimulation with PPOS or CPOS would offer better outcomes?Summary answerData from this trial concludes that stimulation with CPOS or PPOS seem to offer comparable outcomes in high responders individuals.What is known alreadyProgesterone and Clomiphene Citrate have been used to suppress premature LH surge in patients undergoing controlled ovarian stimulation (COS) for In Vitro Fertilization. Their use will negate the need of using additional injections and thereby would improve the patient acceptability and reduce pain and drop out rates. This Randomized Control Trial (RCT) intends to look at the efficiency of these protocols.Study design, size, durationThis is a Prospective RCT conducted between September 2020-December 2021 with prior approval from Institutional Ethical committee (ECR/1312/INST/TG/2019). HR patients as defined by Antral Follicular Count (AFC), Anti-Mullerian hormone (AMH) or previous response were randomized into PPOS (n = 50) & CPOS (n = 50) arm at start of stimulation based on a computer generated randomization sheet.Exclusion criteriaAge > 35 yrs, history of Total Fertilization Failure, Inadequate post-trigger hormonal values, incomplete retrieval of oocytes.Participants/materials, setting, methodsAfter randomization, all patients were started on Inj rFSH & Inj HP-HMG (dosage depending upon BMI). PPOS arm- Tab.Medroxy Progesterone Acetate10 mg/day started from day 2 of the cycle along with gonadotropins and continued until trigger. CPOS arm- Clomiphene citrate 150 mg/day (divided doses) starting from the 8thday of stimulation or when lead follicle reached 12 mm diameter and continued until trigger.All the subjects underwent Frozen Embryo replacement cycle with two good grade blastocysts.Main results and the role of chanceBaseline variables of patients were comparable between both arms. There were 6-dropouts in PPOS arm and 8 dropouts in CPOS arm due to Covid -19 infection. Hence a total of 44 patients in PPOS arm and 42 patients in CPOS arm were available for analysis.Premature LH surge rates, cycle cancellation rate, blastocyst rate (BR), Implantation Rate (IR) per initiated FET cycle were the primary outcomes.Dose and duration of gonadotropins, number of oocytes, maturation rate, fertilization rate (FR), and OHSS rate were the secondary outcomesOutcomes between PPOS Vs CPOS were as follows: LH Surge – 2.3% vs 2.5% (p = 1)Cycle cancellation rate – 9.1% Vs 10% (p = 1)BR – 57% vs 56% (p = 0.547)IR – 44% Vs 49% (p = 0.687)Secondary outcomes - Dose and duration of gonadotropins, number of oocytes retrieved, fertilization rate, maturation rate & OHSS rate were comparable in both groups.All the outcomes compared between the two arms seemed to be similar with no statistical significance. Progesterone or Clomiphene priming seems to offer optimal outcomes with no superiority of one protocol over the other.Limitations, reasons for cautionThe RCT was performed on a small sample size and should be confirmed on a larger cohort. Moreover, this is the first study comparing both the drugs in high responders and confirms the efficacy of both drugs as LH suppressants without compromising outcomes.Wider implications of the findingsThis study provides assuring data on using the two oral agents, progesterone and clomiphene citrate with equal efficacy and without affecting the outcomes. These agents can help in reducing the dosage of gonadotropins and this in turn can help in minimizing the complications like OHSS during controlled ovarian stimulation.Trial registration numberNot applicable

The addition of oral iron improves chemotherapy-induced anemia in patients receiving erythropoiesis-stimulating agents.

Although many studies have shown that supplementation with iron and erythropoiesis-stimulating agents (ESA) is frequently used for managing chemotherapy-induced anemia (CIA), optimal combination therapy using these agents together to ameliorate anemia is not well characterized. To assess the effects of ESA combined with oral or intravenous (IV) iron on relieving CIA, PubMed, Cochrane Library, Embase and China National Knowledge Infrastructure (CNKI) were searched for articles. Data collected in the articles were meta-analyzed using RevMan 5.3 software with a random-effects model. Our comprehensive search yielded 1666 potentially relevant trials. A total of 41 trials randomizing 4200 patients with CIA fulfilled inclusion criteria, including 34 Chinese articles and 7 English articles. Meta-analysis showed that treatment with both ESA and iron more effectively improved CIA relative to iron supplementation alone, with increased hemoglobin, hematocrit, red blood cell count and hematopoietic response rate. Subgroup analyses revealed iron administration, both oral and IV iron, improved anemia in ESA-treated cancer patients with CIA. Our analysis demonstrates that iron supplementation combined with ESA more effectively ameliorates CIA relative to iron supplementation alone, without regard to whether IV or oral iron was used. Together, our findings may contribute to the clinical treatment of CIA using iron therapy with or without ESA.

P1140: TIME TO TUMOR, SYMPTOMATIC AND LABORATORY RESPONSES FOLLOWING SILTUXIMAB TREATMENT IN IDIOPATHIC MULTICENTRIC CASTLEMAN DISEASE

Background: Idiopathic multicentric Castleman disease (iMCD) is a rare, heterogeneous disorder involving multicentric lymphadenopathy, systemic inflammation, and cytokine-driven organ dysfunction. Siltuximab—a monoclonal antibody against interleukin-6—is the only FDA- and EMA-approved treatment for iMCD. A phase 2, randomized, double-blind, placebo-controlled trial of siltuximab for the treatment of iMCD (NCT01024036) showed that 18/53 patients (34%) responded to treatment, compared with 0% in the placebo group, but it is not known how long patients should be maintained on siltuximab before deciding whether the treatment is beneficial. Aims: To determine the time to and sequence of normalization of laboratory, clinical, and lymph node responses in patients who responded to siltuximab. Methods: The phase 2 trial enrolled adults with symptomatic iMCD who were human immunodeficiency virus seronegative and human herpesvirus 8 negative. In this post hoc analysis, we aimed to determine the sequence of and time to normalization of laboratory, clinical, and lymph node responses in patients who responded to siltuximab. The Kaplan–Meier and cumulative incidence with competing risks methods with corresponding log-rank tests were produced to estimate and compare the progression-free survival (PFS), overall survival, time to treatment failure, time to lymph node response, time to durable symptomatic response, and time to normalization of laboratory values. Results: Seventy-nine patients were enrolled in the trial (n=53 siltuximab, n=26 placebo; all patients received best supportive care). The median duration of follow-up was 422 days (range 55‒1051). Siltuximab treatment improved PFS compared with placebo (p=0.0001). The median PFS was 14.5 months (95% CI 13.6–upper bound not reached) for patients on placebo, whereas it was not reached for patients on siltuximab. The 2-year estimates for overall survival were 93% (95% CI 85–100%) for the siltuximab arm and 77% (95% CI 55–98%) for the placebo arm (p=0.11). Time to treatment failure in the placebo arm was 4.8 months and was not reached with siltuximab (p=0.005). In the 18 siltuximab-treated patients who achieved the primary endpoint of durable tumor (radiologic) and symptomatic response, most first achieved rapid normalization of various laboratory parameters and symptomology (median of 0.8 months to normalization based on a 34-point MCD symptom score) (Table 1). Lymph node responses occurred later (median of 4.1 months to normalization). Image:Summary/Conclusion: Significant improvements in biochemical parameters such as platelet count, albumin, and symptomatic responses occur within 3 months in the majority of responders, showing them as early indicators of response. Lymph nodes were slower to show an improvement in response to treatment, and so involution of these should not be used to drive early therapeutic decisions in iMCD patients following siltuximab. The present study shows the recovery sequence of different parameters over time following initiation of treatment with siltuximab.

The Impact of BRCA1- and BRCA2 Mutations on Ovarian Reserve Status

This study aimed to investigate whether female BRCA1- and BRCA2 mutation carriers have a reduced ovarian reserve status, based on serum anti-Mullerian hormone (AMH) levels, antral follicle count (AFC) and ovarian response to ovarian hyperstimulation. A prospective, multinational cohort study was performed between October 2014 and December 2019. Normo-ovulatory women, aged 18–41 years old, applying for their first PGT-cycle for reason of a BRCA mutation (cases) or other genetic diseases unrelated to ovarian reserve (controls), were asked to participate. All participants underwent a ICSI-PGT cycle with a long-agonist protocol for controlled ovarian hyperstimulation. Linear and logistic regression models were used to compare AMH, AFC and ovarian response in cases and controls. Sensitivity analyses were conducted on BRCA1- and BRCA2 mutation carrier subgroups. Thirty-six BRCA mutation carriers (18 BRCA1- and 18 BRCA2 mutation carriers) and 126 controls, with mean female age 30.4 years, were included in the primary analysis. Unadjusted median AMH serum levels (IQR) were 2.40 (1.80–3.00) ng/ml in BRCA mutation carriers and 2.15 (1.30–3.40) ng/ml in controls (p = 0.45), median AFC (IQR) was 15.0 (10.8–20.3) and 14.5 (9.0–20.0), p = 0.54, respectively. Low response rate was 22.6% among BRCA mutation carriers and 9.3% among controls, p = 0.06. Median number of retrieved oocytes was 9 (6–14) in carriers and 10 (7–13) in controls, p = 0.36. No substantial differences were observed between BRCA1- and BRCA2 mutation carriers. Based on several biomarkers, no meaningful differences in ovarian reserve status were observed in female BRCA mutation carriers compared to controls in the context of ICSI-PGT treatment.

The Impact of Purple-Flesh Potato (Solanum tuberosum L.) cv. "Shadow Queen" on Minor Health Complaints in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Study.

The purple-flesh potato (Solanum tuberosum L.) cultivar “Shadow Queen” (SQ) naturally contains anthocyanins. This randomized, double-blind, placebo-controlled study determines whether ingesting purple potatoes increases the number of mesenchymal stem cells (MSC) and improves stress response, a minor health complaint in healthy adults (registration number: UMIN000038876). A total of 15 healthy subjects (ages: 50–70 years) with minor health complaints were randomly assigned to one of two groups. For 8 weeks, the placebo group received placebo potatoes cv. “Haruka” and the test group received test potato cv. SQ containing 45 mg anthocyanin. The MSC count and several stress responses were analyzed at weeks 0 and 8 of the intake periods. The ingestion of a SQ potato did not affect the MSC count but markedly improved psychological stress response, irritability, and depression as minor health complaints compared with “Haruka”. No adverse effects were noted. Hence, an 8-week intake of SQ could improve stress responses.