Changes In Blood Counts Research Articles

Safety and Efficacy Results of BonoFill First-in-Human, Phase I/IIa Clinical Trial for the Maxillofacial Indication of Sinus Augmentation and Mandibular Bone Void Filling

The gold standard for bone regeneration of bone deficiencies is still an autologous bone graft, which has considerable disadvantages; namely, the need for a second major surgery and the limited volume of bone available for harvesting. BonoFill (BF) is a novel, tissue-engineered, bone graft with intrinsic osteoinductive, osteoconductive, and osteogenic properties, consisting of the patient's own adipose tissue-derived mesenchymal stem cells, attached to hydroxyapatite particles. Here, we present the safety and efficacy results of BF first-in-human clinical study for maxillofacial bone tissue regeneration. Eleven eligible male and female subjects, aged 49-65years, were enrolled into the clinical study in 2 clinical indications: Bone augmentation and bone void grafting in the jaws. Clinical follow-up was performed throughout a period of 6 months after BF treatment and included clinical examination, blood tests, CT scans, and biopsies collected from the transplantation site to assess chronic bone infection, changes in complete blood count, and adequate bone augmentation for implant placement. The study results demonstrated that BF promoted adequate bone tissue regeneration without complications. Per our evaluation, there were no incidents of chronic bone infection, or significant changes in complete blood count, and the patients reported overall good health for the duration of the study. At trial end, in the sinus augmentation indication, the BF treated sites residual bone was augmented at an average of 6.36mm (Δ new bone, n=10) and the total bone height at the treated area was on average 11.44mm (n=10). In the indication of filling of bone voids, the patient's average residual bone height of 2.91mm was 15.76mm (n=1) at trial end. BF treatment was shown to be safe and resulted in newly generated bone, which provided adequate bone height for placement of dental implants. Thus, BF is a promising novel autologous bone graft for bone tissue repair.

A novel haemocytometric COVID-19 prognostic score developed and validated in an observational multicentre European hospital-based study.

COVID-19 induces haemocytometric changes. Complete blood count changes, including new cell activation parameters, from 982 confirmed COVID-19 adult patients from 11 European hospitals were retrospectively analysed for distinctive patterns based on age, gender, clinical severity, symptom duration, and hospital days. The observed haemocytometric patterns formed the basis to develop a multi-haemocytometric-parameter prognostic score to predict, during the first three days after presentation, which patients will recover without ventilation or deteriorate within a two-week timeframe, needing intensive care or with fatal outcome. The prognostic score, with ROC curve AUC at baseline of 0.753 (95% CI 0.723-0.781) increasing to 0.875 (95% CI 0.806-0.926) on day 3, was superior to any individual parameter at distinguishing between clinical severity. Findings were confirmed in a validation cohort. Aim is that the score and haemocytometry results are simultaneously provided by analyser software, enabling wide applicability of the score as haemocytometry is commonly requested in COVID-19 patients.

Gamma Tocotrienol Protects Mice From Targeted Thoracic Radiation Injury.

Radiation injury will result in multiorgan dysfuntion leading to multiorgan failure. In addition to many factors such as radiation dose, dose rate, the severity of the injury will also depend on organ systems which are exposed. Here, we report the protective property of gamma tocotrienol (GT3) in total as well as partial body irradiation (PBI) model in C3H/HeN male mice. We have carried out PBI by targeting thoracic region (lung-PBI) using Small Animal Radiation Research Platform, an X-ray irradiator with capabilities of an image guided irradiation with a variable collimator with minimized exposure to non-targeted tissues and organs. Precise and accurate irradiation of lungs was carried out at either 14 or 16 Gy at an approximate dose rate of 2.6 Gy/min. Though a low throughput model, it is amenable to change the field size on the spot. No damage to other non-targeted organs was observed in histopathological evaluation. There was no significant change in peripheral blood counts of irradiated mice in comparison to naïve mice. Femoral bone marrow cells had no damage in irradiated mice. As expected, damage to the targeted tissue was observed in the histopathological evaluation and non-targeted tissue was found normal. Regeneration and increase of cellularity and megakaryocytes on GT3 treatment was compared to significant loss of cellularity in saline group. Peak alveolitis was observed on day 14 post-PBI and protection from alveolitis by GT3 was noted. In irradiated lung tissue, thirty proteins were found to be differentially expressed but modulated by GT3 to reverse the effects of irradiation. We propose that possible mode of action of GT3 could be Angiopoietin 2-Tie2 pathway leading to AKT/ERK pathways resulting in disruption in cell survival/angiogenesis.

Thrombosis at hospital presentation in patients with and without coronavirus disease 2019

ObjectiveIn the present study, we sought to better characterize the patients with coronavirus disease 2019 (COVID-19) most at risk of severe, outpatient thrombosis by defining the patients hospitalized with COVID-19 with arterial or venous thrombosis diagnosed at admission. MethodsWe conducted a single-center, retrospective analysis of COVID-19 patients. We found a shift in the proportions of thrombosis subtypes from 2019 to 2020, with declines in ST-segment myocardial infarction (from 22.0% to 10.1% of thrombotic events) and stroke (from 48.6% to 37.2%) and an increase in venous thromboembolism (from 29.4% to 52.7%). The patients with COVID-19–associated thrombosis were younger (age, 58 years vs 64 years; P = .043) and were less frequently women (31.3% vs 43.9%; P = .16). However, no differences were found in the body mass index or major comorbidities between those with and without COVID-19. COVID-19–associated thrombosis correlated with greater mortality (15.2% vs 4.3%; P = .016). The biometric profile of patients admitted with COVID-19–associated thrombosis compared with regular thrombosis showed significant changes in the complete blood count, liver function test results, D-dimer levels, C-reactive protein, ferritin, and coagulation panels. ConclusionsOutpatients with COVID-19 who developed thrombosis requiring hospitalization had increased mortality compared with outpatients without COVID-19 who developed thrombosis requiring hospitalization. Given the significantly higher inflammatory marker levels, it is possible this is related to different mechanisms of thrombotic disease in these patients. The inflammation could be a therapeutic target to reduce the risk, or aid in the treatment, of thrombosis. We call for more studies elucidating the role that immunothrombosis might be playing in patients with COVID-19.

Multicenter Validation of a Personalized Model to Predict Hypomethylating Agent Response in Myelodysplastic Syndromes (MDS)

Background While hypomethylating agents (HMAs) can improve cytopenias and even survival for MDS patients (pts), only 30-40% of pts respond to HMAs. Predicting response or resistance to therapy can improve pt outcomes, decrease cost and toxicities, and suggest alternative therapies when response is unlikely. No clinical or molecular model can reliability predict response or resistance to HMAs. We developed and validated a model to provide personalized predictions of response or resistance to HMAs during 12 weeks of treatment by monitoring changes in blood counts during therapy. Methods MDS pts treated with HMAs (azacitidine or decitabine) at Cleveland Clinic (314 pts) and the Moffit Cancer Center (100) and had their CBCs with differential monitored every 1-2 weeks in the first 12 weeks of therapy compromised the training cohort. The final model was externally validated in 80 MDS pts treated with HMAs at Sunnybrook hospital. Responses were defined per 2006 IWG criteria and pts with complete response (CR), marrow CR, partial response (PR), or hematologic improvement (HI) were considered responders. Time series analysis (analysis of serial changes in blood count parameters) using machine learning technology was used to develop the model, analogous to voice recognition algorithms such as Apple's Siri and Alexa, in which the sequence of words allows these algorithms to understand sentences. Changes in blood counts and monitoring the patterns of these changes during HMA therapy similarly can predict response/resistance to treatment. The area under the curve (AUC) was used to evaluate the performance of the final model. A feature importance algorithm was used to define the variables that most impacted the algorithm's decision for a given pt. Results For 494 included pts from all cohorts, the median age was 72 years (range: 40-94), 145 (29%) were female. Pts' IPSS-R scores at the time of treatment were: very low 4%; low 21%; intermediate 24%; high 21%; and very high 22%. Responses included: 56 (11%) complete remission (CR), 17 (3%) marrow CR, 6 (3%) partial remission (PR), and 143 (29%) hematologic improvement (HI). When trained exclusively on serial CBC values (adding other clinical or molecular values did not improve the model's performance), the model achieved an AUC of 0.82 in a cross-validated train/test schema and a similar AUC of 0.78 when it was applied to the Sunnybrook cohort. Feature importance algorithms identified improvements in hemoglobin from baseline between days 21-30 of therapy, improvement in platelets between days 51 and 60, changes in monocyte % between days 41 and 50, and changes in MCV and RDW between days 31 and 60 as predictors of response, Figure 1a. The model also can provide a personalized heatmap that summarizes the variables that impacted the response or resistance to HMAs and are specific for a given pt, Figure 1b, 1c. Conclusions We developed and externally validated a personalized prediction model that uses changes in blood counts during the initial 3 cycles of HMA therapy and can predict response or resistance to treatment with high accuracy. The model can provide personalized explanations of the variables that inform a given outcome. It can be used to develop novel clinical trial designs in which pts who are predicted not to respond within 3 cycles of HMA therapy can receive an investigational agent in addition to continuing HMA or change treatment entirely, whereas patients who are predicted to respond continue to receive HMA monotherapy. Disclosures Sallman: Agios, Bristol Myers Squibb, Celyad Oncology, Incyte, Intellia Therapeutics, Kite Pharma, Novartis, Syndax: Consultancy; Celgene, Jazz Pharma: Research Funding. Buckstein:Celgene: Research Funding; Takeda: Research Funding; Celgene: Honoraria; Astex: Honoraria; Novartis: Honoraria. Brunner:Forty Seven, Inc: Consultancy; Biogen: Consultancy; Acceleron Pharma Inc.: Consultancy; Jazz Pharma: Consultancy; Novartis: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Xcenda: Consultancy; GSK: Research Funding; Janssen: Research Funding; Astra Zeneca: Research Funding; Celgene/BMS: Consultancy, Research Funding. Mukherjee:Celgene/Acceleron: Membership on an entity's Board of Directors or advisory committees; Aplastic Anemia and MDS International Foundation: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Bristol Myers Squib: Honoraria; Partnership for Health Analytic Research, LLC (PHAR, LLC): Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; EUSA Pharma: Consultancy. Komrokji:Abbvie: Honoraria; Agios: Speakers Bureau; BMS: Honoraria, Speakers Bureau; Jazz: Honoraria, Speakers Bureau; Incyte: Honoraria; Acceleron: Honoraria; Geron: Honoraria; Novartis: Honoraria. Maciejewski:Novartis, Roche: Consultancy, Honoraria; Alexion, BMS: Speakers Bureau. Sekeres:BMS: Consultancy; Pfizer: Consultancy; Takeda/Millenium: Consultancy. Nazha:Jazz: Research Funding; Incyte: Speakers Bureau; Novartis: Speakers Bureau; MEI: Other: Data monitoring Committee.

Pure Pathologic Response Is Associated with Improved Overall Survival in Patients with Advanced Systemic Mastocytosis Receiving Avapritinib in the Phase I EXPLORER Study

Pure Pathologic Response Is Associated with Improved Overall Survival in Patients with Advanced Systemic Mastocytosis Receiving Avapritinib in the Phase I EXPLORER Study

Salubrinal Mediated Fetal Hemoglobin Induction through the eIF2α-ATF4 Signaling Pathway

Sickle cell disease (SCD) is a genetic disorder caused by a mutation in the adult β-globin gene, affecting ~100,000 people in the United States and millions worldwide. Clinical symptoms of SCD include anemia, pain, and progressive organ damage creating a great burden to annual healthcare costs. An effective therapeutic intervention for SCD is fetal hemoglobin (HbF) induction by pharmacologic agents to ameliorate clinical symptoms. Hydroxyurea (HU) is the only FDA-approved drug used to induce HbF in SCD, however, it is not effective in all people. Therefore, the goal of this study is to determine the ability of Salubrinal (SAL), to induce HbF. Salubrinal is a selective inhibitor of protein phosphatase 1 leading to increased levels of p-eIF2α (phosphorylated eukaryotic initiation factor 2α) and inhibition of global protein synthesis. Activating transcription factor 4 (ATF4) is a downstream target of p-eIF2α activated during oxidative stress. The main function of these signaling events is to attenuate stress to the endoplasmic reticulum. Previously we identified a Gγ-globin cAMP response element (G-CRE) that binds ATF2, a binding partner of ATF4 involved in HbF induction (Sangerman J et al. Blood 2006). Furthermore, ENCODE analysis showed ATF4 sites at -822Gγ and β-globin gene second intron. Thus, studies were performed to determine if p-eIF2α-ATF4 signaling is involved in mechanisms of HbF induction by SAL. Initial experiments involved the use of day 8 erythroid progenitors generated from human CD34+ stem cells; treatments included SAL 12, 18 and 24 µM, and 0.5% DMSO (vehicle control) for 48 h; cell viability remained >90% in all drug conditions. The level of γ-globin mRNA increased 1.2-fold and 1.3-fold at SAL 18 and 24 µM respectively (p<0.05). Comparable, HbF was induced by SAL 24 µM alone and combined SAL/HU treatments to 1.8-fold. To gain insights into mechanisms of HbF induction by SAL, we next quantified the level of p-eIF2α. We observed a 1.7-fold increase in p-eIF2α with SAL 12 and 24 µM and parallel increase in ATF4 (4.8-fold). Flow cytometry revealed SAL increased F-cells (HbF positive cells) from 30.9% (DMSO treated) to 90.6%. Similarly, studies were performed using sickle erythroid progenitors generated from peripheral blood mononuclear cells. On day 8, SAL (9, 18, 24 µM) dissolved in water was added for 48 h; cell viability remained >90% for all drug conditions. SAL (18 μM) increased γ-globin mRNA 3.2-fold and F-cells 2.5-fold (p<0.05) compared to the untreated control. We used mean fluorescence intensity (MFI) to quantify HbF protein per cells, which showed a dose-dependent increase with SAL treatment. Since sickle red blood cells are under oxidative stress, we measured the levels of reactive oxygen species (ROS) by flow cytometry. SAL 12, 18, 24 µM decreased ROS levels in a dose-dependent manner by 7.6%, 8.7% and 10% respectively. Interestingly, SAL/HU treatment decreased ROS levels by 10.2% compared to a 4.3% mediated by the nitric oxide donor HU. Western blot analysis showed a dose-dependent increase in HbF and a 3.3-fold increase in p-eIF2α (p<0.05) and ATF4, without changing HbS expression. To generate data for clinical development, we utilized the Townes SCD mouse model. SCD mice (n=5 per group) were treated with SAL (3 and 5mg/kg), HU (100mg/kg; positive control) or water control (vehicle), 5 days a week for 4 weeks. Blood was drawn at week 0 (baseline), 2 and 4 at treatment completion. All data were normalized for each group and treatment response at week 2 and 4 compared to week 0 using a paired t-test and ANOVA to compare across treatment groups; statistical significance set at p<0.05. All groups showed normal weight gain and no significant changes in complete blood counts, differential or reticulocyte counts. Flow cytometry of peripheral blood showed that SAL (3mg/kg) produced a 2-fold increase in F-cells by 2 and 4 weeks while SAL (5mg/kg) produced a further 3.1-fold increase in F-cells by week 4 (p<0.05) without toxicity. Our initial in vitro findings, supports HbF induction by SAL involving p-eIF2α-ATF4 signaling. The interaction of ATF4 in the G-CRE and/or other predicted binding sites will be investigated. To support clinical trials, studies in the SCD preclinical model support the ability of SAL to induce HbF in vivo; additional studies are underway. Defining the mechanism of HbF induction by SAL has the potential to impact treatment for SCD. Disclosures No relevant conflicts of interest to declare.

Changes in Blood Counts of Patients with Chronic Atrophic Rhinitis

Chronic atrophic rhinitis among all ENT organ diseases happens in 10% of cases. This process is very rarelydiffuse and mainly from an ailment, the nasal cavity and nasopharynx are sometimes tracheal membranes.The aim of the study was to study the indicators of a general analysis of blood, iron and ferritin in the blood.A study was conducted of 20 people with a diagnosis of atrophic rhinitis. After the initial reaction, expressedin the form of increased bone marrow production, a significant predominance of lymphocytes sets in again.Based on this, it can be concluded that a degenerative shift with an increase in the number of lymphocytesshould apparently indicate a chronic infectious irritant.

Pharmacokinetic and Safety Evaluation of Various Oral Doses of a Novel 1:20 THC:CBD Cannabis Herbal Extract in Dogs.

Objective: To determine the pharmacokinetics (PK) and safety of various oral doses of a Cannabis herbal extract (CHE) containing a 1:20 ratio of Δ9-tetrahydrocannabinol (THC):cannabidiol (CBD) in 13 healthy Beagle-cross dogs.Methods: Single-dose PK was assessed after oral administration of CHE at low, medium, or high doses [2, 5, or 10 mg CBD and 0.1, 0.25, or 0.5 mg THC per kg of body weight (bw), respectively; n = 6 per group]. Dogs were monitored for adverse events for up to 48 h post-dose. Evaluations of neurological signs, clinical laboratory abnormalities, and other adverse events were performed in two separate study phases: a multiple-dose phase with 12 dogs receiving five medium doses (5 mg CBD/kg bw) at 12 h intervals, and a single low-dose (2 mg CBD/kg bw), randomized, blinded, negative controlled study with 13 dogs.Results: Cannabinoids CBD, THC, CBC, and metabolites 6-OH-CBD, 7-OH-CBD, 11-OH-THC, and THC-COOH were quantified in plasma. CBD and THC were rapidly absorbed (mean Tmax of 1.9–2.3 h) and initially depleted rapidly (mean CBD T1/2β of 2.3–2.6 h). A prolonged elimination phase (mean CBD T1/2λ of 13.3–24.4 h) was observed. CBD and THC concentrations increased in a dose-dependent (non-linear) manner, with disproportionally greater cannabinoid exposure relative to the dose increase. Neurological signs (hyperesthesia or proprioceptive deficits) were noted in five of six dogs in the high-dose group, but only occasionally or rarely in the medium- and low-dose groups, respectively. Presence and severity of clinical signs correlated with plasma cannabinoid concentrations. Dogs appeared to develop a tolerance to cannabinoid effects after multiple CHE doses, with fewer neurological signs noted after the final (fifth) vs. first dose. No clinically meaningful changes in blood count or chemistry values occurred after multiple CHE doses.Clinical Significance: Dogs tolerated the 1:20 THC:CBD formulation well at low and medium doses, but clinically meaningful neurological signs were observed at high doses. Because of non-proportional increases in plasma cannabinoid concentrations with increasing doses, as well as potential differences in CHE product composition and bioavailability, the possibility of adverse events and dose regimen consistency should be discussed with dog owners.

Endovascular treatment of wide-necked aneurysms of the visceral and renal arteries using the double microcatheter technique via a single access route

We aimed to evaluate the utility of and complications associated with the double microcatheter technique for the treatment of wide-necked visceral and renal artery aneurysms (VRAAs). Nine patients (mean age, 58 years; age range, 42-69 years; 4 men, 5 women) with wide-necked VRAAs who underwent treatment with the double microcatheter technique from January 2016 to July 2018 were included in the study. For all patients, anatomical features were confirmed using cone-beam computed tomography (CT) with rotational angiography. The aneurysmal location, size, volume, neck-to-dome ratio, number of coils used, and coil packing density were investigated. Technical success, complications (coil migration and organ ischemia), changes in the complete blood count or serum creatine level, and recurrence were also evaluated. Three renal artery aneurysms and 6 splenic artery aneurysms were treated by the double microcatheter technique. The mean size of the aneurysms was 26.09±4.76 mm, mean volume was 6.19±3.69 cm3, and mean neck-to-dome ratio was 1.53±0.24. The number of coils used ranged from 7 to 16. The mean packing density was 11.32%±3.72%. Technical success was achieved in all 9 patients. Renal ischemia occurred in two patients with renal artery aneurysm, one of whom showed minimal scar formation on follow-up CT after infarction. No coil migrations or disease recurrences were observed. The double microcatheter technique for the treatment of wide-necked VRAAs appears to be relatively safe and useful. However, complex renal artery aneurysm should be carefully managed in order to prevent infarction.

Levantamento de mielogramas com ênfase em pacientes portadores de leishmaniose visceral canina

This survey aims to present reports and other information about myelograms performed in 2017 and 2018 at the Anhembi Morumbi University Veterinary Hospital, emphasizing animals with canine visceral leishmaniasis (CVL), to verify and report the number of patients with Leishmania spp. Infection. The results of cytological and serological exams of these animals were also analyzed for comparison and scoring of diagnostic accuracy and more common serum and microscopic laboratory changes caused by this disease, respectively. Changes in blood count and myelogram were observed, but animals with a low degree of parasitism didn’t show Leishmania spp. on bone marrow exams.

The Efficacy of Periodic Complete Blood Count Tests in Evaluation of the Health Status of Radiation Workers in Iran: A Systematic Review

Periodic medical examinations of radiation workers are routinely conducted in many countries. Although low dose radiation (LDR) is not expected to cause a significant effect on blood count, the periodic examination usually includes reviewing the work history, general medical history, a physical examination and collecting a blood sample. Despite lymphocytes are the most sensitive cells to radiation, their counts do not show any significant change as long as the radiation level is less than a few hundreds of millisievert (mSv). In spite of this, in Iran, radiation workers, even those who work in diagnostic radiology departments, are regularly examined for blood count changes. After a detailed search in PubMed, ISI, Scopus, SID and Google Scholar, only 12 out of 650 articles matched our criteria. A review of these 12 reports was conducted. The full texts were fully reviewed by the authors. The complete blood count (CBC) test has a very low efficacy in evaluation of the adverse health effects of ionizing radiation in radiation workers. Therefore, finding alternative methods with a higher efficacy is recommended. CBC tests cannot be introduced as valid markers of potential radiation effects in most occupational exposures. Given this consideration, in periodic tests of radiation workers, cytogenetic tests can be the gold-standard method. In particular, due to its relatively low cost and good sensitivity and specificity, the dicentric assay can be promising. Moreover, the simple and rapid evaluation of micronuclei by fast automated scoring systems can be a good alternative for current low efficacy CBC tests.

Correlating immune toxicity, blood cell counts, and overall survival in cancer patients receiving immune therapy.

3043 Background: Baseline circulating white blood cell differential counts have been proposed as possible markers of response to Immune therapy (ICI) and immune toxicity (irAE), but have not been validated for clinical practice. Methods: 214 patients with various cancers receiving ICI had clinical lab results and overall/organ specific irAE analyzed. Absolute lymphocyte (ALC), eosinophil (AEC) and neutrophil (ANC) counts <7 days of starting and 3-12 weeks after ICI were correlated with survival and development of irAE. The association between overall irAE and cell count changes was evaluated using multivariate logistic regression, adjusting for patients’ age, gender, race, and including all 3 types of cell count changes in one model. The association between overall survival and cell counts changes was tested using multivariate Cox proportional hazard model, adjusting for age, gender, race, and overall irAE (yes/no). Results: The combination of MEDIAN rise or fall in ALC, ANC and AEC after ICI combined with development of irAE was associated with altered overall survival (OS). Higher statistically significant (p=<0.05) OS was seen in patients with AEC↑/irAE+(n=94; median OS 14.9 months), ANC↓/irAE+(60; 17.9 mo), ALC↑/irAE+(65; 11.5 mo), ALC↓/irAE+(92; 12.2 mo). Lower OS was seen with ANC↑/irAE-(21; 5.4 mo), ALC↑/irAE-(9; 5.8 mo), ALC↓/irAE-(24; 6.1 mo). All these relationships were unchanged if patients were grouped into ANY rise during the 3-12 weeks rather than median. After multivariable adjustment for age/sex/race there was statistically significant association between higher baseline ALC and development of any irAE (p=0.05) and grade ≥2 irAE (p=0.02). No association was seen between overall toxicities and ANC or AEC. Organ-specific irAE’s with statistically significant associations included pneumonitis:↓AEC (p=0.05), hepatitis:↓ANC (p=0.05), hypothyroidism:↓ANC (p=0.02), colitis:↑ALC (p=0.02). Skin rash, hypophysitis and adrenalitis were not associated with any cell count changes. Conclusions: In patients with cancer receiving immune therapy, the predictive value of serial monitoring in ALC, AEC and ANC is greatly enhanced by the addition of irAE detection. irAEs appear to be a greater predictor of survival than changes in blood counts. In contrast to prior reports we found ANC/ALC/AEC in isolation were less reliable in predicting improved survival. Lack of standardized methods of assessing irAE’s confound identifying strong associations with clinical lab-derived cell counts.

Dynamic changes in full blood count (FBC) occurring in patients treated with immune checkpoint inhibitors (ICIs) to predict responses in patients with metastatic renal cell carcinoma (mRCC).

e17110 Background: ICI transformed the treatment of 1L mRCC, yet early clinical predictors of response are still unknown. Methods: Retrospective database analysis from Barts Cancer Institute, London was carried out. Patients with treatment naïve mRCC were identified and grouped according to their 1L treatment: 1: VEGF inhibitor 2: IO/IO 3: IO/VEGF Data on hemoglobin, neutrophil-to-lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR) at baseline, 6weeks and 12weeks after treatment initiation was correlated with outcome. Results: Between Jan 2014 - Dec 2019; 28, 29 and 21 patients received 1L VEGF, IO/IO or IO/VEGF respectively. Patient receiving 1L VEGF inhibitors showed a decrease in Hb levels both in responding and non-responding groups (significant group effect: F(1,6) = 6.6, p = 0.04); significant time effect:F(2,12) = 12.4, p = 0.001). Group x time interaction was not significant. NLR levels decreased both in responding and non-responding groups over time (significant time effect: F(2,12) = 16.7, p = 0.001. PLR levels in non-responders increased over time, whereas in responding group, PLR levels steadily decreased over 6 and 12 weeks (significant time effect: F(2,12) = 0.3, 0.044). Patients receiving IO/IO combination therapy; within the non-responder group, Hb levels didn’t change significantly whereas in the responding group Hb levels increased significantly and overtook Hb levels of non-responding group (P = 0.001). NLR levels significantly decreased in the responding group (0.041) and a similar trend was observed at 12 weeks with a decrease in PLR among non-responders, with a significant group affect (F(1,5) = 0.18, 0.035). In patient treated with 1L IO/VEGF, among non-responders Hb levels increased slightly, only to return to baseline levels again at 12 weeks after treatment initiation. Whereas, Hb levels in the responding group increased significantly in both 6weeks and 12weeks after starting therapy. Significant time effect:F(2,20) = 3.65, p = 0.044. NLR levels in the responding group presented a steady decrease over time with a significant group and time effect. Both responders and non-responders experienced an increase in PLR over time. However, while PLR decreased at 12 weeks among responders, it continued to increase among non responders (significant time effect: F(2,20) = 0.3, 0.03), (significant group effect: F(1,10) = 0.05, 0.005) and significant interaction: F(2,20) = 0.1, 0.01) Conclusions: Close monitoring of FBC changes may predict response to ICI.

Dynamic Changes in the Neutrophil-to-Lymphocyte Ratio Predict the Prognosis of Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.

PurposeTo examine the effect of dynamic changes in neutrophil-to-lymphocyte ratio (NLR) on tumor response and overall survival (OS) in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE).Patients and MethodsData from 181 patients with HCC were retrospectively collected. White blood cell, neutrophil and lymphocyte counts, and the NLR were obtained 1–3 days before as well as 3–6 weeks and 3 months after TACE. Patients were divided into two groups at each time point according to the mean value of NLR, and also divided into continuous decrease, fluctuating increase-decrease (I-D), fluctuating decrease-increase (D-I), and continuous increase groups according to the dynamic changes in the NLR. The dynamic changes in blood counts and NLR were analyzed using repeated-measures ANOVA. The odds ratios (ORs) for tumor response in different NLR groups were examined using a multivariate logistic regression model. Finally, the prognostic value of the dynamic changes in the NLR was examined using Cox regression models.ResultsContinuous decline of white blood cell counts, neutrophil counts and lymphocyte counts were observed at 3–6 weeks and 3 months after TACE treatment. The NLR increased slightly and then decreased substantially in responders, while it increased slightly and then significantly in non-responders, with a significant interaction effect of Time × Tumor response (P = 0.005). NLR grouping before TACE, 3–6 weeks and 3 months after TACE was not associated with tumor response, and only 3 months after TACE did, it shows a significant difference in univariate survival analyses (NLR > 2.5 vs NLR ≤ 2.5, hazard ratio [HR] = 2.442, 95% confidence interval (CI): 1.545, 3.860). The changes in the NLR were significantly correlated with tumor response and OS. Non-responders for TACE were more common in the continuous NLR increase group (OR = 6.230, 95% CI: 1.848–21.001) and in the fluctuating D-I group (OR = 5.702, 95% CI: 1.480–21.957). Multivariate analyses revealed that these two patient groups also showed poorer OS (HR = 2.351, 95% CI: 1.120–4.605 and HR = 2.320, 95% CI: 1.187–4.533, respectively).ConclusionDynamic changes in the NLR may be better predictors of tumor response and OS than static NLR values, but more data are needed.

The Evaluation of Pretreatment and Posttreatment Platelet/Lymphocyte and Neutrophil/Lymphocyte Ratios in Patients with Hyperthyroidism

Amaç: Hipertiroidizm, yüksek serbest triiyodotironin (serbest T3) ve / veya serbest tiroksin düzeyleri (serbest T4) ile birlikte subnormal (genellikle saptanamayan) bir serum tirotropin (TSH) olarak tanımlanır. Endojen hipertiroidi en sık Graves hastalığı (GH) veya nodüler tiroid hastalığına bağlıdır. GH başta tiroid bezi olmak üzere, göz ve nadiren cildi tutan otoimmün bir hastalıktır. Hastalık genelde hipertiroidiye bağlı semptomlar ile tanınır. Tedavisinde anti-tiroid ilaçlar kullanılmakta olup, bu ilaçlar tiroid hormon sentezinin yanısıra anti-inflamatuar özelliklere de sahiptir. Trombosit/lenfosit (TLO) ve nötrofil/lenfosit (NLO) oranları ise rutin kan sayımından elde edilen, ucuz ve tekrarlanabilir, sistemik inflamasyon belirteçleridir. Hipertirodide tedavi öncesi ve tedavi sonrası TLO ve NLO’ nın değerlendirilmesi amaçlanmıştır.Materyal ve Metod: Çalışmaya Harran Üniversitesi Tıp Fakültesi Endokrinoloji Polikliniği’ne başvuran hastaların geçmişe yönelik kayıtları incelenerek hipertiroidi tanısı alan ve medikal tedavi başlanan hastalar alındı. Aktif enfeksiyonu ve hematolojik patolojisi olan hastalar çalışmaya dahil edilmedi. Hastaların kayıtlarından tanı anındaki ve 3-6 ay sonraki laboratuvar sonuçları değerlendirildi. Medikal tedavi öncesi ve sonrası NLO ve TLO değerlerinin karşılaştırılması planlandı.Bulgular: GH grubunda tedavi öncesi ve tedavi sonrası TSH, sT3, sT4, lökosit, nötrofil, lenfosit ve hemoglobin düzeylerinde artış vardı ve bu artış istatistiksel anlamlıydı. Bununla birlikte toksik nodüler guatr (TNG)/multınodüler guatr (MNG) grubunda TSH, sT3, sT4 değerlerinde anlamlı artış varken, lökosit, nötrofil, lenfosit ve hemoglobin düzeylerinde tedavi öncesi ve sonrası anlamlı bir fark yoktu. GH grubunda NLO tedavi sonrası öncesine göre anlamlı yüksekti ancak TLO’nda anlamlı fark gözlenmediSonuç: Hipertiroidi özellikle en sık nedeni olan GH hemotolojik parametrelerde çeşitli mekanızmalarla değişiklik yapabilmektedir. Antitiroid ilaçlar tiroid hormon düzeyleriyle birlikte kan sayımında da değişikliklere neden olur

Envenenamento por Crotalus durissus marajoensis em Muaná, Ilha de Marajó, estado do Pará, Brasil

OBJECTIVE: Report a case of envenomation by Crotalus durissus marajoensis Hoge, 1966 in Muana, Marajo archipelago, Para State, Brazil. CASE REPORT: Fisherman, 48 years old, bitten by a rattlesnake on his right ankle when walking in the field. After the envenomation, he reported paresthesia without local pain. Then, he experienced heaviness in the head, difficulty in opening his eyes, dysarthria, blurred vision, and diplopia. He was admitted to the Municipal Hospital of Muana, 9 h after the snake bite, with the mentioned signs and symptoms, plus nausea, dizziness, difficulty in walking, and myalgia. Due to the absence of specific antivenom at the city hospital, the patient was referred to the Municipal Emergency Room in Belem, Para State, where he arrived after 18 h of the accident, presenting neurotoxic facies, mydriasis, choluria, and oliguria. The case was classified as severe envenomation, and the patient received specific antivenom vaccine. After four days, the patient with evidence of neurotoxicity was transferred to the Joao de Barros Barreto University Hospital, where clinical support and lab tests were conducted. Changes in complete blood count, coagulation test, levels of urea, creatinine, transaminases, and creatinophosphokinase were observed, showing rhabdomyolysis. Although serotherapeutic treatment and clinical support were done after a long period of time, there was an evolution towards clinical cure. CONCLUSION: The importance of early serotherapy and the rarity of such envenomation by this subspecies whose clinical features are the same as those of other crotalic accidents reported in Brazil.

Assessment of changes in complete blood count and serum chemistry in fed Holstein steers with or without liver abscesses

ABSTRACT Objective This research compared whole blood and serum analyses from cattle with and without liver abscesses to quantify differences associated with the presence and severity of liver abscesses in fed beef steers. Materials and Methods Blood samples for complete blood count and sera were collected from fed Holsteins (n = 153; 51 samples from cattle with no, minor, and major abscesses) approximately 30 s after exsanguination; liver abscesses were visually assessed after evisceration. Data were analyzed using mixed model ANOVA and logistic regression procedures; carcass was the experimental unit. Results and Discussion Of the complete-blood-count variables analyzed, platelet counts were increased (P = 0.02) and hemoglobin and hematocrit values (P Implications and Applications These results indicate that cattle with major liver abscesses undergo physiologic differentiation, which can be detected in whole blood and serum. This baseline research improves our understanding of the systemic influences of liver abscesses. Identifying blood parameter outcomes associated with liver abscesses antemortem may allow future useful implications for cattle welfare and feedlot management.

Scanning Beam Proton Therapy versus Photon IMRT for Stage III Lung Cancer: Comparison of Dosimetry, Toxicity, and Outcomes

PurposeThere are limited clinical data on scanning-beam proton therapy (SPT) in treating locally advanced lung cancer, as most published studies have used passive-scatter technology. There is increasing interest in whether the dosimetric advantages of SPT compared with photon therapy can translate into superior clinical outcomes. We present our experience of SPT and photon intensity modulated radiation therapy (IMRT) with clinical dosimetry and outcomes in patients with stage III lung cancer. Methods and MaterialsPatients with stage III lung cancer treated at our center between 2013 and May 2018 were identified in compliance with our institutional review board (64 patients = 34 SPT + 30 IMRT). Most proton patients were treated with pencil beam scanning (28 of 34), and 6 of 34 were treated with uniform scanning. Fisher exact test, χ2 test, and Mann-Whitney test were used to compare groups. All tests were 2-sided. ResultsPatient characteristics were similar between the IMRT and SPT patients, except for worse lung function in the IMRT group. Mean dose to lung, heart, and esophagus was lower in the SPT group, with most benefit in the low-dose region (lungs, 9.7 Gy vs 15.7 Gy for SPT vs IMRT, respectively [P = .004]; heart, 7 Gy vs 14 Gy [P = .001]; esophagus, 28.2 Gy vs 30.9 Gy [P = .023]). Esophagitis and dermatitis grades were not different between the 2 groups. Grade 2+ pneumonitis was 21% in the SPT group and 40% in the IMRT group (P = .107). Changes in blood counts were not different between the 2 groups. Overall survival and progression-free survival were not different between SPT and IMRT (median overall survival, 41.6 vs 30.7 months, respectively [P = .52]; median progression-free survival, 19.5 vs 14.6 months [P = .50]). ConclusionsWe report our experience with SPT and IMRT in stage III lung cancer. Our cohort of patients treated with SPT had lower doses to normal organs (lungs, heart, esophagus) than our IMRT cohort. There was no statistically significant difference in toxicity rates or survival, although there may have been a trend toward lower rates of pneumonitis.

Impact of Anterior Kidney Calyx Involvement of Complex Stones on Outcomes for Patients Undergoing Percutaneous Nephrolithotomy

Introduction: A number of factors that can impact the outcomes of percutaneous nephrolithotomy (PCNL) procedures have previously been investigated. Complex stones that extend to the anterior calyx could affect the success and complication rates of PCNL. Objective: We analyzed the effect of anterior calyx involvement on the outcomes of patients with complex stones treated with PCNL. Methods: A total of 132 consecutive patients who underwent PCNL due to complex stones (multiple, partial staghorn, or staghorn stones) between 2015 and 2017 were enrolled in this study. They were stratified into two groups based on whether the stone extended to the anterior calyx (group 1, n = 45) or not (group 2, n = 87). The stratification was achieved through contrast-enhanced computerized tomography (CT). Demographics, laboratory tests, and peri- and postoperative findings (operation and fluoroscopy duration, hospital stay, utilization of flexible instruments, access numbers, total blood count change, stone-free rate [SFR], and complications) were compared between the groups. The SFR was evaluated by plain kidney-ureter-bladder radiography or CT. Results: The demographics, operation and fluoroscopy duration, access number, and hospital stay were similar between the groups (p < 0.05). A higher drop in the hemoglobin level in group 1 was identified (group 1 [2.14 ± 1.49 g/dL] vs. group 2 [1.43 ± 1.31 g/dL]) (p = 0.006). The SFR among the patients with extension to the anterior calyx was 60%, compared to 77% among the patients with no extension to the anterior calyx (p = 0.041). Flexible instruments were utilized in 60% of the patients of group 1, which was a higher rate than for group 2 (36%) (p = 0.007). Complication rates were similar in the two groups according to the Clavien-Dindo classification (p > 0.05). Conclusions: Our study demonstrated that complicated stones with extension to the anterior calyx are more challenging than cases without extension to the anterior calyx. This was noted by a lower SFR, a more prominent drop in total blood count, and more frequent utilization of flexible scopes.