Blood Leukocyte Count Research Articles

THE CLOZAPINE EFFECT ON BLOOD GLUCOSE LEVELS, LEUKOCYTES AND PLATELETS IN SCHIZOPHRENIC PATIENTS IN THE MENTAL SERVICE UNIT OF BANYUMAS HOSPITAL

Schizophrenia is a disorder of strange and disordered thoughts, delusions, hallucinations, inappropriate influences, and disorders of psychosocial functioning. One of the management of schizophrenia therapy is the administration of atypical antipsychotic drugs, namely clozapine. Clozapine is an antagonist of serotonin (5-HT2) and dopamine type 2 (D2) receptors. However, the risk of using clozapine provides a risk of side effects in the form of metabolic syndromes such as impaired blood glucose regulation and disorders of blood elements such as leukocytes and platelets. This study aims to determine the effect of using clozapine on blood glucose, leukocyte, and platelet levels in schizophrenia patients at Banyumas General Hospital. This research method was carried out by cross-sectional study in outpatient schizophrenia at Banyumas General Hospital who received clozapine therapy and had met the inclusion and exclusion criteria, taken by consecutive sampling, then examined blood glucose levels, leukocyte counts, and platelet counts before and after giving clozapine therapy. Samples were taken on day 1 and day 10 of drug use. Paired t-test statistical analysis was used to see the effect of using clozapine on glucose, leucocyte, and platelet levels. In the T-test, it was found that there was a relationship between the use of clozapine on the patient's blood glucose levels, the use of clozapine did not have a significant effect on the increase in leukocyte levels and there was also a relationship between the use of clozapine and the patient's platelet levels. The results showed that the patient had an increase in blood glucose levels by a percentage (100%), the patient had leukopenia by a percentage (63.5%), the patient had thrombocytopenia by a percentage (75%), while the other patients had thrombocytosis. Patients with hyperglycemia, leucopenia, and thrombocytopenia were those who used clozapine> 12 months

THE CLOZAPINE EFFECT ON BLOOD GLUCOSE LEVELS, LEUKOCYTES AND PLATELETS IN SCHIZOPHRENIC PATIENTS IN THE MENTAL SERVICE UNIT OF BANYUMAS HOSPITAL

Schizophrenia is a disorder of strange and disordered thoughts, delusions, hallucinations, inappropriate influences, and disorders of psychosocial functioning. One of the management of schizophrenia therapy is the administration of atypical antipsychotic drugs, namely clozapine. Clozapine is an antagonist of serotonin (5-HT2) and dopamine type 2 (D2) receptors. However, the risk of using clozapine provides a risk of side effects in the form of metabolic syndromes such as impaired blood glucose regulation and disorders of blood elements such as leukocytes and platelets. This study aims to determine the effect of using clozapine on blood glucose, leukocyte, and platelet levels in schizophrenia patients at Banyumas General Hospital. This research method was carried out by cross-sectional study in outpatient schizophrenia at Banyumas General Hospital who received clozapine therapy and had met the inclusion and exclusion criteria, taken by consecutive sampling, then examined blood glucose levels, leukocyte counts, and platelet counts before and after giving clozapine therapy. Samples were taken on day 1 and day 10 of drug use. Paired t-test statistical analysis was used to see the effect of using clozapine on glucose, leucocyte, and platelet levels. In the T-test, it was found that there was a relationship between the use of clozapine on the patient's blood glucose levels, the use of clozapine did not have a significant effect on the increase in leukocyte levels and there was also a relationship between the use of clozapine and the patient's platelet levels. The results showed that the patient had an increase in blood glucose levels by a percentage (100%), the patient had leukopenia by a percentage (63.5%), the patient had thrombocytopenia by a percentage (75%), while the other patients had thrombocytosis. Patients with hyperglycemia, leucopenia, and thrombocytopenia were those who used clozapine> 12 months

Suppression of cytokine storm and associated inflammatory mediators by salicylaldehyde derivative of pregabalin: An innovative perspective for alleviating airway inflammation and lung remodeling

ObjectivesPregsal is a novel salicylaldehyde derivative of pregabalin, a structural analogue of gamma-aminobutyric acid approved for treating epilepsy, neuropathic pain and diabetic peripheral neuropathy but not trialled to date for airway inflammatory diseases. The current study evaluated a preclinical model of airway inflammation and lung remodelling induced by ovalbumin (OVA) for the potential benefits of pregsal. MethodsWistar rats (N = 10 per group) were divided into four groups sensitized intraperitoneally (i.p.) and then challenged intranasally with OVA, with or without i.p. pregsal (100 mg/kg) or methylprednisolone (MP) (15 mg/kg). Airway inflammation was assessed through inflammatory cell infiltration in the lungs, delayed-type hypersensitivity (DTH), and nitric oxide (NO) level using bronchoalveolar lavage fluid (BALF) and lung tissues. The mRNA expression levels of a panel of inflammatory mediators (cytokines, chemokine and growth factors) in the lungs were measured by the reverse transcription-polymerase chain reaction (RT-PCR). Systemic inflammation was assessed using splenocyte proliferation and total and differential leucocyte count in blood and BALF. Lung remodelling was assessed by wet/dry lung weight ratio, epithelial thickness and goblet cell hyperplasia, hydroxyproline and osteopontin (OPN) levels, arginase activity in lungs, and ornithine decarboxylase (ODC) activity in lung mitochondria. ResultsPregsal significantly alleviated the total and differential leucocyte count in blood and BALF, NO production in BALF and recruitment of inflammatory cells in the lungs. It suppressed the T-cell response and attenuated the OVA-induced lung epithelial thickness, goblet cell hyperplasia, wet/dry lung weight ratio, hydroxyproline and OPN levels, arginase and ODC activity. Levels of inflammatory mediators were also downregulated in the lungs by pregsal. ConclusionsThe key findings of this study indicate that pregsal significantly reduces the development of airway inflammation and lung remodelling by suppression of cytokine storm and associated inflammatory mediators.

Clinical and Laboratory Characteristics and Outcome of Illness Caused by Tick-Borne Encephalitis Virus without Central Nervous System Involvement.

Information on febrile illness caused by tick-borne encephalitis virus (TBEV) without central nervous system involvement is limited. We characterized 98 patients who had TBEV RNA in their blood but no central nervous system involvement at the time of evaluation. Median duration of illness was 7 days; 37 (38%) patients were hospitalized. The most frequent findings were malaise or fatigue (98%), fever (97%), headache (86%), and myalgias (54%); common laboratory findings were leukopenia (88%), thrombocytopenia (59%), and abnormal liver test results (63%). During the illness, blood leukocyte counts tended to improve, whereas thrombocytopenia and liver enzymes tended to deteriorate. At the time of positive PCR findings, 0/98 patients had serum IgG TBEV and 7 serum IgM TBEV; all patients later seroconverted. Viral RNA load was higher in patients with more severe illness but did not differ substantially in relation to several other factors. Illness progressed to tick-borne encephalitis in 84% of patients within 18 days after defervescence.

Dietary glycine supplementation modulates antioxidant and immune responses of beluga, Huso huso, juveniles

Glycine is a non-essential amino acid used in fish nutrition, and possess several important roles in physiological process. Despite such functions, little is known about the glycine roles in fish, particularly in sturgeons. Therefore, the present study aimed at assessing the effects of dietary glycine supplementation on growth performance, antioxidant, and immunological parameters in beluga, Huso huso. Four hundred eighty fish (~ 48 g) were randomly distributed in 12 fiberglass tanks (1200 L) at a stocking density of 40 fish per tank. Four diets supplemented with 0% (control), 0.25% (Gly0.25), 0.5% (Gly0.5), and 1% (Gly1) glycine were offered to the fish (each diet to a batch of three tanks) for eight weeks at water temperature of 23.2 ± 0.70 °C. At the end of the feeding trial, the fish were blood-sampled for blood leukocyte count, plasma cortisol, glucose, triglyceride, cholesterol, reduced glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), malondialdehyde (MDA), lysozyme, and alternative complement activity (ACH50) analysis. The results indicated there were no significant differences in the fish final weight (197–213 g; P = 0.511), weight gain (299–311%; P = 0.956) specific growth rate (2.46–2.52%/d; P = 0.944), feed conversion ratio (0.97–1.03; P = 0.863), protein efficiency ratio (2.29–2.45; P = 0.775), and survival (91.7–100%; P = 0.306) among the treatments. Plasma cortisol level significantly decreased in Gly0.25 treatment, compared to the control (24.7 vs. 28.8 ng/mL; P = 0.035). Plasma glucose levels exhibited significant (P < 0.001) elevation in Gly0.5 (51.0 mg/dL) and Gly1 (53.0 mg/dL) treatments, compared to the control (42.0 mg/dL). The treatment Gly0.5 showed significant elevations in blood leukocyte count (11.4 vs. 8.23 ×1000cell/µL; P = 0.032), plasma triglyceride (581 vs. 410 mg/dL; P = 0.017), cholesterol (71.3 vs. 59.8 mg/dL; P = 0.011), GSH (2.67 vs. 2.21 mM/mL; P = 0.003), GPx (243 vs. 217 U/mL; P < 0.001), and MDA (123 vs. 99 mM/L; P < 0.001), compared to the control treatment. Plasma GR (P < 0.001) showed significant decrease in Gly0.5 (1154 vs. 1784 U/mL) and Gly1 (1171 vs. 1784 U/mL) treatments. Besides, Gly0.25 and Gly0.5 treatments showed significantly higher plasma lysozyme (45.8–45.9 vs. 36.5 U/mL; P = 0.001) and ACH50 (138–139 vs. 130 U/mL; P < 0.001), compared to the control. Based on the results, dietary glycine supplementation at 0.25–0.5% could suppress plasma cortisol levels and improve antioxidant and immunological parameters on beluga, although has no beneficial effects on the fish growth performance.

Denture Adhesive Containing Microparticles for Delivery of Miconazole: In Vivo Toxicity

The choice treatment for denture stomatitis are topical antifungals such as miconazole nitrate (MN). Targeting denture wearers, an experimental denture adhesive (EA) was developed containing polymeric microparticles (MPs) for the delivery of MN. Objectives: To investigate the systemic toxicity in rats of the EA added with MN MPs. Methods: Thirty-five Wistar rats received intraperitoneal injection of the materials: artificial saliva (AS) as solvent, Corega Cream® (CCDA), pure EA or EA added with MN MPs (sigla), and pure MN or MNMP. Animal behavior impairment (level 0-4) and weight (g) analyses were carried out at 0, 24, 48 and 72 h. Blood was collected to detect C-reactive protein. The intraperitoneal washing was analyzed through red blood cell and leukocyte counts and turbidity degree. Descriptive statistical analysis was performed for behavior and turbidity. Normality of red blood cells (thousand/L) and leukocytes (million/L) counts was verified (Shapiro-Wilk, p&lt;0.0001). Statistical analysis was performed using Kruskall-Wallis and Mann-Whitney U tests with Bonferroni adjustment. Results: No significant difference between weights of groups was found for time (p=0,551). No behavior alterations level 2, 3 or 4 were observed. The C-Reactive protein was negative for all groups. The leukocyte and red blood cell counts showed significant difference between the groups AS and EA+MNMP (p=0.016 and p=0.009, respectively). No significant difference was found between EA+MNM and the CCA (p=0.917) group in the leukocyte count. Significance: The denture adhesive with antifungal presented similar results to those of the commercially available adhesive, and pure saliva was sufficient to cause peritoneum systemic toxicity.

Meta-analysis of the effect of low-level occupational benzene exposure on human peripheral blood leukocyte counts in China

To investigate the effect of low-level occupational benzene exposure on human peripheral blood leukocyte counts of the workers, domestic and foreign published research data on the change of human peripheral blood leukocyte counts under low-level occupational benzene exposure from January 1990 to December 2020 were collected and analyzed. According to the literature inclusion and exclusion criteria, 18 independent studies from 12 publications were selected for meta-analysis to explore the effect of low-level occupational benzene exposure on human peripheral blood leukocyte counts. The results showed that the peripheral blood leukocyte counts abnormal rates of low-level occupational benzene exposure group were higher than those of the control group, and the difference was statistically significant. Low-level occupational benzene exposure could result in a relatively higher abnormal rate of peripheral blood leukocyte counts in the exposed population, indicating that low-level occupational benzene exposure at workplaces specified by the current benzene occupational exposure limit in China would affect the peripheral blood leukocyte counts of the workers, thus benzene with concentrations under the limit in the ambient air of workplace could be still harmful to the health of the exposed workers. The results of this study could provide a scientific basis for future revision of the benzene occupational exposure limit in China, and could also be a reference for the formulation of environmental standard concerning benzene in China in the future.

Nutritional feed additives reduce the adverse effects of transport stress in the immune system of Tambaqui (Colossoma macropomum)

Here we show that selected nutritional feed additives reduce the adverse effects of transport stress on the immune system and hematology of tambaqui. We formulated a control diet to contain normal dietary levels of vitamin E (21.6mg/ kg diet) and C (143mg/kg), then we added supra levels of these vitamins (vit E - 264mg/kg and vit C - 1000mg/kg) to a second diet. Finally, a third diet was produced to contain similar levels of vitamins from diet 2 with 0.1% beta-glucan supplementation. Four hundred thirty-two tambaquis (20.91g±0.27g) were randomly assigned to 12 aquaria and fed the diets for 15 days; then, all fish were transported for five h and then returned to the aquaria. Blood samples were collected before and after the transport and at the end of the trial (60 days). Transportation significantly increased blood glucose that returned to baseline levels at the end of the trial. However, cortisol seemed to be unresponsive to the stress. Surprisingly, the stress significantly increased the immunoglobulin level after transport. Additionally, the transport markedly reduced the red blood cell count and leukocyte and lymphocytes counts while increasing the control group's neutrophil number. These effects lasted until the end of the trial in the control group. Supra levels of the vitamins and glucan supplementation prevented the decrease in red blood cell and leukocyte count after the stress. Additionally, beta-glucan supplementation induced lower cortisol levels in all the sampling points. However, the effect on the immune parameters was limited, increasing only the lysozyme activity and serum protein levels in the beta-glucan supplemented group and the group fed only the supra levels of vitamins, respectively. In sum, our results indicated that transport for five h induced a limited effect on stress biomarkers. The use of supra levels of antioxidant vitamins alone or in combination with beta-glucan could restore or prevent the adverse effects of stress on hematology and the immune system.

Spectrum of immunophenotypic aberrancies in acute leukemia along with their correlation with adverse hematological parameters

BACKGROUND: The identification of aberrant phenotypes in acute leukemia is crucial for treatment monitoring and minimal residual disease analysis. Flowcytometric immunophenotyping in acute leukemia is an important tool for the detection of these aberrancies. There is wide variation in the incidence of aberrant antigens in acute leukemia in different studies and its correlation with prognostic markers.AIMS AND OBJECTIVES: The aim and objective of this study is to assess the frequency of aberrant markers in acute leukemia and determine any association with hematological parameters.MATERIALS AND METHODS: A total of 150 newly diagnosed cases of acute leukemia during the period January 2018–December 2020 were included. The flowcytometric immunophenotyping of all the above cases was done using BD FACS Canto II.RESULTS: Out of the total 150 cases of acute leukemia, 56.7% expressed aberrant phenotype. The proportional frequency of aberrant antigen expression in B-acute lymphoid leukemia (ALL), T-ALL and acute myeloid leukemia (AML) was 56.6%, 50%, and 58.5%, respectively. CD13, CD13, and CD7 were the most common aberrancies in B-ALL, T-ALL, and AML, respectively. Aberrant myeloid phenotype in B-ALL was associated with lower mean total leukocyte count (TLC) and blast percentage in peripheral blood as compared to the B-ALL with conventional phenotypes. Aberrant lymphoid phenotype in AML was associated with a higher TLC and greater blast percentage in peripheral blood than the AML with conventional phenotypes.CONCLUSION: Aberrant lymphoid phenotype in AML is associated with unfavorable hematological features. However, aberrant myeloid phenotype in B-ALL is not associated with adverse features.

Treatment of multidrug-resistant Klebsiella pneumoniae pneumonia in rats with the Wen Run Fei Ning formula: A preliminary study.

To determine the effect of Wen Run Fei Ning formula (WRFNF) intervention in class I integron-mediated carbapenem-resistant Klebsiella pneumoniae. A drug-susceptibility test and PCR amplification were used to screen for carbapenem-resistant K. pneumoniae containing class I integrons. Following nasal drip and tail vein injection to infect healthy male rats with carbapenem-resistant K. pneumoniae, three models were created: control (group A); model (group B, tail vein injection); and model-WRFNF treatment group (group C, by tail vein injection). Rats in Group C were gavaged with pre-warmed WRFNF extract. On the third, fifth, and seventh days after the experiment, the rats in groups A and B were gavaged with an equal quantity of saline and killed in batches. Group C showed considerably higher serum IL-6 and TNF- levels on days 3, 5, and 7 compared to group A, as well as a significant increase in peripheral blood leukocyte count and a histopathologic inflammatory cell infiltration of the lungs. As the WRFNF delivery duration was prolonged, group C's histopathologic inflammatory cell infiltration gradually improved in contrast to group B, with the biggest improvement occurring on day 7. Compared to group B, group C's serum IL-6 and TNF- levels were lower. When the trial's duration was increased to 7 days, the levels of IL-6 and TNF- in group C decreased on day 7 compared to on day 5. WRFNF decreased inflammatory cell infiltration as well as IL-6 and TNF expression in the lung of the rats infected with carbapenem-resistant K. pneumoniae.

Prevention of the calcification of porcine heart valve leaflets implanted subcutaneously in rats by an interleukin-8 receptors antagonist (SCH527123)

Bioprosthetic heart valve calcification may result from interactions between the host's immune system and the glutaraldehyde (GA)-fixed tissue that makes up the leaflets. We hypothesized that antagonizing interleukin-8 (IL-8) receptors, CXCR-1 and CXCR-2, may prevent the calcification of GA-fixed porcine aortic valves implanted subcutaneously in rats. Three-week-old Sprague Dawlay males were transplanted with 2 aortic valve leaflets isolated from pigs and implanted into the dorsal wall. Four groups of 3–4 rats (6–8 independent leaflets each time) were compared: glutaraldehyde (GA)-free leaflets, GA-fixed leaflets (0.6% GA for 24 h before implantation), GA-fixed leaflets and treatment of rats with 1 mg/kg SCH5217123 (a CXCR1/2 antagonist) injected once a day locally subcutaneously (SC) or intraperitoneally (IP). Fourteen days later, rats underwent blood leukocyte count and CT-scan, before porcine leaflets explantation and histology and biochemistry analyses. As expected, strong calcification of ectopic valves was induced by the GA. However, we observed a significant about 40% decrease in this effect when rats were treated with the SCH527123. These effects were confirmed by CT-scan acquisitions and Alizarin red staining of valves. Besides, GA pre-incubation of valves significantly increased leukocytes count in rat blood, an effect that is significantly prevented by IP SCH527123 (6.9, 16.6 and 6.8 × 10 9 /L in the GA-free, GA and GA + IP SCH527123 groups respectively, P = 0.0129). Immunohistochemistry of ectopic valves highlighted higher infiltration of CD3 (lymphocytes) and CD68 (macrophages) cells in the GA group compared to the GA-free and GA + SCH527123 groups. Therefore, the calcification of GA-fixed porcine aortic valve leaflets, implanted subcutaneously in rats, is significantly prevented by antagonizing IL-8 receptors with SCH527123. This effect might partly result from an inhibition of the GA-induced leukocytes activation and recruitment into the graft tissue.

691. Infective Endocarditis with an Indication for Cardiac Surgery in a Tertiary Care Educational Hospital: Does Cardiac Surgery Improve Outcomes?

BackgroundIn this retrospective cohort study, it was aimed to compare the clinical characteristics and outcomes of IE cases without and with an indication for cardiac surgery in terms of whether they have been operated or not, in a tertiary-care educational hospital. MethodsPatients that were followed up for definite IE (diagnosed according to modified Duke criteria between March 2007 and November 2020) with an indication for cardiac surgery according to European Society of Cardiology Guidelines, comprised the study group. Subjects were evaluated in terms of whether these cases have been operated or not, demographic features, underlying diseases, risk factors, clinical and laboratory findings, therapy responses, complications, and mortality. The timing of surgery is defined as emergency; surgery performed within 24 hours, urgent; within a few days, elective; after at least one-two weeks of antibiotic therapy. Statistical analysis was performed via Chi square and Student T tests and a p value < 0.05 was considered significant.ResultsA total of 90 patients with an indication for surgery, 33.3% patients in underwent surgery, 66.6% patients in not underwent surgery group fulfilled the study criteria. The most frequently seen complaints in patients were fever (91.1%), cold-shiver (56.6%), weight-loss (27.7%), dyspnea (25.5%), and tachycardia (20%). Heart murmur was detected during cardiac auscultation of 44 patients. Mean blood leukocyte count, C-reactive protein and erythrocyte sedimentation rate were 12324 ± 6558/mm3 (1408-30330), 11.46 ± 8.38 mg/dl (0.18-34.6) and 61.43 ± 33.4 mm/h (2-130), respectively. There was no significant difference between two groups in terms of cardiac/non-cardiac risk factors, age, gender, etiologic agents, laboratory findings, septic embolisms and complaints (Table 1). In total IE with an indication for surgery mortality was 27.7%. Mortality rate was significantly less and heart murmur was significantly higher in cases who underwent surgery than those did not undergo surgery (p: 0.0447). Table 1. Comparison of basic characteristics of patients in the two operated / unoperated cohorts. ConclusionThese data support the importance of the guidelines’ criteria for cardiac surgery in the management of IE. Assuming that only 1/3 of the surgery needing cases received surgery, more interventions are needed to decrease the barriers against surgery. Disclosures All Authors: No reported disclosures

Anti-inflammatory effect of Helix aspersa extracts in sephadex-induced model of lung inflammation: possible modulation of neutrophils

The focus of our study is to compare the anti-inflammatory effect of extracts prepared from Algerian mollusk called Helix ,on induced lung inflammation in rats: aqueous AE, HE and organic OE extracts. Animals were classified into six groups: control group T was instilled with NaCl (0.9%) in the trachea, negative control group was instilled with in trachea (5mg//Kg), positive control group was instilled with and treated with an anti-inflammatory drug, groups SAE, SHE and SOE were instilled with and treated with aqueous, and organic extracts respectively (4mg//Kg). 24h after instillation, we sacrificed animals, blood samples and fluid lavage (BALF) were collected. Lungs were for investigation. We measured activity (MPO) in BALF. Results showed induces a massive in lungs. HE and OE decreased leukocyte count in BALF and blood. AE increased leukocyte count in blood and decreased it in BALF. The three extracts decreased MPO activity in BALF, reduced number of inflammatory cells in the and protected lung from beads injuries. Both AE and HE reduced edema in lung. We conclude that treatment with Helix had an anti-inflammatory effect on inflammation.

Efficacy of trimetazidine - an inhibitor of free fatty acids oxidation in the treatment of patients with stable angina pectoris and heart failure.

Aim To evaluate efficacy of modified-release trimetazidine (TMZ) included into the standard therapy for patients with stable angina and chronic heart failure (CHF) as a part of a subgroup analysis in the PERSPECTIVE study.Material and methods The study included 806 patients: group 1 (n=691), patients receiving a standard therapy and modified-release TMZ (TMZ group); and group 2 (n=115), patients receiving a standard therapy (control group). Total duration of the study was 12 months.Results In the TMZ group, the weekly number of angina attacks decreased by 41.9% (p&lt;0.0001) in 2 months and by 69.6 % (from baseline, р&lt;0.0001) in 12 months, and the frequency of nitroglycerine dosing decreased by 40.8 % (р&lt;0.0001) and 67.7 % (р&lt;0.0001), respectively. In the control group, the respective values did not change. In the TMZ group compared to the control group, the QT interval was shorter (7.9 %; р&lt;0.05), the left ventricular (LV) end-systolic dimension was reduced (13.4 %; р&lt;0.01), interventricular septal thickness and LV posterior wall thickness were decreased (9.5 %; р&lt;0.01 and 12.2 %; р&lt;0.01, respectively), and the ejection fraction was increased (11.4; р&lt;0.05). Following the TMZ treatment, the leukocyte count in peripheral blood was decreased (5.3 %; р&lt;0.01) and the serum concentration of high-sensitivity C-reactive protein was decreased (30.7 %; р&lt;0.01) vs. increases of these indexes in the control group (17.9 %; р&lt;0.05 and 17.8 %; р&lt;0.05, respectively). The proportion of patients hospitalized for exacerbation of CHF or angina for 12 months was 8.6 % in the TMZ group and 15.7 % in the control group (p=0,001).Conclusion In patients with stable angina and CHF, inclusion of modified-release TMZ into the standard therapy decreases the number of angina attacks, reduces the activity of inflammatory factors, and improves the course of disease.

The clinical relevance of lymphocyte to monocyte ratio in patients with Idiopathic Pulmonary Fibrosis (IPF)

Disease course in Idiopathic Pulmonary Fibrosis (IPF) is highly heterogeneous and markers of disease progression would be helpful. Blood leukocyte count has been studied in cancer patients and a reduced lymphocyte to monocyte ratio (LMR) has been show to predict survival. Thus, we aimed to investigate the role of monocytes count and LMR in three distinct population of patients with IPF: 77 newly-diagnosed IPF, 40 with end-stage IPF and 17 IPF with lung cancer. In newly-diagnosed IPF patients, we observed a negative correlation between forced vital capacity (FVC) at diagnosis and both white blood cells and monocytes count (r = −0.24; p = 0.04 and r = −0.27; p = 0.01; respectively). Moreover, a high monocytes count was independently associated with functional decline (OR: 1.004, 95%CI 1.00–1.01; p = 0.03). In newly-diagnosed IPF, the LMR cut-off at diagnosis was 4.18 with an AUC of 0.67 (95%CI 0.5417–0.7960; p = 0.025), and overall survival was significantly worse in patients with a LMR<4.18 compared to patients with a LMR≥4.18 (HR: 6.88, 95%CI 2.55–18.5; p = 0.027). LMR was significantly lower in IPF patients with lung cancer compared to those newly diagnosed with IPF [2.2 (0.8–4.4), 3.5 (0.8–8.8); p < 0.0001] and those with end-stage disease [3.6 (2–6.5); p < 0.0001]. In conclusion, a LMR<4.18 is associated with significantly shorter survival in newly-diagnosed IPF patients. In addition, LMR is significantly lower in patients with IPF and lung cancer compared to patients with newly-diagnosed IPF. High monocytes count at baseline negatively correlates with FVC and is an independent predictor of disease progression in newly-diagnosed IPF patients.

Genetic ablation of Pim1 or pharmacologic inhibition with TP-3654 ameliorates myelofibrosis in murine models.

Myelofibrosis (MF) is the deadliest form of myeloproliferative neoplasm (MPN). The JAK inhibitor Ruxolitinib can reduce constitutional symptoms but it does not substantially improve bone marrow fibrosis. Pim1 expression is significantly elevated in MPN/MF hematopoietic progenitors. Here, we show that genetic ablation of Pim1 blocked the development of myelofibrosis induced by Jak2V617F and MPLW515L. Pharmacologic inhibition of Pim1 with a second-generation Pim kinase inhibitor TP-3654 significantly reduced leukocytosis and splenomegaly, and attenuated bone marrow fibrosis in Jak2V617F and MPLW515L mouse models of MF. Combined treatment of TP-3654 and Ruxolitinib resulted in greater reduction of spleen size, normalization of blood leukocyte counts and abrogation of bone marrow fibrosis in murine models of MF. TP-3654 treatment also preferentially inhibited Jak2V617F mutant hematopoietic progenitors in mice. Mechanistically, we show that TP-3654 treatment significantly inhibits mTORC1, MYC and TGF-β signaling in Jak2V617F mutant hematopoietic cells and diminishes the expression of fibrotic markers in the bone marrow. Collectively, our results suggest that Pim1 plays an important role in the pathogenesis of MF, and inhibition of Pim1 with TP-3654 might be useful for treatment of MF.

Nontraditional risk factors of coronary artery disease among Palestinians: A case-control study

BackgroundCoronary Artery Disease (CAD) is one of the most common causes of death in Palestine. This study aimed to assess the nontraditional risk factors among CAD patients underwent invasive coronary angiography in Gaza-Palestine. MethodsUnmatched one-to-one case-control study was conducted among 200 participants. Cases were recruited from newly discovered CAD patients after a confirmed diagnosis of CAD by interventional cardiologist post catheterization "coronary angiography" in Al-Shifa Cardiovascular Catheterization Center. Controls were enrolled from individuals with no history of CAD. An interview-based questionnaire was used to assess patient's characteristic data and medical history; anthropometric, and the Ankle Brachial Index(ABI) was measured and calculated. Furthermore, biochemical analysis of high sensitivity C-reactive protein (hs-CRP) level and Random blood glucose level (RBG) and Leukocyte count (WBCs)were investigated. All required ethical approvals were obtained. Data were managed and analyzed by STATA version 14. Correlation analysis by multivariate logistic regression was done. Resultshs-CRP, RBG, and WBCs remained significant predictors for CAD adjusted for age, education level, employment status, and monthly income. As, the odds of CAD increased by 3% for each unit increased in hs-CRP (Odd Ratio (OR)=1.03; 95% confidence interval (CI):1.01, 1.06; P = 0.020); and the odds of CAD was augmented by 30% for each unit increased in WBCs (OR= 1.30; 95% CI: 1.07, 1.67; P = 0.010); While the odds of CAD was 5 times more for each unit increased in RBG (OR=5.04; 95% CI: 1.17, 14.88; P = 0.003). Still, age remained a significant risk factor as the odds of CAD was 19% more for each increased year in age (OR=1.19; 95%CI: 1.13, 1.26; P<0.001). ConclusionNontraditional factors (hs-CRP, RBG, and WBCs) are significant predictors of CAD, and should be considered in adult patients coming with attacks of angina pain.

Soluble triggering receptor expressed on myeloid cells-1 as a serum biomarker of early neurologic deterioration and prognosis in acute supratentorial intracerebral hemorrhage

BackgroundTriggering receptor expressed on myeloid cells-1 (TREM-1) participates in neuroinflammation. We intended to ascertain whether serum soluble TREM-1 (sTREM-1) could be utilized as a biomarker of inflammation, severity, early neurologic deterioration (END) and outcome after primary intracerebral hemorrhage (ICH). MethodsSerum sTREM-1 levels were gauged in 104 ICH patients and 104 healthy controls. END was diagnosed when the National Institutes of Health Stroke Scale (NIHSS) score increased ≥ 4 points or death between admission and 24 h after admission. Patients with a modified Rankin scale score of > 2 at 3 months were considered to have poor outcome. ResultsAs compared to controls, patients exhibited significantly elevated serum sTREM-1 levels (median: 309.0 vs 67.9 pg/ml). Serum sTREM-1 concentrations were intimately correlated with NIHSS score (r = 0.574), hematoma volume (r = 0.554), blood leukocyte count (r = 0.529) and serum C-reactive protein concentrations (r = 0.509). Serum sTREM-1 concentrations > 309.0 pg/ml independently predicted END and poor outcome with odds ratio values of 4.054 and 4.721 respectively. Serum sTREM-1 concentrations distinguished END and poor outcome with areas under receiver operating characteristic curve of 0.789 and 0.813 respectively. ConclusionSerum sTREM-1 may represent a promising inflammatory biomarker for assessment of severity and prediction of END and poor outcome after ICH.

Association of hepatic and systemic inflammation with localized stage II/III periodontitis in young males: The CHIEF oral health study.

To clarify the association between systemic and hepatic inflammation and localized periodontitis which has been reported to vary among races. The study included 1112 military males, aged 18-40 years, in Taiwan. Participants were classified as periodontally healthy/stage I (n = 796) or stage II/III periodontitis (n = 316), according to the 2017 world workshop criteria. Systemic and hepatic inflammation were defined by the highest tertiles of blood leukocyte counts (7.51 × 103 /μl) and alanine aminotransferase (30 U/L), respectively. Multiple logistic regression analysis with adjustments for age, metabolic syndrome, betel nut consumption and smoking was carried out. There was a significant association between high systemic inflammation, irrespective of hepatic inflammation severity, and localized stage II/III periodontitis (odds ratio [OR], 1.62 [1.09-2.42] and 1.47 [1.00-2.15], respectively, in the presence of high or no hepatic inflammation. However, no significant association was found among participants with low systemic inflammation, irrespective of the severity of hepatic inflammation (OR, 1.31 [0.91-1.91]). An association between hepatic inflammation and localized periodontitis in Taiwanese was observed only if systemic inflammation coexisted, possibly accounting for the reported differences in the association between Japanese and non-Asian populations in prior studies.

Factors Contributing to Attenuation of Cerebral Venous Sinus in Brain Noncontrast Computed Tomography Scan.

Background/Aim In noncontrast computed tomography (NCCT), an apparently hyper-attenuated cerebral venous sinus (CVS) may lead to suspicion of CVS thrombosis. Understanding the factors affecting attenuation of CVS can guide us toward true diagnosis. Hence, the aim of the study was to determine the effect of different factors such as hematocrit, hemoglobin, age, blood urea nitrogen (BUN), creatinine, leukocyte and platelet count, and sex on the attenuation of CVS on brain NCCT. Material and Methods Total 1,680 patients were included in this study, and their demographic and laboratory data and brain NCCT were reviewed. In their brain NCCT, the average attenuation of superior sagittal sinus and both right and left sigmoid sinuses was measured. Data analysis was conducted using the Statistical Package for the Social Sciences version 21.0 software by Kolmogorov-Smirnov, Spearman's correlation coefficient, and multiple linear regression tests. The significance level was considered less than 0.05. Results Hematocrit (B = 0.251, p < 0.001), hemoglobin (B = 0.533, p < 0.001), and creatinine (B = − 0.270, p = 0.048) were determined as predictors of attenuation of superior sagittal sinus. For both sigmoid sinuses, hematocrit ( p < 0.001) and hemoglobin ( p < 0.001) were determined as positive predictors, and creatinine ( p < 0.001) and BUN ( p < 0.002) were determined as negative and positive predictors, respectively. Conclusion Hemoglobin, hematocrit, creatinine, and BUN are the main factors that should be considered in the assessment of CVS density on brain NCCT. As with increasing hematocrit and hemoglobin of the subject, the CVS density in NCCT increases, and with increasing creatinine and in some instance decreasing BUN of the subject, the CVS density in NCCT decreases.