Hematological Effects and Benchmark Doses of Long-Term Co-Exposure to Benzene, Toluene, and Xylenes (BTX) in BTX-Exposed Petrochemical Workers Cohort (BEPWC)

Background Ubiquitous benzene, toluene, and xylenes (BTX) frequently occur together. Exposure to single BTX component and BTX-rich mixtures could induce hematological effects. However, it still needs to clarify the hematological influences of long-term co-exposure to BTX components, and propose reference exposure levels (REL) base on their hematological effects. Objective We sought to evaluate the hematological effects of long-term BTX co-exposure and estimate REL based on these effects. Methods We established BTX-Exposed Petrochemical Workers Cohort (BEPWC), quantified long-term BTX exposure levels by calculating cumulative exposure doses (CED), and detected multiple hematologic parameters in both baseline and follow-up stages. Generalized weighted quantile sum (gWQS) regression models were used to evaluate the combined effects of BTX components and identify their contributions. Benchmark Dose (BMD) Software was used to calculate BMD and the lower confidence limits (BMDL). Results Most hematologic parameters were decreased after four-year follow-up (P<0.05). We found a positive association of benzene with the decline in monocyte counts (β = 0.012), and a negative association of toluene with the decline in mean corpuscular hemoglobin concentrations (β =-0.905) after false discovery rate (FDR) adjustment. The associations of BTX components with the decline in hematologic parameters were mostly significantly stronger in subjects with higher baseline parameters, males, drinkers, and overweighted subjects (FDR-adjusted Pinteraction <0.05). BTX components had positive combined effects on the decline in monocyte counts, red blood cell counts, and hemoglobin concentrations (Ptrend for WQS index <0.05). BMD (and BMDL) for CED levels of benzene, toluene, and xylene were estimated at 2.138 (1.559), 1.449 (1.325), and 2.937 (2.312) mg/m3×year, respectively. Conclusions Our study revealed complex hematological effects of long-term BTX occupational co-exposure, and proposed some REL-TWA around 0.01 ppm for BTX components based on their hematological effects. All these findings are worthy of further investigation.

Hematological effects of antiviral drugs for Hepatitis C virus

Objective The treatment of HCV infection has evolved from interferon-based treatment approaches to direct-acting antivirals (DAAs). Despite the overall success, antiviral treatment of certain groups of patients remains challenging. Even if severe side effects are rare, they are not completely absent especially in patients with advanced liver disease. So, we aimed to evaluate hematological effects of antiviral drugs in chronic HCV patients. Patients and methods We randomly assigned 50 patients to treatment with daclatasvir/sofosbuvir for 12 weeks. Laboratory data were collected 3 and 6 months after end of treatment and compared to those before treatment. Results Our study showed SVR of 100% (P-value &lt; 0.001). there was statistically significant increase of mean corpuscular volume (MCV) and hematocrit (HCT) (P-value = 0.035 and 0.048 respectively) 3 and 6 months after treatment. Hemoglobin was increased 3 months after treatment however changes in hemoglobin wasn’t statistically significant (P-value = 0.719). There was statistically improvement of hemoglobin 6 months after treatment (P-value = 0.019). There was statistically significant increase of platelet count 6 months after treatment (P-value = 0.038). Our study showed statistically significant improvement of total bilirubin (P-value = 0.001), ALT (P-value = 0.012), AST (P-value = 0.001), AFP (P-value = 0.002) 6 months after treatment. Conclusions Results support the safety of sofosbuvir-daclatasvir regimen among Egyptians and suggest a significant role of those drug regimens in the treatment of HCV with least adverse events.

Immunological and hematological effects of Irvingia gabonensis stem bark in sodium arsenite-exposed rats

This study investigated the effect of ethanol stem bark extract of Irvingia gabonensis (ESEIG) on sodium arsenite (SA)-induced pro-inflammatory cytokines and hematological perturbations in Wistar rats. Fifty-five Wistar rats weighing 100 g - 179 g were distributed into eleven groups (n=5). Group 1 had feed and water only. Group 2 received 4.1 mg/kg body weight (kgbw) of SA. Groups 3-11 received SA and/or ESEIG. Treatment was done orally for 14 days. Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-4 (IL-4) concentrations, hemoglobin (HB) concentration, red blood cell (RBC) count, packed cell volume (PCV), mean cell hemoglobin concentration (MCHC), mean cell hemoglobin (MCH), mean corpuscular volume (MCV), white blood cell (WBC) count and its differentials and platelet (PLT) count were used to investigate the immunological and hematological effects of ESEIG. Exposure to SA produced significant (p ˂ 0.05) increases in hepatic IL-1β, TNF-α, IL-10 and IL-4 concentrations relative to control. Administration of SA also caused significant (p ˂ 0.05) decreases in HB, RBC, PCV, MCHC, MCH, MCV and PLT and significant (p ˂ 0.05) increases in WBC, lymphocytes, monocytes, eosinophils and neutrophils compared with control. Treatment with ESEIG concomitantly and 2 weeks after SA exposure, mitigated the deleterious effect of SA. However, ESEIG alone at various doses caused significant (p ˂ 0.05) increases in some of the assayed parameters, compared with control. These results imply that ESEIG may be protective against SA-induced inflammation and hematological derangements in Wistar rats. Its exclusive administration on chronic basis may also be slightly toxic.

RISPERIDONE INDUCED LEUCOPENIA AND NEUTROPENIA: A CASE REPORT AND BRIEF REVIEW OF LITERATURE

Hematological abnormalities are frequently encountered during treatment with antipsychotic drugs. Most of these are mild and of no clinical significance, but in a small minority of patients, hazardous, potentially life-threatening hematological effects, including leucopenia, neutropenia, agranulocytosis, thrombocytopenia, anaemia , leucocytosis, thrombocytosis, eosinophilia and altered platelet function. (1). Clozapine is associated with several well-known abnormalities of blood cell count (2), but some case reports associate novel antipsychotics, such as risperidone with leucopenia and agranulocytosis (3). This report describes a case of leucopenia under treatment with Oral Risperidone , suggesting the necessity of early recognition of leucopenia in order to prevent occurrence of potentially life-threatening agranulocytosis. ( 1) .

External validity of docetaxel triplet trials in advanced gastric cancer: are there patients who still benefit?

Background The purpose of our study was to develop an online calculator to estimate the effect of docetaxel triplets (DPF) in first line of advanced gastric cancer (AGC), and to assess the external validity of docetaxel trials in individual patients. Methods The study includes patients with HER2(-) AGC treated with platin and fluoropyrimidine (PF) or with DPF in first line. Treatment effect and interactions were assessed using Bayesian accelerated failure time models. Result The series comprises 1376 patients; 238 treated with DPF and 1138 with PF between 2008 and 2019. DPF was associated with increased progression-free survival (PFS) and overall survival (OS) with time ratio (TR) 1.27 (95% credible interval [CrI], 1.15–1.40), and TR 1.19 (95% CrI, 1.09–1.27), respectively. Serious adverse events were more common with DPF, particularly hematological effects (32% vs 22%). Younger participants received greater DPF dose density without achieving greater disease control, while severe toxicity was likewise higher. DPF yielded superior OS in Lauren intestinal (TR 1.27, 95% CrI, 1.08–1.11) vs diffuse subtype (TR 1.17, 95% CrI, 1.09–1.24) and the probability of increasing OS > 15% was 90% vs 67% in each subtype, respectively. The effect dwindles over time, which can be attributed to pathological changes and clinical practice changes. Conclusion Our study confirms the effect of DPF is highly dependent on several clinical–pathological variables, with discreet and gradually declining benefit over platinum doublets in later years, at the expense of increased toxicity. These results may help to underpin the idea that external validity of AGC trials should be revised regularly.

Seroprevalence of Toxoplasma gondii and associated hematological alterations in small ruminants of D.G. Khan district of Southern Punjab, Pakistan

ABSTRACT The present study was carried out to evaluate the prevalence and hematological effects of Toxoplasma gondii in sheep and goat in district Dera Ghazi Khan. Blood samples (n=204) were collected comprise goats (n=101) and sheep (n=103) alongwith age, gender and breeds of animals. Samples were collected randomly from 25 flocks of 7 different union council Viz. Vehova, Tibbi Qaisrani, Lakhani, Kohar, Tuman Qaisrani, Nutkani and Kot Qaisrani of Tehsil Taunsa Sharif at least 4 animals from each flock. All ruminants divide into three groups based on age, breed and gender. The prevalence was detected through two different kits Viz. LAT and ELISA kit. The overall prevalence suspected in goats through LAT and ELISA kit was (35.64%), (32.67%) and in sheep was (25.24%), (23.30%) respectively. The Toxoplasma gondii had a significant effect on goats in age groups and non-significant all other groups of goats and sheep. Toxoplasma gondii had a significant effect on all hematological parameters like Hemoglobin, total leukocyte cells, granulocytes, lymphocytes, platelets, and red blood cells, except monocytes. In conclusion of the current study, toxoplasmosis is prevalent among ruminants, reveals the possibility of transmission to humans on the use of host animals as protein source.