Hematological Effects Research Articles

Haematological parameters and biochemical indices of African catfish (Clarias gariepinus) exposed to glyphosate-based herbicide (Force up®) for 96 hours

IntroductionGeometric aquaculture growth has resulted in exponentially increasing use of agrochemicals as either parasiticides or herbicides in the aquaculture environment. This study determines some of the toxicological (haematological and biochemical) effects of glyphosate-based herbicides on non-target aquatic animals using Clarias gariepinus as the animal model.MethodSeventy-five apparently healthy adult C. gariepinus (300 g) were sourced from a local farmer and acclimatised for 2 weeks; of these, sixty subjects were divided into four treatment groups (fifteen fish per group and five replicates per unit) by simple randomisation and labelled as T0 (control), T1 (first treatment), T2 (second treatment), and T3 (third treatment). The treatments were replicated thrice. Four concentrations of Force up® [0 mL, 0.15 mL (0.003 mL/L or 5.1 mg/L), 0.225 mL (0.0045 mL/L or 7.65 mg/L), and 0.3 mL (0.006 mL/L or 10.2 mg/L) were added to a 50-L tank of water for T0, T1, T2, and T3, respectively. Approximately 5 mL of blood was collected from the fish in each treatment group 96 h post-exposure for measurement of the blood parameters and biochemical indices using standard analytical methods as well as calculation of the mean values.ResultThe mean values of the packed cell volume, haemoglobin concentration, red blood cell count, and white blood cell count compared to the control group showed an initial increase at T1 but decreased as the glyphosate concentrations increased at T2 (0.0045 mL/L) and T3 (0.006 mL/L). The platelet mean values decreased at T1, increased at T2, and decreased at T3, while the mean values of the corpuscular volume, corpuscular haemoglobin, and corpuscular haemoglobin concentration increased with glyphosate concentration, with the mean corpuscular haemoglobin concentration decreasing at T2. Only the platelet value was statistically significant at a p-value of <0.05 using ANOVA and post hoc Tukey test. The biochemical indices showed decreases in the mean values of aspartate transaminase, blood urea nitrogen, creatinine, and triglycerides at T1, increases at T2, and decreases at T3, while the total protein (g/dL), cholesterol, alanine transaminase, and alkaline phosphatase values showed increases at T1 and decreases at T2 and T3. All these values were not statistically significant based on ANOVA and had p-values >0.05.DiscussionBased on the results of this study, it is deduced that glyphosate-based herbicide (Force up®) has genotoxic, hepatotoxic, and nephrotoxic effects on C. gariepinus even at sublethal doses, with more adverse effects at increasing concentrations.

DDEL-17. INTRA-TUMORAL CONVECTION ENHANCED DELIVERY OF DEXAMETHASONE REDUCES INFLAMMATORY SIGNATURES AND EXTENDS SURVIVAL IN GBM MODEL

Abstract Dexamethasone is the most widely utilized drug for glioblastoma (GBM). However, systemic delivery of dexamethasone in GBM patients is associated with significant side effects and increasing doses with worse survival. Convection-enhanced delivery (CED) can deliver high doses of immunotherapy directly into the tumor microenvironment (TME) while avoiding systemic toxicity. Here, we report that high doses of dexamethasone can be delivered locally by CED without side effects and increase survival in a GBM model along with reduced inflammatory myeloid signatures. We investigated CED of dexamethasone treatment on survival(n=40), adverse side effects, and the immunological TME through peripheral analyses, liquid chromatography–mass spectrometry, and histology in a preclinical syngeneic mouse model. Additionally, we assessed the transcriptional responses of human GBM slices and stem-cell-derived human microglia after steroid treatment through bulk and single-cell RNA sequencing. We found that 7-day treatment with CED of dexamethasone produced a significant survival advantage in glioma-bearing mice compared to non-treated control(p=0.03). Systemic dexamethasone achieved low levels of drug in the TME and caused dysregulated blood glucose, blood counts, and peripheral organ weights, while high CED doses avoided these side effects(p< 0.05 each). Steroid treatment of acute GBM slices and lipopolysaccharide-activated microglia in-vitro both reversed inflammatory myeloid signatures associated with poor survival and recurrence on RNA sequencing analyses. We demonstrate the preclinical efficacy of delivering high local doses of dexamethasone in a GBM model through CED and observed prolonged survival along with reduced adverse inflammatory myeloid signatures. No side effects were demonstrated after chronic CED treatment of dexamethasone while systemic delivery achieved poor tumor penetration and caused known hematologic and metabolic side effects supporting the potential to optimize the clinical use of this therapy. CED of dexamethasone provides us a new treatment paradigm to locally control inflammatory signatures in the glioma TME in a controlled fashion.

Antibiotic-associated neutropenia is marked by the depletion of intestinal Lachnospiraceae and associated metabolites in pediatric patients.

Prolonged antibiotic exposure causes dangerous hematologic side effects, including neutropenia, in up to 34% of patients. Murine studies established a link between the intestinal microbiota and hematopoiesis. To identify factors that predispose to neutropenia in pediatric patients, we evaluated changes in microbiota-derived metabolites and intestinal microbiota composition after prolonged courses of antibiotics. In this multi-center study, patients with infections requiring anticipated antibiotic treatment of two or more weeks were enrolled. Stool samples were obtained at the start and completion of antibiotics or at neutropenia onset (prospective arm). Some patients were enrolled in a retrospective arm in which a stool sample was collected at the time of neutropenia during antibiotic therapy and 2-4 weeks after completion of antibiotics with recovery of blood counts. We identified 10 patients who developed neutropenia on antibiotics and 29 controls matched for age, sex, race, and ethnicity. Clinical data demonstrated no association between neutropenia and the type of infection or antibiotic used; however, patients with neutropenia were admitted to the intensive care unit more often and received longer courses of antibiotics. Reduced intestinal microbiome richness and, specifically, decreased abundance of Lachnospiraceae family members correlated with neutropenia. Untargeted stool metabolomic profiling revealed several metabolites that were depleted exclusively in patients with neutropenia, including members of the urea cycle pathway, pyrimidine metabolism, and fatty acid metabolism that are known to be produced by Lachnospiraceae. Our study shows a relationship between intestinal microbiota disruption and abnormal hematopoiesis and identifies taxa and metabolites likely to contribute to microbiota-sustained hematopoiesis.

Efficacy of Adding Veliparib to Temozolomide for Patients With MGMT-Methylated Glioblastoma

The prognosis for patients with glioblastoma is poor following standard therapy with surgical resection, radiation, temozolomide, and tumor-treating fields. To evaluate the combination of veliparib and temozolomide in glioblastoma based on preclinical data demonstrating significant chemosensitizing effects of the polyadenosine diphosphate-ribose polymerase 1/2 inhibitor veliparib when combined with temozolomide. Patients with newly diagnosed glioblastoma with MGMT promoter hypermethylation who had completed concomitant radiation and temozolomide were enrolled between December 15, 2014, and December 15, 2018, in this Alliance for Clinical Trials in Oncology trial. The data for this analysis were locked on April 21, 2023. Patients were randomized and treated with standard adjuvant temozolomide (150-200 mg/m2 orally, days 1-5) combined with either placebo or veliparib (40 mg orally, twice daily, days 1-7) for 6 cycles. The primary end point for the phase 3 portion of the trial was overall survival (OS). There were 322 patients randomized during the phase 2 accrual period and an additional 125 patients randomized to complete the phase 3 accrual, for a total of 447 patients in the final phase 3 analysis. The median (range) age for patients was 60 (20-85) years and 190 patients (42.5%) were female. The median OS was 24.8 months (90% CI, 22.6-27.7) for the placebo arm and 28.1 months (90% CI, 24.3-33.3) for the veliparib arm (P = .17). The difference in survival did not meet the prespecified efficacy end point. However, there was a separation of the survival curves that favored the veliparib arm over 24 to 48 months of follow-up. The experimental combination was well tolerated with an acceptable elevation in grade 3 or 4 hematologic toxic effects. This trial found that adding veliparib to adjuvant temozolomide did not significantly extend OS in patients with newly diagnosed, MGMT-hypermethylated glioblastoma. ClinicalTrials.gov Identifier: NCT02152982.

Haematological effect of a bi-herbal composition on phenyl hydrazine-induced anaemia in Albino Wistar rats

Picralima nitida and Cymbopogon citratus are plants known for their anti-inflammatory, antioxidant, and haematopoietic properties. This study aimed to determine the haematological effect of a dual herb composition of these plants on phenylhydrazine-induced anaemia in albino Wistar rats. Sixty adult male rats were divided into six groups: control, phenylhydrazine group, ferrous sulphate group, and three groups receiving phenylhydrazine plus 100 mg/kg, 200 mg/kg, and 400 mg/kg of the extract. Haematological parameters were measured using an autoanalyzer and analyzed with SPSS software V22. The red blood cell count was significantly higher in the control group compared to other groups (p<0.05). Haemoglobin was significantly higher in the control, ferrous sulphate, 100 mg/kg, and 400 mg/kg groups compared to the phenylhydrazine and 200 mg/kg groups (p<0.05). Mean cell volume was significantly lower in the control group compared to all other groups (p<0.05). Mean cell haemoglobin was significantly lower in the control group compared to other groups while MCHC was higher in the control group compared to phenylhydrazine, ferrous sulphate, 100mg/kg and 200mg/kg groups (p<0.05). RDWSD was significantly lower in the control group compared to all other groups (p<0.05). Total white blood cell count was significantly lower in the control and phenylhydrazine groups compared to others (p<0.05). Lymphocyte was significantly higher in the ferrous sulphate group compared to others, while monocyte count was significantly lower in the control, phenylhydrazine, and ferrous sulphate groups (p<0.05). Neutrophil was significantly higher in the control and phenylhydrazine groups (p<0.05). Platelet was significantly lower in the control group compared to ferrous sulphate, 200 mg/kg, and 400 mg/kg groups (p<0.05). Mean platelet volume was significantly lower in the control, phenylhydrazine, ferrous sulphate, and 100 mg/kg groups compared to the 400 mg/kg group (p<0.05). The study concludes that the biherbal formulation of the plants caused significant alterations in haematological parameters.

Hematological Side Effects of Psychiatric Drugs

This review article focuses on hematological disorders caused by psychiatric drugs, including neutropenia, leukopenia, leukocytosis, and anemia. Most major psychiatric drugs induce neutropenia and thrombocytopenia through various mechanisms, such as toxic bone marrow suppression and drug-dependent antineutrophil antibodies against hematopoietic precursors. Among these, agranulocytosis associated with phenothiazines is a well-discussed hematological side effect. Although rare, agranulocytosis is a dangerous and often fatal complication that may go unnoticed until infection occurs. We conducted a comprehensive literature search from 1977 to 2021, identifying 64 relevant articles. Our study aims to analyze outcomes related to pancytopenia, leucopenia, neutropenia, agranulocytosis, thrombocytopenia, and other hematological complications leading to hospitalization.

The Haematotoxicity and Nephrotoxicity Effects of Diazepam Administration in Male Albino Rats

Objectives: This study aimed to assess the haematological and nephrotoxic effects of diazepam at varying doses in male albino rats. Materials and Methods: Rats were administered therapeutic (0.062 mg/kg/day), high (0.33 mg/kg/day), and extremely high (0.661 mg/kg/day) doses of diazepam orally for 14 and 28 days. Blood and kidney samples were collected for haematological and biochemical analysis.Results: Diazepam administration significantly reduced red blood cell count (RBC), packed cell volume (PCV), and platelet count (PLT), while other haematological indices were not notably affected. Plasma creatinine and urea levels increased, and total protein decreased across all doses. The treatment also elevated renal thiobarbituric acid reactive substances (TBARS) levels, while reducing antioxidant enzyme activity superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH). Conclusions: Diazepam poses significant risks of oxidative stress, haematotoxicity, and nephrotoxicity. While effective in managing anxiety, caution is necessary due to its potentially harmful effects on blood and renal function.

Could macrocytosis predict survival In advanced breast cancer patients that were treated with CDK 4–6 inhibitors?

IntroductionCyclin Dependent Kinase (CDK) 4–6 inhibitors are the recommended first-line treatment option for hormone-positive metastatic breast cancer (MBC). They show their effects by causing cell cycle arrest in G1-S phase. Neutropenia is the most common haematological side effect. In the literature, data on the association between CDK 4–6 inhibitors and macrocytosis are limited. We aimed to investigate the effect of macrocytosis on survival. MethodsWe retrospectively analysed 133 patients with de novo hormone positive MBC using CDK 4–6 inhibitors in first line treatment. Mean Corpuscular Volume (MCV) > 100 was considered macrocytosis and patients were divided into two groups; MCV<100 and MCV >100. The association of macrocytosis with clinicopathological features, Progression Free Survival (PFS) and Overall Survival (OS) were evaluated. Results42 patients were receiving palbociclib and 81 patients were receiving ribociclib. Median OS was determined as 33 months and median PFS was determined as 22 months. Macrocytosis ever rate was 45.8 % during follow-up. Macrocytosis was observed in 4.2 % of the patients in the first month, 16.7 % in the third month, 41.6 % in the sixth month and 42.2 % in the twelfth month. ER receptor level, ki-67, macrocytosis at 6–12 months and macrocytosis-ever which were found to affect OS as a result of univariate Cox regression analysis, were evaluated with multivariate Cox regression models and it was observed that they had significant effect on PFS and OS. ConclusionMacrocytosis may be a useful biomarker for the prediction of PFS and OS in MBC patients receiving CDK 4–6 inhibitors.

Lactational performance and hematological effects of capsaicin supplementation in dairy cows: A meta-analysis

A meta-analysis was performed to investigate the effects of capsaicin (CAP) on lactational performance and blood chemistry and cell counts in dairy cattle. The database comprised 11 peer-reviewed studies published between 2011 and 2024. The overall effect of CAP, challenge (e.g., ketosis, glucose tolerance, LPS), and dose were considered explanatory variables in the analysis. Lactation performance response variables included DMI, milk yield (MY), ECM yield, feed efficiency (FE), milk components, and BW. Hematological response variables included red and white blood cell counts and blood BHB, total fatty acids, insulin, and glucose concentrations. Data were analyzed using random- and mixed-effect models in the "robumeta" package in RStudio. Milk yield was increased by 2.9% by CAP when compared with control. Capsaicin supplementation increased FE by 3.4% compared with control. Milk fat concentration and yield were also increased by CAP compared with control by 2.6% and 4.0%, respectively. Blood glucose concentrations were decreased 2.5% by CAP supplementation, whereas insulin levels were unaffected. Cows fed CAP during a challenge had higher MY and FE and tended to have lower blood glucose than their control counterparts. Overall, this analysis suggests that CAP supplementation may be directly affecting host physiology by altering glucose metabolism, but further research to define the mechanism is warranted.

Haematological and Histological Effects of Nanoplastics Released from Nonfood-grade Nonwoven Polyethene Bags on Mice

Nonfood-grade nonwoven polyethene (NFWP) bags which are frequently used in microwave cooking or carrying hot foods have been reported for releasing large amount of nanoplastics. Hence, the present study was designed to investigate the harmful effects of nanoplastics released from NFWP bags on mice. NFWP bags were cut into small pieces which were then boiled in water for 5 minutes. Then the boiled water was used as nanoplastic-contaminated drinking water for treated mice for 50 days. Surprisingly, the body weights and organ weight were increased remarkably for treated mice than control mice. The total Red Blood Cell (RBC) count decreased remarkably while total WBC count increased significantly in treated mice than in control. The percentage of neutrophils decreased remarkably while percentage of Monocytes increased significantly in treated mice as compared with control. The consumption of nanoplastics caused histological damage to intestine, heart, lung, kidney and liver of treated mice. The layers of intestinal muscles in the villi of treated mice were disrupted and infiltrated with foam cells. Destruction of alveoli and fibrosis was observed in the lungs of the treated mice. The heart muscles of treated mice were also disrupted and irregularly arranged with fibrosis. In the kidney of treated mouse, enhancement of renal spaces, shrinkage of glomeruli, eroded Bowman’s capsule, deleted and congested glomeruli along with blood vessel were found. The liver of the treated mice was affected by apoptosis, fibrosis, vacuole formation in hepatocyte, congested in hepatic tissue and dilation of blood vessel. Therefore, it can be concluded that consumption of nanoplastics released from hot NFWP bags has serious deleterious effect on haematopoiesis and tissue integrity of different organs of Mice.

Impact on Growth and Nutrient Utilization on Health and Hematological Effects of Cassia tora (L) on Clarias gariepinus (Burchell, 1882)

Impact on Growth and Nutrient Utilization on Health and Hematological Effects of Cassia tora (L) on Clarias gariepinus (Burchell, 1882)

Clinical characteristics, treatment, and outcomes of nivolumab induced immune thrombocytopenia.

Immune thrombocytopenia (ITP) represents an uncommon hematological side effect associated with nivolumab, and its distinct clinical attributes remain poorly defined. This research aimed to explore the clinical manifestations and outcomes of ITP induced by nivolumab. Reports on nivolumab induced ITP up to April 30, 2024, were collected for retrospective analysis. The study involved 34 patients with a median age of 67 years (range 32, 82). The onset of ITP varied from 10 to 100 days post initial dosage, with a median onset at 70 days. The majority of patients exhibited no symptoms, with only 23.5% experiencing clinically significant bleeding and 11.8% facing non-clinically significant bleeding. The median platelet count was 12 × 109/L (range 0, 115), with 67.6% of patients having platelet levels below 25 × 109/L. Bone marrow biopsy revealed mainly elevated megakaryocytes. Platelet-associated IgG levels were elevated with a median of 210 ng/107 cells (range 73, 1130). Subsequent interventions, which included cessation of nivolumab, administration of systemic corticosteroids, intravenous immunoglobulin therapy, a thrombopoietin receptor agonist, platelet transfusion, and rituximab treatment, resulted in 82.4% of subjects achieving normalized platelet counts, whereas 5.9% passed away due to ITP. ITP is a rare life-threatening immune-related adverse event and necessitates close monitoring. Systemic steroids are the primary treatment for ITP, while intravenous immunoglobulin, thrombopoietin receptor agonist and rituximab are other options.

Treatment of avian pathogenic Escherichia coli infected broilers with aqueous extracts of Vernonia amygdalina in a challenge experiment

Colibacillosis, which is the leading cause of infectious diseases resulting in mortality and economic losses in poultry is triggered by Avian pathogenic Escherichia coli (APEC). Conventionally, antibiotic growth promoters (AGP) are incorporated into poultry diets to control infectious diseases and boost performance. However, because of the problem of antimicrobial resistance, synthetic antibiotics are now restricted or banned in animal production in some countries. In this study, we carried out a challenge experiment by inoculating healthy broilers with APEC (106 cfu/mL) by oral gavage on day 21 of the experiment and orally administering various treatments five days post challenge for five days; synthetic antibiotics (T2), Vernonia amygdalina (bitter leaf) extracts (T3), no treatment (T4), which were compared with the control that wasn’t challenged (T1). The experiment lasted for 42 days. Performance, hematological and histological studies were carried out. The results show that the challenged birds became diseased with the development of visible lesions, which ameliorated over time to varying extents with the use of synthetic antibiotics and Vernonia treatments. Overall, the performance of the birds with the use of Vernonia (T3) was comparable with that of synthetic antibiotics (T2) without eliciting any adverse hematological effects on the broilers. We therefore conclude that Vernonia can be safely used as a supplement for disease prevention in broiler chicken production

Safety of teplizumab in patients with high-risk for diabetes mellitus type 1: A systematic review.

The incidence of diabetes mellitus type 1 (DM1) has been rising worldwide because of improvements in diagnostic techniques and improved access to care in countries with lower socioeconomic status. A new anti-CD4 antibody, Tep-lizumab, has been shown to delay the progression of DM1 and is the only medication approved for this indication. However, more information is needed about the safety profile of this drug. To identify the odds ratios (OR) of systems-based adverse effects for Teplizumab when compared to Placebo. An extensive systematic review was conducted from the inception of the medication until December 31, 2023. All clinical trials and studies that evaluated Teplizumab vs placebo were included in the initial review. The study protocol was designed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines guidelines and was registered in PROSPERO (ID: CRD42024496169). Crude OR were generated using RevMan Software version 5.4. After screening and review, 5 studies were selected to determine the risk of adverse effects of teplizumab compared to placebo. A total of 561 patients were included in the study population. Total adverse effects and system-based adverse effects were studied and reported. We determined that patients receiving Teplizumab had a higher risk of developing gastrointestinal (GI) (OR = 1.60, 95%CI: 1.01-2.52, P = 0.04), dermatological (OR = 6.33, 95%CI: 4.05-9.88, P < 0.00001) and hematological adverse effects (OR = 19.03, 95%CI: 11.09-32.66, P < 0.00001). These patients were also significantly likely to have active Epstein-Barr Virus infection (OR = 3.16, 95%CI: 1.51-6.64, P < 0.002). While our data showed that patients receiving Teplizumab did have a higher incidence of total adverse effects vs placebo, this finding did not reach statistical significance (OR = 2.25, 95%CI: 0.80-6.29, P = 0.12). Our systematic review suggests that Teplizumab patients are at risk for significant adverse effects, primarily related to GI, dermatological, and hematological systems. The total adverse effect data is limited as study populations are small. More studies should be conducted on this medication to better inform the target population of potential adverse effects.

Targeted polymeric primaquine nanoparticles: optimization, evaluation, and in-vivo liver uptake for improved malaria treatment

Primaquine (PQ) is a widely used antimalarial drug, but its high dosage requirements can lead to significant tissue damage and adverse gastrointestinal and hematological effects. Recent studies have shown that nanoformulations can enhance the bioavailability of pharmaceuticals, thereby increasing efficacy, reducing dosing frequency, and minimizing toxicity. In this study, PQ-loaded PLGA nanoparticles (PQ-NPs) were prepared using a modified double emulsion solvent evaporation technique (w/o/w). The PQ-NPs exhibited a mean particle size of 228 ± 2.6 nm, a zeta potential of +27.4 mV, and an encapsulation efficiency of 81.3 ± 3.5%. Scanning electron microscopy (SEM) confirmed their spherical morphology, and the in vitro release profile demonstrated continuous drug release over 72 h. Differential scanning calorimetry (DSC) thermograms indicated that the drug was present in the nanoparticles, with improved physical stability. Fourier-transform infrared spectroscopy (FTIR) analysis showed no interactions between the various substances in the NPs. In vivo studies in Swiss albino mice infected with Plasmodium berghei revealed that the nanoformulated PQ was 20% more effective than the standard oral dose. Biodistribution studies indicated that 80% of the NPs accumulated in the liver, highlighting their potential for targeted drug delivery. This research demonstrates the successful development of a nanomedicine delivery system for antimalarial drugs, offering a promising strategy to enhance treatment efficacy while reducing adverse effects.

Biochemical and haematological effects of serum PFOA, ADV and cC6O4 in workers of a chemical company producing fluoropolymers, Italy, 2013–2022

IntroductionPerfluoroalkyl and polyfluoroalkyl substances (PFAS) are widely used in the manufacture of fluoropolymers. We evaluated biochemical and haematological effects of three PFAS, serum perfluorooctanoic acid (PFOA), ADV, and cC6O4 in workers of a fluoropolymer company. MethodsUsing data (2013–2022), we fitted random intercept regression models adjusted for several covariates and reciprocal adjustment between the three PFAS. ResultsWe analysed data of 814 workers (698 men, 116 women), 607 from the chemical plant, 207 from the research centre, for a total of 4912 blood samples (2065 with all three PFAS measured). Median levels of PFOA and ADV were 21.3 and 120 μg/L. Most (65.5%) cC6O4 measurements were below the limits of quantification (which varied over time from 5 to 0.1 μg/L). For PFOA, we observed positive associations with total cholesterol (+1.1% increase per ln(PFOA) increase) and apolipoprotein B (+1.4%) and negative associations with alkaline phosphatase (−1.5%); suggestive associations were also found with RBC (−0.4%), IgA (−1.5%), IgM (−1.4%). ADV was positively associated with total and LDL cholesterol (+1.0% and +1.6% per ln(ADV) increase), apolipoprotein B (+1.0%), GGT (+2.1%), IgM (+1.4%), and WBC (+1.5%) and negatively associated with direct bilirubin (−2.3%) and alpha-2-globulins (−0.7%); suggestive associations were found for indirect bilirubin (−2.0%), oestradiol (−2.1%), ad CRP (+6.0%). For samples with detectable cC6O4 levels we observed higher values of ALP (+2.3%), proteins (+0.5%), IgG (+0.7%) and platelets (+1.6%) and suggestively increased total bilirubin (+3.9%), RBC (+0.6%), and oestradiol (+5.8%). Some associations (total cholesterol, apolipoprotein B, WBC, total bilirubin, and alkaline phosphatase showed reverse time trends in parallel with the strong decrease of serum PFOA and ADV over the study period. DiscussionWe found associations of serum PFOA and ADV with lipid metabolism, liver function, and immunoglobulins. The reverse time trends of some endpoints in parallel with decrease of serum PFOA and ADV reinforce causal interpretation of results. cC6O4 showed a different pattern of associations.

In utero treatment of congenital cytomegalovirus infection with valganciclovir: an observational study on safety and effectiveness.

The treatment of congenital cytomegalovirus (CMV) infection is usually administered to neonates after birth; however, it can be anticipated during the prenatal period by treating pregnant women in order to reduce the severity of the congenital disease. The most commonly used treatment for CMV during pregnancy is valaciclovir; however, valganciclovir has a higher potency against CMV and is the first choice for neonates with congenital CMV disease. We investigated neonatal and maternal safety of tertiary prevention in infected fetuses showing ultrasound features of infection using valganciclovir. Retrospective cohort study of pregnant women and their symptomatic infected fetuses taking valganciclovir, 3 × 450 mg per day. All fetuses presented at least one prenatal feature on ultrasound. We assessed fetal/neonatal and maternal safety, as well as neonatal efficacy of treatment. The main outcome was neutropenia. Secondary outcomes included other haematological side effects, symptoms at birth and neonatal CMV-PCR was positive. Seventeen women with singleton pregnancies received valganciclovir from a median (IQR) of 27.1 (26.0-30.3) to 11.6 (6.5-12.9) weeks of gestation. No neonatal neutropenia was reported. One pregnancy was terminated for severe features. Three newborns (18%) were asymptomatic at birth, including one with negative CMV-PCR from blood and saliva. CMV-PCR was positive for 12/13 symptomatic newborns, with a median (IQR) log10 viral load of 3.36 (3.30-4.20), 4.03 (1.75-4.27) and 3.04 (0.00-3.40) log10 copies/mL in blood, urine and saliva, respectively. Tertiary prevention by valganciclovir appears to be well tolerated for both fetus and mother. However, more extensive trials accompanied by long-term follow-up are needed.

Evaluation of Erythrocytes Indices, Platelet Indices and Complete Blood Count in Feline Mammary Carcinomas

The aim of this study was to evaluate the differences in the platelet (PLT) indices and complete blood count (CBC) parameters between the cats with mammary tumor and healthy individuals. Also, the differences in above mentioned parameters are going to be investigated in cats with mammary tumors with regard to clinicopathological characteristics of the primary tumor. A total of 44 female cats were included in the study. The study groups consisted of cats with mammary tumors (Group MT, n=22) and healthy cats presented for neutering (Group H, n=22). The ages of the cats were ranged between 5-15 years. All data on CBC, thoracic radiography, clinical examination findings and histopathology were obtained from the the patient archive in the animal hospital automation system. While the highest red blood cell (RBC) and hemoglobulin (HGB) levels were observed in Group H, Group MT had the highest white blood cell (WBC), mean platelet volume (MPV) and plateletcrit (PCT) levels. The mean corpuscular volume (MCV) level in T1 was significantly lower than in T2-T3. The MCV level in G1-G2 tended to be higher compared to G3. In Group MT, CBC parameters were not significantly different related to the presence of metastasis, presence of ulceration and inflammation on the tumor. It was concluded that evaluation of CBC and PLT indices in cats with mammary tumors would be useful in understanding the hematological effects of the disease and tumor characteristics (tumor size and histological grade).

Severe neutropenia probably caused by enzalutamide and abiraterone in a prostate cancer patient.

Abiraterone and enzalutamide are two androgen receptor pathway inhibitors approved, among others, for the treatment of metastatic castration-resistant prostate cancer in adult men whose disease has progressed on or after a docetaxel-based regimen. Although hematological effects, especially neutropenia, are one of the main complications of other oral antineoplastic drugs, these adverse effects are infrequent in the case of androgen receptor pathway inhibitors. We report the case of a patient diagnosed with metastatic castration-resistant prostate cancer who discontinued an androgen receptor pathway inhibitor due to drug-related grade 4 neutropenia. His control blood counts before enzalutamide starting were normal. After one month of treatment, he developed a grade 4 neutropenia, with complete neutrophil count recovery four weeks later. He underwent a bone marrow aspiration, which revealed normocelullar results, and enzalutamide was restarted. Three weeks later, the treatment was eventually discontinued due to neutropenia reappearance. Neutrophil count recovery was achieved one month later. Then, he started treatment with abiraterone, but two weeks later neutropenia reappeared. Abiraterone was withdrawn, and the patient recovered from neutropenia 2 weeks later. This case exposes not only the occurrence of rare toxicity of two individual drugs but also the description of a probable drug-class adverse event not reported before. The patient recovered from neutropenia after the androgen receptor pathway inhibitor was withdrawn, thereby supporting the diagnosis of probable drug-induced neutropenia. There is scarce evidence in the literature concerning androgen receptor pathway inhibitor-related neutropenia. However, its life-threatening potential cannot be ignored, so healthcare professionals should be warned of the possibility of the occurrence of such adverse reactions.

Combination of neoadjuvant and adjuvant chemotherapy with FOLFOX compared with adjuvant chemotherapy in management of locally advanced rectal cancers: a randomized trial of a promising therapeutic approach

BackgroundColorectal cancer (CRC) is a significant malignancy with widespread implications. Despite progress in surgical interventions for rectal cancer, improvements in overall prognosis remain disproportionate. Standard preoperative chemoradiation, while established as the standard treatment for the majority of rectal cancers, exhibits limited effectiveness in enhancing disease-free survival (DFS) and mitigating distant metastases, particularly in cases of locally advanced rectal cancer (LARC).MethodsThis randomised clinical trial assessed 286 patients with LARC in two paralleled groups. Group A underwent six courses of neoadjuvant MFOLFOX chemotherapy, chemoradiation, surgery, and six adjuvant chemotherapy cycles. Group B received concurrent chemoradiation, surgery, and twelve adjuvant chemotherapy cycles. Patient evaluations were achieved at multiple stages of treatment and follow-up.ResultsGroup A had significantly lower local recurrence (11.64%) than Group B (21.74%, P = 0.025). The distant metastasis rate in Group A (8.90%) was lower than in Group B (20.29%) but was not significant (p = 0.143). More patients in Group A experienced downstaging (80.82% vs. 60.87%, p < 0.001). Specifically, 72.60% demonstrated downstaging of tumour invasion and 54.79% downstaging of lymph node involvement, compared to 57.25% and 41.30% in Group B (p = 0.009 and p = 0.025, respectively) as well as higher pCR rate (26.03% vs. 15.25%, p = 0.030) and three-year DFS rate (82.19% vs. 71.01%, p = 0.035) in group A compare to group B.ConclusionThis innovative strategy for LARC showed promising results with lower local recurrence and higher rates of downstaging and pCR. Treatment side effects were similar in both groups but less frequent in Group A. Anaemia was the most common haematological side effect (A: 58%, B: 68%), and peripheral sensory neuropathy was the most common non-haematological complication (A: 63%, B: 64%). These findings suggest this regimen could be a valuable therapeutic approach for LARC.Trial RegistrationThis trial was registered on 2023–12-08 within the IRCT.IR database under the number IRCT20210308050628N1.