RESUMO
Balkan endemic nephropathy (BEN) is a chronic kidney disease that predominantly affects inhabitants of rural farming communities along the Danube River tributaries in the Balkans. Long-standing research has identified dietary exposure to aristolochic acids (AAs) as the principal toxicological cause. This study investigates the pathophysiological role of anemia in BEN, noting its earlier and more severe manifestation in BEN patients compared to those with other chronic kidney diseases. Utilizing a mouse model, our research demonstrates that prolonged exposure to aristolochic acid I (AA-I) (the most prevalent AA variant) leads to significant red blood cell depletion through DNA damage, such as DNA adduct formation in bone marrow, prior to observable kidney function decline. Furthermore, in vitro experiments with kidney cells exposed to lowered oxygen and pH conditions mimicking an anemia environment show enhanced DNA adduct formation, suggesting increased AA-I mutagenicity and carcinogenicity. These findings indicate for the first time a positive feedback mechanism of AA-induced anemia, DNA damage, and kidney impairment in BEN progression. These results not only advance our understanding of the underlying mechanisms of BEN but also highlight anemia as a potential target for early BEN diagnosis and therapy.
Assuntos
Anemia , Ácidos Aristolóquicos , Nefropatia dos Bálcãs , Adutos de DNA , Ácidos Aristolóquicos/toxicidade , Ácidos Aristolóquicos/efeitos adversos , Nefropatia dos Bálcãs/induzido quimicamente , Nefropatia dos Bálcãs/metabolismo , Nefropatia dos Bálcãs/genética , Adutos de DNA/metabolismo , Animais , Camundongos , Humanos , Anemia/induzido quimicamente , Anemia/metabolismo , Anemia/genética , Masculino , Dano ao DNA/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Rim/efeitos dos fármacos , Rim/metabolismo , FemininoRESUMO
BACKGROUND: Anemia is common in low- and middle-income countries (LMICs), causing significant health issues and social burdens. Exposure to household air pollution from using biomass fuels for cooking and heating has been associated with anemia, but the exposure-response association has not been studied. OBJECTIVES: We evaluated the associations between personal exposure to air pollution and both hemoglobin levels and anemia prevalence among pregnant women in a multi-country randomized controlled trial. METHODS: We studied 3,163 pregnant women aged 18-35 years with 9-20 weeks of gestation, recruited as part of the Household Air Pollution Intervention Network (HAPIN) randomized controlled trial in Guatemala, India, Peru, and Rwanda. We assessed 24-hour personal exposures to fine particulate matter (PM2.5), black carbon (BC), and carbon monoxide (CO), and measured hemoglobin levels at baseline (15 ± 3 weeks gestation). Linear and logistic regression models were used to examine the associations of measured pollutants with hemoglobin levels and anemia prevalence, adjusting for confounding. RESULTS: Single-pollutant models showed associations of CO with higher hemoglobin levels and lower anemia prevalence. Bipollutant models involving CO and PM2.5 also revealed that an interquartile range (IQR) increase in CO concentrations (2.26 ppm) was associated with higher hemoglobin levels [ß = 0.04; 95 % confidence interval (CI): 0.01, 0.07], and a lower odds of anemia prevalence [odds ratios (OR) = 0.90; 95 % CI: 0.83, 0.98]. PM2.5 was inversely related to hemoglobin and positively associated with anemia, but results were not statistically significant at the 0.05 alpha level. County-specific results showed that 3 of 4 countries showed a similar association between CO and hemoglobin. We found no association of BC levels with hemoglobin levels or with anemia prevalence. CONCLUSION: Our findings suggest that exposure to CO is associated with higher hemoglobin and lower anemia prevalence among pregnant women, whereas PM2.5 showed the opposite associations.
Assuntos
Poluição do Ar em Ambientes Fechados , Anemia , Monóxido de Carbono , Hemoglobinas , Material Particulado , Humanos , Feminino , Gravidez , Poluição do Ar em Ambientes Fechados/estatística & dados numéricos , Poluição do Ar em Ambientes Fechados/análise , Poluição do Ar em Ambientes Fechados/efeitos adversos , Adulto , Anemia/epidemiologia , Anemia/sangue , Anemia/induzido quimicamente , Adulto Jovem , Material Particulado/análise , Índia/epidemiologia , Adolescente , Monóxido de Carbono/análise , Hemoglobinas/análise , Guatemala/epidemiologia , Peru/epidemiologia , Ruanda/epidemiologia , Prevalência , Culinária , Poluentes Atmosféricos/análise , Exposição Ambiental/estatística & dados numéricosRESUMO
BACKGROUND: Natalizumab is a monoclonal antibody used to treat patients with relapsing-remitting multiple sclerosis. Anemia is a recognized side effect, but it is usually mild and of a short duration when natalizumab is stopped. Here, we describe a case of a young woman with severe and especially long lasting anemia associated with treatment with natalizumab, persisting up to a year after treatment was stopped. CASE PRESENTATION: A 24 year-old Caucasian woman with relapsing-remitting multiple sclerosis developed severe transfusion dependent anemia after 27 infusions with natalizumab, which was her first and only treatment for her multiple sclerosis. Extensive hematologic diagnostics did not reveal any malignant cause or any other plausible non-malignant cause for her anemia. The bone marrow was found to be hypercellular, with a maturation arrest of the erythropoiesis and with grade 1-2 fibrosis. No specific treatment for the anemia was given. The hemoglobin level showed signs of spontaneous increase after nearly one year after natalizumab was discontinued. CONCLUSION: Severe anemia can be caused by treatment with natalizumab. This case adds information to the few other similar reported cases, demonstrating the potential duration of the anemia, as well as detailed description of hematologic findings. The mechanism is most likely due to inhibition of α4 subunit of the α4ß1-integrin, which is present on both lymphocytes and erythroid precursor cells.
Assuntos
Anemia , Esclerose Múltipla Recidivante-Remitente , Natalizumab , Humanos , Natalizumab/efeitos adversos , Natalizumab/uso terapêutico , Feminino , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Anemia/induzido quimicamente , Adulto Jovem , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêuticoRESUMO
BACKGROUND: Chewing fresh leaves of Catha edulis (khat) is a popular pastime activity among Ethiopians where 12% women chew it. Reports show that khat use has been associated with poor nutritional status. This study aimed to determine whether khat chewing is linked to underweight and anemia. METHOD: We analyzed data from the 2016 Ethiopian Demographic and Health Survey (EDHS). The EDHS used two stage stratified cluster sampling to collected data from 16,650 households. We used data from a total of 15,683 respondents and 1904 respondents who chewed ever chewed khat in their lives. We used Pearson's chi-square, and logistic regression while stratifying by residence (urban vs rural) to control for confounders. RESULT: Our results indicated 10.7% (95%CI: 10.92,11.26) of women chewed khat for an average of 16.5 days in the previous month. A woman's current khat chewing status was significantly associated with age, educational level, region, religion, wealth group, and marital status. Women aged 40-44 were significantly more likely to chew (AOR = 2.89,) compared to those aged 15-19. Compared with Protestant women, Muslim women were 210 times more likely (AOR = 210, 95% CI 102,435.7) to chew and women in the poorest wealth quintile had 73% higher odds (AOR = 1.73, 95% CI 1.22,2.44) of chewing khat when compared with the richest. Anemia was not associated with a woman's chewing status, whereas rural women who chewed khat for more than 26 days in a month had a 78% increased risk (OR = 1.78) of being underweight when compared to non-chewers. CONCLUSION: Khat chewing is associated with sociodemographic factors and current khat use is associated with a higher risk of underweight among women living in rural areas. Implementing targeted awareness campaigns for women about the risks of khat chewing is recommended.
Assuntos
Anemia , Catha , Inquéritos Epidemiológicos , Magreza , Humanos , Catha/efeitos adversos , Feminino , Adulto , Etiópia/epidemiologia , Magreza/epidemiologia , Anemia/epidemiologia , Anemia/induzido quimicamente , Estudos Transversais , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Mastigação , População Rural/estatística & dados numéricosRESUMO
OBJECTIVE: BRCA1/2 are integral to the DNA repair mechanism and their germline pathogenic variants (gBRCA) result in a high risk for developing breast and ovarian cancer. Patients with gBRCA mutations showed increased sensitivity to DNA cross-linking agent but might have increased treatment-related toxicities. Thus, we hypothesized that gBRCA mutation ovarian cancer patients who underwent platinum-based chemotherapy might be at higher risk of developing chemotherapy-induced hematologic toxicity. METHODS: This study enrolled 160 patients with ovarian cancer who received frontline platinum-based chemotherapy between 2011 and 2019 in Kyungpook National University Chilgok Hospital. Incidence rate and severity of chemotherapy-induced hematologic toxicity (neutropenia, anemia, thrombocytopenia) was compared for BRCA mutation and wild patients. RESULTS: 160 women, including 62 BRCA1/2 (38 BRCA1, and 25 BRCA2) mutation group, and 98 noncarriers, were analyzed. A higher frequency of G2 anemia was noted in the BRCA -mutant group (22% vs. 1%, p = 0.07). Furthermore, G3 anemia was significantly common among BRCA group (12.9% vs. 3%, p = 0.02). In the subgroup analysis according to BRCA1/2 status, BRCA1 mutated patients showed a significantly higher frequency of G1 anemia than BRCA2 (89% vs. 60%, p = 0.01). In terms of neutropenia and thrombocytopenia, BRCA mutated patients and noncarriers had similar hematologic toxicity. CONCLUSION: Germline BRCA mutations were associated with a higher frequency of G2/3 anemia in ovarian cancer patients who underwent first-line platinum-based chemotherapy. Moreover, the BRCA1 mutation appeared to be more strongly associated with the incidence of chemotherapy-induced anemia. Our findings warrant further investigation in larger, prospective studies to confirm these current findings and determine whether preventive interventions may be necessary.
Assuntos
Proteína BRCA1 , Proteína BRCA2 , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Pessoa de Meia-Idade , Proteína BRCA1/genética , Proteína BRCA2/genética , Idoso , Adulto , Mutação em Linhagem Germinativa , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Anemia/induzido quimicamente , Anemia/genética , Estudos Retrospectivos , Trombocitopenia/induzido quimicamente , Trombocitopenia/epidemiologia , Trombocitopenia/genética , Doenças Hematológicas/induzido quimicamente , Doenças Hematológicas/epidemiologia , MutaçãoRESUMO
Serious hematological adverse drug reactions (HADRs) may lead to or prolong hospitalization and even cause death. The aim of this study was to determine the regulatory factors associated with HADRs caused by drugs that were authorized up to July 2023 by the European Medicines Agency (EMA) and to evaluate the frequency of HADRs. Using a cross-sectional approach, the type and frequency of HADRs were collected from the Summaries of Product Characteristics of Drugs Authorized by the EMA and analyzed within proprietary, nonproprietary, and biosimilar/biological frameworks. Multivariate statistical analysis was used to investigate the associations of generic status, biosimilar status, conditional approval, exceptional circumstances, accelerated assessment, orphan drug status, years on the market, administration route, and inclusion on the Essential Medicines List (EML) with HADRs. In total, 54.78% of proprietary drugs were associated with HADRs at any frequency, while anemia, leucopenia, and thrombocytopenia were observed in approximately 36% of the patients. The predictors of any HADR, anemia, and thrombocytopenia of any frequency are generic status, biosimilar status, and inclusion on the EML, while the only protective factor is the administration route. Biosimilars and their originator biologicals have similar frequencies of HADRs; the only exception is somatropin. Knowledge of the regulatory factors associated with HADRs could help clinicians address monitoring issues when new drugs are introduced for the treatment of patients.
Assuntos
Anemia , Medicamentos Biossimilares , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Medicamentos Essenciais , Leucopenia , Trombocitopenia , Humanos , Preparações Farmacêuticas , Medicamentos Biossimilares/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Medicamentos Genéricos , Trombocitopenia/induzido quimicamente , Leucopenia/induzido quimicamente , Anemia/induzido quimicamente , Anemia/tratamento farmacológico , Aprovação de DrogasRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese herb Panax notoginseng (PN) tonifies blood, and its main active ingredient is saponin. PN is processed by different methods, resulting in different compositions and effects. AIM OF THE STUDY: To investigate changes in the microstructure and composition of fresh PN processed by different techniques and the anti-anemia effects on tumor-bearing BALB/c mice after chemotherapy with cyclophosphamide (CTX). MATERIALS AND METHODS: Fresh PN was processed by hot-air drying (raw PN, RPN), steamed at 120 °C for 5 h (steamed PN, SPN), or fried at 130 °C, 160 °C, or 200 °C for 8 min (fried PN, FPN1, FPN2, or FPN3, respectively); then, the microstructures were compared with 3D optical microscopy, quasi-targeted metabolites were detected by liquid chromatography tandem mass spectrometry (LCâMS/MS), and saponins were detected by high-performance liquid chromatography (HPLC). An anemic mouse model was established by subcutaneous H22 cell injection and treatment with CTX. The antianemia effects of PN after processing via three methods were investigated by measuring peripheral blood parameters, performing HE staining and measuring cell proliferation via immunofluorescence. RESULTS: 3D optical profiling revealed that the surface roughness of the SPN and FPN was greater than that of the other materials. Quasi-targeted metabolomics revealed that SPN and FPN had more differentially abundant metabolites whose abundance increased, while SPN had greater amounts of terpenoids and flavones. Analysis of the composition and content of the targeted saponins revealed that the contents of rare saponins (ginsenoside Rh1, 20(S)-Rg3, 20(R)-Rg3, Rh4, Rk3, Rg5) were greater in the SPN. In animal experiments, the RBC, WBC, HGB and HCT levels in peripheral blood were increased by SPN and FPN. HE staining and immunofluorescence showed that H-SPN and M-FPN promoted bone marrow and spleen cell proliferation. CONCLUSION: The microstructure and components of fresh PN differed after processing via different methods. SPN and FPN ameliorated CTX-induced anemia in mice, but the effects of PN processed by these two methods did not differ.
Assuntos
Anemia , Ciclofosfamida , Camundongos Endogâmicos BALB C , Panax notoginseng , Saponinas , Animais , Ciclofosfamida/toxicidade , Panax notoginseng/química , Camundongos , Saponinas/farmacologia , Anemia/induzido quimicamente , Anemia/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Masculino , Linhagem Celular Tumoral , FemininoRESUMO
In this study, we investigate the veliparibinduced toxicity in cancer patients. Databases were searched for RCTs treated with veliparib. We found veliparib could increase the risk of hematologic and gastrointestinal toxicities. Anemia, neutropenia, thrombocytopenia, and nausea were the most common toxicities. Patients diagnosed with gastrointestinal tumors tend to have a higher risk of high-grade neutropenia; patients in the first-line setting tend to have a higher risk of high-grade anemia and neutropenia than those in the ≥ second line setting. Patients receiving higher dosage of veliparib tend to have a higher risk of all-grade anemia. Veliparib could also increase the risk of insomnia, myalgia, pneumonia, dyspnea, hyponatremia, and fatigue.
Assuntos
Benzimidazóis , Neoplasias , Humanos , Benzimidazóis/efeitos adversos , Benzimidazóis/uso terapêutico , Neoplasias/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Antineoplásicos/efeitos adversos , Anemia/induzido quimicamenteRESUMO
Hematocrit (Hct) is a powerful tool often used in a clinical setting for the diagnosis of blood conditions such as anemia. It is also used in the research field as a hematological parameter in both human and mouse models. Measuring Hct, however, involves the use of expensive standardized equipment (such as a CritSpin™ Microhematocrit Centrifuge). Here, we describe a novel, simple, and affordable method to determine the Hct in untreated wild-type (WT) mice and phenylhydrazine (PHZ)-induced anemic mice with reasonable accuracy, using a benchtop centrifuge commonly available in laboratories. Hct of murine samples processed with a benchtop centrifuge, when compared to the standardized method CritSpin™, showed comparable results. This approach for determining Hct of murine can prove useful to research laboratories that cannot afford specialized equipment for Hct studies. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Affordable Method for Hematocrit Determination in Murine Models Basic Protocol 2: Murine Sample Validation Support Protocol: Phenylhydrazine-induced anemia in wild-type (WT) mice.
Assuntos
Anemia , Camundongos , Humanos , Animais , Hematócrito/métodos , Modelos Animais de Doenças , Anemia/induzido quimicamente , Anemia/diagnóstico , Fenil-Hidrazinas/toxicidadeRESUMO
BACKGROUND: Pancreatic ductal adenocarcinoma is characterised by low immunogenicity and an immunosuppressive tumour microenvironment. LOAd703, an oncolytic adenovirus with transgenes encoding TMZ-CD40L and 4-1BBL, lyses cancer cells selectively, activates cytotoxic T cells, and induces tumour regression in preclinical models. The aim of this study was to evaluate the safety and feasibility of combining LOAd703 with chemotherapy for advanced pancreatic ductal adenocarcinoma. METHODS: LOKON001 was a non-randomised, phase 1/2 study conducted at the Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA, and consisted of two arms conducted sequentially; the results of arm 1 are presented here. In arm 1, patients 18 years or older with previously treated or treatment-naive unresectable or metastatic pancreatic ductal adenocarcinoma were treated with standard 28-day cycles of intravenous nab-paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2 (up to 12 cycles) and intratumoural injections of LOAd703 every 2 weeks. Patients were assigned using Bayesian optimal interval design to receive 500 µL of LOAd703 at 5 × 1010 (dose 1), 1 × 1011 (dose 2), or 5 × 1011 (dose 3) viral particles per injection, injected endoscopically or percutaneously into the pancreatic tumour or a metastasis for six injections. The primary endpoints were safety and treatment-emergent immune response in patients who received at least one dose of LOAd703, and antitumour activity was a secondary endpoint. This study was registered with ClinicalTrials.gov, NCT02705196, arm 2 is ongoing and open to new participants. FINDINGS: Between Dec 2, 2016, and Oct 17, 2019, 23 patients were assessed for eligibility, leading to 22 patients being enrolled. One patient withdrew consent, resulting in 21 patients (13 [62%] men and eight [38%] women) assigned to a dose group (three to dose 1, four to dose 2, and 14 to dose 3). 21 patients were evaluable for safety. Median follow-up time was 6 months (IQR 4-10), and data cutoff was Jan 5, 2023. The most common treatment-emergent adverse events overall were anaemia (96 [8%] of 1237 events), lymphopenia (86 [7%] events), hyperglycaemia (70 [6%] events), leukopenia (63 [5%] events), hypertension (62 [5%] events), and hypoalbuminaemia (61 [5%] events). The most common adverse events attributed to LOAd703 were fever (14 [67%] of 21 patients), fatigue (eight [38%]), chills (seven [33%]), and elevated liver enzymes (alanine aminotransferase in five [24%], alkaline phosphatase in four [19%], and aspartate aminotransferase in four [19%]), all of which were grade 1-2, except for a transient grade 3 aminotransferase elevation occurring at dose 3. A maximum tolerated dose was not reached, thereby establishing dose 3 as the highest-evaluated safe dose when combined with nab-paclitaxel plus gemcitabine. Proportions of CD8+ effector memory cells and adenovirus-specific T cells increased after LOAd703 injections in 15 (94%) of 16 patients for whom T-cell assays could be performed. Eight (44%, 95% CI 25-66) of 18 patients evaluable for activity had an objective response. INTERPRETATION: Combining LOAd703 with nab-paclitaxel plus gemcitabine in patients with advanced pancreatic ductal adenocarcinoma was feasible and safe. To build upon this novel chemoimmunotherapeutic approach, arm 2 of LOKON001, which combines LOAd703, nab-paclitaxel plus gemcitabine, and atezolizumab, is ongoing. FUNDING: Lokon Pharma, the Swedish Cancer Society, and the Swedish Research Council.
Assuntos
Adenocarcinoma , Anemia , Vírus Oncolíticos , Neoplasias Pancreáticas , Trombocitopenia , Masculino , Humanos , Feminino , Gencitabina , Vírus Oncolíticos/genética , Teorema de Bayes , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/tratamento farmacológico , Paclitaxel , Anemia/induzido quimicamente , Trombocitopenia/induzido quimicamente , Adenocarcinoma/terapia , Adenocarcinoma/tratamento farmacológico , Albuminas , Terapia Genética/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Microambiente TumoralRESUMO
INTRODUCTION: Clozapine, a second-generation antipsychotic (SGA), is considered the gold standard medication to treat patients with treatment-resistant schizophrenia (TRS). Despite its efficacy, clozapine is associated with adverse effects, notably neutropenia and agranulocytosis. Other hematological adverse effects are less common. Severe anemia is a rare adverse effect seldom reported in the literature and is typically associated with pure red cell aplasia (PRCA). Nevertheless, the benefits of clozapine in managing TRS make rechallenge a reasonable option. CASE REPORT: We present the case of a 35-year-old man with TRS, resistant to previous antipsychotics, who experienced severe anemia during clozapine treatment. An investigation for clozapine-induced anemia revealed PRCA on myelogram. After discontinuing clozapine, the patient's hemoglobin levels recovered. Subsequent treatments with olanzapine, zuclopenthixol, and aripiprazole proved ineffective, leading us to consider a clozapine rechallenge. The rechallenge, monitored for 58 days, resulted in improved psychiatric symptoms and stable hemoglobin levels. The patient remained stable during 6 months of follow-up, with no hematological changes. DISCUSSION: PRCA is a very rare adverse effect of clozapine. The cause of drug-induced PRCA is still unknown; for clozapine, there are no studies. Rechallenge after a severe and rare adverse effect is a complex decision. This case is the first to report a successful clozapine rechallenge following severe anemia without other blood dyscrasias, emphasizing the imperative need for close monitoring during the rechallenge process. Further study is warranted to understand the predictive factors for a successful outcome in clozapine rechallenges.
Assuntos
Anemia , Antipsicóticos , Clozapina , Esquizofrenia Resistente ao Tratamento , Humanos , Clozapina/efeitos adversos , Clozapina/administração & dosagem , Masculino , Adulto , Antipsicóticos/efeitos adversos , Antipsicóticos/administração & dosagem , Anemia/induzido quimicamente , Esquizofrenia Resistente ao Tratamento/tratamento farmacológicoRESUMO
Undernutrition in children with cancer is associated with complications during cancer therapy. The study objective was to determine the association between specific anthropometric parameters and short-term chemotherapy-related complications and mortality. This was a hospital-based, prospective cohort study of children, age ≤12 years, with a new cancer diagnosis at the Paediatric Oncology Unit, Korle Bu Teaching Hospital, Ghana. Socio-demographic information, cancer characteristics and anthropometric measurements were obtained at enrolment. Participants were followed up for twelve weeks from commencement of chemotherapy and selected treatment-related complications such as anaemia and thrombocytopenia requiring transfusions, prolonged neutropenia resulting in treatment delays, febrile neutropenia, mucositis and death were recorded. A total of 133 participants were recruited with a median age of 4.5 years. Eighty-one (60.9%) were diagnosed with solid tumours, 31 (23.3%) had leukaemias and 21 (15.8%) had lymphomas. Of the anthropometric parameters assessed, only arm anthropometry using upper arm muscle area (UAMA) and mid-upper arm circumference (MUAC) were associated with complications. Participants with wasting were more likely to develop anaemia and mucositis. However, the incidence of prolonged neutropenia was significantly higher among participants with average UAMA (p = 0.043) and low average UAMA (p = 0.049) compared to those with low UAMA. Risk of neutropenia was also significantly less among those with wasting by MUAC compared to those well-nourished (p = 0.045). Twenty-three participants (17.3%) died with a greater proportion (11/44; 25%) occurring in those who were wasted using MUAC. These findings underscore the need for nutritional surveillance at diagnosis and during chemotherapy, particularly where co-morbid disease is prevalent.
Assuntos
Anemia , Desnutrição , Mucosite , Neoplasias , Neutropenia , Humanos , Criança , Pré-Escolar , Estudos Prospectivos , Gana/epidemiologia , Desnutrição/complicações , Desnutrição/epidemiologia , Desnutrição/diagnóstico , Hospitais de Ensino , Antropometria/métodos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Braço/anatomia & histologia , Anemia/induzido quimicamente , Anemia/epidemiologia , Neutropenia/induzido quimicamente , Neutropenia/epidemiologiaRESUMO
A 90-year-old man on maintenance hemodialysis was admitted due to severe symptomatic anemia. Biopsies under esophagogastroduodenoscopy demonstrated that the cause of anemia was intermittent blood oozing from multiple gastric hyperplastic polyps. Even after successful eradication of Helicobacter pylori, he showed hypergastrinemia (480 pg/mL) owing to esomeprazole (proton-pump inhibitor) therapy for the past 4.5 years to treat reflux esophagitis. Seven months after we switched esomeprazole to famotidine (H2-receptor antagonist), those gastric polyps and anemia were remarkably ameliorated with lowered gastrin levels. This case indicates that long-term use of a proton-pump inhibitor triggers chronic hypergastrinemia, leading to gastric hyperplastic polyps and subsequent severe anemia.
Assuntos
Anemia , Inibidores da Bomba de Prótons , Masculino , Humanos , Idoso de 80 Anos ou mais , Inibidores da Bomba de Prótons/efeitos adversos , Esomeprazol/efeitos adversos , Anemia/induzido quimicamente , Biópsia , Hiperplasia/induzido quimicamente , Diálise Renal/efeitos adversosRESUMO
Soluble guanylate cyclase (sGC) modulation has been scrutinized in several disease states including heart failure (HF). Recently, it was shown that an sGC modulator improved HF-related hospitalization significantly, though, there was no benefit related to mortality. Herein, a comprehensive meta-analysis of randomized controlled trials (RCTs) for sGC modulation in HF patients was provided in agreement with the PRISMA statement. A total of 10 RCTs yielding 12 papers were included. There were 7526 patients with heart failure of each phenotype, 4253 in the sGC modulator group and 3273 in the placebo group. Use of sGC modulators in HF patients yielded no significant difference in the risk of all-cause mortality compared to placebo (RR = 0.97, 95% CI 0.88-1.08, p = 0.62). The use of sGC modulators was associated with a trend toward a considerable but non-significant increase in the incidence of SAEs (RR = 1.10, 95% CI 0.99-1.22, p = 0.07), as well as an increased incidence of hypotension and anemia. There was an overall neutral effect of sGC modulation on NT-proBNP levels, 6MWD and mortality, at a cost of slight increase in hypotension and anemia. Of note, the improvement in EQ-5D-based quality of life was significant. Hence, the benefit seems to be driven by distinctive domains of quality of life.
Assuntos
Insuficiência Cardíaca , Guanilil Ciclase Solúvel , Humanos , Anemia/induzido quimicamente , Insuficiência Cardíaca/tratamento farmacológico , Hipotensão/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como Assunto , Guanilil Ciclase Solúvel/efeitos adversosRESUMO
BACKGROUND: Globally, 80 million people are suffering from chronic Hepatitis C virus (HCV) infection. Sofosbuvir ribavirin-based anti-HCV therapy is associated with anemia and other adverse effects. Polymorphisms of Inosine triphosphatase (ITPA) gene may cause functional impairment in the Inosine triphosphate pyrophosphatase enzyme, resulting in enhanced sustained viral response (SVR) and protection from ribavirin-associated anemia in patients on therapy. The study objective was to investigate the effect of Inosine triphosphatase gene polymorphism on SVR achievement, hemoglobin decline and ribavirin dose reduction in patients on therapy. METHODS: This prospective cohort study was of 170 hepatitis C infected patients received 6-month sofosbuvir ribavirin therapy. Patient viral load, reduction in ribavirin amount, liver function test, and complete blood count were noted monthly. Inosine triphosphatase variants rs1127354 and rs7270101 were assessed through the restriction fragment length polymorphism and confirmed using Sanger sequencing. The impact of polymorphism on cumulative reduction of ribavirin, and anti-HCV therapy outcome were studied. RESULTS: A total of 74.3% of patients had ITPA rs1127354 CC genotype, 25.7% were CA and AA 0%. The frequency of ITPA genotype rs7270101-AA was 95%, AC 5%, and CC was 0%. ITPA rs1127354-CA had a notably positive impact on SVR achievement with a zero-relapse rate. ITPA rs1127354-CA genotype was significantly (P Ë0.05) protective against ≥ 2 g/dl Hb reduction from baseline to 1st, 2nd and 6th months of therapy. During treatment, Hb reduction ≥ 10 g/dl was frequently observed in rs1127354-CC genotype and rs7270101-AA genotype patients. Ribavirin dose reduction was significantly (P Ë0.05) high in rs1127354-CC genotype as compared to genotype CA whereas no significant difference was observed in ribavirin dose reduction in rs7270101 AA and non-AA genotype. Patient baseline characteristics such as age, body mass index, rs1127354-CC genotype, and baseline Hb were significantly associated with significant Hb reduction. CONCLUSION: Pretreatment evaluation of ITPA polymorphism can be a diagnostic tool to find out patients at risk of anemia and improve treatment adherence. ITPA genotype rs1127354-CA contributes to improved compliance with ribavirin dose and protects against hemoglobin decline in HCV patients while taking ribavirin-based therapy. However, ITPA rs1127354, rs7270101 polymorphism have no significant impact on SVR achievement.
Assuntos
Anemia , Hepatite C Crônica , Hepatite C , Humanos , Ribavirina/efeitos adversos , Sofosbuvir/efeitos adversos , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/genética , Antivirais/efeitos adversos , Inosina Trifosfatase , Hepacivirus/genética , Estudos Prospectivos , Polimorfismo de Nucleotídeo Único , Pirofosfatases/genética , Pirofosfatases/uso terapêutico , Anemia/induzido quimicamente , Anemia/genética , Hepatite C/tratamento farmacológico , Genótipo , Hemoglobinas/genética , Resultado do TratamentoRESUMO
BACKGROUND: The management of chemotherapy induced anemia (CIA) remains challenging. The potential risk and benefits in providing patient-centered care need to be balanced; the disease is multifactorial; and the major treatments including red blood cell (RBC) transfusions, erythropoiesis-stimulating agents (ESAs) and intravenous injection (i.v.)iron supplementation have a unique set of strengths and limitations. Also, most previous survey based on the patient data could not reveal the process of evaluation and decision-making for CIA treatment from a physician's perspective. As the comparison of China Society of Clinical Oncology (CSCO), National Comprehensive Cancer Network (NCCN) and European Society of Medical Oncology (ESMO) guidelines, the standard of CIA treatment in China will vary from United States and Europe, for example, the initial hemoglobin (Hb) for RBC transfusions. In order to understand the diagnosis, treatment, and unmet medical needs of CIA patients, the China Medical Education Association (CMEA), in conjunction with Cancer Hope Medium, initiated the first national survey of Chinese physicians regarding the diagnosis and treatment of CIA. METHODS: The CMEA sent an online, 12-item questionnaire (via wjx.cn) to physicians across China from September 1, 2022 to October 22, 2022. Two hundred and sixty-five samples were calculated usingsurveyplanet.com. The questionnaire evaluated the impact of anemia on chemotherapy interruption, initial treatment, the target Hb level of CIA in, and the current status of ESAs prescription in clinical practice. Respondents were asked to score their reasons for not using ESAs (including safety issues, drug access in practice or adherence) and the risk options of the current treatment including ESAs, RBC transfusion, and i.v.iron. RESULTS: A total of 331 questionnaires among 5,000 web visits were gathered, covering 247 hospitals in 29 provinces across China, of which 130 (53%) were tier IIIA hospitals, 50 (20%) were tier III B hospitals, 59 (24%) were tier IIA hospitals, and 8 (3%) were tier II B hospitals. The frequency of chemotherapy dose delay/reduction due to anemia was 24% [standard deviation (SD) 49%]. Most responding physicians rated an initial Hb level for ESAs treatment to be 80 g/L, with a favorable Hb level for chemotherapy being 100 g/L (60%), which would not limit treatment availability. The majority (67.6%, n=221) of physicians who responded indicated that they had used ESAs for anemia correction, while the others (32.4%, n=106) reported never using them. CONCLUSIONS: This is the first study in conducting a large-scale survey on the diagnosis and treatment of CIA in China from a physicians' perspective. We found that in China, nearly one-quarter of patients undergoing chemotherapy with concurrent anemia may experience interruption of chemotherapy and that the initiation of anemia treatment is not adequately timed. In treating CIA, most physicians prioritize the completion of chemotherapy via Hb level over treating the symptoms of anemia.
Assuntos
Anemia , Antineoplásicos , Hematínicos , Neoplasias , Médicos , Humanos , Estados Unidos , Antineoplásicos/uso terapêutico , Anemia/induzido quimicamente , Anemia/tratamento farmacológico , Ferro/efeitos adversos , Hematínicos/efeitos adversos , Neoplasias/tratamento farmacológico , Neoplasias/complicações , Inquéritos e Questionários , PercepçãoRESUMO
Electronic health records (EHRs) provide meaningful knowledge of drug-related adverse events (AEs) that are not captured in standard drug development and postmarketing surveillance. Using variables obtained from EHR data in the University of California San Francisco de-identified Clinical Data Warehouse, we aimed to evaluate the potential of machine learning to predict two hematological AEs, thrombocytopenia and anemia, in a cohort of patients treated with linezolid for 3 or more days. Features for model input were extracted at linezolid initiation (index), and outcomes were characterized from index to 14 days post-treatment. Random forest classification (RFC) was used for AE prediction, and reduced feature models were evaluated using cumulative importance (cImp) for feature selection. Grade 3+ thrombocytopenia and anemia occurred in 31% of 2,171 and 56% of 2,170 evaluable patients, respectively. Of the total 53 features, as few as 7 contributed at least 50% cImp, resulting in prediction accuracies of 70% or higher and area under the receiver operating characteristic curves of 0.886 for grade 3+ thrombocytopenia and 0.759 for grade 3+ anemia. Sensitivity analyses in strictly defined patient subgroups revealed similarly high predictive performance in full and reduced feature models. A logistic regression model with the same 50% cImp features showed similar predictive performance as RFC and good concordance with RFC probability predictions after isotonic calibration, adding interpretability. Collectively, this work demonstrates potential for machine learning prediction of AE risk in real-world patients using few variables regularly available in EHRs, which may aid in clinical decision making and/or monitoring.
Assuntos
Anemia , Trombocitopenia , Humanos , Linezolida/efeitos adversos , Anemia/induzido quimicamente , Anemia/epidemiologia , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico , Trombocitopenia/epidemiologia , Modelos Logísticos , São FranciscoRESUMO
Oral iron therapy is often the most common way of treating anaemia; however intravenous iron is considered effective due to rapid iron replenishment. We have dearth of evidence on clinical outcomes post treatment of anaemia. We have searched studies published in English in PubMed, Cochrane, Scopus, ProQuest, and Google Scholar. Our study analysed the clinical outcomes amongst neonates and mother and the adverse events post treatment and assessed the mean change in maternal haemoglobin concentration in both the groups. Forest plots for the clinical outcomes are presented. From a total of 370 studies, 34 Randomized and quasi experimental studies comparing clinical outcomes post-treatment of anaemia in pregnancy were included for quantitative evidence synthesis. Pooled results of maternal clinical outcomes using random effect model [OR: 0.79 (95% CI 0.66; 0.95); 10 outcomes; 17 studies] showed statistically significant difference among both the groups [Moderate quality evidence]; however no significant difference [OR: 0.99 (95% CI 0.86; 1.14); 7 outcomes; 8 studies] have been observed for neonatal complications [Low quality evidence]. The study found that pregnant women receiving IV iron were significantly less likely to experience adverse events as compared with those receiving oral iron [OR 0.39; (95% CI 0.26-0.60)]; 34 studies; 13,909 women; [Low quality evidence]. Findings from meta-regression analysis showed that IV iron is more likely to reduce maternal complications by 21% compared to oral iron. Increase in odds of adverse maternal outcomes was observed due to increase in gestational age and publication year but no effect for the type of drug used. IV iron increases Hb more and at a higher pace than oral iron. Intravenous iron is more likely to avert adverse maternal outcomes and adverse reactions. However, there is no conclusive evidence on its effectiveness on individual maternal outcome or neonatal outcome/s. Protocol registered with PROSPERO CRD42022368346).
Assuntos
Anemia Ferropriva , Anemia , Complicações Hematológicas na Gravidez , Recém-Nascido , Feminino , Gravidez , Humanos , Suplementos Nutricionais/efeitos adversos , Ferro , Anemia/tratamento farmacológico , Anemia/induzido quimicamente , Complicações Hematológicas na Gravidez/tratamento farmacológico , Anemia Ferropriva/tratamento farmacológicoRESUMO
INTRODUCTION: Chemotherapy during pregnancy can increase the risk of fetal anemia. Severe fetal anemia can lead to the development of hydrops fetalis and potentially fetal demise. Hence, it is imperative to implement consistent monitoring methods in the context of chemotherapy treatment. This study aimed to diagnose and monitor fetal anemia using middle cerebral artery peak systolic velocity (MCA-PSV) as a diagnostic tool during chemotherapy in pregnant women. MATERIAL AND METHODS: The study employed a prospective analysis involving a case series of 15 patients diagnosed with cancer during pregnancy and subsequently underwent chemotherapy. MCA-PSV was used to identify fetal anemia. The patients were scheduled for ultrasound examinations of the MCA-PSV. The first examination was performed on the same day as the administration of chemotherapy, while the second occurred on the 10th day after chemotherapy. The measurement technique used in the study was based on the methodology proposed by Mari and Barr. The multiples of the median were calculated using the calculators provided by Medicina Fetal Barcelona. Based on these values anemia severity was determined. When moderate or severe anemia was identified, chemotherapy was individually modified. Additionally, a blood count analysis was conducted immediately after the delivery of the newborn. RESULTS: Five patients were diagnosed with fetal or newborn anemia. With MCA-PSV, we identified moderate fetal anemia in two patients and severe fetal anemia in one. The complete blood count testing of newborns revealed mild anemia in three patients. One case was unrelated to chemotherapy-induced anemia. During treatment, fetal anemia did not corelate with maternal anemia. CONCLUSIONS: In four cases of anemia the combination of cisplatin and iphosphamide was used as a chemotherapy agent. No anemia was observed in other drug combinations. Our findings suggest that MCA-PSV is a reliable method for identifying anemia and should be included in the treatment protocol for chemotherapy-induced fetal anemia.
Assuntos
Anemia , Antineoplásicos , Doenças Fetais , Humanos , Feminino , Recém-Nascido , Gravidez , Artéria Cerebral Média/diagnóstico por imagem , Velocidade do Fluxo Sanguíneo , Ultrassonografia Pré-Natal , Anemia/induzido quimicamente , Anemia/diagnóstico , Doenças Fetais/induzido quimicamente , Doenças Fetais/diagnóstico por imagemRESUMO
Dietary cadmium (Cd2+) intake is implicated in the pathogenesis of hypertension and anaemia, but there is a paucity of information on the haematological changes in hypertensive conditions. This study, therefore, aims to evaluate the effects of Cd2+ on blood pressure (BP) and haematological indices in the Sprague-Dawley rat model. Three cohorts (n = 10 each) of control and Cd2+-fed male Sprague-Dawley rats were selected. Cd2+-exposed rats received 2.5 or 5 mg/kg b.w. cadmium chloride via gavage thrice-weekly for eight weeks, while control animals received tap water. BP and flow were measured non-invasively from rat tails twice-weekly using a CODA machine, while weights were measured thrice-weekly. Haematological indices were assessed using the Cell-Dyn Emerald Haematology Analyzer. Data were reported as mean ± SEM, and statistically analyzed using One-Way Analysis of Variance. Bonferroni post hoc test was used for multiple comparisons. Cd2+-exposure induced hypertension by significantly (p < 0.05) elevating systolic, diastolic, and mean arterial BPs, pulse pressure, and heart rate (HR), and increased (p < 0.05) blood flow. Mean cell volume (MCV) and haemoglobin (MCH) were significantly (p < 0.05) reduced, and red cell distribution width (RDW) significantly (p < 0.01) increased by exposure to 5 mg/kg b.w. Cd2+. Haemoglobin concentration (MCHC), haematocrit, haemoglobin, red blood cell, platelet, mean platelet volume, and white blood cell counts were unaffected by Cd2+-exposure. Cd2+ induced hypertension, microcytosis, hypochromicity, and anisocytosis without anaemia, which may be precursor to microcytic anaemia and coronary artery disease. This study is important in Cd2+-exposed environments and warrants further investigations.