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Exploring the gut microbiome's influence on cancer-associated anemia: Mechanisms, clinical challenges, and innovative therapies.

BackgroundAnemia is a prevalent and challenging complication in patients with hematologic and solid malignancies, which stems from the direct effects of malignancy, treatment-induced toxicities, and systemic inflammation. It affects patients' survival, functional status, and quality of life profoundly. Recent literature has highlighted the emerging role of the gut microbiome in the pathogenesis of cancer-associated anemia. The gut microbiota, through its intricate interplay with iron metabolism, inflammatory pathways, and immune modulation, may either exacerbate or ameliorate anemia depending

Pernicious Anemia: The Hematological Presentation of a Multifaceted Disorder Caused by Cobalamin Deficiency.

Pernicious anemia is still a neglected disorder in many medical contexts and is underdiagnosed in many patients. Pernicious anemia is linked to but different from autoimmune gastritis. Pernicious anemia occurs in a later stage of autoimmune atrophic gastritis when gastric intrinsic factor deficiency and consequent vitamin B12 deficiency may occur. The multifaceted nature of pernicious anemia is related to the important role of cobalamin, which, when deficient, may lead to several dysfunctions, and thus, the proteiform clinical presentations of pernicious anemia. Indeed, pernicious anemia may l

Disorders of the Gastrointestinal System

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Фармакомикробиомика: От взаимодействия хост-микробиома-наркотики к клиническому переводу в докторскую медицину.

Заметная межиндивидуальная изменчивость реакции на наркотики по-прежнему является серьезной проблемой в области клинической фармакологии и не может быть в полной мере объяснена только генетикой принимающей страны. Растущие данные свидетельствуют о том, что кишечная микробиота является дополнительным фактором, определяющим эффективность и токсичность наркотиков посредством двустороннего взаимодействия с фармакологической терапией. Это признание привело к появлению фармакомикробиомики - области, которая изучает, как микробные сообщества влияют на утилизацию наркотиков и реагирование на них, и ка

Imatinib, sunitinib and pazopanib: From flat-fixed dosing towards a pharmacokinetically guided personalized dose.

Tyrosine kinase inhibitors (TKIs) are anti-cancer drugs that target tyrosine kinases, enzymes that are involved in multiple cellular processes. Currently, multiple oral TKIs have been introduced in the treatment of solid tumours, all administered in a fixed dose, although large interpatient pharmacokinetic (PK) variability is described. For imatinib, sunitinib and pazopanib exposure-treatment outcome (efficacy and toxicity) relationships have been established and therapeutic windows have been defined, therefore dose optimization based on the measured blood concentration, called therapeutic dru

Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is a degenerative condition of the back of the eye that occurs in people over the age of 50 years. Antioxidants may prevent cellular damage in the retina by reacting with free radicals that are produced in the process of light absorption. Higher dietary levels of antioxidant vitamins and minerals may reduce the risk of progression of AMD. This is the third update of the review. OBJECTIVES: To assess the effects of antioxidant vitamin and mineral supplements on the progression of AMD in people with AMD. SEARCH METHODS: We searched CENTRAL, ME

Foetal haemoglobin inducers for reducing blood transfusion in non-transfusion-dependent beta-thalassaemias.

BACKGROUND: Non-transfusion-dependent β-thalassaemia (NTDβT) is a subset of inherited haemoglobin disorders characterised by reduced production of the β-globin chain of haemoglobin leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it may be required to prevent complications of chronic anaemia, such as impaired growth and hypercoagulability. People with NTDβT also experience iron overload due to increased iron absorption from food sources which becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin

Consideration on Food Effect Studies for Anticancer Drugs Approved in Japan Between 2001 and 2022.

In developing a new drug, studies to evaluate the food effect (FE) on the drug's pharmacokinetics (FE studies) are generally conducted in healthy subjects in the early stages of clinical development. Conversely, for anticancer drugs, which have many adverse effects, it is assumed that FE studies cannot be conducted in healthy subjects. However, many unknowns exist about how FE on oral anticancer drugs is examined in clinical development. In this study, we aimed to examine the characteristics of conducting FE studies on anticancer drugs approved in Japan to date. Between 2001 and 2022, 70 new o

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… In Japan, the “Clinical Pharmacology Studies of Drugs” issued in 2001 mentions that FE on gastrointestinal absorption of oral drugs should be examined in the early stages of clinical development and that FE should be examined in the final formulation [ 7 ]. …

Pancreatitis among patients with cystic fibrosis: correlation with pancreatic status and genotype.

OBJECTIVE: Pancreatitis is an infrequent complication among patients with cystic fibrosis (CF). It has mainly been reported for patients with pancreatic sufficiency (PS). Previous studies involved only a small number of patients because they contained data from single centers. The aim of this study was to evaluate the incidence of pancreatitis in a large heterogeneous CF population, to determine the relationship with pancreatic function, and to assess whether pancreatitis is associated with specific CFTR mutations. METHODS: Physicians caring for patients with CF were approached through the CF

Human Health and Ocean Pollution.

BACKGROUND: Pollution - unwanted waste released to air, water, and land by human activity - is the largest environmental cause of disease in the world today. It is responsible for an estimated nine million premature deaths per year, enormous economic losses, erosion of human capital, and degradation of ecosystems. Ocean pollution is an important, but insufficiently recognized and inadequately controlled component of global pollution. It poses serious threats to human health and well-being. The nature and magnitude of these impacts are only beginning to be understood. GOALS: (1) Broadly examin

When Iron Bites Back: Severe Thrombocytopenia After Intravenous Iron Sucrose Therapy (Venofer).

Iron deficiency anemia (IDA) commonly presents with normal or elevated platelet counts, while thrombocytopenia is rare. Intravenous iron sucrose (Venofer) is widely used and generally well tolerated. We report the case of a 71-year-old female with chronic IDA who developed severe thrombocytopenia following iron sucrose therapy. Baseline hemoglobin was 6.3 g/dL with a platelet count of 229 × 10³/µL. After two doses of intravenous iron, hemoglobin improved to 9.3 g/dL, but platelets rapidly declined to 11 × 10³/µL. Extensive workup excluded thrombotic microangiopathy, autoimmune disease, infecti

Recent Advances in Doxorubicin Formulation to Enhance Pharmacokinetics and Tumor Targeting.

Doxorubicin (DOX), a widely used drug in cancer chemotherapy, induces cell death via multiple intracellular interactions, generating reactive oxygen species and DNA-adducted configurations that induce apoptosis, topoisomerase II inhibition, and histone eviction. Despite its wide therapeutic efficacy in solid tumors, DOX often induces drug resistance and cardiotoxicity. It shows limited intestinal absorption because of low paracellular permeability and P-glycoprotein (P-gp)-mediated efflux. We reviewed various parenteral DOX formulations, such as liposomes, polymeric micelles, polymeric nanopar

Is There a Role for Bismuth in Diarrhea Management?

Diarrhea, an illness of both the developed and developing world, involves the burdensome characteristics of frequent bowel movements, loose stools, and abdominal discomfort. Diarrhea is a long-standing challenge in palliative care and can have a myriad of causes, making symptomatic treatment pertinent when illness evaluation is ongoing, when there is no definitive treatment approach, or when effective treatment cannot be attained. Symptomatic therapy is a common approach in palliative care settings. Bismuth is a suitable agent for symptomatic therapy and can be effectively employed for managem

Roux-en-Y reconstruction alleviates radical gastrectomy-induced colitis via down-regulation of the butyrate/NLRP3 signaling pathway.

BackgroundDifferent methods for digestive tract reconstruction have a complex impact on the nutritional status of gastric cancer (GC) patients after radical gastrectomy. Previous studies reported that Roux-en-Y (R-Y) reconstruction resulted in obvious weight reduction and improvement in type 2 diabetes in obese patients. We investigated the relationship between R-Y reconstruction, gut microbiota, and the NLRP3 inflammasome in GC patients with poor basic nutrition.MethodsChanges in the gut microbiota after radical gastrectomy accomplished by different methods of digestive tract reconstruction w

Изучение механизма Shengmai San для лечения аденокарциномы легких на основе биоинформатики и моделирования молекулярной динамики.

Изучение механизма Shengmai San (SMS) в лечении аденокарциномы легких (LUAD) на основе комплексной стратегии, сочетающей «сетевую фармакологию, биоинформатику, стыковку молекулярной стыковки и моделирование молекулярной динамики», в целях разработки точной стратегии комбинированной терапии и выявления потенциальных биоактивных соединений. Дифференцированные гены в LUAD были выявлены в базе данных Gene Express Omnibus с использованием R (первоначально разработанные в Bell Laboratories и в настоящее время управляемые Lucent Technologies). Из энциклопедии традиционной китайской медицины были извл

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… Gastrointestinal absorption [ 45 ] is an indicator used to evaluate the degree of gastrointestinal absorption of a compound. … High gastrointestinal absorption indicates that the compound has higher potential for oral bioavailability. [ 45 ] P-glycoprotein is a transport protein found in cell membranes, such as those in the gastrointestinal tract and the blood-brain barrier. [ 44 , 46 ] It actively expels foreign substances, …

Bile Acid Malabsorption as a Consequence of Cancer Treatment: Prevalence and Management in the National Leading Centre.

The aim was to establish prevalence of bile acid malabsorption (BAM) and management in patients who underwent treatment for malignancy. Retrospective evaluation of data in patients seen within six months (August 2019-January 2020) was carried out. Demographic, nuclear medicine (Selenium Homocholic Acid Taurine (SeHCAT) scan result), clinical (previous malignancy, type of intervention (medication, diet), response to intervention) and laboratory (vitamin D, vitamin B12 serum levels) data were searched. In total, 265 consecutive patients were reviewed. Out of those, 87/265 (33%) patients (57 fema

The Effects of Artificial Sweeteners on Intestinal Nutrient-Sensing Receptors: Dr. Jekyll or Mr. Hyde?

The consumption of artificial and low-calorie sweeteners (ASs, LCSs) is an important component of the Western diet. ASs play a role in the pathogenesis of metabolic syndrome, dysbiosis, inflammatory bowel diseases (IBDs), and various inflammatory conditions. Intestinal nutrient-sensing receptors act as a crosstalk between dietary components, the gut microbiota, and the regulation of immune, endocrinological, and neurological responses. This narrative review aimed to summarize the possible effects of ASs and LCSs on intestinal nutrient-sensing receptors and their related functions. Based on the

Management of an oral ingestion of transdermal fentanyl patches: a case report and literature review.

Purpose. Fentanyl is available as a transdermal system for the treatment of chronic pain in opioid-tolerant patients; however, it carries a black box warning due to both the potency of the product and the potential for abuse. In this report, we describe a case of transbuccal and gastrointestinal ingestion of fentanyl patches and the management of such ingestion. Summary. A 32-year-old man was brought to the emergency department (ED) via emergency medical services for toxic ingestion and suicide attempt. The patient chewed and ingested two illegally purchased transdermal fentanyl patches. In th

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… However, ingesting an intact patch would not necessarily result in significant gastrointestinal absorption (i.e., the drug would still remain within the intact system). … If the entire contents of one patch were removed and administered transbuccally, this systemic level would be approximately three times that achieved with gastrointestinal absorption (i.e., approximately 5000 micrograms of fentanyl or 375 milligrams of intravenous morphine). …

Hypercalcemia in Cancer: Causes, Effects, and Treatment Strategies.

Calcium plays central roles in numerous biological processes, thereby, its levels in the blood are under strict control to maintain homeostatic balance and enable the proper functioning of living organisms. The regulatory mechanisms ensuring this balance can be affected by pathologies such as cancer, and as a result, hyper- or hypocalcemia can occur. These states, characterized by elevated or decreased calcium blood levels, respectively, have a significant effect on general homeostasis. This article focuses on a particular form of calcium metabolism disorder, which is hypercalcemia in neoplasm

Management of Pneumocystis Jirovecii pneumonia in HIV infected patients: current options, challenges and future directions.

The discovery of the Human Immunodeficiency Virus (HIV) was led by the merge of clustered cases of Pneumocystis jirovecii Pneumonia (PCP) in otherwise healthy people in the early 80's.1,2 In the face of sophisticated treatment now available for HIV infection, life expectancy approaches normal limits. It has dramatically changed the natural course of HIV from a nearly fatal infection to a chronic disease.3-5 However, PCP still remains a relatively common presentation of uncontrolled HIV. Despite the knowledge and advances gained in the prevention and management of PCP infection, it continues to

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… Case reports of dapsone-induced methemoglobinemia in the literature describe the improvement of mild symptoms with discontinuation of therapy and supportive measures. 46 While more symptomatic presentations are treated with methylene blue and activated charcoal to prevent further gastrointestinal absorption …