Search Results (370)

Background/Objectives: Pica, the compulsive ingestion of non-nutritive substances, has long been observed in patients with iron deficiency anemia (IDA). This behavior is particularly noted in adults, including pregnant women, and poses both diagnostic and management challenges. We conducted a review of studies from the past decade to evaluate the epidemiology and nature of pica in adult IDA patients and the outcome of various treatment strategies on anemia and pica behaviors. Methods: We searched PubMed, Scopus, and Cochrane Library for peer-reviewed articles (including observational studies, clinical trials, and reviews) published in English between 2015 and 2025. Inclusion criteria targeted studies of adult populations with IDA that reported on pica prevalence, characteristics, or treatment outcomes. We also reviewed clinical guidelines and meta-analyses on IDA treatment in adults for recommended management approaches. Results: Pica was found to be a prevalent symptom among individuals with IDA, but was readily treatable with appropriate iron deficiency treatment. Among treatment options, both oral and parenteral iron supplementation were found to be effective in resolving iron deficiency and pica. Choice of treatment depends on tolerance to oral iron, speed of resolution required, and comorbid conditions. Conclusions: Pica is closely intertwined with IDA; our review highlighted the prevalence of pica among individuals with IDA, which serves as both a clinical clue to underlying anemia and a potential source of complications. Crucially, the treatment of IDA is also effective for pica. We recommend oral iron therapy on alternate-day dosing as first-line therapy to minimize side effects, alongside dietary optimization. If IDA and pica are resistant to oral iron supplementation or oral iron cannot be tolerated, parenteral iron therapy can be considered. Full article

After the first release of synthalin B (dodecamethylenbiguanide) in 1928 and its later retraction in the 1940s in Germany, the retraction of phenformin (N-Phenethylbiguanide) and of Buformin in the USA (but not outside) because of the lethal complication of acidosis seemed to have put an end to the era of the biguanides as oral antidiabetics. The strongly hygroscopic metformin (1-1-dimethylbiguanide), first synthesized 1922 and resuscitated as an oral antidiabetic (type 2 of the elderly) compound first released in 1959 in France and in other European countries, was used in the first large multicenter prospective long-term trial in England in the UKPDS (1977–1997). It was then released in the USA after a short-term prospective trial in healthy overweight “young” type 2 diabetics (mean age 53 years) in 1995 for oral treatment of type 2 diabetes. It was, however, prescribed to mostly multimorbid older patients (above 60–65 years of age). Metformin is now the most used oral drug for type 2 diabetes worldwide. While intravenous administration of biguanides does not have any glucose-lowering effect, their oral administration leads to enormous increase in their intestinal concentration (up to 300-fold compared to that measured in the blood), to reduced absorption of glucose from the diet, to increased excretion of glucose through the stool, and to decrease in insulin serum level through increased hepatic uptake and decreased production. Intravenously injected F18-labeled glucose in metformin-treated type 2 diabetics accumulates in the small and even more in the large intestine. The densitometry picture observed in metformin-treated overweight diabetics is like that observed in patients after bowel-cleansing or chronically taking different types of laxatives, where the accumulated radioactivity can even reach values observed in colon cancer. The glucose-lowering mechanism of action of metformin is therefore not only due to inhibition of glucose uptake in the small intestine but also to “attraction” of glucose from the hepatocyte into the intestine, possibly through the insulin-mediated uptake in the hepatocyte and its secretion into the bile. Furthermore, these compounds have also a diuretic effect (loss of sodium and water in the urine) Acute gastrointestinal side effects accompanied by fluid loss often lead to the drugs’ dose reduction and strongly limit adherence to therapy. Main long-term consequences are “chronic” dehydration, deficiency of vitamin B12 and of iron, and, as observed for all the biguanides, to “chronic” increase in fasting and postprandial lactate plasma level as a laboratory marker of a clinical condition characterized by hypotension, oliguria, adynamia, and evident lactic acidosis. Metformin is not different from the other biguanides: synthalin B, buformin, and phenformin. The mechanism of action of the biguanides as antihyperglycemic substances and their side effects are comparable if not even stronger (abdominal pain, nausea, vomiting, diarrhea, fluid loss) to those of laxatives. Full article

Iron deficiency (ID) is the most prevalent micronutrient deficiency globally, affecting approximately one in four individuals, with a particularly high burden among children, women of reproductive age, and populations in low- and middle-income countries. It contributes significantly to the global burden of disease, with consequences ranging from impaired cognitive and motor development in children to increased risks during pregnancy, including low birth weight, preterm delivery, and maternal mortality, as well as reduced physical performance and quality of life in adults. ID often precedes iron deficiency anemia (IDA), though clinical and functional impairments—such as cognitive deficits, immune dysfunction, and fatigue—can occur even in the absence of anemia. Despite its widespread nature, challenges remain in precisely defining, diagnosing, and treating ID effectively. Advances in diagnostic tools allow for earlier detection, while novel therapeutic strategies, including updated oral dosing regimens and modern intravenous iron formulations, offer improved efficacy and tolerability. These approaches are particularly valuable in minimizing gastrointestinal side effects and enhancing patient adherence. This review is based on a comprehensive literature search conducted primarily through PubMed and Scopus, emphasizing studies published within the past 10–15 years. It is thematically structured to explore the epidemiology, health consequences, diagnostic complexities, and therapeutic developments related to ID. It highlights the multifactorial nature of ID and underscores the urgent need for early identification, targeted interventions, and updated clinical guidelines to reduce the long-term health and societal impacts of this preventable and treatable condition. Full article

Background/Objectives: Patients undergoing hemodialysis frequently receive oral or intravenous iron supplementation to treat iron-deficiency anemia and enhance the efficacy of erythropoiesis-stimulating agents. However, this approach may lead to iron overload. Experimental studies have suggested that iron overload may contribute to the development of sarcopenia through oxidative stress and inflammation. This study aimed to investigate the association between iron status and sarcopenia in patients undergoing hemodialysis. Methods: Serum ferritin levels were measured, and sarcopenia was assessed using the Asian Working Group for Sarcopenia criteria in 104 stable outpatients undergoing maintenance hemodialysis therapy. Results: Sarcopenia was identified in 25 (24.0%) patients. Serum ferritin levels were significantly higher in patients with sarcopenia than in those without (median: 170.6 ng/mL vs. 92 ng/mL, p = 0.023). An increase of 10 ng/mL in serum ferritin levels was independently associated with sarcopenia. The high-ferritin group (≥132 ng/mL as a cutoff value determined using receiver operating characteristic curve analysis) exhibited a higher prevalence of sarcopenia compared with the low-ferritin group (37.3% vs. 11.3%, p = 0.001). Furthermore, serum ferritin levels were negatively correlated with skeletal muscle mass and skeletal muscle strength, which constitute the components of the sarcopenia diagnostic criteria. Conclusions: Elevated serum ferritin levels were independently associated with sarcopenia in patients undergoing hemodialysis. This finding implies that excessive iron supplementation may contribute to the progression of sarcopenia. Routine evaluation of iron status and careful assessment of the necessity for iron therapy are recommended in this population. Full article

Background/Objectives: The development of hypophosphatemia has been associated with intravenous iron products, with the rate of hypophosphatemia found to be higher with ferric carboxymaltose. This consensus statement provides clinical guidance on the risk of hypophosphatemia development with ferric carboxymaltose and the approaches for management. To develop consensus recommendations regarding the clinical implications of hypophosphatemia after the administration of ferric carboxymaltose, the assessment of patient risk profile, and recommended approaches for risk reduction. Methods: Consensus statements were developed from an in-person meeting of specialists with expertise in iron pathophysiology and iron therapy and further supplemented with literature review. The multidisciplinary expert panel comprised global iron specialists spanning anesthesiology, cardiology, gastroenterology, obstetrics/gynecology, hematology, nephrology, and iron molecular biology. Structured discussions were held in an in-person meeting to gather expert opinion on the evidence base regarding intravenous iron and hypophosphatemia. Consolidated summary opinions underwent further iterations of panel review to form consensus recommendation statements. Results: The expert panel developed the following consensus statements: (1) Routine serum phosphate level measurement is not recommended for low-risk patients before or after treatment with ferric carboxymaltose, as most cases of hypophosphatemia that occur following the administration of ferric carboxymaltose are asymptomatic and transient; (2) patients receiving ferric carboxymaltose should be assessed for the degree of risk for developing symptomatic or severe hypophosphatemia prior to administration; (3) monitoring serum phosphate is recommended for patients at an increased risk for developing low serum phosphate or who require repeated courses of ferric carboxymaltose treatment at higher doses; (4) prophylactic oral phosphorus after ferric carboxymaltose is unlikely to effectively elevate phosphate and is not recommended for routine clinical practice; and (5) hypophosphatemic osteomalacia is rare and the risk of development after the administration of ferric carboxymaltose, in particular single infusion, is low. Conclusions: Hypophosphatemia following ferric carboxymaltose is predominantly asymptomatic and transient. Individuals at higher risk for developing hypophosphatemia with ferric carboxymaltose treatment include those who receive multiple infusions, higher cumulative doses, or long-term iron treatment or who have underlying clinical risk factors. These consensus statements provide structured guidance on the risk of hypophosphatemia with ferric carboxymaltose and the approaches to clinical management. Full article

Iron has many important functions related to energy metabolism. However, hemoglobin synthesis is always a priority. Iron deficiency can be caused by increased loss, insufficient intake, or decreased absorption from the intestine and reduced release from depots in systemic inflammation. Anemia appears when stores are depleted or when utilization of iron from the stores is impaired. Treatment with oral iron is the first choice when the intestine is healthy, and the patient is free of inflammation. Intravenous iron is indicated when oral iron is ineffective or not tolerated and if more rapid correction is clinically indicated as in severe anemia not requiring transfusion. Full article

Background/Objectives: Chronic anemia and iron overload in thalassemia lead to organ failures, including the heart, liver, endocrine glands, and spleen. Comprehensive multidisciplinary management is pivotal in improving patients’ clinical outcomes and well-being. The report aims to present a rare case of improved clinical condition in a transfusion-dependent thalassemia patient. Methods: Medical summaries were collected to compare patients’ conditions at various time frames. Furthermore, the report was composed in chronological order. Results: A 31-year-old male diagnosed with beta-thalassemia major and multiple comorbidities, including diabetes with a history of diabetic ketoacidosis, heart failure with a history of cardiac arrest, hepatomegaly, severe thoracolumbar scoliosis, and depression, exhibited a high physical endurance. The patient managed to maintain a strong treatment adherence and undergo intensive regular multidisciplinary follow-ups. The patient gained cardiac function improvement and metabolic stabilization, leading to completing a 5 k marathon without complication. Conclusions: Intensive management of iron overload through double oral chelation allows organ function improvement. Better mental health attenuates the patient’s overall well-being and is attributed to the ability to gain high physical endurance. Full article

Background/Objectives: The emergence of multidrug-resistant Acinetobacter baumannii (MDR A. baumannii) as a leading cause of fatal hospital-acquired infections underscores the urgent need for effective vaccines. While oral vaccines using live Bacillus subtilis spores expressing A. baumannii TonB-dependent receptor (TBDR) show promise, biosafety concerns regarding recombinant spore persistence necessitate alternative strategies. Here, we evaluated chemically inactivated B. subtilis spores displaying TBDR as a safer yet immunogenic vaccine candidate. Methods: Recombinant spores were inactivated using iron-ethanol sporicidal solution and administered to BALB/c mice (8–12 weeks old) to assess safety and immunogenicity. Toxicity was evaluated through clinical monitoring, serum biochemistry, and histopathology. Immune responses were characterized by T/B cell activation, IgG/IgA titers, and mucosal sIgA levels. Protective efficacy was determined by challenging immunized mice with MDR A. baumannii Ab35 and quantifying bacterial loads and examining tissue pathology. Results: The inactivated spores exhibited an excellent safety profile, with no adverse effects on clinical parameters, organ function, or tissue integrity. Immunization induced robust systemic and mucosal immunity, evidenced by elevated CD4+/CD8+ T cells, B cells, and antigen-specific IgG/IgA in serum and mucosal secretions. Following the challenge, vaccinated mice showed significantly reduced pulmonary bacterial burdens (>90% reduction), and preserved lung and spleen architecture compared to controls, which developed severe inflammation and tissue damage. Conclusions: These findings demonstrate that inactivated B. subtilis spores expressing TBDR are a safe, orally administrable vaccine platform that elicits protective immunity against MDR A. baumannii. By addressing biosafety concerns associated with live spores while maintaining efficacy, this approach represents a critical advance toward preventing high-risk nosocomial infections. Full article

Serious oral infections are frequently caused by Candida species, which have lately demonstrated resistance to antifungal medications. As a result, new therapeutic strategies, like photodynamic therapy (PDT), are desperately needed. Lactoferrin (LF), a salivary enzyme, is a natural protein that binds iron and has antifungal properties. Given its chemical structure and light absorption at 310–350 nm, LF appears to be a good photosensitizer in a PDT process for treating oral candidiasis. The purpose of this work was to assess the effectiveness of lactoferrin (LF) as a photosensitizer (PS) in photodynamic treatment (PDT) against oral multidrug-resistant (MDR) isolates of Candida spp. using an in vitro investigation. For this in vitro investigation, oral MDR isolates of Candida albicans, Candida kruseii, and Candida glabrata were employed. Using a Kirby–Bauer test (Eucast protocol), a solution of 20 mg of bovine lactoferrin dissolved in 1 mL of Sabouraud’s broth was tested in four different experimental combinations: (i) the solution as it is; (ii) the solution activated with 3% H₂O₂; (iii) the solution activated by light at 310–350 nm; and (iv) the solution activated with both 3% H₂O₂ and light at 310–350 nm. A control group and one with only H₂O₂ were also tested. After that, the Petri plates were incubated for 48 h at 37 °C. With inhibitory halos ranging from 30 to 40 mm for all Candida spp. MDR analyzed, group (iv) displayed the greatest results. H₂O₂ + lactoferrin-based solutions are thought to be potential PS in PDT for MDR Candida spp. eradication. Full article

Background/Objectives: Oral candidiasis is a prevalent fungal infection in young children, often associated with underlying factors such as immunosuppression, poor oral hygiene, or nutritional deficiency. This study aimed to investigate the relationship between nutritional biochemical markers and the presence and severity of oral candidiasis in children aged 6 months to six years. Methods: A total of 60 participants were enrolled in a cross-sectional observational study, equally divided into a case group with clinically diagnosed oral candidiasis and a control group without fungal infection. Serum levels of vitamin D, iron, zinc, albumin, and vitamin A were measured in all participants. The severity of candidiasis was assessed using a standardized clinical scoring system. Results: Statistical analysis revealed that children with candidiasis exhibited significantly lower levels of all measured biochemical markers than healthy controls. However, no significant correlations were found between the severity of candidiasis and individual nutritional parameters. Conclusions: These findings suggest that even moderate deficiencies in essential nutrients may increase susceptibility to oral fungal infections, although they may not directly influence disease severity. Full article

Background: Iron metabolism has emerged as a critical factor in cancer biology, with elevated intracellular iron levels contributing to increased oxidative stress and tumorigenesis. However, the molecular determinants governing ferroptosis sensitivity remain incompletely understood. Triosephosphate isomerase 1 (TPI1), a key glycolytic enzyme, has been implicated in cancer progression, but its role in ferroptosis regulation, particularly in the context of chemoresistance, is largely unexplored. In this study, we investigated the impact of TPI1 silencing on ferroptosis in cisplatin-resistant oral squamous cell carcinoma (OSCC), aiming to elucidate its mechanistic role and therapeutic potential. Methods: We conducted in vitro and in vivo analyses to evaluate the functional consequences of TPI1 knockdown in cisplatin-resistant OSCC cell lines and tumor xenograft models. The effects of TPI1 silencing and/or cisplatin treatment were assessed with respect to cell proliferation, migration, and invasion, along with ferroptosis-associated markers, including lipid ROS, free iron levels, lipid peroxidation, and the expression of key ferroptosis-related genes. Additionally, we analyzed the clinical relevance of TPI1 expression in human OSCC tissue samples, examining its association with clinicopathological features and patient prognosis. Results: TPI1 was found to be significantly upregulated in both OSCC tissues and cell lines, and high TPI1 expression correlated with poor clinical outcomes. Multivariate analysis identified TPI1 as an independent prognostic factor for tumor progression. Functionally, TPI1 knockdown suppressed OSCC cell proliferation, migration, and invasion, while its overexpression enhanced these oncogenic behaviors. Mechanistically, silencing TPI1 led to increased intracellular ROS accumulation, elevated free iron, and enhanced lipid peroxidation, collectively promoting ferroptotic cell death in cisplatin-resistant OSCC cells. In vivo, TPI1 depletion resulted in marked tumor growth inhibition and synergized with cisplatin to further suppress tumor burden in xenograft models. Moreover, TPI1 silencing disrupted the epithelial–mesenchymal transition (EMT), a key driver of cancer metastasis and drug resistance. Conclusions: Our study reveals a previously unrecognized role of TPI1 in protecting oral cancer cells from ferroptosis, especially in the setting of cisplatin resistance. These findings suggest that TPI1 not only contributes to tumor aggressiveness but also mediates resistance to ferroptosis. Targeting TPI1 may therefore represent a promising therapeutic strategy to overcome chemoresistance and enhance ferroptosis-based therapies in oral cancer. Full article

Background: Previous attempts to treat oral potentially malignant disorders OPMDs) effectively have failed. Longitudinal studies investigating the effects of comorbid diseases improvement on OPMDs are not yet available. Therefore, the current study examined the effects of comorbid disease improvement on OPMDs healing, both in oral lichen planus (OLP) and oral leukoplakia (OL) patients. Methods: The data from 197 consecutive patients (144 females and 53 males, age ± SD: 55.19 ± 12.37 years, with ages ranging from 23 to 91 years), with oral lesions considered OLP and OL, were processed and evaluated. The frequency of comorbid diseases and the presence of HPV (here, subtypes were not evaluated) in the lesions in OLP and OL patient groups were evaluated and compared to the results of controls (n = 139). Risk models for OLP and OL lesions were established. High-risk models for erosive–atrophic OLP and non-homogeneous OLP were also described. The influence of comorbid disease improvement was also evaluated. Lesions were scored at the first and last visit (full recovery = 0, improvement = 1, and no improvement = 2). Results: One hundred and ninety-seven patients (144 OLP + 53 OL) were followed up for an average of 47.66 months (min–max: 1–203 months, SD: 54.19). Based on the established models, HPV infection, iron deficiency, diabetes, and thyroid function disorders seem to act as risk factors for OLP and may also affect OL formation. The improvement in comorbid diseases can cause significant improvement in OLP and OL lesions. Conclusions: By meticulous follow-up of comorbid diseases, improvement in OLP and OL lesions can be achieved. Full article

Background/Objectives: Iron deficiency anemia in pregnancy poses risks to mothers and infants. This study aimed to correlate maternal iron indices in the second trimester with cord blood indices and pregnancy outcomes. Methods: This prospective cohort study was nested within the RAPIDIRON Trial (Reducing Anaemia in Pregnancy in India) at Jawaharlal Nehru Medical College, Karnataka, India. A total of 292 pregnant women with moderate anemia who received oral iron supplementation were enrolled from April 2021 to May 2023. Maternal iron indices were measured at multiple time points and correlated with cord blood indices and pregnancy outcomes. Results: Increased hemoglobin levels were observed in mothers of preterm and term neonates from 8.92 ± 0.81 vs. 9.02 ± 0.77 g/dL at 12–16 weeks to 11.14 ± 1.31 vs. 10.73 ± 1.24 g/dL at 26–30 weeks. A similar trend was observed in mothers across birth weight groups. Ferritin and TSAT levels significantly increased in all outcome groups (p < 0.001), peaking at 20–24 weeks and then slightly declining at 26–30 weeks. Additionally, maternal sTfR levels significantly improved from the early (7.72 ± 1.33 vs. 7.51 ± 1.61) to late second trimester (5.87 ± 0.81 vs. 5.76 ± 1.11) in mothers of both anemic and non-anemic neonates (p < 0.001). Maternal sTfR in other outcome groups also showed a similar pattern. A negligible correlation was found between maternal and cord blood iron indices. Conclusions: Maternal iron indices increased from the early to mid-second trimester, followed by a slight fall in the late second trimester. Notably, higher iron indices were observed in mothers of preterm and low-birth-weight neonates. Full article

Background/Objectives: Iron deficiency anemia is a prevalent hematological condition globally, with treatment often complicated by adverse effects that compromise patient adherence and clinical outcomes. This study investigated the prevalence, severity, and management of side effects associated with anemia treatments among Romanian patients, aiming to identify key factors influencing treatment adherence and patient satisfaction. Methods: A prospective observational cross-sectional study was conducted using a questionnaire distributed to adult patients diagnosed with anemia. Data were collected from 382 participants, covering demographic variables, anemia causes, treatment types, and patient-reported side effects. Results: Of the participants, 45% reported side effects, with a higher prevalence in intravenous (52%) than oral administration (48%). Common side effects included gastrointestinal symptoms (nausea/vomiting, heartburn, abdominal pain) and systemic symptoms (fatigue, headaches). Our analysis revealed that as the patient age increased, the severity of treatment-related side effects also intensified (p < 0.01), particularly in gastrointestinal discomfort. Similarly, BMI was a significant predictor (p < 0.05), suggesting that metabolic factors play a role in symptom manifestation. Notably, severe side effects were significantly associated with treatment modifications and lower patient satisfaction. Supplements like magnesium and vitamin D3 showed positive effects in mitigating the side effects, whereas probiotics and vitamin C had mixed outcomes. Conclusions: The study highlights the significant burden of side effects in anemia treatment, emphasizing the need for personalized management strategies to improve adherence and clinical outcomes. Full article

Iron deficiency (ID) is a common comorbidity in heart failure (HF), affecting nearly 50% of patients and worsening symptoms, exercise capacity, and prognosis. This review summarizes recent evidence from meta-analyses, clinical trials, and guidelines on the pathophysiology, diagnosis, and treatment of ID in HF. ID in HF results from chronic inflammation, intestinal congestion, and impaired iron metabolism. Diagnosis is based on serum ferritin and transferrin saturation (TSAT) levels. While oral iron therapy has limited efficacy, intravenous iron, particularly ferric carboxymaltose and ferric derisomaltose, improves symptoms and exercise tolerance and reduces hospitalizations. Timely diagnosis and treatment of ID in HF are essential. Intravenous iron is the preferred therapeutic approach, but further research is needed to optimize long-term management. Full article