Search Results (333)

Anemia is a major global public health problem and is most commonly associated with iron deficiency; however, deficiencies in other micronutrients, including vitamin B₁₂, may also contribute to its development. Increasing evidence suggests that Helicobacter pylori infection may influence the occurrence of anemia through several mechanisms related to alterations in the gastric environment. Chronic gastric inflammation and increased gastric pH associated with H. pylori infection may impair the absorption of non-heme iron and reduce the concentration of vitamin C in gastric juice. Since vitamin C enhances iron bioavailability by reducing ferric iron (Fe³⁺) to the more absorbable ferrous form (Fe²⁺), decreased levels of this vitamin may further limit iron absorption. At the same time, the increase in gastric pH may hinder the release of vitamin B₁₂ from food proteins, potentially contributing to disturbances in its absorption. This review aimed to present an integrated overview of the relationships between H. pylori infection, alterations in the gastric environment, and mechanisms that may contribute to the development of anemia, including disturbances in vitamin B₁₂ absorption, with particular emphasis on the potential role of vitamin C. Full article

Background/Objectives: VEXAS (Vacuoles, E1-Enzyme, X-linked, Autoinflammatory, and Somatic) syndrome is a recently described adult-onset autoinflammatory disorder. It is characterized by somatic mutations in the UBA1 gene, systemic inflammation, macrocytic anemia, cytopenias, and bone marrow vacuolization and frequently overlaps with Sweet’s syndrome, relapsing polychondritis, and myelodysplastic syndrome (MDS). Because treatment options are evolving, we reviewed the current and latest evidence of clinical features and therapeutic methods. Methods: A comprehensive literature review was conducted using PubMed and MEDLINE for studies published between 1 January 2020 and 1 July 2025. Search terms included “VEXAS” and “treatment.” Eligible publications comprised clinical trials, multicenter and observational studies, and case reports containing therapeutic data. Findings were analyzed narratively with emphasis on treatment response, steroid-sparing effects, survival outcomes, and molecular responses. Results: Glucocorticoids remain the first-line therapy for acute management; however, this comes with near-universal steroid dependence. DMARDs and TNF-α inhibitors showed limited benefits. IL-6 inhibitors and JAK inhibitors showed improvement in overall response, with JAK inhibitors demonstrating a superior effect. Ruxolitinib showed a higher complete response rate and transfusion independence compared to other JAK inhibitors. Hypomethylating agents, particularly azacitidine, improved hematologic responses in patients with co-existing MDS and reduced UBA1 variant allele burden. Allogeneic hematopoietic stem cell transplantation may be the only current curative method, though with notable transplant-related mortality. Conclusions: JAK inhibitors and hypomethylating agents offer promising disease-modifying potential, while transplant may provide curative intent in selected patients. Ongoing clinical trials are taking place to dictate the treatment direction of VEXAS syndrome. Full article

Sickle cell anemia (SCA) is a genetic disorder characterized by chronic hemolysis, primarily driven by red blood cell lysis. Its pathophysiology is centered, though not exclusively, on the increased release of intracellular components, such as hemoglobin degradation products, which are known to stimulate innate immune responses and promote prothrombotic states. Current therapies alleviate symptoms, yet patients remain exposed to a chronic inflammatory milieu punctuated by episodes of acute pain. The recurrence of these crises can be life-threatening due to ischemia–reperfusion injury, hypercoagulability, and respiratory complications. Central mechanisms are marked by elevated hemolysis, heightened inflammatory signaling, and increased procoagulant activity, largely driven by soluble molecules released into the plasma, such as hemoglobin, nuclear molecules and other products. These compounds are recognized from sensors on immune and endothelial cells, named Pattern Recognition Receptors (PRRs), and constitute canonical pathways for intracellular activation. Four main types have been extensively studied in the literature over recent years in both infectious and sterile inflammatory contexts; still, only a few have elucidated the mechanisms underlying acute and chronic inflammation in patients with SCA. Although Toll receptors were shown to be major in triggering immunity, other receptors were found to be important regarding this function, which suggested a multifactorial mechanism for this triggering. Therefore, here, we propose a comprehensive review of previously published findings regarding the expression, activation, and dynamics of Toll-like, NOD-like, and RIG-I–like receptors in the progression of SCA and its associated inflammatory features. Full article

Background: Influenza is a common cause of hospitalization in young children, particularly infants. While most infections are self-limited, severe and life-threatening complications may occur. Diffuse alveolar hemorrhage (DAH) is a rare pulmonary manifestation of influenza, predominantly reported in adults, and is exceedingly uncommon in immunocompetent infants. Case Presentation: We report the case of an 8-month-old previously healthy female infant who presented with influenza A infection and rapidly progressed to acute respiratory failure and shock despite antiviral therapy. Bleeding was noted from the nasal cavity prior to clinical deterioration, and during emergent endotracheal intubation, blood was observed flooding the bronchial tree, consistent with massive pulmonary hemorrhage. Flexible bronchoscopy showed diffusely erythematous and friable airway mucosa without an identifiable focal bleeding source, and early bronchoalveolar lavage was nondiagnostic. Nasopharyngeal testing confirmed influenza A (H3). Laboratory findings revealed severe systemic inflammation, leukopenia with neutropenia, and anemia with normal coagulation parameters. Chest imaging demonstrated bilateral pulmonary infiltrates. After exclusion of autoimmune, coagulation, immunodeficiency, and alternative infectious causes, a diagnosis of diffuse alveolar hemorrhage secondary to influenza A infection was established. The patient was successfully managed with supportive care, antiviral therapy, tranexamic acid, and empiric antibiotics, without corticosteroid treatment, and made a full recovery. Conclusions: This case emphasizes that influenza-associated DAH in infants may occur without overt hemoptysis and may not demonstrate classical BAL findings early in the disease course. Clinicians should maintain a high index of suspicion in rapidly deteriorating infants with influenza and diffuse pulmonary infiltrates. The optimal role of corticosteroids remains uncertain and should be individualized. Full article

Objective: The purpose of this study was to determine the biological association between host-derived HSP47 and fungal-derived HSP90 in the context of vulvovaginal candidiasis (VVC) and to examine their relationships with clinical, inflammatory, and metabolic phenotypes in infected and healthy women. Methods: This study followed a six-month case–control design (February–July 2025) and was conducted at the University of Tabuk Hospital in Tabuk, Saudi Arabia. A total of 84 women aged 18–45 years were recruited, of which 42 were VVC-infected, and 42 were healthy controls. ELISA kits were used to test vaginal swabs for HSP47 and HSP90. Clinical, hematological, cytokine, and metabolic markers were also evaluated. Mann–Whitney U, Spearman correlation, and multiple linear regression tests were performed to analyze the data. Results: The levels of HSP47 and HSP90 were significantly higher among infected patients (2.29 ng/mL and 3341 ng/mL, respectively) when compared with controls (0.58 ng/mL and 1025.7 ng/mL; p < 0.001). Women who were infected were older (p = 0.02), but there were no significant differences in terms of BMI (p = 0.29). The levels of vitamin D and adiponectin were significantly decreased (p < 0.001), while pro-inflammatory cytokines (IL-6, TNF-α, IFN-γ, TGF-β, and IL-8) and WBC counts were higher compared to the control group. The hematology results were characterized by inflammation-related anemia and disturbed protein metabolism. The ROC analysis demonstrated good diagnostic performance, with an AUC of 1.0 in the case of HSP47 and 0.905 in the case of HSP90. In the case of the infected patients, the regression models were found to be weak (HSP90 R² = 0.154; HSP47 R² = 0.273), although HSP47 retained significant connections with IL-8 (p = 0.005) and IFN-γ (p = 0.028). Conclusions: High levels of HSP47 and HSP90 are observed in VVC, reflecting an epithelial stress response and fungal persistence. These HSPs have high diagnostic accuracy, which justifies their potential as biomarkers for the timely detection of VVC; they also have further implications as early biomarkers for prognostic and treatment monitoring support, despite the poor predictive models. This study has some limitations that must be addressed; in particular, the regression analyses failed to provide statistically significant predictive models, likely due to the limited sample size. In addition, the specificity of HSP90 and HSP47 for VVC in comparison with other vaginal infections was not evaluated. Full article

Background/Objectives: Iron deficiency (ID) is a critical comorbidity in chronic heart failure (CHF) that impairs myocardial energy metabolism and clinical outcomes. Despite its significance, data regarding ID prevalence in Southeast Asian CHF populations remain insufficient. This study aimed to determine the prevalence of ID and identify its independent clinical correlates among CHF patients at a leading tertiary hospital in Vietnam using high-precision automated diagnostic platforms. Methods: A descriptive cross-sectional study was conducted on 138 adult CHF patients. Serum iron and ferritin were quantified using photometric and electrochemiluminescence immunoassay (ECLIA) methods on cobas c702 and e602 systems. ID was defined according to 2021 ESC guidelines (ferritin < 100 ng/mL or ferritin 100–299 ng/mL with TSAT < 20%). Multivariable logistic regression identified independent factors associated with ID. Results: The overall ID prevalence was 75.4%, consisting of functional (39.9%) and absolute ID (35.5%). A significant gender disparity was observed (p = 0.0326): absolute ID was more prevalent in females (44.4%), while functional ID predominated in males (47.4%). Multivariable analysis revealed that NT-proBNP (aOR = 2.29; 95% CI: 1.13–4.66; p = 0.021) and C-reactive protein (aOR = 2.17; 95% CI: 1.07–4.43; p = 0.031) were independent correlates of ID status. The association with anemia was borderline non-significant (p = 0.055). Conclusions: ID is nearly ubiquitous among Vietnamese CHF patients in this tertiary setting, driven by hemodynamic severity and systemic inflammation. These findings advocate for integrating routine iron status screening into the standard diagnostic workup for all CHF patients, regardless of hemoglobin levels. Full article

Background and Objectives: Red cell distribution width (RDW) has been associated with adverse cardiometabolic outcomes; however, whether RDW—particularly RDW standard deviation (RDW-SD)—represents an independent determinant of metabolic syndrome (MetS) or reflects cumulative metabolic burden remains unclear. This study evaluated the association between RDW-SD and MetS presence and examined its relationship with the quantitative accumulation of MetS components. Materials and Methods: In this single-center observational study, 222 adults undergoing evaluation for MetS were consecutively recruited. Participants with overt anemia, extreme mean corpuscular volume values, or acute inflammation were excluded. MetS was defined according to revised NCEP ATP-III criteria. Associations between RDW-SD and MetS were assessed using hierarchical multivariable logistic regression models. The relationship between RDW-SD and the number of MetS components was examined using multivariable linear regression. Discriminative performance was evaluated by receiver operating characteristic (ROC) curve analysis. Results: MetS was present in 68.0% of participants. RDW-SD levels were significantly higher in individuals with MetS and increased progressively across quartiles. RDW-SD was independently associated with the number of MetS components (standardized β = 0.226, p < 0.001). However, RDW-SD was not independently associated with MetS presence in fully adjusted logistic models (OR = 1.07, 95% CI: 0.97–1.18, p = 0.198). The addition of RDW-SD provided minimal incremental explanatory value (Nagelkerke R² increase from 0.348 to 0.356). ROC analysis demonstrated poor discriminatory ability (area under the curve [AUC] = 0.611, 95% CI: 0.535–0.687), supporting limited standalone diagnostic utility. Conclusions: RDW-SD was independently associated with cumulative metabolic burden but not with the independent presence of MetS after adjustment for established cardiometabolic factors. Given the cross-sectional design, these findings should be interpreted as associative rather than causal. Full article

Background: Obesity is commonly seen as a condition of overnutrition; however, it is paradoxically associated with micronutrient deficiencies. These deficiencies are clinically relevant and may contribute to the progression of obesity-related comorbidities through interconnected pathways, including chronic low-grade inflammation, oxidative stress, gut dysbiosis, and impaired nutrient absorption. Objectives: This narrative review aims to summarize current evidence regarding the prevalence, underlying mechanisms, and clinical consequences of micronutrient deficiencies in individuals with obesity, with particular emphasis on their metabolic implications and potential therapeutic strategies. Results: Among individuals with obesity, iron, zinc, magnesium, calcium, vitamin D, vitamin B12, and folate are the most frequently reported deficiencies. These deficiencies arise from multiple mechanisms, including poor diet quality, increased metabolic demands, and compromised gastrointestinal absorption. In addition, obesity-related alterations in pharmacokinetics may further interfere with micronutrient distribution and bioavailability. Together, these mechanisms may lead to various clinical outcomes, such as anemia, immune, metabolic, and cardiovascular dysfunctions, along with cognitive impairment. Although several studies suggest that correcting these deficiencies may improve clinical outcomes, findings remain inconsistent, highlighting the complex and multifactorial pathophysiology underlying micronutrient imbalance in obesity. Conclusions: Micronutrient deficiencies represent frequently overlooked contributors to metabolic dysregulation in obesity. Their identification and correction should be considered a central part of the obesity management strategy. A personalized supplementation approach, based on clinical, biological, and pathophysiological characteristics, may provide a complementary support for weight-management treatments. Full article

Background: Chronic critical illness (CCI) affects ~7.6% of ICU patients worldwide and is associated with poor outcomes, including 25% in-hospital and 50% one-year mortality. A proposed key mechanism is the inflammation-immunosuppression-catabolism (ICS) triad, which contributes to multiple organ failure and independently increases mortality. Although early identification of ICS could improve risk stratification, no clinically applicable predictive tool currently exists. This study aimed to develop and validate a prognostic nomogram to predict ICS development in ICU (Intensive Care Unit) patients. Methods: This real-world analysis used electronic health records from the Russian Intensive Care Dataset (RICD). ICS was defined as C-reactive protein > 20 mg/L, albumin < 30 g/L, and lymphocyte count < 0.8 × 10⁹/L. Variables with >30% missing data were excluded, and remaining missing values were handled by multiple imputation. A Cox proportional hazards model was used to construct the nomogram. Internal validation was performed using an 8:2 training–validation split. Results: Among 1963 eligible patients, 540 (27.5%) developed ICS. LASSO (Least Absolute Shrinkage and Selection Operator) regression identified nine significant predictors: age, body mass index, SOFA (Sequential Organ Failure Assessment) and FOUR (Full Outline of UnResponsiveness) scores at admission, pneumonia and anemia at admission, platelet count, total protein, and creatinine. The nomogram showed good discrimination, with C-indices of 0.763 (95% CI: 0.741–0.783) in the training set and 0.735 (95% CI: 0.689–0.784) in the validation set. At the optimal cutoff, sensitivity was 0.75, specificity was 0.63, positive predictive value was 0.43, and negative predictive value was 0.87. Conclusions: This study presents the first nomogram for predicting ICS in ICU patients, using nine admission variables to reliably identify low-risk individuals. Further external validation is required. Full article

Background: In metastatic colorectal cancer (mCRC), systemic inflammation and routine laboratory parameters may reflect host–tumor interactions and provide additional prognostic information. This study evaluated the association between baseline clinicopathological and laboratory parameters, including the derived neutrophil-to-lymphocyte ratio (dNLR), and overall survival (OS) in patients with stage IV colorectal adenocarcinoma. Methods: We conducted a retrospective cohort study including 92 patients diagnosed with metastatic colorectal adenocarcinoma and treated at a single oncology center between February 2022 and December 2024. Baseline laboratory parameters were collected at diagnosis. Survival was analyzed using Kaplan–Meier estimates with log-rank testing. Prognostic associations were evaluated using univariable and multivariable Cox proportional hazards regression models adjusted for relevant clinical and treatment-related factors. Results: The cohort was predominantly male (62%) and younger than 70 years (66%), with 80 deaths recorded during follow-up. In univariable analyses, primary tumor resection, irinotecan-based first-line therapy, elevated AST, and dNLR tertiles were associated with OS. However, after multivariable adjustment, only irinotecan-based first-line therapy remained independently associated with poorer survival (HR 2.10, 95% CI 1.16–3.81; p = 0.022). Continuous dNLR, anemia (WHO sex-specific), and AST elevation did not retain independent prognostic significance. Conclusions: In this cohort of patients with mCRC, inflammation-related laboratory markers demonstrated associations with survival in unadjusted analyses but did not remain independent predictors after adjustment for clinical and treatment-related confounders. These findings highlight the importance of rigorous multivariable modeling when evaluating inflammatory biomarkers in metastatic colorectal cancer. Full article

Background/Objectives: Iron deficiency anemia (IDA) is a widespread nutritional disorder characterized by impaired iron absorption, inflammation-associated iron restriction, and disrupted iron homeostasis. Increasing evidence suggests that gut microbiota play an important role in iron metabolism; however, the mechanisms underlying probiotic-assisted iron supplementation remain unclear. Our research group previously conducted in vitro fermentation screening experiments and obtained a bacterial strain, B. lactis Ca360, which possesses iron absorption-enhancing activity. Methods: In this study, an IDA mouse model induced by a low-iron diet was used to investigate whether B. lactis Ca360 could synergistically improve iron metabolism when combined with iron supplementation. Mice were treated with FeSO₄ alone or FeSO₄ combined with B. lactis Ca360, and hematological parameters, organ indices, serum iron-related markers, histopathological changes, duodenal iron metabolism-related gene expression, hepatic inflammatory responses, gut microbiota composition, short-chain fatty acid (SCFA) levels, and correlation networks were analyzed. Results: Iron deficiency induced typical anemia phenotypes, multi-organ dysfunction, intestinal iron absorption dysregulation, hepatic inflammation, and gut microbiota dysbiosis. Compared with FeSO₄ alone, the combined intervention more effectively improved hematological parameters, reduced organ indices, restored liver and spleen histological integrity, normalized intestinal iron metabolism-related gene expression, and alleviated hepatic inflammation. In addition, B. lactis Ca360 markedly reshaped gut microbiota composition, enriching SCFA-producing anaerobic genera, including Ruminococcus, Roseburia, Acetatifactor, Intestinimonas, Eubacterium_coprostanoligenes_group_unclassified, and Oscillibacter, accompanied by increased acetate, propionate, and butyrate levels. Spearman correlation analysis further revealed close associations between gut microbiota remodeling, improved iron metabolism, reduced inflammatory status, and recovery of anemia-related phenotypes. Conclusions: Overall, these findings demonstrate that B. lactis Ca360 enhances the efficacy of iron supplementation by modulating SCFA-producing and anti-inflammatory gut microbiota, thereby coordinately regulating intestinal iron absorption, inflammation, and systemic iron homeostasis, supporting probiotic-assisted iron supplementation as a promising nutritional strategy for IDA management. Full article

Background/Objectives: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and remains incurable in approximately 30–40% of patients despite advances in immunochemotherapy. Although gene expression profiling has improved risk stratification, there is an ongoing need for non-invasive, cost-effective, and clinically practical biomarkers to identify patients at high risk of treatment resistance or relapse (R/R). Systemic inflammation plays a pivotal role in DLBCL pathogenesis, impacting both tumor progression and treatment response. The C-reactive protein–albumin–lymphocyte (CALLY) index, integrating markers of inflammation, nutritional status, and immune competence, has demonstrated prognostic relevance in solid tumors; however, its relevance in hematologic malignancies remains unexplored. Methods: We retrospectively analyzed 180 adults with newly diagnosed DLBCL, NOS (not otherwise specified) who received frontline rituximab-based immunochemotherapy (R-CHOP or CHOP-like regimens) between January 2014 and December 2019 at three tertiary centers in Serbia. The median age was 67 years (IQR 59–73), and 56.1% were female. Receiver operating characteristic (ROC) analysis determined 6.5 as the optimal CALLY index cut-off (AUC 0.744, 95% CI 0.670–0.817; p < 0.001). Results: A low CALLY index (<6.5) was significantly associated with adverse clinical features, including anemia, elevated lactate dehydrogenase and β2-microglobulin, poor ECOG performance status, bulky disease, advanced stage, and unfavorable IPI, R-IPI, and NCCN-IPI scores (all p < 0.001). In contrast, no associations were observed with tumor subtype, immunophenotype, or comorbidities. Furthermore, patients with CALLY <6.5 showed lower overall response rates to treatment (59.6% vs. 85.5%, p < 0.001) and higher relapse rates (21.0% vs. 6.2%, p = 0.014). They also experienced reduced 3- and 5-year overall survival (OS) and event-free survival (EFS) (all p < 0.001). In multivariate analysis, a low CALLY index independently predicted poorer OS (HR 2.04, 95% CI 1.13–3.67; p = 0.017) and EFS (HR 1.89, 95% CI 1.13–3.14; p = 0.015). In addition, it independently identified patients at risk of relapsed/refractory (R/R) disease (OR 2.50, 95% CI 1.02–10.10; p = 0.04), outperforming standard prognostic indices. Conclusions: The CALLY index is a simple, low-cost, and widely accessible biomarker that independently predicts prognosis in DLBCL, NOS. It outperforms standard indices in identifying R/R cases. The CALLY index may enhance risk stratification and guide individualized treatment strategies. Full article

Background: Patients undergoing hemodialysis commonly exhibit deficiencies in water-soluble vitamins, primarily as a result of inadequate dietary intake and loss into the dialysate. Given the essential role of vitamin C in numerous metabolic pathways, routine supplementation has been proposed as a potentially beneficial intervention in this population. Aim: We aimed to evaluate the current evidence on vitamin C supplementation in patients undergoing hemodialysis, with particular attention to clinical conditions associated with renal replacement therapy, including anemia, chronic inflammation, restless legs syndrome (RLS), and secondary hyperparathyroidism. Methods: This systematic review was conducted in accordance with PRISMA guidelines. The MEDLINE (via PubMed) and EMBASE databases were searched. The initial search yielded 844 articles, of which 37 studies met the inclusion criteria for this review. Results: Evidence indicates that hemodialysis patients exhibit vitamin C deficiency, both in dietary intake and in plasma or serum concentrations. Despite its intrinsic antioxidant properties and proposed anti-inflammatory effects, vitamin C supplementation has demonstrated inconsistent effects on inflammatory markers. Most clinical studies support a beneficial role of vitamin C supplementation in functional iron deficiency and in alleviating symptoms of RLS within this population. Conclusions: Evidence on vitamin C supplementation for functional iron deficiency and RLS suggests that it might be an effective therapeutic approach. However, despite low serum vitamin C level in hemodialysis patients, current data does not justify the routine use of vitamin C in the hemodialyzed population for other comorbidities, including chronic inflammation and secondary hyperparathyroidism. Further high-quality studies are required to establish the broader clinical utility of targeted vitamin C supplementation. Full article

Background: The population of elderly patients undergoing chronic hemodialysis is increasing, and anemia represents a frequent complication. The aim of our study was to evaluate the association between ultrafiltration rate (UFR) in hemodialysis and erythropoietin (EPO) response in elderly patients with end-stage kidney disease (ESKD). Methods: This was a multicenter, retrospective observational study, involving elderly patients (aged 65 years or more) under chronic hemodialysis therapy. Individuals were divided into two groups according to the UFR adjusted to weight (UFR/W): lower (UFR-N) or higher (UFR-H) than 10 mL/h/kg. EPO resistance index (ERI) was calculated. We evaluated the hemogram, reticulocyte count, and quantified markers of iron metabolism and inflammation. Results: A total of 193 patients were enrolled in the study: 141 patients met criteria for inclusion in UFR-N group and 52 in UFR-H group. Compared to UFR-N, patients in the UFR-H group presented significantly higher doses of erythropoiesis-stimulating agents (ESA) and ERI values, with similar hemoglobin (Hb) and inflammatory markers levels. In a sub-analysis, within patients presenting transferrin saturation (TSAT) lower than 20%, a more marked difference in ERI between UFR groups was observed, being much higher in UFR-H compared with UFR-N. In this subgroup (UFR-H with lower TSAT), levels of hepcidin were lower than in the other subgroups. Conclusions: Our data show that UFR appears to be a contributing factor of ESA response in elderly patients under hemodialysis, particularly in those with lower iron availability. These findings suggest that inadequate weight control and/or UF prescription seem to aggravate ESA needs to achieve target Hb. Full article