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Iron deficiency and iron deficiency anaemia are common in inflammatory bowel disease (IBD), to the detriment of the patients' quality of life. Since ferritin, as an acute-phase protein (APP), has limited diagnostic value in IBD, concurrent assessment of C-reactive protein (CRP) is recommended. The World Health Organization suggests using α1-acid glycoprotein (AGP) as an additional biomarker due to its differing half-life. This study aimed to evaluate ferritin levels in patients with IBD using CRP and AGP, individually and in combination. A total of 118 patients with IBD (mean age: 45.48 ± 15.25 years, 47.46% female) were recruited, including 38 with Crohn's disease, 47 with ulcerative colitis, and 33 controls. The results showed that while CRP alone detected an inflammatory increase in ferritin of 29.76%, this increased to 82.14% when AGP or both AGP and CRP were considered (p < 0.05). Elevated AGP levels were more prevalent in patients with ulcerative colitis. However, concordance between high CRP and AGP levels was confirmed in only 55% of cases. Correcting for inflammation using CRP and/or AGP significantly improved the diagnostic accuracy of ferritin levels in patients with IBD, highlighting the challenge posed by inflammation when assessing iron deficiency.
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INTRODUCTION: Obesity is associated with reduced life expectancy and various comorbidities. Surgical interventions are effective but accompanied by risk of serious complications. Less invasive endoscopic procedures mainly comprise the intragastric balloon (IB) and the duodenal-jejunal bypass liner (DJBL). A randomized, sham-controlled study comparing both procedures has not been undertaken so far. METHODS: We performed a randomized, patient- and assessor-blinded, controlled trial comparing weight loss in IB vs. DJBL vs. a sham procedure (2:2:1 ratio). Patients with a BMI > 35 kg/m2 or > 30 with obesity-related comorbidities were included. The IB was removed after 6 months and the DJBL after 12 months. Main objective was successful weight loss (>10% from baseline) 12 months after explantation of the devices. Secondary outcomes were changes in comorbidities, quality of life and complications. RESULTS: 33 patients were randomized. Recruitment has to be stopped suddenly in after the DJBL device lost its CE mark in Europe. 11 patients received DJBL, 15 IB and 7 were allocated to sham group. Blinding was feasible in all patients. Weight decreased from baseline until explantation (DJBL: 129.4±28.3kg to 107.4±16.7kg; IB: 118.3±22.8kg to 107.4±25.7kg; sham: 134.6±18.0kg to 131.2±14.3kg) but patients regained weight almost to baseline level 12 months after explantation. Only one patient in IB group reached the primary endpoint. Severe device-related complications were very rare. CONCLUSION: Endoscopic bariatric procedures failed to achieve effective weight loss 12 months after explantation of the devices. The results of this trial need to be interpreted with caution due to its early termination.
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BACKGROUND: This real-world analysis evaluated iron therapy supplementation in inflammatory bowel disease patients with iron-deficiency anemia, considering disease progression and healthcare resource consumption. METHODS: A retrospective observational study was conducted using administrative databases of a pool of Italian healthcare entities, covering about 9.3 million beneficiaries. Between January 2010 and September 2017, adult patients were enrolled in the presence of either hospitalization or active exemption code for ulcerative colitis/Crohn's disease, or one vedolizumab prescription. Iron-deficiency anemia was identified by at least one prescription for iron and/or hospitalization for iron-deficiency anemia and/or blood transfusion (proxy of diagnosis). Patients were divided in untreated and iron-treated during 12-month follow-up and analyzed before and after propensity score matching. Disease progression, was evaluated through inflammatory bowel disease-related hospitalizations and surgeries, and healthcare resource utilization was assessed. RESULTS: Overall, 1753 patients were included, 1077 (61.4%) treated with iron therapy and 676 (38.6%) untreated. After propensity score matching, 655 patients were included in each group. In unbalanced cohorts, disease progression was significantly reduced in patients receiving iron therapy compared to the untreated (11.0% vs. 15.7%, P â <â 0.01), and this trend was maintained also after applying propensity score matching. The overall mean cost/patient was significantly lower in iron-treated than untreated (4643 vs. 6391, P â <â 0.01). CONCLUSION: The findings of this real-world analysis suggest that iron therapy was associated with significant benefits in inflammatory bowel disease patients with iron-deficiency anemia, in terms of both disease progression and healthcare resource utilization.
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Anemia Ferropriva , Colite Ulcerativa , Doenças Inflamatórias Intestinais , Adulto , Humanos , Anemia Ferropriva/diagnóstico , Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/epidemiologia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Colite Ulcerativa/complicações , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Ferro/uso terapêutico , Progressão da Doença , Suplementos NutricionaisRESUMO
Background: Iron deficiency anemia (IDA) is a common extraintestinal manifestation of inflammatory bowel disease (IBD), affecting around one-third of patients. Objective: To compare IBD progression and healthcare resource utilization in patients with and without a co-diagnosis of IDA in a real-world setting. Design: A retrospective comparative study was conducted using Italian entities' administrative databases, covering 9.3 million health-assisted individuals. Methods: Adult IBD patients diagnosed with ulcerative colitis and/or Crohn's disease were enrolled between January 2010 and September 2017. Within 12 months from IBD diagnosis, IDA was identified by at least one prescription for iron and/or IDA hospitalization and/or blood transfusion (proxy of diagnosis). IBD population was divided according to the presence/absence of IDA. Given the nonrandom patients' allocation, propensity score matching (PSM) was applied to abate potential unbalances between the groups. Before and after PSM, IBD progression (in terms of IBD-related hospitalizations and surgeries), and healthcare resource costs were assessed. Results: Overall, 13,475 IBD patients were included, with an average age at diagnosis of 49.9 years, and a 53.9% percentage of male gender. Before PSM, 1753 (13%) patients were IBD-IDA, and 11,722 (87%) were IBD-non-IDA. Post-PSM, 1753 IBD-IDA patients were matched with 3506 IBD-non-IDA. Before PSM, IBD progression was significantly higher in IBD-IDA (12.8%) than in IBD-non-IDA (6.5%) (p < 0.001). After PSM, IBD progression and IBD-related hospitalizations were significantly (p < 0.001) more frequent in IBD-IDA patients (12.8% and 12.0%, respectively) compared to IBD-non-IDA (8.7% and 7.7%). Consistently, healthcare expenditures resulted significantly higher among IDA patients (p < 0.001), with an overall mean annual cost of 5317 compared to 2798 for patients without IDA. These results were confirmed after PSM matching, as the mean annual total cost/patient in IBD-IDA versus IBD-non-IDA were 3693 and 3046, respectively (p < 0.001). Conclusion: In a real-life setting, IDA co-diagnosis in IBD patients was associated with disease progression and higher related economic burden.
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INTRODUCTION: Obesity is a major global health problem associated with comorbidities such as diabetes, cardiovascular disease, and cancer. Bariatric surgery is recognized to be the most effective weight loss intervention, but it is highly invasive and costly and can have serious side effects. Intragastric balloon (IGB) placement by endoscopy and hypocaloric diets are among a number of techniques that have been used in patients unsuitable for, or unwilling to undergo, obesity surgery. In this study, we compared the efficacy, safety, and cost-effectiveness of the hypocaloric OPTIFAST program (OPT) with endoscopic IGB placement for weight loss. METHODS: In this retrospective observational cohort propensity score-weighted comparison (performed May 2014 to December 2020), participants with a BMI of 30-55 kg/m2, aged 18-70 years, were randomized to OPT or IGB for 26 weeks, followed by a weight maintenance phase. Patients were matched according to age, gender, and BMI. The study outcomes were percentage excess body weight lost, total body weight lost (TBWL), and percentage TBWL (%TBWL). RESULTS: A total of 148 participants (75% of those randomized; 74 OPT, 74 IGB) made up the ITT population. Mean age was 44.1 ± 10.4 years, and the patients were predominantly female (77%). Baseline BMI was 44.1 ± 10.4 kg/m2. At 26 weeks, %TBWL in the OPT group was 19.6 ± 6.8% versus 11.9 ± 6.7% for IGB (p < 0.001). At 52 weeks, %TBWL for OPT was 18.2 ± 9.0% versus 12.0 ± 6.6% for IGB (p < 0.001). The OPT cohort also experienced significantly fewer adverse events compared with the IGB group. CONCLUSION: IGB placement and OPT induce clinically meaningful weight loss. However, OPT appears to induce clinically superior weight loss and has economic advantages through lower rates of complications and adverse events.
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Balão Gástrico , Obesidade Mórbida , Programas de Redução de Peso , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , Balão Gástrico/efeitos adversos , Pontuação de Propensão , Estudos Retrospectivos , Obesidade/cirurgia , Obesidade/etiologia , Aumento de Peso , Redução de Peso , Obesidade Mórbida/cirurgia , Resultado do TratamentoRESUMO
Iron deficiency is the primary cause of anaemia worldwide and is particularly common among children and adolescents. Intravenous (IV) iron therapy is recommended for paediatric patients with certain comorbidities or if oral iron treatment has been unsuccessful. IV ferric carboxymaltose (FCM) has recently been approved by the US Food and Drug Administration for use in children aged > 1 year. This narrative review provides an overview of the available publications on the efficacy and safety of IV FCM in children and adolescents. A literature search using PubMed and Embase yielded 153 publications; 33 contained clinical data or reports on clinical experience relating to IV FCM in subjects < 18 years of age and were included in the review. No prospective, randomised controlled studies on the topic were found. Most publications were retrospective studies or case reports and included patients with various underlying conditions or patients with inflammatory bowel disease. Efficacy data were included in 27/33 publications and improvements in anaemia, and/or iron status parameters were reported in 26 of them. Safety data were included in 25/33 publications and were in line with the adverse events described in the prescribing information. CONCLUSION: The available publications indicate that IV FCM, a nanomedicine with a unique and distinctive therapeutic profile, is an effective and generally well-tolerated treatment for iron deficiency or iron deficiency anaemia in children and adolescents. Despite the wealth of retrospective evidence, prospective, randomised controlled trials in the paediatric setting are still necessary. WHAT IS KNOWN: ⢠Iron deficiency and iron deficiency anaemia are usually managed using oral iron therapy, but intravenous iron therapy is recommended for certain paediatric patients. ⢠Intravenous ferric carboxymaltose (FCM) has recently been approved in the US for use in children aged > 1 year. WHAT IS NEW: ⢠Despite evidence that FCM is effective and generally well tolerated in children and adolescents, so far, only retrospective studies, non-randomised uncontrolled prospective studies, or case reports have been published in full. ⢠There is a strong need for prospective, randomised controlled trials on FCM in the paediatric setting.
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Anemia Ferropriva , Deficiências de Ferro , Administração Intravenosa , Adolescente , Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/etiologia , Criança , Compostos Férricos/efeitos adversos , Humanos , Ferro/uso terapêutico , Maltose/efeitos adversos , Maltose/análogos & derivados , Estudos Prospectivos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Transurethral resection of bladder tumor (TUR-BT) followed by chemoradiation (CRT) is a valid treatment option for patients with muscle-invasive bladder cancer (MIBC). This study aimed to investigate the efficacy of a tetramodal approach with additional regional hyperthermia (RHT). METHODS: Patients with stages T2-4 MIBC were recruited at two institutions. Treatment consisted of TUR-BT followed by radiotherapy at doses of 57-58.2 Gy with concurrent weekly platinum-based chemotherapy and weekly deep RHT (41-43 °C, 60 min) within two hours of radiotherapy. The primary endpoint was a complete response six weeks after the end of treatment. Further endpoints were cystectomy-free rate, progression-free survival (PFS), local recurrence-free survival (LRFS), overall survival (OS) and toxicity. Quality of life (QoL) was assessed at follow-up using the EORTC-QLQ-C30 and QLQ-BM30 questionnaires. Due to slow accrual, an interim analysis was performed after the first stage of the two-stage design. RESULTS: Altogether 27 patients were included in the first stage, of these 21 patients with a median age of 73 years were assessable. The complete response rate of evaluable patients six weeks after therapy was 93%. The 2-year cystectomy-free rate, PFS, LRFS and OS rates were 95%, 76%, 81% and 86%, respectively. Tetramodal treatment was well tolerated with acute and late G3-4 toxicities of 10% and 13%, respectively, and a tendency to improve symptom-related quality of life (QoL) one year after therapy. CONCLUSION: Tetramodal therapy of T2-T4 MIBC is promising with excellent local response, moderate toxicity and good QoL. This study deserves continuation into the second stage.
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Hipertermia Induzida , Neoplasias da Bexiga Urinária , Idoso , Terapia Combinada , Humanos , Músculos , Qualidade de Vida , Neoplasias da Bexiga Urinária/radioterapia , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
BACKGROUND AND AIMS: Severe obesity (BMI ≥60 kg/m2) in multimorbid patients can be acutely life-threatening. While emergency weight-loss surgery is urgently needed to preserve life, most patients are in an inoperable state. Pre-surgical bridging therapy is required to achieve technical operability through weight reduction. Standard bridging using an intragastric balloon (IB) can achieve operability in 6 months but is unsuitable for some patients in a critical condition. A non-invasive fast-track rescue therapy to achieve very rapid operability is urgently needed. We investigated whether a rescue weight reduction therapy (RWR) consisting of liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, a leucine-rich amino acid infusion and a hypocaloric diet, can accelerate readiness for emergency surgery in patients with acutely life-threatening severe obesity. METHODS: In this proof-of-concept study, prospective data from patients treated with RWR (intervention group 1, n = 26) were mathematically matched with retrospective biometric data of 26 patients with severe obesity (historic control group 2) who underwent standard 6-month bridging with IB. A rating scale was developed to identify patients needing urgent fast-track bridging. RESULTS: Rapid weight loss was observed in all patients on the RWR therapy. All achieved operability after a mean RWR bridging duration of 20.7 ± 6.9 days. Baseline weight was 236.3 ± 35.8 kg in group 1 compared with 230.1 ± 32.7 kg in group 2. Mean body weight loss during RWR was 27.5 ± 14.1 kg, compared with 20.9 ± 10.5 kg in group 2 (P = 0.0629). CONCLUSIONS: Pre-operative bridging using liraglutide in combination with a leucine-rich amino acid infusion and hypocaloric diet was effective in all cases of acutely life-threatening severe obesity, achieving technical operability within only ca. 2-4 weeks. This therapy has potential as a life-saving rescue therapy for multimorbid patients with severe obesity who were previously untreatable. This study is registered at ClinicalTrials.gov (identifier: NCT02616003).
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Cirurgia Bariátrica , Balão Gástrico , Obesidade Mórbida , Dieta Redutora , Humanos , Leucina , Liraglutida , Obesidade/cirurgia , Obesidade Mórbida/cirurgia , Estudo de Prova de Conceito , Estudos Prospectivos , Estudos Retrospectivos , Redução de PesoRESUMO
INTRODUCTION: Both laparoscopic Roux-en-Y gastric bypass (RYGB) and duodenojejunal bypass liner (DJBL) have been shown to induce weight loss and dramatically ameliorate type 2 diabetes mellitus (T2DM). Since DJBL implantation causes nutrients to pass through the duodenum without contact with the digestive juices and the duodenal mucosa, its mechanisms have been suggested to mimic those of RYGB. This study aimed to compare the outcomes of these two bariatric procedures in terms of glycemic control and BMI in patients with obesity and T2DM. RESEARCH DESIGN AND METHODS: A retrospective observational cohort propensity score-weighted comparison of laparoscopic Roux-en-Y gastric bypass (RYGB) vs duodenojejunal bypass liner (DJBL) was conducted in patients with obesity and T2DM undergoing either procedure from 05/2014 to 12/2017. Propensity scores were weighted for body weight, body mass index (BMI), and glycated hemoglobin A1c (HbA1c). The primary outcome was comparative improvement of HbA1c. Secondary comparative effectiveness outcomes were decrease of body weight and BMI. RESULTS: Forty-six patients were included: 21 (10 male, 11 female; mean age 50.6 ± 11.7 years) underwent RYGB, while DJBL was implanted in 25 (10 male, 15 female; 52.5 ± 9.5 years). After twelve months, mean ΔBMI was 11.54 ± 4.47 kg/m2 for RYGB vs. 6.23 ± 2.36 kg/m2 for DJBL (p < 0.05). Mean total weight loss was 27.93 ± 8.57% for RYGB vs. 15.04 ± 5.73% for DJBL (p < 0.05). Glycemic control after one year improved significantly in both groups but did not differ significantly. CONCLUSION: RYGB and DJBL seem to be associated with similar remission rates of hyperglycemia after one year. However, RYGB induces more significant weight loss than DJBL.
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Diabetes Mellitus Tipo 2 , Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Adulto , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/cirurgia , Feminino , Derivação Gástrica/métodos , Hemoglobinas Glicadas , Controle Glicêmico , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/cirurgia , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento , Redução de PesoAssuntos
Doenças Inflamatórias Intestinais , Lisofosfolipídeos , Receptores de Esfingosina-1-Fosfato , Esfingosina/análogos & derivados , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , Lisofosfolipídeos/metabolismo , Terapia de Alvo Molecular , Transdução de Sinais/efeitos dos fármacos , Esfingosina/metabolismo , Receptores de Esfingosina-1-Fosfato/metabolismoRESUMO
BACKGROUND: Biotin, a water-soluble B vitamin, has demonstrable anti-inflammatory properties. A biotin-deficient diet induced a colitis-like phenotype in mice, alleviable by biotin substitution. Mice with dextran sulfate sodium (DSS)-induced colitis showed biotin deficiency and diminished levels of sodium-dependent multivitamin transporter, a protein involved in biotin absorption. Biotin substitution induced remission by reducing activation of NF-κB, a transcription factor involved in intestinal permeability and inflammatory bowel disease (IBD). We investigated for the first time a possible clinical role of biotin status in IBD. METHODS: In a comparative, retrospective, cross-sectional study, serum samples of 138 patients with IBD (67 female; 72 Crohn's disease (CD), 66 ulcerative colitis (UC)) aged 18-65 years and with a mean age (±SD) of 42.5 ± 14.3 years as well as 80 healthy blood donors (40 female; 40.0 ± 10.0 years; range 20-60 years) were analyzed. Inflammation was defined as hsCRP ≥5 mg/L, and to determine biotin status, serum 3-hydroxyisovaleryl carnitine (3HIVc) levels were measured by LC-MS/MS. RESULTS: A total of 138 patients with IBD (67f; 72CD/66 UC; 42.5 ± 14.3 years) were enrolled: 83/138 had inflammation. Mean serum 3HIVc levels were significantly higher in IBD patients but unaffected by inflammation. Biotin deficiency (95th percentile of controls: >30 nmol/L 3HIVc) was significantly more common in IBD patients versus controls. CONCLUSION: High serum 3HIVc levels and biotin deficiency were associated with IBD but not inflammatory activity or disease type. Our findings suggest biotin may play a role as cause or effect in IBD pathogenesis. Routine assessment and supplementation of biotin may ameliorate IBD and support intestinal integrity.
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Background: Osteopontin (OPN) is a glycosylated phosphoprotein found in human tissues and body fluids. OPN in breast milk is thought to play a major role in growth and immune system development in early infancy. Here, we investigated maternal factors that may affect concentrations of OPN in breast milk, and the possible associated consequences for the health of neonates. Methods: General characteristics, health status, dietary patterns, and anthropometric measurements of 85 mothers and their babies were recorded antenatally and during postnatal follow-up. Results: The mean concentration of OPN in breast milk was 137.1 ± 56.8 mg/L. Maternal factors including smoking, BMI, birth route, pregnancy weight gain, and energy intake during lactation were associated with OPN levels (p < 0.05). Significant correlations were determined between body weight, length, and head circumference, respectively, and OPN levels after one (r = 0.442, p = < 0.001; r = -0.284, p = < 0.001; r = -0.392, p = < 0.001) and three months (r = 0.501, p = < 0.001; r = -0.450, p = < 0.001; r = -0.498, p = < 0.001) of lactation. A negative relation between fever-related infant hospitalizations from 0-3 months and breast milk OPN levels (r = -0.599, p < 0.001) was identified. Conclusions: OPN concentrations in breast milk differ depending on maternal factors, and these differences can affect the growth and immune system functions of infants. OPN supplementation in infant formula feed may have benefits and should be further investigated.
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Desenvolvimento Infantil , Saúde do Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Fenômenos Fisiológicos da Nutrição Materna , Leite Humano/química , Osteopontina , Adulto , Aleitamento Materno , Ingestão de Energia , Feminino , Humanos , Sistema Imunitário , Lactente , Fórmulas Infantis , Recém-Nascido , Lactação , Mães , Gravidez , Adulto JovemRESUMO
Chronic intestinal failure (CIF) is a rare but feared complication of Crohn's disease. Depending on the remaining length of the small intestine, the affected intestinal segment, and the residual bowel function, CIF can result in a wide spectrum of symptoms, from single micronutrient malabsorption to complete intestinal failure. Management of CIF has improved significantly in recent years. Advances in home-based parenteral nutrition, in particular, have translated into increased survival and improved quality of life. Nevertheless, 60% of patients are permanently reliant on parenteral nutrition. Encouraging results with new drugs such as teduglutide have added a new dimension to CIF therapy. The outcomes of patients with CIF could be greatly improved by more effective prevention, understanding, and treatment. In complex cases, the care of patients with CIF requires a multidisciplinary approach involving not only physicians but also dietitians and nurses to provide optimal intestinal rehabilitation, nutritional support, and an improved quality of life. Here, we summarize current literature on CIF and short bowel syndrome, encompassing epidemiology, pathophysiology, and advances in surgical and medical management, and elucidate advances in the understanding and therapy of CIF-related complications such as catheter-related bloodstream infections and intestinal failure-associated liver disease.
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Doença de Crohn , Enteropatias , Nutrição Parenteral no Domicílio , Síndrome do Intestino Curto , Doença Crônica , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Doença de Crohn/terapia , Humanos , Enteropatias/epidemiologia , Enteropatias/etiologia , Enteropatias/terapia , Nutrição Parenteral no Domicílio/efeitos adversos , Qualidade de Vida , Síndrome do Intestino Curto/terapiaRESUMO
BACKGROUND: In the absence of a feasible noninvasive gold standard, iron deficiency (ID) anemia (IDA) is best measured using multiple indicators. However, the choice of an appropriate single iron biomarker for ID screening continues to be debated. Low hemoglobin density (LHD%) from Coulter counters has been suggested as a useful tool to detect ID. This study investigated the reliability of LHD% for the assessment of iron status in patients with inflammatory bowel disease (IBD) and IDA, anemia of chronic disease (ACD) or mixed anemia (MIX). METHODS: The study population consisted of 143 patients with IBD (aged 39.03±12.53 years, 61.5% female). Blood count, transferrin saturation, serum ferritin, and C-reactive protein were determined by routine assays. Patients with anemia were divided into 3 groups: IDA, ACD and MIX, according to specific criteria. Receiver operator characteristic (ROC) curves were constructed. RESULTS: ROC analysis for LHD% in the detection of ID yielded a cutoff value of 3.8%. In anemic patients, LHD% values did not differ statistically significantly between groups (IDA, ACD, MIX) and no significant difference in LHD% values was observed between patients with IDA and ID. CONCLUSIONS: These results demonstrate that LHD% is a reliable biomarker for the detection of iron deficiency in patients with IBD and anemia, regardless of whether inflammation is present. Our findings indicate that LHD% can provide added value in diagnosing iron deficiency.
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Iron deficiency (ID) is a common manifestation of inflammatory bowel disease (IBD), arising primarily due to chronic inflammation and/or blood loss. There is no gold standard for ID diagnosis, which is often complicated by concomitant inflammation. Zinc protoporphyrin (ZnPP) correlates with parameters of iron homeostasis and has been identified as a promising marker for ID, irrespective of inflammation. We investigated the diagnostic performance of ZnPP in ID, iron deficiency anemia, anemia of chronic disease and mixed anemia in a cross-sectional study in 130 patients with IBD. Different parameters were compared by receiver operator characteristic (ROC) analysis as detectors of iron-restricted erythropoiesis (IRE). IRE was detected in 91 patients (70.0%); fifty-nine (64.8%) had absolute ID and 23 (25.4%) functional ID. When inflammation was present, ZnPP was a more reliable sole biomarker of IRE than MCV, transferrin saturation (TSAT) or ferritin (AUC; 0.855 vs. 0.763, 0.834% and 0.772, respectively). The specificity of TSAT was significantly lower than ZnPP when inflammation was present (38% vs. 71%, respectively). We conclude that ZnPP is a reliable biomarker of functional ID in patients with IBD and more dependable than ferritin or TSAT, which are influenced by chronic inflammation. We propose that ZnPP may also have utility in patients with other chronic diseases.
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Iron deficiency, with or without anemia, is the most frequent hematological manifestation in individuals with cancer, and is especially common in patients with colorectal cancer. Iron is a vital micronutrient that plays an essential role in many biological functions, in the context of which it has been found to be intimately linked to cancer biology. To date, however, whereas a large number of studies have comprehensively investigated and reviewed the effects of excess iron on cancer initiation and progression, potential interrelations of iron deficiency with cancer have been largely neglected and are not well-defined. Emerging evidence indicates that reduced iron intake and low systemic iron levels are associated with the pathogenesis of colorectal cancer, suggesting that optimal iron intake must be carefully balanced to avoid both iron deficiency and iron excess. Since iron is vital in the maintenance of immunological functions, insufficient iron availability may enhance oncogenicity by impairing immunosurveillance for neoplastic changes and potentially altering the tumor immune microenvironment. Data from clinical studies support these concepts, showing that iron deficiency is associated with inferior outcomes and reduced response to therapy in patients with colorectal cancer. Here, we elucidate cancer-related effects of iron deficiency, examine preclinical and clinical evidence of its role in tumorigenesis, cancer progression and treatment response. and highlight the importance of adequate iron supplementation to limit these outcomes.
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Anemia Ferropriva/metabolismo , Transformação Celular Neoplásica/metabolismo , Neoplasias Colorretais/metabolismo , Ferro/metabolismo , Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/imunologia , Animais , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/imunologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/prevenção & controle , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Humanos , Ferro/imunologia , Compostos de Ferro/uso terapêutico , Estresse Oxidativo , Evasão Tumoral , Microambiente TumoralRESUMO
BACKGROUND AND AIMS: KRP203 is a potent oral agonist of the sphingosine-1-phosphate receptor subtype 1 that induces the sequestration of peripheral lymphocytes, thereby potentially reducing the number of activated lymphocytes circulating to the gastrointestinal tract. METHODS: We conducted a multicentre, double-blind, placebo-controlled, parallel-group, proof-of-concept study to evaluate the efficacy, safety, and tolerability of KRP203 in patients with moderately active 5-aminosalicylate-refractory ulcerative colitis (UC). Patients were randomly assigned to receive 1.2 mg KRP203 or placebo daily for 8 weeks. Primary efficacy variable was clinical remission, defined as partial Mayo Score 0-1 and modified Baron Score 0-1 with rectal bleeding subscore 0. RESULTS: KRP203 was safe and well tolerated overall. The most common adverse events (AEs) were gastrointestinal disorders and headache. Importantly, no KRP203-related cardiac AEs were reported. Total peripheral lymphocytes and selectively affected lymphocyte subtypes decreased, causing marked decreases in naive and central memory CD4+ and CD8+ T cells, and also in B cells. Clinical remission occurred in 2/14 (14%) patients under KRP203, compared with 0/8 (0%) under placebo. CONCLUSIONS: Overall, KRP203 was safe and well tolerated by patients with UC. Importantly, no cardiac AEs were reported. Although KRP203 did not meet the minimum clinically relevant threshold for efficacy, the results may suggest that KRP203 treatment is superior to placebo. However, in this small study population, the difference was insignificant. Based on these data, studies with an improved design and a larger population should be considered.