Insights into the diagnosis and management of iron deficiency in inflammatory bowel disease.

INTRODUCTION: Iron deficiency is a frequent comorbidity of chronic diseases such as inflammatory bowel disease that can severely impact the health and quality of life of affected individuals. It can exist as a silent condition and manifest in non-specific symptoms even in the absence of anemia. Even though iron deficiency anemia is the most common complication and extra-intestinal manifestation of inflammatory bowel disease, the majority of inflammatory bowel disease patients who are diagnosed with iron deficiency anemia are not treated. Areas covered: In this review, we discuss iron deficiency and iron deficiency anemia in patients with inflammatory bowel disease, and review diagnostic and therapeutic options. Expert commentary: We invite international gastroenterological societies and associations to refine the practice guidelines and include iron deficiency as a potential morbidity associated with IBD in analogy to arthritis, uveitis or any other extra intestinal manifestations. There should a more unanimous agreement among different societies on the specific diagnostic cutoff values for C-reactive protein levels, serum ferritin, and transferrin saturation in order to differentiate iron deficiency anemia from anemia of chronic disease.

Anemia in the elderly: a consequence of aging?

INTRODUCTION: Anemia in the elderly is a common finding that is associated with a poorer quality of life, worse outcomes, and increased mortality. While this entity is frequently overlooked, there is often an underlying cause that is correctable. Areas covered: In this review, we shed light on the prevalence of anemia in the elderly population, review the most common causes, particularly iron deficiency anemia and anemia of chronic disease, and describe the available treatment modalities. When a clear etiology for the anemia is ruled-out, the term unexplained anemia may be utilized; while still an under-explored field, one of the underlying pathophysiological mechanisms appears to be associated with an age-related inflammatory process. Expert commentary: Treating anemia secondary to nutritional deficiencies can be straightforward, but the management of the other types of anemia is not always the case. Treating anemia of chronic disease and anemia of chronic kidney disease may be limited by elevated levels of hepcidin and new promising treatments are still in pre-clinical and clinical trial phases. Caution should be employed when using erythropoiesis stimulating agents due to safety concerns, and when prescribing blood transfusion therapy, both of which lack the specific guidelines for use in the elderly.

Hepatocellular carcinoma as an emerging morbidity in the thalassemia syndromes: A comprehensive review.

The incidence of hepatocellular carcinoma (HCC) in patients with thalassemia is on the rise. The 2 well recognized HCC risk factors in thalassemia are iron overload and chronic viral infection with hepatitis C. The carcinogenicity of iron is related to its induction of oxidative damage, which results in genotoxicity, and to immunologic dysregulation, which attenuates cancer immune surveillance. Chronic hepatitis B and C infections lead to necroinflammation, which can prompt progression to HCC, but an independent role of hepatitis B virus in hepatic carcinogenesis among patients with thalassemia has not been demonstrated. Screening patients who have thalassemia using magnetic resonance imaging-based liver iron concentration measurement and liver ultrasound is recommended for early detection of iron overload and HCC, respectively. Prevention primarily resides in hepatitis B vaccination, donor blood screening, hepatitis treatment, and iron chelation. Although solid data is lacking on the outcomes of HCC treatment in patients with thalassemia, a personalized approach tailored to the individual patient's comorbidities remains necessary for treatment success. Treatment modalities for HCC include surgical resection, chemoembolization, and liver transplantation, among others. Multicenter studies are needed to better explore therapeutic targets that can improve the prognosis of these patients. Cancer 2017;123:751-58. © 2016 American Cancer Society.

Physical symptom profile for adult cancer inpatients at a Lebanese cancer unit.

BACKGROUND: Hospital-based palliative care programs in Lebanon are nonexistent in a structured form. One of obstacles is the lack of knowledge about symptom prevalence and burden of cancer patients in Lebanon. METHODS: This is a cross-sectional observational study where 100 adult cancer patients admitted to the American University of Beirut Medical Center inpatient unit completed a survey to assess 20 physical symptoms according the National Cancer Institute's Common Terminology Criteria for Adverse Events 4.0 (NCI-CTCAE 4.0) guidelines. RESULTS: Hematologic, gastrointestinal, breast, and lung cancers were the most common. Mean age was 51.5 years; 51% were female. 74% of patients with solid tumors had metastatic disease. Treatment approaches were palliative chemotherapy, followed by curative chemotherapy and best supportive care. The most common symptoms were fatigue, appetite loss, nausea, and pain; most distressing were nausea, pain, and fatigue. Nausea and vomiting were more prevalent among females than males. Females reported more severe vomiting than males, but males had more intense pain. Overall symptom burden difference was statistically significant across age groups, with the 51-60 year group having the most symptoms, but not among different genders. Difference was significant among different treatment intents, with the best supportive care group having most symptoms. CONCLUSION: Fatigue should be better addressed as a legitimate symptom. Subgroup differences must be considered when managing gastrointestinal symptoms. Pain should be more effectively managed, and vulnerable subgroups such as the 51-60 year age group and those on best supportive care should receive special consideration.

Sesquiterpene lactones isolated from indigenous Middle Eastern plants inhibit tumor promoter-induced transformation of JB6 cells.

BACKGROUND: Sesquiterpene lactones (SL) are plant secondary metabolites that are known for their anti-fungal, anti-bacterial, anti-inflammatory, and anti-tumor properties. Considering that several SL-derived drugs are currently in cancer clinical trials, we have tested two SL molecules, 3-ß-methoxy-iso-seco-tanapartholide (ß-tan) isolated from Achillea falcata and salograviolide A (Sal A) isolated from Centaurea ainetensis, for their anti-tumor properties. We used the mouse epidermal JB6P + cells as a model for tumor promotion and cellular transformation. Key players that are involved in cellular transformation and tumorigenesis are the AP-1 and NF-κB transcription factors; therefore, we assessed how ß-tan and Sal A modulate their signaling pathways in JB6P + cells. METHODS: The effects of ß-tan and Sal A on the growth of normal and neoplastic keratinocytes and on the tumor promotion-responsive JB6P + cells were determined using the MTT assay. Anchorage-independent cell growth transformation assays were used to evaluate the anti-tumor promoting properties of these SL molecules in JB6P + cells and dual luciferase reporter assays and western blot analysis were used to investigate their effects on tumor promoter-induced AP-1 and NF-κB activities and protein levels of key AP-1 and NF-кB target genes. RESULTS: ß-tan and Sal A selectively inhibited tumor promoter-induced cell growth and transformation of JB6P + cells at concentrations that do not affect JB6P + and primary keratinocytes basal cell growth. In addition, both molecules reduced basal and tumor promoter-induced NF-κB transcriptional activities, differentially regulated basal and tumor promoter-induced AP-1 transcriptional activities, and modulated key players of the AP-1 and NF-κB signaling pathways. CONCLUSIONS: These results highlight the anti-tumor promoting properties of ß-tan and Sal A. These SL molecules isolated from two plant species native to the Middle East may provide opportunities for complementary medicine practices.

Prevalence of depression and anxiety in adult patients with ß-thalassemia major and intermedia.

OBJECTIVE: To evaluate and compare the prevalence and risk factors for anxiety and depression in adults with beta-thalassemia major (TM) and intermedia (TI). METHOD: A cross-sectional study of TI and TM patients at a Chronic Care Center in Lebanon. A total of 80 patients agreed to participate (32 TI (median age 24 years) and 48 TM (median age 23 years)). The Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) questionnaires were used to assess the depression and anxiety levels of patients, respectively. Data on patient demographics, clinical complications, and socioeconomic status were also collected. RESULTS: Patients with TM had a significantly longer median duration with a known thalassemia diagnosis than patients with TI (p < 0.001). A considerable proportion of patients had depression (35.0%), State (S)-anxiety (22.5%) or Trait (T)-anxiety (36.2%). Patients with TI had a higher median S-anxiety score compared with TM (p = 0.035), although the median T-anxiety and depression scores were similar. On linear regression analysis, the significant association between the thalassemia diagnosis (TM versus TI) and S-anxiety score (beta: 5.740; 95% CI: 0.201 to 11.278; p = 0.042) was no longer observed upon adjustment for the co-variate duration with a known thalassemia diagnosis (beta: 3.162; 95% CI: -2.949 to 9.274; p = 0.306). CONCLUSIONS: A considerable proportion of adult patients with TM and TI show evidence of depression and anxiety. Patients with TI are more liable to state anxiety than TM patients of a similar age, which is attributed to a shorter duration of living with a thalassemia diagnosis.

Frequency of triple mutations involving factor V, prothrombin, and methylenetetrahydrofolate reductase genes among patients referred for molecular thrombophilia workup in a tertiary care center in Lebanon.

AIM: Molecular diagnostics has markedly improved the diagnosis and workup of different clinical conditions including hypercoagulable state or thrombophilia where different genes are involved. In this report, which is the largest report in the medical literature and the first in Lebanon, we describe the prevalence of simultaneous mutations in the three major thrombophilia genes Factor V, Factor II, and methylenetetrahydrofolate reductase. MATERIALS AND METHODS: Using a polymerase chain reaction and reverse hybridization assay for the corresponding mutations identification, 2248 referred cases were analyzed. RESULTS: Only 25 cases were found to be simultaneously positive for the three mutations at a prevalence rate of 1.1%. CONCLUSION: Compared with other populations, this prevalence rate is considered high, possibly the highest, and warrants future clinical studies and follow-up.

Levels of growth differentiation factor-15 are high and correlate with clinical severity in transfusion-independent patients with ß thalassemia intermedia.

Transfusion-independent patients with ß thalassemia intermedia (TI) experience a variety of clinical complications attributed to the underlying ineffective erythropoiesis and subsequent anemia, hemolysis, and iron overload. Growth differentiation factor-15 (GDF-15) was recently investigated as a marker of ineffective erythropoiesis in several anemias. In this work, we evaluated GDF-15 levels in 55 patients with TI. The mean GDF-15 level was 25,197.8±16,208.9pg/ml which is lower than values reported for patients with thalassemia major, yet considerably higher than those reported in patients with other congenital and acquired anemias. GDF-15 levels were significantly higher in splenectomized compared to non-splenectomized patients and correlated with anemia, markers of iron overload, and a pre-defined clinical severity score. Further studies are needed to determine the practical utility of GDF-15 measurement and its potential to reflect the severity of the clinical course in TI patients.

Health-related quality of life in adults with transfusion-independent thalassaemia intermedia compared to regularly transfused thalassaemia major: new insights.

BACKGROUND: In patients with ß thalassaemia intermedia (TI), the milder anaemia and transfusion independence imply better health-related quality of life (HR-QoL). However, the unbalanced pathophysiology of the disease allows for several serious clinical complications to manifest, which may have a negative impact on HR-QoL. METHODS: This was a cross-sectional study on adult patients with transfusion- and iron chelation-independent TI and ß thalassaemia major (TM) attending the Chronic Care Center, Hazmieh, Lebanon. A total of 80 patients agreed to participate in the study [32 TI (median age 24 yr) and 48 TM (median age 23 yr)]. The RAND SF-36 survey was used to assess HR-QoL. Data on patient demographics, clinical complications and socioeconomic status were collected. RESULTS: Patients with TI and TM were comparable with age and gender, but patients with TM had a significantly longer median duration with a known thalassaemia diagnosis. Patients with TI had a higher proportion of multiple complications. Socioeconomic parameters were comparable, except for patients with TI being more commonly married. The mean Total, Physical Health and Mental Health Scores were significantly lower in patients with TI compared to TM, indicating poorer HR-QoL. There was a statistically significant positive correlation between the duration with a known thalassaemia diagnosis and a higher Mental Health Score (r(s) = 0.73, P = 0.020). The mean Physical Health Score was significantly lower in patients with multiple clinical complications compared to patients with single or no complications (P = 0.012). Associations remained independently significant at multivariate analysis. CONCLUSION: Patients with transfusion-independent TI have lower HR-QoL compared to TM patients. At a comparable age, the shorter duration since diagnosis and the multiplicity of complications may explain these findings.