Predictive comorbidities of hospital admission in 1,571 SARS- CoV-2 positive patients: analysis of administrative data from an Italian Local Health Autority.

Purpose: Globally, age and some comorbidities have been associ-ated with the risk of more severe outcomes of COVID-19. The purpose of this research is to calculate the hospitalization rate of SARS-CoV-2 positive patients in an Italian Local health Authority (LHA) and to examine whether medical comorbidities encoded through pharmaceutical administrative data are predictors of hospital admission in patients with a positive SARS-CoV-2 naso-pharyngeal swab. Methods: This retrospective observational study was conducted in a LHA of Pescara. Comorbidities were coded through the consumption of drugs, using the WHO's Anatomical Therapeutic Chemical (ATC) classification System. The admission was ascertained by checking the hospital discharge records where generated. Results: During the study period, 1571 patients were tested positive for SARS-CoV-2 oro-and-nasopharyngeal swab. Multivariable logistic analisys showed as predictors of admission an age ≥65 in the total sample (aOR 10.91; 95%CI 6.86-17.36) as well as in the male (aOR 12.64;95%CI 6.42-24.87) and female. (aOR 9.27; 95%CI 4.87-17.66) in SARS-CoV-2 positive patients. Comorbidities assiociated with admission were (GERD) in overall (AdjOR 1.58; 95% CI 1.06-2.34) and male (AdjOR 2.30; 95%CI 1.12-4.72) samples and anticoagulants drugs use in male (AdjOR 3.90; 95% 1.11-13.65) sample, the presence of congestive heart failure (CHF) in female (AdjOR 0.47;95%CI 0.27-0.83) sample results as protective factor. Conclusion: In conclusion, increasing age, male gender and PPI use are positively associated while female gender and CHF-related drug use are negatively associated with hospitalization in SARS-CoV-2 positive patients.

Virological outcomes with dolutegravir plus either lamivudine or two NRTIs as switch strategies: a multi-cohort study.

OBJECTIVES: To compare the efficacy of dolutegravir plus lamivudine dual therapy (DT) with that of dolutegravir plus two NRTIs triple therapy (TT) as switch strategies. METHODS: A multicentre cohort of HIV-positive, HBsAg-negative patients with viral suppression (HIV-RNA ≤50 copies/mL) switching to DT or TT was retrospectively selected from the ARCA database. The effect of DT versus TT on virological failure (VF; defined as two consecutive HIV-RNA values >50 copies/mL or one HIV-RNA value ≥200 copies/mL) was evaluated by multivariable Cox regression models, overall and after stratifying for the presence of NRTI resistance-associated mutations (RAMs). RESULTS: From December 2014 to June 2020, 628 patients were eligible: 118 (18.8%) started tenofovir/emtricitabine/dolutegravir, 306 (48.7%) abacavir/lamivudine/dolutegravir and 204 (32.5%) lamivudine/dolutegravir. The DT group had significantly higher nadir and baseline CD4 counts, a higher duration of viral suppression and a lower prevalence of RAMs at historical genotype. Overall, 41 VF occurred after a median of 1.7 years of follow-up, with a lower, but not statistically significant, rate for DT [versus TT, adjusted HR (aHR) = 0.58, 95% CI = 0.25-1.34]. However, DT was associated with less VF in the absence of RAMs when compared with tenofovir-based TT (aHR = 0.20, 95% CI = 0.06-0.67), but not with abacavir-based TT (aHR = 0.43, 95% CI = 0.17-1.11). Conversely, in the setting of pre-existing M184V/I, DT showed a trend to increased risk of VF (versus tenofovir-based TT, aHR = 137.50, 95% CI = 4.24-4464.06; versus abacavir-based TT, aHR = 33.88, 95% CI = 1.75-656.47). CONCLUSIONS: Lamivudine/dolutegravir maintenance DT showed similar efficacy to dolutegravir-based TT; however, past M184V/I may favour VF.

An Aharonov-Bohm interferometer for determining Bloch band topology.

The geometric structure of a single-particle energy band in a solid is fundamental for a wide range of many-body phenomena and is uniquely characterized by the distribution of Berry curvature over the Brillouin zone. We realize an atomic interferometer to measure Berry flux in momentum space, in analogy to an Aharonov-Bohm interferometer that measures magnetic flux in real space. We demonstrate the interferometer for a graphene-type hexagonal optical lattice loaded with bosonic atoms. By detecting the singular π Berry flux localized at each Dirac point, we establish the high momentum resolution of this interferometric technique. Our work forms the basis for a general framework to fully characterize topological band structures.

Combination of deferasirox and deferoxamine in clinical practice: an alternative scheme of chelation in thalassemia major patients.

The availability of three iron chelators improved the scenario of chelation therapy for transfusion-dependent thalassemia (TDT) patients, allowing tailoring of drugs according to the goals expected for each patient. The use of Deferiprone/Deferoxamine (DFP/DFO) combined in different schemes has been reported since many years. Only recently data from combination of Deferasirox/Deferoxamine (DFX/DFO) have been reported showing that it can be safe and efficacious to remove iron overload, particularly in patients who do not respond adequately to a single chelating agent. We investigated the efficacy, tolerability and safety of combined DFX/DFO in thalassemia major patients. Ten TDT patients have started DFX/DFO for different reasons: 1) lack of efficacy in removing liver/cardiac iron with monotherapy; 2) agranulocytosis on DFP; and 3) adverse events with elevated doses of monotherapies. The study design included: cardiac and hepatic T2* magnetic resonance (CMR), transient elastography evaluation (Fibroscan), biochemical evaluation, and audiometric and ocular examinations. The drugs' starting doses were: DFO 32 ± 4 mg/kg/day for 3-4 days a week and DFX 20 ± 2 mg/kg/day. Seven patients completed the one-year follow-up period. At baseline the mean pre-transfusional Hb level was 9.4 ± 0.4 g/dl, the mean iron intake was 0.40 ± 0.10mg/kg/day, the median ferritin level was 2254 ng/ml (range 644-17,681 ng/ml). Data available at 1 year showed no alteration of renal/hepatic function and no adverse events. A marked reduction in LIC (6.54 vs 11.44 mg/g dw at baseline) and in median ferritin (1346 vs 2254 ng/ml at baseline) was achieved. A concomitant reduction of non-transferrin-bound iron (NTBI) at six months was observed (2.1 ± 1.0 vs 1.7 ± 1.2 µM). An improvement in cardiac T2* values was detected (26.34 ± 15.85 vs 19.85 ± 12.06 at baseline). At 1 year an increased dose of DFX was administered (27 ± 6 mg/kg/day vs 20 ± 2 mg/kg/day at baseline, p=0.01) with a stable dose of DFO (32 ± 4 mg/kg/day). Combined or alternated DFX/DFO can be considered when monotherapy is not able to remove the iron overload or in the presence of adverse events.

Targeting focal adhesion assembly by ethoxyfagaronine prevents lymphoblastic cell adhesion to fibronectin.

BACKGROUND: Leukemic cell adhesion to proteins of the bone marrow microenvironment provides signals which control morphology, motility and cell survival. We described herein the ability of ethoxyfagaronine (etxfag), a soluble synthetic derivative of fagaronine, to prevent leukemic cell adhesion to fibronectin peptide (FN/V). METHODS: Phosphorylation of fak and pyk2 were evaluated by immunoblotting. Labelled proteins were localized by confocal microscopy. PI 3-kinase activity was evaluated by in vitro kinase assay. RESULTS: Subtoxic concentration of etxfag reduced L1210 cell adhesion to FN/V dependently of ß1 integrin engagement. Etxfag impaired FN-dependent formation of ß1 clustering without modifying ß1 expression at the cell membrane. This was accompanied by a decrease of focal adhesion number, a diminution of fak and pyk2 phosphorylation at Tyr-576, Tyr-861 and Tyr-579, respectively leading to their dissociations from ß1 integrin and inhibition of PI 3-kinase activity. Etxfag also induced a cell retraction accompanied by a redistribution of phosphorylated fak and pyk2 in the perinuclear region and lipid raft relocalization. CONCLUSION: Through its anti-adhesive potential, etxfag, combined with conventional cytotoxic drugs could be potentially designed as a new anti-leukemic drug.

Rapidly controlled outbreak of Serratia marcescens infection/colonisations in a neonatal intensive care unit, Pescara General Hospital, Pescara, Italy, April 2011.

In April 2011, an outbreak of Serratia marcescens infection/ colonisations occurred in the neonatal intensive care unit of Pescara General Hospital. Rapid microbiological investigations lead to identification of five cases of likely cross-transmission from a neonate hospitalised for S. marcescens sepsis: four infections and one neonate colonised post-mortem. Two low birth weight neonates died. The environmental investigation detected S. marcescens from two soap dispensers. Strict hygiene measures lead to early interruption of the outbreak, without recurrences to date.

Nontransferrin-bound iron in transfused patients with sickle cell disease.

The value of nontransferrin-bound iron (NTBI) as an index of iron overload in patients with thalassemia has been evaluated; however, data in patients with sickle cell disease (SCD) is limited. NTBI levels were evaluated in a cross-sectional study of 43 transfused patients with SCD. Patient charts were reviewed for demographics, status of the spleen, and total number of lifetime transfusions. All patients were chelation naïve and none of the patients had evidence of hepatitis B or C infection. Blood samples were taken for assessment of NTBI and serum ferritin (SF); liver iron concentration (LIC) was determined by R2 magnetic resonance imaging. NTBI levels were generally low with a median of -0.01 µm (range -2.56 to 6.37 µm). Among study variables, NTBI levels were only significantly correlated to age and total number of lifetime transfusions, whereas LIC and SF only significantly correlated with total number of lifetime transfusions. On multivariate analysis, only total number of lifetime transfusions remained independently correlated with NTBI (P = 0.001), SF (P < 0.001), and LIC (P < 0.001). On multivariate stepwise linear regression analysis, SF was a better predictor of LIC than NTBI. In transfused patients with SCD, NTBI levels are low yet correlate significantly with transfusion burden. However, they offer poor predictability of LIC when compared with SF.

Elastin-derived peptides enhance melanoma growth in vivo by upregulating the activation of Mcol-A (MMP-1) collagenase.

BACKGROUND: Elastin peptides possess several biological activities and in vitro data suggest they could be involved in the early phase of melanoma growth. METHODS: Using diverse in vitro and in vivo techniques (cell proliferation, invasion and migration assays, zymography, western blots, collagen degradation assay, reverse transcription PCR, melanoma allographs and immunohistochemistry), we analysed the effect of elastin-derived peptides (EDPs) on B16F1 melanoma growth and invasion, as well as on the proteolytic systems involved. RESULTS: We found that EDPs dramatically promote in vivo tumour development of B16F1 melanoma, as well as their in vitro migration and invasion. The inhibition of serine proteases and matrix metalloproteinases (MMPs) activities, by aprotinin and galardin, respectively, demonstrated that these enzymes were involved in these processes. However, we found that EDPs did not increase urokinase-type plasminogen activator, tissue-type plasminogen activator or MMP-2 expression and/or activation, neither in vitro nor in vivo. Nevertheless, we observed a strong increase of pro-MMP-9 secretion in EDPs-treated tumours and, more importantly, an increase in the expression and activation of the murine counterpart of MMP-1, named murine collagenase-A (Mcol-A). Moreover, we show that plasminogen system inhibition decreases collagen degradation by this enzyme. Finally, the use of a specific blocking antibody against Mcol-A abolished EDP-induced B16F1 invasion in vitro, showing that this MMP was directly involved in this process. CONCLUSION: Our data show that in vivo, EDPs are involved in melanoma growth and invasion and reinforced the concept of elastin fragmentation as a predictive factor.

Elastokine-mediated up-regulation of MT1-MMP is triggered by nitric oxide in endothelial cells.

Membrane-type I matrix metalloproteinase (MT1-MMP) has been previously reported to be up-regulated in human microvascular endothelial cell-1 line (HMEC) by elastin-derived peptides (elastokines). The aim of the present study was to identify the signaling pathways responsible for this effect. We showed that elastokines such as (VGVAPG)(3) peptide and kappa elastin induced nitric oxide (NO) production in a time-, concentration- and receptor-dependent manner as it could be abolished by lactose and a receptor-derived competitive peptide. As evidenced by the use of NO synthase inhibitors, elastokine-mediated up-regulation of MT1-MMP and pseudotube formation on Matrigel required NO production through activation of the PI(3)-kinase/Akt/NO synthase and NO/cGMP/Erk1/2 pathways. Elastokines induced both PI(3)-kinase p110gamma sub-unit, Akt and Erk1/2 activation, as shown by a transient increase in phospho-Akt and phospho-Erk1/2, reaching a maximum after 5 and 15 min incubation, respectively. Inhibitors of PI(3)-kinase and MEK1/2 suppressed elastokine-mediated MT1-MMP expression at both the mRNA and protein levels, and decreased the ability of elastokines to accelerate pseudotube formation. Besides, elastokines mediated a time- and concentration-dependent increase of cGMP, suggesting a link between NO and MT1-MMP expression. This was validated by the use of a guanylyl cyclase inhibitor, a NO donor and a cGMP analog. The guanylyl cyclase inhibitor abolished the stimulatory effect of elastokines on MT1-MMP expression. Inversely, the cGMP analog, mimicked the effect of both elastokines and NO donor in a concentration- and time-dependent manner. Overall, our results demonstrated that such elastokine properties through NO and MT1-MMP may be of importance in the context of tumour progression.

Annexin A1 processing is associated with caspase-dependent apoptosis in BZR cells.

Annexins are widely distributed and have been described in lung as well as in other cells and tissues. Annexin I (ANX AI) is a member of the calcium-dependent phospholipid binding protein family. Besides its anti-inflammatory function, ANX AI has been involved in several mechanisms such as the Erk repression pathway or apoptosis. To investigate the role of ANX AI on apoptosis in broncho-alveolar cells, we have constructed a plasmid containing the ANX AI full length cDNA. Transfected BZR cells displayed a higher level of both forms of ANX AI (37 and 33 kDa) as well as a decrease in cell viability (two-fold versus cells transfected with an empty vector). In order to analyse the endogenous ANX AI processing during stimulus-induced apoptosis, BZR cells were treated with a commonly used inducer, i.e. C2 ceramides. In these conditions, microscopic analysis revealed chromatin condensation in dying cells and the Bcl-2, Bcl-x(L)/Bax mRNA balance was altered. Caspase-3 is one of the key executioners of apoptosis, being responsible for the cleavage of many proteins such as the nuclear enzyme poly(ADP-ribose) polymerase (PARP). We demonstrate that caspase-3 was activated after 4 h treatment in the presence of ceramide leading to the cleavage of PARP. Dose-response experiments revealed that cell morphology and viability modifications following ceramide treatment were accompanied by an increase in endogenous ANX AI processing. Interestingly, in both ceramide and transfection experiments, the ANX AI cleaved form was enhanced whereas pre-treatment with the caspase inhibitor Z-VAD-fmk abolished ANX AI cleavage. In conclusion, this study demonstrates a complex regulatory role of caspase-dependent apoptosis where ANX AI is processed at the N-terminal region which could give susceptibility to apoptosis upon ceramide treatment.

Design of a trial comparing sirolimus plus mycophenolate mofetil versus sirolimus plus cyclosporine.

We present the study design of a prospective, multicenter, randomized trial aimed at comparing the effects of two different combinations of sirolimus. Renal transplant recipients will be allocated to receive either sirolimus and mycophenolate mofetil (group A) or sirolimus and cyclosporine (group B). The primary endpoint will be the graft function at 3, 6, 12, 24, 36, 48, and 60 months. A number of secondary endpoints will also be considered. To obtain a significant difference in the primary endpoint 180 patients will be enrolled.

Red blood cell antioxidant and iron status in alcoholic and nonalcoholic cirrhosis.

BACKGROUND: Iron overload has been reported in alcoholic liver cirrhosis but it remains to be established whether iron is involved in inducing oxidative damage to erythrocytes in alcoholic cirrhosis. The aim of this study was to assess oxidative damage and red cell indicators of antioxidant defences in alcoholics with mild-to-severe liver cirrhosis, taking into account the iron status. MATERIALS AND METHODS: Twenty-nine patients with alcoholic liver cirrhosis (AC) and 27 with nonalcoholic cirrhosis (NAC) were studied. Serum lipid peroxides (LPO) were assayed by a colourimetric method. Serum-free malonyldialdehyde (MDA) was assayed by selected ion monitoring in positive chemical ionization; serum 4-hydroxy-2(E)-nonenal (4-HNE) was determined by a colorimetric method. Reduced (GSH) and oxidized glutathione (GSSG), adenine and pyridine cofactors were assayed in whole blood extracts by HPLC. Hexose-monophosphate shunt (HMPS), glycolytic pathway (EMP) and antioxidant enzyme activities were determined by standard methods. Iron status was evaluated by standard clinical chemistry and by histological grading of liver iron. Nontransferrin-bound iron (NTBI) was measured in serum by HPLC. RESULTS: GSH progressively decreased with increasing severity of liver involvement in AC and NAC. MDA, 4-HNE and NTBI were significantly higher in AC serum. Stimulation of red cell HMPS and reducing potential, in terms of NADPH production, were more pronounced in AC. CONCLUSIONS: These results suggest that NTBI is more important than the decrease of antioxidant defences in inducing lipid peroxidation. NTBI may play a catalytic role in free radical reactions in the presence of cellular reductants such as NADPH.

Oxidative status and malondialdehyde in beta-thalassaemia patients.

BACKGROUND: In beta-thalassaemia syndromes, decreased or impaired biosynthesis of beta-globin leads to accumulation of unpaired alpha-globin chains. Moreover, the iron overload in beta-thalassaemia patients generates oxygen-free radicals and peroxidative tissue injury. The aim of this study was to detect and correlate iron overload parameters with the oxidative stress and the antioxidant capability in beta-thalassaemia patients. DESIGN: Serum iron, transferrin saturation, serum ferritin, nontransferrin-bound iron (NTBI), levels of serum free and total (free + bound) malondialdehyde (MDA) and total peroxyl radical-trapping antioxidant parameter (TRAP) were evaluated in 21 regularly transfused beta-thalassaemia major (TM) patients, 13 untransfused beta-thalassaemia intermedia (TI) patients and 17 healthy controls. Blood from the TM patients was drawn 48 h after the last desferoxamine (20-40 mg kg(-1)) infusion and just before transfusion. RESULTS: Free and total MDA and NTBI levels were higher in the TM patients than in the TI. In the TM patients the free MDA levels correlated positively with serum iron (r = +0.3, P = 0.0006), whereas the total MDA correlated positively with NTBI (r = +0.45, P = 0.037). However, a negative correlation was observed between TRAP and NTBI (r = -0.4, P = 0.0006). In the TI patients there was no significant correlation between free or total MDA and TRAP or NTBI. CONCLUSIONS: Our results confirm the peroxidative status generated by iron overload in thalassaemia patients and highlight the rapid formation of marked amounts of free MDA despite the chelation therapy in TM patients.

Non-transferrin-bound iron in alcohol abusers.

BACKGROUND: Non-transferrin-bound iron, a low-molecular-weight iron complex capable of initiating free radical formation and lipid peroxidation, has been detected in the serum of animals experimentally fed with alcohol, but no data have been reported in alcohol abusers. The purpose of this study was to evaluate whether non-transferrin-bound iron is present in chronic alcohol abusers with liver involvement and whether alcohol plays any part in its appearance. METHODS: We measured non-transferrin-bound iron in a cohort of chronic alcohol abusers with and without liver cirrhosis at presentation, when 43 were active abusers and 33 were abstainers, and in a smaller group during a follow-up period. RESULTS: At presentation, non-transferrin-bound iron was detectable in 83.7% of active abusers but only in 21.2% of abstainers, and within the group of abusers, patients with cirrhosis had significantly higher non-transferrin-bound iron than patients without. Non-transferrin-bound iron was present not only in patients with transferrin saturation >45% but also in those with transferrin saturation < or =45%. Multiple regression analyses revealed that only alcohol intake and total bilirubin were associated independently with non-transferrin-bound iron values. Longitudinal study confirmed the data of the cross-sectional study. CONCLUSIONS: Non-transferrin-bound iron could have a role in initiating or promoting alcohol-induced liver damage.

Membrane-bound iron contributes to oxidative damage of beta-thalassaemia intermedia erythrocytes.

Iron-dependent oxidative reactions in beta-thalassaemic erythrocyte membranes are involved in premature cell removal and anaemia. We studied 22 beta-thalassaemia intermedia patients (i) to assess if membrane iron accumulation influences the oxidative damage to thalassaemic cells, and (ii) to see whether the mechanisms of haemoglobin destabilization described in vitro have indicators in circulating erythrocytes. Serum non-transferrin-bound iron as potentially toxic iron for erythrocytes was also evaluated. Membrane-bound free iron significantly correlated to bound haemichromes, suggesting a causal relation, but was poorly related to serum non-transferrin iron, which seems to contribute little to damage from outside the cells. The spleen played an important role in the removal of cells with more membrane iron.

Non-transferrin-bound iron in myelodysplastic syndromes: a marker of ineffective erythropoiesis?

INTRODUCTION: Iron overload is usually observed in patients (even untransfused) with myelodysplastic syndromes (MDS), and contributes towards the generation of low molecular weight iron complexes or non-transferrin-bound iron (NTBI), which in turn favors oxidative DNA damage and consequent apoptosis. MATERIALS AND METHODS: Levels of NTBI and lipid peroxidation were evaluated by means of free serum malondyaldehyde (MDA) in untransfused MDS patients and we tried to correlate them with ineffective erythropoiesis, apoptosis and the pattern of in vitro growth. RESULTS: NTBI levels were found to be significantly higher in low-risk than in high-risk MDS patients, as well as in patients with a lower myeloid/erythroid ratio. MDA was found to be uniformly higher in the MDS patients as a whole than in normal controls. The bone marrow progenitor cells in the MDS patients with high NTBI levels showed a higher degree of apoptosis, but this difference was not statistically significant. Patients with a leukemic growth pattern had lower NTBI levels than those with a non-leukemic pattern. CONCLUSION: These data suggest that NTBI is related to the degree of ineffective erythropoiesis and that it contributes towards inducing apoptosis in MDS bone marrow precursors. The presence of leukemic growth is associated with low NTBI levels, probably due to increased iron consumption by blast cells.

Metabolic indicators of oxidative stress correlate with haemichrome attachment to membrane, band 3 aggregation and erythrophagocytosis in beta-thalassaemia intermedia.

Haematological data, genotype, transfusion requirements, metabolic indicators of oxidative stress (flux via hexose-monophosphate shunt (HMPS); steady state level of GSH and GSSG, NADPH and NADP; activity of anti-oxidant enzymes), parameters of membrane damage (aggregated band 3; membrane-bound haemichromes, autologous immunoglobulins (Igs) and C3 complement fragments) and erythrophagocytosis were measured in erythrocytes (RBC) of 15 beta-thalassaemia intermedia patients (nine splenectomized) with low, if any, transfusion requirements. Patients presented increased aggregated band 3, bound haemichromes, Igs and C3 complement fragments, and increased erythrophagocytosis. Bound haemichromes strongly correlated with aggregated band 3. Anti-band 3 Igs were predominantly associated with aggregated band 3. Erythrophagocytosis positively correlated with aggregated band 3, haemichromes and Igs, suggesting the involvement of haemichrome-induced band 3 aggregation in phagocytic removal of beta-thalassaemic RBC. Splenectomized patients showed higher degrees of membrane damage and phagocytosis, significantly higher numbers of circulating RBC precursors, and tendentially higher numbers of reticulocytes. Basal flux via HMPS was increased twofold, but HMPS stimulation by methylene blue was decreased, as was the glucose flux via HMPS. GSH was remarkably decreased, whereas NADPH was increased. Except for unchanged catalase and glutathione reductase, anti-oxidant enzymes had increased activity. Negative correlation between HMPS stimulation by methylene blue and bound haemichromes indicated that the ability to enhance HMPS may counteract haemichrome precipitation and limit consequent membrane damage leading to erythrophagocytosis.

Carbohydrate-deficient transferrin, a sensitive marker of chronic alcohol abuse, is highly influenced by body iron.

Carbohydrate-deficient transferrin (CDT), a microheterogeneous form of serum transferrin (Tf), has been proposed as the most reliable marker of chronic alcohol consumption, although unexplained false-positive and -negative results have been reported. We investigated whether body iron influenced CDT serum levels by studying alcohol abusers with or without iron overload and nonabusers with iron deficiency or iron overload caused by genetic hemochromatosis (GH). In alcohol abusers, CDT was significantly lower in the presence of iron overload than in the absence (24.6 +/- 16.5 U/L vs. 33.3 +/- 11.7 U/L; P <.01), with false-negative results almost exclusively in patients with iron overload. Similarly, in nonabusers with GH, CDT was lower than in normal controls (9.6 +/- 2. 2 U/L vs. 15.7 +/- 3.3 U/L; P <.0001), whereas, patients with iron deficiency anemia had significantly higher levels than controls (28. 1 +/- 5.8 U/L vs. 15.7 +/- 3.3 U/L; P <.0001). In nonabusers, iron supplementation therapy significantly decreased CDT levels in patients with iron deficiency anemia (33.7 +/- 6.6 U/L vs. 21.7 +/- 5.2 U/L; P =.0007), while iron-depletion treatment significantly increased CDT levels in patients with GH (9.7 +/- 2.0 U/L vs. 14.7 +/- 4.0 U/L; P =.001). Alcohol abusers had a significant relationship between liver iron concentration (LIC) and the reciprocal of CDT (r =.65; P <.0001), while in nonabusers, there was a significant correlation between Tf and CDT (r =.72; P <.0001). In conclusion, CDT serum levels are markedly affected by the patient's iron status, with iron overload reducing its sensitivity in alcohol abusers and iron deficiency its specificity in nonabusers. CDT can be considered a reliable marker of alcohol abuse only when iron stores are normal.