Deferasirox in MDS patients with transfusion-caused iron overload—a phase-II study

Blood transfusions represent a main component of supportive care in myelodysplastic syndromes (MDS). To avoid organ damage caused by transfusion-dependent iron overload, an adequate iron chelation therapy is required. Recently, a new oral iron chelator deferasirox (ICL670, Exjade) has become available. A study was conducted to demonstrate the efficacy and tolerability of deferasirox in transfusion-dependent iron-overloaded patients with MDS. The efficacy of deferasirox was monitored by changes in serum ferritin, bone marrow iron, and liver iron concentration (LIC), as determined by T2*-weighted magnetic resonance imaging. Twelve patients with MDS of different subtypes (median age 76 years, range 53-91) were enrolled. Deferasirox administered in a once-daily dose of 20-30 mg/kg for 12 months was effective in reducing median ferritin concentration from 1,515 microg/L (range 665-6,900) to 413 microg/L (range 105-3,052). Within the first 4 weeks of treatment before the continuous decline of ferritin levels, the values markedly rose in eight of 12 patients. The median LIC declined from 315 to 230 micromol/g (p=0.02) at the end of study, accompanied by a reduction of bone marrow siderosis. The most common adverse events were mild and transient gastrointestinal disturbances, skin rash, nonprogressive transient increases in serum creatinine and urine beta2-microglobulin, and a temporary reduction of the creatinine clearance. The renal parameters normalized after end of treatment. No hematologic toxicities were observed. Deferasirox proved to be effective in transfusion-dependent iron overload in MDS by mobilizing iron deposits in liver and at least stabilizing iron stores in bone marrow.     

Thyroid cancer in patients with acromegaly: a case–control study

Several studies have associated acromegaly with an increased risk of benign and malignant tumors. While simple and multinodular goiters are common findings in acromegaly, the prevalence of thyroid cancer is uncertain. The objective of this study was to estimate the prevalence of thyroid cancer in a series of acromegalic patients from three hospitals in northeast of Brazil. The methodology used included morphological, cytological and histological thyroid analysis of acromegalic patients and volunteers over 18 years, matched for age and sex and with nodule (s) ≥1 cm. The subjects of this study were 124 acromegalic patients, including 76 females (61.3%) and 48 men (38.7%), with a mean age 45.1 years. Results of the study showed that thyroid ultrasonography was normal in 31 cases (25%), 25 had diffuse goiter (20.1%), 67 had nodules (54%) and one agenesis of the right lobe (0.8%). Thirty-six patients underwent fine needle aspiration biopsy (FNAB) of their nodules and 9 cases of papillary cancer were found (7.2%). The control group consisted of 263 subjects, 156 females (59.3%) and 107 males (40.7%), mean age 44.7 years. In ultrasound assessment, 96 had nodules (36.5%). Of these, 13 were punctured and 2 cases of papillary carcinoma were found (0.7%). These results gave an odds ratio of 10.21 (p = 0.0011, 95% CI 2.17 to 48.01). These findings demonstrate an increased prevalence of thyroid cancer, statistically significant when compared to our control group. Thus, it is suggested that acromegalic patients should be routinely submitted to thyroid ultrasound evaluation, followed by FNAB of nodules when indicated.     

The effect of erythroferrone suppression by transfusion on the erythropoietin–erythroferrone–hepcidin axis in transfusion-dependent thalassaemia: A pre–post cohort study

To track post-transfusion changes on the erythropoietin (EPO)–erythroferrone (ERFE)–hepcidin axis, we collected blood samples from 82 regularly transfused patients with β-thalassaemia major (β-TM) immediately before and 4–6 days after transfusion. The post-transfusion haemoglobin, hepcidin, and ferritin levels were increased, while the EPO, ERFE, and soluble transferrin receptor were suppressed. In addition, hepcidin change was inversely associated with erythropoietic change, which was confirmed by an increase in the hepcidin-to-ERFE ratio after transfusion. Age was the main predictor of serum ERFE, followed by EPO, transfusion frequencies, and ferritin. We found ERFE to be a highly sensitive indicator of erythroid activity in β-TM and that the hepcidin-to-ERFE ratio after transfusion may be used as an appropriateness index of serum hepcidin regulation relative to the degree of erythropoiesis.     

Fibroblast growth factor-23 in patients with systemic sclerosis: A case–control study

BackgroundFibroblast growth factor-23 (FGF-23) is actively involved in phosphate homeostasis and skeletogenesis.Aim of the workTo assess the serum level of FGF-23 in systemic sclerosis (SSc) patients (both diffuse dSSc and limited lSSc subtypes) in order to find if it has a role in the pathogenesis of the disease and study its relation to the clinical manifestations.Patients and methodsThe study included 30 dSSc patients, 30 lSSc and 28 age and sex matched controls. In patients, clinical examination and laboratory investigations were performed and Medsger severity scale assessed. Serum FGF-23 was measured using ELISA.ResultsThe age of dSSc patients was 36.94 ± 9.89 years and the lSSc 38.36 ± 10.04 years. The serum FGF-23 level was 23.44 ± 14.86 pg/ml in dSSc patients, 20.01 ± 13.92 pg/ml in lSSc patients and 23.09 ± 11.45 pg/ml in the control (p = 0.58). No significant difference in the FGF-23 level was found according to the presence of lung fibrosis (p = 0.6). There was no significant difference in FGF levels among patients according to the severity (p = 0.39). In SSc patients there was a significant correlation between FGF and serum phosphorus especially in dSSc patients (r = 0.6, p = 0.003). Serum urea significantly correlated with FGF-23 in those with dSSc (r = 0.46, p = 0.037). There was no significant difference in the FGF-23 levels (p = 0.18) between those with a normal and impaired glomerular filtration rate.ConclusionThe mean serum level of FGF-23 in this study showed no significant difference between systemic sclerosis patients and their subtypes with the normal subjects. It seems to have no role in the clinical manifestations of the disease.     

Bone disease in adult patients with β-thalassaemia major: a case–control study

Despite the extraordinary improvements carried out in diagnostic and therapeutic management of thalassaemia major over the past few decades, bone demineralization is still a common finding, even in optimally treated patients. The relationships between bone density and several clinical characteristics or hematological markers have been described, and many factors contributing to demineralization have been identified; among them endocrine complications seem to play an important role. Nevertheless, the complex etiological mechanisms of this heterogeneous osteopathy still remains incompletely clarified. While previous studies focused on the characteristics of thalassaemic patients affected from bone demineralization, we conducted a case–control study focused on thalassaemic patients free from bone disease, aimed to detect the distinctive characteristics and any possible protective feature. Among a large cohort of 150 adult patients with β-thalassaemia major, we enrolled 20 patients with normal bone mineralization and 20 patients with osteoporosis matched for gender, BMI, age at first transfusion, serum ferritin and pre-transfusional hemoglobin (Hb) levels. The differences in demographic, clinical and endocrinological profiles were investigated, correcting for physical and hematological features known as confounding variables. The comparison of the two groups for biochemical parameters and endocrine function showed a protective role of normal gonadic function and IGF-1 levels against osteoporosis, and a similar influence of hypoparathyroidism. Treatment-corrected hypothyroidism and diabetes seemed not to affect bone mineralization. In conclusion, from a different perspective our results corroborate the role of endocrinopathies in thalassaemic osteopathy, and once again underline the crucial importance of an early and multi-disciplinary intervention in preventing bone complications in thalassaemic patients.     

Symptomatic knee osteonecrosis in patients with systemic lupus erythematosus: a case–control study

To explore the associated risk factors of symptomatic knee osteonecrosis (KON) in patients with systemic lupus erythematosus (SLE), we conducted a retrospective case–control study to compare the clinical and laboratory features between SLE patients with and without symptomatic KON matched by age and gender. Univariate and multivariate regression analyses were used to evaluate possible associated risk factors. Twenty (one male, nineteen females) out of 3941 lupus patients were identified as symptomatic KON, which was confirmed by magnetic resonance imaging. The mean age at KON onset was 34.4 (range 12–67) years, and the median course of lupus at KON onset was 72.5 (range 8–123) months. Univariate and multivariate analyses identified that the prevalence of cutaneous vasculitis (OR 5.23; 95 % CI 1.11–24.70), hyperfibrinogenemia (OR 4.75; 95 % CI 1.08–20.85), and elevated IgG levels (OR 6.05; 95 % CI 1.58–23.16) were statistically higher in KON group, and hydroxychloroquine (HCQ) usage was statistically lower in KON group (OR 0.27; 95 % CI 0.07–0.97). Glucocorticoid usage, in terms of maximal dose, duration of treatment, and the percentage of receiving methylprednisolone pulse therapy, did not show statistical difference between the two groups (p > 0.05). Symptomatic KON is a relatively rare complication of SLE. Cutaneous vasculitis, hyperfibrinogenemia, and elevated IgG levels are possible risk factors, whereas HCQ may provide a protective effect. Our results suggest that lupus activity as well as hypercoagulation status may play a role in the pathogenesis of KON in lupus.     

Esophageal epithelial surface in patients with gastroesophageal reflux disease： An electron microscopic study

A/M： To investigate the intercellular spaces between the most superficially located esophageal epithelial cells in patients with gastroesophageal reflux disease （GERD）.
METHODS： Eighteen patients with erosive esophagitis, 10 patients with non-erosive reflux disease （NERD）, and 18 normal asymptomatic volunteers were enrolled. Biopsy specimens were obtained from the lower esophageal mucosa without ulcer or erosion. Scanning electron microscopy was employed to investigate the tightness of the superficial cellular attachment.
RESULTS： The intercellular space between the most superficially located epithelial cells in patients with erosive esophagitis or NERD was not different from that in asymptomatic healthy individuals.
CONCLUSION： Widened luminal intercellular spaces of esophageal superficial epithelium are not responsible for the induction of reflux symptoms in patients with GERD.     

Efficacy of anorectal biofeedback in scleroderma patients with fecal incontinence: a case–control study

Objective: To determine whether anorectal biofeedback therapy can improve the symptoms of fecal incontinence (FI) in patients with scleroderma when compared to patients with functional FI, and also whether there is any effect on anorectal physiology or quality of life (QOL). FI in patients with scleroderma is highly prevalent and is associated with significant loss of QOL. Biofeedback has been proven to be an effective treatment for functional FI, but there are no data to support its use in scleroderma.

Materials and methods: 13 consecutive female patients (median age 59, IQR 47–65 years) with scleroderma, and 26 age- and parity-matched female patients with functional FI (disease controls, 2:1), underwent biofeedback therapy for management of FI. Fecal incontinence severity index (FISI), anorectal physiology, feeling of control and QOL were collected before and after 6 weeks of biofeedback therapy, with additional scoring repeated at 6-month follow-up.

Results: After biofeedback treatment FISI, feeling of control and QOL significantly improved in both groups (p?p?Conclusions: Patients with scleroderma benefit from biofeedback therapy to the same extent as that achieved in patients with functional FI. There are significant improvements in symptoms, physiology and QOL. Biofeedback is an effective, low-risk treatment option in this patient group.     

Manometric study in ulcerative colitis patients with modified ileal pouch–anal anastomosis

Background and aims Sphincter-saving operations and construction of intestinal reservoirs aim at additional improvement quality of life of patients with restorative proctocolectomy. The conventional ileoanal anastomosis affects the function of the anal sphincters. There is a need for operative techniques that provide sufficient intraluminal anal pressure and thus a better postoperative continence and quality of life.Materials and methods Ileal pouch-anal anastomosis (IPAA) after restorative proctocolectomy was carried out in 42 consecutive ulcerative colitis patients (age range: 19–55 years and mean age of 35.52 years). There were 17 males (40.48%) and 25 females (59.52%). IPAA was performed at dentate line, according to a standard method, in 20 patients (47.62% of the cases; mean age of 35.20 years), 19 of which were in 1986–1995 and one patient in 1998. In 1996–2002, however, IPAA was performed after plicating the demucosed segment of rectal residual in 22 patients (52.38% of the cases; mean age of 35.82 years). This modification consisted in strengthening the internal anal sphincter by creation of a smooth muscle cuff through plication of a mucosectomized segment of rectal residual. The basal anal-canal and squeeze pressures were recorded prior to the operation as well as 1 month afterwards and then every 6 months for 2 years. Kelly–Hohlschneider’s continence scores after Herold’s modification were applied in 14 consecutive patients.Results Thanks to strengthening the internal anal sphincter by this segment, the basal pressure increased from a preoperative value of 68±6 mmHg up to 80±6 mmHg at the end of the second postoperative year (P<0.001). This favourable effect could be explained with the additional contractile potential of the plicated rectal segment resulting from the interference of the contractile potential of the internal anal sphincter with that of the smooth muscle cuff.Conclusion The modified IPAA creates a novel and probably functionally active anatomical substrate. The basal anal-canal pressure is maintained sufficiently high through the tone of the smooth muscle cuff and internal anal sphincter. Our preliminary results suggest that the presented technique for performing IPAA may contribute to better functional results.An invited commentary on this paper is available at     

Persistent symptoms in patients with Crohn’s disease in remission: An exploratory study on the role of diet

Objectives: Patients with Crohn’s disease (CD) often report food hypersensitivities with gastrointestinal (GI) symptoms despite being in clinical remission. We aimed to identify the most frequent symptoms and dietary triggers in such patients, and also explored whether a strict elimination diet may reduce their GI symptoms.

Methods: We assessed GI symptoms and dietary triggers in 16 patients with CD in clinical remission. Of these, 12 patients subsequently participated in a dietary intervention trial: two weeks on a habitual diet including wheat and dairy products followed by two weeks of a strict elimination diet. The severity of seven symptoms (overall symptoms, abdominal pain, bloating, abnormal feces, wind, fatigue, and musculoskeletal pain) was measured by using visual analog scales throughout the four weeks intervention period.

Main results: The most common symptoms were abdominal pain, wind, bloating, odorous wind/feces, and diarrhea. Dairy and wheat products were reported as the most frequent dietary symptom triggers. All symptoms improved (p?Conclusion: Our exploratory study suggests that dietary interventions such as an elimination diet may reduce GI symptoms in patients with CD in remission.     

Achieving treatment goals of reducing or maintaining body iron burden with deferasirox in patients with β-thalassaemia: results from the ESCALATOR study

This analysis evaluated the effects of deferasirox on liver iron concentration in moderate and heavily iron-overloaded patients with β-thalassaemia from the ESCALATOR trial (n = 231). Mean liver iron concentrations (LIC) decreased significantly from 21.1 ± 8.2 to 14.2 ± 12.1 mg Fe/g dry weight (dw) at 2 yr (P < 0.001) in patients with LIC ≥ 7 mg Fe/g dw at baseline; patients with LIC < 7 mg Fe/g dw maintained these levels over the treatment period. The proportion of patients with LIC < 7 mg Fe/g dw increased from 9.4% at core baseline to 39.3% by the end of year 2. The results showed that deferasirox enabled therapeutic goals to be achieved, by maintaining LIC in patients with LIC < 7 mg Fe/g dw at a mean dose of 22.4 ± 5.2 mg/kg/d and significantly reducing LIC in patients with LIC ≥ 7 mg Fe/g dw at a mean dose of 25.7 ± 4.2 mg/kg/d, along with a manageable safety profile.