Transfusional hemosiderosis in childhood cancer patients and survivors.

BACKGROUND: Children treated for cancer are at risk for adverse effects of iron due to transfusions administered during prolonged marrow suppression, which may increase exposure to toxic forms of iron, extrahepatic iron accumulation, and long-term organ damage. OBJECTIVE: This study aimed to characterize the severity and organ distribution of clinically significant, multisystem iron overload (IO) in an at-risk cohort of pediatric cancer patients. METHODS: This was a retrospective, cross-sectional study of childhood cancer patients who underwent a magnetic resonance imaging (MRI) due to clinical concern for IO. Data regarding cancer type and treatment, transfusion history, MRI and laboratory results, and treatment for IO were collected. Severity of IO was analyzed by non-parametric tests with respect to clinical characteristics. RESULTS: Of the 103 patients, 98% of whom had a Cancer Intensity Treatment Rating (ITR-3) of 3 or higher, 53% (54/102) had moderate or greater hepatic siderosis, 80% (77/96) had pancreatic siderosis, 4% (3/80) had cardiac siderosis, and 45% (13/29) had pituitary siderosis and/or volume loss. Pancreatic iron was associated with both cardiac (p = .0043) and pituitary iron (p = .0101). In the 73 off-therapy patients, ferritin levels were lower (p = .0008) with higher correlation with liver iron concentration (LIC) (p = .0016) than on-therapy patients. Fifty-eight subjects were treated for IO. CONCLUSION: In this heavily treated cohort of pediatric cancer patients, more than 80% had extrahepatic iron loading, which occurs with significant exposure to toxic forms of iron related to decreased marrow activity in setting of transfusions. Further studies should examine the effects of exposure to reactive iron on long-term outcomes and potential strategies for management.

Cerebellar Superficial Siderosis in Cerebral Amyloid Angiopathy on 1.5T T2*-Weighted Imaging.

BACKGROUND: Cerebellar superficial siderosis (SS) has been recently reported to be present in about 10% of both hereditary and sporadic cerebral amyloid angiopathy (CAA) on 3T MRI using primarily susceptibility-weighted imaging. OBJECTIVES: Our aim was to assess cerebellar SS in sporadic CAA patients using 1.5T T2*-weighted MRI and to evaluate possible underlying mechanisms. METHOD: We retrospectively screened MRI scans of sporadic probable CAA patients initially presenting with intracerebral hemorrhage-, acute subarachnoid hemorrhage- or cortical SS-related symptoms between September 2009 and January 2022 registered in our stroke database. Patients with familial CAA were excluded. On 1.5T T2*-weighted MRI, cerebellar SS (including kappa statistics for interobserver agreement) was assessed together with typical CAA hemorrhagic features and with the presence of supratentorial macrobleed and cortical SS adjacent to the tentorium cerebelli (TC) and TC hemosiderosis. RESULTS: We screened 151 patients and finally included 111 CAA patients (median age 77) with cerebellar SS observed in 6 (5%) patients. Cerebellar SS presence was associated with a higher number of supratentorial macrobleeds (median n = 3 vs. n = 1, p = 0.0012), presence of supratentorial macrobleed adjacent to the TC (p = 0.002), and TC hemosiderosis (p = 0.005). CONCLUSIONS: Cerebellar SS in CAA patients can be identified on 1.5T T2*-weighted imaging. Associated MRI characteristics suggest contamination from supratentorial macrobleeds.

Cerebellar Superficial Siderosis in Cerebral Amyloid Angiopathy.

BACKGROUND AND PURPOSE: Although evidence accumulates that the cerebellum is involved in cerebral amyloid angiopathy (CAA), cerebellar superficial siderosis is not considered to be a disease marker. The objective of this study is to investigate cerebellar superficial siderosis frequency and its relation to hemorrhagic magnetic resonance imaging markers in patients with sporadic and Dutch-type hereditary CAA and patients with deep perforating arteriopathy-related intracerebral hemorrhage. METHODS: We recruited patients from 3 prospective 3 Tesla magnetic resonance imaging studies and scored siderosis and hemorrhages. Cerebellar siderosis was identified as hypointense linear signal loss (black) on susceptibility-weighted or T2*-weighted magnetic resonance imaging which follows at least one folia of the cerebellar cortex (including the vermis). RESULTS: We included 50 subjects with Dutch-type hereditary CAA, (mean age 50 years), 45 with sporadic CAA (mean age 72 years), and 43 patients with deep perforating arteriopathy-related intracerebral hemorrhage (mean age 54 years). Cerebellar superficial siderosis was present in 5 out of 50 (10% [95% CI, 2-18]) patients with Dutch-type hereditary CAA, 4/45 (9% [95% CI, 1-17]) patients with sporadic CAA, and 0 out of 43 (0% [95% CI, 0-8]) patients with deep perforating arteriopathy-related intracerebral hemorrhage. Patients with cerebellar superficial siderosis had more supratentorial lobar (median number 9 versus 2, relative risk, 2.9 [95% CI, 2.5-3.4]) and superficial cerebellar macrobleeds (median number 2 versus 0, relative risk, 20.3 [95% CI, 8.6-47.6]) compared with patients without the marker. The frequency of cortical superficial siderosis and superficial cerebellar microbleeds was comparable. CONCLUSIONS: We conclude that cerebellar superficial siderosis might be a novel marker for CAA.

High-Grade Fetal Vascular Malperfusion Is Associated With Diffuse Chorionic Hemosiderosis.

INTRODUCTION: Diffuse chorionic hemosiderosis (DCH) is an abnormality of the placental membranes characterized by the deposition of iron pigment. It is usually secondary to recurrent venous bleeding in early pregnancy. In many papers, it is associated with pre-term delivery. Fetal vascular malperfusion (FVM) is an abnormality of the feto-placental circulation that may be seen at any stage of gestation, but most often in the third trimester. It may be graded as low grade (LGFVM) or high grade (HGFVM). No link has been identified in the placental literature between DCH and FVM, but we have noted the 2 co-existing in placentas submitted for analysis. This study explored a possible association of these 2 entities. METHODS: Laboratory records were searched for singleton cases coded as DCH based on diagnosis on H&E stain over a 6-year period. Of 4478 placentas reported, 66 cases were coded as DCH (1.5%). These were classified as showing HGFVM, LGFVM, or no FVM. Controls (n = 132) were gestational age-matched cases without DCH. Cord length, coiling, insertion, or other abnormalities were noted. Membranes were classified as normal or circumvallate. Results were analyzed using Graphpad. RESULTS: Gestation ranged between 16 and 41 weeks gestation. 14/66 (21%) cases of DCH showed HGFVM and 2/66 (3%) showed LGFVM. 16/132 (12%) controls showed HGFVM and 21/132 (15.9%) had LGFVM. Where FVM is present, high-grade FVM is significantly associated with DCH versus controls (P < .0031 Fischer's Test). DISCUSSION: HGFVM occurs significantly more often in placentas with DCH than in controls. Both FVM and DCH are associated with adverse perinatal outcomes, and a possible relationship between the 2 remains to be clarified.

In vivo calibration of the T2* cardiovascular magnetic resonance method at 1.5 T for estimation of cardiac iron in a minipig model of transfusional iron overload.

BACKGROUND: Non-invasive estimation of the cardiac iron concentration (CIC) by T2* cardiovascular magnetic resonance (CMR) has been validated repeatedly and is in widespread clinical use. However, calibration data are limited, and mostly from post-mortem studies. In the present study, we performed an in vivo calibration in a dextran-iron loaded minipig model. METHODS: R2* (= 1/T2*) was assessed in vivo by 1.5 T CMR in the cardiac septum. Chemical CIC was assessed by inductively coupled plasma-optical emission spectroscopy in endomyocardial catheter biopsies (EMBs) from cardiac septum taken during follow up of 11 minipigs on dextran-iron loading, and also in full-wall biopsies from cardiac septum, taken post-mortem in another 16  minipigs, after completed iron loading. RESULTS: A strong correlation could be demonstrated between chemical CIC in 55 EMBs and parallel cardiac T2* (Spearman rank correlation coefficient 0.72, P < 0.001). Regression analysis led to [CIC] = (R2* - 17.16)/41.12 for the calibration equation with CIC in mg/g dry weight and R2* in Hz. An even stronger correlation was found, when chemical CIC was measured by full-wall biopsies from cardiac septum, taken immediately after euthanasia, in connection with the last CMR session after finished iron loading (Spearman rank correlation coefficient 0.95 (P < 0.001). Regression analysis led to the calibration equation [CIC] = (R2* - 17.2)/31.8. CONCLUSIONS: Calibration of cardiac T2* by EMBs is possible in the minipig model but is less accurate than by full-wall biopsies. Likely explanations are sampling error, variable content of non-iron containing tissue and smaller biopsies, when using catheter biopsies. The results further validate the CMR T2* technique for estimation of cardiac iron in conditions with iron overload and add to the limited calibration data published earlier.

Renal hemosiderosis presenting with acute kidney Injury and macroscopic hematuria in Immunoglobulin A nephropathy: a case report.

BACKGROUND: Macroscopic hematuria-associated acute kidney injury (AKI) is a well-known complication of immunoglobulin A (IgA) nephropathy. In such cases, intratubular obstruction by red blood cell (RBC) casts and acute tubular necrosis are mainly observed pathologically. Herein, we report the case of a patient with IgA nephropathy presenting with AKI following an episode of macrohematuria. The patient presented with severe renal tubular hemosiderosis and acute tubular necrosis and without any obvious obstructive RBC casts. CASE PRESENTATION: A 68-year-old woman, who was diagnosed with IgA nephropathy on renal biopsy 6 years ago, was admitted to our hospital after an episode of macroscopic glomerular hematuria and AKI following upper respiratory tract infection. Renal biopsy showed mesangial proliferation of the glomeruli, including crescent formation in 17 % of the glomeruli, and acute tubular necrosis without obvious hemorrhage or obstructive RBC casts. The application of Perls' Prussian blue stain showed hemosiderin deposition in the renal proximal tubular cells. Immunofluorescence showed granular mesangial deposits of IgA and C3. Based on these findings, she was diagnosed with acute tubular necrosis with a concurrent IgA nephropathy flare-up. Moreover, direct tubular injury by heme and iron was considered to be the cause of AKI. She was treated with intravenous pulse methylprednisolone followed by oral prednisolone. Thereafter, the gross hematuria gradually faded, and her serum creatinine levels decreased. CONCLUSIONS: IgA nephropathy presenting with acute kidney injury accompanied by macrohematuria may cause renal hemosiderosis and acute tubular necrosis without obstructive RBC casts. Hemosiderosis may be a useful indicator for determining the pathophysiology of macroscopic hematuria-associated AKI. However, renal hemosiderosis may remain undiagnosed. Thus, Perls' Prussian blue iron staining should be more widely used in patients presenting with hematuria.

Cardiac complications and iron overload in beta thalassemia major patients-a systematic review and meta-analysis.

Despite the major improvement in therapeutic management of thalassemia major, iron overload is considered a challenging conundrum in these patients and heart disease still remains a major cause of morbidity and mortality in these patients. Therefore, this study aimed to investigate the prevalence of cardiac iron overload and cardiovascular complications in transfusion-dependent thalassemia patients in the worldwide. The following databases were searched: ISI/Web of Science, Embase, PubMed, Scopus, up to February 30, 2018. The quality of the studies was evaluated using the Joanna Briggs Institute Prevalence Critical Appraisal Tool. The random model based on Metaprop was used. One hundred forty-two studies were included. The total number of patients included was 26,893. The mean age of patients was 22.6 (SD = 1.7) years. Based on Metaprop, the overall prevalence of cardiac iron overload/myocardial sidoresis (T2* < 20 ms) and cardiac complications in thalassemia major patients in the worldwide was 25% (95% CI 22-28%) and 42% (95% CI 37-46%), respectively. The results of this study show that the prevalence of cardiac iron overload and cardiovascular complications in patients with thalassemia major is almost high. Therefore, iron chelation and careful monitoring of serum ferritin level will prevent the cardiac iron overload, and interval monitoring of patients with transfusion-dependent thalassemia (TDT) by echocardiography and electrocardiography will help with early detection of cardiovascular complications.

Hepatic Hemosiderosis Contributes to Abnormal Vitamin D-PTH Axis in Thalassemia Major.

OBJECTIVE: The aim of this study was to evaluate the vitamin D-PTH axis in thalassemia major (TM) in relation to hepatic siderosis liver iron content. DESIGN AND PARTICIPANTS: In this case-controlled observational study, vitamin D-PTH axis was studied in 158 TM and 84 age and ethnicity-matched healthy nonthalassemic controls attending University College Hospital, London. Patients were classified as 25-hydroxy vitamin D (25-OHD) insufficient and sufficient if the value was less than or greater than 50 nmol/L, respectively. 25-OHD data were evaluated in relation to markers of iron load in TM. RESULTS: In TM, 25-OHD insufficiency was 8-fold higher than the control group (odds ratio [OR], 8.1; 95% confidence interval [CI], 4.3-15.0; P<0.001). Similarly, serum PTH (P<0.001), calcium (P<0.001), and phosphate levels (P<0.05) were also significantly lower in TM compared with the controls. In TM, serum ferritin of >2500 µg/L (OR, 5.3; 95% CI, 2.3-12.3; P<0.01), liver iron of >7 mg/g dry weight (OR, 8.8; 95% CI, 3.5-10.3; P<0.001), and serum alanine aminotransferase of >50 IU/L (OR, 9.7; 95% CI, 4.0-23.5; P<0.001) were independent risk factors for low 25-OHD levels. CONCLUSIONS: Our results suggest that TM had a 8-fold higher risk of 25-OHD insufficiency compared with the controls. This was likely to be associated with hepatic hemosiderosis.

Anatomical hemispherectomy revisited-outcome, blood loss, hydrocephalus, and absence of chronic hemosiderosis.

PURPOSE: To evaluate microsurgical trans-sylvian trans-ventricular anatomical hemispherectomy with regard to seizure outcome, risk of hydrocephalus, blood loss, and risk of chronic hemosiderosis in patients with intractable seizures selected for surgery using current preoperative assessment techniques. METHODS: Out of 86 patients who underwent hemispherectomy between February 2000 and April 2019, by a single surgeon, at a tertiary care referral center, 77 patients (ages 0.2-20 years; 40 females) who had an anatomical hemispherectomy were analyzed. Five of these were 'palliative' surgeries. One-stage anatomical hemispherectomy was performed in 55 children, two-stage anatomical hemispherectomy after extraoperative intracranial monitoring in 16, and six hemispherectomies were done following failed previous resection. Mean follow-up duration was 5.7 years (range 1-16.84 years). Forty-six patients had postoperative MRI scans. RESULTS: Ninety percent of children with non-palliative hemispherectomy achieved ILAE Class-1 outcome. Twenty-seven patients were no longer taking anticonvulsant medications. Surgical failures (n = 4) included one patient with previous meningoencephalitis, one with anti-GAD antibody encephalitis, one with idiopathic neonatal thalamic hemorrhage, and one with extensive tuberous sclerosis. There were no failures among patients with malformations of cortical development. Estimated average blood loss during surgery was 387 ml. Ten (21%) children developed hydrocephalus and required a shunt following one-stage hemispherectomy, whereas 10 (50%) patients developed hydrocephalus among those who had extraoperative intracranial monitoring. Only 20% of the shunts malfunctioned in the first year. Early malfunctions were related to the valve and later to fracture disconnection of the shunt. One patent had a traumatic subdural hematoma. None of the patients developed clinical signs of chronic 'superficial cerebral hemosiderosis' nor was there evidence of radiologically persistent chronic hemosiderosis in patients who had postoperative MRI imaging. CONCLUSION: Surgical results of anatomical hemispherectomy are excellent in carefully selected cases. Post-operative complications of hydrocephalus and intraoperative blood loss are comparable to those reported for hemispheric disconnective surgery (hemispherotomy). The rate of shunt malfunction was less than that reported for patients with hydrocephalus of other etiologies Absence of chronic 'superficial hemosiderosis', even on long-term follow-up, suggests that anatomical hemispherectomy should be revisited as a viable option in patients with intractable seizures and altered anatomy such as in malformations of cortical development, a group that has a reported high rate of seizure recurrence related to incomplete disconnection following hemispheric disconnective surgery.

The growing clinical spectrum of cerebral amyloid angiopathy.

PURPOSE OF REVIEW: Cerebral amyloid angiopathy (CAA) is diagnosed primarily as a cause of lobar intracerebral hemorrhages (ICH) in elderly patients. With improving MRI techniques, however, the role of CAA in causing other symptoms has become clear. Recognizing the full clinical spectrum of CAA is important for diagnosis and treatment. In this review we summarize recent insights in clinical CAA features, MRI biomarkers, and management. RECENT FINDINGS: The rate of ICH recurrence in CAA is among the highest of all stroke subtypes. Cortical superficial siderosis (cSS) and cortical subarachnoid hemorrhage (cSAH) are important imaging predictors for recurrent ICH. CAA also causes cognitive problems in multiple domains. In patients with nondemented CAA, the risk of developing dementia is high especially after ICH. CAA pathology probably starts years before the first clinical manifestations. The first signs in hereditary CAA are white matter lesions, cortical microinfarcts, and impaired occipital cerebral vasoreactivity. Visible centrum semiovale perivascular spaces, lobar located lacunes, and cortical atrophy are new nonhemorrhagic MRI markers. SUMMARY: CAA should be in the differential diagnosis of elderly patients with lobar ICH but also in those with cognitive decline and episodic transient neurological symptoms. Physicians should be aware of the cognitive effects of CAA. In patients with a previous ICH, cSS, or cSAH, anticoagulation should be considered risky. The increasing number of MRI markers may help to discriminate CAA from other small vessel diseases and dementia subtypes.

Infratentorial superficial siderosis: Classification, diagnostic criteria, and rational investigation pathway.

Central nervous system infratentorial superficial siderosis (iSS) is increasingly detected by blood-sensitive magnetic resonance imaging (MRI) sequences. Despite this, there are no standardized diagnostic criteria, and the clinical-radiological spectrum, causes, and optimum investigation strategy are not established. We reviewed clinical and radiological details of patients with iSS assessed at a specialist neurological center during 2004-2016 using predefined standardized radiological criteria. All imaging findings were rated blinded to clinical details. We identified 65 patients with iSS, whom we classified into 2 groups: type 1 (classical) and type 2 (secondary) iSS. Type 1 (classical) iSS included 48 patients without any potentially causal radiologically confirmed single spontaneous or traumatic intracranial hemorrhage, of whom 39 (83%) had hearing loss, ataxia, or myelopathy; type 2 (secondary) iSS included 17 patients with a potentially causal radiologically confirmed spontaneous or traumatic intracranial hemorrhage, of whom none had hearing loss, ataxia, or myelopathy. Of the patients with type 1 (classical) iSS, 40 (83%) had a potentially causal cranial or spinal dural abnormality, 5 (11%) had an alternative cause, and 3 (6%) had no cause identified. Intra-arterial digital subtraction angiography did not identify any underlying causal lesions for type 1 iSS. Type 1 (classical) iSS, defined using simple radiological criteria, is associated with a characteristic neurological syndrome. Rational investigation, including spinal MRI, nearly always reveals a potential cause, most often a dural abnormality. Catheter angiography appears to be unhelpful, suggesting that classical iSS is not associated with macrovascular arterial pathology. Recognition of type 1 (classical) iSS should allow timely diagnosis and early consideration of treatment. Ann Neurol 2017;81:333-343.

[Obstructive sleep apnea hypopnea syndrome and alveolar hypoventilation syndrome in motor neuron disease: A case report and literature review].

OBJECTIVE: To investigate the clinical characteristics of a patient with motor neuron disease, which caused sleep-disordered breathing (SDB) and alveolar hypoventilation syndrome, and to improve the diagnosis rate for this disease.
 Methods: Retrospectively analyze the diagnosis and treatment process for a 52 year-old male patient, who was accepted by the Second Xiangya Hospital, Central South University because of dyspnea, shortness of breath and malaise for 4 months, and eventually was diagnosed as motor neuron disease associated with obstructive sleep apnea hypopnea syndrome and alveolar hypoventilation syndrome. In addition, we searched CNKI, Wanfang and PubMed databases to review relevant literature with keywords (motor neuron disease or amyotrophic lateral sclerosis or progressive bulbar palsy or progressive muscular atrophy or primary lateral sclerosis) AND (sleep apnea or sleep disordered breathing) from January 1990 to May 2017.
 Results: The major clinical manifestation of motor neuron disease included impaired upper and lower motor neuron displayed with proximal muscle weakness, muscle tremor, amyotrophy, bulbar symptoms and pyramidal sign. It was a chronic, progressive disease with worse prognosis, low survival and difficult in diagnosis. Electroneuromyography was a vital way for diagnosis. Furthermore, sleep disordered breathing was common in patients with motor neuron disease, which was featured as decreased rapid eye movement sleep, increased awaking time, apnea and hypopnea. The main mechanism for sleep disordered breathing in motor neuron disease might be due to the disturbed central nervous system and paralysis of diaphragm and respiratory muscle. Moreover, the patient suffered from restrictive ventilatory dysfunction, alveolar hypoventilation and subsequent partial pressure of carbon dioxide and hypoxemia. Therefore, respiratory failure was the most frequent cause of death for patients with motor neuron disease. Non-invasive positive pressure ventilation was suggested to apply to such patients, whose forced vital capability was less than 75 percent of predicted value.
 Conclusion: Sleep disordered breathing is common in patients with motor neuron disease. Hence, polysomnography is suggested as a routine examination to confirm the potential complications and give timely therapy. Treatment with non-invasive positive pressure ventilation is important for patients to improve life quality, survival rate and prognosis.

Residual erythropoiesis protects against myocardial hemosiderosis in transfusion-dependent thalassemia by lowering labile plasma iron via transient generation of apotransferrin.

Cardiosiderosis is a leading cause of mortality in transfusion-dependent thalassemias. Plasma non-transferrin-bound iron and its redox-active component, labile plasma iron, are key sources of iron loading in cardiosiderosis. Risk factors were identified in 73 patients with or without cardiosiderosis. Soluble transferrin receptor-1 levels were significantly lower in patients with cardiosiderosis (odds ratio 21). This risk increased when transfusion-iron loading rates exceeded the erythroid transferrin uptake rate (derived from soluble transferrin receptor-1) by >0.21 mg/kg/day (odds ratio 48). Labile plasma iron was >3-fold higher when this uptake rate threshold was exceeded, but non-transferrin-bound iron and transferrin saturation were comparable. The risk of cardiosiderosis was decreased in patients with low liver iron, ferritin and labile plasma iron, or high bilirubin, reticulocyte counts or hepcidin. We hypothesized that high erythroid transferrin uptake rate decreases cardiosiderosis through increased erythroid re-generation of apotransferrin. To test this, iron uptake and intracellular reactive oxygen species were examined in HL-1 cardiomyocytes under conditions modeling transferrin effects on non-transferrin-bound iron speciation with ferric citrate. Intracellular iron and reactive oxygen species increased with ferric citrate concentrations especially when iron-to-citrate ratios exceeded 1:100, i.e. conditions favoring kinetically labile monoferric rather than oligomer species. Excess iron-binding equivalents of apotransferrin inhibited iron uptake and decreased both intracellular reactive oxygen species and labile plasma iron under conditions favoring monoferric species. In conclusion, high transferrin iron utilization, relative to the transfusion-iron load rate, decreases the risk of cardiosiderosis. A putative mechanism is the transient re-generation of apotransferrin by an active erythron, rapidly binding labile plasma iron-detectable ferric monocitrate species.

Screening for hemosiderosis in patients receiving multiple red blood cell transfusions.

BACKGROUND: The dramatic impact of hemosiderosis on survival in chronically transfused patients with hereditary anemia is well known. We evaluated whether patients receiving multiple red blood cell (RBC) transfusions are adequately screened for hemosiderosis. METHODS: We retrospectively assessed hemosiderosis screening and prevalence in adult patients that received over twenty RBC units in the University Medical Centre Utrecht from 2010 till 2015. Hemosiderosis was defined as ferritin ≥1000 µg/L. Adequate screening for chronically transfused patients was defined as any ferritin determined up to 3 months before or any moment after the last transfusion, while for patients that received all transfusions within 3 months (bulk transfusion), ferritin had to be determined after at least twenty transfusions. RESULTS: Of 471 patients, only 38.6% was adequately screened and hemosiderosis prevalence was 46.7%. Hemosiderosis prevalence was 47% in the chronic transfusion group and 12% in the bulk transfusion group. In patients transfused because of hematological malignancy or cardiothoracic surgery, respectively, 74% and 31% were adequately screened and hemosiderosis prevalence was 53% and 13%, respectively. CONCLUSION: Hemosiderosis screening in our routine practice is suboptimal. Hemosiderosis is not an exclusive complication of multiple transfusions in the hematology ward. We recommend screening for hemosiderosis in all patients receiving multiple transfusions.

Long-term safety and efficacy of deferasirox in young pediatric patients with transfusional hemosiderosis: Results from a 5-year observational study (ENTRUST).

BACKGROUND: Children with red blood cell disorders may receive regular transfusions from an early age and consequently accumulate iron. Adequate iron chelation therapy can prevent organ damage and delayed growth/development. Deferasirox is indicated for treatment of pediatric patients with chronic iron overload due to transfusional hemosiderosis; however, fewer than 10% of patients in the registration studies were aged 2 to less than 6 years. PROCEDURE: Deferasirox, a once-daily oral iron chelator, was evaluated in young pediatric patients with transfusional hemosiderosis during the observational 5-year ENTRUST study. Patients aged 2 to less than 6 years at enrollment received deferasirox according to local prescribing information, with the primary objective of evaluating safety, specifically renal and hepatic function. Serum ferritin was observed as a surrogate efficacy parameter. RESULTS: In total, 267 patients (mean age 3.2 years) predominantly with ß-thalassemia (n = 176, 65.9%) were enrolled. Mean ± standard deviation deferasirox dose was 25.8 ± 6.5 mg/kg per day over a median of 59.9 months. A total of 145 patients (54.3%) completed 5 years' treatment. The proportion of patients with two or more consecutive postbaseline measurements (≥7 days apart) of serum creatinine higher than age-adjusted upper limit of normal (ULN) and alanine aminotransferase more than five times the ULN was 4.4% (95% confidence interval [CI]: 2.1-7.9) and 4.0% (95% CI: 1.8-7.4), respectively. Median serum ferritin decreased from 1,702 ng/ml at baseline to 1,127 ng/ml at 5 years. There were no new safety signals. CONCLUSIONS: Safety and efficacy of deferasirox in young pediatric patients in this long-term, observational study in everyday clinical practice were consistent with the known deferasirox profile.

Auricular Hemosiderosis in a Diabetic Patient.

A 74-year-old Caucasian man with poorly controlled diabetes and hypertension was seen in the dermatology clinic for treatment of a nodular basal cell carcinoma on his right temple. He had poorly controlled diabetes for decades and had been insulin dependent for 20 to 25 years. He had not been on any anticoagulation therapy in the past or present and had no history of a hematologic disorder. He was retired and did woodworking as a hobby. During a routine presurgical head and neck skin examination, he was noted to have macular bluegray dyspigmentation of the central portion of the anterior portion of his ear lobes, bilaterally (Figure 1). He had first noticed this color change approximately 2 years ago and thought the pigmentation was darkening. It was not symptomatic. A punch biopsy was obtained.

Acute Convexity Subarachnoid Hemorrhage Related to Cerebral Amyloid Angiopathy: Clinicoradiological Features and Outcome.

BACKGROUND: The specificities of acute convexity subarachnoid hemorrhage (cSAH) related to cerebral amyloid angiopathy (CAA) and its evolution are not well known. We aimed to describe the clinicoradiological pattern, the magnetic resonance imaging (MRI) evolution, and the risk of recurrent bleeding in such patients. METHODS: Among consecutive patients with an acute nontraumatic cSAH, subjects with available MRI who meet the modified Boston criteria for probable CAA were included. Review of medical records, MRI findings, and follow-up data was performed. RESULTS: Twenty-three patients (14 women; mean age ± standard deviation: 75.9 ± 7.3 years) were included. cSAH was revealed by transient focal neurological episodes (TFNEs) in 18 of 23 (78.3%) patients. In all patients, acute cSAH appeared as a sulcal fluid-attenuated inversion recovery hyperintensity and GRE T2 hypointensity. Cortical superficial siderosis and cortical microbleeds, respectively, were observed in 21 (91.3%) and 20 (86.9%) patients. Twenty patients (87%) had available follow-up data with a mean duration of 29.8 ± 20.2 months. Recurrent TFNEs occurred in 40% of patients. Acute cSAH evolved into cortical superficial siderosis in all patients. New subarachnoid bleedings defined by recurrent acute cSAH (n = 8) or extension of siderosis (n = 14) were detected in 83.3% of the patients. Lobar intracerebral hemorrhage (ICH) occurred in 7 patients (35%). CONCLUSION: CAA-related cSAH has a specific pattern defined by a high prevalence of TFNEs and cortical superficial siderosis, with a high risk of recurrent bleeding, either cSAH or lobar ICH. The systematic evolution from cSAH to focal cortical superficial siderosis reveals data on siderosis physiopathology.