Misleading behavioural phenotype with adenylosuccinate lyase deficiency

Adenylosuccinate lyase deficiency is a rare autosomal disorder of de novo purine synthesis, which results in the accumulation of succinylpurines in body fluids. Patients with adenylosuccinate lyase deficiency show a variable combination of mental retardation, epilepsy and autistic features and are usually discovered during screens for unexplained encephalopathy using the Bratton-Marshall assay that reveals the excretion of the succinylaminoimidazolecarboxamide riboside (SAICAr). Here, we report on two sisters aged 11 and 12 years presented with global developmental delay, motor apraxia, severe speech deficits, seizures and behavioural features, which combined excessive laughter, a very happy disposition, hyperactivity, a short attention span, the mouthing of objects, tantrums and stereotyped movements that gave a behavioural profile mimicking Angelman syndrome. Both patients had an increased succinyladenosine/SAICAr ratio of 1.6, and exhibited a novel homozygous missense mutation (c.674T>C; p.Met225Thr) in the exon 6 of the ADSL gene. We suggest that these clinical features might be a new presentation of adenylosuccinate lyase deficiency. On the basis of this observation, although adenylosuccinate lyase deficiency is a rare disorder, this diagnosis should be considered in patients with mental retardation and a behavioural profile suggestive of Angelman syndrome.     

Late potentials in patients with hypertension

The presence of late potentials (LP) is considered as the evidence of an anatomical and electrophysiological condition which can give rise to life threatening ventricular arrhythmias. The aim of this work has been to study the incidence of LP in the setting of hypertension and to study their relation to ventricular hypertrophy on one hand and to ventricular arrhythmias on the other. Our study was conducted in 45 hypertensive patients (mean age +/- SD = 53 +/- 12). None of them had clinical evidences of a coronaropathy and only 5 had never been treated. For every patient we carried out a signal averaged electrocardiogram to detect LP, an echocardiogram to determine the myocardial mass index and 48 hours Holter monitoring to record ventricular arrhythmias filed according to the Lown classification. RESULTS: LP have been found in 13 patients. The following table summaries relations between LP, ventricular arrhythmias and myocardial hypertrophy: [table: see text] CONCLUSION: LP are frequently found in hypertensive patients (29%); their incidence is not higher in patients with left ventricular hypertrophy although they more frequently have serious ventricular arrhythmias; the severity of ventricular arrhythmias is not correlated with the presence of LP.     

A Modular View of Cytokine Networks in Atopic Dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease known for its complex pathophysiology involving several immune pathways. In the lesion, signals from barrier disruption, allergens, and microbial colonization are integrated and transmitted to diverse immune cell types, which initiate and maintain the disease. Cytokines are critical in the allergic intercellular communication networks. This review focuses on up-to-date knowledge on the role of cytokines in AD, including recently described functions as well as novel cellular sources. We propose three modules defined as the cellular source of groups of cytokines: (1) keratinocytes, (2) innate immune cells, and (3) T cells. This view enables to better position the function of novel cytokine players, such as thymic stromal lymphopoetin, IL-21, IL-25, and IL-33, in linking different modules and ultimately leading to the allergic inflammatory phenotype. Persistent efforts in the detailed characterization of cytokine networks will be fundamental for the understanding of the complex pathogenic mechanisms of the disease and for guiding targeted therapeutic interventions.     

Perioperative use of iloprost in cardiac surgery patients diagnosed with heparin‐induced thrombocytopenia‐reactive antibodies or with true HIT (HIT‐reactive antibodies plus thrombocytopenia): An 11‐year experience

Thrombocytopenia and thromboembolism(s) may develop in heparin immune‐mediated thrombocytopenia (HIT) patients after reexposure to heparin. At the Onassis Cardiac Surgery Center, 530 out of 17,000 patients requiring heart surgery over an 11‐year period underwent preoperative HIT assessment by ELISA and a three‐point heparin‐induced platelet aggregation assay (HIPAG). The screening identified 110 patients with HIT‐reactive antibodies, out of which 46 were also thrombocytopenic (true HIT). Cardiac surgery was performed in HIT‐positive patients under heparin anticoagulation and iloprost infusion. A control group of 118 HIT‐negative patients received heparin but no iloprost during surgery. For the first 20 patients, the dose of iloprost diminishing the HIPAG test to ≤5% was determined prior to surgery by in vitro titration using the patients’ own plasma and donor platelets. In parallel, the iloprost “target dose” was also established for each patient intraoperatively, but before heparin administration. Iloprost was infused initially at 3 ng/kg/mL and further adjusted intraoperatively, until ex vivo aggregation reached ≤5%. As a close correlation was observed between the “target dose” identified before surgery and that established intraoperatively, the remaining 90 patients were administered iloprost starting at the presurgery identified “target dose.” This process significantly reduced the number of intraoperative HIPAG reassessments needed to determine the iloprost target dose, and reduced surgical time, while maintaining similar primary clinical outcomes to controls. Therefore, infusion of iloprost throughout surgery, under continuous titration, allows cardiac surgery to be undertaken safely using heparin, while avoiding life‐threatening iloprost‐induced hypotension in patients diagnosed with HIT‐reactive antibodies or true HIT. Am. J. Hematol. 90:608–617, 2015. © 2015 Wiley Periodicals, Inc.     

Preoperative intravenous hydration confers renoprotection in patients with chronic kidney disease undergoing cardiac surgery

Patients with chronic kidney disease (CKD) are at risk to develop acute renal failure (ARF) after open heart surgery. This complication is associated with high morbidity, mortality, and cost. Because the ability to concentrate urine is lost early in the progression of CKD, renal patients kept on fluid restriction prior to surgery may develop severe dehydration, a situation consistently found to be one of the most critical risk factors for postoperative ARF. Our goal was to investigate whether intravenous hydration for 12 h prior to cardiac surgery could prevent acute renal injury in patients with CKD. This is a prospective study in a tertiary cardiac surgery center. Forty-five patients admitted for elective open heart surgery with moderate-to-severe CKD, as evidenced by a quantified glomerular filtration rate less than 45 mL/min, were assigned using a 2/1 randomization process, to either receive an intravenous infusion of half-isotonic saline (1 mL/kg/h) for 12 h before the operation (hydration group, n = 30, 29 men, 64 + 1.7 years old), or to be simply kept on fluid restriction (control group, n = 15, 14 men, 64.2 + 2.8 years old). Groups were not different in clinical and intraoperative variables associated with postoperative renal injury. ARF developed in 8 of 15 (53%) patients in the control group, but in only 9 of the 30 (30%) patients in the hydration group. Four patients in the control group (27%), but no one in the hydration group, required dialysis after the operation (P < 0.01). Peak creatinine and blood urea nitrogen values were two to three times higher in the control group than in the hydration group. Preoperative intravenous hydration may ameliorate renal damage in patients with moderate-to-severe renal insufficiency undergoing cardiac surgery.     

A prospective,double-blind study on the efficacy of the bioline surface-heparinized extracorporeal perfusion circuit

BACKGROUND: We evaluated the newly introduced Bioline heparin coating and tested the hypothesis that surface heparinization limited to the oxygenator and the arterial filter will ameliorate systemic inflammation and preserve platelets during cardiopulmonary bypass (CPB). METHODS: In a prospective double-blind study, 159 patients underwent coronary revascularization using closed-system CPB with systemic heparinization, mild hypothermia (33 degrees C), a hollow-fiber oxygenator, and an arterial filter. The patients were randomly divided in three groups. In group A (controls, n = 51), surface heparinization was not used. In group B (n = 52), the extracorporeal circuits were totally surface-heparinized with Bioline coating. In group C (n = 56), surface heparinization was limited to oxygenator and arterial filter. RESULTS: No significant difference was noted in patient characteristics and operative data between groups. Operative (30-day) mortality was zero. Platelet counts dropped by 12.3% of pre-CPB value among controls at 15 minutes of CPB, but were preserved in groups B and C throughout perfusion (p = 0.0127). Platelet factor 4, plasmin-antiplasmin levels, and tumor necrosis factor-alpha increased more in controls during CPB than in groups B or C (p = 0.0443, p = 0.0238 and p = 0.0154 respectively). Beta-thromboglobulin, fibrinopeptide-A, prothrombin fragments 1 + 2, factor XIIa levels, bleeding times, blood loss, and transfusion requirements were similar between groups. Intensive care unit stay was shorter in groups B and C than in controls (p = 0.037). CONCLUSIONS: Surface heparinization with Bioline coating preserves platelets, ameliorates the inflammatory response and is associated with a reduced fibrinolytic activity during CPB. Surface heparinization limited to the oxygenator and the arterial filter had similar results as totally surface-heparinized circuits.     

Neutrophil depletion reduces myocardial reperfusion morbidity

BACKGROUND: We tested the hypothesis that depletion of neutrophil leukocytes from the cardioplegic and the initial myocardial reperfusion perfusates reduces clinical indices of reperfusion injury in patients undergoing elective coronary artery bypass. METHODS: We studied 160 consecutive patients who underwent standard coronary revascularization with cardiopulmonary bypass. Patients with recent myocardial infarction or coronary angioplasty were excluded. Cold blood cardioplegia was used. Just before aortic unclamping, the hearts were perfused retrograde with 250 mL of normothermic cardioplegic solution and 750 mL of blood (pump perfusate). Patients were randomly assigned to two groups. In 80 patients (treated), neutrophils and platelets were removed from all cardiac perfusate during aortic crossclamping with leukocyte filtration. In the remaining 80 patients (control group), leukocyte filtration was not used. RESULTS: There was no significant difference between groups in age, sex, severity of disease, and number of bypass grafts implanted. Treated patients showed lower prevalence of low cardiac index and reperfusion ventricular fibrillation and lower levels of creatinine kinase MB isoenzyme and troponin I early postoperatively (p < 0.05). CONCLUSIONS: Neutrophil-filtered blood cardioplegia/reperfusion significantly reduced clinical and biochemical indices of myocardial reperfusion injury after elective coronary revascularization with cardiopulmonary bypass.     

Incidental carcinoma in multinodular goiter: risk factors

The aim of the study was to analyze the frequency of incidental thyroid carcinoma (unknown tumor smaller than or equal to 10 mm) in a consecutive series of 462 total thyroidectomies for multinodular goiter and to investigate the clinical risk factors for this type of malignancy. A retrospective, single-center study of outcome data collected from patients with preoperative diagnosis of multinodular goiter who underwent total thyroidectomy at the General Surgery Unit of Pavia (Italy) between January 2000 and December 2008 was performed. Possible risk factors for malignancy were: gender, age, time of evolution of goiter, presence of a dominant nodule in multinodular goiter, hyperthyroidism, history of radiation to the neck, residence in an area of endemic goiter, prior thyroid surgery, calcifications in the goiter detected by neck ultrasound or chest X-rays, and a family history of thyroid diseases. In a 9-year period, 462 patients underwent total thyroidectomy. We found 41 cases of incidental thyroid carcinoma; the most common histopathological type was papillary. The multivariable analysis demonstrated that the clinical variables associated with occult carcinoma were a personal history of radiation therapy to the neck, the presence of calcifications detected by ultrasound or neck X-rays, and a family history of thyroid diseases; residence in an area of endemic goiter was a protective factor. A personal history of radiation to the neck, detection of calcifications by ultrasound or by neck X-rays, and a family history of thyroid diseases should be considered clinical risk factors for malignancy in multinodular goiter.