Long‐term outcome and prognostic factors of juvenile dermatomyositis: A multinational,multicenter study of 490 patients

Objective

To investigate the long‐term outcome and prognostic factors of juvenile dermatomyositis (DM) through a multinational, multicenter study.

Methods

Patients consisted of inception cohorts seen between 1980 and 2004 in 27 centers in Europe and Latin America. Predictor variables were sex, continent, ethnicity, onset year, onset age, onset type, onset manifestations, course type, disease duration, and active disease duration. Outcomes were muscle strength/endurance, continued disease activity, cumulative damage, muscle damage, cutaneous damage, calcinosis, lipodystrophy, physical function, and health‐related quality of life (HRQOL).

Results

A total of 490 patients with a mean disease duration of 7.7 years were included. At the cross‐sectional visit, 41.2–52.8% of patients, depending on the instrument used, had reduced muscle strength/endurance, but less than 10% had severe impairment. Persistently active disease was recorded in 41.2–60.5% of the patients, depending on the activity measure used. Sixty‐nine percent of the patients had cumulative damage. The frequency of calcinosis and lipodystrophy was 23.6% and 9.7%, respectively. A total of 40.7% of the patients had decreased functional ability, but only 6.5% had major impairment. Only a small fraction had decreased HRQOL. A chronic course, either polycyclic or continuous, consistently predicted a poorer outcome. Mortality rate was 3.1%.

Conclusion

This study confirms the marked improvement in functional outcome of juvenile DM when compared with earlier literature. However, many patients had continued disease activity and cumulative damage at followup. A chronic course was the strongest predictor of poor prognosis. These findings highlight the need for treatment strategies that enable a better control of disease activity over time and the reduction of nonreversible damage.     

Ultrasonic-mediated laparoscopic liver transection

Parenchymal liver transection represents a fundamental phase of liver surgery. Several devices have been described for safe and careful dissection of the liver parenchyma during laparoscopic liver surgery, but the ideal technique has not yet been defined. This report describes the combined use of ultrasonic dissector and the ultrasonic coagulating cutter for laparoscopic liver resection. The ultrasonic dissector is used to fracture the parenchyma along the line of proposed division, and the uncovered bridging structures are sealed using the ultrasonic coagulating cutter. The combined use of ultrasonic dissector and harmonic scalpel allows liver resection to be safely performed, with the advantage of minimal surgical complication and low blood losses.     

Pattern of interleukin-1beta secretion in response to lipopolysaccharide and ATP before and after interleukin-1 blockade in patients with CIAS1 mutations

OBJECTIVE: To examine the synthesis, processing, and secretion of interleukin-1beta (IL-1beta), as well as the clinical and biologic effects of IL-1 blockade, in patients with chronic infantile neurologic, cutaneous, articular (CINCA) syndrome and Muckle-Wells syndrome (MWS), in an effort to understand the molecular mechanisms linking mutations of the CIAS1 gene and IL-1beta hypersecretion, and the underlying response to IL-1 receptor antagonist (IL-1Ra). METHODS: Six patients with CINCA syndrome or MWS were treated with IL-1Ra and followed up longitudinally. Monocytes obtained from the patients and from 24 healthy donors were activated with lipopolysaccharide (LPS) for 3 hours, and intracellular and secreted IL-1beta levels were determined by Western blotting and enzyme-linked immunosorbent assay before and after exposure to exogenous ATP. RESULTS: LPS-induced IL-1beta secretion was markedly increased in monocytes from patients with CIAS1 mutations. However, unlike in healthy subjects, secretion of IL-1beta was not induced by exogenous ATP. Treatment with IL-1Ra resulted in a dramatic clinical improvement, which was paralleled by an early and strong down-regulation of LPS-induced IL-1beta secretion by the patients' cells in vitro. CONCLUSION: Our results showed that the requirements of ATP stimulation for IL-1beta release observed in healthy individuals are bypassed in patients bearing CIAS1 mutations. This indicates that cryopyrin is the direct target of ATP and that the mutations release the protein from the requirement of ATP for activation. In addition, the dramatic amelioration induced by IL-1Ra treatment is at least partly due to the strong decrease in IL-1beta secretion that follows the first injections of the antagonist. These findings may have implications for other chronic inflammatory conditions characterized by increased IL-1beta.     

Novel reliable real-time PCR for differential detection of MSRVenv and syncytin-1 in RNA and DNA from patients with multiple sclerosis

Two components of the HERV-W family of human endogenous retroviruses are activated during multiple sclerosis (MS) and proposed immunopathogenic co-factors: MSRV (MS-associated retrovirus), and ERVWE1 (whose env protein, syncytin-1, reaches the plasma membrane). MSRVenv and syncytin-1 are closely related, and difficult to distinguish each other. The sequences of extracellular MSRVenv and of syncytin-1 available in GenBank were compared with those found in MS patients and controls of the cohort under study. With respect to syncytin-1, MSRVenv sequences have a 12-nucleotide insertion in the trans-membrane moiety. Based on this insertion, discriminatory real-time PCR assays were developed, that can amplify selectively either MSRVenv or syncytin-1. The data of MS patients and controls indicated that MSRV and ERVWE1 are both expressed in the brain of MS patients, while only MSRV is present in the blood; MSRV was released in culture by PBMCs of MSRV-producer individuals. These cells expressed the complete MSRVenv gene in the absence of syncytin-1 expression, up to the final, fully glycosylated envelope protein product, since western blot staining with anti-HERV-Wenv antibody detected two bands of the same molecular weight (73 and 61 kDa) of the fully glycosylated and partially glycosylated HERV-Wenv uncleaved proteins. Beyond MSRVenv DNA copy numbers were more abundant in MS patients than in healthy humans, while syncytin-1 were unchanged. These findings reinforce the link between MSRV and MS.     

A prospective evaluation of ultrasonic dissector plus harmonic scalpel in liver resection

Several techniques have been described for safe dissection of the liver parenchyma. The aim of this study was to evaluate the feasibility and effectiveness of combining two different electronic devices, the ultrasonic dissector and the harmonic scalpel, during hepatic resection. One hundred consecutive patients who underwent liver resection between January and December 2004 were enclosed in the study. Patients requiring concomitant colic resection or biliary-enteric anastomosis were excluded from the study. Operative variables (type of procedure, operating time, Pringle time, blood losses, transfusions, and histological tumor exposure at the transection surface), hospital stay, and complications were recorded. The extent of hepatic resection was a minor resection in 31 and major in 69 cases. Median blood loss was 500 mL (range, 100-2000 mL) and the Pringle maneuver was used in 58 patients. Median operative time was 367 minutes (range, 150-660 minutes). Hepatic resection was performed in 32 cirrhotic livers. Surgical complications included one postoperative hemorrhage and two bile leaks. The overall morbidity and mortality rate was 14 and 1 per cent, respectively. In conclusion, the combined use of these electronic devices allows liver resection to be safely performed, even in cirrhotic patients, with the advantage of reducing surgical complications. A prospective randomized trial is needed to clarify the clinical benefits of liver resections performed combining these two devices.     

Childhood thalidomide neuropathy: a clinical and neurophysiologic study

Thalidomide was recently reintroduced to treat several immune-mediated pathologies. Peripheral neuropathy is a significant side effect limiting its clinical use. Our aims include: (1) describing and identifying the incidence of clinical or electrophysiologic peripheral neuropathy in children, (2) determining whether peripheral neuropathy correlates with cumulative dose of thalidomide and with age, and (3) defining its reversibility rate. We studied 13 children manifesting immune-mediated pathologies treated with thalidomide at doses ranging from 25-100 mg/day. Clinical and neurophysiologic evaluation was performed before and after starting treatment. Seven children (53.8%) showed neurophysiologic signs of sensory peripheral axonal polyneuropathy. Five presented associated clinical symptoms, while the other two only presented subclinical, neurophysiologic signs of peripheral neuropathy. We found a significant correlation between the incidence of peripheral neuropathy and thalidomide cumulative dose (P = 0.02). We observed a lower incidence of peripheral neuropathy at a cumulative dose <20 gm, and a correlation with age (P < 0.01). The clinical and electrophysiologic recovery rate was 40%, and clinical improvement alone was observed in another 40%. Thalidomide induces dose-dependent and age-dependent peripheral neuropathy at a significant frequency in childhood (53.8%). In our experience a cumulative dosage at >20 gm and long-term administration for >10 months seem to increase the risk of peripheral neuropathy. We propose clinical and neurophysiologic follow-up every 3 months to identify and monitor possible side effects.     

CYP11B2 -344T/C gene polymorphism and blood pressure in patients with acromegaly

CONTEXT: The pathogenesis of increased blood pressure (BP) in acromegaly is unclear, and the role of IGF-I levels and the renin-angiotensin-aldosterone system (RAAS) in this disease remains controversial. OBJECTIVE AND DESIGN: The aim of this study was to investigate the role of gene polymorphisms of the RAAS and involved in sodium handling on BP in acromegaly. SETTING AND PATIENTS: We conducted a multicentric retrospective study that included 100 consecutive patients with acromegaly referred during the period 2000-2003. INTERVENTION: All patients were genotyped for ACE I/D, AGT M235T, CYP11B2 -344T/C, B2R -58T/C, and alpha-adducin G460W polymorphisms. MAIN OUTCOME MEASURE: We assessed the prevalence of hypertension and BP according to the genotype. RESULTS: Patients with the CYP11B2 -344CC genotype displayed a significant increase in the risk of hypertension compared with patients with CT/TT genotypes (odds ratio = 4.0; 95% confidence interval = 1.4-11.6; P = 0.01). Consistently, a significant proportion of patients with the CYP11B2 -344CC genotypes were under antihypertensive treatment (73.1%) compared with patients with the TT/TC genotypes (38.2%; P = 0.003). Patients with the -344CC genotype displayed a significant increase in systolic BP (10.2 +/- 4.3 mm Hg; P = 0.02) but not a significant increase in diastolic BP (2.6 +/- 2.6 mm Hg; P = 0.32) compared with patients with the CT/TT genotype. CONCLUSIONS: We have shown an association of the -344T/C CYP11B2 gene polymorphism with BP in patients affected by acromegaly. These findings suggest that the RAAS is implicated in the pathogenesis of hypertension in acromegaly.     

Association between the HTR1A rs6295 gene polymorphism and suicidal behavior: an updated meta-analysis

European Archives of Psychiatry and Clinical Neuroscience - Several association studies have indicated that the HTR1A gene is associated with suicidal behavior (SB). Thus, a systematic assessment...