Antinuclear antibody–positive patients should be grouped as a separate category in the classification of juvenile idiopathic arthritis

Objective

We undertook this study to test the hypothesis that in the International League of Associations for Rheumatology (ILAR) classification of juvenile idiopathic arthritis (JIA), patients with similar characteristics can be classified into different categories. We sought to investigate whether antinuclear antibody (ANA)–positive patients having disease in the ILAR categories of oligoarthritis, rheumatoid factor–negative polyarthritis, psoriatic arthritis, and undifferentiated arthritis share homogeneous features and to compare these features with those of ANA‐negative patients having the same categories of disease.

Methods

We identified JIA patients who had been followed up during a 22‐year period. ANA positivity was defined as ≥2 positive results at a titer of ≥1:160. Demographic and clinical features were recorded retrospectively and compared between ANA‐positive and ANA‐negative patients.

Results

Of a total of 971 patients, 711 were ANA positive, 149 were ANA negative, and 111 had an indeterminate ANA status. Patients with indeterminate ANA status were excluded. ANA‐positive patients in the different ILAR categories were similar in terms of age at disease presentation, female‐to‐male ratio, and frequency of asymmetric arthritis and iridocyclitis. Compared with ANA‐positive patients, the ANA‐negative group was older at disease presentation and had a lower prevalence of females, a lower frequency of iridocyclitis and asymmetric arthritis, a greater number of affected joints over time, and a different pattern of arthritis. The close relationship between the presence of ANAs and younger age at disease presentation, female predominance, asymmetric arthritis, development of iridocyclitis, lower number of affected joints over time, and lack of hip involvement was also confirmed by multivariate and multiple correspondence analysis.

Conclusion

Our findings substantiate the hypothesis that ANA‐positive patients classified into different JIA categories by current ILAR criteria constitute a homogeneous patient population.

     

Safety profile of tinzaparin versus subcutaneous unfractionated heparin in elderly patients with impaired renal function treated for acute deep vein thrombosis: the Innohep® in Renal Insufficiency Study (IRIS)

Introduction

Trials comparing the use of full dose unfractionated heparin (UFH) or low molecular weight heparins (LMWHs) in very elderly patients with impaired renal function are lacking. IRIS aimed to assess whether LMWH is at least as safe as UFH in this population.

Materials and methods

The study included renally impaired patients ≥ 70 years with acute symptomatic lower limb deep vein thrombosis (DVT). Patients were randomized to initial treatment with either tinzaparin 175 IU/kg once daily (n = 269) or activated partial thromboplastin time-adjusted UFH twice daily (n = 270). After acute management both groups received vitamin K antagonist to day 90.

Results

The trial was stopped prematurely due to a difference in mortality favoring the UFH group (11.5 vs. 6.3%; p = 0.035). Rates of clinically relevant bleedings by day 90 were similar in the tinzaparin (11.9%) and UFH (11.9%) groups, as were rates of confirmed recurrent venous thromboembolism (VTE) (2.6 vs. 1.1%; p = 0.34). As the mortality difference could not be explained by bleedings or recurrent VTE, a post-hoc analysis was performed. This identified six baseline characteristics significantly correlated with mortality, of which five were over-represented in the tinzaparin group.

Conclusion

The IRIS study was a challenging study involving patients (mean age 83 years) usually excluded from clinical studies, but its early termination has left questions unanswered. The mortality difference observed with tinzaparin vs. UFH in elderly, renally-impaired patients with DVT cannot be explained on the basis of bleedings or recurrent VTE, and may reflect an imbalance of mortality risk factors at baseline.     

Splenectomy for hereditary spherocytosis: complete, partial or not at all?

Hereditary spherocytosis (HS) is an hematologic disorder, common in the Northern European population, which is characterized by hemolytic anemia and splenomegaly. The pathophysiological bedrock of HS consists of the retention and damage of abnormal red cells, caused by an intrinsic erythrocyte membrane defect. Hemolysis within the spleen is the main detrminant of erythrocyte destruction in patients with HS. Splenectomy removes the primary ?graveyard? for spherocytes and, thus, eliminates anemia and hyperbilirubinemia and lowers the high reticulocyte number to nearly normal levels. Spleen removal is an effective therapeutic option but it is not without risks. The incidence and public health impact of spleen surgery in children with HS is substantial. Unfortunately, splenectomy is sometimes recommended erroneously for young children who have a mild clinical phenotype or is performed without relying on careful assessment of the risks and benefits. This article aims to present criticism and address controversy about HS management. Unclear and still controversial issues are tackled according to the author?s personal viewpoint, because strong evidence in different aspects of HS management is lacking.     

Hypokalemic rhabdomyolysis without watery diarrhea: an unexpected presentation of a pancreatic neuro-endocrine tumor

Pancreatic polypeptide (PP) islet cell tumors are usually not associated with a distinct clinical syndrome, although some reports suggest that they can cause a watery diarrhea syndrome similar to vasoactive intestinal polypeptide (VIP) cell tumors. We report the case of a young woman with an unusual presentation of a pancreatic neuroendocrine tumor mainly secreting PP. The patient developed a reversible hypokalemic rhabdomyolysis very likely secondary to the presence of the tumor. The myopathy resolved following the restoration of normokaliemia using potassium supplementation and a partial laparoscopic pancreasectomy. Isolated cases of hypokalemic rhabdomyolysis induced by intestinal diseases have been described in literature but these did not include gastroenteropancreatic neoplasms. We suggest that pancreatic neuroendocrine tumors should be added to the list of intestinal diseases capable of producing hypokalemic myopathy.     

Mesenteric adenitis caused by Yersinia pseudotubercolosis in a patient subsequently diagnosed with Crohn＇s disease of the terminal ileum

Although the association between inflammatory bowel disease and gastrointestinal infections has been suggested, the mechanisms involved in the pathogenesis of Crohn's disease (CD) are still undetermined. We report the case of a man, who presented with mesenteric adenitis initially due to a Yersinia pseudotubercolosis infection, who was later diagnosed with Crohn's disease. This case is in keeping with recent evidence in the literature which suggests that CD is a disease linked to abnormal immune responses to enteric bacteria in genetically susceptible individuals.     

Topical prophylaxis of conjunctivitis induced by high-dose cytosine arabinoside

We investigated the efficacy of dexamethasone plus diclofenac eye drops as prophylaxis for conjunctivitis induced by high-dose (HD) cytarabine (Ara-C). Sixty patients were randomized to receive either dexamethasone (group A, n=29) or dexamethasone plus diclofenac (group B, n=31). Conjunctivitis was experienced by 13/29 (45%) patients in group A, and 4/31 (13%) patients in group B (p相似文献   

Role of scaffold internal structure on in vivo bone formation in macroporous calcium phosphate bioceramics

Purpose of this study was the analysis of the role of density and pore interconnection pathway in scaffolds to be used as bone substitutes. We have considered 2 hydroxyapatite bioceramics with identical microstructure and different macro-porosity, pore size distribution and pore interconnection pathway. The scaffolds were obtained with two different procedures: (a) sponge matrix embedding (scaffold A), and (b) foaming (scaffold B). Bone ingrowth within the two bioceramics was obtained using an established model of in vivo bone formation by exogenously added osteoprogenitor cells. The histological analysis of specimens at different time after in vivo implantation revealed in both materials a significant extent of bone matrix deposition. Interestingly enough, scaffold B allowed a faster occurrence of bone tissue, reaching a steady state as soon as 4 weeks. Scaffold A on the other hand reached a comparable level of bone formation only after 8 weeks of in vivo implantation. Both scaffolds were well vascularised, but larger blood vessels were observed in scaffold A. Here we show that porosity and pore interconnection of osteoconductive scaffolds can influence the overall amount of bone deposition, the pattern of blood vessels invasion and finally the kinetics of the bone neoformation process.     

Correlation of fetal DNA levels in maternal plasma with Doppler status in pathological pregnancies

OBJECTIVES: To evaluate whether intrauterine growth restriction (IUGR) as seen in preeclampsia is associated with high levels of fetal DNA in maternal circulation, and whether fetal DNA is related to altered uterine and/or umbilical artery Doppler velocimetry. METHODS: Fetal DNA quantification was performed by real-time PCR on SRY sequences in 64 male-bearing pregnant women with IUGR and/or preeclampsia and 89 controls. RESULTS: Fetal DNA content was significantly elevated in IUGR pregnancies similar to preeclampsia and correlated with altered umbilical Doppler velocimetry, while no correlation was found with uterine Doppler status. CONCLUSION: Increased fetal DNA levels in maternal plasma may be a sign of placental or fetal pathology even in the presence of normal uterine Doppler velocimetry, allowing a more precise diagnostic evaluation. The finding that elevated fetal DNA in IUGR pregnancies correlates with abnormal umbilical Doppler velocimetry suggests that fetal DNA release is associated more with fetal chronic hypoxia than with fetal size.     

The prevalence of growth hormone deficiency and celiac disease in short children

OBJECTIVES: To assess the occurrence of growth hormone deficiency (GHD) in patients with celiac disease (CD) referred for short stature. DESIGN: A retrospective, multi-center study. A total of 7066 children with short stature were referred to a number of centers for second-line evaluation over a 5-year period. All patients were screened for CD by antiendomysial antibodies (EMA) and antitissue transglutaminase IgA.Those with positive sera underwent intestinal biopsy. The EMA-negative patients and the EMA-positive ones who did not grow after 1 year of gluten-free diet underwent endocrinological investigation. RESULTS: Among the 7066 short children (age 2-14 years) evaluated, 650 (9.2%) had GHD and 44 (0.63%) had CD. An association of both CD and GHD was found in 16 short children (0.23%); these children did not grow after 1 year of gluten-free diet and therefore GH treatment was started. CONCLUSIONS: GH secretion should be evaluated in celiac patients showing no catch-up growth after an appropriate period on a gluten-free diet in spite of reversion to seronegativity for EMA.