Incomplete Kawasaki syndrome followed by systemic onset-juvenile idiopathic arthritis mimicking Kawasaki syndrome

A 3-month-old child was first treated for incomplete Kawasaki syndrome with three cycles of intravenous immunoglobulins and aspirin, then with methylprednisolone which led to fever remission. The same child was re-hospitalized after a 10-month-period of well-being for the suspicion of a new episode of Kawasaki syndrome, which appeared to be immunoglobulin-resistant: extensive testing failed to provide an alternative diagnosis of any infectious or infiltrative disease. Diagnosis of systemic onset-juvenile idiopathic arthritis was postulated upon the long persistence of fever and inflammatory signs, which subsided only after starting corticosteroid treatment.     

Inflammatory myoglandular polyp of the cecum: case report and review of literature

Background  

Inflammatory myoglandular polyp (IMGP) is a rare non-neoplastic polyp of the large bowel, commonly with a distal localization (rectosigmoid), obscure in its pathogenesis. Up till now, 60 cases of IMGP have been described in the literature, but none located in the cecum.     

Description of two measles outbreaks in the Lazio Region,Italy (2006-2007). Importance of pockets of low vaccine coverage in sustaining the infection

Background  

Despite the launch of the national plan for measles elimination, in Italy, immunization coverage remains suboptimal and outbreaks continue to occur. Two measles outbreaks, occurred in Lazio region during 2006-2007, were investigated to identify sources of infection, transmission routes, and assess operational implications for elimination of the disease.     

Sirolimus Therapy to Halt the Progression of ADPKD

Activation of mammalian target of rapamycin (mTOR) pathways may contribute to uncontrolled cell proliferation and secondary cyst growth in patients with autosomal dominant polycystic kidney disease (ADPKD). To assess the effects of mTOR inhibition on disease progression, we performed a randomized, crossover study (The SIRENA Study) comparing a 6-month treatment with sirolimus or conventional therapy alone on the growth of kidney volume and its compartments in 21 patients with ADPKD and GFR ≥40 ml/min per 1.73 m². In 10 of the 15 patients who completed the study, aphthous stomatitis complicated sirolimus treatment but was effectively controlled by topical therapy. Compared with pretreatment, posttreatment mean total kidney volume increased less on sirolimus (46 ± 81 ml; P = 0.047) than on conventional therapy (70 ± 72 ml; P = 0.002), but we did not detect a difference between the two treatments (P = 0.45). Cyst volume was stable on sirolimus and increased by 55 ± 75 ml (P = 0.013) on conventional therapy, whereas parenchymal volume increased by 26 ± 30 ml (P = 0.005) on sirolimus and was stable on conventional therapy. Percentage changes in cyst and parenchyma volumes were significantly different between the two treatment periods. Sirolimus had no appreciable effects on intermediate volume and GFR. Albuminuria and proteinuria marginally but significantly increased during sirolimus treatment. In summary, sirolimus halted cyst growth and increased parenchymal volume in patients with ADPKD. Whether these effects translate into improved long-term outcomes requires further investigation.Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disorder with major renal manifestations, which occurs in 1 of 400 to 1000 individuals.¹ ADPKD is genetically heterogeneous. Mutations of the two genes PKD1 (85% of the cases) and PKD 2 (15% of cases), encoding polycystin-1 (PC1) and polycystin-2 (PC2), respectively, are implicated in the disease development.² The functions of PC1 and PC2 have not been defined with certainty; however, PC1 is thought to interact with and regulate PC2, which is a member of a subfamily of transient receptor potential channels³ and may act as a cation channel allowing Ca²⁺ entry from the extracellular environment. Consistent with the PC1/PC2 complex having a role in Ca²⁺ regulation, PKD epithelial cells display altered intracellular Ca²⁺ homeostasis,⁴ which alters the response to increased levels of intracellular cAMP.^5–7Another change consistently found in PKD cells is activation of the Ser/Thr kinase mammalian target of rapamycin (mTOR), an enzyme that coordinates cell growth, cell-cycle progression, and proliferation.⁸ mTOR is made up of two distinct complexes: mTORC1 and TORC2. The direct downstream targets of mTORC1, the eukaryotic initiation factor 4E-binding protein and ribosomal protein S6 kinase (p70S6K1),^9,10 tightly regulate the translational initiation machinery to control cell growth and proliferation.⁸ In vitro studies demonstrated that the N-terminal cytoplasmic domain of PC1 co-localizes and interacts with tuberin.¹¹ Activated phospho-mTOR and p70S6K are induced in cyst-lining epithelial cells in cysts from human and mouse kidneys.¹¹ Moreover, p70S6K is increased in Han:SPRD rat kidneys with PKD.¹² These observations led to the hypothesis that defects in PC1 in ADPKD promote disruption of the tuberin-mTOR complex, leading to aberrant mTOR activation and signaling.¹¹ There is also evidence that IGF-1 by binding to its receptor is a major regulator of the mTOR pathway via signaling to phosphatidylinositol-3 kinase, protein kinase B (Akt), and mTOR.⁸ Increase in IGF-1 mRNA levels in the kidneys of the pcy mouse model of PKD¹³ and in IGF-1 protein in Han:SPRD rats¹⁴ has been reported. In addition, the amount of phospho-Akt in cystic Pkd1^−/− mouse kidneys was more than that in wild-type kidneys.¹⁵ Thus, if mTOR is such a converging point in PKD cells, it would be worthwhile as a possible drug target for treatment of renal cystic disorders.Sirolimus (originally referred to as rapamycin) is a macrocyclic lactone that is derived from Streptomyces hygroscopicus and exerts antiproliferative and growth-inhibiting effects as well as antifibrotic effect by inhibition of the mTOR enzyme.^16,17 The drug has been used in kidney transplant recipients as part of maintenance immunosuppressive therapy¹⁸ and more recently as an antitumor agent^19,20 and in drug-eluting stents to prevent coronary artery stenosis.²¹ Short-term treatment with sirolimus markedly reduced kidney size and lowered renal total cyst volume (TCV) density in PKD animal models.^11,12,22 In addition, in renal transplant recipients who had progressed to ESRD because of ADPKD, the size of native kidney and liver cysts decreased while on mTOR inhibitor therapy but did not change appreciably during treatment with other immunosuppressants.^11,23Thus, to assess formally the risk/benefit profile of mTOR inhibitor therapy in PKD, we designed the Sirolimus Treatment in Patients with Autosomal Dominant Polycystic Kidney Disease: Renal Efficacy and Safety (SIRENA; http://clinicaltrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT00491517","term_id":"NCT00491517"}}NCT00491517), a proof-of-concept, randomized clinical trial aimed to compare the changes in total kidney volume (TKV) and in the kidney''s various compartments. This was assessed by serial computed tomography (CT) scan evaluations during 6 months of treatment with sirolimus or conventional therapy alone in 21 patients with ADPKD and normal or moderately decreased kidney function. The study secondarily evaluated whether and to which extent treatment-induced changes in kidney volume and structure translated into concomitant changes in GFR as assessed by standard techniques. The results of these analyses formed the basis of this report.     

Chordoma of the Mobile Spine and Sacrum: A Retrospective Analysis of a Series of Patients Surgically Treated at Two Referral Centers

Background

Chordoma is a rare tumor, and its natural history is still not well known.

Materials and Methods

All patients affected by localized chordoma surgically treated at Istituto Ortopedico Rizzoli, Bologna, and Istituto Nazionale Tumori, Milan, Italy, between 1980 and 2008 were reviewed. Local recurrence, distant metastasis, and overall survival (OS) were analyzed both from time of diagnosis and from time of local recurrence/distant metastasis. A multivariable analysis to identify independent prognostic factors was carried out.

Results

A total of 138 consecutive patients were identified (sacrum 78%, lumbar spine 15%, cervical-dorsal spine 7%). Of these, 130 underwent surgical resection. Median follow-up was 142 months. The 5- and 10-year OS, local relapse-free survival (LRFS), and distant relapse-free survival (DRFS) were, respectively, 78% and 54%, 52% and 33%, and 86% and 72%. Size was an independent prognostic factor for OS (P value < .001), LRFS (P value: .038), and DRFS (P value: .004), while surgical margins independently predicted LRFS (P value: .003) with a trend for OS. The 5- and 10-year OS, LRFS, and DRFS after the first local relapse were 50% and 26%, 47% and 31%, and 64% and 61%. The size of the recurrence and quality of surgical margins did not influence postrelapse OS. The 5-year OS after the second local relapse was 19%. 22% of patients developed distant metastases with a 5-year post-metastases OS of 33%.

Conclusions

Tumor size and surgical margins affected outcome only on initial presentation. However, wide surgery was feasible in a minority of cases. Most patients died of local–regional disease even when metastases occurred. Indeed, long-term prognosis was such that disease-free survival at 10 years was only 26%.     

Frequency of α-Globin Gene Triplications and Their Interaction with β-Thalassemia Mutations

Our protocol for specialized diagnostics includes routine α-globin gene analysis for all blood samples referred to our diagnostic laboratory. α-Globin gene triplication is found to be present in more than 1%?of samples tested. Since all cases with single α-gene triplications are associated with normal hematological parameters, we assume that preselection does not bias our observation and that α-globin gene triplications should be expected at the same frequency in the unselected Dutch multiethnic population as well. We have compared the average hematological parameters of β-thalassemia (β-thal) carriers with those of carriers with an associated α-gene triplication. In all cases, a single additional α gene had a very limited effect on the β-thal minor phenotypes.