Clinical and diagnostic aspects of cystic insulinoma

Cystic endocrine tumors of the pancreas rarely occur, and only a few cases of cystic insulinoma have been reported to date. Diagnosis of insulinoma could be difficult if the functional activity is incomplete, possibly leading to blunted symptoms of hypoglycemia and failure in the laboratory to provide evidence of hyperinsulinemia. We report a clinical case of cystic insulinoma confirmed by histological examination after surgery, characterized by a high intracystic insulin concentration despite normal blood basal levels of the hormone. New diagnostic findings from dynamic tests and cystic fluid examination have been carefully focused on.     

TCF7L2 gene polymorphisms and type 2 diabetes: association with diabetic retinopathy and cardiovascular autonomic neuropathy

Type 2 diabetes (T2DM) is a complex disease resulting from the contribution of both environmental and genetic factors. Recently, the list of genes implicated in the susceptibility to T2DM has substantially grown, also as a consequence of the great development of the genome-wide association studies in the last decade. Common polymorphisms in TCF7L2 gene have shown to have a strong effect with respect to many other involved genes. The aims of our study were to confirm the role of TCF7L2 in the susceptibility to T2DM in the Italian population and to investigate whether TCF7L2 genotypes also contribute to the clinical phenotypes variability and to diabetic complications development. Three TCF7L2 polymorphisms (rs7903146, rs7901695 and rs12255372) have been analyzed by allelic discrimination assays in a cohort of 154 Italian patients with T2DM and 171 healthy controls. A case–control association study and a genotype–phenotype correlation study have been carried out. Consistent with previous studies, all three SNPs showed a strong association with susceptibility to T2DM, both at genotypic (P = 0.003, P = 0.004 and P = 0.012) and at allelic level (P = 0.0004, P = 0.0004 and P = 0.003). Moreover, we observed associations between TCF7L2 variants and the following diabetic complications: diabetic retinopathy, cardiovascular disease and coronary artery disease. We also found a strong correlation between the rs7903146 and the presence of cardiovascular autonomic neuropathy (P = 0.02 with a high OR = 8.28). In conclusion, our study, in addition to confirming the involvement of TCF7L2 gene in the T2DM susceptibility, has shown that TCF7L2 genetic variability also contributes to the development of diabetic complications such as retinopathy and cardiovascular autonomic neuropathy.     

Safety of sugammadex for reversal of neuromuscular block

ABSTRACT

Introduction: Sugammadex is a modified cyclodextrin that is able to reverse neuromuscular block induced by aminosteroidal neuromuscular blocking drugs. Compared to reversal with neostigmine, it reverses neuromuscular block quicker and more predictable and without cholinergic side effects. However, there have been concerns about sugammadex ability to bind other drugs and its effects on QT interval and clotting times. In addition, sugammadex might induce hypersensitivity reactions more frequently than initially anticipated. This review summarizes current evidence with regard to these and other safety aspects of sugammadex.

Areas covered: This review provides an overview of the efficacy of sugammadex in various patient populations, evaluates potential interactions with other drugs and discusses adverse effects and reactions that have been reported in the literature.

Expert opinion: Sugammadex quickly reverses aminosteroid neuromuscular block with less side effects compared to neostigmine. As such, it has the potential to significantly reduce the incidence of residual neuromuscular block and to improve postoperative pulmonary outcome. Current safety concerns mainly focus on hypersensitivity reactions and cardiac arrhythmias. Although the absolute risk for these events is low, ongoing vigilance and research in this area are needed.     

Development and validation of a new short and simple measure of physical function for juvenile idiopathic arthritis

OBJECTIVE: To develop and validate a new short and simple measure of physical function in children with juvenile idiopathic arthritis (JIA). METHODS: The Juvenile Arthritis Functionality Scale (JAFS) is a 15-item questionnaire that explores physical function in 3 body areas (lower limbs, hand/wrist, and upper segment). Validation of the Italian version of the instrument was accomplished by evaluating 211 consecutive JIA patients ages 2.2-18 years. The instrument's feasibility, face and content validity, construct and discriminative ability, internal consistency, interrater reliability, and responsiveness to clinical change were examined. JAFS psychometric properties were compared with those of the Childhood Health Assessment Questionnaire (C-HAQ). RESULTS: The JAFS was found to be feasible and to possess both face and content validity. The JAFS score correlated with most of the other JIA outcome measures in the range predicted, thereby demonstrating good construct validity, and discriminated well among different levels of disability. The internal consistency (Cronbach's alpha) was 0.82. The intraclass correlation coefficients between raters (mothers, fathers, and children) and between reported and observed level of function ranged from 0.65 to 0.84. The JAFS revealed fair responsiveness, with a standardized response mean ranging from 0.42 to 0.56. Comparison with the C-HAQ indicated that the JAFS may be superior in terms of construct validity and reliability, and at least as good in terms of discriminant validity and responsiveness. CONCLUSION: The JAFS exhibited good reliability, construct validity, and discriminative ability and fair responsiveness, and is therefore a valid instrument for the assessment of physical function in children with JIA.     

Ipsilateral right testicular metastasis from renal cell carcinoma in a responder patient to interleukine-2 treatment

We present a case of metastatic spreading to the testicle in a 46-year-old patient with renal cell carcinoma, "clear-cell" type, during interleukin-2 combined subcutaneous plus aerosol treatment. Testicular metastasis occurred while the patient showed a response to the treatment with disappearance of lung lesions and reduction of lymph-nodes lesions. After orchiectomy with spermatic cord resection and disease re-evaluation confirming the previous response, the patient re-started immunotherapy. The contrast between systemic disease response to treatment and disease testicular progression might be explained by a relative insensitivity of the testicle to interleukin-2 immunotherapy as a result of a possible establishment of an immunosuppressive microenvironment. We believe that the rarity of this metastatic site and the intriguing possible mechanisms at its base, makes an interesting case for clinicians.     

Detection of B lymphocytes (CD20+) in renal allograft biopsy specimens

Acute allograft rejection represents an important complication after transplantation with significant impact on long-term graft survival. The involvement and relevance of B lymphocytes in this process is still not clear. The aim of this study was to quantify in renal allograft biopsy specimens the number of cells positive for CD20, a specific marker for B lymphocytes. Immunohistochemical techniques using monoclonal anti-CD20 antibody was used on paraffin sections from 38 renal allograft biopsy specimens. The biopsy specimens were classified into 3 groups, according to clinical and histological criteria: normal kidney, acute rejection, and chronic allograft nephropathy (CAN). In the normal kidney, no CD20(+) cells were detected. In contrast, in all cases of acute rejection and CAN, there were CD20(+) cells. The CD20(+) cells occurred in the infiltrate in 2 distinct patterns: scattered or nodular. In cases of acute rejection, the number of CD20(+) cells was significantly higher than in CAN cases (137.0 +/- 57.2 vs 45.4 +/- 9.8 cells/mm(2); P < 0.05). The nodular pattern was observed in 4 of 11 cases (36%) in the acute rejection group, and in 4 of 20 cases (20%) in the CAN cohort. In the acute rejection group, the presence of B-cell clusters tender to be associated with a higher level of serum creatinine (3.7 +/- 1.8 mg/dL vs 2.8 +/- 0.1 mg/dL in the scattered pattern group; not significant [ns]). In conclusion, these preliminary results demonstrated B lymphocytes in cases of renal allograft dysfunction, which were more pronounced in acute allograft rejection. Further analyses are required to determine whether the detection of CD20(+) cells in renal allograft biopsy specimens can be used as a prognostic marker.