Depression in Behçet’s disease patients: Relationship with disease pattern,activity and quality of life

Aim of the workTo determine the frequency of depression in Behçet’s disease (BD) patients and to clarify its burden on patients’ clinical manifestations, disease activity status and quality of life (QoL).Patients and methods35 BD patients with 35 matched control were included in this study. Disease activity was assessed by Behçet Syndrome Activity Score (BSAS). All participants were requested to complete the Hamilton depression rating scale (HDRS), Multidimensional assessment of fatigue (MAF) questionnaire and the short form-36 (SF-36) QoL Scale.ResultsThe mean age of the patients was 40.3 ± 13.5 years (17–72 years) and they were 27 males and 8 females. The frequency of depression in BD patients was 74.3% with increased male frequency (p = 0.007) and major organ involvement (p = 0.04) among depressed patients. Significant differences (p < 0.001, p = 0.04, p = 0.001 respectively) between depressed and non depressed BD patients with respect to BSAS, MAF and SF-36. Highly significant positive correlations between HDRS and number of major organ, BSAS, MAF, (p < 0.001) and significant correlation with number of non major organs (r = 0.3, p = 0.04). Significant negative associations were observed between HDRS and SF-36 (r = ?0.6, p < 0.001). On regression number of major organ involvement (p < 0.001), BSAS (p = 0.01), MAF (p = 0.002), and SF-36 QoL (p < 0.001) significantly correlated with HDRS.ConclusionDepression is a significant comorbidity in patients with BD and is closely related to fatigue, number of major organ involvement and overall disease activity with a negative impact on QoL. Therefore, early interference and depression management in routine clinical practice is important to reduce patients’ symptoms, and improve QoL.     

In vitro structure–activity relationship of Re-cyclized octreotide analogues

IntroductionDevelopment of radiolabeled octreotide analogues is of interest for targeting somatostatin receptor (SSTR)-positive tumors for diagnostic and therapeutic purposes. We are investigating a direct labeling approach for incorporation of a Re ion into octreotide analogues, where the peptide sequences are cyclized via coordination to Re rather than through a disulfide bridge.MethodsVarious octreotide analogue sequences and coordination systems (e.g., S₂N₂ and S₃N) were synthesized and cyclized with nonradioactive Re. In vitro competitive binding assays with ¹¹¹In-DOTA-Tyr³-octreotide in AR42J rat pancreatic tumor cells yielded IC₅₀ values as a measure of SSTR affinity of the Re-cyclized analogues. Three-dimensional structures of Re-cyclized Tyr³-octreotate and its disulfide-bridged analogue were calculated from two-dimensional NMR experiments to visualize the effect of metal cyclization on the analogue's pharmacophore.ResultsOnly two of the 11 Re-cyclized analogues investigated showed moderate in vitro binding affinity toward somatostatin subtype 2 receptors. Three-dimensional molecular structures of Re- and disulfide-cyclized Tyr³-octreotate were calculated, and both of their pharmacophore turns appear to be very similar with minor differences due to metal coordination to the amide nitrogen of one of the pharmacophore amino acids.ConclusionsVarious Re-cyclized analogues were developed and analogue 4 had moderate affinity toward somatostatin subtype 2 receptors. In vitro stable studies that are in progress showed stable radiometal cyclization of octreotide analogues via NS₃ and N₂S₂ coordination forming five- and six-membered chelate rings. In vivo biodistribution studies are underway of ^99mTc-cyclized analogue 4.     

Managing diabetes and liver disease association

There is strong association between liver diseases and diabetes (DM) which is higher than expected by a chance association of two very common disorders. It can be classified into three categories: Liver disease related to diabetes, hepatogenous diabetes (HD), and liver disease occurring coincidentally with DM. The criteria for the diagnosis of diabetes associating liver disease are the same for primary diabetes. Two hours post glucose load is a better screening test for HD. HbA1c may not be suitable for diagnosis or monitoring of diabetes associating advanced liver disease. Apart from the increased cardiovascular risk in patients with type 2 DM (T2 DM) and NAFLD, the cardiovascular and retinopathy risk is low in HD. Patients with metabolic derangement should be screened for NAFLD which in turn may predict T2 DM development. Similarly, patients with established T2 DM should also be screened for NAFLD which further contributes to diabetes worsening.Diabetes is a significant risk factor for progression of the chronic liver disease. It is associated with poor patient survival.Treatment of diabetes associating liver disease appears beneficial. Metformin, if tolerated and not contraindicated, is recommended as a first-line therapy for patients with diabetes and chronic liver disease (CLD). If the hepatic disease is severe, insulin secretagogues should be avoided because of the increased risk of hypoglycaemia. Pioglitazone may be useful in patients with fatty liver disease. DPP-4 inhibitors showed effectiveness and safety for the treatment of T2 DM in CLD patients up to those with child B stage. GLP-1 receptor agonists and SGLT-2 inhibitors exhibit positive effects on weight and are associated with minimal risk of hypoglycaemia. Insulin must be used with caution, as hypoglycaemia may be a problem. Insulin analogues are preferred in the context of hypoglycaemiaStatins can be used to treat dyslipidaemia in NAFLD, also the use of angiotensin II receptor antagonist for hypertension is safe and beneficialGiven the clear association between diabetes mellitus and hepatocellular carcinoma, the strict control of glycaemia with insulin sensitizers can be essential in its prevention.The addition of DM to the currently used scores (Child-Pugh and MELD scores) may enhance the sensitivity and the specificity for prediction of morbidity and mortality rates in cirrhotic patients.In the new era of directly acting antiviral agents (DAAs) for HCV treatment, it is recommended to follow up lipid profile and blood sugar levels following SVR in order to adjust doses of medications used in diabetic (SVR is associated with reduction in insulin requirements) and dyslipidaemic patients (rebound increase in the lipid profile after clearing the virus may increase risk of cardiovascular disease (CVD)). The issues of post liver transplant diabetes and relation between DM and chronic HBV are highlighted.This narrative review and Consensus-based practice guidance (under revision and criticism) are based on a formal review and analysis of the recently published world literature on the topic (Medline search up to September 2017); and the experience of the authors and independent reviewers.     

Kawasaki disease in Jordan: demographics, presentation, and outcome

Kawasaki disease is the leading cause of acquired coronary artery disease in young children. There is a lack of data on Kawasaki disease and its effect on coronary arteries in Jordan and other developing countries. We report clinical and demographic data of Kawasaki disease in Jordan from a single institution, with emphasis on cardiac involvement and short to intermediate follow-up. Review of the medical records of 34 patients with Kawasaki disease from 1997 to 2010 was done for clinical and demographic variables. Echocardiographic and angiographic images were reviewed for patients at presentation and follow-up. The median age at presentation was 19 months, ranging from 2 months to 8 years, with a male to female ratio of 3.9:1. In all, 12 patients (35%) had incomplete Kawasaki disease. There was a high incidence of coronary artery involvement (41%), where 20.5% had aneurysms and 20.5% had ectasia without aneurysm. Most coronary aneurysms were present at the time of diagnosis. The only independent variable for prediction of coronary involvement was age, with an odds ratio of 0.63 per year (95% confidence interval 0.41-0.95).     

Tumor Dosimetry Using [124I]m-iodobenzylguanidine MicroPET/CT for [131I]m-iodobenzylguanidine Treatment of Neuroblastoma in a Murine Xenograft Model

Purpose

[¹²⁴I]m-iodobenzylguanidine (¹²⁴I-mIBG) provides a quantitative tool for pretherapy tumor imaging and dosimetry when performed before [¹³¹I]m-iodobenzylguanidine (¹³¹I-mIBG) targeted radionuclide therapy of neuroblastoma. ¹²⁴I (T _1/2?=?4.2?days) has a comparable half-life to that of ¹³¹I (T _1/2?=?8.02?days) and can be imaged by positron emission tomography (PET) for accurate quantification of the radiotracer distribution. We estimated expected radiation dose in tumors from ¹³¹I-mIBG therapy using ¹²⁴I-mIBG microPET/CT imaging data in a murine xenograft model of neuroblastoma transduced to express high levels of the human norepinephrine transporter (hNET).

Procedures

In order to enhance mIBG uptake for in vivo imaging and therapy, NB 1691-luciferase (NB1691) human neuroblastoma cells were engineered to express high levels of hNET protein by lentiviral transduction (NB1691-hNET). Both NB1691 and NB1691-hNET cells were implanted subcutaneously and into renal capsules in athymic mice. ¹²⁴I-mIBG (4.2?C6.5?MBq) was administered intravenously for microPET/CT imaging at 5 time points over 95?h (0.5, 3?C5, 24, 48, and 93?C95?h median time points). In vivo biodistribution data in normal organs, tumors, and whole-body were collected from reconstructed PET images corrected for photon attenuation using the CT-based attenuation map. Organ and tumor dosimetry were determined for ¹²⁴I-mIBG. Dose estimates for ¹³¹I-mIBG were made, assuming the same in vivo biodistribution as ¹²⁴I-mIBG.

Results

All NB1691-hNET tumors had significant uptake and retention of ¹²⁴I-mIBG, whereas unmodified NB1691 tumors did not demonstrate quantifiable mIBG uptake in vivo, despite in vitro uptake. ¹²⁴I-mIBG with microPET/CT provided an accurate three-dimensional tool for estimating the radiation dose that would be delivered with ¹³¹I-mIBG therapy. For example, in our model system, we estimated that the administration of ¹³¹I-mIBG in the range of 52.8?C206?MBq would deliver 20?Gy to tumors.

Conclusions

The overexpression of hNET was found to be critical for ¹²⁴I-mIBG uptake and retention in vivo. The quantitative ¹²⁴I-mIBG PET/CT is a promising new tool to predict tumor radiation doses with ¹³¹I-mIBG therapy of neuroblastoma. This methodology may be applied to tumor dosimetry of ¹³¹I-mIBG therapy in human subjects using ¹²⁴I-mIBG pretherapy PET/CT data.