Long-term efficacy and safety of interferon α-2a therapy in severe refractory ophthalmic Behcet’s disease

Ophthalmic involvement is the most debilitating complication of Behcet’s disease (BD). The aim of the current study is to report on the efficacy and safety of a long-term use of interferon alpha-2a (IFNα-2a) in the treatment of refractory ophthalmic BD in the Azari population of Iran. We retrospectively analyzed the clinical data of 12 patients with ophthalmic BD who were under IFNα-2a therapy. All these patients had previously been treated unsuccessfully with corticosteroid and at least one conventional immunosuppressive drug. IFNα-2a was administered at a daily dose of 6 million IU (MIU). After controlling the symptoms, a dose of 6 MIU three times per week was applied for 8–12 weeks, and then, a dose of 3 MIU was administered three times per week as a subcutaneous injection. Visual acuity and total inflammatory activity index (TIAI) were used in order to assess the response to the treatment. Response to the treatment and complete eye remission were obtained in 10 (83.3 %) and 7 (58.3 %) patients, irrespectively. Improvement or stabilization of visual acuity was observed in 18 (81.8 %) out of 22 eyes. After a mean period of 29.6 months, the use of IFNa-2a was discontinued in eight (66.7 %) patients. Unaltered vision for 2 years after IFNa-2a discontinuation happened in eight (100 %) patients. IFNa-2a is probably effective and safe in the treatment of refractory sight-threatening ophthalmic BD in the Azari population of Iran.     

Mendelian Randomization and Type 2 Diabetes

Type 2 diabetes (T2DM) is a common, complex disease that poses a substantial burden on individual and population health, but we have relatively limited understanding of its underlying pathophysiology. Observational studies have highlighted large numbers of risk factors for T2DM, some of which are modifiable through behavioural or pharmacological intervention. Determining which of these risk factors plays a causal role in the development of T2DM has been a challenge, but Mendelian randomisation (MR) studies are harnessing genetic data in population studies to offer new insights. Using evolving analytical methods, MR studies continue to address questions of causality related to T2DM, including exploring the roles of adiposity, blood lipids and inflammation. The causal roles of a number of important modifiable risk factors have been confirmed by MR studies, while the relevance of others has been called into question. As more MR studies are conducted, methods are developed and refined in order to make the most efficient and reliable use of available genetic and phenotypic data. In this review, the design and findings of some important MR studies related to T2DM are explored and their relevance for translation to clinical practice considered.     

A rare case of eccrine spiradenoma—treatment and management

A young male patient presented with multiple swellings on his chest and the nape of his neck. Physical examination revealed multiple small papulonodular swellings measuring 0.5?×?0.5 cm to 2?×?2 cm, that were soft without discharge with no surrounding skin changes or induration. Skin biopsy samples were diagnosed as benign adnexal neoplasm consistent with eccrine spiradenoma, trichoepithelioma, and cylindroma, i.e., Brooke–Spiegler syndrome. Having confirmed this to be a case of eccrine spiradenoma, surgical excision was performed and the raw area was covered with a split thickness skin graft taken from the right thigh and sutured over the raw area. The sternal lesion was circumferentially excised and the wound was primarily closed by Z-plasty. Surgical excision is considered the gold standard for the treatment of these cases, with low rates of recurrence. Around 50 such cases have been reported in the literature to date. Although eccrine spiradenomas are usually solitary and small, the findings in our case underscore the fact that a variety of presentations are possible. With strict clinical suspicion and histological criteria, the correct diagnosis can be achieved, especially when combined with pertinent clinical information and laboratory studies.Level of Evidence: Level V, therapeutic study.     

Penile Arterial Waveform Analyzer for Assessing Penile Vascular Function in Young Adults

Not only does erectile dysfunction (ED) reflect penile vascular disorder in the majority of patients, but it also implicates their high systemic cardiovascular risk. Based on the principle of reactive hyperemia after a brief period of penile ischemia, in this study, we tested the validity of a new Penile Arterial Waveform Analyzer (PAWA) in assessing the relative increase in post-ischemic penile perfusion. Twenty young adult males (mean age 24.24 ± 2.45) without known history of cardiovascular diseases were recruited, whose anthropometric characteristics were recorded and their serum testosterone levels as well as biochemical profiles were determined. A penile cuff was applied to each subject, with cuff pressure being increased from 80 to 250 mmHg, each for 4 min, followed by reperfusion for 7 min. By dividing the area under waveform contour of hyperemic and baseline signals after Ensemble Empirical Mode Decomposition (EEMD), a Penile Perfusion Index (PPI) was calculated. Penile Brachial Index (PBI) was also obtained for comparison. The results not only showed a significant agreement between PPI and serum testosterone levels, but also a superiority of PPI to PBI in distinguishing the high- and low-risk groups for potential ED (PPI: p = 0.039 vs. PBI: p = 0.147). PPI was also demonstrated to show significant correlations with waist circumference (p < 0.001), body mass index (p = 0.005), body weight, total triglyceride, high-density lipoprotein, and systolic and diastolic pressures (all p < 0.05). In conclusion, we proposed a portable and easy-to-operate system in assessing the relative increase in penile perfusion after brief ischemia. The PPI thus obtained correlated significantly with serum testosterone levels as well as key anthropometric and serum biochemical parameters even in apparently healthy young adults, suggesting its potential as a sensitive tool in monitoring penile vascular function and risk for ED.     

Slow versus standard up-titration of paroxetine for the treatment of depression in cancer patients: a pilot study

Objectives  

This study aimed to compare the tolerability and efficacy of two different titrations of paroxetine (slow and standard) in a population of cancer patients with depression.     

Prospective technical validation and assessment of intra-tumour heterogeneity of a low density array hypoxia gene profile in head and neck squamous cell carcinoma

Background and purposeTumour hypoxia is associated with a poor prognosis in head and neck squamous cell carcinoma (HNSCC), however there is no accepted method for assessing hypoxia clinically. We aimed to conduct a technical validation of a hypoxia gene expression signature using the TaqMan Low Density Array (TLDA) platform to investigate if this approach reliably identified hypoxic tumours.Materials and methodsTumour samples (n = 201) from 80 HNSCC patients were collected prospectively from two centres. Fifty-three patients received pimonidazole prior to surgery. TaqMan Low Density Array-Hypoxia Scores (TLDA-HS) were obtained by quantitative real-time PCR (qPCR) using a 25-gene signature and customised TLDA cards. Assay performance was assessed as coefficient of variation (CoV).ResultsThe assay was sensitive with linear reaction efficiencies across a 4log₁₀ range of inputted cDNA (0.001–10 ng/μl). Intra- (CoV = 6.9%) and inter- (CoV = 2.0%) assay reproducibility were excellent. Intra-tumour heterogeneity was lower for TLDA-HS (23.2%) than for pimonidazole (67.2%) or single gene measurements of CA9 (62.2%), VEGFA (45.0%) or HIG2 (39.4%). TLDA-HS in HNSCC cell lines increased with decreasing pO₂. TLDA-HS correlated with Affymetrix U133 Plus 2.0 microarray HS (p < 0.01) and positive pimonidazole scores (p = 0.005).ConclusionsGene expression measurements of hypoxia using a 25-gene signature and TLDA cards are sensitive, reproducible and associated with lower intra-tumour heterogeneity than assaying individual genes or pimonidazole binding. The approach is suitable for further assessment of prognostic and predictive capability in clinical trial material.     

Characterization of a novel tymovirus on tomato plants in Brazil

A tymovirus was isolated in Brazil from tomato plants with severe symptoms of leaf mosaic and blistering. The virus was mechanically transmissible to solanaceous indicator host species. The infected plants contained icosahedral particles and chloroplasts with membrane deformations which are typical cytopathic effects caused by tymoviruses. Its coat protein amino acid sequence shares the maximum of 64 % identity with the tymovirus Chiltepin yellow mosaic virus, which suggested that it can be considered as a distinct member of the genus Tymovirus. In a phylogenetic tree, this tymovirus was clustered with other solanaceous-infecting tymoviruses. It was tentatively named as Tomato blistering mosaic virus (ToBMV).