Periodic Therapeutic Plasma Exchange in Patients With Moderate to Severe Chronic Myasthenia Gravis Non‐Responsive to Immunosuppressive Agents: An Eight Year Follow‐Up

Few patients with moderate or severe myasthenia gravis (MG) do not respond to immunosuppressive treatment. We present our experience with periodic therapeutic plasma exchange (TPE), in 11 patients with MG resistant to intravenous immunoglobulin (IVIg) therapy, who had frequent relapses even whilst on high doses of immunosuppressive drugs, over a period of 8 years. All patients underwent TPE until control of their symptoms was achieved, and afterwards TPE sessions were continued periodically in an attempt to achieve remission of the disease, without immunosuppressant therapy. Two of the patients were progressively weaned off immunosuppressive agents, as well as TPE, and they are now symptom free. The other nine patients are still under a periodic TPE regime. Seven of them were weaned off all medications and required an average of 3.7 TPE sessions per year during the last 5 years. In the other two patients, those with the most severe form of the disease, the immunosuppressant dosage has been decreased and a TPE session every 2–3 weeks is required in order to control their symptoms. Through all these years TPE has been well tolerated and only minor side‐effects were observed in two patients. Finally, during this 8 year follow‐up period, nine of the patients treated with periodic TPE have been in good control of their symptoms over the last 5 years, and the other two patients live a normal life without any treatment in the last 3 years. Our results suggest that periodic TPE is safe and effective in the control of symptoms in patients with moderate to severe MG who do not respond to immunosuppressive therapies.     

Sjogren's syndrome in a patient with ulcerative colitis and primary sclerosing cholangitis: Case report and review of the literature

Inflammatory bowel disease has been reported to co-exist with other autoimmune diseases. Sjogren's syndrome is an autoimmune disorder characterized by xerostomy and/or xerophthalmy. Sjogren's syndrome occurring in IBD has been very rarely reported.A 45-year old woman diagnosed ten years ago with ulcerative pancolitis and primary sclerosing cholangitis was referred to our outpatient IBD clinic because of xerostomy but not for xerophthalmy for the previous three months. The patient had been under azathioprine maintenance treatment (2 mg/kg) and achieved long-term disease remission for the past 4 years. Patient clinical examination and laboratory tests were unremarkable. Salivary gland biopsy and complete ophthalmologic investigation were performed and the patient was diagnosed with Sjogren's syndrome.Understanding sicca manifestations in IBD is difficult since the pathogenesis of this intestinal disorder is not yet clear. Of these complex autoimmune phenomena which occur along with IBD it is quite difficult to categorize concomitant Sjogren's syndrome as primary or secondary and literature is conflicting. The possibility of Sjogren's syndrome should always be considered and properly investigated in patients diagnosed with inflammatory bowel disease who develop a constellation of constitutional sicca symptoms.     

The direct effects of tacrolimus and cyclosporin A on isolated human islets: A functional, survival and gene expression study

The use of immunosuppressive drugs in transplanted patients is associated with the development of diabetes, possibly due to β-cell toxicity. To better understand the mechanisms leading to post-transplant diabetes, we investigated the actions of prolonged exposure of isolated human islets to therapeutical levels of tacrolimus (Tac) or cyclosporin A (CsA). Islets were isolated from the pancreas of multiorgan donors by enzymatic digestion and density gradient centrifugation. Functional, survival and molecular studies were then performed after 4 days of incubation with therapeutical concentrations of Tac or CsA. Glucose-induced insulin secretion was significantly decreased in Tac, but not in CsA exposed islets, which was associated with a reduction of the amount of insulin granules as shown by electron microscopy. The percentage of apoptotic β-cells was higher in Tac than CsA exposed islets. Microarray experiments followed by Gene Set Enrichment Analysis revealed that gene expression was more markedly affected upon Tac treatment. In conclusion, Tac and CsA affect features of beta-cell differently, with several changes occurring at the molecular level.     

Predictors of all-cause mortality for patients with Chagas' cardiomyopathy listed for heart transplantation

This study sought to determine independent predictors of all-cause mortality for patients with Chagas' disease heart failure listed for heart transplantation. Need of inotropic support (p=0.01; hazard ratio=14.68, 95% Confidence Interval 1.86 to 115.82) and the Transpulmonary Gradient (p=0.02; HR=1.15, 95% Confidence Interval 1.03 to 1.30) were established independent predictors of all-cause mortality.     

Downgrading BIRADS 3 to BIRADS 2 category using a computer-aided microcalcification analysis and risk assessment system for early breast cancer

This paper explores the potential of a computer-aided diagnosis system to discriminate the real benign microcalcifications among a specific subset of 109 patients with BIRADS 3 mammograms who had undergone biopsy, thus making it possible to downgrade them to BIRADS 2 category. The system detected and quantified critical features of microcalcifications and classified them on a risk percentage scale for malignancy. The system successfully detected all cancers. Nevertheless, it suggested biopsy for 11/15 atypical lesions. Finally, the system characterized as definitely benign (BIRADS 2) 29/88 benign lesions, previously assigned to BIRADS 3, and thus achieved a reduction of 33% in unnecessary biopsies.     

<Emphasis Type="Italic">In Vitro</Emphasis> Comparison of the Effect of Stent Configuration on Wall Shear Stress Using Time-resolved Particle Image Velocimetry

Time resolved particle image velocimetry was used to measure wall shear stress (WSS) and oscillatory shear index (OSI) within a 3.0 mm diameter compliant vessel model implanted with an Abbott Vascular XIENCE V^® stent in five configurations: baseline, over-expanded, increased vessel diameter, two overlapped stents, and increased stent length. Flow through unstented vessels was also tested for comparison. Flow conditions featured a realistic coronary pressure-flow offset and reversal at average flow rates corresponding to resting (Re = 160, f = 70 bpm) and exercise conditions (Re = 300, f = 120 bpm). Comparisons revealed that the WSS was similar for all cases behind the first strut and downstream of the device, indicating that changes in configuration have little effect downstream. However, there were notable differences within each stent revealing reduced WSS values for all cases due to the stent-imposed expansion of the vessel wall (0.20–9.29 dynes/cm² for Re = 160 and d = 3.0 mm). Over-expanding the stent with a second balloon affected the alignment of the stent geometry, and led to higher WSS at the inlet and lower values at mid-stent. The overlapped stents showed disturbed flow and a WSS deficit region downstream of the overlapped region. Analysis of the longer stent showed that the WSS within the vessel recovers with distance. An overall correlation was noted between decreased WSS values and elevated OSI. Results of this study are important because decreased WSS has been implicated in endothelial cell changes and increased restenosis, and clinical research has shown that a link exists between deployment configurations and negative patient outcomes.     

Right coronary ostium agenesis with absence of the right coronary artery: a rare case of non-ST elevation coronary syndrome

We present a case with right coronary ostium agenesis with anomalous origin of the right coronary artery from the left circumflex artery, which caused a non-ST elevation coronary syndrome. A review of the literature indicates this to be an extremely rare case.