Carotid artery disease: Stenting versus endarterectomy

Atherosclerotic carotid artery stenosis is a major cause of disabling stroke or death. Although carotid endarterectomy (CEA) is currently considered to be the standard of care for patients with a severe symptomatic stenosis and selected patients with an asymptomatic carotid stenosis, carotid angioplasty and stenting (CAS) is increasingly being used as an alternative treatment modality. This article briefly summarizes the current trial data on CEA and CAS. More importantly, potential risk factors for CEA and CAS are reviewed and the complementary role of these techniques in the management of the individual patient is discussed.     

Pharmacological versus invasive treatment in patients with atrial fibrillation

Aim of this prospective study was to assess quality of life (QoL), left ventricular (LV) function and exercise performance in two groups of patients (pts) with atrial fibrillation (Af) treated with: radiofrequency catheter ablation (RFA) and antiarrhythmic drugs (AA). Between 1996 and 2000 - 74 patients, 28 women, with drug refractory Af were enrolled by clinical indications for two modes of therapy: RFA and AA. RFA group consisted of 38 pts, 63.7 +/- 11.5 years old: 28 pts with RF AV Node ablation and pacemaker implantation (PI) and 10 pts with AV Node modification or right atrial isthmus RF ablation due to Af conversion to atrial flutter (Aflu) during medical therapy. AA group consisted of 36 pts, aged 59.7 +/- 13.8 years. Patients from RFA group suffered significantly more serious diseases than pts from AA group. No significant (sign.) differences between two groups were found in age, gender, arrhythmia history and number of AA taken. Pts were analyzed before entry, after 3 and 12 months of follow-up (3 mo. FU, 12 mo. FU) with following indices: LV function (Echo: EF & FS), exercise performance (treadmill test), QoL questionnaires, number of hospital admissions connected to arrhythmia or procedures (RFA & PI), number of AA drugs taken in RFA group. RFA group: Two deaths occurred due to end stage respiratory insufficiency (COPD), one pt required reposition of pacemaker lead. AA group: 3 pts required RFA due to uncontrolled Af/Aflu (AV Node ablation with PI - 1 pt, right atrial isthmus ablation - 2 pts). Analysis of two patients groups: LV function: Sign. improvement (EF & FS) in both groups in 12 mo. FU; Exercise performance: no sign. changes in 3 and 12 mo. FU. QoL: Arrhythmia scale: 3 mo. FU sign. reduction in both groups; 12 mo. FU reduction in RFA group only; Anxiety scale: 3 and 12 mo. FU sign. reduction of anxiety level in RFA group; Exercise and activity scales: 3 and 12 mo. FU sign. improvement in RFA group. During 3 and 12 mo. FU sign. less pts from RFA group required hospital admission versus pts from AA group. Sign. reduction in AA was noted in RFA group. Patients with symptomatic Af treated with RFA benefit from this kind of therapy more than patients treated with AA. Quality of life improvement visible in short term observation in patients from RFA group is still present after one year observation. Improvement in LV function is observed after one year in both groups of pts with Af.     

Effect of adding albumin to solutions of somatostatin on inhibiting pentagastrin-stimulated acid secretion in dogs

In five conscious dogs with chronic gastric fistulas we studied the effect of somatostatin solutions on pentagastrin-stimulated acid secretion. Somatostatin was dissolved in 0.154 M NaCl alone or in the same amount of saline to which dog albumin had been added to give a 0.5% solution. Somatostatin produced a dose-dependent inhibition of pentagastrin-stimulated gastric secretion. However, the inhibition was significantly less when somatostatin was dissolved in saline as compared to saline plus albumin. This study suggests that albumin should be added to somatostatin solutions to preserve biological activity, and it confirms previous reports indicating that, without albumin, basic peptides have a tendency to stick to infusion systems.     

Psychometric methods for diagnosing and monitoring minimal hepatic encephalopathy —current validation level and practical use

Metabolic Brain Disease - Hepatic encephalopathy (HE) is cerebral dysfunction caused by liver failure and inflicts 30-40% of patients with liver cirrhosis during their disease course. Clinically...     

Effective and safe translation of intensified insulin therapy to general internal medicine departments

Summary Up to now all published experience with intensified insulin therapy has originated from specialized diabetes centres. However, even in diabetes centres and under research conditions intensification of insulin therapy may substantially increase the risk of severe hypoglycaemia. The aim of the present study was to demonstrate the feasibility of effectively and safely transfering intensified insulin therapy based upon a 5-day in-patient treatment and teaching programme from a University diabetes centre to non-specialized general hospitals. A total of nine general hospitals were recruited; the University diabetes centre served as a reference centre. From each general hospital a nurse and a dietitian were trained as diabetes educators, and a diabetes unit with about 10 beds was organized within each department of internal medicine. A total of 697 consecutively admitted Type 1 (insulin-dependent) diabetic patients (age 26±7 years, duration of diabetes 8±7 years) who participated in the programme either in one of the general hospitals (n=579) or in the reference centre (n=118) were re-examined after 1, 2 and 3 years. Insulin therapy was intensified to a similar extent in the reference centre and the general hospitals: at the 3-year follow-up about 80% of the patients injected insulin at least three times daily or used continuous subcutaneous insulin infusion (10%), and about 70% reported measuring blood glucose levels more than twice per day. HbA₁ levels were lowered (p<0.0001) to comparable levels, i. e. from 10.6 % (reference centre) and 9.9 % (general hospital), respectively, at baseline to 9.4 % and 9.3 %, respectively, at the 3-year follow-up. The yearly incidence rates of severe hypoglycaemia decreased from 0.23 (reference centre) and 0.29 (general hospitals), respectively, during the year before intensification of insulin therapy, to 0.19 (NS) and 0.12 (p<0.005), respectively, during the third year of follow-up. Days spent in hospital were reduced in both groups (from 11 and 7 days per patient per year, respectively, to 5 and 4 days, respectively, p<0.0001). In conclusion, this study shows that intensified insulin therapy based upon a structured and comprehensive training of the patients by diabetes educators can be effectively and safely translated from a specialized University diabetes centre to general medicine departments.     

The use of dendritic cells in cancer immunotherapy

Cancer immunotherapy aims at eliciting an immune response directed against tumor antigens to help fight off residual tumor cells and thereby improve survival and quality of life of cancer patients. Different immunotherapeutic approaches share the use of dendritic cells (DCs) to present tumor-associated antigens to T-lymphocytes. Ex vivo generated DCs can be loaded with antigens and re-infused to the patients, or they can be used for ex vivo expansion of antitumor lymphocytes. Alternatively, methods exist to target antigens to DCs in vivo without need for ex vivo cell manipulations. The clinical studies have shown that DC administration to patients is safe and induces antigen-specific immunity. However, it seldom elicits objective clinical responses in patients with advanced-stage malignancies. Novel insights into DC and lymphocyte regulation are expected to lead to more effective vaccines in the near future. Meanwhile, efforts are directed at identifying the most appropriate clinical targets for active specific immunotherapies. Data suggests that vaccinations may indeed be beneficial when given in the adjuvant setting rather than to treat metastatic cancers. These issues are discussed here together with an overview of the DC-based antitumor immunotherapy studies.     

ICOS-ligand, expressed on human endothelial cells, costimulates Th1 and Th2 cytokine secretion by memory CD4+ T cells

Endothelial cells (EC) play a central role in inflammatory immune responses and efficiently induce effector functions in T cells, despite lacking the classical costimulatory ligands CD80 and CD86. By using the mAb HIL-131 we now demonstrate that human inducible costimulator-ligand (ICOS-L), a molecule related to CD80/CD86, is constitutively expressed on human EC in vivo. In vitro, ICOS-L expression was strongly enhanced on human umbilical vein EC and microvascular EC by the inflammatory cytokines tumor necrosis factor alpha and IL-1beta, and to a lower extent by stimulation of EC by CD40 or lipopolysaccharide. Coculture of MHC class II(+) EC with resting memory CD4(+) T cells in the presence of superantigen led to a marked up-regulation of ICOS on T cells and to the production of Th1 (IFN-gamma, IL-2) and Th2 cytokines (IL-4, IL-10, IL-13). When these cocultures were performed in the presence of the inhibitory mAb HIL-131, secretion of all cytokines was reduced by about 50-80%, indicating that ICOS-L is a major costimulator in EC-mediated T cell activation. Taken together, our data suggest an important physiological role of ICOS-L in the reactivation of effector/memory T cells on the endothelium controlling the entry of immune cells into inflamed tissue.     

Risk of malignancy in an unselected cohort of Icelandic patients with systemic lupus erythematosus

In the present literature there is still controversy as to whether patients with systemic lupus erythematosus (SLE) are at increased risk of developing malignant diseases. In recent years a number of epidemiological studies have been conducted and some have suggested an association between SLE and malignant diseases while other studies have not. The objective of this study was to investigate this relationship in an unselected cohort of Icelandic patients with SLE. All patients diagnosed with SLE registered in the Icelandic SLE database were compared to the Icelandic cancer registry. For completeness, hospital charts and outpatient notes were also reviewed. The study period was from 1957 to the end of 2001. The O/E (observed/expected ratio), CI and P-value were calculated for total number of malignancies as well as individual malignancy types. Of 238 patients diagnosed with SLE (213 women and 25 men) 39 malignancies were diagnosed in 36 patients; 32 women and four men. Of the 36 patients, 27 were diagnosed subsequently with SLE and malignant disease. The mean age at diagnosis of SLE was 43.2 years (range 10-81) and at time of diagnosis of malignancy 62.7 years (range 43-86). The O/R for the whole study population was 1.38 (CI 0.89-1.87, P = 0.063), 1.45 for the women (CI 0.91-1.99, P = 0.051) and 1.03 for the men (CI 0.22-2.66, P = 0.560). The O/R for the most frequent malignancies diagnosed subsequently to SLE was 6.43 for squamous cell skin cancer (CI 1.31-18.5, P = 0.012), 5.48 for lymphoma (CI 0.64-19.6, P = 0.052), 2.46 for uterine cancer (CI 0.29-8.78, P = 0.196), 2.0 for ovarian cancer (CI 0.23-7.14, P = 0.264), 1.72 for lung cancer (CI 0.36-4.95, P = 0.254) and 1.6 for breast cancer (CI 0.65-3.23, P = 0.154). The total number of patient-years at risk was 2774 years. The results from this study on an unselected cohort of Icelandic SLE patients do not suggest an overall association between SLE and malignancy. Squamous cell skin cancer was the only individual cancer type that was statistically increased in the population and the numbers for lymphoma were borderline statistically significant.     

Assessing neuropathic pain in patients with low back‐related leg pain: Comparing the painDETECT Questionnaire with the 2016 NeuPSIG grading system

Background

Low back‐related leg pain with nerve root involvement is conceptually regarded as a neuropathic condition. However, it is uncertain to what extent patients with this condition can be formally classified with neuropathic pain.

Method

First, we used the 2016 revision of the IASP Special Interest Group on Neuropathic Pain (NeuPSIG) grading system for neuropathic pain to grade patients suffering from low back‐related leg pain and a corresponding disc herniation with either unlikely, possible, probable or definite neuropathic pain. Examination included bedside quantitative sensory testing. Next, we used the clinical classification based on the 2016 NeuPSIG grading system as a reference standard to assess the ability of the painDETECT Questionnaire to identify patients with neuropathic pain.

Results

Of the 50 included patients, six (12%) fulfilled the clinical classification criteria for probable and 44 (88%) for definite neuropathic pain, while none were graded unlikely or possible. According to painDETECT, 23 patients (46%) were classified with unlikely neuropathic pain, 18 patients (36%) had an uncertain condition and in nine patients (18%) neuropathic pain was likely. Among the 44 patients graded as having definite neuropathic pain by the clinical classification, eight were classified as likely neuropathic pain by painDETECT, resulting in an agreement of 18%. Of these 44 patients graded with definite neuropathic pain, painDETECT classified 21 patients (48%) as unlikely and 15 (34%) as uncertain.

Conclusion

Our results do not support the use of painDETECT as a screening tool to classify or grade neuropathic components in patients with low back‐related leg pain.

Significance

The painDETECT Questionnaire performed poorly at detecting neuropathic pain among patients with low back‐related leg pain, compared to clinical examination based on the 2016 NeuPSIG grading system as a reference standard. Our results do not support the use of painDETECT as a screening tool to classify or grade neuropathic components in this population.