Clinical features and practical diagnosis of bullous pemphigoid

Bullous pemphigoid (BP) represents the most common autoimmune subepidermal blistering disease. BP typically affects the elderly and is associated with significant morbidity. It has usually a chronic course with spontaneous exacerbations. The cutaneous manifestations of BP can be extremely protean. While diagnosis of BP in the bullous stage is straightforward, in the non-bullous stage or in atypical variants of BP signs and symptoms are frequently non-specific with eg, only itchy excoriated, eczematous, papular and/or urticarial lesions that may persist for several weeks or months. Diagnosis of BP critically relies on immunopathologic examinations including direct immunofluorescence microscopy and detection of serum autoantibodies by indirect immunofluorescence microscopy or BP180-ELISA.

Early closure of ileostomy is associated with less postoperative nausea and vomiting

Background/Aims: Temporary loop ileostomy is increasingly used in colorectal surgery but necessitates secondary closure. We evaluated postoperative complications, particularly nausea and vomiting, in patients with early, intermediate, or late elective ileostomy closure. Methods: We included all patients undergoing ileostomy closure from 2001 to 2008. Time from ileostomy construction to closure was classified as early (EC, <12 weeks), intermediate (IC, 12–18 weeks), and late (LC, >18 weeks). Using multivariable logistic regression, we compared the frequency of postoperative complications between the groups. Results: We included 134 patients (87 males; median age 71 years, range 29–91). Carcinoma of the rectum (n = 67, 50%) was the main reason for ileostomy construction. The median time to ileostomy closure was 103 days (range 8–461). Among patients with EC, IC, and LC, postoperative nausea occurred in 50.0, 73.1, and 78.6%, respectively (p = 0.006), and postoperative vomiting in 22.5, 57.7, and 59.5%, respectively (p = 0.001). Adjusting for important covariates, the odds ratio for postoperative nausea was 2.0 (95% CI 0.76–5.1) for IC and 4.1 (95% CI 1.2–14.3) for LC compared to EC (p = 0.069). For postoperative vomiting, adjusted odds ratios were 3.8 (95% CI 1.4–10.4) for IC and 4.6 (95% CI 1.4–15.5) for LC (p = 0.012). Other complications did not differ between the groups. Conclusions: These findings suggest that early ileostomy closure might reduce postoperative nausea and vomiting.

Improved sensitivity of an interferon-gamma release assay (T-SPOT.TB™) in combination with tuberculin skin test for the diagnosis of latent tuberculosis in the presence of HIV co-infection

Background Interferon-gamma release assays (IGRA) are more specific than the tuberculin skin test (TST) for the diagnosis of Mycobacterium tuberculosis infection. Data on sensitivity are controversial in HIV infection. Methods IGRA (T-SPOT.TB) was performed using lymphocytes stored within 6 months before culture-confirmed tuberculosis was diagnosed in HIV-infected individuals in the Swiss HIV Cohort Study. Results 64 individuals (69% males, 45% of non-white ethnicity, median age 35 years (interquartile range [IQR] 31-42), 28% with prior AIDS) were analysed. Median CD4 cell count was 223 cells/μl (IQR 103-339), HIV-RNA was 4.7 log10 copies/mL (IQR 4.3-5.2). T-SPOT.TB resulted positive in 25 patients (39%), negative in 18 (28%) and indeterminate in 21 (33%), corresponding to a sensitivity of 39% (95% CI 27-51%) if all test results were considered, and 58% (95% CI 43-74%) if indeterminate results were excluded. Sensitivity of IGRA was independent of CD4 cell count (p = 0.698). Among 44 individuals with available TST, 22 (50%) had a positive TST. Agreement between TST and IGRA was 57% (kappa = 0.14, p = 0.177), and in 34% (10/29) both tests were positive. Combining TST and IGRA (at least one test positive) resulted in an improved sensitivity of 67% (95% CI 52-81%). In multivariate analysis, older age was associated with negative results of TST and T-SPOT.TB (OR 3.07, 95% CI 1,22-7.74, p = 0.017, per 10 years older). Conclusions T-SPOT.TB and TST have similar sensitivity to detect latent TB in HIV-infected individuals. Combining TST and IGRA may help clinicians to better select HIV-infected individuals with latent tuberculosis who qualify for preventive treatment.

Monogenic forms of hypertension

Arterial hypertension in childhood is less frequent as compared to adulthood but is more likely to be secondary to an underlying disorder. After ruling out more obvious causes, some patients still present with strongly suspected secondary hypertension of yet unknown etiology. A number of these children have hypertension due to single gene mutations inherited in an autosomal dominant or recessive fashion. The finding of abnormal potassium levels (low or high) in the presence of suppressed renin secretion, and metabolic alkalosis or acidosis should prompt consideration of these familial diseases. However, mild hypertension and the absence of electrolyte abnormalities do not exclude hereditary conditions. In monogenic hypertensive disorders, three distinct mechanisms leading to the common final pathway of increased sodium reabsorption, volume expansion, and low plasma renin activity are documented. The first mechanism relates to gain-of-function mutations with a subsequent hyperactivity of renal sodium and chloride reabsorption leading to plasma volume expansion (e.g., Liddle's syndrome, Gordon's syndrome). The second mechanism involves deficiencies of enzymes that regulate adrenal steroid hormone synthesis and deactivation (e.g., subtypes of congenital adrenal hyperplasia, apparent mineralocorticoid excess (AME)). The third mechanism is characterized by excessive aldosterone synthesis that escapes normal regulatory mechanisms and leading to volume-dependent hypertension in the presence of suppressed renin release (glucocorticoid remediable aldosteronism). Hormonal studies coupled with genetic testing can help in the early diagnosis of these disorders.

In vitro diagnosis of T cell-mediated drug allergy

Diagnosis of drug hypersensitivity relies on history, skin tests, in vitro tests and provocation tests. In vitro tests are of great interest, due to possible reduction of drug provocation tests. In this review we focus on best investigated in vitro techniques for the diagnosis of T cell-mediated drug hypersensitivity reactions. As drug hypersensitivity relies on different pathomechanisms and as a single diagnostic test usually does not cover all possible reactions, it is advisable to combine different tests to increase the overall sensitivity. Recently, proliferation-based assays have been supplemented by a panel of novel in vitro tests including analysis of cytotoxic potential of effector cells (granzyme B, granulysin, CD107a), evaluation of cytokine secretion (IL-2, IL-5, IL-13, and IFN-γ) and up-regulation of cell surface activation markers (CD69). We discuss the latest findings and readout systems to identify causative drugs by detecting functional and phenotypic markers of drug-reacting cells, and their ability to enable a more conclusive diagnosis of drug allergy.

Early detection of subclinical organ dysfunction by microdialysis of the rectus abdominis muscle in a porcine model of critical intra-abdominal hypertension

The aim of this study was to evaluate microdialysis of the rectus abdominis muscle (RAM) for early detection of subclinical organ dysfunction in a porcine model of critical intra-abdominal hypertension (IAH). Microdialysis catheters for analyses of lactate, pyruvate, and glycerol levels were placed in cervical muscles (control), gastric and jejunal wall, liver, kidney, and RAM of 30 anesthetized mechanically ventilated pigs. Catheters for venous lactate and interleukin 6 samples were placed in the jugular, portal, and femoral vein. Intra-abdominal pressure (IAP) was increased to 20 mmHg (IAH20 group, n = 10) and 30 mmHg (IAH30, n = 10) for 6 h by controlled CO2 insufflation, whereas sham animals (n = 10) exhibited a physiological IAP. In contrast to 20 mmHg, an IAH of 30 mmHg induced pathophysiological alterations consistent with an abdominal compartment syndrome. Microdialysis showed significant increase in the lactate/pyruvate ratio in the RAM of the IAH20 group after 6 h. In the IAH30 group, the strongest increase in lactate/pyruvate ratio was detected in the RAM and less pronounced in the liver and gastric wall. Glycerol increased in the RAM only. After 6 h, there was a significant increase in venous interleukin 6 of the IAH30 group compared with baseline. Venous lactate was increased compared with baseline and shams in the femoral vein of the IAH30 group only. Intra-abdominal pressure-induced ischemic metabolic changes are detected more rapidly and pronounced by microdialysis of the RAM when compared with intra-abdominal organs. Thus, the RAM represents an important and easily accessible site for the early detection of subclinical organ dysfunction during critical IAH.

Early detection of action potential duration alternans using an autoregressive model

Annual Meeting of the Biophysical Society, San Diego, USA

Using an adaptive autoregressive model for the early detection of action potential duration alternans

Cardiostim 2012, Nice, France

Challenges in the early detection of psychosis in children and adolescents

The early detection and treatment of persons at-risk for psychosis is currently regarded a promising strategy in fighting the devastating consequences of psychotic disorders. The two current at-risk approaches, i.e., the "ultra high risk" and the "basic symptom" criteria, were mainly developed on adult samples. Initial evidence suggests, however, that they cannot simply be applied to children and adolescents. For ultra high risk criteria, there is indication of some attenuated psychotic symptoms being potentially non-specific in adolescents and of brief limited intermittent symptoms being difficult to clinically classify in children when observable behavioral correlates are missing. For basic symptoms, too, only preliminary indication of their usefulness in children and adolescents exists. Since developmental peculiarities in the assessment of basic symptoms should be considered, a child and youth version of the Schizophrenia Proneness Instrument (SPI-CY) was developed. In conclusion, research on the clinical-prognostic validity of the at-risk criteria and their potential adoption to the special needs of children and adolescents is needed. If a Prodromal Risk Syndrome for Psychosis or Attenuated Psychotic Symptoms Syndrome will be included into DSM-V, it has to be highlighted that its suitability for children and adolescents is only insufficiently known.