Measurement issues in trials of pediatric acute diarrheal diseases: a systematic review

BACKGROUND: Worldwide, diarrheal diseases rank second among conditions that afflict children. Despite the disease burden, there is limited consensus on how to define and measure pediatric acute diarrhea in trials. OBJECTIVES: In RCTs of children involving acute diarrhea as the primary outcome, we documented (1) how acute diarrhea and its resolution were defined, (2) all primary outcomes, (3) the psychometric properties of instruments used to measure acute diarrhea and (4) the methodologic quality of included trials, as reported. METHODS: We searched CENTRAL, Embase, Global Health, and Medline from inception to February 2009. English-language RCTs of children younger than 19 years that measured acute diarrhea as a primary outcome were chosen. RESULTS: We identified 138 RCTs reporting on 1 or more primary outcomes related to pediatric acute diarrhea/diseases. Included trials used 64 unique definitions of diarrhea, 69 unique definitions of diarrhea resolution, and 46 unique primary outcomes. The majority of included trials evaluated short-term clinical disease activity (incidence and duration of diarrhea), laboratory outcomes, or a composite of these end points. Thirty-two trials used instruments (eg, single and multidomain scoring systems) to support assessment of disease activity. Of these, 3 trials stated that their instrument was valid; however, none of the trials (or their citations) reported evidence of this validity. The overall methodologic quality of included trials was good. CONCLUSIONS: Even in what would be considered methodologically sound clinical trials, definitions of diarrhea, primary outcomes, and instruments employed in RCTs of pediatric acute diarrhea are heterogeneous, lack evidence of validity, and focus on indices that may not be important to participants.

Equine botulism and acute pasture myodystrophy: new soil-borne emerging diseases in Switzerland?

In Switzerland, the incidence of equine botulism and acute pasture myodystrophy have remarkably increased in the last five years. Equine fodder-borne botulism in Europe is most likely caused by Clostridium botulinum types C and D that produce the toxins BoNT/C and BoNT/D. Horses showing signs suggestive of botulism (muscle weakness and tremors, reduced tongue tone, slow chewing, salivation and difficulties swallowing, drooping eyelids, mydriasis), especially patients that have fed on suspect fodder (mostly haylage), must be treated with anti-serum as soon as possible.They also need intensive care, which is often difficult to provide and always expensive in the face of a guarded to poor prognosis. Therefore, prevention (high standards of forage quality and vaccination) is all the more important. Pasture myodystrophy is an acute disease with signs of rhabdomyolysis and lethality rate over 90%. It affects grazing horses under frosty, windy and rainy conditions. Preliminary results indicate that Clostridium sordellii and Clostridium bifermentans producing lethal toxin may play a role in pasture myodystrophy. Our efforts concentrate on developing a new subunit vaccine for equine botulism and understanding the ethiology and pathogenesis of pasture myodystrophy with the goal of improving prevention against these highly fatal diseases that present a significant risk to our horse population.

Immunophenotyping of acute leukemia and lymphoproliferative disorders: a consensus proposal of the European LeukemiaNet Work Package 10

The European LeukemiaNet (ELN), workpackage 10 (WP10) was designed to deal with diagnosis matters using morphology and immunophenotyping. This group aimed at establishing a consensus on the required reagents for proper immunophenotyping of acute leukemia and lymphoproliferative disorders. Animated discussions within WP10, together with the application of the Delphi method of proposals circulation, quickly led to post-consensual immunophenotyping panels for disorders on the ELN website. In this report, we established a comprehensive description of these panels, both mandatory and complementary, for both types of clinical conditions. The reason for using each marker, sustained by relevant literature information, is provided in detail. With the constant development of immunophenotyping techniques in flow cytometry and related software, this work aims at providing useful guidelines to perform the most pertinent exploration at diagnosis and for follow-up, with the best cost benefit in diseases, the treatment of which has a strong impact on health systems.

TNF suppresses acute intestinal inflammation by inducing local glucocorticoid synthesis

Although tumor necrosis factor (alpha) (TNF) exerts proinflammatory activities in a variety of diseases, including inflammatory bowel disease, there is increasing evidence for antiinflammatory actions of TNF. In contrast, glucocorticoids (GCs) are steroid hormones that suppress inflammation, at least in part by regulating the expression and action of TNF. We report that TNF induces extraadrenal production of immunoregulatory GCs in the intestinal mucosa during acute intestinal inflammation. The absence of TNF results in a lack of colonic GC synthesis and exacerbation of dextran sodium sulfate-induced colitis. TNF seems to promote local steroidogenesis by directly inducing steroidogenic enzymes in intestinal epithelial cells. Therapeutic administration of TNF induces GC synthesis in oxazolone-induced colitis and ameliorates intestinal inflammation, whereas inhibition of intestinal GC synthesis abrogates the therapeutic effect of TNF. These data show that TNF suppresses the pathogenesis of acute intestinal inflammation by promoting local steroidogenesis.

Urinary soluble HLA-DR is a potential biomarker for acute renal transplant rejection

BACKGROUND.: Urine is a potentially rich source of biomarkers for monitoring kidney dysfunction. In this study, we have investigated the potential of soluble human leukocyte antigen (sHLA)-DR in the urine for noninvasive monitoring of renal transplant patients. METHODS.: Urinary soluble HLA-DR levels were measured by sandwich enzyme-linked immunosorbent assay in 103 patients with renal diseases or after renal transplantation. sHLA-DR in urine was characterized by Western blotting and mass spectrometry. RESULTS.: Acute graft rejection was associated with a significantly elevated level of urinary sHLA-DR (P<0.0001), compared with recipients with stable graft function or healthy individuals. A receiver operating characteristic curve analysis showed the area under the curve to be 0.88 (P<0.001). At a selected threshold, the sensitivity was 80% and specificity was 98% for detection of acute renal transplant rejection. sHLA-DR was not exosomally associated and was of lower molecular weight compared with the HLA-DR expressed as heterodimer on the plasma membrane of antigen-presenting cells. CONCLUSIONS.: sHLA-DR excreted into urine is a promising indicator of renal transplant rejection.

Prognostic importance of anaemia in patients with acute pulmonary embolism

Although associated with adverse outcomes in other cardiopulmonary diseases, limited evidence exists on the prognostic value of anaemia in patients with acute pulmonary embolism (PE). We sought to examine the associations between anaemia and mortality and length of hospital stay in patients with PE. We evaluated 14,276 patients with a primary diagnosis of PE from 186 hospitals in Pennsylvania, USA. We used random-intercept logistic regression to assess the association between anaemia at the time of presentation and 30-day mortality and discrete-time logistic hazard models to assess the association between anaemia and time to hospital discharge, adjusting for patient (age, gender, race, insurance type, clinical and laboratory variables) and hospital (region, size, teaching status) factors. Anaemia was present in 38.7% of patients at admission. Patients with anaemia had a higher 30-day mortality (13.7% vs. 6.3%; p <0.001) and a longer length of stay (geometric mean, 6.9 vs. 6.6 days; p <0.001) compared to patients without anaemia. In multivariable analyses, anaemia remained associated with an increased odds of death (OR 1.82, 95% CI: 1.60-2.06) and a decreased odds of discharge (OR 0.85, 95% CI: 0.82-0.89). Anaemia is very common in patients presenting with PE and is independently associated with an increased short-term mortality and length of stay.

Outcome after Thrombolysis for Acute Isolated Posterior Cerebral Artery Occlusion

To date, there is limited data on intra-arterial thrombolysis (IAT) and intravenous thrombolysis (IVT) for isolated posterior cerebral artery (PCA) occlusion. We aimed to evaluate recanalization, outcome and quality of life in patients who undergo thrombolysis for isolated PCA occlusion.

Tracking the transcriptional host response from the acute to the regenerative phase of experimental pneumococcal meningitis

Despite the availability of effective antibiotic therapies, pneumococcal meningitis (PM) has a case fatality rate of up to 30% and causes neurological sequelae in up to half of the surviving patients. The underlying brain damage includes apoptosis of neurons in the hippocampus and necrosis in the cortex. Therapeutic options to reduce acute injury and to improve outcome from PM are severely limited.With the aim to develop new therapies a number of pharmacologic interventions have been evaluated. However, the often unpredictable outcome of interventional studies suggests that the current concept of the pathophysiologic events during bacterial meningitis is fragmentary. The aim of this work is to describe the transcriptomic changes underlying the complex mechanisms of the host response to pneumococcal meningitis in a temporal and spatial context using a well characterized infant rat model.

Intra-Arterial Thrombolysis for Acute Ischemic Stroke in Octogenarians

It is unclear whether octogenarians benefit from intra-arterial thrombolysis (IAT) for the treatment of acute ischemic stroke (AIS). The aim of the present study was to compare baseline characteristics, clinical outcome and complications of patients aged ≥80 with those of patients aged <80 years.

Comparative trends in hospitalizations for osteoporotic fractures and other frequent diseases between 2000 and 2008

In Switzerland, the number, incidence, and cost of acute hospitalizations for major osteoporotic fractures (MOF) and major cardiovascular events (MCE) increased in both women and men between 2000 and 2008, although the mean length of stay (LOS) was significantly reduced. Similar trend patterns were observed for hip fractures and strokes (decrease) and nonhip fractures and acute myocardial infarctions (increase).

Role of integrins in fibrosing liver diseases

Integrins and other cell adhesion molecules regulate numerous physiological and pathological mechanisms by mediating the interaction between cells and their extracellular environment. Although the significance of integrins in the evolution and progression of certain cancers is well recognized, their involvement in nonmalignant processes, such as organ fibrosis or inflammation, is only beginning to emerge. However, accumulating evidence points to an instrumental role of integrin-mediated signaling in a variety of chronic and acute noncancerous diseases, particularly of the liver.

Nasopharyngeal microbiota in infants with acute otitis media

Interspecies interactions of the nasopharyngeal microbiota are likely to be involved in the pathogenesis of acute otitis media (AOM). Capturing the breadth of microbial interactions requires a detailed description of the microbiota during health and AOM.

Vascular Diseases of the Spinal Cord: A Review

OPINION STATEMENT: • In acute spinal cord ischemia syndrome (ASCIS), treatment recommendations are derived from data of cerebral ischemic stroke, atherosclerotic vascular disease and acute spinal cord injury. Besides acute management, secondary prevention is of major importance. Pathologies affecting the aorta as well as underlying cerebrovascular conditions should be treated whenever possible.• ASCIS may occur after aortic surgery, less often after thoracic endovascular aortic repair (TEVAR). Protocols are proposed.• Acute spinal cord hemorrhage can be treated surgically and/or pharmacologically.• Symptomatic treatment in patients with a spinal cord lesion is of major importance. Depending on level and extension of the lesion, there is a risk for systemic and neurological complications, which may be life-threatening.• Each spinal vascular malformation is a unique lesion that needs an individualized treatment algorithm. In case of a symptomatic vascular malformation, endovascular intervention is the primary treatment option.• Spinal dural Arteriovenous fistula (AVF) may be treated endovascularly or surgically. If preoperative localization of the fistula is possible, surgery is feasible with a low complication rate. In comparison, endovascular approaches are less invasive.• Spinal AVM are rather treated endovascularly than surgically or in a stepwise multidisciplinary approach.• Symptomatic and exophytic spinal cavernous angiomas should be treated surgically. Deep spinal cavernous angiomas that are asymptomatic or only show mild symptoms can be observed.