Is iron oxide a tissue-specific contrast medium in diagnostic ultrasound? A case report

We present a patient with Hodgkin's disease in whom computed tomography suggested focal lesions in the liver. As no lesions were detected by diagnostic ultrasound, magnetic resonance imaging (MRI) with iron oxide as contrast medium was performed for verification. MRI confirmed at least 3 small lesions. The ultrasound study performed immediately after this MRI scan easily detected these lesions. A biopsy was taken and histology showed infiltrates of Hodgkin's disease. The change in echogenicity of the liver and/or the lymphomatous tissue may be an effect of iron oxide. This observation has not been reported before.     

Is evening primrose oil of value in the treatment of premenstrual syndrome?

A systematic literature search of clinical trials of evening primrose oil (EPO) for the treatment of the premenstrual syndrome (PMS) was carried out with a view to performing a meta-analysis. Only seven placebo-controlled trials were found but only in five trials was randomization clearly indicated. Inconsistent scoring and response criteria made statistical pooling and hence a rigorous meta-analysis inappropriate. The two most well-controlled studies failed to show any beneficial effects for EPO, although because the trials were relatively small modest effects cannot be excluded. Nonetheless, on current evidence EPO is of little value in the management of premenstrual syndrome.     

Is early analgesia associated with delayed treatment of appendicitis?

Purpose

We sought to investigate the relationship between delay in treatment of appendicitis and early use of analgesia.

Basic Procedures

We designed a matched case-control study, with patients having delayed treatment of appendicitis as the cases and patients with no delay in treatment of appendicitis as controls matched for age, sex, Alvarado score, and date of diagnosis. Of 957 patients with appendicitis, there were 103 delayed cases. Matching patients were identified yielding 103 controls.

Main Findings

In comparing cases and controls for early opiate use (26/103 cases, 24/103 controls), there was no association with delayed treatment (odds ratio, 1.11; P = .745; 95% confidence interval, 0.59-3.89). When comparing cases and controls for early NSAID use (29/103 cases, 17/103 controls), an association was found with delayed treatment (odds ratio, 1.98; P = .045; 95% confidence interval, 1.01-3.89).

Conclusion

For early analgesia in appendicitis, we did not find an association with delayed treatment for opiate analgesia, but there did appear to be an association with nonsteroidal anti-inflammatory analgesia.     

Is delayed chemotherapy-induced emesis well managed in oncological clinical practice?

Nausea and vomiting have a negative influence on the quality of life of patients receiving chemotherapy. The Consensus Conference held in 1997 outlined the therapeutic procedure to prevent delayed emesis that might otherwise be induced by chemotherapy. So far, no study has evaluated the correct management of delayed emesis in clinical practice. This study was performed in an attempt to verify the conformity of the delayed emesis therapy administered in some oncological centres with the Consensus Conference guidelines. A total of 149 patients were observed for a minimum of one up to a maximum of four chemotherapy cycles; analysis of the data took account of whether the chemotherapy had a high (HEC), moderate (MEC) or low (LEC) emetogenic potential. Among 42 patients who received HEC, 18 (43%) received antiemetic prophylaxis conforming to standards; 23 (54.7%) of these 42 had delayed emesis, only 8 (34.7%) of whom were treated with adequate antiemetic protection. MEC was administered to 72 patients, 46 (64%) of whom received adequate prophylaxis; delayed emesis was observed in 31 (43%) of the 72 patients, 20 (64.5%) of whom received antiemetic prophylaxis according to established guidelines. Of 35 patients treated with LEC, 22.8% manifested delayed emesis; a high percentage of these patients, 68.5%, received prophylaxis, even though it was unnecessary. Of all patients observed, only 50.3% received correct antiemetic protection. We deduce from the study that antiemetic treatment for delayed emesis in clinical practice needs more attention. Correct prophylaxis is necessary when HEC is given, and antiemetic protection for patients receiving MEC must be improved; among patients treated with LEC those at high risk must be identified so that overtreatment can be avoided.     

Is FENO50 useful diagnostic tool in suspected asthma?

Background: Asthma diagnosis is based on the presence of symptoms and the demonstration of airflow variability. Airway inflammation measured by fractional exhaled nitric oxide, measured at a flow rate of 50 ml/s (FE_NO50) remains a controversial diagnostic tool. Aim: To assess the ability of FE_NO50 to identify bronchial hyperresponsiveness (BHR) to methacholine (provocative concentration of methacholine causing a 20% fall in FEV₁; PC20M ≤ 16 mg/ml) and to establish whether or not symptoms relate to FE_NO50 and PC20M in patients with no demonstrated reversibility to β₂‐agonist. Methods: We conducted a prospective study on 174 steroid naive patients with respiratory symptoms, forced expiratory volume in 1 s (FEV₁) ≥ 70% predicted and no demonstrated reversibility to β₂‐agonist. Patients answered to a standardised symptom questionnaire and underwent FE_NO50 and methacholine challenge. Receiver‐operating characteristic (ROC) curve and logistic regression analysis assessed the relationship between PC20M and FE_NO50, taking into account covariates (smoking, atopy, age, gender and FEV₁). Results: A total of 82 patients had a PC20M ≤ 16 mg/ml and had significantly higher FE_NO50 (19 ppb vs. 15 ppb; p < 0.05). By constructing ROC curve, we found that FE_NO50 cut‐off value of 34 ppb was able to identify not only BHR with high specificity (95%) and positive predictive value (88%) but low sensitivity (35%) and negative predictive value (62%). When combining all variables into the logistic model, FE_NO50 (p = 0.0011) and FEV₁ (p < 0.0001) were independent predictors of BHR whereas age, gender, smoking and atopy had no influence. The presence of diurnal and nocturnal wheezing was associated with raised FE_NO50 (p < 0.001 and p < 0.05, respectively). Conclusion: The value of FE_NO50 > 34 ppb has high predictive value of PC20M < 16 in patients with suspected asthma in whom bronchodilating test failed to demonstrate reversibility or was not indicated. However, FE_NO50 ≤ 34 ppb does not rule out BHR and should prompt the clinician to ask for a methacholine challenge.     

Is simultaneous presence of IgG4-positive plasma cells and giant-cell hepatitis a coincidence in autoimmune hepatitis? A case report

BACKGROUNDThe immune-mediated invasion of IgG4-positive plasma cells in the liver is found in some autoimmune hepatitis. Giant-cell hepatitis (GCH) is a very rare pathological feature in adults, and the clinical characteristics of the simultaneous appearance of the two pathological phenomena are not clear.CASE SUMMARYA 68-year-old woman was hospitalized with fatigue, poor appetite, and yellow urine for 20 d. Liver function tests and immunological indexes were significantly abnormal and accompanied by elevated serum IgG4 levels. Liver pathology revealed severe inflammation of the interface between the portal tract and hepatocytes, portal area inflammation, plasma cell infiltration, formation of rosette cells, IgG4-positive plasma cells > 10/high-power field, IgG4/IgG > 40%, and multinucleated liver cell swelling. IgG4-related autoimmune hepatitis (AIH) combined with GCH was diagnosed, and methylprednisolone was administered at 40 mg/day. Two weeks later, the clinical symptoms disappeared, and the liver function and immunological indicators were significantly improved. Methylprednisolone was reduced at a rate of 4–8 mg per week to 8 mg/day for maintenance. A second liver biopsy 48 wk later indicated that liver inflammation and fibrosis were significantly improved. IgG4-positive plasma cells and GCH were not detected. A literature search was conducted to analyze articles reporting similar pathological phenomena.CONCLUSIONAIH with simultaneous IgG4-positive plasma cell infiltration and GCH, liver inflammation, and fibrosis is possibly more severe than typical AIH but sensitive to corticosteroids.     

Is there still room for large registrative trials in unselected cancer patients? The case of anti-epidermal growth factor receptor antibodies in advanced non-small-cell lung cancer

Necitumumab, a monoclonal antibody directed against EGFR, is currently under development as a treatment for advanced NSCLC. Two Phase III randomized trials are ongoing, testing the addition of necitumumab to first-line platinum-based chemotherapy. In the same setting, cetuximab produced a statistically significant but clinically modest benefit in the whole study population, and no solid data have been produced about predictive factors of efficacy. Will the difference in structure between the two antibodies be enough to obtain a clinically relevant advantage, making real progress in the treatment of advanced NSCLC? Large Phase III trials in unselected patients risk demonstrating statistically significant results with debatable clinical relevance in the whole population, and the study of predictive factors is often left to subgroup analysis performed after the conduction of the trial. We do not need further ‘me-too’ drugs, or drugs that produce a small benefit in the unselected population. On the contrary, the oncologic community needs drugs to be used with a proper selection of patients, to obtain larger, relevant benefits in molecularly characterized subgroups. Final results of randomized trials with necitumumab in advanced NSCLC are expected in a couple of years.     

Is there still room for large registrative trials in unselected cancer patients? The case of anti-epidermal growth factor receptor antibodies in advanced non-small-cell lung cancer

Necitumumab, a monoclonal antibody directed against EGFR, is currently under development as a treatment for advanced NSCLC. Two Phase III randomized trials are ongoing, testing the addition of necitumumab to first-line platinum-based chemotherapy. In the same setting, cetuximab produced a statistically significant but clinically modest benefit in the whole study population, and no solid data have been produced about predictive factors of efficacy. Will the difference in structure between the two antibodies be enough to obtain a clinically relevant advantage, making real progress in the treatment of advanced NSCLC? Large Phase III trials in unselected patients risk demonstrating statistically significant results with debatable clinical relevance in the whole population, and the study of predictive factors is often left to subgroup analysis performed after the conduction of the trial. We do not need further 'me-too' drugs, or drugs that produce a small benefit in the unselected population. On the contrary, the oncologic community needs drugs to be used with a proper selection of patients, to obtain larger, relevant benefits in molecularly characterized subgroups. Final results of randomized trials with necitumumab in advanced NSCLC are expected in a couple of years.     

Diagnostic assays for Anti-PM/Scl IgG antibodies: Heterogeneity in antibody response or lack of standardization?

BackgroundThe aim of this study was to compare the correlation between new diagnostic methodologies for detecting anti-polymyositis/scleroderma (anti-PM/Scl) IgG antibodies associated with myositis and/or systemic scleroderma assays with existing platforms.MethodsSera from 164 samples previously tested for anti-PM/Scl IgG antibody by immunodiffusion, ID; 171 sera screened for anti-PM/Scl IgG by immunoprecipitation, IP; an additional group of 215 sera tested by ID and 46 healthy blood donor sera were retrospectively evaluated. Anti-PM/Scl IgG antibodies were measured using three PM/Scl-100 specific enzyme immunoassays (EIAs), PM1-alpha (PM1-α) EIA and a line immunoblot assay (LIA) for anti-PM/Scl-75 and ? 100 IgG antibodies. Selected samples were tested for the presence of antinuclear antibody (ANA) by indirect fluorescent antibody (IFA) assay.ResultsThe overall agreement between ID and all anti-PM/Scl IgG EIAs as determined by Crohnbach's alpha was unacceptable (α < 0.50). The concordance between the IP and either LIA or PM1-α EIA was greater than 90% however, the best agreement was seen between the IP and LIA PM/Scl-100 assays (98.3%). Compared to the LIA PM/Scl-75 and PM1-α tests, the LIA PM/Scl-100 IgG assay showed the best specificity in the healthy control group.ConclusionsOur results demonstrate considerable differences between assays for detecting anti-PM/Scl IgG antibodies which cannot be attributable to heterogeneity in antibody response alone. Further characterization and standardization of these assays are needed.     

Is there a case for paternalism in forensic nursing?

Forensic nurses often face a competing duty to patients and society. This article explores possible solutions to the ethical conflict.     

The diagnostic value of iron oxide nanoparticles for imaging of myocardial inflammation – quo vadis?

Cardiovascular magnetic resonance (CMR) is an integral part in the diagnostic work-up of cardiac inflammatory diseases. In this context, superparamagnetic iron oxide-based contrast agents can provide additional diagnostic information regarding the assessment of myocardial infarction and myocarditis. After intravenous administration, these nanoparticles are taken up by activated monocytes and macrophages, which predominantly accumulate in regions associated with inflammation as was successfully shown in recent preclinical studies. Furthermore, first clinical studies with a new iron oxide-complex that was clinically approved for the treatment of iron deficiency anaemia recently demonstrated a superior diagnostic value of iron oxide nanoparticles compared to gadolinium-based compounds for imaging of myocardial inflammation in patients with acute myocardial infarction. In this article, we outline the basic features of superparamagnetic iron oxide-based contrast agents and review recent studies using such nanoparticles for cardiac imaging in case of acute myocardial infarction as well as acute myocarditis. Moreover, we highlight the translational potential of these agents and possible research applications with regard to imaging and therapy.     

Can antibodies with specificity for soluble antigens mimic the therapeutic effects of intravenous IgG in the treatment of autoimmune disease?

Intravenous Ig (IVIg) mediates protection from the effects of immune thrombocytopenic purpura (ITP) as well as numerous other autoimmune states; however, the active antibodies within IVIg are unknown. There is some evidence that antibodies specific for a cell-associated antigen on erythrocytes are responsible, at least in part, for the therapeutic effect of IVIg in ITP. Yet whether an IVIg directed to a soluble antigen can likewise be beneficial in ITP or other autoimmune diseases is also unknown. A murine model of ITP was used to determine the effectiveness of IgG specific to soluble antigens in treating immune thrombocytopenic purpura. Mice experimentally treated with soluble OVA + anti-OVA versus mice treated with OVA conjugated to rbcs (OVA-rbcs) + anti-OVA were compared. In both situations, mice were protected from ITP. Both these experimental therapeutic regimes acted in a complement-independent fashion and both also blocked reticuloendothelial function. In contrast to OVA-rbcs + anti-OVA, soluble OVA + anti-OVA (as well as IVIg) did not have any effect on thrombocytopenia in mice lacking the inhibitory receptor FcgammaRIIB (FcgammaRIIB(-/-) mice). Similarly, antibodies reactive with the endogenous soluble antigens albumin and transferrin also ameliorated ITP in an FcgammaRIIB-dependent manner. Finally, broadening the significance of these experiments was the finding that anti-albumin was protective in a K/BxN serum-induced arthritis model. We conclude that IgG antibodies directed to soluble antigens ameliorated 2 disparate IVIg-treatable autoimmune diseases.     

Is there value in kinetic modeling of thrombin generation? No (unless…)

See also Stuijver DJF, Hooper JMW, Orme SM, van Zaane B, Squizzato A, Piantanida E, Hess K, Alzahrani S, Ajjan RA. Fibrin clot structure and fibrinolysis in hypothyroid individuals: the effects of normalising thyroid hormone levels. This issue, pp 1708–10.     

Value of case studies in disaster assessment?

Case studies can be useful in assessing and learning lessons from emergency situations. In this paper, different uses for disaster case studies, are explored with identification of potential pitfalls that should be avoided. In addition, ways to improve the rigor and significance of case studies are suggested. Case studies can be used as examples or as a research tool. If conducted properly, they can provide robust and compelling results. It is argued that sharing a common guide to conducting and writing case studies among all disaster risk reduction professionals could improve the quality of case study reports and thereby strengthen their value in advancing the prevention, preparedness, and management of disasters and emergencies.