Observer variability in the pulmonary examination

Observer variability in the pulmonary examination was assessed by having four blindfolded observers (two medical students and two pulmonary physicians) twice examine 31 patients with abnormal pulmonary findings. Examiners were consistent in the repetitive detection of pulmonary abnormalities in 74–89% of the examinations; conversely, 11–26% of the time they disagreed with themselves. Although pulmonary specialists recorded fewer (55% of observations) abnormal findings than did medical students (74%), they were significantly (p=0.008) less self-consistent than were the students. There was no clear trend in agreement between examiners (kappa=0.20−0.49). Each examiner’s findings were compared with those of physicians specially trained in pulmonary examination. Dichotomous variables (wheezes, crackles, rubs) were more reliably detected (kappa=0.30−0.70) than graded variables (tympany, dullness, breath sound intensity), where kappa=0.16−0.43. The authors suggest that dichotomous variables deserve greatest clinical reliance; that time in training, alone, does not improve clinical performance; and that there is a disconcertingly large amount of inter- and intraobserver disagreement in this fundamental clinical task. Received from the Division of General Internal Medicine, Department of Medicine; the Division of Biometry, Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina; and the Ambulatory Care Service and Health Services Research Field Program, Durham V.A. Medical Center, Durham, North Carolina.     

Proportion of Patients With Hypertension Resolution Following Adrenalectomy for Primary Aldosteronism: A Systematic Review and Meta‐Analysis

Unilateral primary aldosteronism (PA) is often treated with adrenalectomy, but hypertension resolution rates are variable. A valid estimate of the postoperative normotension rate is necessary to inform the utility of PA testing and treatment. The authors searched MEDLINE In‐Process & Other Non‐Indexed Citations, Embase, and Cochrane Central Register of Controlled Trials. Prospective adult cohort studies with surgically treated PA that reported resolution of hypertension without the aid of medications were included. Among 2620 abstracts identified by the search, 25 studies in the systematic review with data on 1685 patients were investigated. The pooled proportion of normotension following adrenalectomy was 52% (95% confidence interval, 0.44–0.60). Meta‐regression demonstrated a significant negative association between length of follow‐up and proportion of normotension, with normotension dropping by 6.7% per year of follow‐up (coefficient −0.006; 95% confidence interval, −0.01 to 0.002). Overall, approximately half of the patients experienced hypertension resolution, although this outcome may not be durable in all patients.

Primary aldosteronism (PA) is defined as a form of drug‐resistant and potentially curable hypertension with evidence of excess aldosterone secretion, suppressed plasma renin activity, and often hypokalemia.¹ Initially thought to be rare, PA is the leading cause of secondary hypertension. With increased screening and detection, the incidence of PA among hypertensive patients is currently reported at approximately 10%.² This syndrome has multiple etiologies, including inherited gene mutations,³ development of autoantibodies,⁴ and ectopic aberrant functional adrenal receptors.⁵ The clinical management is guided by the definition of unilateral vs bilateral adrenal involvement. With rare exception, adrenalectomy is reserved for unilateral adrenal disease.The proportion “cured” following adrenalectomy for patients with PA has been reported to range from 0% to 100%.⁶ However, “cure” is variably defined in the literature. These definitions include normal blood pressure (BP), normal BP without aid of antihypertensive medications, a reduced need for antihypertensive medications, and biochemical normalization, among others. Biochemical normalization of the aldosterone‐renin ratio is likely a necessary part of a definition of “cure.” At this time, however, there is no global consensus on the interpretation of postoperative aldosterone‐renin ratios with the existence of variable assays and cutoffs for even initial diagnosis. Therefore, from the patient''s perspective and in the absence of patient‐level clinical end point data, attainment of medication‐free normotension may be the most uniform and recognizable health benefit of surgical PA treatment. Individually reported results of long‐term resolution of hypertension without antihypertensive medications are between 30% and 70% following adrenalectomy.⁷ The primary aim of this systematic review and meta‐analysis was to determine the proportion of hypertension resolution without the aid of antihypertensive agents following adrenalectomy in patients with PA. To our knowledge, no previous meta‐analysis has been performed. A secondary objective was to identify patient‐level factors reported to be associated with hypertension resolution in patients managed with adrenalectomy.     

Monoclonal IgM radioimmunoassay for hepatitis B surface antigen: high binding activity in serum that is unreactive with conventional antibodies.

Using a monoclonal IgM antibody (anti-HBs) to hepatitis B surface antigen (HBsAg) in a radioimmunoassay for hepatitis B, we have detected high binding activity in human serum that was unreactive in assays employing conventional anti-HBs reagents. The binding material was isolated from serum by affinity chromatography on monoclonal IgM anti-HBs, and comparison of the material with HBsAg (by sodium dodecyl sulfate/polyacrylamide gel electrophoresis) demonstrated that the two shared several similar polypeptides. Furthermore, comparison of the binding properties of HBsAg and concentrated monoclonal immunoreactive material with conventional and monoclonal anti-HBs reagents demonstrated some antigenic crossreactivity. The molecular weight of the monoclonal immunoreactive material was approximately 2 X 10(6). Immunoprecipitation of the material with monoclonal IgM antibodies and examination by electron microscopy revealed clumped and "spiculated" particles that resembled 22-nm hepatitis B particles coated with the same antibody. Thus, this study suggests that the high-binding-activity material, detected in serum only by the monoclonal radioimmunoassay, is not identical with HBsAg, but it shares some common properties.     

Metastatic metaplastic breast carcinoma mimicking pulmonary squamous cell carcinoma on fine‐needle aspiration

Metaplastic squamous cell carcinoma (SCC) of the breast is a rare type of breast cancer. Metastases to the lung, which can be a major site of second primary tumor development among breast cancer patients, are difficult to distinguish from primary SCC of the lung and present a unique challenge for pathologists. There are few available discriminating immunohistochemical markers as squamous differentiation typically leads to loss of expression of characteristic primary epithelial cell markers of both breast and lung origin. GATA protein binding 3 (GATA‐3) is a useful marker of breast origin in metastatic ductal and lobular carcinomas including poorly differentiated triple‐negative carcinomas and some metaplastic carcinomas. Here, we present a case of metastatic SCC presenting as a solitary lung mass with regional lymph node metastases and a single satellite lesion in a patient with a history of metaplastic SCC of the breast. In addition to the routine markers of squamous differentiation, the metastases were also positive for estrogen receptor (ER) and GATA‐3 on cytologic material obtained by transbronchial FNA. This suggests that immunoreactivity for ER and GATA‐3 may support a diagnosis of metastatic SCC in the context of a prior metaplastic SCC of the breast. Diagn. Cytopathol. 2015;43:844–849. © 2015 Wiley Periodicals, Inc.     

Bacterial colonization dynamics associated with respiratory syncytial virus during early childhood

Respiratory syncytial virus (RSV) is an important cause of early life acute respiratory infections. Potentially pathogenic respiratory bacteria, including Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae are frequently detected during RSV infections and associated with increased illness severity. However, the temporal dynamics of bacterial colonization associated with RSV infection remain unclear. We used weekly nasal swab data from a prospective longitudinal birth cohort in Brisbane, Australia, to investigate bacterial colonization patterns within children aged less than 2 years in the 4‐week period before and after an RSV infection. During 54 RSV infection episodes recorded in 47 children, both S. pneumoniae and M. catarrhalis were detected frequently (in 33 [61.1%] and 26 [48.1%] RSV infections, respectively). In most cases, S. pneumoniae and M. catarrhalis colonization preceded the viral infection, with the nasal load of each increasing during RSV infection. Generally, the dominant serotype of S. pneumoniae remained consistent in the 1 to 2 weeks immediately before and after RSV infection. Little evidence was found to indicate that prior colonization with either bacteria predisposed participants to developing RSV infection during the annual seasonal epidemic. Possible coacquisition events, where the bacteria species was first detected with RSV and not in the preceding 4 weeks, were observed in approximately 20% of RSV/S. pneumoniae and RSV/M. catarrhalis codetections. Taken together our results indicate that RSV generally triggered an outgrowth, rather than a new acquisition, of S. pneumoniae and M. catarrhalis from the resident microbial community.     

Mapping and ablation of ventricular fibrillation—how and for whom?

The involvement of the Purkinje system in a subset of patients with idiopathic ventricular fibrillation or polymorphic VT/VF related to structural heart disease was first demonstrated in the pioneering work of Michel Haissaguerre and co-workers (Circulation 106:962–967, 2002 and Lancet 359:677–678, 2002). It is very important to identify these patients with recurrent episodes of ventricular fibrillation and/or ICD shocks with regard to the presence of triggering premature ventricular contractions (PVC), which may be amenable to mapping and catheter ablation by screening Holter and ICD recordings. The practical problem, which is frequently encountered, is the absence of these PVCs when the patients are brought to the EP lab. However, catheter ablation is an important adjunctive tool to antiarrhythmic drug treatment, beta blocker therapy, and general anesthesia in this setting. Local electrogram criteria related to this phenomenon have been identified guiding mapping and ablation (e.g., low amplitude, high-frequency Purkinje potentials preceding a closely coupled ventricular signal (Fig. 1a)). The favorable long-term follow-up after catheter ablation has been demonstrated in the setting of right and left ventricular Purkinje-related PVCs leading to polymorphic VT/VF (Leenhardt et al., Circulation 89:206–215, 1994) and also following myocardial infarction (Baensch et al., Circulation 108:3011–3016, 2003) and right ventricular outflow tract-associated VF (Noda et al., Journal of the American College of Cardiology 46:1288–1294, 2005). Most recently, epicardial ablation strategies leading to suppression of polymorphic VT/VF episodes related to the Brugada syndrome have been described irrespective to the presence of premature ventricular beats (Nademanee et al., Circulation 123:1270–1279, 2011).     

Frequency of laboratory testing and associated abnormalities in patients with hypertension

Clinical practice guidelines recommend several routine laboratory tests in patients diagnosed with hypertension. However, the rates of clinically relevant laboratory abnormalities are unknown. Therefore, we conducted a retrospective cohort study using administrative and laboratory data of patients diagnosed with hypertension between April 2010 and March 2015 in Alberta, Canada. Laboratory investigations for renal function, serum electrolytes (sodium and potassium), low‐density lipoprotein (LDL) cholesterol, and diabetes (fasting blood glucose and hemoglobin A1c), measured within 1 year of diagnosis, were examined, and the frequency of abnormalities determined. A total of 225 296 cases of incident hypertension were identified. Of these, 74.3% received at least one of the four guideline‐recommended laboratory tests, but only 42.3% received all four tests. Patients who received any testing, compared to subjects who did not, were on average older (median age 55.9 vs 51.2 years, P < .001) and had more comorbidity (14.5% vs 2.8% with a Charlson comorbidity index ≥ 3, P < .001). Laboratory abnormalities with the potential to affect clinical decision‐making were more common among multi‐comorbid patients. Patients with renal dysfunction (6.7% vs 11.6%, 26.3%, P < .001), electrolyte abnormalities (9.8% vs 12.6%, 20.5%, P < .001), and diabetes (13.4% vs 25.1% vs 38.8%, P < .001) were found in patients with Charlson scores of 0 vs 1‐2 vs ≥3, respectively. Our study found most patients diagnosed with hypertension received some laboratory testing, but rates of laboratory testing and frequency of abnormalities varied by clinical context. Testing and abnormalities detected were both more common among older patients and patients with comorbidities.     

Continent-wide risk assessment for the establishment of nonindigenous species in Antarctica

Invasive alien species are among the primary causes of biodiversity change globally, with the risks thereof broadly understood for most regions of the world. They are similarly thought to be among the most significant conservation threats to Antarctica, especially as climate change proceeds in the region. However, no comprehensive, continent-wide evaluation of the risks to Antarctica posed by such species has been undertaken. Here we do so by sampling, identifying, and mapping the vascular plant propagules carried by all categories of visitors to Antarctica during the International Polar Year''s first season (2007–2008) and assessing propagule establishment likelihood based on their identity and origins and on spatial variation in Antarctica''s climate. For an evaluation of the situation in 2100, we use modeled climates based on the Intergovernmental Panel on Climate Change''s Special Report on Emissions Scenarios Scenario A1B [Nakićenović N, Swart R, eds (2000) Special Report on Emissions Scenarios: A Special Report of Working Group III of the Intergovernmental Panel on Climate Change (Cambridge University Press, Cambridge, UK)]. Visitors carrying seeds average 9.5 seeds per person, although as vectors, scientists carry greater propagule loads than tourists. Annual tourist numbers (∼33,054) are higher than those of scientists (∼7,085), thus tempering these differences in propagule load. Alien species establishment is currently most likely for the Western Antarctic Peninsula. Recent founder populations of several alien species in this area corroborate these findings. With climate change, risks will grow in the Antarctic Peninsula, Ross Sea, and East Antarctic coastal regions. Our evidence-based assessment demonstrates which parts of Antarctica are at growing risk from alien species that may become invasive and provides the means to mitigate this threat now and into the future as the continent''s climate changes.     

Hydroxyurea therapy of a murine model of sickle cell anemia inhibits the progression of pneumococcal disease by down-modulating E-selectin

Sickle cell anemia is characterized by chronic hemolysis coupled with extensive vascular inflammation. This inflammatory state also mechanistically promotes a high risk of lethal, invasive pneumococcal infection. Current treatments to reduce vaso-occlusive complications include chronic hydroxyurea therapy to induce fetal hemoglobin. Because hydroxyurea also reduces leukocytosis, an understanding of the impact of this treatment on pneumococcal pathogenesis is needed. Using a sickle cell mouse model of pneumococcal pneumonia and sepsis, administration of hydroxyurea was found to significantly improve survival. Hydroxyurea treatment decreased neutrophil extravasation into the infected lung coincident with significantly reduced levels of E-selectin in serum and on pulmonary epithelia. The protective effect of hydroxyurea was abrogated in mice deficient in E-selectin. The decrease in E-selectin levels was also evident in human sickle cell patients receiving hydroxyurea therapy. These data indicate that in addition to induction of fetal hemoglobin, hydroxyurea attenuates leukocyte-endothelial interactions in sickle cell anemia, resulting in protection against lethal pneumococcal sepsis.