Conclusion-This comprehensive approach aids the accurate direction of treatment and, while CVA, PNDS and GOR remain the most important causes of CNPC to consider, a group with no identifiable aetiology remains. (Thorax 1998;53:738-743)

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Background Acute stress induced (takotsubo) cardiomyopathy can result in a heart failure phenotype with a prognosis comparable to myocardial infarction. In this study, we hypothesized that inflammation is central to the pathophysiology and natural history of takotsubo cardiomyopathy. Methods In a multi-centre study, we prospectively recruited 55 patients with takotsubo cardiomyopathy and 51 age, sex and co-morbidity matched control subjects. During the index event and at 5 months follow-up, patients with takotsubo cardiomyopathy underwent multiparametric cardiac magnetic resonance imaging including ultrasmall superparamagnetic particles of iron oxide (USPIO) enhancement for detection of inflammatory macrophages in the myocardium. Blood monocyte subpopulations and serum cytokines were assessed as measures of systemic inflammation. Matched controls underwent investigation at a single time point. Results Subjects were predominantly middle aged (64±14years) women (90%). When compared to control subjects, patients with takotsubo cardiomyopathy had greater USPIO enhancement (expressed as the difference between pre-USPIO and post-USPIO T2*) in both ballooning (14.3±0.6 versus 10.5±0.9 ms, p<0.001) and non-ballooning (12.9±0.6 versus 10.5±0.9 ms, p=0.02) left ventricular myocardial segments. Serum interleukin-6 (23.1±4.5 versus 6.5±5.8 pg/mL, p< 0.001) and chemokine (C-X-C motif) ligand 1 (1903±168 versus 1272±177 pg/mL, p=0.01) concentrations, and classical CD14++CD16- monocytes (90±0.5 versus 87±0.9%, p=0.01) were also increased whilst intermediate CD14++CD16+ (5.4±0.3 versus 6.9±0.6%, p=0.01) and non-classical CD14+CD16++ (2.7±0.3% versus 4.2±0.5%, p=0.006) monocytes were reduced in patients with takotsubo cardiomyopathy. At 5 months, USPIO enhancement was no longer detectable in the left ventricular myocardium although there remained persistent elevations in serum interleukin-6 concentrations (p=0.009) and reductions in intermediate CD14++CD16+ monocytes (5.6±0.4 versus 6.9±0.6%, p=0.01). Conclusions We demonstrate for the first time that takotsubo cardiomyopathy is characterized by a myocardial macrophage inflammatory infiltrate, changes in the distribution of monocyte subsets and an increase in systemic pro-inflammatory cytokines. Many of these changes persisted for at least 5 months suggesting a low-grade chronic inflammatory state.

Background: The aim of this study was to identify key factors on admission predicting the development of complicated parapneumonic effusion or empyema in patients admitted with community-acquired pneumonia. Methods: A prospective observational study of patients admitted with community-acquired pneumonia in NHS Lothian, UK, was conducted. Multivariate regression analyses were used to evaluate factors that could predict the development of complicated parapneumonic effusion or empyema, including admission demographics, clinical features, laboratory tests and pneumonia-specific (Pneumonia Severity Index (PSI), CURB65 (New onset confusion, urea .7 mmol/l, Respiratory rate >30 breaths/min, Systolic blood pressure , 90 mm Hg and/or diastolic blood pressure #60 mm Hg and age >65 years) and CRB65 (New onset confusion, Respiratory rate >30 breaths/min, Systolic blood pressure ,90 mm Hg and/or diastolic blood pressure #60 mm Hg and age >65 years)) and generic sepsis scoring systems (APACHE II (Acute Physiology and Chronic Health Evaluation II), SEWS (standardised early warning score) and systemic inflammatory response syndrome (SIRS)). Results: 1269 patients were included in the study and 92 patients (7.2%) developed complicated parapneumonic effusion or empyema. The pneumonia-specific and generic sepsis scoring systems had no value in predicting complicated parapneumonic effusion or empyema. Multivariate logistic regression identified albumin ,30 g/l adjusted odds ratio (AOR) 4.55 (95% CI 2.45 to 8.45, p,0.0001), sodium ,130 mmol/l AOR 2.70 (1.55 to 4.70, p = 0.0005), platelet count .400610 9 /l AOR 4.09 (2.21 to 7.54, p,0.0001), C-reactive protein .100 mg/l AOR 15.7 (3.69 to 66.9, p,0.0001) and a history of alcohol abuse AOR 4.28 (1.87 to 9.82, p = 0.0006) or intravenous drug use AOR 2.82 (1.09 to 7.30, p = 0.03) as independently associated with development of complicated parapneumonic effusion or empyema. A history of chronic obstructive pulmonary disease was associated with decreased risk, AOR 0.18 (0.06 to 0.53, p = 0.002). A 6-point scoring system using these combined variables had good discriminatory value: area under the receiver operator characteristic curve (AUC) 0.84 (95% CI 0.81 to 0.86, p,0.0001). Conclusion: This study has identified seven clinical factors predicting the development of complicated parapneumonic effusion or empyema. Independent validation is needed.Complicated parapneumonic effusions and empyema are key complications of communityacquired pneumonia necessitating prolonged treatment, intercostal drainage and frequently surgical management, leading to prolonged hospital stay.

Takotsubo syndrome is a condition characterized by acute transient left ventricular systolic dysfunction, which at presentation can be challenging to distinguish from acute myocardial infarction. Although previously thought to be a benign, self-limiting condition, recent studies have confirmed that patients with takotsubo syndrome have persistent subtle ongoing cardiac dysfunction, and many continue to have limiting symptoms despite restoration of left ventricular ejection fraction. Moreover, these patients have a substantial burden of morbidity and mortality, as well, with high rates of subsequent major adverse cardiovascular events that approach those of patients with acute coronary syndrome. The mechanisms behind this condition remain elusive. Despite substantial research, the medical community continues to have an incomplete understanding of its underlying pathogenesis and pathophysiology. Catecholamine-induced myocardial injury is the most established and well-known theory, but this does not explain all the clinical features and presentations of the condition, and numerous other pathways and abnormalities are emerging. Because of the poor understanding of its underlying pathophysiology, there is a lack of evidence-based interventions to treat the acute episode, to avoid recurrences, and to prevent major adverse cardiovascular events. This highlights the need for further research to gain a better understanding of the underlying pathophysiology to inform appropriate randomized controlled trials of interventions targeting the causative pathways. Only then can evidence-based management strategies be established to improve clinical outcomes of this potentially lethal condition.

Background: Takotsubo syndrome is an increasingly recognized cause of chest pain and occasionally of cardiogenic shock. Despite rapid improvement of the Left Ventricular Ejection Fraction (LV EF), recent registry data raises concerns about long term prognosis. We hypothesized that restoration of normal EF after acute tako-tsubo is not equivalent to full functional recovery. Methods: We prospectively recruited 52 takotsubo patients [according to the Mayo criteria plus cardiac magnetic resonance imaging (CMR) to exclude myocardial infarction] and 44 healthy controls of the same age, gender and cardiovascular co-morbidity distribution. We focused the investigation on takotsubo patients presenting with ST-elevation type ECG or malignant arrhythmias and with LV apical ballooning variant and examined a 4 months recovery end-point. Patients underwent Echocardiography assessment of LV myocardial deformation (Global longitudinal, radial and circumferential strain, LV twist, torsion, untwist, time to peak twist and untwist) and assessment of LV myocardial structure by pre and post contrast-enhanced CMR by T1 mapping acutely and at 4 months follow-up. Controls had a single time-point investigation. Data were analyzed using paired or unpaired tests, as appropriate for their distribution and corrected for multiple comparisons. Results: The patients' mean age was 66 years (range 28-87) and 92% were women. All abnormal echocardiographic indices observed acutely in takotsubo patients improved (but not necessarily normalized) at followup. Significant mechano-temporal alterations characterizing both systole (global longitudinal strain, apical circumferential strain, both p<0.01; left ventricular twist, twist rate and torsion, all p<0.0001) and diastole (untwist rate and time to peak untwisting, all p<0.001) persisted at 4 months follow-up when compared with controls, despite normalization of LV ejection fraction and volumes. Whilst native T1 (which demonstrates edema) normalized at 4 months follow-up only in segments contracting normally during the acute phase [T1=1180± 40.6ms (normally contracting, p=0.2 vs control values of 1189±16 ms) and 1208± 60.3 ms (dysfunctional segments, p<0.05 vs control)], the extracellular volume fraction (ECV, which demonstrates diffuse fibrosis) remained significantly abnormal in all LV segments (whether normally contracting, 0.328±0.043, p<0.001 or ballooning during acute presentation, 0.320±0.044, p<0.001, both vs control values of 0.273±0.045). Conclusion: In patients with the most clinically severe spectrum of takotsubo cardiomyopathy, regional LV systolic and diastolic deformation abnormalities persist beyond the acute event, despite normalization of global LV EF and size. In addition, although myocardial edema partly subsides, a process of global microscopic fibrosis develops in its place, detected as early as 4 months.Suggested Reviewers:Opposed Reviewers: 1 24 th March, 2017 Dear Dr Pearlman, Thank you once again for your comments and those of the associate editors. I think it i...

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Biomarkers and clinical prediction rules predict outcome in acute PE. Addition of troponin to the PESI scoring system improves the predictive value for 30-day mortality and may be useful for guiding initial management of patients presenting with PE.