Skin and superficial soft tissue neoplasms with multinucleated giant cells: Clinical, histologic, phenotypic, and molecular differentiating features.

Multinucleated giant cells (MGC) are commonly seen in an array of neoplastic and non-neoplastic conditions, to include: granulomatous dermatitis, fibrohistiocytic lesions such as xanthogranulomas, and soft tissue tumors such as giant cell tumors of soft tissue. In addition, multinucleated giant cells are infrequently seen in melanoma, squamous cell carcinoma, and atypical fibroxanthoma. There are many different types of MGCs and their presence, cytologic, and immunohistochemical features within these pathologic entities vary. Thus, correct identification of the different types of MGCs can aid the practicing pathologist in making the correct diagnosis of the overall pathologic disease. The biologic diversity and variation of MGCs is currently best exemplified in cytologic appearance and immunohistochemical profiles. However, much remains unknown about the origination and evolution. In this review, we i) reflect on the various types of MGCs and the current understanding of their divergent development, ii) describe the histologic, immunohistochemical, and molecular (if previously reported) differentiating features of common skin and superficial soft tissue neoplasms that may present with multinucleated giant cells.

Statins for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are common causes of elevated liver enzymes in the general population. NASH and to some extent NAFLD have been associated with increased liver-related and all-cause mortality. No effective treatment is yet available. Recent reports have shown that the use of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) in patients with elevated plasma aminotransferases may result in normalisation of these liver enzymes. Whether this is a consistent effect or whether it can lead to improved clinical outcomes beyond normalisation of abnormal liver enzymes is not clear. OBJECTIVES: To assess the beneficial and harmful effects of statins (that is, lovastatin, atorvastatin, simvastatin, pravastatin, rosuvastatin, and fluvastatin) on all-cause and liver-related mortality, adverse events, and histological, biochemical, and imaging responses in patients with NAFLD or NASH. SEARCH METHODS: We performed a computerised literature search in the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded up to March 2013. We did fully recursive searches from the reference lists of all retrieved relevant publications to ensure a complete and comprehensive search of the published literature. We did not apply any restrictions regarding language of publication or publication date. SELECTION CRITERIA: All randomised clinical trials using statins as the primary treatment for NAFLD or NASH versus no treatment, placebo, or other hypolipidaemic agents. DATA COLLECTION AND ANALYSIS: Data were extracted, and risk of bias of each trial was assessed independently by two or more review authors. Meta-analyses were performed whenever possible. Review Manager 5.2 was used. MAIN RESULTS: When the described search method was used and the eligibility criteria of the search results were applied, 653 records were found. Only two of these were randomised clinical trials that were considered eligible for inclusion. We assessed both trials as trials with high risk of bias. One of the trials was a pilot trial in which 16 participants with biopsy-proven NASH were randomised to receive simvastatin 40 mg (n = 10) or placebo (n = 6) once daily for 12 months. No statistically significant improvement in the aminotransferase level was seen in the simvastatin group compared with the placebo group. Liver histology was not significantly affected by simvastatin.The other trial had three arms. The trial compared atorvastatin 20 mg daily (n = 63) versus fenofibrate 200 mg daily (n = 62) versus a group treated with a combination of the two interventions (n = 61). There were no statistically significant differences between any of the three intervention groups regarding the week 54 mean activity levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, and alkaline phosphatase. The triglyceride levels seemed higher in the fenofibrate group compared with the atorvastatin group. Liver histology was not assessed in this trial. The presence of biochemical and ultrasonographic evidence of NAFLD seemed to be higher in the fenofibrate group compared with the atorvastatin group (58% versus 33%). Three patients discontinued treatment due to myalgia and elevated serum creatine kinase activity; one from the atorvastatin group and two from the combination group. Another patient from the atorvastatin group discontinued treatment due to alanine aminotransferase activity that was over three times the upper normal limit.No data for all-cause mortality and hepatic-related mortality were reported in the included trials. AUTHORS' CONCLUSIONS: Based on the findings of this review, which included two trials with high risk of bias and a small numbers of participants, it seems possible that statins may improve serum aminotransferase levels as well as ultrasound findings. Neither of the trials reported on possible histological changes, liver-related morbidity or mortality. Trials with larger sample sizes and low risk of bias are necessary before we may suggest statins as an effective treatment for patients with NASH. However, as statins can improve the adverse outcomes of other conditions commonly associated with NASH (for example, hyperlipidaemia, diabetes mellitus, metabolic syndrome), their use in patients with non-alcoholic steatohepatitis may be justified.

Utility of Whole Slide Imaging for Intraoperative Consultation: Experience of a Large Academic Center.

CONTEXT.­: In the United States, review of digital whole slide images (WSIs) using specific systems is approved for primary diagnosis but has not been implemented for intraoperative consultation. OBJECTIVE.­: To evaluate the safety of review of WSIs and compare the efficiency of review of WSIs and glass slides (GSs) for intraoperative consultation. DESIGN.­: Ninety-one cases previously submitted for frozen section evaluation were randomly selected from 8 different anatomic pathology subspecialties. GSs from these cases were scanned on a Leica Aperio AT2 scanner at ×20 magnification (0.25 µm/pixel). The slides were deidentified, and a short relevant clinical history was provided for each slide. Nine board-certified general pathologists who do not routinely establish primary diagnoses using WSIs reviewed the WSIs using Leica Aperio ImageScope viewing software. After a washout period of 2-3 weeks, the pathologists reviewed the corresponding GSs using a light microscope (Olympus BX43). The pathologists recorded the diagnosis and time to reach the diagnosis. Intraobserver concordance, time to diagnosis, and specificity and sensitivity compared to the original diagnosis were evaluated. RESULTS.­: The rate of intraobserver concordance between GS results and WSI results was 93.7%. Mean time to diagnosis was 1.25 minutes for GSs and 1.76 minutes for WSIs (P < .001). Specificity was 91% for GSs and 90% for WSIs; sensitivity was 92% for GSs and 92% for WSIs. CONCLUSIONS.­: Time to diagnosis was longer with WSIs than with GSs, and scanning GSs and uploading the data to whole slide imaging systems takes time. However, review of WSIs appears to be a safe alternative to review of GSs. Use of WSIs allows reporting from a remote site during a public health emergency such as the COVID-19 pandemic and facilitates subspecialty histopathology services.

Predictors and early outcome of prolonged mechanical ventilation in contemporary heart valve surgery.

BACKGROUND: During last decades mechanical ventilation has been an important support in the postoperative management of patients undergoing cardiac surgery. This study was designed to determine the predictors of prolonged mechanical ventilation (PMV) in patients undergoing heart valve surgery. METHODS: This retrospective study considered of 1056 patients who underwent isolated valve surgery at Tehran Heart Center from March 2002 to March 2009. PMV is considered as mechanical ventilation period of > or =24 hours at postoperative hospital stay in this study. RESULTS: PMV occurred in 6.6% of patients. Initial ventilation hours, atrial fibrillation, cardiac arrest and reintubation were the most prevalent postoperative complications. Preoperative renal failure, postoperative stroke, intra aortic balloon pump insertion, emergent operation, complete heart block, longer perfusion time were independent predictors of PMV in our patients. CONCLUSION: PMV is associated with significant comorbidities and increased hospital mortality. Strategies to delineate the patients at risk and to modify these risk factors by prophylactic measures should probably lead to a lower incidence of prolonged mechanical ventilation for patients undergoing isolated valve surgery.

Metachronous vulvar ectopic breast cancer, a case report and literature review.

•When two or more primary tumors arise at the same time, they are considered synchronous.•A metachronous tumor in a new primary that develops after an initial cancer diagnosis.•The diagnosis of vulvar breast cancer is primarily histopathologic, based on morphology and immunostaining.•Identifying a cancer as a metastasis versus as synchronous/metachronous significantly impacts staging and treatment.

Prognostic Usefulness of Proenkephalin in Stable Ambulatory Patients With Heart Failure.

Patients with heart failure have a poor prognosis, yet outcomes might be improved by early identification of risk. Proenkephalin (proENK), a novel biomarker, is a stable surrogate marker for endogenous enkephalins and is an independent predictor of heart failure and death in patients who had an acute myocardial infarction. This is the first study to evaluate the prognostic utility of this biomarker in stable ambulatory patients. We conducted a 4-year single-center prospective cohort study of 200 patients who were referred for an outpatient echocardiogram. Blood samples were obtained to analyze levels of proENK at the time of the initial echocardiogram. Patients were evaluated for the combined end point cardiovascular-related hospital admission or death. Participants with higher proENK levels were older and had higher serum creatinine and lower estimated glomerular filtration rate, lower ejection fraction, and higher rates of hypertension and diabetes (p ≤0.009). Highest proENK tertile had a hazard ratio of 3.0 (95% confidence interval 1.4 to 6.7) compared with the first tertile (p <0.007) for the primary end point. In conclusion, proENK demonstrated significant prognostic utility for cardiovascular-related hospital admission or death.

New Targets in the Drug Treatment of Heart Failure.

Heart failure is a complex syndrome that has been a major contributor to readmissions into hospitals in the USA. Currently, a large number of medications are being used to treat the symptoms of the disease-digoxin, diuretics, renin-angiotensin-aldosterone system inhibitors, ß-blockers, and vasodilators. There is no doubt that the given pharmaceutical therapy has been effective in lowering hospital readmission rates and prolonging life in individual chronic heart failure patients. Despite this, admission rates following heart failure hospitalization remain high, resulting in a substantial financial strain on healthcare institutions. Clearly, there is much room for improvement in heart failure therapy and management in reducing readmission rates. In this review, we address the unmet needs in the current drug treatment of chronic heart failure and describe novel drug targets that are currently under investigation.

Novel biomarkers for heart failure.

Heart failure (HF) has proven to be a major burden on the health system. The continuing prevalence of the condition and its rising associated costs and care, has amplified the need for earlier diagnosis, better risk stratification and cost-effective treatment to cut rates of hospitalization. Biomarkers seem poised to undertake such tasks, with biomarker management of patients with HF quickly evolving over the past several years. Biomarker guided diagnosis and treatment has become vital, especially during the acute setting in which the majority of patients with HF, were initially present. An adequate assessment of risk requires a multi-marker approach to a given HF patient. Established markers including brain natriuretic peptide and NT-proBNP are a significant clinical aid to physicians, though their utility is limited. In the past few years, momentous effort has been put into the discovery of new biomarkers. These endeavors have led to the emergence of several capable and promising biomarkers for HF management including troponins, mid-regional pro-adrenomedullin, GDF-15, C-reactive protein, Galectin-3, IL-6, ST-2, neutrophil gelatinase-associated lipocalin, copeptin and procalcitonin. This review will offer an insight into the novel biomarkers considered as the cutting-edge in the diagnosis and management of HF.

Cardiorenal biomarkers in acute heart failure.

Managing patients with heart failure (HF) is a challenging task within itself, but the presence of associated worsening renal function can greatly increase mortality and morbidity. Early diagnosis and treatment is the key to prevent re-hospitalizations and reduce healthcare costs. Biomarkers have long been established as highly sensitive and specific tools in diagnosing and prognosticating patients with HF. Reflecting distinct pathophysiological events and ongoing cellular insult, biomarkers have been proven superior to conventional laboratory tests. Availability of better assays and rapid analysis has allowed the use of biomarkers as point-of-care tests in the emergency department and at the patient's bed-side. Acute HF patients often go on to develop worsening renal function, termed as acute cardiorenal syndrome. The growing breadth of studies has shown the implications of combining multiple biomarkers to better chart outcomes and produce desirable results in such patients.

Determinants of postoperative atrial fibrillation and associated resource utilization in cardiac surgery.

INTRODUCTION AND OBJECTIVES: Atrial arrhythmias occur after cardiac surgery in 10-65% of patients. The most common postoperative arrhythmia is atrial fibrillation (AF). METHODS: The Tehran Heart Center Cardiovascular Research database (of 15 580 patients) was used to identify all patients who developed any form of AF as a postoperative complication following their first cardiac surgery (e.g. for coronary artery bypass grafting [CABG], valve surgery or both), with and without cardiopulmonary bypass, between June 2002 and March 2008. RESULTS: Of the 15 580 patients who underwent a first cardiac surgery, 11 435 (73.4%) were male and their mean age was 58.16+/-10.11 years. New-onset AF developed postoperatively in 1129 (7.2%). New-onset AF occurred most frequently in patients who were aged > or =60 years and who had no history of beta-blocker use. In addition, patients were more likely to develop new-onset AF if they had valve surgery alone (16.5%) or CABG plus valve surgery combined (9.6%), needed intra-aortic balloon counterpulsation (IABC), or had a long cardiopulmonary bypass time. Multivariate analysis identified the following predictors of postoperative AF: older age, history of renal failure, congestive heart disease, operation type, longer perfusion time, and use of IABC. The incidence of early readmission (4.4%) was significantly higher in patients with postoperative AF, as was the duration of hospitalization, both overall and postoperatively. The short-term postoperative mortality rate was 3.8%. CONCLUSIONS: Atrial fibrillation frequently develops after cardiac surgery and is associated not only with increased morbidity and mortality, but also with increased use of health-care resources.

Is severely left ventricular dysfunction a predictor of early outcomes in patients with coronary artery bypass graft?

BACKGROUND: Traditionally, the Coronary artery bypass grafting (CABG) surgery outcomes of patients with low ejection fraction (EF) have been worse compared to patients with moderate to good left ventricular function. During the past decade, despite improvements in surgical techniques, the trend in the outcomes of these patients remained unclear. AIM: We sought to determine the effect of left ventricular dysfunction on early mortality and morbidity and to specify predictors of early mortality of isolated CABG in a large group of patients EF≤35%. METHOD: We retrospectively analyzed data of 14 819 consecutive patients undergoing isolated CABG from February 2002 to March 2008 at Tehran Heart Center. Patients were divided into two groups based on their LVEF (EF≤35% and EF>35%). Differences in case-mix between patients with EF≤35% and those without were controlled by constructing a propensity score. RESULTS: Mean age of our patients was 58.7±9.5 years. EF≤35% was present in 1342 (9.1%) of patients. In-hospital mortality was significantly increased univariate in EF≤35%, while this association diminished after confounders were adjusted for by using the propensity score (p=0.242). Following adjustment it was demonstrated that renal failure, cardiac arrest, heart block, infectious complication, total ventilation time, and total ICU hours were more frequent in patients with EF≤35%. CONCLUSION: We demonstrated EF≤35% was not predictor of in-hospital mortality in patients underwent CABG. Careful preoperative patient selection remains essential in patients with EF≤35% undergoing CABG.