Diagnostic mesothelioma biomarkers in effusion cytology

Malignant mesothelioma is a rare malignancy with a poor prognosis whose development is related to asbestos fiber exposure. An increasing role of genetic predisposition has been recognized recently. Pleural biopsy is the gold standard for diagnosis, in which the identification of pleural invasion by atypical mesothelial cell is a major criterion. Pleural effusion is usually the first sign of disease; therefore, a cytological specimen is often the initial or the only specimen available for diagnosis. Given that reactive mesothelial cells may show marked atypia, the diagnosis of mesothelioma on cytomorphology alone is challenging. Accordingly, cell block preparation is encouraged, as it permits immunohistochemical staining. Traditional markers of mesothelioma such as glucose transporter 1 (GLUT1) and insulin-like growth factor 2 mRNA-binding protein 3 (IMP3) are informative, but difficult to interpret when reactive proliferations aberrantly stain positive. BRCA1-associated protein 1 (BAP1) nuclear staining loss is highly specific for mesothelioma, but sensitivity is low in sarcomatoid tumors. Cyclin-dependent kinase inhibitor 2A (CDKN2A)/p16 homozygous deletion, assessed by fluorescence in situ hybridization, is more specific for mesothelioma with better sensitivity, even in the sarcomatoid variant. The surrogate marker methylthioadenosine phosphorylase (MTAP) has been found to demonstrate excellent diagnostic correlation with p16. The purpose of this review is to provide an essential appraisal of the literature regarding the diagnostic value of many of these emerging biomarkers for malignant mesothelioma in effusion cytology.     

Mutational landscape of patients with acute promyelocytic leukemia at diagnosis and relapse

Despite the high probability of cure of patients with acute promyelocytic leukemia (APL), mechanisms of relapse are still largely unclear. Mutational profiling at diagnosis and/or relapse may help to identify APL patients needing frequent molecular monitoring and early treatment intervention. Using an NGS approach including a 31 myeloid gene-panel, we tested BM samples of 44 APLs at the time of diagnosis, and of 31 at relapse. Mutations in PML and RARA genes were studied using a customized-NGS-RNA panel. Patients relapsing after ATRA-chemotherapy rarely had additional mutations (P = .009). In patients relapsing after ATRA/ATO, the PML gene was a preferential mutation target. We then evaluated the predictive value of mutations at APL diagnosis. A median of two mutations was detectable in 9/11 patients who later relapsed, vs one mutation in 21/33 patients who remained in CCR (P = .0032). This corresponded to a significantly lower risk of relapse in patients with one or less mutations (HR 0.046; 95% CI 0.011-0.197; P < .0001). NGS-analysis at the time of APL diagnosis may inform treatment decisions, including alternative treatments for cases with an unfavorable mutation profile.     

Intraventricular entrapment of a Sapien-3 balloon in transapical TAVR: A near missed catastrophe

Balloon rupture is an uncommon complication during balloon-expandable transcatheter aortic valve replacement (TAVR). We describe a balloon rupture and tearing with intraventricular entrapment complicating transapical-TAVR, as well as our bailout retrieval of the failed device.     

Update on treatment in multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. In recent years, many disease-modifying therapies (DMT) have been approved for MS treatment. For this reason, a profound knowledge of the characteristics and indications of the available compounds is required to tailor the therapeutic strategy to the individual patient characteristics. This should include the mechanism of action and pharmacokinetic of the drug, the safety and efficacy profile provided by clinical trials, as well as the understanding of possible side effects. Moreover, the evolving knowledge of the disease is paving the way to new and innovative therapeutic approaches, as well as the development of new biomarkers to monitor the therapeutic response and to guide the clinician's therapeutic choices. In this review we provide a comprehensive overview on currently approved therapies in MS and the emerging evidence-based strategies to adopt for initiating, monitoring, and eventually adapting a therapeutic regimen with DMT.     

Adding Blood to Agitated Saline Significantly Improves Detection of Right-to-Left Shunt by Contrast-Transcranial Color-Coded Duplex Sonography

Contrast-transcranial Doppler and contrast-transcranial color-coded duplex sonography (c-TCCD) have been reported to have high sensitivity in detecting patent foramen ovale as compared with transesophageal echocardiography. An international consensus meeting (Jauss and Zanette 2000) recommended that the contrast agent for right-to left-shunt (RLS) detection using contrast-transcranial Doppler be prepared by mixing 9 mL of isotonic saline solution and 1 mL of air. The aim of our study was to determine whether adding blood to the contrast agent results in improved detection of RLS. We enrolled all consecutive patients admitted to our neurosonology laboratory for RLS diagnosis. For each patient, we performed c-TCCD both at rest and during the Valsalva maneuver using two different contrast agents: ANSs (1 mL of air mixed with 9 mL of normal saline) and ANSHBs (1 mL of air mixed with 8 mL of normal saline and 1 mL of the patient's blood). To classify RLS, we used a four-level visual categorization: (i) no occurrence of micro-embolic signals; (ii) grade I, 1–10 signals; (iii) grade II, >10 signals but no curtain; grade III, curtain pattern. We included 80 patients, 33 men and 47 women. RLS was detected in 18.8% at rest and in 35% during the Valsalva maneuver using ANSs, and in 31.3% and in 46.3% using ANSHBs, respectively (p < 0.0001). There was a statistically significant increase in the number of micro-embolic signals with the use of ANSHBs. The use of blood mixed with saline solution and air as a c-TCCD contrast agent produced an increase in positive tests and a higher grade of RLS compared with normal saline and air alone, either with or without the Valsalva maneuver.     

Effects of two aerobic exercise training protocols on parameters of oxidative stress in the blood and liver of obese rats

We evaluated the effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) protocols on the alterations in oxidative stress parameters caused by a high-fat diet (HFD), in the blood and liver of rats. The HFD enhanced thiobarbituric acid reactive substances (TBA-RS) and protein carbonyl content, while reducing total sulfhydryl content and catalase (CAT) and glutathione peroxidase (GSH-Px) activities in the blood. Both training protocols prevented an increase in TBA-RS and protein carbonyl content, and prevented a reduction in CAT. HIIT protocol enhanced SOD activity. In the liver, HFD didn’t alter TBA-RS, total sulfhydryl content or SOD, but increased protein carbonyl content and CAT and decreased GSH-Px. The exercise protocols prevented the increase in protein carbonyl content and the MICT protocol prevented an alteration in CAT. In conclusion, HFD elicits oxidative stress in the blood and liver and both protocols prevented most of the alterations in the oxidative stress parameters.