Thymomas: a review.

Thymomas are neoplasma of thymic epithelial cells. They may be benign or malignant and may associate with locai ìnvasiveness and paraneoplastic diseases. Myasthenia gravis is often associated with thymomas, bui this is not thè rule. Several classifications have been proposed: some of them follow thè histopathological findings (Rosai and Levine, Snover, Marino and Muller- Hermelink classification), other emphasizes thè clinic-pathological stage (Masaoka, Verley and Hollmann stadiation). One third of thymomas is asymptomatic. Diagnosis is made often by plain X-ray and confirmed by Computed Tomography or fine needle biopsy. Surgery is effective in 100% of noninvasive cases and in 58% of invasive ones. Radio and chemotherapy are recommended only in advanced or inoperable stages

Cancer of the Thyroid in patients over the age of fifty.

Aim. The authors performed a retrospective investigation of patients over thè age of 50, in order to detect any peculiarities of cancer of thè thyroid possibly affecting surgical treatment and whether age itself represented an independent prognostic factor. Methods. A total of 152 patients were examined at thè Department of Surgical Science of "La Sapienza" University of Rome with a minimum follow- up of 10 years. The 152 subjects recruited were divided into 3 age groups: from 51 to 60 years, (74 patients); from 61 to 70 years, (57 patients); from 71 to 80 years, (21 patients). Resulti. Relating thè different histologic types to age group, there was found to be a lower incidence of well-differentiated carcinoma and a relative increase in thè epidermoid and undifferentiated forms in older patients. In thè 51-60 age group 80% of thè patients were at stages I and II, while in thè 71-80 age group 56.2% of cases were at stages III and IV. Conclusion. In thè elderly patient undifferentiated, anaplastic or epidermoid forms and those with a higher biologica! aggressiveness are more frequently found. We believe that prompt diagnosis would present thè surgeon with neoplasms at an early stage and with less aggressive histotypes, thus ensuring greater scope for radicai surgical treatment and appreciably enhancing prognosis

Index of T-wave variation as a predictor of sudden cardiac death in chronic heart failure patients with atrial fibrillation

Chronic heart failure (CHF) and atrial fibrillation (AF) are worldwide leading causes of morbidity and mortality in elders, a large part due to sudden cardiac deaths (SCD). The high irregularity of ventricular response in AF patients makes the use of standard SCD-risk markers inappropriate in this target population. The aim of this study was twofold: i) to propose a new index, suitable for AF patients, able to quantify ventricular repolarization changes; and ii) to evaluate its prognostic value in a CHF population with AF. Holter ECG recordings from 176 consecutive CHF patients with AF (22 SCD) were analyzed. The index of T-wave variation (ITV), quantifying the average T-wave changes in pairs of consecutive beats under stable rhythm conditions, was computed using a fully-automatic method. Survival analysis was performed considering SCD as an independent endpoint. ITVwas higher for SCD than non-SCD victims (median (Q1;Q3): 24.9 (14.4;85.4) μV vs 17.1 (11.3;28.2) μV, p=0.06). In a survival analysis where the threshold was set on the third quartile of ITVvalues, ITV(+) outcome was successfully associated to SCD (Hazard Ratio (CI):3.22 (1.36, 7.58)per μV, p=0.008). In conclusion, we show in this work that Ijy stratifies CHF patients with AF according to their risk of SCD, with larger ITVassociated to lower survival probability

Index of T-wave variation as a predictor of sudden cardiac death in chronic heart failure patients with atrial fibrillation

Chronic heart failure (CHF) and atrial fibrillation (AF) are worldwide leading causes of morbidity and mortality in elders, a large part due to sudden cardiac deaths (SCD). The high irregularity of ventricular response in AF patients makes the use of standard SCD-risk markers inappropriate in this target population. The aim of this study was twofold: i) to propose a new index, suitable for AF patients, able to quantify ventricular repolarization changes; and ii) to evaluate its prognostic value in a CHF population with AF. Holter ECG recordings from 176 consecutive CHF patients with AF (22 SCD) were analyzed. The index of T-wave variation (ITV), quantifying the average T-wave changes in pairs of consecutive beats under stable rhythm conditions, was computed using a fully-automatic method. Survival analysis was performed considering SCD as an independent endpoint. ITV was higher for SCD than non-SCD victims (median (Q1;Q3): 24.9 (14.4;85.4) µV vs 17.1 (11.3;28.2) µV, p=0.06). In a survival analysis where the threshold was set on the third quartile of ITV values, ITV (+) outcome was successfully associated to SCD (Hazard Ratio (CI):3.22 (1.36, 7.58)per µV, p=0.008). In conclusion, we show in this work that Ijy stratifies CHF patients with AF according to their risk of SCD, with larger ITV associated to lower survival probability

Thyroid autoantibodies and breast cancer

Dear Editor We read with interest the recent article by Shi and colleagues (2014) reporting a meta-analysis on the relationship between thyroid hormones, thyroid autoantibodies and breast cancer (BC). In the paper, the authors analyzed eight different studies, including 4,189 participants, and concluded that serum levels of free-triiodothyronine, thyroperoxidase and thyroglobulin autoantibodies are higher in patients affected by BC, compared with the control group. These findings are in agreement with the meta-analysis reported by Hardefeldt and colleagues, showing an increased risk of BC in patients with autoimmune thyroid disease, and with a recent article by our group in which the prevalence of BC in 3,921 female patients affected by both benign and malignant thyroid diseases was evaluated (Hardefeldt et al., 2012; Prinzi et al., 2014). In the latter, we showed that the prevalence of BC in patients affected by thyroid disease, as a whole, was significantly higher, compared to the general population (OR 3.3). Moreover, the age-matched analysis showed that the risk of BC was higher in younger patients (0–44 yr, OR 15.2), to decline with the increasing age. In the same study, when patients were dichotomized based on the presence or the absence of thyroglobulin and/or thyroperoxidase autoantibodies, both groups showed a higher risk of BC, compared to the general female population. When the two groups were compared to each other, however, the risk of BC was significantly lower in autoantibody positive patients. Thus, as clearly stated in our article, among patients affected by thyroid diseases, the presence of thyroid autoantibodies may have a protective role against BC (Prinzi et al., 2014). As a consequence, the sentence reported by Shi and colleagues in the Discussion section of their article stating that their findings are in disagreement with our data is not correct and should be, if at all possible, amended

Transforming acidic coiled-coil 3 and Aurora-A interact in human thyrocytes and their expression is deregulated in thyroid cancer tissues

Aurora-A kinase has recently been shown to be deregulated in thyroid cancer cells and tissues. Among the Aurora-A substrates identified, transforming acidic coiled-coil (TACC3), a member of the TACC family, plays an important role in cell cycle progression and alterations of its expression occur in different cancer tissues. In this study, we demonstrated the expression of the TACC3 gene in normal human thyroid cells (HTU5), and its modulation at both mRNA and protein levels during cell cycle. Its expression was found, with respect to HTU5 cells, unchanged in cells derived from a benign thyroid follicular tumor (HTU42), and significantly reduced in cell lines derived from follicular (FTC-133), papillary (B-CPAP), and anaplastic thyroid carcinomas (CAL-62 and 8305C). Moreover, in 16 differentiated thyroid cancer tissues, TACC3 mRNA levels were found, with respect to normal matched tissues, reduced by twofold in 56% of cases and increased by twofold in 44% of cases. In the same tissues, a correlation between the expression of the TACC3 and Aurora-A mRNAs was observed. TACC3 and Aurora-A interact in vivo in thyroid cells and both proteins localized onto the mitotic structure of thyroid cells. Finally, TACC3 localization on spindle microtubule was no more observed following the inhibition of Aurora kinase activity by VX-680. We propose that Aurora-A and TACC3 interaction is important to control the mitotic spindle organization required for proper chromosome segregation

No need for secondary Pneumocystis jirovecii pneumonia prophylaxis in adult people living with HIV from Europe on ART with suppressed viraemia and a CD4 cell count greater than 100 cells/µL

Introduction: Since the beginning of the HIV epidemic in resource-rich countries, Pneumocystis jirovecii pneumonia (PjP) is one of the most frequent opportunistic AIDS-defining infections. The Collaboration of Observational HIV Epidemiological Research Europe (COHERE) has shown that primary Pneumocystis jirovecii Pneumonia (PjP) prophylaxis can be safely withdrawn in patients with CD4 counts of 100 to 200 cells/µL if plasma HIV-RNA is suppressed on combination antiretroviral therapy. Whether this holds true for secondary prophylaxis is not known, and this has proved difficult to determine due to the much lower population at risk. Methods: We estimated the incidence of secondary PjP by including patient data collected from 1998 to 2015 from the COHERE cohort collaboration according to time-updated CD4 counts, HIV-RNA and use of PjP prophylaxis in persons >16 years of age. We fitted a Poisson generalized additive model in which the smoothed effect of CD4 was modelled by a restricted cubic spline, and HIV-RNA was stratified as low (10,000copies/mL). Results: There were 373 recurrences of PjP during 74,295 person-years (py) in 10,476 patients. The PjP incidence in the different plasma HIV-RNA strata differed significantly and was lowest in the low stratum. For patients off prophylaxis with CD4 counts between 100 and 200 cells/µL and HIV-RNA below 400 copies/mL, the incidence of recurrent PjP was 3.9 (95% CI: 2.0 to 5.8) per 1000 py, not significantly different from patients on prophylaxis in the same stratum (1.9, 95% CI: 0.1 to 3.7). Conclusions: HIV viraemia importantly affects the risk of recurrent PjP. In virologically suppressed patients on ART with CD4 counts of 100 to 200/µL, the incidence of PjP off prophylaxis is below 10/1000 py. Secondary PjP prophylaxis may be safely withheld in such patients. While European guidelines recommend discontinuing secondary PjP prophylaxis only if CD4 counts rise above 200 cells/mL, the latest US Guidelines consider secondary prophylaxis discontinuation even in patients with a CD4 count above 100 cells/µL and suppressed viral load. Our results strengthen and support this US recommendation. Keywords: opportunistic infections; Pneumocystis jirovecii pneumonia; prophylaxi

EGFR Inhibition Abrogates Leiomyosarcoma Cell Chemoresistance through Inactivation of Survival Pathways and Impairment of CSC Potential

Background: Tumor cells with stem-like phenotype and properties, known as cancer stem cells (CSC), have been identified in most solid tumors and are presumed to be responsible for driving tumor initiation, chemoresistance, relapse, or metastasis. A subpopulation of cells with increased stem-like potential has also been identified within sarcomas. These cells are endowed with increased tumorigenic potential, chemoresistance, expression of embryonic markers, and side population(SP) phenotype. Leiomyosarcomas (LMS) are soft tissue sarcomas presumably arising from undifferentiated cells of mesenchymal origin, the Mesenchymal Stem Cells (MSC). Frequent recurrence of LMS and chemoresistance of relapsed patients may likely result from the failure to target CSC. Therefore, therapeutic cues coming from the cancer stem cell (CSC) field may drastically improve patient outcome. Methodology/Principal Findings: We expanded LMS stem-like cells from patient samples in vitro and examined the possibility to counteract LMS malignancy through a stem-like cell effective approach. LMS stem-like cells were in vitro expanded both as "tumor spheres" and as "monolayers" in Mesenchymal Stem Cell (MSC) conditions. LMS stem-like cells displayed MSC phenotype, higher SP fraction, and increased drug-extrusion, extended proliferation potential, self-renewal, and multiple differentiation ability. They were chemoresistant, highly tumorigenic, and faithfully reproduced the patient tumor in mice. Such cells displayed activation of EGFR/AKT/MAPK pathways, suggesting a possibility in overcoming their chemoresistance through EGFR blockade. IRESSA plus Vincristine treatment determined pathway inactivation, impairment of SP phenotype, high cytotoxicity in vitro and strong antitumor activity in stem-like cell-generated patient-like xenografts, targeting both stem-like and differentiated cells. Conclusions/Significance: EGFR blockade combined with vincristine determines stem-like cell effective antitumor activity in vitro and in vivo against LMS, thus providing a potential therapy for LMS patients. \uc2\ua9 2012 Sette et al