Drop-out rate from the liver transplant waiting list due to HCC progression in HCV-infected patients treated with direct acting antivirals.

BACKGROUND & AIM: concerns about an increased hepatocellular carcinoma (HCC) recurrence rate following directly acting antiviral (DAA) therapy in cirrhotic patients with a prior complete oncological response have been raised. Data regarding the impact of HCV-treatment with DAAs on waiting list drop-out rates in patients with active HCC and HCV-related cirrhosis awaiting liver transplantation (LT) are lacking. MATERIALS AND METHODS: HCV-HCC patients listed for LT between January 2015 and May 2016 at Padua Liver Transplant Centre were considered eligible for the study. After enrollment patients were divided into 2 groups, depending on whether they underwent DAAs treatment while awaiting LT or not. For each patient clinical, serological and virological data were collected. HCC characteristics were radiologically evaluated at baseline and during follow-up (FU). For transplanted patients, pathological assessment of the explants was performed and recurrence-rates were calculated. RESULTS: twenty-three patients treated with DAAs and 23 controls were enrolled. HCC characteristics at time of LT-listing were comparable between the 2 groups. Median FU was 10 and 7 months, respectively, during which 2/23 (8.7%) and 1/23 (4.3%) drop-out events due to HCC-progression were registered (p = 0.9). No significant differences in terms of radiological progression were highlighted (p = 0.16). Nine out of 23 cases (39%) and 14/23 (61%) controls underwent LT, and histopathological analysis showed no differences in terms of median number and total tumor volume of HCC nodules, tumor differentiation or microvascular invasion. During post-LT FU, 1/8 DAAs treated patient (12,5%) and 1/12 control (8,3%) experienced HCC recurrence (p = 0.6). CONCLUSIONS: Viral eradication does not seem to be associated with an increased risk of drop-out due to neoplastic progression in HCV-HCC patients awaiting LT

Long-Term Survival in Patients with Post-Operative Atrial Fibrillation after Cardiac Surgery: Analysis from a Prospective Cohort Study

9noopenBackground: Post-operative (POP) atrial fibrillation (AF) is frequent in patients who undergo cardiac surgery. However, its prognostic impact in the long term remains unclear. Methods: We followed 1386 patients who underwent cardiac surgery for an average of 10 ± 3 years. According to clinical history of AF before and after surgery, four subgroups were identified: (1) patients with no history of AF and without episodes of AF during the first 30 days after surgery (control or Group 1, n = 726), (2) patients with no history of AF before surgery in whom new-onset POP AF was detected during the first 30 days after surgery (new-onset POP AF or Group 2, n = 452), (3) patients with a history of paroxysmal/persistent AF before cardiac surgery (Group 3, n = 125, including 87 POP AF patients and 38 who did not develop POP AF), and (4) patients with permanent AF at the time of cardiac surgery (Group 4, n = 83). All-cause mortality was the primary outcome of the study. We tested the associations of potential determinants with all-cause mortality using univariable and multivariable statistical analyses. Results: Overall, 473 patients (34%) died during follow-up. After adjustment for multiple confounders, new-onset POP AF (hazard ratio (HR) = 1.31, 95% confidence interval (CI): 0.90-1.89; p = 0.1609), history of paroxysmal/persistent AF before cardiac surgery (HR = 1.33, 95% CI: 0.71-2.49; p = 0.3736), and permanent AF (Group 4) (HR = 1.55, 95% CI 0.82-2.95; p = 0.1803) were not associated with a significantly increased risk of mortality when compared with Group 1 (patients with no history of AF and without episodes of AF during the first 30 days after surgery). In new-onset POP AF patients, oral anticoagulation was not associated with mortality (HR = 1.13, 95% CI: 0.83-1.54; p = 0.4299). Conclusions: In this cohort of patients who underwent different types of heart surgery, POP AF was not associated with an increased risk of mortality. In this setting, the role of long-term anticoagulation remains unclear.openMarazzato, Jacopo; Masnaghetti, Sergio; De Ponti, Roberto; Verdecchia, Paolo; Blasi, Federico; Ferrarese, Sandro; Trapasso, Monica; Spanevello, Antonio; Angeli, FabioMarazzato, Jacopo; Masnaghetti, Sergio; De Ponti, Roberto; Verdecchia, Paolo; Blasi, Federico; Ferrarese, Sandro; Trapasso, Monica; Spanevello, Antonio; Angeli, Fabi

Pain treatment with high-dose, controlled-release oxycodone: an Italian perspective

To investigate the possible role and tolerability of high-dose (>160 mg/day) oxycodone controlled release (CR) for the treatment of cancer and non-cancer pain. 227 patients with cancer or non-cancer pain were enrolled in an open-label, multi-center, Italian study in order to assess the adequacy of their existing pain management (using a numerical rating scale [NRS]) and the possible benefit high-dose oxycodone CR may offer patients experiencing uncontrolled pain. Results: Pain was poorly controlled at baseline, with only 18.1% of patients reporting adequate pain relief (NRS <3.5). All other patients reported uncontrolled pain, with an average NRS of 7.81. At baseline assessment, 47.89% of patients had been in pain for up to 3 months, 32.82% for 3–6 months, and 19.19% for more than 6 months. After baseline assessment, patients were switched to oxycodone CR monotherapy. The starting dose was individualized to each patient and titrated up over a 3- to 4-day period until effective pain management was achieved. Treatment was continued for an average of 37.24 days during the study. Pain control (final mean NRS of 2.85) was attained with an average dose of oxycodone CR 221.84 mg/day. Standard adverse events (including constipations, nausea, and vomiting) were recorded in 39.64% of patients receiving high-dose oxycodone CR monotherapy. Side-effects tended to subside after the initial week of treatment and did not result in any participants leaving the study. High-dose oxycodone CR can achieve rapid and effective management of moderate to severe cancer and non-cancer pain with minimum side-effects

The HST Key Project on the Extragalactic Distance Scale XXVI. The Calibration of Population II Secondary Distance Indicators and the Value of the Hubble Constant

A Cepheid-based calibration is derived for four distance indicators that utilize stars in the old stellar populations: the tip of the red giant branch (TRGB), the planetary nebula luminosity function (PNLF), the globular cluster luminosity function (GCLF) and the surface brightness fluctuation method (SBF). The calibration is largely based on the Cepheid distances to 18 spiral galaxies within cz =1500 km/s obtained as part of the HST Key Project on the Extragalactic Distance Scale, but relies also on Cepheid distances from separate HST and ground-based efforts. The newly derived calibration of the SBF method is applied to obtain distances to four Abell clusters in the velocity range between 3800 and 5000 km/s, observed by Lauer et al. (1998) using the HST/WFPC2. Combined with cluster velocities corrected for a cosmological flow model, these distances imply a value of the Hubble constant of H0 = 69 +/- 4 (random) +/- 6 (systematic) km/s/Mpc. This result assumes that the Cepheid PL relation is independent of the metallicity of the variable stars; adopting a metallicity correction as in Kennicutt et al. (1998), would produce a (5 +/- 3)% decrease in H0. Finally, the newly derived calibration allows us to investigate systematics in the Cepheid, PNLF, SBF, GCLF and TRGB distance scales.Comment: Accepted for publication in the Astrophysical Journal. 48 pages (including 13 figures and 4 tables), plus two additional tables in landscape format. Also available at http://astro.caltech.edu/~lff/pub.htm K' SBF magnitudes have been update

The impact of histopathology and NAB2-STAT6 fusion subtype in classification and grading of meningeal solitary fibrous tumor/hemangiopericytoma.

Meningeal solitary fibrous tumor (SFT)/hemangiopericytoma (HPC) is a rare tumor with propensity for recurrence and metastasis. Although multiple classification schemes have been proposed, optimal risk stratification remains unclear, and the prognostic impact of fusion status is uncertain. We compared the 2016 WHO CNS tumor grading scheme (CNS-G), a three-tier system based on histopathologic phenotype and mitotic count, to the 2013 WHO soft-tissue counterpart (ST-G), a two-tier system based on mitotic count alone, in a cohort of 133 patients [59 female, 74 male; mean age 54&nbsp;years (range 20-87)] with meningeal SFT/HPC. Tumors were pathologically confirmed through review of the first tumor resection (n = 97), local recurrence (n = 35), or distant metastasis (n = 1). A STAT6 immunostain showed nuclear expression in 132 cases. NAB2-STAT6 fusion was detected in 99 of 111 successfully tested tumors (89%) including the single STAT6 immunonegative tumor. Tumors were classified by CNS-G as grade 1 (n = 43), 2 (n = 41), or 3 (n = 49), and by ST-G as SFT (n = 84) or malignant SFT (n = 49). Necrosis was present in 16 cases (12%). On follow-up, 42 patients had at least one subsequent recurrence or metastasis (7 metastasis only, 33 recurrence only, 2 patients had both). Twenty-nine patients died. On univariate analysis, necrosis (p = 0.002), CNS-G (p = 0.01), and ST-G (p = 0.004) were associated with recurrence-free (RFS) but not overall survival (OS). NAB2-STAT6 fusion type was not significantly associated with RFS or OS, but was associated with phenotype. A modified ST-G incorporating necrosis showed higher correlation with RFS (p = 0.0006) and remained significant (p = 0.02) when considering only the primary tumors. From our data, mitotic rate and necrosis appear to stratify this family of tumors most accurately and could be incorporated in a future grading scheme

The HST Key Project on the Extragalactic Distance Scale. XXII. The Discovery of Cepheids in NGC 1326-A

We report on the detection of Cepheids and the first distance measurement to the spiral galaxy NGC 1326-A, a member of the Fornax cluster of galaxies. We have employed data obtained with the Wide Field and Planetary Camera 2 on board the Hubble Space Telescope. Over a 49 day interval, a total of twelve V-band (F555W) and eight I-band (F814W) epochs of observation were obtained. Two photometric reduction packages, ALLFRAME and DoPHOT, have been employed to obtain photometry measures from the three Wide Field CCDs. Variability analysis yields a total of 17 Cepheids in common with both photometry datasets, with periods ranging between 10 and 50 days. Of these 14 Cepheids with high-quality lightcurves are used to fit the V and I period-luminosity relations and derive apparent distance moduli, assuming a Large Magellanic Cloud distance modulus (m-M) (LMC) = 18.50 +- 0.10 mag and color excess E(B-V) = 0.10 mag. Assuming A(V)/E(V-I) = 2.45, the DoPHOT data yield a true distance modulus to NGC 1326-A of (m-M)_0 = 31.36 +- 0.17 (random) +- 0.13 (systematic) mag, corresponding to a distance of 18.7 \pm 1.5 (random) \pm 1.2 (systematic) Mpc. The derived distance to NGC 1326-A is in good agreement with the distance derived previously to NGC 1365, another spiral galaxy member of the Fornax cluster. However the distances to both galaxies are significantly lower than to NGC 1425, a third Cepheid calibrator in the outer parts of the cluster.Comment: 33 pages A gzipped tar file containing 12 figures can be obtained from http://www.ipac.caltech.edu/H0kp/n1326a/n1326a.htm

Dissipationless Formation and Evolution of the Milky Way Nuclear Star Cluster

Abridged: In one widely discussed model for the formation of nuclear star clusters (NSCs), massive globular clusters spiral into the center of a galaxy and merge to form the nucleus. It is now known that at least some NSCs coexist with supermassive black holes (SBHs); this is the case, for instance, in the Milky Way (MW). In this paper, we investigate how the presence of a SMBH at the center of the MW impacts the merger hypothesis for the formation of its NSC. Starting from a model consisting of a low-density nuclear stellar disk and the SMBH, we use N-body simulations to follow the successive inspiral and merger of globular clusters. The clusters are started on circular orbits of radius 20 pc, and their initial masses and radii are set up in such a way as to be consistent with the galactic tidal field at that radius. The total accumulated mass by ~10 clusters is about 1.5x10^7 Solar masses. Each cluster is disrupted by the SMBH at a distance of roughly one parsec. The density profile that results after the final inspiral event is characterized by a core of roughly this radius, and an envelope with density that falls off as 1/r^2. These properties are similar to those of the MW NSC, with the exception of the core size, which in the MW is a little smaller. But by continuing the evolution of the model after the final inspiral event, we find that the core shrinks substantially via gravitational encounters in a time (when scaled to the MW) of 10 Gyr as the stellar distribution evolves toward a Bahcall-Wolf cusp. We also show that the luminosity function of the MW NSC is consistent with the hypothesis that a large fraction of the mass comes from (~10Gyr) old stars, brought in by globular clusters. We conclude that a model in which a large fraction of the mass of the MW NSC arose from infalling globular clusters is consistent with existing observational constraints.Comment: 15 pages, 13 figures. ApJ accepte

The Hubble Space Telescope Extragalactic Distance Scale Key Project XXIII. The Discovery of Cepheids In NGC 3319

The distance to NGC 3319 has been determined from Cepheid variable stars as part of the Hubble Space Telescope Key Project on the Extragalactic Distance Scale. Thirteen and four epochs of observations, using filters F555W (V) and F814W (I) respectively, were made with the Wide Field Planetary Camera 2. Thirty-three Cepheid variables between periods of 8 and 47 days were discovered. Adopting a Large Magellanic Cloud distance modulus of 18.50 +- 0.10 mag and extinction of E(V-I)=0.13 mag, a true reddening-corrected distance modulus (based on an analysis employing the ALLFRAME software package) of 30.78 +- 0.14 (random) +- 0.10 (systematic) mag and the extinction of E(V-I) = 0.06 mag were determined for NGC 3319. This galaxy is the last galaxy observed for the HST H0 Key Project.Comment: 22 pages. A gzipped tar file containing 16 figures can be obtained from http://www.ipac.caltech.edu/H0kp/n3319/n3319.htm