Are Selective Serotonin Reuptake Inhibitors Associated With Hepatocellular Carcinoma in Patients With Hepatitis C?

BACKGROUND AND AIMS: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for patients with chronic hepatitis C virus (HCV) infection. Research suggests that serotonin promotes the development and growth of hepatocellular carcinoma (HCC). We tested the hypothesis whether exposure to SSRIs is associated with an increased risk of HCC in HCV patients. METHOD: Patients who entered the United States Veterans Affairs (VA) Hepatitis C Clinical Case Registry in 2000 to 2009 were analyzed. During the 8 years of follow-up, 36,192 patients filled at least 1 SSRI prescription. Cases of HCC were identified by diagnosis codes (ICD-9 155.0). Multivariable Cox regression analyses estimated adjusted HCC hazard ratios (HRs) for SSRI-exposed versus SSRI-unexposed subjects and categories of average SSRI doses. RESULTS: The annual incidence of HCC in the VA registry cohort of 109,736 patients was 0.5% and significantly greater in the 8% with cirrhosis at baseline (HR = 5.2; 95% CI, 4.7-5.7). There was no evidence for significant interactions between the effect of SSRI-exposure and cirrhosis. Baseline characteristics of the exposed (n = 36,192) and unexposed (n = 73,544) subjects were similar. The median (interquartile range [IQR]) follow-up period after SSRI-exposure began was 44 (20-74) months with 18 (3-49) months between the first and last prescription. The median average SSRI dose during follow-up expressed as a fraction of initial recommended doses for depression was 0.94 (IQR, 0.5 to 1.3). The risk of HCC was not significantly increased after SSRI exposure (HR = 0.96; 95% CI, 0.87-1.05) or with increasing SSRI doses. CONCLUSIONS: Analysis of a large cohort of HCV patients did not support the hypothesis that SSRIs increase the risk of developing HCC.

Completion and Publication Rates of Randomized Controlled Trials in Surgery: An Empirical Study.

OBJECTIVE: To investigate the prevalence of discontinuation and nonpublication of surgical versus medical randomized controlled trials (RCTs) and to explore risk factors for discontinuation and nonpublication of surgical RCTs. BACKGROUND: Trial discontinuation has significant scientific, ethical, and economic implications. To date, the prevalence of discontinuation of surgical RCTs is unknown. METHODS: All RCT protocols approved between 2000 and 2003 by 6 ethics committees in Canada, Germany, and Switzerland were screened. Baseline characteristics were collected and, if published, full reports retrieved. Risk factors for early discontinuation for slow recruitment and nonpublication were explored using multivariable logistic regression analyses. RESULTS: In total, 863 RCT protocols involving adult patients were identified, 127 in surgery (15%) and 736 in medicine (85%). Surgical trials were discontinued for any reason more often than medical trials [43% vs 27%, risk difference 16% (95% confidence interval [CI]: 5%-26%); P = 0.001] and more often discontinued for slow recruitment [18% vs 11%, risk difference 8% (95% CI: 0.1%-16%); P = 0.020]. The percentage of trials not published as full journal article was similar in surgical and medical trials (44% vs 40%, risk difference 4% (95% CI: -5% to 14%); P = 0.373). Discontinuation of surgical trials was a strong risk factor for nonpublication (odds ratio = 4.18, 95% CI: 1.45-12.06; P = 0.008). CONCLUSIONS: Discontinuation and nonpublication rates were substantial in surgical RCTs and trial discontinuation was strongly associated with nonpublication. These findings need to be taken into account when interpreting surgical literature. Surgical trialists should consider feasibility studies before embarking on full-scale trials.

De Beruria Judaeorum doctissima foemina, ad historiam literariam eius gentis seculo secundo post C.n.

Altdort, Univ., Diss., 1714

Augenblicke der Weihe : neun kleine Stücke für Harmonium, Orgel oder Klavier ; op. 44

komponiert von L. Lewandowski

How often parametrial involvement leads to post-operative adjuvant treatment in locally advanced cervical cancer after neoadjuvant chemotherapy and type C radical hysterectomy?

OBJECTIVE Parametrial involvement (PMI) is one of the most important factors influencing prognosis in locally advanced stage cervical cancer (LACC) patients. We aimed to evaluate PMI rate among LACC patients undergoing neoadjuvant chemotherapy (NACT), thus evaluating the utility of parametrectomy in tailor adjuvant treatments. METHODS Retrospective evaluation of consecutive 275 patients affected by LACC (IB2-IIB), undergoing NACT followed by type C/class III radical hysterectomy. Basic descriptive statistics, univariate and multivariate analyses were applied in order to identify factors predicting PMI. Survival outcomes were assessed using Kaplan-Meier and Cox models. RESULTS PMI was detected in 37 (13%) patients: it was associated with vaginal involvement, lymph node positivity and both in 10 (4%), 5 (2%) and 12 (4%) patients, respectively; while PMI alone was observed in only 10 (4%) patients. Among this latter group, adjuvant treatment was delivered in 3 (1%) patients on the basis of pure PMI; while the remaining patients had other characteristics driving adjuvant treatment. Considering factors predicting PMI we observed that only suboptimal pathological responses (OR: 1.11; 95% CI: 1.01, 1.22) and vaginal involvement (OR: 1.29 (95%) CI: 1.17, 1.44) were independently associated with PMI. PMI did not correlate with survival (HR: 2.0; 95% CI: 0.82, 4.89); while clinical response to NACT (HR: 3.35; 95% CI: 1.59, 7.04), vaginal involvement (HR: 2.38; 95% CI: 1.12, 5.02) and lymph nodes positivity (HR: 3.47; 95% CI: 1.62, 7.41), independently correlated with worse survival outcomes. CONCLUSIONS Our data suggest that PMI had a limited role on the choice to administer adjuvant treatment, thus supporting the potential embrace of less radical surgery in LACC patients undergoing NACT. Further prospective studies are warranted.

Changes of coronary plaque composition correlate with C-reactive protein levels in patients with ST-elevation myocardial infarction following high-intensity statin therapy.

OBJECTIVES Levels of inflammatory biomarkers associate with changes of coronary atheroma burden in statin-treated patients with stable coronary artery disease. This study sought to determine changes of plaque composition in vivo in relation to high-sensitivity C-reactive protein (hs-CRP) levels in patients with ST-elevation myocardial infarction (STEMI) receiving high-intensity statin therapy. METHODS The IBIS-4 study performed serial (baseline and 13-month), 2-vessel intravascular ultrasound (IVUS) and radiofrequency-IVUS of the non-infarct-related arteries in patients with STEMI treated with high-intensity statin therapy. The present analysis included 44 patients (80 arteries) with serial measurements of hs-CRP. RESULTS At follow-up, median low-density lipoprotein cholesterol (LDL-C) levels decreased from 126 to 77 mg/dl, HDL-C increased from 44 to 47 mg/dl, and hs-CRP decreased from 1.6 to 0.7 mg/L. Regression of percent atheroma volume (-0.99%, 95% CI -1.84 to -0.14, p = 0.024) was accompanied by reduction of percent fibro-fatty (p = 0.04) and fibrous tissue (p < 0.001), and increase in percent necrotic core (p = 0.006) and dense calcium (p < 0.001). Follow-up levels of hs-CRP, but not LDL-C, correlated with changes in percent necrotic core (p = 0.001) and inversely with percent fibrous tissue volume (p = 0.008). Similarly, baseline-to-follow-up change of hs-CRP correlated with the change in percent necrotic core volume (p = 0.02). CONCLUSIONS In STEMI patients receiving high-intensity statin therapy, stabilization of VH-IVUS-defined necrotic core was confined to patients with lowest on-treatment levels and greatest reduction of hs-CRP. Elevated CRP levels at follow-up may identify progression of high-risk coronary plaque composition despite intensive statin therapy and overall regression of atheroma volume.

Na 1 Nachlass Max Horkheimer, 44 - Korrespondenzen u.a. mit Marthe Roth (p. I 21, 313-463)

2 Briefe und 1 Lebenslauf von Max Horkheimer an Arthur Rosenberg, 1939, 1941; 2 Briefe zwischen Kurt Rosenfeld und Karl Brandt, 22.04.1937, 27.04.1937; 5 Briefe von Kurt Rosenfeld an Max Horkheimer, 1937-19378; 4 Brief und Beilage an Kurt Rosenfeld, 1937-1943; 11 Briefe zwischen Hans W. Rosenhaupt und Max Horkheimer, 1935, 1941, 1942, 1947; 4 Briefe zwischen Samuel I. Roseman und Max Horkheimer, 1939, 03.01.1940; 2 Briefe zwischen J. Rosenstock und Max Horkheimer, 15.07.1946; 2 Briefe zwischen Joseph Adolphe Rosenthal und Max Horkheimer, 09.04.1941, 08.05.1941, sowie Briefwechsel mit Sophie Ries; 2 Briefe zwischen Sophie Ries und Max Horkheimer, 08.05.1941, 11.05.1941; 1 Brief von Max Horkheimer an Lore Woedthke, 08.05.1941; 2 Briefe zwischen Morris Rosenthal und Max Horkheimer, 01.10.1935, 04.10.1935; 1 Brief von Max Horkheimer an das Rosenwald Capital Outlay Fund New York, 30.01.1940; 1 Brief B. Lifschitz an Marthe Roth, 21.04.1937; 1 Brief von Chamorel et Simond an Marthe Roth, 11.06.1937; 1 Brief von F.K. Sung an Marthe Roth, 24.06.1937; 12 Briefe zwischen Marthe Roth und Max Horkheimer, Juli 1937-1938, sowie Briefwechsel mit Louis Vogt; 4 Briefe zwischen Louis Vogt und Max Horkheimer, 10.08.1937, 1937; 1 Brief von Max Horkheimer an Dr. Rothen, 31.01.1935; 1 Umzugsmitteilung von Hans Rothmann; 2 Briefe zwischen Richard C. Rothschild und Max Horkheimer, 11.05.1940, 13.05.1940; 4 Briefe zwischen Ludwig Rothschild, Hilde Rothschild und Max Horkheimer, 1936-15.09.1939; 2 Briefe zwischen S. Rothschildt und Max Horkheimer, 23.11.1940, 29.11.1940; 4 Brief zwischen J. S. Roucek und Max Horkheimer, 1941; 1 Brief von Joseph Rovan an Max Horkheimer, 11.05.1948; 2 Brief zwischen Wilmina Rowland und Max Horkheimer, 13.03.1949, 11.04.1949; 2 Briefe zwischen dem Royal Automobile Club und Max Horkheimer, 26.08.1937, 22.09.1937; 2 Briefe zwischen Royal Motors Inc. und Max Horkheimer, 05.02.1940, 06.03.1940; 1 Beitrag von Nina Rubinstein zur Soziologie des Fremden; 1 Brief von Theodor W. Adorno an Rudd, 09.09.1940; 1 Brief von Jay Rumney an Goldstein, 18.06.1936; 20 Briefe und Beilage zwischen Jay Rumney und Max Horkheimer, 1934- 1937, 1949 sowie Briefwechsel mit D. Mitrany; 3 Briefe zwischen D. Mitrany und Max Horkheimer, 01.12.1937, 1937; 3 Briefe von Theodor W. Adorno an Dagobert D. Runes, 1941; 1 Brief und 1 Beilage von N. Waterman an Georg Rusche, 03.05.1939; 12 Briefe und Beilage zwischen Georg Rusche und Max Horkheimer, 1939-1942 sowie Briefwechsel mit N. Waterman; 1 Brief von N. Waterman an Georg Rusche, 03.04.1939; 2 Briefe zwischen N. Waterman und Max Horkheimer, 21.04.1939, 05.05.1939; 1 Brief von Ruth an Max Horkheimer;

Ms. germ. oct. 350 - Geometrischer Grundriss der dem Freiherrn C. M. von Rothschild, in Bornheimer Gemarkung, zustehenden Guenthersburg nebst den dazu gehörenden Gärten und deren nächsten Umgebung.

Vorbesitzer: Freiherrlich Carl von Rothschild'sche Bibliothek Frankfurt am Main; alte Signatur: Gs 215/300; Akzessionsnummer: 19195

Diversity and faunal composition of benthic foraminifera in Hole 44-390A on the Blake Nose Plateau

Benthic foraminiferal assemblages are a widespread tool to understand changes in organic matter flux and bottom-water oxygenation and their relation to paleoceanographic changes in the Upper Cretaceous oceans. In this study, assemblage data (diversity, total number, and number per species and gram) from Deep Sea Drilling Project (DSDP) Site 390 (Blake Nose, western North Atlantic) were processed for the lower Maastrichtian (Globotruncana falsostuarti - Gansserina gansseri Planktic Foraminiferal Zone). These data document significant changes in nutrient flux to the sea floor as well as bottom-water oxygenation during this time interval. Parallel to the observed changes in the benthic foraminiferal assemblages the number of inoceramid shells decreases, reflecting also a significant increase in bottom-water oxygenation. We speculate, that these data could reflect the onset of a shift from warmer low-latitude to cooler high-latitude deep-water sources. This speculation will predate the major reorganization of the oceanic circulation resulting in a circulation mode similar to today at the Early/Late Maastrichtian boundary by ~1 Ma and therefore improves our understanding of Late Cretaceous paleoceanography.

Geochemical parameters of sediments and water of the Black Sea, data of Cruise 8 of R/V Vityaz-2

The book presents results of comprehensive geological investigations carried out during Cruise 8 of R/V "Vityaz-2" to the western part of the Black Sea in 1984. Systematic studies in the Black Sea during about hundred years have not weakened interest in the sea. Lithological and geochemical studies of sediments in estuarine areas of the Danube and the Kyzyl-Irmak rivers, as well as in adjacent parts of the deep sea and some other areas were the main aims of the cruise. Data on morphological structures of river fans, lithologic and chemical compositions of sediments in the fans and their areal distribution, forms of occurrence of chemical elements, role of organic matter and gases in sedimentation and diagenesis are given and discussed in the book.