Twenty-Seven Years of Phase III Trials for Patients with Extensive Disease Small-Cell Lung Cancer: Disappointing Results

BACKGROUND: Few studies have formally assessed whether treatment outcomes have improved substantially over the years for patients with extensive disease small-cell lung cancer (ED-SCLC) enrolled in phase III trials. The objective of the current investigation was to determine the time trends in outcomes for the patients in those trials. METHODS AND FINDINGS: We searched for trials that were reported between January 1981 and August 2008. Phase III randomized controlled trials were eligible if they compared first-line, systemic chemotherapy for ED-SCLC. Data were evaluated by using a linear regression analysis. RESULTS: In total, 52 trials were identified that had been initiated between 1980 and 2006; these studies involved 10,262 patients with 110 chemotherapy arms. The number of randomized patients and the proportion of patients with good performance status (PS) increased over time. Cisplatin-based regimens, especially cisplatin and etoposide (PE) regimen, have increasingly been studied, whereas cyclophosphamide, doxorubicin, and vincristine-based regimens have been less investigated. Multiple regression analysis showed no significant improvement in survival over the years. Additionally, the use of a PE regimen did not affect survival, whereas the proportion of patients with good PS and the trial design of assigning prophylactic cranial irradiation were significantly associated with favorable outcome. CONCLUSIONS AND SIGNIFICANCE: The survival of patients with ED-SCLC enrolled in phase III trials did not improve significantly over the years, suggesting the need for further development of novel targets, newer agents, and comprehensive patient care

Brucella abortus Choloylglycine Hydrolase Affects Cell Envelope Composition and Host Cell Internalization

Choloylglycine hydrolase (CGH, E.C. 3.5.1.24) is a conjugated bile salt hydrolase that catalyses the hydrolysis of the amide bond in conjugated bile acids. Bile salt hydrolases are expressed by gastrointestinal bacteria, and they presumably decrease the toxicity of host's conjugated bile salts. Brucella species are the causative agents of brucellosis, a disease affecting livestock and humans. CGH confers Brucella the ability to deconjugate and resist the antimicrobial action of bile salts, contributing to the establishment of a successful infection through the oral route in mice. Additionally, cgh-deletion mutant was also attenuated in intraperitoneally inoculated mice, which suggests that CGH may play a role during systemic infection other than hydrolyzing conjugated bile acids. To understand the role CGH plays in B. abortus virulence, we infected phagocytic and epithelial cells with a cgh-deletion mutant (Δcgh) and found that it is defective in the internalization process. This defect along with the increased resistance of Δcgh to the antimicrobial action of polymyxin B, prompted an analysis of the cell envelope of this mutant. Two-dimensional electrophoretic profiles of Δcgh cell envelope-associated proteins showed an altered expression of Omp2b and different members of the Omp25/31 family. These results were confirmed by Western blot analysis with monoclonal antibodies. Altogether, the results indicate that Brucella CGH not only participates in deconjugation of bile salts but also affects overall membrane composition and host cell internalization

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

Orguljski festival "Anabasis" : Orguljski romantizam (studenti Muzičke akademije Sveučilišta u Zagrebu, 27. 4. 2021.)

Koncert je održan na Muzičkoj akademiji u Koncertnoj dvorani "Blagoje Bersa" 27. 4. 2021. Izvođači: studenti orgulja Klara Čanić, Goran Gregorin, Jelena Horvat, Ivana Hrkać, Mladen Bonomi i Dubravko Čepulić Polgar. Program: 1. E. Gigout: Toccata u h-molu (izvođač: Klara Čanić); 2. M. Reger: Erste suite, op. 16 Den manen Johann Sebastian Bachs (Passacaglia) (izvođač: Goran Gregorin); 3. Ch. M. Widor: Iz 6. simfonije, op. 42 u g-molu (Cantabile) (izvođač: Jelena Horvat): 4. J. Bonnet: Variations de concert, op. 1 (izvođač: Ivana Hrkać); 5. F. Liszt: Fantazija i fuga na ime B-A-C-H (izvođač: Mladen Bonomi); 6. Ch. M. Widor: iz 5. simfonije, op. 42 u f-molu (Allegro vivace) (izvođač: Dubravko Čepulić Polgar)

Orguljski festival "Anabasis" : Orguljski romantizam (studenti Muzičke akademije u Zagrebu, 27.4.2021.)

Koncert je održan na Muzičkoj akademiji u Zagrebu u Koncertnoj dvorani "Blagoje Bersa" 27.4.2021. Izvođači: studenti orgulja Muzičke akademije u Zagrebu: Klara Čanić (mentorica: Ljerka Očić), Goran Gregorin (mentor: Mario Penzar), Jelena Horvat (mentorica: Ljerka Očić), Ivana Hrkać (mentor: Mario Penzar), Mladen Bonomi (mentorica: Ljerka Očić), Dubravko Čepulić Polgar (mentor: Mario Penzar). Program: 1. E. Gigout: Toccata u h-molu (izvođač: Klara Čanić); 2. M. Reger: Erste suite, op. 16 Den manen Johann Sebastian Bachs (Passacaglia) (izvođač: Goran Gregorin); 3. Ch. M. Widor: Iz 6. simfonije, op. 42 u g-molu (IV. Cantabile) (izvođač: Jelena Horvat): 4. J. Bonnet: Variations de concert, op. 1 (izvođač: Ivana Hrkać); 5. F. Liszt: Fantazija i fuga na ime B-A-C-H (izvođač: Mladen Bonomi); 6. Ch. M. Widor: iz 5. simfonije, op. 42 u f-molu (Allegro vivace) (izvođač: Dubravko Čepulić Polgar)

Wheat IgE-mediated food allergy in European patients: alpha-amylase inhibitors, lipid transfer proteins and low-molecular-weight glutenins:Allergenic molecules recognized by double-blind, placebo-controlled food challenge

Background: Three main problems hamper the identification of wheat food allergens: (1) lack of a standardized procedure for extracting all of the wheat protein fractions; (2) absence of double-blind, placebo-controlled food challenge studies that compare the allergenic profile of Osborne's three protein fractions in subjects with real wheat allergy, and (3) lack of data on the differences in IgE-binding capacity between raw and cooked wheat. Methods: Sera of 16 wheat-challenge-positive patients and 6 patients with wheat anaphylaxis, recruited from Italy, Denmark and Switzerland, were used for sodium dodecyl sulfate-polyacrylamide gel electrophoresis/immunoblotting of the three Osborne's protein fractions (albumin/globulin, gliadins and glutenins) of raw and cooked wheat. Thermal sensitivity of wheat lipid transfer protein (LTP) was investigated by spectroscopic approaches. IgE cross-reactivity between wheat and grass pollen was studied by blot inhibition. Results: The most important wheat allergens were the \u3b1-amylase/trypsin inhibitor subunits, which were present in all three protein fractions of raw and cooked wheat. Other important allergens were a 9-kDa LTP in the albumin/globulin fraction and several low-molecular-weight (LMW) glutenin subunits in the gluten fraction. All these allergens showed heat resistance and lack of cross-reactivity to grass pollen allergens. LTP was a major allergen only in Italian patients. Conclusions: The \u3b1-amylase inhibitor was confirmed to be the most important wheat allergen in food allergy and to play a role in wheat-dependent exercise-induced anaphylaxis, too. Other important allergens were LTP and the LMW glutenin subunits. Copyrigh