Decision-making among experts in advanced Hodgkin Lymphoma.

BACKGROUND In the treatment of advanced Hodgkin Lymphoma (aHL), based on guidelines a multitude of treatment options are available. The availability of PET guided decision-making and new therapeutic agents increase the complexity of the decision-making process. METHODS Thirteen experts of Swiss university and cantonal hospitals in Switzerland were asked to describe their institutional decision-making practice in aHL. Variables influencing the decision-making process were identified, standardized and converted into decision trees for analysis of consent and discrepancies. The algorithms of all participating experts were analyzed with the objective consensus methodology. RESULTS Four decision criteria (age, fertility preservation, fitness, interim PET) and 12 unique treatment regimens were identified. Consensus for the treatment of aHL for young and fit, as well as for older patients without comorbidity was found. Large heterogeneity was identified with use of a variety of different regimens for unfit patients with aHL and for young female patients with a desire of fertility preservation. CONCLUSION Four major decision criteria were identified allowing the representation of expert's approach to first-line treatment of aHL. Among Swiss experts, consensus for a PET guided curative treatment of aHL was identified. The use of a multitude of treatment regimens was observed for older and comorbid (unfit) aHL patients, highlighting the need for clinical trials and recommendations for this group of patients

Cell-Free DNA Genomic Profiling and Its Clinical Implementation in Advanced Prostate Cancer.

Most men with prostate cancer (PCa), despite potentially curable localized disease at initial diagnosis, progress to metastatic disease. Despite numerous treatment options, choosing the optimal treatment for individual patients remains challenging. Biomarkers guiding treatment sequences in an advanced setting are lacking. To estimate the diagnostic potential of liquid biopsies in guiding personalized treatment of PCa, we evaluated the utility of a custom-targeted next-generation sequencing (NGS) panel based on the AmpliSeq HD Technology. Ultra-deep sequencing on plasma circulating free DNA (cfDNA) samples of 40 metastatic castration-resistant PCa (mCRPC) and 28 metastatic hormone-naive PCa (mCSPC) was performed. CfDNA somatic mutations were detected in 48/68 (71%) patients. Of those 68 patients, 42 had matched tumor and cfDNA samples. In 21/42 (50%) patients, mutations from the primary tumor tissue were detected in the plasma cfDNA. In 7/42 (17%) patients, mutations found in the primary tumor were not detected in the cfDNA. Mutations from primary tumors were detected in all tested mCRPC patients (17/17), but only in 4/11 with mCSPC. AR amplifications were detected in 12/39 (31%) mCRPC patients. These results indicate that our targeted NGS approach has high sensitivity and specificity for detecting clinically relevant mutations in PCa

Mast Cells in Allergic Asthma and Beyond

Mast cells have been regarded for a long time as effector cells in IgE mediated type I reactions and in host defence against parasites. However, they are resident in all environmental exposed tissues and express a wide variety of receptors, suggesting that these cells can also function as sentinels in innate immune responses. Indeed, studies have demonstrated an important role of mast cells during the induction of life-saving antibacterial responses. Furthermore, recent findings have shown that mast cells promote and modulate the development of adaptive immune responses, making them an important hinge of innate and acquired immunity. In addition, mast cells and several mast cell-produced mediators have been shown to be important during the development of allergic airway diseases. In the present review, we will summarize findings on the role of mast cells during the development of adaptive immune responses and highlight their function, especially during the development of allergic asthma

Microstructures of Pratt and Whitney EB-PVD TBCs

The goal of this project was to fully characterize the microstructure of the EB-PVD TBCs deposited on "shadow bar" cylinders and three turbine blades as a function of position in Pratt & Whitney's coater one as well as location on the substrate. Using image analysis software, data models were constructed for TBC thickness, density and angle of crystal growth. Additionally, crystallographic orientation was determined for the cylinder's as well as PW4000 2nd stage turbine blades using x-ray diffraction

Swiss experience of atezolizumab for platinum-pretreated urinary tract carcinoma: the SAUL study in real-world practice.

AIMS OF THE STUDY Atezolizumab is an approved therapy for urothelial carcinoma based on results from the IMvigor 210 and IMvigor211 phase II and III trials. The global SAUL study evaluated atezolizumab in a broader patient population more representative of real-world populations. Among approximately 1000 patients treated in SAUL, 25 were treated in Swiss oncology centres. We evaluated outcomes in these patients to provide a better understanding of atezolizumab treatment for urinary tract carcinoma in Swiss clinical practice. METHODS Eligible patients had locally advanced or metastatic urothelial or non-urothelial urinary tract carcinoma that had progressed during or after one to three prior therapies for inoperable, locally advanced or metastatic disease. Patient populations typically excluded from clinical trials (e.g., patients with renal impairment, treated central nervous system [CNS] metastases, stable controlled autoimmune disease or Eastern Cooperative Oncology Group performance status 2) were also eligible. All patients received atezolizumab 1200 mg every 3 weeks until loss of clinical benefit or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included overall survival (OS), overall response rate (ORR) and disease control rate (DCR). RESULTS All 25 Swiss patients had previously received a gemcitabine/platinum doublet. Disease had progressed within 12 months of platinum-based therapy in all but one patient, and 19 (76%) had received one prior line of therapy for metastatic disease. The median duration of atezolizumab therapy was six cycles (range 1–27) corresponding to 3.6 months. Five patients (20%) had received >20 cycles and four (16%) remained on treatment at the data cut-off. Grade 3 adverse events (AEs) occurred in 13 patients (52%) and were considered to be treatment-related in four patients (16%; liver enzyme increases, musculoskeletal pain, diverticulitis and autoimmune hepatitis). There was one grade 4 AE (hypercalcaemia) and no grade 5 AEs. After median follow-up of 17.3 months, median OS was 7.9 months (95% confidence interval [CI] 5.3–not evaluable), the 1-year OS rate was 47% (95% CI 27–65%), the ORR was 12% (95% CI 3–31%) and the DCR was 40% (95% CI 21–61%). Durable clinical benefit (>1 year on treatment) was observed in seven patients (28%), including one with CNS metastases and one with small-cell carcinoma. CONCLUSIONS Atezolizumab is an active treatment option for platinum-pretreated urinary tract carcinoma, including patients with conditions that typically exclude them from clinical trials. (Trial registration no.: NCT02928406)

Culture dependent analysis of bacterial diversity in Canada’s Raspberry Rising Cave revealed antimicrobial properties

Bacteria and archaea thrive in terrestrial subsurface environments because of their unique physiology. Over time, these unique microorganisms may have adapted to possess specialized metabolic pathways that sustain their continued existence in caves, one of harshest environments on earth. The present study elucidates cultivation based microbial diversity of the cave sediments and wall scrapings collected from seven different locations in Raspberry Rising Cave located in the Columbia Mountain Range, British Columbia, Canada. A total of 103 cultivable bacteria from the cave were isolated on various agar media including R2A, Hickey-Tresner, and DifcoTM Actinomycetes Isolation agar media. Taxonomical phylogenetic analysis of the 16S rRNA gene of the bacterial isolates identified three major phyla: Proteobacteria (Class: Gammaproteobacteria) (51.45%), Actinobacteria (43.68%) and Bacteroidetes (3.88%). Among them, the major genus was Pseudomonas (48.54%) followed by Rhodococcus (39.80%) and Flavobacterium (3.88%). The genus Janthinobacterium and Arthrobacter contributed about 2.91% each, of the total population. Noteworthy, 0.99% were recognized as endophytic Proteobacteria. Furthermore, these bacterial isolates were evaluated for their potential antimicrobial activities against the multidrug resistant bacterial strains. Two bacterial isolates (RRC23, RRC75) showed antimicrobial activities against multi-drug resistant (MDR) Escherichia coli #15-318 while RRC48 exhibited against methicillin resistant (MRSA) Staphylococcus aureus. The isolates RRC36 and RRC38 were identified to show antimicrobial activities against non-pathogenic isolates of Staphylococcus aureus. To the best of our knowledge, this is the first scientific study conducted and provides the insight in occurrence and distribution of the cultivated bacterial diversity from the Raspberry Rising Cave. Moreover, the antimicrobial properties exhibited by some of the bacterial isolates suggested that this cave system could be a resource for potential antibiotics, drugs or novel biologics of clinical relevance