Local crystallographic texture and voiding in passivated copper interconnects

A correlation between local crystallographic texture and stress‐induced void formation in tantalum‐encapsulated, copper interconnects was revealed by electron backscattering diffraction studies in a scanning electron microscope. Lines exhibiting an overall stronger 〈111〉 texture showed better resistance to void formation. Furthermore, grains adjacent to voids exhibited weaker 〈111〉 texture than grains in unvoided regions of the same line. The locally weaker 〈111〉 texture at voided locations suggests the presence of higher diffusivity, twist boundaries. This work, which represents the first characterization of local texture in stress voided, copper lines, helps to elucidate the relative importance of the thermodynamic and kinetic factors which govern void formation and growth. © 1996 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70319/2/APPLAB-69-26-4017-1.pd

The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0 % were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5 %). The diagnosis was deep-vein thrombosis (DVT) in 59.5 % and pulmonary embolism (PE) in 40.5 %. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5 %), hypertension (42.3 %) and dyslipidaemia (21.1 %). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2 %), almost half received a vitamin K antagonist (48.7 %) and nearly a quarter received a DOAC (24.5 %). Almost a quarter of all presentations were for recurrent VTE, with >80 % of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes

Pathological features of Prostate Imaging Reporting and Data System (PI-RADS) 3 MRI lesions in biopsy and radical prostatectomy specimens

Objective To assess the whole pathology spectrum of Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, identified on magnetic resonance imaging, using systematic (SB), targeted biopsy (TB) and radical prostatectomy (RP) specimen analysis. Methods From a prospective database of patients undergoing RP after a combination of SB (median 12 cores) and fusion TB (median 3 cores), we included 150 PI-RADS 3 cases. Clinically significant prostate cancer (csPCa) was defined by a Grade Group 2 or more. The primary endpoints were unfavourable features in RP specimens. Results Targeted biopsy was negative in 20.7% of patients. Final Grade Group 3 or more and a pT3 stage was reported in 36.7% and 38.7% of RP specimens. The upgrading rate was 38.2% between biopsy and RP specimens. The concordance rate between Grade Group on TB and RP was only 38.0%. The two independent predictive factors for unfavourable disease (pT3-4 and/or final Grade Group 3-5) were prostate-specific antigen density (PSAD; P = 0.001) and presence of csPCa on TB (odds ratio 3.7; P = 0.001). The risk of unfavourable disease was increased 2.3-fold and 5.8-fold, respectively, for patients with a PSAD between 0.15 and 0.20, and a PSAD >0.20 ng/mL/g. The 5-year biochemical recurrence-free survival rate was 93.2%. Conclusions PI-RADS 3 lesions exhibited aggressive features in almost 40% of cases. PSAD and presence of csPCa on TB are independent predictive factors for high-grade and/or extraprostatic disease. A combination of SB and TB improve grade prediction compared to use of TB alone

Urinary microbiota and prostatic diseases: the key for the lock? A systematic review

Background Urinary microbiota is implicated in many diseases of the urinary tract. The aim of this study was to perform a systematic review of the role of urinary microbiota in prostatic diseases. Methods A PubMed/Medline search was undergone from inception through June 2022 for studies investigating urinary microbiota alterations in prostatic diseases, subdivided into benign prostatic hyperplasia (BPH), prostate cancer (PCa), and chronic prostatitis (CP). Study selection followed the PRISMA statement. Phylum, family, genus and species of each bacterium in cancer patients and controls were recorded. Quality of included studies was evaluated using the Critical Appraisal Skills Program (CASP) checklist for non-randomized studies. Results A total of 16 studies (4 studies on BPH, 9 studies on PCa and 3 studies on CP) comprising 1486 patients were included in our final analysis. Patients with BPH had a different urinary microbial composition, with a certain pattern proven to be associated with a higher lower urinary tract symptoms severity. Regarding PCa, some bacterial phyla/genera/classes/species were more abundant in PCa and others predicted a higher grade disease. In patients with CP, a different microbiota composition and a higher diversity were found, with the symptom severity being influenced mainly by microbiota composition, favoring aerobic microorganisms. Conclusion Urinary microbiota is implicated in prostatic diseases, especially in BPH, PCa and CP. However, given the relative heterogeneity among published studies, this implication suggests better delineation is needed. Further studies are needed to confirm these findings

Immune checkpoint inhibitors for BCG-resistant NMIBC: The dawn of a new era

INTRODUCTION: High risk non-muscle invasive bladder cancer (NMIBC) is a recurring and potentially lethal disease. To date, with the exception of radical surgery, there are no validated strategies for patients not responding to intravesical BCG therapy. Immune checkpoint inhibitors (ICI) are currently being tested for BCG-resistant NMIBC. We report current available data and ongoing trials exploring the efficacy and safety of ICI in this setting.EVIDENCE ACQUISITION: A narrative search was performed including the combination of the following words: ("immunotherapy") AND ("BCG" AND "resistant" OR "non-muscle AND invasive") AND ("bladder AND "cancer"). Three search engines: PubMed, Embase and Web of Science were queried up to November 1, 2020. Congress abstracts reporting results and not only trials' design were also referenced. The US National Library of Medicine was queried via clinicaltrials.gov to explore ongoing trials on the subject.EVIDENCE SYNTHESIS: Pembrolizumab demonstrated a promising 40.6% (95% CI: 30.7-51.1) complete response within the KEYNOTE-057, with a median duration of response of 16.2 months. Preliminary data in the phase II SWOG S1605 trial with atezolizumab showed a 41.1% complete response at 3 months. Avelumab is being tested in the PREVERT phase II study exploring ICI with radiotherapy (60-66 Gy) of the whole bladder. CheckMate 9UT analyzes nivolumab monotherapy versus nivolumab + BMS-986205 (IDO-1 inhibitor) with or without BCG in patients with BCG-unresponsive, carcinoma in situ with or without papillary component. Finally, durvalumab is being studied in the BCG resistant space with radiotherapy in the ADAPT-BLADDER study. After proving its safety profile in the phase 1, the trial will randomize patients to durvalumab + BCG, durvalumab + radiation therapy (6Gy 3x) or BCG rechallenge.CONCLUSIONS: Pembrolizumab has received FDA approval in the treatment of BCG-resistant NMIBC. All five other ICI molecules are currently being extensively tested within clinical trials. The results of the currently ongoing studies are awaited with impatience by the uro-oncologic community and will probably open a new era in the treatment of BCG-resistant NMIBC