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21.
M. Corral-Blanco V.C. Prudencio-Ribera M.E. Jarrín-Estupiñán R. Alonso-Moralejo V. Pérez-González J.C. Meneses-Pardo A. Hermira-Anchuelo A. De Pablo-Gafas 《Transplantation proceedings》2019,51(2):380-382
Background
Pulmonary hypertension (PH) is a comorbidity associated with interstitial lung disease (ILD). The purpose of this study was to evaluate the influence of PH on intrahospital mortality in lung transplantation (LT) for ILD.Methods
We conducted a retrospective cohort study of 66 patients who underwent LT for ILD at the 12 de Octubre University Hospital (Madrid, Spain) from October 2008 to June 2014. PH was defined as mean pulmonary arterial pressure (mPAP) ≥25 mmHg on right-sided heart catheterization and intrahospital mortality as any death taken place after the transplantation of patients not being discharged.Results
We retrospectively analyzed data of 66 patients; they were stratified by the presence or absence of PH before LT. Twenty-seven patients (41%) had PH. The PH group had a lower diffusing capacity of carbon monoxide (DLCO), carbon monoxide transfer coefficient (KCO), and 6-minute walk distance test (6MWT) and a higher total lung capacity (TLC), modified medical research council dyspnea scale (mMRC), and lung allocation score (LAS) than the non-PH group. Patients with PH more often underwent double lung transplantation (DLT; 59%) than single lung transplantation (SLT).Intrahospital mortality was 13% (9/66). No significant differences were observed in Kaplan-Meier survival curves for the PH and non-PH groups with a median survival time of 46 days versus 33 days (IQR 26–74; log-rank P = .056); however, the postoperative length of stay in the hospital was greater in the PH group.Conclusions
In our cohort, pulmonary hypertension was not related to early mortality in lung transplantation recipients for interstitial lung diseases. 相似文献22.
Anna-Maria Lutz Rüdiger Hampe Malgorzata Roos Nina Lümkemann Marlis Eichberger Bogna Stawarczyk 《The Journal of prosthetic dentistry》2019,121(1):166-172
Statement of problem
Polymeric material for 3-dimensional printing can be used to fabricate occlusal devices. However, information about fracture resistance and wear is scarce.Purpose
The purpose of this in vitro study was to investigate the fracture resistance and 2-body wear of 3-dimensional–printed (3DP) (FotoDent splint; Dreve Dentamid GmbH), milled polymethylmethacrylate (CAM) (Temp Basic; Transpa 95H16, Zirkonzahn GmbH), and conventionally fabricated polymethylmethacrylate (CAST) (Castdon; Dreve Dentamid GmbH) occlusal devices.Material and Methods
A total of 96 occlusal devices were prepared according to the 3 different manufacturing techniques 3DP, CAM, and CAST (n=32). For each manufacturing technique, specimens were further divided into initial fracture resistance tests (n=16) and artificial aging in the mastication simulator (50 N, 37°C) with 2-body wear followed by fracture resistance tests (n=16). The fracture resistance was determined using a universal testing machine (1 mm/min). The wear was measured after 20?000 and 120?000 mastication cycles with the replica technique, mapped with a laser scanner, and quantified in R software. Data were analyzed using a 2-way ANOVA followed by a 1-way ANOVA with Scheffé or Games-Howell post hoc tests, repeated measures ANOVA with corrected Greenhouse-Geisser P values, and the Levene, Mann-Whitney, and paired t tests (α=.05).Results
CAM presented higher initial fracture resistance than 3DP or CAST (P<.001). After mastication simulation, CAM followed by 3DP showed higher fracture resistance than CAST (P<.001). Mastication simulation decreased the fracture resistance for CAM and CAST (P<.001) but not for 3DP (P=.78). Three-dimensional–printed occlusal devices showed the highest material volume loss, followed by CAM and the lowest in CAST (P<.001).Conclusions
Three-dimensional–printed occlusal devices showed lower wear resistance and lower fracture resistance than those milled or conventionally fabricated. Therefore, only short-term application in the mouth is recommended. Further developments of occlusal device material for 3-dimensional printing are necessary. 相似文献23.
24.
David C. Johnson Steven S. Raman Sohrab A. Mirak Lorna Kwan Amirhossein M. Bajgiran William Hsu Cleo K. Maehara Preeti Ahuja Izak Faiena Aydin Pooli Amirali Salmasi Anthony Sisk Ely R. Felker David S.K. Lu Robert E. Reiter 《European urology》2019,75(5):712-720
Background
Multiparametric magnetic resonance imaging (mpMRI) undoubtedly affects the diagnosis and treatment of localized prostate cancer (CaP). However, clinicians need a better understanding of its accuracy and limitations in detecting individual CaP foci to optimize management.Objective
To determine the per-lesion detection rate for CaP foci by mpMRI and identify predictors of tumor detection.Design, setting, and participants
We carried out a retrospective analysis of a prospectively managed database correlating lesion-specific results from mpMRI co-registered with whole-mount pathology (WMP) prostatectomy specimens from June 2010 to February 2018. Participants include 588 consecutive patients with biopsy-proven CaP undergoing 3-T mpMRI before radical prostatectomy at a single tertiary institution.Outcome measurements and statistical analysis
We measured mpMRI sensitivity in detecting individual CaP and clinically significant (any Gleason score ≥7) CaP foci and predictors of tumor detection using multivariate analysis.Results and limitations
The final analysis included 1213 pathologically confirmed tumor foci in 588 patients with primarily intermediate- (75%) or high-risk (12%) CaP. mpMRI detected 45% of all lesions (95% confidence interval [CI] 42–47%), including 65% of clinically significant lesions (95% CI 61–69%) and nearly 80% of high-grade tumors. Some 74% and 31% of missed solitary and multifocal tumors, respectively, were clinically significant. The majority of missed lesions were small (61.1% ≤1 cm); 28.3% were between 1 and 2 cm, and 10.4% were >2 cm. mpMRI missed at least one clinically significant focus in 34% of patients overall, and in 45% of men with multifocal lesions. On multivariate analysis, smaller, low-grade, multifocal, nonindex tumors with lower prostate-specific antigen density were more likely to be missed. Limitations include selection bias in a prostatectomy cohort, lack of specificity data, an imperfect co-registration process, and uncertain clinical significance for undetected lesions.Conclusions
mpMRI detects less than half of all and less than two-thirds of clinically significant CaP foci. The moderate per-lesion sensitivity and significant proportion of men with undetected tumor foci demonstrate the current limitations of mpMRI.Patient summary
Magnetic resonance imaging of the prostate before surgical removal for prostate cancer finds less than half of all individual prostate cancer tumors. Large, solitary, aggressive tumors are more likely to be visualized on imaging. 相似文献25.
S. Kim M.J. Graham R.G. Lee L. Yang S. Kim V. Subramanian J.D. Layne L. Cai R.E. Temel D. Shih A.J. Lusis J.A. Berliner S. Lee 《Nutrition, metabolism, and cardiovascular diseases : NMCD》2019,29(3):306-315
Background and aims
Heparin-binding EGF-like growth factor (HB-EGF) is a representative EGF family member that interacts with EGFR under diverse stress environment. Previously, we reported that the HB-EGF-targeting using antisense oligonucleotide (ASO) effectively suppressed an aortic aneurysm in the vessel wall and circulatory lipid levels. In this study, we further examined the effects of the HB-EGF ASO administration on the development of hyperlipidemia-associated atherosclerosis using an atherogenic mouse model.Methods and results
The male and female LDLR deficient mice under Western diet containing 21% fat and 0.2% cholesterol content were cotreated with control and HB-EGF ASOs for 12 weeks. We observed that the HB-EGF ASO administration effectively downregulated circulatory VLDL- and LDL-associated lipid levels in circulation; concordantly, the HB-EGF targeting effectively suppressed the development of atherosclerosis in the aorta. An EGFR blocker BIBX1382 administration suppressed the hepatic TG secretion rate, suggesting a positive role of the HB-EGF signaling for the hepatic VLDL production. We newly observed that there was a significant improvement of the insulin sensitivity by the HB-EGF ASO administration in a mouse model under the Western diet as demonstrated by the improvement of the glucose and insulin tolerances.Conclusion
The HB-EGF ASO administration effectively downregulated circulatory lipid levels by suppressing hepatic VLDL production rate, which leads to effective protection against atherosclerosis in the vascular wall. 相似文献26.
M. Iachina P.M. Ljungdalh R.G. Sørensen L. Kaerlev J. Blaakær O. Trosko N. Qvist B.M. Nørgård 《Clinical oncology (Royal College of Radiologists (Great Britain))》2019,31(2):115-123
Aims
To examine the influence of pre-existing psychiatric disorder on the choice of treatment in patients with gynaecological cancer.Materials and methods
The analyses were based on all patients who underwent surgical treatment for endometrial, ovarian or cervical cancer who were registered in the Danish Gynecological Cancer Database in the years 2007–2014 (3059 patients with ovarian cancer, 5100 patients with endometrial cancer and 1150 with cervical cancer). Logistic regression model and Cox regression model, adjusted for relevant confounders, were used to estimate the effect of pre-existing psychiatric disorder on the course of cancer treatment. Our outcomes were (i) presurgical oncological treatment, (ii) macroradical surgery for patients with ovarian cancer, (iii) radiation/chemotherapy within 30 days and 100 days after surgery and (iv) time from surgery to first oncological treatment.Results
In the group of patients with ovarian cancer, more patients with a psychiatric disorder received macroradical surgery versus patients without a psychiatric disorder, corresponding to an adjusted odds ratio of 1.24 (95% confidence interval 0.62–2.41) and the chance for having oncological treatment within 100 days was odds ratio = 1.26 (95% confidence interval 0.77–2.10). As for patients with endometrial cancer, all outcome estimates were close to unity. The adjusted odds ratio for oncological treatment within 30 days after surgery in patients with cervical cancer with a history of psychiatric disorder was 0.20 (95% confidence interval 0.03–1.54).Conclusions
We did not find any significant differences in the treatment of ovarian and endometrial cancer in patients with pre-existing psychiatric diagnoses. When it comes to oncological treatment, we suggest that increased attention should be paid to patients with cervical cancer having a pre-existing psychiatric diagnosis. 相似文献27.
Warren Fiskus Christopher P. Mill Behnam Nabet Dimuthu Perera Christine Birdwell Taghi Manshouri Bernardo Lara Tapan M. Kadia Courtney DiNardo Koichi Takahashi Naval Daver Prithviraj Bose Lucia Masarova Naveen Pemmaraju Steven Kornblau Gautam Borthakur Guillermo Montalban-Bravo Guillermo Garcia Manero Sunil Sharma Matthew Stubbs Xiaoping Su Michael R. Green Cristian Coarfa Srdan Verstovsek Joseph D. Khoury Christopher R. Vakoc Kapil N. Bhalla 《Blood cancer journal》2021,11(5)
There is an unmet need to overcome nongenetic therapy-resistance to improve outcomes in AML, especially post-myeloproliferative neoplasm (MPN) secondary (s) AML. Studies presented describe effects of genetic knockout, degradation or small molecule targeted-inhibition of GFI1/LSD1 on active enhancers, altering gene-expressions and inducing differentiation and lethality in AML and (MPN) sAML cells. A protein domain-focused CRISPR screen in LSD1 (KDM1A) inhibitor (i) treated AML cells, identified BRD4, MOZ, HDAC3 and DOT1L among the codependencies. Our findings demonstrate that co-targeting LSD1 and one of these co-dependencies exerted synergistic in vitro lethality in AML and post-MPN sAML cells. Co-treatment with LSD1i and the JAKi ruxolitinib was also synergistically lethal against post-MPN sAML cells. LSD1i pre-treatment induced GFI1, PU.1 and CEBPα but depleted c-Myc, overcoming nongenetic resistance to ruxolitinib, or to BETi in post-MPN sAML cells. Co-treatment with LSD1i and BETi or ruxolitinib exerted superior in vivo efficacy against post-MPN sAML cells. These findings highlight LSD1i-based combinations that merit testing for clinical efficacy, especially to overcome nongenetic therapy-resistance in AML and post-MPN sAML.Subject terms: Acute myeloid leukaemia, Targeted therapies 相似文献
28.
29.
Elizabeth D. Krebs William Z. Chancellor Jared P. Beller J. Hunter Mehaffey Robert B. Hawkins Robert G. Sawyer Leora T. Yarboro Gorav Ailawadi Nicholas R. Teman 《The Annals of thoracic surgery》2021,111(2):594-599
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30.
Roy Rabbie Peter Ferguson Kim Wong Dominique-Laurent Couturier Una Moran Clinton Turner Patrick Emanuel Kerstin Haas Jodi M. Saunus Morgan R. Davidson Sunil R. Lakhani Brindha Shivalingam Georgina V. Long Christine Parkinson Iman Osman Richard A. Scolyer Pippa Corrie David J. Adams 《British journal of cancer》2021,124(1):156
Brain metastases are a major cause of melanoma-related mortality and morbidity. We undertook whole-exome sequencing of 50 tumours from patients undergoing surgical resection of brain metastases presenting as the first site of visceral disease spread and validated our findings in an independent dataset of 18 patients. Brain metastases had a similar driver mutational landscape to cutaneous melanomas in TCGA. However, KRAS was the most significantly enriched driver gene, with 4/50 (8%) of brain metastases harbouring non-synonymous mutations. Hotspot KRAS mutations were mutually exclusive from BRAFV600, NRAS and HRAS mutations and were associated with a reduced overall survival from the resection of brain metastases (HR 10.01, p = 0.001). Mutations in KRAS were clonal and concordant with extracranial disease, suggesting that these mutations are likely present within the primary. Our analyses suggest that KRAS mutations could help identify patients with primary melanoma at higher risk of brain metastases who may benefit from more intensive, protracted surveillance.Subject terms: CNS cancer, Metastasis, Melanoma, Tumour biomarkers, Cancer 相似文献