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11.
Jae Eun Choi Tyler Werbel Zhenping Wang Chia Chi Wu Tony L. Yaksh Anna Di Nardo 《Journal of dermatological science》2019,93(1):58-64
Background
Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.Objectives
To investigate the molecular mechanism by which botulinum toxin improves rosacea lesions.Methods
Primary human and murine mast cells were pretreated with onabotulinum toxin A or B or control. Mast cell degranulation was evaluated by β-hexosaminidase activity. Expression of botulinum toxin receptor Sv2 was measured by qPCR. The presence of SNAP-25 and VAMP2 was established by immunofluorescence. In vivo rosacea model was established by intradermally injecting LL-37 with or without onabotulinum toxin A pretreatment. Mast cell degranulation was assessed in vivo by histologic counts. Rosacea biomarkers were analyzed by qPCR of mouse skin sections.Results
Onabotulinum toxin A and B inhibited compound 48/80-induced degranulation of both human and murine mast cells. Expression of Sv2 was established in mouse mast cells. Onabotulinum toxin A and B increased cleaved SNAP-25 and decreased VAMP2 staining in mast cells respectively. In mice, injection of onabotulinum toxin A significantly reduced LL-37-induced skin erythema, mast cell degranulation, and mRNA expression of rosacea biomarkers.Conclusions
These findings suggest that onabotulinum toxin reduces rosacea-associated skin inflammation by directly inhibiting mast cell degranulation. Periodic applications of onabotulinum toxin may be an effective therapy for refractory rosacea and deserves further study. 相似文献12.
13.
D. Gareth Evans Kelly-Anne Phillips Roger L. Milne Robert Fruscio Cezary Cybulski Jacek Gronwald Jan Lubinski Tomasz Huzarski Zerin Hyder Claire Forde Kelly Metcalfe Leigha Senter Jeffrey Weitzel Nadine Tung Dana Zakalik Maria Ekholm Ping Sun Steven A. Narod kConFab Investigators Polish Hereditary
Breast Cancer Consortium Hereditary Breast Cancer Clinical Study Group 《British journal of cancer》2021,124(9):1524
Background The impact of various breast-cancer treatments on patients with a BRCA2 mutation has not been studied. We sought to estimate the impact of bilateral oophorectomy and other treatments on breast cancer-specific survival among patients with a germline BRCA2 mutation.Methods We identified 664 women with stage I–III breast cancer and a BRCA2 mutation by combining five different datasets (retrospective and prospective). Subjects were followed for 7.2 years from diagnosis to death from breast cancer. Tumour characteristics and cancer treatments were patient-reported and derived from medical records. Predictors of survival were determined using Cox proportional hazard models, adjusted for other treatments and for prognostic features.Results The 10-year breast-cancer survival for ER-positive patients was 78.9% and for ER-negative patients was 82.3% (adjusted HR = 1.23 (95% CI, 0.62–2.45, p = 0.55)). The 10-year breast-cancer survival for women who had a bilateral oophorectomy was 89.1% and for women who did not have an oophorectomy was 59.0% (adjusted HR = 0.45; 95% CI, 0.28–0.72, p = 0.001). The adjusted hazard ratio for chemotherapy was 0.83 (95% CI, 0.65–1.53: p = 0.56).Conclusions For women with breast cancer and a germline BRCA2 mutation, positive ER status does not predict superior survival. Oophorectomy is associated with a reduced risk of death from breast cancer and should be considered in the treatment plan.Subject terms: Targeted therapies, Breast cancer 相似文献
14.
Roberto L. Cazzato Pierre De Marini Ian Leonard-Lorant Danoob Dalili Guillaume Koch Pierre A. Autrusseau Theo Mayer Julia Weiss Pierre Auloge Julien Garnon Afshin Gangi 《Diagnostic and interventional imaging》2021,102(6):355-361
PurposeTo retrospectively report on safety, pain relief and local tumor control achieved with percutaneous ablation of sacral bone metastases.Materials and methodsFrom February 2009 to June 2020, 23 consecutive patients (12 women and 11 men; mean age, 60 ± 8 [SD] years; median, 60; range: 48-80 years) with 23 sacral metastases underwent radiofrequency (RFA) or cryo-ablation (CA), with palliative or curative intent at our institution. Patients’ demographics and data pertaining to treated metastases, procedure-related variables, safety, and clinical evolution following ablation were collected and analyzed. Pain was assessed with numerical pain rating scale (NPRS).ResultsSixteen (70%) patients were treated with palliative and 7 (30%) with curative intent. Mean tumor diameter was 38 ± 19 (SD) mm (median, 36; range: 11-76). External radiation therapy had been performed on five metastases (5/23; 22%) prior to ablation. RFA was used in 9 (39%) metastases and CA in the remaining 14 (61%). Thermo-protective measures and adjuvant bone consolidation were used whilst treating 20 (87%) and 8 (35%) metastases, respectively. Five (22%) minor complications were recorded. At mean 31 ± 21 (SD) (median, 32; range: 2-70) months follow-up mean NPRS was 2 ± 2 (SD) (median, 1; range: 0–6) vs. 5 ± 1 (median, 5; range: 4–8; P < 0.001) at the baseline. Three metastases out of 7 (43%) undergoing curative ablation showed local progression at mean 4 ± 4 (SD) (median, 2; range: 1-8) months follow-up.ConclusionPercutaneous ablation of sacral metastases is safe and results in significant long-lasting pain relief. Local tumor control seems sub-optimal; however, further investigations are needed to confirm these findings due to paucity of data. 相似文献
15.
Bo Yang Elizabeth L. Norton Terry Shih Linda Farhat Xiaoting Wu Whitney E. Hornsby Karen M. Kim Himanshu J. Patel G. Michael Deeb 《The Journal of thoracic and cardiovascular surgery》2019,157(4):1313-1321.e2
Objective
To compare perioperative and long-term outcomes in patients undergoing hemiarch and aggressive arch replacement for acute type A aortic dissection (ATAAD).Methods
From 1996 to 2017, we compared outcomes of hemiarch (n = 322) versus aggressive arch replacements (zones 2 and 3 arch replacement with implantation of 2-4 arch branches, n = 150) in ATAAD. Indications for aggressive arch were arch aneurysm >4 cm or intimal tear in the aortic arch that was not resectable by hemiarch replacement, or dissection of arch branches with malperfusion.Results
Patients in the aggressive arch group were significantly younger (mean age: 57 vs 61 years old) and had significantly longer hypothermic circulatory arrest, cardiopulmonary bypass, and aortic crossclamp times. There were no significant differences in perioperative outcomes between hemiarch and aggressive arch groups, including 30-day mortality (5.3% vs 7.3%, P = .38) and postoperative stroke rate (7% vs 7%, P = .96). Over 15 years, Kaplan–Meier survival was similar between hemiarch and aggressive arch groups (log-rank P = .55, 10-year survival 70% vs 72%). Given death as a competing factor, incidence rates of reoperation over 15 years (2.1% vs 2.0% per year, P = 1) and 10-year cumulative incidence of reoperation (14% vs 12%, P = .89) for arch and distal aorta pathology were similar between the 2 groups.Conclusions
Both hemiarch and aggressive arch replacement are appropriate approaches for select patients with ATAAD. Aggressive arch replacement should be considered for an arch aneurysm >4 cm or an intimal tear at the arch unable to be resected by hemiarch replacement, or dissection of the arch branches with malperfusion. 相似文献16.
Alazne Belar Maria Arantzamendi Alfredo Rodríguez-Núñez Yolanda Santesteban Marina Martinez Mario López-Saca Sara Consigli Jesús López-Fidalgo Carlos Centeno 《Journal of pain and symptom management》2019,57(3):627-634
Context
Demoralization is a state of existential distress in patients with advanced illness, typically with coping difficulties, feelings of loss of sense, and purpose in life and despair, among other things. The New Demoralization Scale (DS-II) is an evaluation tool for this syndrome, which has recently been reformulated on a shorter scale.Objectives
The objective of this study was to obtain a Spanish version of the DS-II and to assess its psychometric properties in advanced cancer patients in Spain and a number of Latin American countries.Methods
Following a translation–back translation process, a validation study and a confirmatory analysis using structural equation models with their corresponding latent constructs were undertaken. Patients completed the DS-II in Spanish (DS-II (es)), the Hospital Anxiety and Depression Scale, and the Edmonton Symptom Assessment System–revised. Reliability was studied according to internal consistency; construct validity and concurrent validity with the Hospital Anxiety and Depression Scale and the Edmonton Symptom Assessment System–revised; discriminant validity using the Karnofsky Performance Status scale; and feasibility, with response ratio and required time. Cutoff points were established, and sensitivity and specificity were studied.Results
The DS-II (es) was obtained. One hundred fifty patients completed the validation study. The confirmatory analysis showed coherence, and all items correlated positively with their subscales and with the overall scale. Cronbach's alpha for the DS-II (es) was 0.88, for the sense and purpose subscale 0.83, and for the coping ability 0.79. Demoralization correlated significantly with emotional distress (rho = 0.73, P < 0.001). The tool distinguished between patients with diverse functional levels (rho = ?0.319, P = 0.001). Cutoff points at 10 and 20 out of 32 were established. The scale showed high sensitivity (81.97%) and specificity (80.90%). The prevalence of demoralization was 33% in our sample.Conclusion
The Spanish version of the new Kissane DS-II demoralization scale has shown to be valid, reliable, and feasible with adequate psychometric properties. 相似文献17.
Aasha I. Hoogland Hailey W. Bulls Brian D. Gonzalez Brent J. Small Lianqi Liu Joseph Pidala Heather S.L. Jim Asmita Mishra 《Journal of pain and symptom management》2019,57(5):952-960.e1
Context
Quality of life (QoL) is increasingly recognized as an important outcome of cancer treatment. Previous studies have examined clinical predictors of QoL, but with the increasing prevalence of wearable sensors that monitor sleep and activity patterns, further investigation into whether these behaviors are predictive of post-treatment QoL is now feasible. Among patients receiving aggressive cancer treatment such as hematopoietic cell transplantation (HCT), analysis of circadian rhythms (24-hour patterns of sleep and activity) via wearable sensors is limited.Objective
To evaluate the relationship between overall QoL and circadian rhythms in patients receiving allogeneic HCT.Methods
Patients wore an ActiGraph GT3X (Pensacola, FL) activity monitor for at least 72 hours before the initiation of conditioning chemotherapy and transplantation and completed a QoL (Functional Assessment of Cancer Therapy-General [FACT-G]) assessment. QoL assessments were also completed 1, 3, and 6 months after HCT.Results
Patients (n = 45, M age = 55) were mostly male (66%) with a total FACT-G score of 80.96 (SD = 16.05) before HCT. Mixed models revealed robust cross-sectional associations between overall QoL and multiple circadian rhythmicity parameters, including durations of high physical activity, overall circadian rhythmicity, and earlier starts of daily activity (P's < .01). Recovery of QoL after transplant was predicted by longer pre-transplant durations of high physical activity (P = .04) and earlier evening retirement (P = .04).Conclusion
Our findings suggest that wearable sensor information is a promising method of predicting recovery of QoL after HCT. Additional studies are needed to confirm these findings in a larger sample. 相似文献18.
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19.
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20.
Katherine M. Stenson Benjamin O. Patterson Matthew Joe Grima Jorg L. De Bruin Peter J.E. Holt Ian Loftus 《Journal of vascular surgery》2019,69(1):53-62.e1