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1.
Laure Gossec Anna Molto Xavier Romand Déborah Puyraimond-Zemmour Matthieu Lavielle Catherine Beauvais Eric Senbel René-Marc Flipo Sophie Pouplin Christophe Richez Alain Saraux Maryse Mézières Loriane Gutermann Philippe Gaudin Daniel Wendling Maxime Dougados 《Joint, bone, spine : revue du rhumatisme》2019,86(1):13-19
Background
Adherence to treatment is a key issue in chronic inflammatory rheumatic diseases (CIRDs).Objective
To develop recommendations to facilitate in daily practice, the management of non-adherence to disease-modifying drugs in patients with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, connective tissue diseases or other CIRDs.Methods
The process comprised (a) systematic literature reviews of methods (including questionnaires) to measure non-adherence, risk factors for non-adherence and efficacy of targeted interventions; (b) development of recommendations through consensus of 104 rheumatologist and nurse experts; (c) assessment of agreement and ease of applicability (1–5 where 5 is highest) by the 104 experts.Results
(a) Overall, 274 publications were analysed. (b) The consensus process led to 5 overarching principles and 10 recommendations regarding adherence. Key points include that adherence should be assessed at each outpatient visit, at least using an open question; questionnaires and hydroxychloroquine blood level assessments may also be useful. Risk factors associated to non-adherence were listed. Patient information and education, and patient/physician shared decision, are key to optimize adherence. Other techniques such as formalized education sessions, motivational interviewing and cognitive behavioral therapy may be useful. All health professionals can get involved and e-health may be a support. (c) The agreement with the recommendations was high (range of means, 3.9–4.5) but ease of applicability was lower (2.7–4.4).Conclusions
Using an evidence-based approach followed by expert consensus, this initiative should improve the assessment and optimization of adherence in chronic inflammatory rheumatic disorders. 相似文献2.
Anne Tournadre Bruno Pereira Laure Gossec Martin Soubrier Maxime Dougados 《Joint, bone, spine : revue du rhumatisme》2019,86(1):55-60
Objectives
To analyze the factors associated with fatigue focusing on comorbidities in a large cohort of rheumatoid arthritis (RA).Methods
Cross-sectional analyses were performed on RA patients from the French COMEDRA cohort study, a nurse-led program for comorbidities management. Fatigue was assessed using Question 3 of the Rheumatoid Arthritis Impact of Disease (RAID) score on a 0–10 numerical rating scale (NRS). Fatigue was defined as acceptable if?≤?2, moderate if 3 or 4, or severe if?≥?5 out of 10. Using univariate and multivariate models, the relationship between fatigue and demographics, social, disease characteristics, comorbidities (cardiovascular, infections, cancer, pulmonary, osteoporosis, and psychiatric disorders), physical activity, quality of life, and treatments was investigated.Results
In total, 962 patients were analyzed. The mean fatigue score was 3.8?±?2.7, 40% of patients reported severe fatigue. Patients had an average of 1.8 additional morbid conditions, with anxiety/depression the most common (52%). In univariate analysis, severe fatigue was more frequent in women, in patients not working, and in those with less physical activity. It was associated with disease duration and activity, mHAQ, pain, sleeping and emotional difficulties. Severe fatigue correlated with Multimorbidity index assessing the number of morbid conditions and was associated with obesity, hypertension, COPD, and anxiety/depression. In multivariate models, the risk of severe fatigue was associated with female gender, disease activity, mHAQ, current treatment with NSAIDs and biologics, multimorbidity, obesity and anxiety/depression.Conclusions
Assessment of comorbidities, psychological health and physical activity should be taken into account in order to address frequent RA-related severe fatigue. 相似文献3.
Umberto Capitanio Karim Bensalah Axel Bex Stephen A. Boorjian Freddie Bray Jonathan Coleman John L. Gore Maxine Sun Christopher Wood Paul Russo 《European urology》2019,75(1):74-84
Context
Despite the improvement in renal cell carcinoma (RCC) diagnosis and management observed during the last 2 decades, RCC remains one of the most lethal urological malignancies. With the expansion of routine imaging for many disorders, an increasing number of patients who harbour RCC are identified incidentally.Objective
To summarise and compare RCC incidence and mortality rates, analyse the magnitude of risk factors, and interpret these epidemiological observations in the context of screening and disease management.Evidence acquisition
The primary objective of the current review was to retrieve and describe worldwide RCC incidence/mortality rates. Secondly, a narrative literature review about the magnitude of the known risk factors was performed. Finally, data retrieved from the first two steps were elaborated to define the clinical implications for RCC screening.Evidence synthesis
RCC incidence and mortality significantly differ among individual countries and world regions. Potential RCC risk factors include behavioural and environmental factors, comorbidities, and analgesics. Smoking, obesity, hypertension, and chronic kidney disease represent established risk factors. Other factors have been associated with an increased RCC risk, although selection biases may be present and controversial results have been reported.Conclusions
Incidence of RCC varies worldwide. Within the several RCC risk factors identified, smoking, obesity, and hypertension are most strongly associated with RCC. In individuals at a higher risk of RCC, the cost effectiveness of a screening programme needs to be assessed on a country-specific level due to geographic heterogeneity in incidence and mortality rates, costs, and management implications. Owing to the low rates of RCC, implementation of accurate biomarkers appears to be mandatory.Patient summary
The probability of harbouring kidney cancer is higher in developed countries and among smokers, obese individuals, and individuals with hypertension. 相似文献4.
Ben A. Hickey Andrew Cleves Raza Alikhan Neil Pugh Len Nokes Anthony Perera 《Foot and Ankle Surgery》2019,25(1):59-62
Background
Our aim was to determine whether plasma levels of Tissue Factor (TF), Vascular Cell Adhesion Molecule 1 (VCAM-1), Interleukin 6 (IL-6) or D-dimer after foot and ankle injury could predict which patients would develop deep vein thrombosis (DVT).Methods
Patients aged 18–60 years with acute foot and ankle injury had venous blood sample to measure TF, VCAM-1, IL-6 and D-dimer within 3 days of injury. Patients had bilateral lower limb venous ultrasound to assess for DVT on discharge from clinic.Results
21 of 77 patients were found to have DVT (27%). There was no statistically significant association between levels of TF, VCAM-1, IL-6 or D-dimer and subsequent development of DVT.Conclusion
Tissue Factor (TF), Vascular Cell Adhesion Molecule-1 (VCAM-1), Interleukin-6 (IL-6) and D-dimer levels were not associated with development deep vein thrombosis in patients with acute foot and ankle injury. 相似文献5.
Minh Vu Chuong Nguyen Athan Baillet Xavier Romand Candice Trocmé Anaïs Courtier Hubert Marotte Thierry Thomas Martin Soubrier Pierre Miossec Jacques Tébib Laurent Grange Bertrand Toussaint Thierry Lequerré Olivier Vittecoq Philippe Gaudin 《Joint, bone, spine : revue du rhumatisme》2019,86(2):195-201
Objectives
Tumour necrosis factor-alpha inhibitors (TNFi) are effective treatments for Rheumatoid Arthritis (RA). Responses to treatment are barely predictable. As these treatments are costly and may induce a number of side effects, we aimed at identifying a panel of protein biomarkers that could be used to predict clinical response to TNFi for RA patients.Methods
Baseline blood levels of C-reactive protein, platelet factor 4, apolipoprotein A1, prealbumin, α1-antitrypsin, haptoglobin, S100A8/A9 and S100A12 proteins in bDMARD naive patients at the time of TNFi treatment initiation were assessed in a multicentric prospective French cohort. Patients fulfilling good EULAR response at 6 months were considered as responders. Logistic regression was used to determine best biomarker set that could predict good clinical response to TNFi.Results
A combination of biomarkers (prealbumin, platelet factor 4 and S100A12) was identified and could predict response to TNFi in RA with sensitivity of 78%, specificity of 77%, positive predictive values (PPV) of 72%, negative predictive values (NPV) of 82%, positive likelihood ratio (LR + ) of 3.35 and negative likelihood ratio (LR?) of 0.28. Lower levels of prealbumin and S100A12 and higher level of platelet factor 4 than the determined cutoff at baseline in RA patients are good predictors for response to TNFi treatment globally as well as to Infliximab, Etanercept and Adalimumab individually.Conclusion
A multivariate model combining 3 biomarkers (prealbumin, platelet factor 4 and S100A12) accurately predicted response of RA patients to TNFi and has potential in a daily practice personalized treatment. 相似文献6.
Marcus M. Ilg Marta Mateus William J. Stebbeds Uros Milenkovic Nim Christopher Asif Muneer Maarten Albersen David J. Ralph Selim Cellek 《European urology》2019,75(2):329-340
Background
Peyronie's disease (PD) is a fibrotic disorder of the penile tunica albuginea, characterised by the formation of a localised fibrous plaque that can lead to deformity and erectile dysfunction. Nonsurgical therapeutic options for PD are limited in efficacy and safety. Myofibroblasts are key cells in the pathogenesis of PD, and inhibition of myofibroblast transformation has been suggested as a therapeutic option.Objective
To identify potential drugs using a novel phenotypic assay and then to test them using in vitro and in vivo models of PD.Design, setting, and participants
We have developed and validated a phenotypic screening assay that measures myofibroblast transformation, by which we tested 21 compounds that were suggested to be efficacious in treating PD. The successful hits from this assay were further tested using in vitro and in vivo models of PD.Results and limitations
The new assay was able to detect transforming growth factor-β1–induced myofibroblast transformation. Using this assay, phosphodiesterase type 5 inhibitors (PDE5i) and selective oestrogen receptor modulators (SERMs) were identified to significantly inhibit myofibroblast transformation. A PDE5i (vardenafil) and an SERM (tamoxifen) inhibited myofibroblast transformation, collagen gel contraction, and extracellular matrix production in a synergistic fashion. In a rat model of PD, the antifibrotic effect of the combination of vardenafil and tamoxifen was greater than that of each drug alone. This study is limited by not providing a molecular mechanism for the proposed synergy.Conclusions
This is the first demonstration of a synergistic activity between a PDE5i and an SERM discovered through a phenotypic screening approach. Future clinical trials using a combination of these drugs should be considered during the active phase of PD, given the early evidence of benefit in both in vitro and in vivo models.Patient summary
This report suggests that the combination of a phosphodiesterase type 5 inhibitor and a selective oestrogen receptor modulator may be efficacious in treating Peyronie's disease in its active phase. 相似文献7.
Mark A. Preston Travis Gerke Sigrid V. Carlsson Lisa Signorello Daniel D. Sjoberg Sarah C. Markt Adam S. Kibel Quoc-Dien Trinh Mark Steinwandel William Blot Andrew J. Vickers Hans Lilja Lorelei A. Mucci Kathryn M. Wilson 《European urology》2019,75(3):399-407
Background
Prostate-specific antigen (PSA) measurement in midlife predicts long-term prostate cancer (PCa) mortality among white men.Objective
To determine whether baseline PSA level during midlife predicts risk of aggressive PCa in black men.Design, setting, and participants
Nested case-control study among black men in the Southern Community Cohort Study recruited between 2002 and 2009. A prospective cohort in the southeastern USA with recruitment from community health centers. A total of 197 incident PCa patients aged 40–64 yr at study entry and 569 controls matched on age, date of blood draw, and site of enrollment. Total PSA was measured in blood collected and stored at enrollment.Outcome measurements and statistical analysis
Total and aggressive PCa (91 aggressive: Gleason ≥7, American Joint Committee on Cancer stage III/IV, or PCa-specific death). Exact conditional logistic regression estimated odds ratios (ORs) with 95% confidence intervals (CIs) for PCa by category of baseline PSA.Results and limitations
Median PSA among controls was 0.72, 0.80, 0.94, and 1.03 ng/ml for age groups 40–49, 50–54, 55–59, and 60–64 yr, respectively; 90th percentile levels were 1.68, 1.85, 2.73, and 3.33 ng/ml. Furthermore, 95% of total and 97% of aggressive cases had baseline PSA above the age-specific median. Median follow-up was 9 yr. The OR for total PCa comparing PSA >90th percentile versus ≤median was 83.6 (95% CI, 21.2–539) for 40–54 yr and 71.7 (95% CI, 23.3–288) for 55–64 yr. For aggressive cancer, ORs were 174 (95% CI, 32.3–infinity) for 40–54 yr and 51.8 (95% CI, 11.0–519) for 55–64 yr. A composite endpoint of aggressive PCa based on stage, grade, and mortality was used and is a limitation.Conclusions
PSA levels in midlife strongly predicted total and aggressive PCa among black men. PSA levels among controls were similar to those among white controls in prior studies.Patient summary
Prostate-specific antigen (PSA) level during midlife strongly predicted future development of aggressive prostate cancer among black men. Targeted screening based on a midlife PSA might identify men at high risk while minimizing screening in those men at low risk. 相似文献8.
Matthew R. Walker Ashraf N. El Naga Omar H. Atassi Christopher H. Perkins Scott A. Mitchell 《Injury》2019,50(3):686-689
Objectives
Hip dislocations are highly morbid injuries necessitating prompt reduction and post-reduction assessment for fracture and incarcerated fragments. Recent literature has questioned the need for initial pelvic radiographs for acute trauma patients, resulting in computed tomography (CT) scans as the initial evaluation. This study investigates the relationship between choice of pre-reduction imaging and treatment of acute hip dislocations.Design
Retrospective Case-Control.Setting
Single Academic Level I Trauma Center.Methods
All acute hip dislocations from 2011 to 2016 were reviewed. Exclusion criteria were diagnosis of dislocation at another facility, death prior to reduction, emergent surgical or ICU intervention, and periprosthetic dislocation. Patients were grouped by those with only a radiograph prior to reduction, Group I, versus those with a pre-reduction CT scan, Group II. The primary outcomes were time to reduction and the acquisition of a second CT scan.Results
Of the 123 hip dislocations identified, 35 patients were excluded, mostly for transfer with a known dislocation. Group I included 29 patients and Group II included 59 patients. The mean time to reduction was 74?min in Group I and 129?min in Group II for a difference of 55?min (p?<?0.001). The rate of repeat CT scan was 0 in Group I versus 48 (81%) in Group II (p?<?0.001).Conclusion
Initial trauma pelvic radiography prior to CT is still important in the setting of suspected hip pathology to decrease time to hip reduction and unnecessary radiation exposure.Level of evidence
Prognostic Level III. 相似文献9.
Giorgio Gandaglia Guillaume Ploussard Massimo Valerio Agostino Mattei Cristian Fiori Nicola Fossati Armando Stabile Jean-Baptiste Beauval Bernard Malavaud Mathieu Roumiguié Daniele Robesti Paolo Dell’Oglio Marco Moschini Stefania Zamboni Arnas Rakauskas Francesco De Cobelli Francesco Porpiglia Francesco Montorsi Alberto Briganti 《European urology》2019,75(3):506-514
Background
Available models for predicting lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP) might not be applicable to men diagnosed via magnetic resonance imaging (MRI)-targeted biopsies.Objective
To assess the accuracy of available tools to predict LNI and to develop a novel model for men diagnosed via MRI-targeted biopsies.Design, setting, and participants
A total of 497 patients diagnosed via MRI-targeted biopsies and treated with RP and extended pelvic lymph node dissection (ePLND) at five institutions were retrospectively identified.Outcome measurements and statistical analyses
Three available models predicting LNI were evaluated using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analyses. A nomogram predicting LNI was developed and internally validated.Results and limitations
Overall, 62 patients (12.5%) had LNI. The median number of nodes removed was 15. The AUC for the Briganti 2012, Briganti 2017, and MSKCC nomograms was 82%, 82%, and 81%, respectively, and their calibration characteristics were suboptimal. A model including PSA, clinical stage and maximum diameter of the index lesion on multiparametric MRI (mpMRI), grade group on targeted biopsy, and the presence of clinically significant PCa on concomitant systematic biopsy had an AUC of 86% and represented the basis for a coefficient-based nomogram. This tool exhibited a higher AUC and higher net benefit compared to available models developed using standard biopsies. Using a cutoff of 7%, 244 ePLNDs (57%) would be spared and a lower number of LNIs would be missed compared to available nomograms (1.6% vs 4.6% vs 4.5% vs 4.2% for the new nomogram vs Briganti 2012 vs Briganti 2017 vs MSKCC).Conclusions
Available models predicting LNI are characterized by suboptimal accuracy and clinical net benefit for patients diagnosed via MRI-targeted biopsies. A novel nomogram including mpMRI and MRI-targeted biopsy data should be used to identify candidates for ePLND in this setting.Patient summary
We developed the first nomogram to predict lymph node invasion (LNI) in prostate cancer patients diagnosed via magnetic resonance imaging-targeted biopsy undergoing radical prostatectomy. Adoption of this model to identify candidates for extended pelvic lymph node dissection could avoid up to 60% of these procedures at the cost of missing only 1.6% patients with LNI. 相似文献10.
Joost C. Schrier Noel L. Keijsers Giovanni A. Matricali Cees C.P.M. Verheyen Jan Willem K. Louwerens 《Foot and Ankle Surgery》2019,25(1):37-46
Background
Despite impressive results of the pharmacological management of rheumatoid arthritis, still certain patients suffer from rheumatoid forefoot problems. Surgical treatment of these forefoot deformities can be an option. In literature no high-quality studies on this topic can be found.The goal of present study is to compare the results of a metatarsal head (MTH) resecting technique with a MTH preserving technique in the operative treatment of severe rheumatoid forefoot deformity.Methods
Patients suffering from well-defined rheumatoid forefoot deformity were prospectively enrolled in three institutions. This non-blinded study had a randomised clinical design and eligible patients were randomly assigned to undergo either resection of preservation of the MTH. The primary outcome measure consisted of the AOFAS score. Secondary outcome measures were: the FFI, the VAS for pain and the SF-36.Results
Twenty-three patients (10 in MTH preservation group) were included and analysed. After one year follow-up no significant differences in AOFAS score and additional outcome factors were found. A total of 10 complications in 23 patients were reported.Conclusions
This randomised clinical study did not show significant clinical difference between a MTH resecting and a preserving procedure in patients suffering from rheumatoid forefoot deformity. Both procedures resulted in considerable improvement of pain and activity scores. 相似文献11.
Silvia Valverde José Luis Sánchez García José Antonio Pereira Manel Armengol Manuel López-Cano 《Cirugía espa?ola》2019,97(2):97-102
Background
Incisional hernias are a frequent complication, and their prevention includes proper closure of the abdominal wall.Methods
A prospective study was conducted at a third-level hospital after the introduction of a midline laparotomy closure protocol. An objective measurement of the suture length to incision length ratio was made. and the postoperative results were analyzed.Results
127 patients were included and 34 of them (26.8%) had received a technically deficient closure. Incisional hernia was described in 20.5% of cases. An improvement in the quality of the abdominal wall closure was demonstrated over time.Conclusion
The abdominal wall closure was deficient in nearly one- quarter of the laparotomies performed at a third-level medical center. A protocol improved the quality of the laparotomy closure. 相似文献12.
Objective
To analyse whether early post-operative full weight bearing following syndesmotic ankle fixation affected radiographic outcomes suggestive of diastasis.Design
Retrospective comparative cohort study over a two year period.Setting
Level 1 trauma centrePatients/Participants
152 consecutive patients sustaining an unstable ankle fracture requiring syndesmotic stabilisation were included. Exclusions were 49 patients who had trimalleolar fixation without syndesmosis screws, one patient who had concomitant ankle and talar fracture. Five patients were lost to follow up and eleven patients were followed up in other centres. A total of 86 patients were analysedIntervention
Protected or full weight bearing.Main Outcome Measurement
The primary outcome measure was early diastasis. The secondary outcomes were late diastasis, wound complications and re-operation. Analysis of variance was used for the predictor variable of weight bearing status. We assumed a priori that p values of less than 0.05 were significant.Results
Median age was 36 (IQR 30), with 54 males and 32 females. Median follow up was 12 weeks (IQR 6). There was no significant difference when comparing weight bearing status and change in radiographic measurements intra-operatively compared to 6 and 12 week follow up radiographs (tibiofibular clear space p?=?0.799, tibiofibular overlap p?=?0.733 and medial clear space p?=?0.261).Conclusion
After surgical stabilization of an unstable syndesmotic injury, full weight bearing did not lead to syndesmotic diastasis in the early post-operative period. Full weight bearing is recommended following ankle fixation which includes syndesmotic fixation. 相似文献13.
14.
Tero T. Yli-Kyyny Reijo Sund Mikko Heinänen Antti Malmivaara Heikki Kröger 《Injury》2019,50(2):403-408
Introduction
Hip fracture surgery is associated with a considerable amount medical and surgical complications, which adversely impacts the patient’s outcome and/or increases costs. We evaluated what risk factors were associated with the occurrence of early readmission due to surgical complications after hip fracture surgery.Material and methods
A nationwide database with 68,800 hip fracture patients treated between 1999 and 2011 was studied to uncover the association of readmissions with co-morbidities, fracture types, different hospital types and treatment methods using the Cox proportional hazards model.Results
Early readmission within three months due to hip fracture surgery complications occurred at a rate of 4.6%. Increased occurrence of readmission was found among patients with: heavy alcoholism (HR 1.38; 95% CI: 1.23–1.53); Parkinson’s disease (PD; HR 1.22; 95% CI: 1.05–1.42); pre-existing osteoarthritis (HR 2.02; 95% CI: 1.83–2.23); rheumatic disease (HR 1.44; 95% CI: 1.27–1.65); as well as those with a fracture of the femur neck, depression, presence of a psychotic disorder, an operative delay of at least three days, or previous treatment with total hip arthroplasty.Conclusion
Our results indicate that there are several factors associated with an increased risk of early readmission. We suggest that in the presence of these factors, the surgical treatment method and postoperative protocol should be carefully planned and performed. 相似文献15.
Marthe Løvf Sen Zhao Ulrika Axcrona Bjarne Johannessen Anne Cathrine Bakken Kristina Totland Carm Andreas M. Hoff Ola Myklebost Leonardo A. Meza-Zepeda A. Kathrine Lie Karol Axcrona Ragnhild A. Lothe Rolf I. Skotheim 《European urology》2019,75(3):498-505
Background
Most primary prostate cancers are multifocal with individual tumors harboring different aggressiveness; however, the genomic heterogeneity among these tumors is poorly understood.Objective
To better understand the biological basis for clinical variability among different lesions, we sought to comprehensively characterize the heterogeneity of somatic gene mutations in multifocal prostate cancer.Design, setting, and participants
High-coverage whole-exome sequencing of 153 frozen tissue samples, taken from two to three distinct tumor foci and one non-cancerous area from each of 41 patients, covering a total of 89 tumor foci.Outcome measurements and statistical analysis
State-of-the-art bioinformatics tools for mutation calling and copy number determination from whole-exome sequencing data.Results and limitations
We found a very high degree of interfocal heterogeneity among tumors, that is, 76% of pairwise-compared tumor foci from the same prostatectomy specimen had no point mutations in common and DNA copy number changes were rarely shared across cancer foci. The few point mutations shared across tumor foci were seldom in cancer-critical genes.Conclusions
In this first large genomic heterogeneity study of primary prostate cancer, we observe that different tumor foci within the same patient are genetically distinct, only rarely sharing any somatic gene mutations, including those in cancer driver genes. This heterogeneity affects how genomics-based management of prostate cancer can be implemented, as information from all tumor foci is necessary to draw valid conclusions about the cancer's genomic alterations.Patient summary
Most primary prostate cancers consist of multiple tumors within the same organ, but little is known about their relationships. We have compared the sets of gene mutations among such tumors and found that they only exceptionally have any in common. This will influence treatment decisions in the future as each tumor's mutations will render it unique and have to be considered to gain the best treatment results. 相似文献16.
17.
Julien Dagenais Riccardo Bertolo Juan Garisto Matthew J. Maurice Pascal Mouracade Onder Kara Jaya Chavali Jianbo Li Ryan Nelson Amr Fergany Robert Abouassaly Jihad H. Kaouk 《European urology》2019,75(4):628-634
Background
Understanding physician-level discrepancies is increasingly a target of US healthcare reform for the delivery of quality-focused patient care.Objective
To estimate the relative contributions of patient and surgeon characteristics to the variability in key outcomes after partial nephrectomy (PN).Design, setting, and participants
Retrospective review of 1461 patients undergoing PN performed by 19 surgeons between 2011 and 2016 at a tertiary care referral center.Intervention
PN for a renal mass.Outcomes measurements and statistical analysis
Hierarchical linear and logistic regression models were built to determine the percentage variability contributed by fixed patient and surgeon factors on peri- and postoperative outcomes. Residual between- and within-surgeon variability was calculated while adjusting for fixed factors.Results and limitations
On null hierarchical models, there was significant between-surgeon variability in operative time, estimated blood loss (EBL), ischemia time, excisional volume loss, length of stay, positive margins, Clavien complications, and 30-d readmission rate (all p < 0.001), but not chronic kidney disease upstaging (p = 0.47) or percentage preservation of glomerular filtration rate (p = 0.49). Patient factors explained 82% of the variability in excisional volume loss and 0–32% of the variability in the remainder of outcomes. Quantifiable surgeon factors explained modest amounts (10–40%) of variability in intraoperative outcomes, and noteworthy amounts of variability (90–100%) in margin rates and patient morbidity outcomes. Immeasurable surgeon factors explained the residual variability in operative time (27%), EBL (6%), and ischemia time (31%).Conclusions
There is significant between-surgeon variability in outcomes after PN, even after adjusting for patient characteristics. While renal functional outcomes are consistent across surgeons, measured and unmeasured surgeon factors account for 18–100% of variability of the remaining peri- and postoperative variables. With the increasing utilization of value-based medicine, this has important implications for the goal of optimizing patient care.Patient summary
We reviewed our institutional database on partial nephrectomy performed for renal cancer. We found significant variability between surgeons for key outcomes after the intervention, even after adjusting for patient characteristics. 相似文献18.
Background
The response to first-line, platinum-based treatment of muscle-invasive bladder cancer has not improved in 3 decades.Objective
To identify genes that influence cisplatin resistance in bladder cancer.Design, setting, and participants
We performed a whole-genome CRISPR screen in a bladder cancer cell line to identify genes that mediate resistance to cisplatin.Outcome measurements and statistical analysis
Targeted validation was performed in two bladder cancer cell lines. The top gene candidate was validated in a publicly available bladder cancer dataset.Results and limitations
From the CRISPR screen, we identified MSH2 as the most significantly enriched gene and mismatch repair as the most significantly enriched pathway that promoted resistance to cisplatin. Bladder cancer cells with knockdown of MSH2 showed a reduction in cisplatin-mediated apoptosis. MSH2 loss did not impact the sensitivity to other chemotherapies, including the cisplatin analog oxaliplatin. Bladder tumors with low MSH2 protein levels, quantified using reverse-phase protein array, showed poorer survival when treated with cisplatin- or carboplatin-based therapy; these results require future validation using immunohistochemistry. Additionally, results are retrospective from patients with primarily high-grade tumors; thus, validation in a controlled clinical trial is needed.Conclusions
We generated in vitro evidence that bladder cancer cell lines depleted of MSH2 are more resistant to cisplatin. We additionally found an association between low MSH2 in bladder tumors and poorer patient survival when treated with platinum-based chemotherapy. If successfully validated prospectively, MSH2 protein level could assist in the selection of patients for chemotherapy.Patient summary
We report the first evidence that MSH2 protein level may contribute to chemotherapy resistance observed in muscle-invasive bladder cancer. MSH2 has potential as a biomarker predictive of response to platinum-based therapy. 相似文献19.
Cheng-He Qin Hong-An Zhang Yu-Han Chee Astuti Pitarini Abdulnassir Adem Ali 《Injury》2019,50(2):508-514