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1.
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2.
Wanda Bekker Matthew C. Hernandez Martin D. Zielinski Victor Y. Kong Grant L. Laing John L. Bruce Vassil Manchev Michelle T.D. Smith Damian L. Clarke 《Injury》2019,50(1):27-32
Background
The mesentery may be injured in trauma and few grading systems describe mesenteric injury severity. We aimed to develop and validate an intra-operative mesenteric injury grading system.Methods
A modified Delphi technique was used to generate an intraoperative grading system for blunt mesenteric injury called the mesenteric injury score (MIS). We performed a retrospective review (2010–2016) of patients >15 years old with blunt abdominal trauma. Patient demographics, injury severity score (ISS) and mechanism, clinical, operative, and outcome data were abstracted. The intraoperative grading system was used to describe patient outcomes including duration of stay and management approach. We compared the correlation of abdominal abbreviated injury score, Blunt Injury Prediction Score (BIPS) and the MIS with clinical outcomes using Spearman’s rho.Results
There were fifty-one patients of which 86% were male. Injury mechanisms included motor vehicle accidents (n?=?37, 73%), pedestrian vehicle accidents (n?=?7, 13%), assaults (n?=?4, 8%), falls (n?=?2, 4%), and a single airplane crash (2%). Median [IQR] ISS was 16 [10–25] and GCS at hospital admission was 15 [15–15]. The median [IQR] international normalized ratio was 1.2 [1.1–1.5], lactate was 2.7 [1.7–4.9], and hemoglobin was 11.4 [8.6–12.2]. The distributions of MIS included Grade I (3, 5%), Grade II (10, 20%), Grade III (10, 20%), Grade IV, 5 (10%), and Grade V (23, 45%). Increasing mesenteric injury grade was associated with longer duration of stay, need for bowel resection, and damage control laparotomy.Conclusions
We developed an intra-operative mesenteric injury grading system (MIS) and provided an initial retrospective validation using a series of patients with blunt abdominal trauma. The proposed MIS corresponded with both the AIS and the BIPS. Future study comparing cross sectional imaging and operative findings based on MIS criteria is needed. 相似文献3.
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4.
Introduction
Large animal-related human injuries are associated with high morbidity and mortality. There are no studies on biomechanics of the camel-related head, face, and neck (HFN) injuries. We aimed to study the mechanism, anatomical distribution and severity of camel-related HFN injuries.Methods
We analyzed our prospectively collected data of patients who were admitted to Al Ain Hospital with camel-related HFN injury during the period of October 2001 to January 2010.Results
Seventy-three patients were studied; all were males having a median (range) age of 28 (5–89) years. Camel kick was the most common mechanism of injury (45%) followed by falling from a camel (22%). Facial fractures were significantly more common in patients who were kicked by a camel. Severe head injuries were significantly more in patients who fell from a camel or who had a car collision with a camel. Car collision with a camel was significantly associated with lower cervical spine fractures (p?=?0.017) and severe cervical spine injuries (p?=?0.004). Two patients died (overall mortality 3%)Conclusions
Our study provides an insight into the complex biomechanics and severity of camel-related HFN injuries. It is essential to adopt protective measures in our community so as to reduce camel-related HFN injuries. 相似文献5.
José Antonio Pereira Miguel Pera Manuel López-Cano Marta Pascual Sandra Alonso Silvia Salvans Marta Jiménez-Toscano Alba González-Martín Luis Grande-Posa 《Cirugía espa?ola》2019,97(1):20-26
Objectives
To determine the incidence of incisional hernia (IH) in the extraction incision (EI) in colorectal resection for cancer. To analyze whether the location of the incision has any relationship with the incidence of hernias and whether mesh could be useful for prevention in high-risk patients.Methods
Retrospective review of the colon and rectal surgery database from January 2015 to December 2016. Data were classified into 2 groups, transverse (TI) and midline incision (MI), and the latter was divided into 2 subgroups (mesh [MIM] and suture [MIS]). Patients were classified using the HERNIAscore. Hernias were diagnosed by clinical and/or CT examination.Results
A total of 182 out of 210 surgical patients were included. After a median follow-up of 13.0 months, 39 IH (21.9%) were detected, 23 of which (13.4%) were in the EI; their frequency was lower in the TI group (3.4%) and in the MIM group (5.9%) than in the MIS group (29.5%; p = 0.007). The probability of developing IH in the MIS group showed an OR = 11.7 (95%CI: 3.3-42.0) compared to the TI group and 4.3 (IC 95%: 1.1-16.3) versus the MIM group.Conclusions
The location of the incision is relevant to avoid incisional hernias. Transverse incisions should be used as the first option. When a midline incision is needed, a prophylactic mesh could be considered in high risk patients because it is safe and associated with low morbidity. 相似文献6.
Nicola Fossati R. Jeffrey Karnes Michele Colicchia Stephen A. Boorjian Alberto Bossi Thomas Seisen Nadia Di Muzio Cesare Cozzarini Barbara Noris Chiorda Claudio Fiorino Giorgio Gandaglia Paolo Dell’Oglio Shahrokh F. Shariat Gregor Goldner Steven Joniau Antonino Battaglia Karin Haustermans Gert De Meerleer Alberto Briganti 《European urology》2018,73(3):436-444
Background
Salvage radiation therapy (SRT) is a recommended treatment option for biochemical recurrence after radical prostatectomy (RP). However, its effectiveness may be limited to specific categories of patients.Objective
We aimed to identify the optimal candidates for early SRT after RP.Design, setting, and participants
The study included 925 node-negative patients treated with SRT after RP at seven institutions. Patients received SRT for either prostate-specific antigen (PSA) rising, or PSA persistence after RP that was defined as PSA level ≥0.1 ng/ml at 1 mo after surgery. All patients received local radiation to the prostate and seminal vesicle bed.Outcome measurements and statistical analysis
The primary outcome measured was distant metastasis after SRT. Regression tree analysis was used to develop a risk-stratification tool. Multivariable Cox regression analysis and nonparametric curve fitting methods were used to explore the relationship between PSA level at SRT and the probability of metastasis-free survival at 8 yr.Results and limitations
At a median follow-up of 8.0 yr, 130 patients developed distant metastasis. At multivariable analysis, pre-SRT PSA level was significantly associated with distant metastasis (hazard ratio: 1.06, p < 0.0001). However, when patients were stratified into five risk groups using regression tree analysis (area under the curve: 85%), early SRT administration provided better metastasis-free survival in three groups only: (1) low risk: undetectable PSA after RP, Gleason score ≤7, and tumour stage ≥pT3b, (2) intermediate risk: undetectable PSA after RP with Gleason score ≥8, (3) high risk: PSA persistence after RP with Gleason score ≤7.Conclusions
We developed an accurate risk stratification tool to facilitate the individualised recommendation for early SRT based on prostate cancer characteristics. Early SRT proved to be beneficial only in selected groups of patients who are more likely to be affected by clinically significant but not yet systemic recurrence at the time of salvage treatment administration.Patient summary
In patients affected by prostate cancer recurrence after radical prostatectomy, the early administration of salvage radiation therapy is beneficial only for selected subgroups of patients. In this study, these groups of patients were identified. 相似文献7.
F. Virdis I. Reccia S. Di Saverio G. Tugnoli S.H. Kwan J. Kumar J. Atzeni M. Podda 《Diagnostic and interventional imaging》2019,100(2):65-75
Purpose
This purpose of this systematic review was to determine the safety and efficacy of arterial embolization as the primary treatment for grade III-V liver trauma, excluding the postoperative use of arterial embolization.Material and methods
A total of 24 studies published between January 2000 and June 2018 qualified for inclusion in this study. Four of them were prospective studies and 20 were retrospective. A total of 3855 patients (mean age, 33.5 years; range: 22–52.5 years) were treated non-operatively and 659 patients (659/3855; 17.09%) with hepatic hemorrhage underwent primary arterial embolization from 2000 to 2017. Indication for arterial embolization was a contrast blush visible on computed tomography in hemodynamically stable patient in all studies.Results
The arterial embolization success rate ranged from 80% to 97%. The most commonly reported complication was bile leak, with an incidence of 5.7%. Nineteen bilomas (2.8%) were reported in five studies with a range between 4% and 45%. Hepatic ischemia was reported in eight studies, with a mean incidence of 8.6%.Conclusion
Primary arterial embolization has a high success rate in patients with hepatic trauma. Complications, including biloma and hepatic ischemia, have acceptable rates in the context of a minimally-invasive procedure that allows stabilization of life-threatening, complex liver injuries. 相似文献8.
K. Young A. Aquilina T.J.S. Chesser M.L. Costa S. Hettiaratchy M.B. Kelly C.G. Moran I. Pallister M. Woodford 《Injury》2019,50(2):497-502
Aims
To assess current national practice in the management of severe open tibial fractures against national standards, using data collected by the Trauma and Audit Research Network.Materials and methods
Demographic, injury-specific, and outcome data were obtained for all grade IIIB/C fractures admitted to Major Trauma Centres in England from October 2014 to January 2016.Results
Data was available for 646 patients with recorded grade IIIB/C fractures. The male to female ratio was 2.3:1, mean age 47 years. 77% received antibiotics within 3?h of admission, 82% were debrided within 24?h. Soft tissue coverage was achieved within 72?h of admission in 71%. The amputation rate was 8.7%. 4.3% of patients required further theatre visits for infection during the index admission. The timing of antibiotics and surgery could not be correlated with returns to theatre for early infection. There were significant differences in the management and outcomes of patients aged 65 and over, with an increase in mortality and amputation rates.Conclusions
Good outcomes are reported from the management of IIIB/C fractures in Major Trauma Centres in England. Overall compliance with national standards is particularly poor in the elderly. Compliance did not appear to affect rates of returning to theatre or early infection. Appropriately applied patient reported outcome measures are needed to enhance the evidence-base for management of these injuries. 相似文献9.
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10.
Aims
The anatomical safe zone for intra-medullary nail insertion through the tibial plateau is small, insertion outside of this area risks damage to intra-articular structures and poor fracture reduction. The purpose of this retrospective study was to determine if the new supra-patella (SP) approach confers improved nail insertion accuracy, when compared with the standard infra-patella (IP) technique.Patients and Methods
Two hundred cases were included in the study (SP 95, IP 105). Insertion accuracy was assessed on AP and lateral radiographic imaging, and measured as the distances between the central axis of the proximal nail and the ideal entry point.Results
The median distance from the ideal entry point was 4.4?mm (SP) and 5.1?mm (IP) (p?=?0.046) in the coronal plane, and 4.0?mm (SP) and 3.7?mm (IP) (p?=?0.527) in the sagittal plane. A narrower range in measurements was observed in the SP technique in both sagittal and coronal planes, 17.8?mm vs 28.6?mm, and 19.7?mm vs 30.3?mm respectively.Conclusion
We found that the SP technique achieved significantly improved nail insertion accuracy in the coronal plane. Insertion accuracy was equivocal between the two techniques in the sagittal plane. A narrower range in entry points was observed in the SP cohort in both planes suggesting improved control in nail insertion using this technique. 相似文献11.
Background
Many patients undergoing below knee amputations (BKA) return for subsequent unplanned operations, hospital readmission, or postoperative complications. This unplanned medical management negatively impacts both patient outcomes and our healthcare system. This study primarily investigates the risk factors for unplanned reoperation following BKA.Methods
Below knee amputations from the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database from the years 2012–2014 were identified by CPT code 27880 for amputation through the tibia and fibula. Our query identified 4631 BKA cases, including 30 day complications. Multivariate logistic regression modeling was performed on several patient demographic and disease factors to assess for independent predictors of unplanned reoperation. Secondary outcomes of unplanned and related readmissions (related to the procedure), major complications, minor complications, and mortality were also included in the analysis.Results
Of 4631 BKAs identified, 9.63% (446/4631) underwent unplanned reoperations and 8.75% (405/4631) had unplanned and related readmissions. Major complications were experienced by 12.8% (593/4631) and minor complications by 8.7% (401/4631). Thirty day mortality rate was 5.14% (238/4631). The most common procedures for unplanned operations were thigh amputations (128/446, 28.7%), debridement/secondary closure (114/446, 25.6%), and revision leg amputations (46/446, 10.32%). Factors associated with an increased risk of unplanned reoperation included patients transferred from another facility (Adjusted Odds Ratio [AOR]?=?1.28; p?=?.04), recent smokers (AOR?=?1.34; p?=?.02), bleeding disorder (AOR?=?1.30; p?=?.02), and preoperative ventilator use (AOR?=?2.38; p?=?.01).Conclusion
Patients that were ongoing/recent smokers, had diagnosed bleeding disorders, required preoperative ventilator use, or were transferred in from another facility were associated with the highest risks of reoperation following BKA. This patient population experiences high rates of reoperation, readmission, complication, and mortality. 相似文献12.
Joaquin Mateo Karim Fizazi Silke Gillessen Axel Heidenreich Raquel Perez-Lopez Wim J.G. Oyen Neal Shore Matthew Smith Christopher Sweeney Bertrand Tombal Scott A. Tomlins Johann S. de Bono 《European urology》2019,75(2):285-293
Context
Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) have rising prostate-specific antigen (PSA) and castrate testosterone levels, with no radiological findings of metastatic disease on computed tomography and bone scan. Given recent drug approvals for nmCRPC, with many other therapeutics and imaging modalities being developed, management of nmCRPC is a rapidly evolving field that merits detailed investigation.Objective
To review current nmCRPC management practices and identify opportunities for improving care of nmCRPC patients.Evidence acquisition
A literature search up to July 2018 was conducted, including clinical trials and clinical practice guidelines (National Comprehensive Cancer Network, European Society for Medical Oncology, European Association of Urology, Prostate Cancer Clinical Trials Working Group, Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence). Keywords included prostate cancer, nonmetastatic, castration resistance, rising PSA, and biochemical relapse.Evidence synthesis
Recommendations regarding indications for, and frequency of, imaging and PSA testing, as well as for initiating systemic therapy in nmCRPC are based on PSA rise kinetics and symptoms. Both enzalutamide and apalutamide have been shown to significantly increase metastasis-free survival in phase III placebo-controlled randomised trials in nmCRPC patients with PSA doubling time (DT) ≤10 mo. The expected impact of new imaging techniques in the assessment of nmCRPC is also reviewed.Conclusions
nmCRPC is a heterogeneous disease; while observation may be an option for some patients, enzalutamide and apalutamide may be appropriate to treat nmCRPC patients with PSA-DT ≤10 mo. The emergence of more accurate imaging modalities as well as circulating tumour biomarker assays will likely redefine the assessment of nmCRPC in the near future.Patient summary
Herein, we review key literature and clinical practice guidelines to summarise the optimal management of patients with prostate cancer and rising prostate-specific antigen despite castrate testosterone levels, but with no evidence of distant metastasis on traditional imaging. New drugs are being developed for this disease setting; novel imaging and tumour biomarker blood tests are likely to define this disease state more accurately. 相似文献13.
14.
Paolo Schiavi Francesco Pogliacomi Massimiliano Colombo Andrea Amarossi Francesco Ceccarelli Enrico Vaienti 《Injury》2019,50(2):420-423
Introduction
Femoral neck fractures are the most frequent fractures in the elderly and hemiarthroplasty is the treatment of choice. The objective of this multicenter study is to identify predictive factors of acetabular erosion after bipolar hemiarthroplasty (surgery between 1997 and 2007) in a mobile independent population during a follow-up of ten years.Materials and methods
Data were prospectively collected and retrospectively analyzed. Inclusion criteria were: age >60 and <85 years, BMI?<?35, normal Abbreviated MiniMental Test score, ability to walk 0.8?km and live independently, non-pathological fracture, hip with no or minimal osteoarthritic changes, and availability of clinical and radiological follow-up. For each Patient were recorded: demographic data, comorbidities, time from fracture to surgery, characteristics of the implant, duration of surgery. Patients included underwent clinical and radiological follow-up.Results
Overall, 209 Patients met inclusion criteria. A press-fit implant was performed in 172 subjects; in contrast a cemented prosthesis was implanted in 37 patients. Nineteen patients underwent implant revision to total hip arthroplasty for acetabular erosion and pain. Classification of X-ray using Baker criteria showed a grade 0 in 54.5%, a grade 1 in 19.6%, a grade 2 in 18.1% and a grade 3 in 7.6%. Multivariate analysis revealed that the size of the femoral head (FH) was the only predictive factor of a higher risk of acetabular erosion. The Kaplan-Meier survival curve verified the risk of implant revision in Group 1 (FH sized >48?mm) and Group 2 (FH sized <48?mm). The probability of implant revision for acetabular erosion at ten years from surgery were 5.5% in Group 1 and 15.6% in Group 2.Conclusion
In bipolar hemiarthroplasty smaller head size lead to a polar wear implying a higher risk of acetabular erosion and migration; in our population this risk was consistent with the use of implant head <48?mm diameter. Considering the absolute risk of a smaller FH size, the surgeon must evaluate the accuracy of measurement of the caliber, since the size can be significantly underestimated. 相似文献15.
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16.
Background
The purpose of this study was to compare the outcomes of trauma patients who were injured in a motor vehicle crash and tested positive for alcohol upon hospital arrival versus those who tested negative.Methods
Study data came from the US National Trauma Data Bank (2007–2010). Any blood alcohol concentration (BAC) found at or above the legal limit (≥0.08?g/dL) was considered “alcohol positive”, and if no alcohol was identified through testing, the patient was considered “alcohol negative”. Patients’ demographics including age >?=?14, race, gender, drug test results, systolic blood pressure, heart rate, injury severity score (ISS), and Glasgow Coma Scale (GCS) were included in the study. Propensity score and exact pair matching were performed between the groups using baseline characteristics.Results
From a total of 88,794 patients, 30.9% tested positive and 69.1% tested negative for alcohol. There were significant differences found between the groups regarding age, gender, race, and GCS (all p?<?0.001) as well as a significantly higher in-hospital mortality rate (3.5% vs. 2.7%, p?<?0.001) and median time to patient expiration (4 vs. 3 days, p?<?0.001) in the alcohol negative group. After running both matching scenarios, there was no evidence of a significant difference seen in the rates of in-hospital mortality or the median time to patient expiration between the alcohol groups in either matched comparison.Conclusion
Patients who tested positive for alcohol following a traumatic motor vehicle crash showed no significant increase in in-hospital mortality or time to expiration when compared to propensity score and exact matched patients who tested negative for alcohol. 相似文献17.
Jiantao Li Lin Han Hao Zhang Zhe Zhao Xiuyun Su Jianfeng Zhou Chen Li Peng Yin Ming Hao Kun Wang Gaoxiang Xu Lihai Zhang Licheng Zhang Peifu Tang 《Injury》2019,50(3):648-656
Objectives
Using finite element analysis and biomechanical tests, the biomechanical behaviors of Medial Sustainable Nail (MSN) and Proximal Femoral Nail Antirotation (PFNA) were compared for the fixation of fracture type of AO/OTA 31-A2.3.Methods
Finite element software Abaqus 6.14 was used to conduct axial loading of 2100?N and we analyzed the von Mises stress distribution and the model displacement of two implant models. Biomechanical tests were separately conducted in the axial stiffness test and axial cyclical loading test on a mechanical testing machine.Results
The results indicate that von Mises stress of MSN was lower than that of PFNA, and the model displacement in the MSN group was lower than that in the PFNA group. In the axial stiffness tests, MSN group was stiffer than PFNA construct. With respect to the axial load to ultimate failure, the PFNA construct exhibited higher loads exceeding 4000?N while the MSN construct withstood 3313.8?±?92.8?N. Specifically, F10mm was 2178.6?±?133.2?N of the MSN group and 1822.6?±?93.1?N of the PFNA group (P?=?0.001). Additionally, X2100N was 9.8?±?0.5?mm of the MSN group and 11.7?±?0.7?mm of the PFNA group (P?=?0.002). The MSN group exhibited superior performances in terms of the mean value of the vertical displacement, frontal rotation angle, and lateral rotation angle.Conclusions
The results indicated that the MSN construct might exhibit a better biomechanical performance when compared with that of the PFNA in reducing displacement and anti-varus in fracture type of AO/OTA 31-A2.3. 相似文献18.
D.E. Orakwe K.H. Tijani E.A. Jeje M.A. Ogunjimi R.W. Ojewola 《The African Journal of Urology》2017,23(2):105-108
Objectives
To compare serum testosterone and prostate specific antigen (PSA) levels of patients diagnosed of prostate cancer to those with benign prostatic hyperplasia (BPH).Subjects and methods
One hundred and thirteen male patients with or without LUTS who had indication(s) for prostate biopsies were recruited. Blood samples were analysed for serum testosterone and serum PSA. Prostate sizes were measured and PSA densities calculated before trans-rectal prostate biopsies were performed.Results
On histology of prostate biopsy specimens, 54 patients (47.8%) had prostate adenocarcinoma while 59 patients (52.2%) had BPH. Serum testosterone levels were lower in the prostate cancer group (23.09 ± 2.31 nmol/L versus 24.37 ± 1.94 nmol/L in the BPH group) but this difference was not statistically significant (p = 0.671). Serum testosterone also did not differ significantly with Gleason grade and Gleason score in patients with prostate cancer.Serum PSA and PSA density (PSAD) values were significantly higher in men with prostate cancer, and also in prostate cancer patients with high grade disease.Conclusion
Serum testosterone levels of patients with prostate cancer did not significantly differ from those of patients with BPH and were not related to grade in prostate cancer patients. 相似文献19.
Boris Gershman Daniel M. Moreira R. Houston Thompson Stephen A. Boorjian Christine M. Lohse Brian A. Costello John C. Cheville Bradley C. Leibovich 《European urology》2018,73(3):469-475
Background
There are little data regarding the morbidity of lymph node dissection (LND) for renal cell carcinoma (RCC) to assess its risk–benefit ratio.Objective
To evaluate the association of LND with 30-d complications among patients undergoing radical nephrectomy (RN) for RCC.Design, setting, and participants
A total of 2066 patients underwent RN for M0 or M1 RCC between 1990 and 2010, of whom 774 (37%) underwent LND.Intervention
RN with or without LND.Outcome measurements and statistical analysis
Associations of LND with 30-d complications were examined using logistic regression with several propensity score techniques. Extended LND, defined as removal of ≥13 lymph nodes, was examined in a sensitivity analysis.Results and limitations
A total of 184 (9%) patients were pN1 and 302 (15%) were M1. Thirty-day complications occurred in 194 (9%) patients, including Clavien grade ≥3 complications in 81 (4%) patients. Clinicopathologic features were well balanced after propensity score adjustment. In the overall cohort, LND was not statistically significantly associated with Clavien grade ≥3 complications, although there was an approximately 40% increased risk of any Clavien grade complication that did not reach statistical significance. Likewise, LND was not significantly associated with any Clavien grade or Clavien grade ≥3 complications when separately evaluated among M0 or M1 patients. Extended LND was not significantly associated with any Clavien grade or Clavien grade ≥3 complications. LND was not associated with length of stay or estimated blood loss. Limitations include a retrospective design.Conclusions
LND is not significantly associated with an increased risk of Clavien grade ≥3 complications, although it may be associated with a modestly increased risk of minor complications. In the absence of increased morbidity, LND may be justified in a predominantly staging role in the management of RCC.Patient summary
Lymph node dissection for renal cell carcinoma is not associated with increased rates of major complications. 相似文献20.
Lauren M. MacCormick Frank Chen Jeff Gilbertson Sikandar Khan Lisa K. Schroder Joan E. Bechtold Peter A. Cole 《Injury》2019,50(2):251-255