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BACKGROUND: Using a health systems approach to investigate low-value care (LVC) may provide insights into structural drivers of this pervasive problem. OBJECTIVE: To evaluate the influence of service area practice patterns on low-value mammography and prostate-specific antigen (PSA) testing. DESIGN: Retrospective study analyzing LVC rates between 2008 and 2018, leveraging physician relocation in 3-year intervals of matched physician and patient groups. SETTING: U.S. Medicare claims data. PARTICIPANTS: 8254 physicians and 56 467 patients aged 75 years or older. MEASUREMENTS: LVC rates for physicians staying in their original service area and those relocating to new areas. RESULTS: Physicians relocating from higher-LVC areas to low-LVC areas were more likely to provide lower rates of LVC. For mammography, physicians staying in high-LVC areas (LVC rate, 10.1% [95% CI, 8.8% to 12.2%]) or medium-LVC areas (LVC rate, 10.3% [CI, 9.0% to 12.4%]) provided LVC at a higher rate than physicians relocating from those areas to low-LVC areas (LVC rates, 6.0% [CI, 4.4% to 7.5%] [difference, -4.1 percentage points {CI, -6.7 to -2.3 percentage points}] and 5.9% [CI, 4.6% to 7.8%] [difference, -4.4 percentage points {CI, -6.7 to -2.4 percentage points}], respectively). For PSA testing, physicians staying in high- or moderate-LVC service areas provided LVC at a rate of 17.5% (CI, 14.9% to 20.7%) or 10.6% (CI, 9.6% to 13.2%), respectively, compared with those relocating from those areas to low-LVC areas (LVC rates, 9.9% [CI, 7.5% to 13.2%] [difference, -7.6 percentage points {CI, -10.9 to -3.8 percentage points}] and 6.2% [CI, 3.5% to 9.8%] [difference, -4.4 percentage points {CI, -7.6 to -2.2 percentage points}], respectively). Physicians relocating from lower- to higher-LVC service areas were not more likely to provide LVC at a higher rate. LIMITATION: Use of retrospective observational data, possible unmeasured confounding, and potential for relocating physicians to practice differently from those who stay. CONCLUSION: Physicians relocating to service areas with lower rates of LVC provided less LVC than physicians who stayed in areas with higher rates of LVC. Systemic structures may contribute to LVC. Understanding which factors are contributing may present opportunities for policy and interventions to broadly improve care. PRIMARY FUNDING SOURCE: National Cancer Institute of the National Institutes of Health.
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Neoplasias de la Mama , Detección Precoz del Cáncer , Mamografía , Medicare , Pautas de la Práctica en Medicina , Antígeno Prostático Específico , Neoplasias de la Próstata , Humanos , Masculino , Estudios Retrospectivos , Femenino , Anciano , Estados Unidos , Antígeno Prostático Específico/sangre , Mamografía/estadística & datos numéricos , Detección Precoz del Cáncer/estadística & datos numéricos , Neoplasias de la Mama/diagnóstico , Neoplasias de la Próstata/diagnóstico , Pautas de la Práctica en Medicina/estadística & datos numéricos , Médicos de Atención Primaria/estadística & datos numéricos , Anciano de 80 o más AñosRESUMEN
PURPOSE: This study aimed to investigate the prevalence of pathogenic germline variants (PGVs) in hereditary cancer genes utilizing a universal testing approach and to determine the rate of PGVs that would have been missed based on National Comprehensive Cancer Network (NCCN) guidelines in genitourinary (GU) malignancies. MATERIALS AND METHODS: A multisite, single-institution prospective germline genetic test (GGT) was universally offered to patients with new or active diagnoses of GU malignancies (prostate, bladder, and renal) from April 2018 to March 2020 at Mayo Clinic sites. Participants were offered GGT using a next-generation sequencing panel of > 80 genes. Demographic, tumor characteristics, and genetic results were evaluated. NCCN GU cancer guidelines were used to identify whether patients had incremental findings, defined as PGV-positive patients who would not have received testing based on NCCN guidelines. RESULTS: Of 3095 individuals enrolled in the study, 601 patients had GU cancer (prostate = 358, bladder = 106, and renal = 137). The mean enrollment age was 67 years (SD 9.1), 89% were male, and 86% of patients were non-Hispanic White. PGVs were identified in 82 (14%) of all GU patients. PGV prevalence breakdown by cancer type was: 14% prostate, 14% bladder, and 13% renal cancer. Nearly one-third of identified PGVs were high penetrance, and the majority of these (67%) were clinically actionable. Incremental PGVs were identified in 28 (57%) prostate, 15 (100%) bladder, and 14 (78%) renal cancer patients. Of the 82 patients with PGV findings, 29 (35%) had at least 1 relative undergo cascade testing for the familial variant(s) identified. CONCLUSIONS: More than 1 in 8 patients with GU malignancies were found to carry a PGV, with 67% of patients with high-penetrance PGVs undergoing clinically actionable changes. The majority of these PGVs would not have been identified based on current testing criteria. These findings support universal GGT for GU malignancies and underscore its potential to enhance risk assessment and guide precision interventions in urologic oncology.
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INTRODUCTION: Bacillus Calmette-Guerin (BCG) is the most effective therapy available to treat high-risk nonmuscle invasive bladder cancer (NMIBC) patients. However, for patients with immunomodulating conditions BCG is a relative contraindication due to efficacy and safety concerns. To our knowledge, no population-level study evaluating the efficacy and safety profile of BCG for immunomodulated patients exists. METHODS: NMIBC patients aged 66 years or older were identified in the Surveillance, Epidemiology, and End Results (SEER) - Medicare database from 1975-2013. All patients completed adequate BCG (at least 5 plus 2 treatments completed within 12 months of diagnosis). Two groups were defined: an immunomodulated population identified by immunomodulating conditions such as solid-organ transplantation, HIV, and autoimmune conditions, and an immunocompetent group. The primary endpoint was 5-year progression-free survival defined as progression to systemic chemotherapy, checkpoint inhibitors, radical or partial cystectomy, metastasis, or cancer-specific death. A safety analysis was performed as a secondary outcome. RESULTS: In a total of 4,277 patients with NMIBC who completed adequate BCG, 606 (14.2%) were immunomodulated. The immunomodulated group was older at diagnosis (P < 0.001), more likely to be female (P < 0.001), more likely to live in a metropolitan area (P < 0.001), and had higher Charlson comorbidity scores (P < 0.001). There were no differences in progression to chemotherapy (Pâ¯=â¯0.17), checkpoint inhibitors (P > 0.99), radical cystectomy (Pâ¯=â¯0.40), partial cystectomy (Pâ¯=â¯0.93), metastasis (Pâ¯=â¯0.19), cancer-specific death (Pâ¯=â¯0.18) or 5-year total bladder cancer progression (Pâ¯=â¯0.30) between the groups. For the safety analysis, rates of disseminated BCG were similar between immunomodulated and immunocompetent patients (0.7% vs. <1.8%, Pâ¯=â¯0.51). On multivariable analysis 5-year total bladder cancer progression (HR 1.07 [CI 0.88-1.30]) was similar between the groups. CONCLUSION: Rates of bladder cancer progression and disseminated BCG complications 5-years after BCG therapy were similar regardless of immunomodulation status. These findings suggest that BCG intravesical therapy can be offered to immunomodulated patients with high-risk NMIBC although theoretical infectious complication risks remain.
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Neoplasias Vesicales sin Invasión Muscular , Neoplasias de la Vejiga Urinaria , Estados Unidos , Humanos , Anciano , Femenino , Masculino , Vacuna BCG/uso terapéutico , Adyuvantes Inmunológicos/uso terapéutico , Medicare , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Recurrencia Local de Neoplasia/patología , Invasividad Neoplásica/patología , Administración IntravesicalRESUMEN
BACKGROUND: Postoperative stress urinary incontinence (SUI) after Holmium Laser Enucleation of the Prostate (HoLEP) has improved with the early apical release (EAR) technique. However, some patients develop SUI despite using EAR HoLEP. The aim of this study is to investigate whether a novel classification of the external sphincter is correlated with postoperative SUI. METHODS: The data of 98 patients who underwent EAR HoLEP for benign prostatic hyperplasia were prospectively analyzed. We propose a novel endoscopic classification of external sphincter appearance after HoLEP graded from 0 (best preserved) to 3 (most degraded). Patients were followed for 6 months postoperatively and administered validated questionnaires. A logistic regression was performed to compare moderate SUI rates at sphincter grade 3, controlling for age, obesity, catheter dependency and grams resected at 6 weeks and 3 months. RESULTS: The sphincter grades included 6 grade 0, 47 grade 1, 30 grade 2, and 15 grade 3. Patients were divided into a group without SUI (n= 51), and a group with SUI (n=47) at 6 weeks postoperatively by International Consultation on Incontinence Questionnaire (ICIQ). Patients with reported SUI on ICIQ were more likely to have sphincter grades > 2 at 6 weeks (p= 0.001) and 3 months (p< 0.0001). At 6 months, persistent SUI was associated with sphincter grade 3 (p< 0.0001). Logistic regression demonstrated that sphincter grade 3 was associated with clinically significant SUI at 3 months (p <0.01) Conclusions: Lower sphincter grades are associated with improved return of continence after EAR HoLEP.
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OBJECTIVE: To investigate the difference in postoperative incontinence and quality of life comparing standard vs early apical release (EAR) Holmium Laser Enucleation of the Prostate (HoLEP). METHODS: A retrospective review was performed to identify patients who underwent HoLEP from December 2021 to December 2022 at a single tertiary referral center with two participating consultant urologists. Patients were assessed with questionnaires and evaluated clinically. We performed propensity score matching with a logistic regression and a 1:1 matching method. A propensity score-adjusted logistic regression (PSRM) was performed to compare the pads per day between surgical techniques controlling for age, prostate size, preoperative survey data, uroflow, and postvoid residual. RESULTS: One hundred fourteen patients underwent HoLEP, of which 60 patients were treated with EAR and 54 patients with standard technique. EAR technique demonstrated shorter operative times (P = .046). The EAR cohort demonstrated improved AUASS (P = .034, P = .001), QOL (P = .001, P <.001), and continence rates (P <.001, P <.001) at 6 and 12weeks postoperatively. PSRM showed that the standard HoLEP increased the risk of requiring ≥2 pads per day 4.2x (P = .031, HR 95%, CI=1.16, 15.35) and 8.3x (P <.001, HR 95% CI 3.17, 21.6) at 6 and 12weeks postoperatively. CONCLUSION: EAR technique promoted earlier return of continence and improved quality of life within 6weeks of surgery.
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Láseres de Estado Sólido , Complicaciones Posoperatorias , Prostatectomía , Hiperplasia Prostática , Calidad de Vida , Incontinencia Urinaria , Humanos , Masculino , Láseres de Estado Sólido/uso terapéutico , Estudios Retrospectivos , Anciano , Hiperplasia Prostática/cirugía , Hiperplasia Prostática/complicaciones , Prostatectomía/métodos , Prostatectomía/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Persona de Mediana Edad , Incontinencia Urinaria/cirugía , Incontinencia Urinaria/etiología , Incontinencia Urinaria/prevención & control , Terapia por Láser/métodosRESUMEN
OBJECTIVE: To evaluate outcomes of robotic-assisted transplant ureteral repair (RATUR) for the management of kidney transplant ureteral strictures (TUS). METHODS: We retrospectively analyzed 41 consecutive patients who underwent RATUR for TUS at multiple tertiary referral centers between January 2016 and December 2022. RATUR was performed utilizing a robotic-assisted transperitoneal approach. The primary outcome was stricture recurrence rate and secondary outcomes included postoperative complicate rate, determining factors impacting with allograft functional recovery, and rate of conversion to open surgery. Categorical and continuous variables are displayed as total number (Percentage) or median [Interquartile Range], respectively. Pearson correlation coefficient was utilized to assess categorical variable correlation with creatinine. RESULTS: The median age was 56years [44,66]. The female-to-male ratio was 1.1:1. Approximately 66% of patients were dialysis-dependent prior to kidney transplantation. TUS was identified at a median time of 4months [2, 15.5] following kidney transplant. Median stricture length was 2 cm [1.22, 2.9 cm]. There were no TUS recurrences with a median follow-up of 36months [24,48]. There were 3 Clavien grade 2 and 1 Clavien grade 3 complications (9.5%). No baseline characteristics or preoperative diagnostics were correlated with a long-term decline in renal allograft function. CONCLUSION: RATUR has excellent and durable outcomes with low complication rates. These findings encourage the use of a minimally invasive definitive repair as a first-line treatment option for the management of TUS.
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OBJECTIVE: To characterize the impact of nephrolithiasis diagnosis and treatment on health care utilization and identify predictors of barriers to care in the patient population. METHODS: We conducted a retrospective cohort study using the All of Us Database, a National Institutes of Health database targeting recruitment of underrepresented populations. Patients with a diagnosis of kidney stones were included and matched to a control group. Primary outcomes were patients' self-reported health care access and utilization. Univariable and multivariable regression analyses were performed. RESULTS: 9173 patients with a diagnosis of nephrolithiasis were included and matched to 9173 controls without a diagnosis of nephrolithiasis. Patients with kidney stones were less likely to have had >1 year since last provider visit (1.7% vs 3.8%, P <.001), but did not report increased delays obtaining care (31%), inability to afford care (11.4%), or higher likelihood of skipping medications (12.9%). Among patients with stones, 1208 (13.2%) had been treated surgically. On multivariable analysis, younger age, female sex, lower income, lower education, non-insured status, and lower physical and mental health were all associated with delays obtaining care, difficulty affording care, skipping medications, and/or prolonged time since seeing a provider. CONCLUSION: A diagnosis of nephrolithiasis and subsequent surgical intervention were not associated with an increase in patient-reported barriers to care. However, among patients with nephrolithiasis, younger, comorbid, female patients from lower socioeconomic status are at significant risk of being unable to access and utilize treatment.
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Accesibilidad a los Servicios de Salud , Nefrolitiasis , Aceptación de la Atención de Salud , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Nefrolitiasis/terapia , Nefrolitiasis/epidemiología , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Aceptación de la Atención de Salud/estadística & datos numéricos , Adulto , Estados Unidos , Anciano , Estudios de CohortesRESUMEN
INTRODUCTION: No professional society guidelines recommend PSA screening in men younger than age 40; however, data suggest testing occurs at meaningful rates in this age group. The purpose of this study was to identify the rate of PSA testing in men under 40. METHODS: This is a population-based, retrospective cohort study from 2008 to 2017. Using the MarketScan database, rates of testing for the sum of the annual population of men at risk were evaluated. Descriptive statistics and statistical analyses were performed in men continuously enrolled in the database for at least 5 year. Results were stratified by receipt of PSA testing and by age group. The association of diagnoses and Charlson Comorbidity Index with receipt of PSA test was evaluated using multivariable logistic regression models. RESULTS: We identified 3,230,748 men ages 18 to 39 who were enrolled for at least 5 years. The rate of ever receiving PSA testing was 0.6%, 1.7%, 8.5%, and 9.1% in men less than 25, 25 to 29, 30 to 34, and 35 to 39 years, respectively. Multivariable logistic regression showed that relative to all men 18 to 39, patients who received PSA testing had higher odds of a diagnosis of hypogonadism (OR 11.77) or lower urinary tract symptoms (OR 4.19). CONCLUSIONS: This study found a remarkable number of young men receive PSA testing, with a strong association with diagnoses of lower urinary tract symptoms and hypogonadism. Clinicians need to be educated that assessment and management guidelines for other urologic diagnoses now defer PSA testing to prostate cancer screening guidelines.
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Hipogonadismo , Seguro , Síntomas del Sistema Urinario Inferior , Neoplasias de la Próstata , Masculino , Humanos , Adulto , Neoplasias de la Próstata/diagnóstico , Antígeno Prostático Específico , Estudios Retrospectivos , Detección Precoz del Cáncer/métodos , Tamizaje Masivo/métodosRESUMEN
Artificial intelligence (AI) is the integration of human tasks into machine processes. The role of AI in kidney cancer evaluation, management, and outcome predictions are constantly evolving. We performed a narrative review utilizing PubMed electronic database to query AI as a method of analysis in kidney cancer research. Key search-words included: Artificial Intelligence, Supervised/Unsupervised Machine Learning, Deep Learning, Natural Language Processing, Neural Networks, radiomics, pathomics, and kidney or renal neoplasms or cancer. 72 clinically relevant and impactful studies related to imaging, histopathology, and outcomes were recognized. We anticipate the incorporation of AI tools into future clinical decision-making for kidney cancer.
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INTRODUCTION: Patients living in rural areas have worse cancer-specific outcomes. This study examines the effect of family-based social capital on genitourinary cancer survival. We hypothesized that rural patients with urban relatives have improved survival relative to rural patients without urban family. METHODS: We examined rural and urban based Utah individuals diagnosed with genitourinary cancers between 1968 and 2018. Familial networks were determined using the Utah Population Database. Patients and relatives were classified as rural or urban based on 2010 rural-urban commuting area codes. Overall survival was analyzed using Cox proportional hazards models. RESULTS: We identified 24,746 patients with genitourinary cancer with a median follow-up of 8.72 years. Rural cancer patients without an urban relative had the worst outcomes with cancer-specific survival hazard ratios (HRs) at 5 and 10 years of 1.33 (95% CI 1.10-1.62) and 1.46 (95% CI 1.24-1.73), respectively relative to urban patients. Rural patients with urban first-degree relatives had improved survival with 5- and 10-year survival HRs of 1.21 (95% CI 1.06-1.40) and 1.16 (95% CI 1.03-1.31), respectively. CONCLUSIONS: Our findings suggest rural patients who have been diagnosed with a genitourinary cancer have improved survival when having relatives in urban centers relative to rural patients without urban relatives. Further research is needed to better understand the mechanisms through which having an urban family member contributes to improved cancer outcomes for rural patients. Better characterization of this affect may help inform policies to reduce urban-rural cancer disparities.
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Neoplasias , Neoplasias Urogenitales , Humanos , Población Urbana , Neoplasias/epidemiología , Modelos de Riesgos Proporcionales , Utah/epidemiología , Población RuralRESUMEN
INTRODUCTION: Obesity in prostate cancer survivors may increase mortality. Better characterization of this effect may allow better counseling on obesity as a targetable lifestyle factor to reduce mortality in prostate cancer survivors. The purpose of this study was to determine whether pre- and post-diagnostic obesity and weight change affect all-cause mortality, cardiovascular disease specific mortality, and prostate cancer specific mortality in patients with nonmetastatic prostate cancer. PATIENTS AND METHODS: We performed a retrospective cohort analysis of 5,077 patients diagnosed with localized prostate cancer from 1997 to 2017 with median follow-up of 15.5 years. The Utah Population Database linked to the Utah Cancer Registry was used to identify patients at a variety of treatment centers. RESULTS: Pre-diagnosis obesity was associated with a 62% increased risk of cardiovascular disease specific mortality and a 34% increased risk of all-cause mortality (HR 1.62, 95% CI 1.05-2.50; HR 1.34, 95% CI 1.07-1.67, respectively). Post-diagnosis obesity increased the risk of cardiovascular disease specific mortality (HR 1.83, 95% CI 1.31-2.56) and all-cause mortality (HR 1.37, 95% CI 1.16-1.64) relative to non-obese men. We found no association between pre-diagnostic obesity or post-diagnostic weight gain and prostate cancer specific mortality. CONCLUSION: Our study strengthens the conclusion that pre-, post-diagnostic obesity and weight gain increase cardiovascular disease and all-cause mortality but not prostate cancer specific mortality compared to healthy weight men. An increased emphasis on weight management may improve mortality for prostate cancer survivors who are obese.
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Supervivientes de Cáncer , Enfermedades Cardiovasculares , Obesidad , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/diagnóstico , Obesidad/complicaciones , Obesidad/epidemiología , Obesidad/mortalidad , Supervivientes de Cáncer/estadística & datos numéricos , Anciano , Estudios Retrospectivos , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Persona de Mediana Edad , Utah/epidemiología , Pérdida de Peso , Factores de Riesgo , Estudios de Seguimiento , Factores de Riesgo de Enfermedad Cardiaca , Aumento de PesoRESUMEN
OBJECTIVE: To evaluate the interest of primary care clinicians in utilizing CDS for PSA screening. Evidence suggests that electronic clinical decision support (CDS) may decrease low-value prostate-specific antigen (PSA) testing. However, physician attitudes towards CDS for PSA screening are largely unknown. METHODS: A survey was sent to 201 primary care clinicians, including both physicians and Advanced Practice Providers (APP), within a large academic health system. Eligible clinicians cared for male patients aged 40 to 80 years and ordered ≥5 PSA tests in the past year. Respondents were stratified into 3 groups, appropriate screeners, low-value screeners, or rare-screeners, based on responses to survey questions assessing PSA screening practices. The degree of interest in electronic CDS was determined via a composite Likert score comprising relevant survey items. RESULTS: Survey response rate was 29% (59/201) consisting of 85% MD/DO and 15% APP respondents. All clinicians surveyed were interested in CDS (P < 0.001) without significant difference between screener groups. Clinicians agreed most uniformly that CDS be evidence-based. Clinicians disagreed on whether CDS would decrease professional discretion over patient decisions. CONCLUSIONS: Primary care clinicians are interested in CDS for PSA screening regardless of their current screening practices. Prioritizing CDS features that clinicians value, such as ensuring CDS recommendations are evidence-based, may increase the likelihood of successful implementation, whereas perceived threat to autonomy may be a hinderance to utilization.
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Sistemas de Apoyo a Decisiones Clínicas , Médicos , Neoplasias de la Próstata , Humanos , Masculino , Antígeno Prostático Específico , Neoplasias de la Próstata/diagnóstico , Detección Precoz del Cáncer , Tamizaje MasivoRESUMEN
INTRODUCTION: Encouraging the appropriate use of staging imaging in patients with newly diagnosed prostate cancer remains a challenge. Assessing the effects of national efforts may help guide future initiatives in curtailing low-value care. The purpose of this study was to determine the impact of the Choosing Wisely campaign on imaging utilization among men with prostate cancer. METHODS: Surveillance, Epidemiology, and End Results - Medicare data were used to complete a longitudinal population-based study of men diagnosed with prostate cancer from 2007 to 2015. An interrupted time series analysis evaluated the impact of the Choosing Wisely campaign on trends of imaging utilization. RESULTS: From 2007 to 2015 imaging utilization in low-risk patients decreased, with computed tomography (CT) usage declining from 45.0% to 34.4% (P<0.001) and nuclear medicine bone scan (NMBS) from 27.8% to 11.7% (P<0.001). Choosing Wisely likely contributed to an absolute reduction of 2.9% (P=0.03) in utilization of NMBS in the low-risk population. Imaging usage for all modalities increased in the high-risk population, but with 32.8% continuing to not receive guideline-supported imaging. CONCLUSIONS: In 2012, the Choosing Wisely campaign sought to decrease inappropriate staging imaging for men with low-risk prostate cancer and encourage stewardship of medical resources. Overall decreases in staging imaging trends suggest a move towards higher value care. However, this study found that the Choosing Wisely recommendations had a modest impact on utilization of NMBS, but not CT or PET scans. These results may help inform future efforts to promote guideline concordant imaging.
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Medicare , Neoplasias de la Próstata , Masculino , Humanos , Anciano , Estados Unidos , Neoplasias de la Próstata/diagnóstico por imagen , Tomografía de Emisión de Positrones , Cintigrafía , Factores de RiesgoRESUMEN
A 29-year-old patient presented to his primary care provider complaining of a painful right inguinal swelling. He was referred for inguinal hernia repair, but during surgery, an enlarged necrotic-appearing testicle was observed and removed. Pathology demonstrated a mixed non-seminomatous germ cell tumor (NSGCT) with evidence of tumor violation. After receiving BEPx3 for elevated post-operative AFP his tumor markers normalized. On surveillance, he was found to have several palpable masses around his inguinal incision. On soft tissue excision he was found to have residual teratoma within his soft tissues. We review the literature on germ cell tumor seeding and atypical recurrences.
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INTRODUCTION: Extended prophylactic anticoagulation therapy with enoxaparin 40 mg daily is effective in reducing the incidence of venous thromboembolism (VTE) after radical cystectomy. In an effort to improve compliance, we modified our extended anticoagulation options to direct oral anticoagulants (DOAs; eg apixaban 2.5 mg twice daily or rivaroxaban 10 mg daily). This study assesses our experience with extended VTE prophylaxis using DOAs. METHODS: This is a retrospective review that included all patients who underwent radical cystectomy at our institution between January 2007 and June 2021. Multivariable logistic regression models were constructed to test the hypothesis that use of extended DOAs is similar to enoxaparin in terms of VTE events and risk of gastrointestinal bleeding. RESULTS: In 657 patients, the median age was 71 years. Of the 101 patients who received extended VTE prophylaxis, 46 (45.5%) patients received rivaroxaban/apixaban. At 90 days of followup, 40 patients (7.2%) who did not receive extended prophylaxis on discharge developed a VTE compared to 2 patients (3.6%) in the enoxaparin group and 0 patients in the DOA group (p=0.11). Seven patients (1.3%) who did not receive extended anticoagulation developed gastrointestinal bleeding compared to 0 patients in the enoxaparin group and 1 (2.2%) in the DOA group (p=0.60). On multivariable analysis, both enoxaparin and DOAs were associated with similar reductions in the risk of developing VTE compared to controls (enoxaparin: OR 0.33, p=0.09 and DOAs: OR 0.19, p=0.15). CONCLUSIONS: These preliminary data suggest that oral apixaban and rivaroxaban are acceptable alternatives to enoxaparin with similar safety and efficacy profiles.
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The intense inflammatory response triggered in the brain after focal cerebral ischemia is detrimental. Recently, we showed that the suppression of toll-like receptors (TLRs) 2 and 4 attenuates infarct size and reduces the expression of pro-inflammatory cytokines in the ischemic brain. In this study, we further examined the effect of unsuppressed induction of TLRs 2 and 4 on the expression of its downstream signaling molecules and pro-inflammatory cytokines 1 week after reperfusion. The primary purpose of this study was to investigate the effect of simultaneous knockdown of TLRs 2 and 4 on M1/M2 microglial polarization dynamics and post-stroke neurological deficits and the recovery. Transient focal cerebral ischemia was induced in young adult male Sprague-Dawley rats by the middle cerebral artery occlusion (MCAO) procedure using a monofilament suture. Appropriate cohorts of rats were treated with a nanoparticle formulation of TLR2shRNA and TLR4shRNA (T2sh+T4sh) expressing plasmids (1 mg/kg each of T2sh and T4sh) or scrambled sequence inserted vector (vehicle control) expressing plasmids (2 mg/kg) intravenously via tail vein immediately after reperfusion. Animals from various cohorts were euthanized during reperfusion, and the ischemic brain tissue was isolated and utilized for PCR followed by agarose gel electrophoresis, real-time PCR, immunoblot, and immunofluorescence analysis. Appropriate groups were subjected to a battery of standard neurological tests at regular intervals until 14 days after reperfusion. The increased expression of both TLRs 2 and 4 and their downstream signaling molecules including the pro-inflammatory cytokines was observed even at 1-week after reperfusion. T2sh+T4sh treatment immediately after reperfusion attenuated the post-ischemic inflammation, preserved the motor function, and promoted recovery of the sensory and motor functions. We conclude that the post-ischemic induction of TLRs 2 and 4 persists for at least 7 days after reperfusion, contributes to the severity of acute inflammation, and impedes neurological recovery. Unlike previous studies in TLRs 2 or 4 knockout models, results of this study in a pharmacologically relevant preclinical rodent stroke model have translational significance.