The prevalence of bilateral and ipsilateral radiographic osteoarthritis is high in White, Asian and Native Hawaiian/Pacific Islanders presenting for unilateral knee or hip arthroplasty.

BACKGROUND: It is estimated that one-third of patients presenting with unilateral joint pain have contralateral osteoarthritis (OA) at first presentation. Most studies have primarily examined White patient cohorts. The purpose of this study was to determine the prevalence of contralateral joint OA for patients presenting for unilateral total knee (TKA), unicompartmental knee (UKA) or total hip arthroplasty (THA) among Asian, Native Hawaiian/Pacific Islander and White patients. METHODS: Bilateral radiographic reports at initial presentation of 2,312 subjects who underwent unilateral arthroplasties (332 UKAs, 933 TKAs and 1,047 THAs) were reviewed. The presence of contralateral OA was recorded and compared by racial group and type of arthroplasty performed. Parametric statistical analyses were performed to determine differences between groups. Multivariable analyses were completed for each arthroplasty group to determine the influence on the presence of contralateral OA, presented as odds ratios and 95% confidence intervals. RESULTS: Contralateral joint OA was present in 86.7%, 90.4% and 70.4% of UKA, TKA and THA patients, respectively. Concurrent hip OA was present in 41.6% and 59.5% of UKA and TKA patients. No racial differences in the prevalence of contralateral knee OA were found for knee arthroplasty patients. White patients (74.6%) had a greater prevalence of contralateral hip OA compared to Asians (66.5%, p = 0.037) amongst THA recipients. Increased age and body mass index were significantly associated with the presence of contralateral knee OA. Increased age, being male and being White were significant contributors for the presence of contralateral hip OA. CONCLUSION: The prevalence of contralateral joint OA and concurrent hip OA is high in all three racial groups. Due to the extensive prevalence of contralateral and concurrent knee and hip OA, bilateral radiographic evaluation should be considered for all patients presenting with unilateral hip or knee pain due to OA.

Sensitization of cancer cells to ferroptosis coincident with cell cycle arrest.

Ferroptosis is a non-apoptotic form of cell death that can be triggered by inhibiting the system xc- cystine/glutamate antiporter or the phospholipid hydroperoxidase glutathione peroxidase 4 (GPX4). We have investigated how cell cycle arrest caused by stabilization of p53 or inhibition of cyclin-dependent kinase 4/6 (CDK4/6) impacts ferroptosis sensitivity. Here, we show that cell cycle arrest can enhance sensitivity to ferroptosis induced by covalent GPX4 inhibitors (GPX4i) but not system xc- inhibitors. Greater sensitivity to GPX4i is associated with increased levels of oxidizable polyunsaturated fatty acid-containing phospholipids (PUFA-PLs). Higher PUFA-PL abundance upon cell cycle arrest involves reduced expression of membrane-bound O-acyltransferase domain-containing 1 (MBOAT1) and epithelial membrane protein 2 (EMP2). A candidate orally bioavailable GPX4 inhibitor increases lipid peroxidation and shrinks tumor volumes when combined with a CDK4/6 inhibitor. Thus, cell cycle arrest may make certain cancer cells more susceptible to ferroptosis in vivo.

Hippocampal sparing radiation therapy for brain metastases: treatment techniques and clinical implementation.

High doses of radiation to the hippocampus have been correlated with increased cognitive decline following radiation therapy for brain metastases. To mitigate these effects, a variety of hippocampal sparing techniques have been implemented for both whole brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS). The goal of this review article is to provide a practical resource for the clinical implementation of hippocampal-sparing radiation therapy, starting with a brief background on the function and delineation of the hippocampal structure, as well as radiation effects on the hippocampus and the most widely recommended dose constraints. Considerations for treatment simulation are discussed, including options for cranial immobilization and optional head tilt. Hippocampal sparing has been demonstrated for WBRT using helical TomoTherapy, static intensity-modulated radiation therapy (IMRT), and volumetric-modulated arc therapy (VMAT) with a variety of patient setup positions, beam arrangements, and planning parameters. Tomotherapy has been shown to achieve slightly greater hippocampal sparing in some studies, while VMAT enables the most efficient treatment delivery. Hippocampal sparing has also been evaluated in a wide range of studies for both GammaKnife and linear accelerator (LINAC)-based SRS, with the proximity of metastases to the hippocampus being the most significant predictor of hippocampal dose. The methods and resulting hippocampal doses from these studies on both WBRT and SRS are discussed, as well as the role of automation in hippocampal sparing radiation therapy.

A Cell Cycle-Dependent Ferroptosis Sensitivity Switch Governed by EMP2.

Ferroptosis is a non-apoptotic form of cell death characterized by iron-dependent lipid peroxidation. Ferroptosis can be induced by system xc- cystine/glutamate antiporter inhibition or by direct inhibition of the phospholipid hydroperoxidase glutathione peroxidase 4 (GPX4). The regulation of ferroptosis in response to system xc- inhibition versus direct GPX4 inhibition may be distinct. Here, we show that cell cycle arrest enhances sensitivity to ferroptosis triggered by GPX4 inhibition but not system xc- inhibition. Arrested cells have increased levels of oxidizable polyunsaturated fatty acid-containing phospholipids, which drives sensitivity to GPX4 inhibition. Epithelial membrane protein 2 (EMP2) expression is reduced upon cell cycle arrest and is sufficient to enhance ferroptosis in response to direct GPX4 inhibition. An orally bioavailable GPX4 inhibitor increased markers of ferroptotic lipid peroxidation in vivo in combination with a cell cycle arresting agent. Thus, responses to different ferroptosis-inducing stimuli can be regulated by cell cycle state.

Household conditions, COVID-19, and equity: Insight from two nationally representative surveys.

Background: With people across the United States spending increased time at home since the emergence of COVID-19, housing characteristics may have an even greater impact on health. Therefore, we assessed associations between household conditions and COVID-19 experiences. Methods: We used data from two nationally representative surveys: the Tufts Equity Study (TES; n = 1449 in 2021; n = 1831 in 2022) and the Household Pulse Survey (HPS; n = 147,380 in 2021; n = 62,826 in 2022). In the TES, housing conditions were characterized by heating/cooling methods; smoking inside the home; visible water damage/mold; age of housing unit; and self-reported concern about various environmental factors. In TES and HPS, household size was assessed. Accounting for sampling weights, we examined associations between each housing exposure and COVID-19 outcomes (diagnosis, vaccination) using separate logistic regression models with covariates selected based on an evidence-based directed acyclic graph. Results: Having had COVID-19 was more likely among people who reported poor physical housing condition (odds ratio [OR] = 2.32; 95% confidence interval [CI] = 1.17-4.59; 2021), visible water damage or mold/musty smells (OR = 1.50; 95% CI = 1.10-2.03; 2022), and larger household size (5+ versus 1-2 people; OR = 1.53, 95% CI = 1.34-1.75, HPS 2022). COVID-19 vaccination was less likely among participants who reported smoke exposure inside the home (OR = 0.53; 95% CI = 0.31-0.90; 2022), poor water quality (OR = 0.42; 95% CI = 0.21-0.85; 2021), noise from industrial activity/construction (OR = 0.44; 95% CI = 0.19-0.99; 2022), and larger household size (OR = 0.57; 95% CI = 0.46-0.71; HPS 2022). Vaccination was also positively associated with poor indoor air quality (OR = 1.96; 95% CI = 1.02-3.72; 2022) and poor physical housing condition (OR = 2.27; 95% CI = 1.01-5.13; 2022). Certain heating/cooling sources were associated with COVID-19 outcomes. Conclusions: Our study found poor housing conditions associated with increased COVID-19 burden, which may be driven by systemic disparities in housing, healthcare, and financial access to resources during the COVID-19 pandemic.

A deep learning approach for automatic delineation of clinical target volume in stereotactic partial breast irradiation (S-PBI).

Accurate and efficient delineation of the clinical target volume (CTV) is of utmost significance in post-operative breast cancer radiotherapy. However, CTV delineation is challenging as the exact extent of microscopic disease encompassed by CTV is not visualizable in radiological images and remains uncertain. We proposed to mimic physicians' contouring practice for CTV segmentation in stereotactic partial breast irradiation (S-PBI) where CTV is derived from tumor bed volume (TBV) via a margin expansion followed by correcting the extensions for anatomical barriers of tumor invasion (e.g. skin, chest wall). We proposed a deep-learning model, where CT images and the corresponding TBV masks formed a multi-channel input for a 3D U-Net based architecture. The design guided the model to encode the location-related image features and directed the network to focus on TBV to initiate CTV segmentation. Gradient weighted class activation map (Grad-CAM) visualizations of the model predictions revealed that the extension rules and geometric/anatomical boundaries were learnt during model training to assist the network to limit the expansion to a certain distance from the chest wall and the skin. We retrospectively collected 175 prone CT images from 35 post-operative breast cancer patients who received 5-fraction partial breast irradiation regimen on GammaPod. The 35 patients were randomly split into training (25), validation (5) and test (5) sets. Our model achieved mean (standard deviation) of 0.94 (±0.02), 2.46 (±0.5) mm, and 0.53 (±0.14) mm for Dice similarity coefficient, 95th percentile Hausdorff distance, and average symmetric surface distance respectively on the test set. The results are promising for improving the efficiency and accuracy of CTV delineation during on-line treatment planning procedure.

Stability and reproducibility comparisons between deep inspiration breath-hold techniques for left-sided breast cancer patients: A prospective study.

PURPOSE: Deep inspiration breath-hold (DIBH) is crucial in reducing the lung and cardiac dose for treatment of left-sided breast cancer. We compared the stability and reproducibility of two DIBH techniques: Active Breathing Coordinator (ABC) and VisionRT (VRT). MATERIALS AND METHODS: We examined intra- and inter-fraction positional variation of the left lung. Eight left-sided breast cancer patients were monitored with electronic portal imaging during breath-hold (BH) at every fraction. For each patient, half of the fractions were treated using ABC and the other half with VRT, with an equal amount starting with either ABC or VRT. The lung in each portal image was delineated, and the variation of its area was evaluated. Intrafraction stability was evaluated as the mean coefficient of variation (CV) of the lung area for the supraclavicular (SCV) and left lateral (LLat) field over the course of treatment. Reproducibility was the CV for the first image of each fraction. Daily session time and total imaging monitor units (MU) used in patient positioning were recorded. RESULTS: The mean intrafraction stability across all patients for the LLat field was 1.3 ± 0.7% and 1.5 ± 0.9% for VRT and ABC, respectively. Similarly, this was 1.5 ± 0.7% and 1.6 ± 0.8% for VRT and ABC, respectively, for the SCV field. The mean interfraction reproducibility for the LLat field was 11.0 ± 3.4% and 14.9 ± 6.0% for VRT and ABC, respectively. Similarly, this was 13.0 ± 2.5% and 14.8 ± 9% for VRT and ABC, respectively, for the SCV. No difference was observed in the number of verification images required for either technique. CONCLUSIONS: The stability and reproducibility were found to be comparable between ABC and VRT. ABC can have larger interfractional variation with less feedback to the treating therapist compared to VRT as shown in the increase in geometric misses at the matchline.

On the feasibility of improved target coverage without compromising organs at risk using online adaptive stereotactic partial breast irradiation (A-SPBI).

PURPOSE: Describe an early-adopting institution's experience with online adaptive radiation for stereotactic partial breast irradiation. METHODS AND MATERIALS: Retrospective review of 22 women treated between May 2021 and March 2022 with adaptive stereotactic partial breast irradiation. A total of 106 of 110 fractions were evaluated for dosimetric changes in target coverage and organ-at-risk (OAR) dose. Patient set up with stereotactic wooden frame and adapted per fraction. Treatment and planning times were collected prospectively by radiation therapists. RESULTS: Scheduled PTV30 Gy was <95% in 72.1% and <90% in 38.5% of fractions, and both PTV and CTV coverage were improved significantly after adaption, and 83.7% of fractions were delivered as adapted per physician choice. There was no difference in OAR coverage. Average adaptive treatment planning took 15 min and average time-on-couch was 34.4 min. CONCLUSIONS: Adaptive stereotactic breast irradiation resulted in improved target coverage with equivalent dosing to OARs in an efficient and tolerated treatment time. Improved target coverage allowed for decreased PTV margins compared to prior trial protocols that may improve acute and late toxicities.

The 5-factor modified frailty index (mFI-5) is predictive of 30-day postoperative complications and readmission in patients with adult spinal deformity (ASD).

BACKGROUND: There is limited research regarding the association between the mFI-5 and postoperative complications among adult spinal deformity (ASD) patients. METHODS: Using the National Surgical Quality Improvement Project (NSQIP) database, patients with Current Procedural Terminology (CPT) codes for > 7-level fusion or < 7-level fusion with International Classification of Diseases, Ninth Revision (ICD-9) codes for ASD were identified between 2008 and 2016. Univariate analyses with post-hoc Bonferroni correction for demographics and preoperative factors were performed. Logistic regression assessed associations between mFI-5 scores and 30-day post-operative outcomes. RESULTS: 2,120 patients met criteria. Patients with an mFI-5 score of 4 or 5 were excluded, given there were<20 patients with those scores. Patients with mFI-5 scores of 1 and 2 had increased 30-day rates of pneumonia (3.5 % and 4.3 % vs 1.6 %), unplanned postoperative ventilation for > 48 h (3.1 % and 4.3 % vs 0.9 %), and UTIs (4.4 % and 7.4 % vs 2.0 %) than patients with a score of 0 (all, p < 0.05). Logistic regression revealed that compared to an mFI-5 of 0, a score of 1 was an independent predictor of 30-day reoperations (OR = 1.4; 95 % CI 1.1-18). A score of 2 was an independent predictor of overall (OR = 2.4; 95 % CI 1.4-4.1) and related (OR = 2.2; 95 % CI 1.2-4.1) 30-day readmissions. A score of 3 was not predictive of any adverse outcome. CONCLUSION: The mFI-5 score predicted complications and postoperative events in the ASD population. The mFI-5 may effectively predict 30-day readmissions. Further research is needed to identify the benefits and predictive value of mFI-5 as a risk assessment tool.

An Interesting Case Report of Myasthenia Gravis Exacerbation Induced by Durvalumab.

Immune checkpoint inhibitors are novel therapy for a wide range of malignancies. They have been associated with numerous side effects resulting in pulmonary, dermatological, gastrointestinal, and neurological complications. There are few reported cases of myasthenia gravis exacerbation from immune checkpoint inhibitors. We present a case of an 82-year-old woman with a history of myasthenia gravis in remission and non-small cell lung cancer who presented with diplopia, dyspnea, and generalized weakness after three cycles of durvalumab. She was diagnosed with a myasthenic crisis and was treated with high-dose steroids and plasmapheresis.

Saliency-guided deep learning network for automatic tumor bed volume delineation in post-operative breast irradiation.

Efficient, reliable and reproducible target volume delineation is a key step in the effective planning of breast radiotherapy. However, post-operative breast target delineation is challenging as the contrast between the tumor bed volume (TBV) and normal breast tissue is relatively low in CT images. In this study, we propose to mimic the marker-guidance procedure in manual target delineation. We developed a saliency-based deep learning segmentation (SDL-Seg) algorithm for accurate TBV segmentation in post-operative breast irradiation. The SDL-Seg algorithm incorporates saliency information in the form of markers' location cues into a U-Net model. The design forces the model to encode the location-related features, which underscores regions with high saliency levels and suppresses low saliency regions. The saliency maps were generated by identifying markers on CT images. Markers' location were then converted to probability maps using a distance transformation coupled with a Gaussian filter. Subsequently, the CT images and the corresponding saliency maps formed a multi-channel input for the SDL-Seg network. Our in-house dataset was comprised of 145 prone CT images from 29 post-operative breast cancer patients, who received 5-fraction partial breast irradiation (PBI) regimen on GammaPod. The 29 patients were randomly split into training (19), validation (5) and test (5) sets. The performance of the proposed method was compared against basic U-Net. Our model achieved mean (standard deviation) of 76.4(±2.7) %, 6.76(±1.83) mm, and 1.9(±0.66) mm for Dice similarity coefficient, 95 percentile Hausdorff distance, and average symmetric surface distance respectively on the test set with computation time of below 11 seconds per one CT volume. SDL-Seg showed superior performance relative to basic U-Net for all the evaluation metrics while preserving low computation cost. The findings demonstrate that SDL-Seg is a promising approach for improving the efficiency and accuracy of the on-line treatment planning procedure of PBI, such as GammaPod based PBI.

Identifying Quality Gaps in Preventive Care for Outpatients With Cirrhosis Within a Large, Academic Health Care System.

We sought to identify specific gaps in preventive care provided to outpatients with cirrhosis and to determine factors associated with high quality of care (QOC), to guide quality improvement efforts. Outpatients with cirrhosis who received care at a large, academic tertiary health care system in the United States were included. Twelve quality indicators (QIs), including preventive care processes for ascites, esophageal varices, hepatic encephalopathy, hepatocellular carcinoma (HCC), and general cirrhosis care, were measured. QI pass rates were calculated as the proportion of patients eligible for a QI who received that QI during the study period. We performed logistic regression to determine predictors of high QOC (≥ 75% of eligible QIs) and receipt of HCC surveillance. Of the 439 patients, the median age was 63 years, 59% were male, and 19% were Hispanic. The median Model for End-Stage Liver Disease-Sodium score was 11, 64% were compensated, and 32% had hepatitis C virus. QI pass rates varied by individual QIs, but were overall low. For example, 24% received appropriate HCC surveillance, 32% received an index endoscopy for varices screening, and 21% received secondary prophylaxis for spontaneous bacterial peritonitis. In multivariable analyses, Asian race (odds ratio [OR]: 3.7, 95% confidence interval [CI]: 1.3-10.2) was associated with higher QOC, and both Asian race (OR: 3.3, 95% CI: 1.2-9.0) and decompensated status (OR: 2.1, 95% CI: 1.1-4.2) were associated with receipt of HCC surveillance. A greater number of specialty care visits was not associated with higher QOC. Conclusion: Receipt of outpatient preventive cirrhosis QIs was variable and overall low in a diverse cohort of patients with cirrhosis. Variation in care by race/ethnicity and illness trajectory should prompt further inquiry into identifying modifiable factors to standardize care delivery and to improve QOC.

Cardiovascular and metabolic disease in the liver transplant recipient.

Liver transplantation has led to great improvements in long-term survival in patients with decompensated liver disease and hepatocellular carcinoma. Cardiovascular disease is the leading cause of non-graft-related deaths and has increased prevalence in liver allograft recipients. This is partly secondary to higher post-transplant rates of metabolic risk factors-notably obesity, hypertension, dyslipidemia, and diabetes mellitus, which comprise metabolic syndrome. Post-transplantation metabolic syndrome is expected to be a growing factor in morbidity and mortality as transplant candidates trend older, the rates of metabolic risk factors in the general population increase, non-alcoholic steatohepatitis grows disproportionally as an indication for transplantation, and post-transplantation survival lengthens. This review discusses the incidence and contributory factors for post-transplant increases in metabolic disease, as well as the burden of cardiovascular disease in the liver allograft recipient. Patients with pre-transplant diabetes or obesity are at particularly high risk for post-transplant metabolic syndrome, and would likely benefit from closer surveillance and more aggressive medical management of risk factors. In metabolic disease resistant to initial medical therapies, tailoring of immunosuppressive regimens may further assist in minimizing long-term cardiovascular disease, although this must be done with caution to avoid worsening the risk of graft failure.

Meeting the WHO hepatitis C virus elimination goal: Review of treatment in paediatrics.

Over 3 million paediatric patients globally and ~50 000 in the United States are estimated to be infected with HCV. Eradicating HCV in children helps prevent liver fibrosis, cirrhosis and hepatocellular carcinoma; reduces extra-hepatic manifestations of HCV; improves quality of life; and increases survival. The 2019 American Association for the Study of Liver Diseases-Infectious Diseases Society of America (AASLD-IDSA) guidelines now recommend direct-acting antiviral (DAA) treatment with an approved regimen for all children and adolescents with HCV infection aged ≥3 years. We conducted a descriptive review of the new DAA treatments for HCV infection in the paediatric population. Ledipasvir/sofosbuvir (LDV/SOF) and sofosbuvir with ribavirin (SOF/RBV) are now approved for those ≥3 years old under specific clinical scenarios; sofosbuvir/velpatasvir (SOF/VEL) is the only pangenotypic agent approved for those ≥6 years or ≥17 kg, and glecaprevir/pibrentasvir (GLE/PIB) is approved for adolescents ≥12 years old or ≥45 kg. These DAA regimens are well-tolerated and have comparable sustained virologic response rates at 12 weeks post-treatment compared to those reported in adults (close to 100%). The introduction of DAAs has significantly changed the landscape of HCV treatment in adults and children with HCV infection and has increased confidence that the 2030 World Health Organization elimination goal may be attainable. Further studies are warranted to determine the optimal treatment for children with HCV infection, including timing, regimen and duration. Additionally, with the recent paediatric approvals, long-term safety data are needed.

Diagnostic and Interventional Imaging Services are Significant Sources of Medicare Revenue for Highly Reimbursed Nonradiologist Providers.

INTRODUCTION: Nonradiologist providers increasingly perform diagnostic imaging examinations and imaging-guided interventions traditionally performed by radiologists, which have raised concerns regarding appropriate utilization and self-referral. The purpose of this study was to assess the contribution of imaging studies to Medicare reimbursements for highly compensated nonradiologist providers in specialties often performing imaging studies. METHODS: The Medicare Provider Utilization and Payment Database was queried for provider information regarding overall reimbursement for providers in anesthesiology, cardiology, emergency medicine, neurology, obstetrics and gynecology, orthopedic surgery, neurology, and vascular surgery. Information regarding imaging studies reported and payment amounts were extracted for the 25 highest-reimbursed providers. Data were analyzed for relative contribution of imaging payments to overall medical Medicare payments. RESULTS: Significant differences between numbers of imaging studies, types of imaging, and payment amounts were noted based on provider specialty (p < 0.001). Highest-reimbursed cardiologists received the greatest percentage of Medicare payments from imaging (18.3%) followed by vascular surgery (11.6%), obstetrics and gynecology (10.9%), orthopedic surgery (9.6%), emergency medicine (8.7%), neurology (7.8%), and anesthesiology (3.2%) providers. Mean imaging payments amongst highly reimbursed nonradiologists were greatest for cardiology ($578,265), vascular surgery ($363,912), and orthopedic surgery ($113,634). Amongst highly reimbursed specialists, most common nonradiologist imaging payments were from ultrasound (45%) and cardiac nuclear medicine studies (40%). CONCLUSIONS: Nonradiologist performed imaging payments comprised substantial proportions of overall Medicare reimbursement for highly reimbursed physicians in several specialties, especially cardiology, vascular surgery, and orthopedic surgery. Further investigation is needed to better understand the wider economic implications of nonradiologist imaging study performance and self-referral beyond the Medicare population.

Utility of CT Texture Analysis in Differentiating Low-Attenuation Renal Cell Carcinoma From Cysts: A Bi-Institutional Retrospective Study.

OBJECTIVE. The purpose of this study was to evaluate the utility of CT texture analysis (CTTA) in differentiating low-attenuation renal cell carcinoma (RCC) from renal cysts on unenhanced CT. MATERIALS AND METHODS. Ninety-four patients with low-attenuation RCC on unenhanced CT were compared with a cohort of 192 patients with benign renal cysts. CT characteristics (size and minimum, maximum, and mean attenuation) and CTTA features were recorded using an ROI approximately two-thirds the size of the mass. Masses were subjectively assessed by two expert genitourinary readers and two novice readers using a 5-point Likert scale (1 = definite cyst, 5 = definite renal cell carcinoma). Results of first-order CTTA and subjective evaluation were compared using ROC analysis. RESULTS. The group of 94 patients with low-attenuation RCC included 62 men and 32 women (mean age, 58.0 years). On unenhanced CT, the RCC were larger than 10 mm and of a median size of 50 mm with less than or equal to 20 HU (mean attenuation, 16 ± 4 HU). Of the RCC cohort, 83 were clear cell subtype. The cohort of 192 patients included 134 men and 58 women (mean age, 64.7 years) with benign renal cysts greater than 10 mm and a median size of 27 mm and less than or equal to 20 HU (mean attenuation, 9 ± 6 HU). The mean follow-up time was 6.2 years. Mean entropy in the low-attenuation RCC group (4.1 ± 0.7) was significantly higher than in the cyst group (2.8 ± 1.3, p < 0.0001). Entropy showed an ROC AUC of 0.89, with sensitivity of 84% and specificity of 80% at threshold 3.9. The AUC was better than subjective evaluation by novice readers (AUC, 0.77) and comparable to subjective evaluation by two expert readers (AUC, 0.90). A model combining the three best texture features (unfiltered mean gray-level attenuation, coarse entropy, and kurtosis) showed an improved AUC of 0.92. CONCLUSION. High entropy revealed with CTTA may be used to differentiate low-attenuation RCC from cysts at unenhanced CT; this technique performs as well as expert readers.

Downregulation of Human DAB2IP Gene Expression in Renal Cell Carcinoma Results in Resistance to Ionizing Radiation.

PURPOSE: Renal cell carcinoma (RCC) is known to be highly radioresistant but the mechanisms associated with radioresistance have remained elusive. We found DOC-2/DAB2 interactive protein (DAB2IP) frequently downregulated in RCC, is associated with radioresistance. In this study, we investigated the underlying mechanism regulating radioresistance by DAB2IP and developed appropriate treatment. EXPERIMENTAL DESIGN: Several RCC lines with or without DAB2IP expression were irradiated with ionizing radiation (IR) for determining their radiosensitivities based on colony formation assay. To investigate the underlying regulatory mechanism of DAB2IP, immunoprecipitation-mass spectrometry was performed to identify DAB2IP-interactive proteins. PARP-1 expression and enzymatic activity were determined using qRT-PCR, Western blot analysis, and ELISA. In vivo ubiquitination assay was used to test PARP-1 degradation. Furthermore, in vivo mice xenograft model and patient-derived xenograft (PDX) model were used to determine the effect of combination therapy to sensitizing tumors to IR. RESULTS: We notice that DAB2IP-deficient RCC cells acquire IR-resistance. Mechanistically, DAB2IP can form a complex with PARP-1 and E3 ligases that is responsible for degrading PARP-1. Indeed, elevated PARP-1 levels are associated with the IR resistance in RCC cells. Furthermore, PARP-1 inhibitor can enhance the IR response of either RCC xenograft model or PDX model. CONCLUSIONS: In this study, we unveil that loss of DAB2IP resulted in elevated PARP-1 protein is associated with IR-resistance in RCC. These results provide a new targeting strategy to improve the efficacy of radiotherapy of RCC.

Cost Effectiveness of Endoscopic Resection vs Transanal Resection of Complex Benign Rectal Polyps.

BACKGROUND & AIMS: Complex benign rectal polyps can be managed with transanal surgery or with endoscopic resection (ER). Though the complication rate after ER is lower than transanal surgery, recurrence is higher. Patients lost to follow up after ER might therefore be at increased risk for rectal cancer. We evaluated the costs, benefits, and cost effectiveness of ER compared to 2 surgical techniques for removing complex rectal polyps, using a 50-year time horizon-this allowed us to capture rates of cancer development among patients lost from follow-up surveillance. METHODS: We created a Markov model to simulate the lifetime outcomes and costs of ER, transanal endoscopic microsurgery (TEM), and transanal minimally invasive surgery (TAMIS) for the management of a complex benign rectal polyp. We assessed the effect of surveillance by allowing a portion of the patients to be lost to follow up. We calculated the cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio or each intervention over a 50-year time horizon. RESULTS: We found that TEM was slightly more effective than TAMIS and ER (TEM, 19.54 QALYs; TAMIS, 19.53 QALYs; and ER, 19.53 QALYs), but ER had a lower lifetime discounted cost (ER cost $7161, TEM cost $10,459, and TAMIS cost $11,253). TEM was not cost effective compared to ER, with an incremental cost-effectiveness ratio of $485,333/QALY. TAMIS was dominated by TEM. TEM became cost effective when the mortality from ER exceeded 0.63%, or if the loss to follow up rate exceeded 25.5%. CONCLUSIONS: Using a Markov model, we found that ER, TEM, and TAMIS have similar effectiveness, but ER is less expensive, in management of benign rectal polyps. As the rate of loss to follow up increases, transanal surgery becomes more effective relative to ER.

A Phase 2 Clinical Trial of SABR Followed by Immediate Vertebroplasty for Spine Metastases.

PURPOSE: To determine the pain response and prevention of vertebral compression fractures (VCFs) after single-fraction stereotactic ablative radiation therapy (SABR) in conjunction with immediate vertebroplasty for spine metastases. METHODS AND MATERIALS: Patients with localized spine metastases free from VCF associated with loss of vertebral height with a pain score ≥4 using the visual analog scale were enrolled. Spine SABR was performed with 20 Gy delivered to the gross disease and 14 Gy to the contiguous bone marrow in a single fraction. Immediate, prophylactic vertebroplasty was performed within 1 month after spine SABR. The primary endpoint was pain response at 3 months compared to the historical control with external beam radiation therapy from Radiation Therapy Oncology Group study 9714. Secondary endpoints included pain response at 1 month, duration of pain response, vertebroplasty rate, VCF rate, local control, and overall survival. RESULTS: Thirty-five patients were enrolled, of whom 29 were deemed eligible and underwent single-fraction spine SABR. Twenty-three of these patients subsequently underwent prophylactic vertebroplasty. The 3-month pain response was significantly improved compared to Radiation Therapy Oncology Group study 9714: 95% versus 51% (P < .0001). The local control with a median follow-up of 9.6 months was 92%. The freedom from VCF was 90% at 1 year. Spine SABR was well tolerated with no grade 2 or higher toxicities. A single patient with disease extending from the vertebral body into the spinal canal developed vertebroplasty-related myelopathy, which was corrected with surgery. CONCLUSIONS: Single-fraction SABR immediately followed by prophylactic vertebroplasty improves pain response compared with conventional radiation therapy while providing long-term pain control and structural stability of the treated spine. Vertebroplasty is well tolerated as a prophylactic measure in patients without loss of vertebral height after spine SABR. Pain response and VCF rates are similar to patients undergoing SABR alone. Thus, patients who would benefit most from the addition of vertebroplasty need to be further identified.