Comparative Analysis of Outcomes of Unibody Endoprosthesis and Aortobifemoral Bypass for Aortoiliac Occlusive Disease.

BACKGROUND: Aortoiliac occlusive disease (AIOD) has traditionally been treated with aortobifemoral bypass (ABF). Unibody endograft (UBE) for AIOD, however, has been increasingly utilized in selected patients. We report outcomes of patients undergoing ABF or UBE for AIOD. METHODS: Patients (2016-2021) undergoing elective ABF or UBE with a unibody device for AIOD were identified at an academic institution. Chi-square and Kaplan-Meier analysis were used to evaluate outcomes by group. RESULTS: One hundred thirty-one patients undergoing UBE or ABF were screened, with 82 included. Twenty-one patients underwent UBE (25.6%) and 61 (74.4%) underwent ABF. UBE patients were older (63.8 vs. 58.2 years; P = 0.01), with a higher prevalence of diabetes (52.4 vs. 19.7%; P = 0.004). Significant differences were seen between UBE and ABF including a shorter surgery length (214 vs. 360 min; P = 0.0001), less blood loss (300 vs. 620 mls; P = 0.001), larger minimum aortic diameter (14.6 vs. 12.6; P = 0.0006), larger common iliac artery (9.5 vs. 7.9; P = 0.005) and lower postoperative ankle-brachial index (0.8 vs. 0.9; P = 0.04). There were no differences in TASC C/D iliac lesions in the UBE than ABF group (66.6% vs. 63.9%; P < 0.82) or Trans-Atlantic Inter-Society Consensus classification femoropopliteal lesions. Unadjusted analysis revealed no significant differences between UBE and ABF for 30-day mortality (0 vs. 1.6%; P = 1), stroke (0 vs. 3.3%; P = 1), or major adverse cardiac events (4.8 vs. 4.9%; P = 1). There were no significant differences in mid-term surgical outcomes over a mean follow-up period of 23.7 months between UBE and ABF groups; specifically endovascular (0 vs. 8.2%; P = 0.3) or open/hybrid reintervention (9.5 vs. 14.8%; P = 0.7) with similar limb occlusion (4.8 vs. 27.8; P = 0.12). Kaplan-Meier estimated primary, primary-assisted, and secondary patency at 36 months were similar with 94%, 100%, and 94% for UBE and 86%, 95%, and 86% for ABF, respectively. Estimated survival at 36 months was 95% for UBE and 97% for ABF (P = 0.8). CONCLUSIONS: Equivalent outcomes were seen between AIOD treated with UBE or ABF in similar patient populations. Mid-term outcomes such as reintervention and patency are similar for UBE and ABF. We still recommend ABF over UBE as a primary modality of treatment in surgically fit patients with greater complexity aortoiliac lesions and with smaller arterial diameters, especially women.

Repeated blood-brain barrier opening with a nine-emitter implantable ultrasound device in combination with carboplatin in recurrent glioblastoma: a phase I/II clinical trial.

Here, the results of a phase 1/2 single-arm trial (NCT03744026) assessing the safety and efficacy of blood-brain barrier (BBB) disruption with an implantable ultrasound system in recurrent glioblastoma patients receiving carboplatin are reported. A nine-emitter ultrasound implant was placed at the end of tumor resection replacing the bone flap. After surgery, activation to disrupt the BBB was performed every four weeks either before or after carboplatin infusion. The primary objective of the Phase 1 was to evaluate the safety of escalating numbers of ultrasound emitters using a standard 3 + 3 dose escalation. The primary objective of the Phase 2 was to evaluate the efficacy of BBB opening using magnetic resonance imaging (MRI). The secondary objectives included safety and clinical efficacy. Thirty-three patients received a total of 90 monthly sonications with carboplatin administration and up to nine emitters activated without observed DLT. Grade 3 procedure-related adverse events consisted of pre syncope (n = 3), fatigue (n = 1), wound infection (n = 2), and pain at time of device connection (n = 7). BBB opening endpoint was met with 90% of emitters showing BBB disruption on MRI after sonication. In the 12 patients who received carboplatin just prior to sonication, the progression-free survival was 3.1 months, the 1-year overall survival rate was 58% and median overall survival was 14.0 months from surgery.

A Comprehensive Global Population-Based Analysis on the Coexistence of Eosinophilic Esophagitis and Inflammatory Bowel Disease.

BACKGROUND: We explored inflammatory bowel disease (IBD) and eosinophilic esophagitis (EoE) coexistence using a global dataset. Investigating their epidemiology, risks, and impact, we aimed to enhance the understanding of concurrent diagnoses and patient outcomes. METHODS: A retrospective population-based cohort study was conducted using deidentified patient data from the TriNetX database (2011-2022). We estimated the incidence and prevalence of EoE in patients with IBD, including both Crohn's disease (CD) and ulcerative colitis (UC), and vice versa. Risks of select immune-mediated conditions and disease complications were compared among patients with EoE, IBD, or concurrent diagnoses. RESULTS: Our results included 174,755 patients with CD; 150,774 patients with UC; and 44,714 patients with EoE. The risk of EoE was significantly higher among patients with CD (prevalence ratio [PR] 11.2) or UC (PR 8.7) compared with individuals without IBD. The risk of IBD was higher in patients with EoE (CD: PR 11.6; UC: PR 9.1) versus those without EoE. A propensity-matched analysis of IBD patients revealed that, when comparing patients with and without EoE, the relative risk of immune-mediated comorbidities was significantly greater for celiac disease, IBD-related inflammatory conditions, eczema and asthma (CD: n = 1896; UC: n = 1231; p < 0.001). Patients with a concurrent diagnosis of EoE and IBD had a higher composite risk of IBD-related complications (CD: adjusted HR (aHR) 1.14, p < 0.005; UC: aHR 1.17, p < 0.01) and lower risk of food bolus impaction (aHR 0.445, p = 0.0011). CONCLUSION: Simultaneous EoE and IBD increased IBD-related complications risk, needing more treatment (glucocorticoids, biologic therapy, abdominal surgery), while reducing EoE-related issues like food bolus impaction.

Shorter-acting glucagon-like peptide-1 receptor agonists are associated with increased development of gastro-oesophageal reflux disease and its complications in patients with type 2 diabetes mellitus: a population-level retrospective matched cohort study.

BACKGROUND: Shorter half-life glucagon-like peptide-1 receptor agonists (GLP-1 RAs) delay gastric emptying (DGE) more than GLP-1 RAs with longer half-lives. DGE is a known risk factor for gastro-oesophageal reflux disease (GERD) and its complications. AIM: To determine whether short-acting or long-acting GLP-1 RAs are associated with an increased risk of new GERD or GERD-related complications DESIGN: We used the TriNetX global database to identify adult patients with type 2 diabetes mellitus and generated two cohorts totalling 1 543 351 patients on (1) GLP-1 RA or (2) other second-line diabetes medication. Using propensity-score matching, Kaplan-Meier Analysis and Cox-proportional hazards ratio (HR), we analysed outcomes and separately examined outcomes in patients starting short-acting (≤1 day) and long-acting (≥5 days) GLP-1 RAs. RESULTS: 177 666 patients were in each propensity-matched cohort. GLP-1 RA exposure was associated with an increased risk (HR 1.15; 95% CI 1.09 to 1.22) of erosive reflux disease (ERD). However, this was solely due to short-acting (HR 1.215; 95% CI 1.111 to 1.328), but not long-acting (HR 0.994; 95% CI 0.924 to 1.069) GLP-1 RA exposure. Short-acting GLP-1 RAs were also associated with increased risk of oesophageal stricture (HR 1.284; 95% CI 1.135 to 1.453), Barrett's without dysplasia (HR 1.372; 95% CI 1.217 to 1.546) and Barrett's with dysplasia (HR 1.505; 95% CI 1.164 to 1.946) whereas long-acting GLP-1 RAs were not. This association persisted in sensitivity analyses, and when individually examining the short-acting GLP-1 RAs liraglutide, lixisenatide and exenatide. CONCLUSION: Starting shorter-acting GLP-1 RAs is associated with increased risks of GERD and its complications.

Raloxifene increases the risk of gastroesophageal reflux disease, Barrett's esophagus, and esophageal stricture in postmenopausal women with osteoporosis.

BACKGROUND AND AIMS: Estrogen-based therapies may increase the risk of gastroesophageal reflux (GERD) and its complications. We aimed to determine the effect of raloxifene on the development of GERD, Barrett's esophagus, and esophageal stricture in postmenopausal women with osteoporosis. METHODS: This was a population-based, propensity-matched cohort study using the TriNetX platform. Patients 50 years and older with a diagnosis of "menopause" and "osteoporosis" were included in this study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for new GERD, esophageal stricture and Barrett's esophagus after raloxifene exposure. The control cohort consisted of patients who did not start any hormonal replacement therapy. We conducted a multivariable logistic regression analysis to evaluate the effect of confounding variables and also addressed common confounding medications with 1:1 propensity score-matching. Internal validity was confirmed by comparing to negative controls (lisinopril, atorvastatin) and positive controls (metformin, ibuprofen, aspirin). RESULTS: Five thousand four hundred and seventy two postmenopausal women with osteoporosis were on raloxifene of which 1908 (34.86%) developed GERD, compared to 296,067 postmenopausal who were not on raloxifene of which 90,643 (30.62%) developed GERD (OR 1.2; 95% CI 1.10-1.31, p < 0.0001). This persisted after adjusting for common medications known to affect GERD. Raloxifene was identified as a risk factor for GERD in a multivariate analysis, controlling for factors including age, obesity, smoking, and alcohol use (OR 1.51, 95% Wald CI 1.47-1.53). Raloxifene was associated with esophageal stricture (OR 1.60; 95% Wald CI 1.51-1.69) and Barrett's esophagus (OR 1.50; 95% Wald CI 1.37-1.63) in multivariate analysis. These associations persisted using sensitivity analyses. CONCLUSION: Raloxifene increases the risk of GERD, esophageal stricture and Barrett's esophagus in postmenopausal women with osteoporosis. Further studies are needed to confirm our findings.

Surgical markup in lung cancer resection, 2015-2020.

Objective: The objective of this study was to assess procedure markup (charge-to-cost ratio) across lung resection procedures and examine variability by geographic region. Methods: Provider-level data for common lung resection operations was obtained from the 2015 to 2020 Medicare Provider Utilization and Payment Data datasets using Healthcare Common Procedure Coding System codes. Procedures studied included wedge resection; video-assisted thoracoscopic surgery; and open lobectomy, segmentectomy, and mediastinal and regional lymphadenectomy. Procedure markup ratio and coefficient of variation (CoV) was assessed and compared across procedure, region, and provider. The CoV, a measure of dispersion defined as the ratio of the SD to the mean, was likewise compared across procedure and region. Results: Median markup ratio across all procedures was 3.56 (interquartile range, 2.87-4.59) with right skew (mean, 4.13). Median markup ratio was 3.59 for lymphadenectomy (CoV, 0.51), 3.13 for open lobectomy (CoV, 0.45), 3.55 for video-assisted thoracoscopic surgery lobectomy (CoV, 0.59), 3.77 for segmentectomy (CoV, 0.74), and 3.80 for wedge resection (CoV, 0.67). Increased beneficiaries, services, and Healthcare Common Procedure Coding System score (total) were associated with a decreased markup ratio (P < .0001). Markup ratio was highest in the Northeast at 4.14 (interquartile range, 3.09-5.56) and lowest in the South (Markup ratio 3.26; interquartile range, 2.68-4.02). Conclusions: We observe geographic variation in surgical billing for thoracic surgery.

Repeated blood-brain barrier opening with an implantable ultrasound device for delivery of albumin-bound paclitaxel in patients with recurrent glioblastoma: a phase 1 trial.

BACKGROUND: Low-intensity pulsed ultrasound with concomitant administration of intravenous microbubbles (LIPU-MB) can be used to open the blood-brain barrier. We aimed to assess the safety and pharmacokinetics of LIPU-MB to enhance the delivery of albumin-bound paclitaxel to the peritumoural brain of patients with recurrent glioblastoma. METHODS: We conducted a dose-escalation phase 1 clinical trial in adults (aged ≥18 years) with recurrent glioblastoma, a tumour diameter of 70 mm or smaller, and a Karnofsky performance status of at least 70. A nine-emitter ultrasound device was implanted into a skull window after tumour resection. LIPU-MB with intravenous albumin-bound paclitaxel infusion was done every 3 weeks for up to six cycles. Six dose levels of albumin-bound paclitaxel (40 mg/m2, 80 mg/m2, 135 mg/m2, 175 mg/m2, 215 mg/m2, and 260 mg/m2) were evaluated. The primary endpoint was dose-limiting toxicity occurring during the first cycle of sonication and albumin-bound paclitaxel chemotherapy. Safety was assessed in all treated patients. Analyses were done in the per-protocol population. Blood-brain barrier opening was investigated by MRI before and after sonication. We also did pharmacokinetic analyses of LIPU-MB in a subgroup of patients from the current study and a subgroup of patients who received carboplatin as part of a similar trial (NCT03744026). This study is registered with ClinicalTrials.gov, NCT04528680, and a phase 2 trial is currently open for accrual. FINDINGS: 17 patients (nine men and eight women) were enrolled between Oct 29, 2020, and Feb 21, 2022. As of data cutoff on Sept 6, 2022, median follow-up was 11·89 months (IQR 11·12-12·78). One patient was treated per dose level of albumin-bound paclitaxel for levels 1 to 5 (40-215 mg/m2), and 12 patients were treated at dose level 6 (260 mg/m2). A total of 68 cycles of LIPU-MB-based blood-brain barrier opening were done (median 3 cycles per patient [range 2-6]). At a dose of 260 mg/m2, encephalopathy (grade 3) occurred in one (8%) of 12 patients during the first cycle (considered a dose-limiting toxicity), and in one other patient during the second cycle (grade 2). In both cases, the toxicity resolved and treatment continued at a lower dose of albumin-bound paclitaxel, with a dose of 175 mg/m2 in the case of the grade 3 encephalopathy, and to 215 mg/m2 in the case of the grade 2 encephalopathy. Grade 2 peripheral neuropathy was observed in one patient during the third cycle of 260 mg/m2 albumin-bound paclitaxel. No progressive neurological deficits attributed to LIPU-MB were observed. LIPU-MB-based blood-brain barrier opening was most commonly associated with immediate yet transient grade 1-2 headache (12 [71%] of 17 patients). The most common grade 3-4 treatment-emergent adverse events were neutropenia (eight [47%]), leukopenia (five [29%]), and hypertension (five [29%]). No treatment-related deaths occurred during the study. Imaging analysis showed blood-brain barrier opening in the brain regions targeted by LIPU-MB, which diminished over the first 1 h after sonication. Pharmacokinetic analyses showed that LIPU-MB led to increases in the mean brain parenchymal concentrations of albumin-bound paclitaxel (from 0·037 µM [95% CI 0·022-0·063] in non-sonicated brain to 0·139 µM [0·083-0·232] in sonicated brain [3·7-times increase], p<0·0001) and carboplatin (from 0·991 µM [0·562-1·747] in non-sonicated brain to 5·878 µM [3·462-9·980] µM in sonicated brain [5·9-times increase], p=0·0001). INTERPRETATION: LIPU-MB using a skull-implantable ultrasound device transiently opens the blood-brain barrier allowing for safe, repeated penetration of cytotoxic drugs into the brain. This study has prompted a subsequent phase 2 study combining LIPU-MB with albumin-bound paclitaxel plus carboplatin (NCT04528680), which is ongoing. FUNDING: National Institutes of Health and National Cancer Institute, Moceri Family Foundation, and the Panattoni family.

The effect of combined oral contraceptives and Nexplanon on gastroesophageal reflux disease in premenopausal women: A nationwide database analysis.

BACKGROUND: Pregnancy, combined oral contraceptives (COC), and hormone replacement therapy have been reported to increase the risk of gastroesophageal reflux disease (GERD). To date, no study has evaluated the effect of Nexplanon, a commonly used progesterone-based contraceptive, on GERD. We aimed to determine the effect of Nexplanon and COC on GERD. METHODS: We performed a population-based analysis using the IBM Explorys national database (1999-2021). The study group included premenopausal women, defined as women less than 50 years of age while excluding the diagnosis of menopause. The effect of Nexplanon and COC on GERD (at least 30 days after Nexplanon/COC was initiated) was assessed by comparing it to premenopausal women who were not on contraceptives. Foregut surgery, esophageal dysmotility disorders, hiatal hernia, and delayed gastric emptying were excluded. Odds ratios (OR) with 95% confidence intervals (CI) were calculated. A multivariate logistic regression analysis was conducted. KEY RESULTS: A total of 23,299,470 patients were identified as being premenopausal, of which 47,260 were on Nexplanon and 5480 on COCs. As compared to premenopausal women with GERD on no contraceptives (n = 565,880), 690 patients developed GERD at least 30 days after being on Nexplanon (OR = 0.55, 95% CI [0.51-0.59], p < 0.001) and 280 developed GERD after COC (1.93, [1.71-2.18], p < 0.001). A multivariate analysis accounting for Caucasian race, obesity, smoking, alcohol use, and NSAIDs revealed that COC is an independent risk factor for GERD (1.16, [1.12-1.20], p < 0.001), and Nexplanon was protective against GERD (0.90, [0.89-0.92], p < 0.001). Hydralazine was used as a control medication for data reliability. A total of 8420 patients developed GERD after initiating hydralazine, which was not statistically nor clinically significant (OR = 1.02, 95% CI [0.99-1.04], p = 0.08) when compared to those not on contraceptives. CONCLUSIONS & INFERENCES: Combined oral contraceptives is an independent risk factor for GERD, while Nexplanon has a limited protective effect. Further studies are needed to confirm the different effects on GERD of these two contraceptives.

A Framework for Harmonization of Radiomics Data for Multicenter Studies and Clinical Trials.

PURPOSE: Variability in computed tomography images intrinsic to individual scanners limits the application of radiomics in clinical and research settings. The development of reproducible and generalizable radiomics-based models to assess lesions requires harmonization of data. The purpose of this study was to develop, test, and analyze the efficacy of a radiomics data harmonization model. MATERIALS AND METHODS: Radiomic features from biopsy-proven untreated hepatic metastasis (N = 380) acquired from 167 unique patients with pancreatic, colon, and breast cancers were analyzed. Radiomic features from volume-match 551 samples of normal liver tissue and 188 hepatic cysts were included as references. A novel linear mixed effect model was used to identify effects associated with lesion size, tissue type, and scanner model. Six separate machine learning models were then used to test the effectiveness of radiomic feature harmonization using multivariate analysis. RESULTS: Proposed model identifies and removes scanner-associated effects while preserving cancer-specific functional dependence of radiomic features on the tumor size. Data harmonization improves the performance of classification models by reducing the scanner-associated variability. For example, the multiclass logistic regression model, LogitBoost, demonstrated the improvement in sensitivity in the range from 15% to 40% for each type of liver metastasis, whereas the overall model accuracy and the kappa coefficient increased by 5% and 8% accordingly. CONCLUSION: The model removed scanner-associated effects while preserving cancer-specific functional dependence of radiomic features.

Disparities in Electronic Screening for Cancer-Related Psychosocial Distress May Promote Systemic Barriers to Quality Oncologic Care.

BACKGROUND: Screening for cancer-related psychosocial distress is an integral yet laborious component of quality oncologic care. Automated preappointment screening through online patient portals (Portal, MyChart) is efficient compared with paper-based screening, but unstudied. We hypothesized that patient access to and engagement with EHR-based screening would positively correlate with factors associated with digital literacy (eg, age, socioeconomic status). METHODS: Screening-eligible oncology patients seen at our Comprehensive Cancer Center from 2014 through 2019 were identified. Patients with active Portals were offered distress screening. Portal and screening participation were analyzed via multivariable logistic regression. Household income in US dollars and educational attainment were estimated utilizing zip code and census data. RESULTS: Of 17,982 patients, 10,279 (57%) had active Portals and were offered distress screening. On multivariable analysis, older age (odds ratio [OR], 0.97/year; P<.001); male gender (OR, 0.89; P<.001); Black (OR, 0.47; P<.001), Hawaiian/Pacific Islander (OR, 1.54; P=.007), and Native American/Alaskan Native race (OR, 0.67; P=.04); Hispanic ethnicity (OR, 0.76; P<.001); and Medicare (OR, 0.59; P<.001), Veteran's Affairs/military (OR, 0.09; P<.01), Medicaid (OR, 0.34; P<.001), or no insurance coverage (OR, 0.57; P<.001) were independently associated with lower odds of being offered distress screening; increasing income (OR, 1.05/$10,000; P<.001) and educational attainment (OR, 1.03/percent likelihood of bachelor's degree or higher; P<.001) were independently associated with higher odds. In patients offered electronic screening, participation rate was 36.6% (n=3,758). Higher educational attainment (OR, 1.01; P=.03) was independently associated with participation, whereas Black race (OR, 0.58; P=.004), Hispanic ethnicity (OR, 0.68; P=.01), non-English primary language (OR, 0.67; P=.03), and Medicaid insurance (OR, 0.78; P<.001) were independently associated with nonparticipation. CONCLUSIONS: Electronic portal-based screening for cancer-related psychosocial distress leads to underscreening of vulnerable populations. At institutions using electronic distress screening workflows, supplemental screening for patients unable or unwilling to engage with electronic screening is recommended to ensure efficient yet equal-opportunity distress screening.

Impact of Comorbidities on Lung Cancer Screening Evaluation.

OBJECTIVES: We used data from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial to examine the impact of self-reported chronic obstructive pulmonary disease, coronary artery disease, stroke, and diabetes mellitus on diagnostic complications in lung cancer screening evaluation. METHODS: In our analysis, we included individuals from the usual care and intervention (annual chest x-ray) of the lung cancer screening trial with equal or greater than 55 years of age with a 20 pack-year smoking history who had undergone an invasive procedure. We performed multivariate logistic regression analysis to estimate the association of comorbidity on procedure complication. Our primary outcome was the incidence of major or moderate complications. RESULTS: Features associated with high-risk complication included older age (OR = 1.03 per year, P = .001), history of coronary artery disease (OR = 1.40, P = .03), history of diabetes mellitus (OR = 0.41, P < .001, current smoking status (OR = 1.46, P ≤ .001), surgical biopsy (OR = 7.39, P < .001), needle biopsy (OR = 1.94, P < .001), and other invasive procedure (OR = 1.58, P < .001). We did not find an associated with complication and history of stroke (OR = 0.84, P = .53) or chronic obstructive pulmonary disease (OR = 1.27, P = .06). CONCLUSION: Patient and procedure-level factors may alter the benefits of lung cancer screening. Data concerning individual risk factors and high-risk complications should therefore be incorporated into diagnostic algorithms to optimize clinical benefit and minimize harm. Further study and validation of the risk factors identified herein are warranted.

Multimodal Presurgical Evaluation of Medically Refractory Focal Epilepsy in Adults: An Update for Radiologists.

Surgery is a potentially curative treatment option for patients with medically refractory focal epilepsy. Advanced neuroimaging modalities often improve surgical outcomes by contributing key information during the highly individualized surgical planning process and intraoperative localization. Hence, neuroradiologists play an integral role in the multidisciplinary management team. In this review, we initially present the conceptual background and practical framework of the presurgical evaluation process, including a description of the surgical treatment approaches used for medically refractory focal epilepsy in adults. This background is followed by an overview of the advanced modalities commonly used during the presurgical workup at level IV epilepsy centers, including diffusion imaging techniques, blood oxygenation level-dependent functional MRI (fMRI), PET, SPECT, and subtraction ictal SPECT, and by introductions to 7-T MRI and electrophysiologic techniques including electroencephalography and magnetoencephalography. We also provide illustrative case examples of multimodal neuroimaging including PET/MRI, PET/MRI-diffusion-tensor imaging (DTI), subtraction ictal SPECT, and image-guided stereotactic planning with fMRI-DTI.

Risk of Cardiovascular Toxicity According to Tumor Laterality Among Older Patients With Early Stage Non-small Cell Lung Cancer Treated With Radiation Therapy.

BACKGROUND: The long-term risk of cardiovascular outcomes from either stereotactic body radiation therapy (SBRT) or three-dimensional conformal radiation therapy (3DCRT) plus intensity-modulated radiation therapy (IMRT) to treat early stage non-small cell lung cancer (NSCLC) is largely unknown. As continued adoption of SBRT accelerates, it is important to delineate unforeseen cardiovascular risks associated with treatment. RESEARCH QUESTION: Does the long-term risk of cardiovascular outcomes for patients with early stage NSCLC treated with either SBRT or 3DCRT plus IMRT differ by tumor laterality? STUDY DESIGN AND METHODS: Data from the Surveillance, Epidemiology, and End Results registry linked to Medicare was analyzed to identify a sample of 3,256 patients (1,506 treated with SBRT and 1,750 treated with 3DCRT plus IMRT) with node-negative stage I or IIA NSCLC. Cardiovascular events were identified using diagnosis codes, and outcomes were compared between left- and right-sided tumors. We assumed that tumor laterality was random and that the radiation field for left-sided tumors likely would result in greater dose to cardiac tissues. Cox regression models were fit to quantify the association of laterality on outcomes. RESULTS: Patients were followed up for a median of 2 years. Those treated with SBRT showed no difference in hazard of any cardiovascular outcomes by tumor laterality, including the cardiovascular composite (hazard ratio [HR] comparing left- vs right-sided tumors, 0.98; 95% CI, 0.84-1.15). In contrast, patients treated with 3DCRT plus IMRT showed a greater risk of congestive heart failure (HR, 1.23; 95% CI, 1.01-1.48) and percutaneous coronary artery intervention (HR, 2.24; 95% CI, 1.12-4.47). INTERPRETATION: Patients with left- vs right-sided early stage NSCLC showed similar rates of cardiovascular events when treated with SBRT. However, these patients also showed higher rates of select cardiac events when they were treated with 3DCRT plus IMRT. This study provides evidence that SBRT may provide a safer option over 3DCRT plus IMRT for patients with left-sided early stage NSCLC and underscores the need for long-term follow-up for patients treated with radiation therapy.

Role of hepatic metastatic lesion size on inter-reader reproducibility of CT-based radiomics features.

OBJECTIVES: To evaluate the effect of hepatic metastatic lesion size on inter-reader reproducibility of CT-based 2D radiomics imaging features. METHODS: Computerized tomography (CT) scans of 59 liver metastases from 34 patients with colorectal cancer were evaluated. Image segmentation was performed manually by three readers blinded to each other's results. For each radiomics feature, we created two datasets by sorting measurements according to size, i.e., (i) from the smallest to the largest lesion and (ii) from the largest to the smallest lesion. The Lin concordance correlation coefficient (CCC) was employed to analyze the reproducibility of radiomics features. In particular, the CCC was computed as a function of a number of elements in the dataset, by gradually adding lesions from each sorted dataset. To evaluate the effect of lesion size, we analyzed the difference between these two functions thus assessing the contribution of small and large lesions into the reproducibility of radiomics features. RESULTS: Inter-reader reproducibility of CT-based 2D radiomics features assessed using Lin's CCC demonstrates tumor-size dependence. For example, the Lin CCC for GLCM contrast equals 0.88 (95% C.I. 0.84 to 0.92, p < 0.003) and could change by an additional + / - 0.06 depending on the presence of large or small lesions. CONCLUSIONS: Groups of "large" and "small" lesions show different inter-reader reproducibility. The inter-reader reproducibility from the mixed group consisting of "large" and "small" lesions depends on the lesion-size distribution and can vary widely. This finding could partially explain variability in reproducibility of radiomics features in the literature. KEY POINTS: • Groups of "large" and "small" lesions show different inter-reader reproducibility. • The inter-reader reproducibility from the mixed group consisting of "large" and "small" lesions depends on the lesion-size distribution.

Psychosocial distress is dynamic across the spectrum of cancer care and requires longitudinal screening for patient-centered care.

PURPOSE: Screening for cancer-related psychosocial distress is recommended for patients with cancer; however, data on the long-term prevalence of distress and its natural history in survivors are scarce, preventing recommendations for screening frequency and duration. We sought to evaluate longitudinal distress in cancer patients. METHODS: We evaluated longitudinal distress screening data for patients with cancer treated or surveilled at our institution from 2010 to 2018. Anxiety, depression, insurance/financial, family, memory, and strength-related distress were separately assessed and analyzed. Multivariable logistic regression was utilized to evaluate factors associated with distress subtypes. RESULTS: In 5660 patients, distress was the highest at diagnosis for anxiety, depression, financial, and overall distress. On multivariable analysis, factors independently associated with distress at diagnosis included younger age, female gender, disease site/stage, payor, and income, varying by subtype-specific analyses. Severe distress in at least one subtype persisted in over 30% of survivors surveyed through 10 years after diagnosis. Over half of patients with initially severe distress at diagnosis improved within 12 months; however, distress worsened in 20-30% of patients with moderate, low, and no initial distress, regardless of the distress subtype. CONCLUSION: Psychosocial distress in cancer survivors is a long-lasting burden with implications for quality of life and oncologic outcomes. Severe distress remains prevalent through 10 years after diagnosis in survivors receiving continued care at cancer centers and results from both persistent and new sources of distress in a variety of psychosocial domains. Longitudinal distress screening is an invaluable tool for providing comprehensive patient-centered cancer care and is recommended to detect new or recurrent distress in cancer survivors.

Clinical Efficacy of Reduced-Dose Gadobutrol Versus Standard-Dose Gadoterate for Contrast-Enhanced MRI of the CNS: An International Multicenter Prospective Crossover Trial (LEADER-75).

BACKGROUND. Gadobutrol and gadoterate are widely used macrocyclic gadolinium-based contrast agents. Given gadobutrol's higher T1 relaxivity, a reduced gadobutrol dose should achieve essentially equivalent diagnostic efficacy as a standard dose of gadoterate. OBJECTIVE. The purpose of our study was to show efficacy of a 25% reduced dose of gadobutrol is noninferior to 100% standard dose of gadoterate for contrast-enhanced MRI of the CNS. METHODS. In this international prospective multicenter open-label crossover trial (LEADER-75 [Lower Administered Dose With Higher Relaxivity: Gadovist vs Dotarem]), adult patients with known or suspected CNS pathology underwent contrast-enhanced brain MRI with standard-dose gadoterate (0.1 mmol/kg); if an enhancing lesion was identified, a second MRI with reduced-dose gadobutrol (0.075 mmol/kg) was performed within 15 days of the first MRI. Three radiologists independently reviewed images to score three primary efficacy measures: subjective lesion enhancement, lesion border delineation, lesion internal morphology. A noninferiority analysis used readers' mean scores of the primary efficacy measures. Noninferiority of reduced-dose gadobutrol to standard-dose gadoterate for primary efficacy measures was defined as the difference in score between reduced-dose gadobutrol images and unenhanced images achieving at least 80% of the difference in score between standard-dose gadoterate images and unenhanced images. A post hoc analysis was performed to directly compare contrast-enhanced images for equivalence. Secondary efficacy variables included the number of lesions detected, reader confidence, diagnostic performance for malignancy, and reader preference in side-by-side comparison. RESULTS. The efficacy analysis included 141 patients (78 men, 63 women; mean age, 58.5 ± 13.5 [SD] years). Improvement of reduced-dose gadobutrol over unenhanced images was noninferior to improvement of standard-dose gadoterate over unenhanced images using a 20% noninferiority margin for all three primary efficacy measures using mean readings (p ≤ .025). In the post hoc analysis, the mean reading for the three primary efficacy measures differed by less than 1% between reduced-dose gadobutrol and standard-dose gadoterate, supporting equivalence of all measures using a narrow ± 5% margin (p ≤ .025). The total number of lesions detected by mean reading was 301 for reduced-dose gadobutrol versus 291 for standard-dose gadoterate. Mean reader confidence was 3.3 ± 0.6 for reduced-dose gadobutrol versus 3.3 ± 0.6 for standard-dose gadoterate. Sensitivity (58.7%), specificity (91.8%), and accuracy (70.2%) for malignancy from majority reading were identical for reduced-dose gadobutrol and standard-dose gadoterate. Reader preference was not different (95% CI, -0.10 to 0.11). CONCLUSION. A 25% reduced dose of gadobutrol is noninferior to standard-dose gadoterate for contrast-enhanced brain MRI. CLINICAL IMPACT. Use of reduced-dose gadobutrol should be considered for brain MRI, particularly in patients undergoing multiple contrast-enhanced examinations. TRIAL REGISTRATION. ClinicalTrials.gov NCT03602339; EU Clinical Trials Register EudraCT 2018-00690-78.

Spinal and paraspinal inflammatory reactions after epidural steroid injection in a patient taking disease-modifying antirheumatic drugs.

BackgroundDisease-modifying anti-rheumatic drugs (DMARDs) are used in the management of rheumatoid arthritis (RA) and are classified as conventional DMARDs and biologic agents. A concern with DMARDs is the increased risk of infection after surgery. A practice advisory from the American Society of Anesthesiologists recommend alternatives to neuraxial injections in patients who are immunocompromized. We describe a patient who was on several DMARDs and developed inflammatory reactions in her bilateral paraspinal muscles and lumbar spine after an epidural steroid injection (ESI). CASE PRESENTATION: The patient was a 79-year-old woman; she was taking methotrexate, adalimumab and prednisone for her RA. She had a left L5-S1 paramedian ESI for her L5 radiculitis. After relief of her back and radicular pain for 5 weeks, she had an acute exacerbation of her back pain. MRI showed bilateral paraspinal fluid accumulations and enhancement in her ligamentum flavum. Cultures of the aspirated fluid and biopsy specimens were negative for fungal, aerobic and anaerobic organisms. A repeat MRI 2 months later showed diminution of the fluid collection but with a new fluid accumulation near the left L4-5 facet and left L4 pedicle. Repeat cultures and gram stain of the specimens taken from the pedicle and the paraspinal muscles were negative. The patient was followed by her rheumatologist and in the pain clinic until resolution of her symptoms. CONCLUSIONS: Several society guidelines recommend the continuation of methotrexate but stoppage of the biologic DMARDS before surgery. The occurrence of an intense inflammatory reaction after an ESI in our patient calls for additional research on the subject and shared decision-making between the pain physician, patient and rheumatologist especially in patients on several DMARDs.

Marginal ulceration following Roux-en-Y gastric bypass: risk factors for ulcer development, recurrence and need for revisional surgery.

BACKGROUND: Marginal ulcer formation is a known complication following RYGB. While most respond to medical therapy, many patients have recurrent or chronic MU. Although non-steroidal anti-inflammatory drug (NSAID) use, smoking and Helicobacter pylori infection are known risk factors of MU, little is known about what increases the likelihood of developing recalcitrant ulcers. The objective of this study is to identify risk factors for marginal ulcer (MU) formation, including recalcitrant ulcers requiring surgical revision, and to define the incidence and outcomes of revisional surgery. METHODS: All patients who underwent RYGB between 2011 and 2017 at a high-volume academic center were included. Patients with a postoperative diagnosis of MU were identified from the institution's bariatric database. Patient characteristics, operative data and surgical outcomes were analyzed using data collected in the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program and the Ontario Bariatric Registry. RESULTS: A total of 2830 RYGB were performed during the study period. The incidence of MU was 6.9% with 1% of patients requiring revisional surgery for a recalcitrant ulcer. Patients with a history of smoking (HR 5.03), immunosuppression (HR 4.60) and preoperative NSAID use (HR 3.11) were significantly more likely to develop a MU requiring surgical revision. Patients undergoing revision reported resolution of their symptoms in only 36% of cases with 57% developing a recurrent ulcer. CONCLUSION: Patients with a history of smoking and use of immunosuppressive medication were at significantly higher risk of developing MU that failed medical therapy. Additional evidence is needed to inform perioperative management of bariatric patients.

Plasticity of the Primary Motor Cortex in Patients with Primary Brain Tumors.

There are two neuron-level mechanisms proposed to underlie neural plasticity: recruiting neurons nearby to support the lost function (ipsilesional plasticity) and uncovering latent pathways that can assume the function that was lost (contralesional plasticity). While both patterns have been demonstrated in patient groups following injury, the specific mechanisms underlying each mode of plasticity are poorly understood. In a retrospective case series of 13 patients, we utilize a novel paradigm that analyzes serial fMRI scans in patients harboring intrinsic brain tumors that vary in location and growth kinetics to better understand the mechanisms underlying these two modes of plasticity in the human primary motor cortex. Twelve patients in our series had some degree of primary motor cortex plasticity, an area previously thought to have limited plasticity. Patients harboring smaller lesions with slower growth kinetics and increasing distance from the primary motor region demonstrated recruitment of ipsilateral motor regions. Conversely, larger, faster-growing lesions in close proximity to the primary motor region were associated with activation of the contralesional primary motor cortex, along with increased activation of the supplementary motor area. These data increase our understanding of the adaptive abilities of the brain and may lead to improved treatment strategies for those suffering from motor loss secondary to brain injuries.