Impact of Size Thresholds on the Diagnosis of Incidental Adrenal Lesions: A Systematic Review and Meta-Analysis.

BACKGROUND: Preferred size-threshold recommendations for management of incidental adrenal lesions remain controversial. PURPOSE: This meta-analysis aimed to compare the diagnostic accuracy of different size thresholds for detecting malignancy in patients with incidental adrenal lesions on imaging. MATERIALS AND METHODS: A systematic review of MEDLINE, Embase, Scopus, the Cochrane Library, and the gray literature, covering the period from inception to September 2021, was performed. Studies with >10 patients evaluating the diagnostic accuracy of imaging size thresholds for detecting malignancy in patients with incidental adrenal lesions and no prior history of cancer were included. Study, clinical, imaging, and accuracy data for eligible studies were independently acquired by two reviewers. Primary meta-analysis was performed using a bivariate mixed-effects regression model. Risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. RESULTS: From 2,690 citations, 40 studies (9,794 patients with mean age ranging from 41 to 66 years) were included. Most (36 of 40) were retrospective single-center studies. CT with or without MRI served as the index test(s). Sensitivity and specificity values, respectively, by size threshold used in the included studies were as follows: 85% (95% confidence interval [CI] 74%-91%) and 39% (95% CI 23%-57%) for 3-cm thresholds; 85% (95% CI 78%-90%) and 75% (95% CI 62%-85%) for 4-cm thresholds; 70% (95% CI 56%-81%) and 74% (95% CI 59%-85%) for 5-cm thresholds; and 75% (95% CI 67%-82%) and 77% (95% CI 62%-87%) for 6-cm thresholds. No cause for variability in sensitivity or specificity was identified on subgroup analysis of the 4-cm threshold. Nearly half of the studies (19 of 40) had at least one QUADAS-2 domain with a high risk of bias. CONCLUSIONS: A 4-cm size threshold demonstrates the highest combined sensitivity and specificity, with a preserved specificity compared with higher size thresholds, but with a trend toward improved sensitivity. Future research reevaluating 4-5 cm size thresholds while excluding characteristically benign lesions by imaging may help redefine a size threshold that has improved specificity but preserved sensitivity, compared with the existing 4-cm threshold.

Diagnostic accuracy of CT and MR features for detecting atypical lipomatous tumors and malignant liposarcomas: a systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis evaluated the diagnostic accuracy of CT and MRI for differentiating atypical lipomatous tumors and malignant liposarcomas from benign lipomatous lesions. METHODS: MEDLINE, EMBASE, Scopus, the Cochrane Library, and the gray literature from inception to January 2022 were systematically evaluated. Original studies with > 5 patients evaluating the accuracy of CT and/or MRI for detecting liposarcomas with a histopathological reference standard were included. Meta-analysis was performed using a bivariate mixed-effects regression model. Risk of bias was evaluated using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). This study is registered on PROSPERO, number CRD42022306479. RESULTS: Twenty-six studies with a total of 2613 patients were included. Mean/median reported patient ages ranged between 50 and 63 years. The summary sensitivity and specificity of radiologist gestalt for detecting liposarcomas was 85% (79-90% 95% CI) and 63% (52-72%), respectively. Deep depth to fascia, thickened septations, enhancing components, and lesion size (≥ 10 cm) all demonstrated sensitivities ≥ 85%. Other imaging characteristics including heterogenous/amorphous signal intensity, irregular tumor margin, and nodules present demonstrated lower sensitivities ranging from 43 to 65%. Inter-reader reliability for radiologist gestalt within studies ranged from fair to substantial (k = 0.23-0.7). Risk of bias was predominantly mixed for patient selection, low for index test and reference standard, and unclear for flow and timing. CONCLUSION: Higher sensitivities for detecting liposarcomas were achieved with radiologist gestalt, deep depth to fascia, thickened septations, enhancing components, and large size. Combined clinical and imaging scoring and/or radiomics both show promise for optimal performance, though require further analysis with prospective study designs. CLINICAL RELEVANCE: This pooled analysis evaluates the accuracy of CT and MRI for detecting atypical lipomatous tumors and malignant liposarcomas. Radiologist gestalt, deep depth to fascia, thickened septations, enhancing components, and large size demonstrate the highest overall sensitivities. KEY POINTS: • The summary sensitivity and specificity of radiologist gestalt for detecting liposarcomas was 85% (79-90% 95% CI) and 63% (52-72%), respectively. • Radiologist gestalt, deep depth to fascia, thickened septations, enhancing components, and large tumor size (≥ 10 cm) showed the highest sensitivities for detecting atypical lipomatous tumors/well-differentiated liposarcomas and malignant liposarcomas. • A combined clinical and imaging scoring system and/or radiomics is likely to provide the best overall diagnostic accuracy, although currently proposed scoring systems and radiomic feature analysis require further study with prospective study designs.

Lack of patient-centered evaluation of outcomes in intermittent claudication literature.

BACKGROUND: Peripheral arterial disease, characterized as arterial atherosclerotic disease, can lead to insufficient flow in the lower extremities and ischemia, with the most common clinical manifestation being intermittent claudication (IC). In 2022, the Society for Vascular Surgery (SVS) developed appropriate use criteria for the management of IC that used this systematic review as a source of evidence. The objective of this study is to synthesize the findings of the systematic review and identify evidence gaps. METHODS: A comprehensive search of literature databases including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus was conducted from January 1, 2000, to November 30, 2022. Noncomparative and comparative observational studies and randomized controlled trials were included. Included studies evaluated exercise therapy, endovascular or open revascularization for the treatment of IC. Outcomes of interest (freedom from major adverse limb event, health-related quality of life, and walking distance) were compared in various subgroups (age, sex, diabetes, smoking status, anatomical location of disease, and optimal medical therapy). RESULTS: Twenty-six studies reported the outcomes of interest for the evidence map. The general conclusions of the studies that reported freedom from major adverse limb events were that reintervention rates for endovascular therapy at ≥2 years were >20%, major amputation rates were often not reported, and, after endovascular therapy, the 1-month mortality was low (<2%). Quality of life and walking distance data were sparse, limited to only endovascular intervention, and insufficient to make any strong conclusions. CONCLUSIONS: IC in patients with peripheral arterial disease poses a significant socioeconomic and health care burden. Major, consequential gaps exist in the IC literature with respect to the assessment of patient reported outcome measures, standardized measures of walking distance and the comparative effectiveness of initial exercise therapy vs invasive intervention. The evidence gaps identified by the Society for Vascular Surgery appropriate use criteria on IC systematic review serve as a guide for future research efforts to optimize care for this patient population.

Patient and Physician Decisional Factors Regarding Hypercalcemia of Malignancy Treatment: A Novel Mixed-Methods Study.

BACKGROUND: Integrating shared decision making between patients and physicians and incorporating their values and preferences in the development of clinical practice guidelines (CPGs) is of critical importance to optimize CPG implementation and treatment adherence. This applies to many debilitating diseases, including hypercalcemia of malignancy (HCM). OBJECTIVE: Evaluate patient and physician values, preferences, and attitudes to better inform CPGs to treat HCM in adults. METHODS: We followed a mixed-methods approach. We conducted a systematic review using 5 databases to identify studies reporting on patient and physician values, costs and resources, feasibility, acceptability, and equity regarding HCM treatment. We also gathered data from different countries on the cost of multiple treatment modalities. We collected data on outcome prioritization from the CPG Working Group. Similarly, we collected data from patients with HCM regarding outcome prioritization and administered a questionnaire to evaluate their attitudes and perceptions toward treatment as well as treatment acceptability and feasibility. RESULTS: In the systematic review, we included 2 cross-sectional surveys conducted on the same population of physicians who agreed that treating HCM alleviates symptoms and improves quality of life; however, harms and benefits should be thoroughly considered when deciding on the duration of treatment. We also included 2 studies on cost showing that intravenous (IV) bisphosphonate is more cost-effective than a combination of IV bisphosphonate and calcitonin and administration of IV zoledronic acid at home is more cost-effective than other IV bisphosphonates. The cost of zoledronic acid, denosumab, and cinacalcet varied widely among countries and types (brand vs generic). Both the CPG Working Group and patients with HCM agreed that the most important outcomes when deciding on treatment were survival and resolution of HCM, but there was some variability in the ratings for other outcomes. CONCLUSION: Using mixed methods, CPG developers can obtain meaningful information regarding evidence to decision criteria. In the case of HCM CPGs, this approach has provided the required contextual information and supported the development of evidence-based recommendations.

Smoking Cessation Interventions in Indigenous North Americans: A Meta-Narrative Systematic Review.

INTRODUCTION: Indigenous North Americans have the highest cigarette smoking prevalence among all racial and ethnic groups in the United States. We seek to identify effective components of smoking cessation interventions in Indigenous people in the United States associated with favorable cessation outcomes. METHODS: A review of literature studying smoking cessation interventions in Indigenous North Americans (American Indians and Alaska Natives) from January 2010 through August 2021 was completed. The primary objective of this study was to identify components of interventions associated with positive smoking cessation outcomes in Indigenous people. The studies identified were synthesized in a meta-narrative approach. RESULTS: Ten studies out of 608 titles were included (6 randomized trials, 2 single-arm studies, 1 cohort study, and 1 prospective observational study). Five categories of smoking cessation interventions were identified; phone or web-based tools, culturally-tailored interventions, the inclusion of Indigenous study personnel, pharmaceutical cessation aids, and behavioral health interventions. Phone and web tools, cultural tailoring, and inclusion of Indigenous personnel conditions inconsistently influenced smoking cessation. Pharmaceutical aids were viewed favorably among participants. Individualized behavioral counseling sessions were effective at promoting smoking cessation, as was input from local communities in the planning and implementation phases of study. CONCLUSION: A successful smoking cessation intervention in Indigenous North Americans includes Tribal or community input in intervention design and implementation; should provide individualized counseling sessions for participants, and offer access to validated smoking cessation tools including pharmacotherapy. IMPLICATIONS: This study identifies a paucity of smoking interventions utilizing standard of care interventions in Indigenous North Americans. Standard of care interventions including individualized cessation counseling and pharmacotherapy were effective at promoting cessation. The use of novel culturally tailored cessation interventions was not more effective than existing evidence-based care with the exception of including Tribal and local community input in intervention implementation. Future smoking cessation interventions in Indigenous North Americans should prioritize the use of standard of care cessation interventions.

Peripartum Antibiotics Exposure and the Risk of Autoimmune and Autism Disorders in the Offspring.

Background As the use of antibiotics during the peripartum period increases, the incidence of autoimmune disorders and autism spectrum disorders (ASDs) is also increasing. In this study, we aim to assess if antibiotic exposure during the peripartum period affects the incidence of autoimmune diseases and ASD in the offspring. Methods We identified children (< 18 years of age) born in Olmsted County from January 1, 2003 through December 31, 2012. Offspring with celiac disease (CD), inflammatory bowel disease (IBD), or ASD diagnoses were matched to two controls on birth date, index date, mother's age at delivery, and sex. Data from the mother's medical records were retrieved to determine peripartum antibiotics use. Results A total of 242 cases and 484 matched controls were included in this study. Median age at the last follow-up was 11.3 years (range: 0.5-14.9), 73% were males in both groups. Odds of CD diagnosis was not statistically different between vaginal delivery with antibiotics compared with vaginal delivery with no antibiotics (odds ratio [OR] = 0.76, 95% confidence interval [CI]: 0.32-1.85), similarly in IBD (OR = 2.41, 95% CI: 0.53-10.98) and ASD (OR = 1.00, 95% CI:0.55-1.79). Preeclampsia or eclampsia was associated with offspring CD (OR = 3.20, 95% CI: 1.05-9.78). Smoking history and diabetes mellitus were associated with offspring ASD (OR = 1.84, 95% CI: 1.22-2.77 and OR = 2.01, 95% CI: 1.03-3.91, respectively). Conclusion In this cohort, we found no statistically significant association between peripartum antibiotics exposure and the development of CD, IBD, or ASD.

Adjuvant Tyrosine Kinase Inhibitors in Renal Cell Carcinoma: A Concluded Living Systematic Review and Meta-Analysis.

PURPOSE: Multiple large clinical trials have investigated adjuvant tyrosine kinase inhibitors (TKIs) to reduce the risk of cancer recurrence and progression to metastasis in high-risk renal cell carcinoma. We sought to maintain living and interactive evidence on this topic, until a high level of certainty is reached for key clinical outcomes such that further updates become unnecessary and unlikely to change clinical practice. METHODS: We created a living interactive evidence synthesis platform to maintain a continuously updated meta-analysis on TKI monotherapy in adjuvant renal cell carcinoma. We implemented an automated search strategy with weekly updates to identify randomized phase 2 and 3 clinical trials. Study selection, appraisal, and data extraction were done in duplicate. Cumulative meta-analysis was performed using Analyzer Module in Living Interactive Evidence platform. For each outcome (overall survival [OS], disease-free survival [DFS], and all-cause and treatment-related adverse events), we assessed certainty of evidence using GRADE approach and conducted trial sequential analysis. RESULTS: This final update includes five randomized trials including recently updated data from PROTECT trial. Meta-analysis shows that adjuvant TKI monotherapy offers no benefit in OS (hazard ratio, 1.01; 95% CI, 0.91 to 1.12, high certainty) or DFS (hazard ratio, 0.92; 95% CI, 0.86 to 1.00, high certainty) and significantly increases adverse event risk. Lack of benefit was consistent across subgroups including highest-risk patients (test for subgroup differences: P = .32). Optimal information size criteria were met, and there was high certainty of evidence for lack of DFS and OS benefit for adjuvant TKIs. CONCLUSION: There is no guidance on when to stop maintaining a living review. In this example, we used trial sequential analysis and high certainty of evidence (future clinical trials unlikely to change current conclusions) as a benchmark to conclude a living review in view of convincing evidence.

Diagnostic Accuracy of MRI for the Detection of Malignant Peripheral Nerve Sheath Tumors: A Systematic Review and Meta-Analysis.

OBJECTIVE. This systematic review and meta-analysis evaluates the diagnostic accuracy of MRI for differentiating malignant (MPNSTs) from benign peripheral nerve sheath tumors (BPNSTs). MATERIALS AND METHODS. A systematic review of MEDLINE, Embase, Scopus, the Cochrane Library, and the gray literature from inception to December 2019 was performed. Original articles that involved at least 10 patients and that evaluated the accuracy of MRI for detecting MPNSTs were included. Two reviewers independently extracted clinical and radiologic data from included articles to calculate sensitivity, specificity, PPV, NPV, and accuracy. A meta-analysis was performed using a bivariate mixed-effects regression model. Risk of bias was evaluated using QUADAS-2. RESULTS. Fifteen studies involving 798 lesions (252 MPNSTs and 546 BPNSTs) were included in the analysis. Pooled and weighted sensitivity, specificity, and AUC values for MRI in detecting MPNSTs were 68% (95% CI, 52-80%), 93% (95% CI, 85-97%), and 0.89 (95% CI, 0.86-0.92) when using feature combination and 88% (95% CI, 74-95%), 94% (95% CI, 89-96%), and 0.97 (95% CI, 0.95-0.98) using diffusion restriction with or without feature combination. Subgroup analysis, such as patients with neurofibromatosis type 1 (NF1) versus those without NF1, could not be performed because of insufficient data. Risk of bias was predominantly high or unclear for patient selection, mixed for index test, low for reference standard, and unclear for flow and timing. CONCLUSION. Combining features such as diffusion restriction optimizes the diagnostic accuracy of MRI for detecting MPNSTs. However, limitations in the literature, including variability and risk of bias, necessitate additional methodologically rigorous studies to allow subgroup analysis and further evaluate the combination of clinical and MRI features for MPNST diagnosis.

A Living, Interactive Systematic Review and Network Meta-analysis of First-line Treatment of Metastatic Renal Cell Carcinoma.

CONTEXT: Identifying the most effective first-line treatment for metastatic renal cell carcinoma (mRCC) is challenging as rapidly evolving data quickly outdate the existing body of evidence, and current approaches to presenting the evidence in user-friendly formats are fraught with limitations. OBJECTIVE: To maintain living evidence for contemporary first-line treatment for previously untreated mRCC. EVIDENCE ACQUISITION: We have created a living, interactive systematic review (LISR) and network meta-analysis for first-line treatment of mRCC using data from randomized controlled trials comparing contemporary treatment options with single-agent tyrosine kinase inhibitors. We applied an advanced programming and artificial intelligence-assisted framework for evidence synthesis to create a living search strategy, facilitate screening and data extraction using a graphical user interface, automate the frequentist network meta-analysis, and display results in an interactive manner. EVIDENCE SYNTHESIS: As of October 22, 2020, the LISR includes data from 14 clinical trials. Baseline characteristics are summarized in an interactive table. The cabozantinib + nivolumab combination (CaboNivo) is ranked the highest for the overall response rate, progression-free survival, and overall survival, whereas ipilimumab + nivolumab (NivoIpi) is ranked the highest for achieving a complete response (CR). NivoIpi, and atezolizumab + bevacizumab (AteBev) were ranked highest (lowest toxicity) and CaboNivo ranked lowest for treatment-related adverse events (AEs). Network meta-analysis results are summarized as interactive tables and plots, GRADE summary-of-findings tables, and evidence maps. CONCLUSIONS: This innovative living and interactive review provides the best current evidence on the comparative effectiveness of multiple treatment options for patients with untreated mRCC. Trial-level comparisons suggest that CaboNivo is likely to cause more AEs but is ranked best for all efficacy outcomes, except NivoIpi offers the best chance of CR. Pembrolizumab + axitinib and NivoIpi are acceptable alternatives, except NivoIpi may not be preferred for patients with favorable risk. Although network meta-analysis provides rankings with statistical adjustments, there are inherent biases in cross-trial comparisons with sparse direct evidence that does not replace randomized comparisons. PATIENT SUMMARY: It is challenging to decide the best option among the several treatment combinations of immunotherapy and targeted treatments for newly diagnosed metastatic kidney cancer. We have created interactive evidence summaries of multiple treatment options that present the benefits and harms and evidence certainty for patient-important outcomes. This evidence is updated as soon as new studies are published.

A Systematic Review Supporting the American Society for Dermatologic Surgery Guidelines on the Prevention and Treatment of Adverse Events of Injectable Fillers.

BACKGROUND: As the use of injectable skin fillers increase in popularity, an increase in the reported adverse events is expected. OBJECTIVE: This systematic review supports the development of American Society for Dermatologic Surgery practice guideline on the management of adverse events of skin fillers. METHODS AND MATERIALS: Several databases for studies on risk factors or treatments of injection-related visual compromise (IRVC), skin necrosis, inflammatory events, and nodules were searched. Meta-analysis was conducted when feasible. RESULTS: The review included 182 studies. However, IRVC was very rare (1-2/1,000,000 patients) but had poor prognosis with improvement in 19% of cases. Skin necrosis was more common (approximately 5/1,000) with better prognosis (up to 77% of cases showing improvement). Treatments of IRVC and skin necrosis primarily depend on hyaluronidase injections. Risk of skin necrosis, inflammatory events, and nodules may be lower with certain fillers, brands, injection techniques, and volume. Treatment of inflammatory events and nodules with antibiotics, corticosteroids, 5-FU, and hyaluronidase was associated with high response rate (75%-80%). Most of the studies were small and noncomparative, making the evidence certainty very low. CONCLUSION: Practitioners must have adequate knowledge of anatomy, elicit history of skin filler use, and establish preemptive protocols that prepare the clinical practice to manage complications.

Diagnostic accuracy of dual-energy CT for the detection of bone marrow edema in the appendicular skeleton: a systematic review and meta-analysis.

OBJECTIVES: This meta-analysis evaluated the diagnostic accuracy of dual-energy CT (DECT) for detecting bone marrow edema (BME) in the appendicular skeleton. METHODS: A systematic review of MEDLINE, EMBASE, Scopus, the Cochrane Library, and gray literature from inception through January 31, 2020, was performed. Original articles with > 10 patients evaluating the accuracy of DECT for detecting BME in the appendicular skeleton with a reference standard of MRI and/or clinical follow-up were included. Study details were independently extracted by two reviewers. Meta-analysis was performed using a bivariate random-effects model with multivariable meta-regression. Risk of bias (RoB) was evaluated with QUADAS-2. RESULTS: Twenty studies evaluating 790 patients for BME in the appendicular skeleton were included in analysis. The summary sensitivity, specificity, and AUC values for BME in the appendicular skeleton were 86% (95% confidence interval [CI] 82-89%), 93% (95% CI 90-95%), and 0.95, respectively. Quantitative analysis had a higher sensitivity than qualitative analysis on meta-regression (p = 0.01), but no difference in specificity (p = 0.28). No other covariates contributed to variability in accuracy (etiology (trauma vs non-trauma); location (upper vs lower extremity); and RoB). Studies demonstrated generally low or unclear RoB and applicability. Eight studies included index tests with high RoB when quantitative assessments used a retrospective cut-off value. CONCLUSIONS: DECT demonstrates a higher specificity than sensitivity and AUC > 0.9. In scenarios where MRI availability is limited or contraindicated, DECT could be an alternative to MRI for detecting BME in the appendicular skeleton. However, limitations in sources of variability and RoB warrant continued study. KEY POINTS: • Twenty studies evaluating 790 patients for bone marrow edema in the appendicular skeleton with dual-energy CT were included in analysis. • The summary sensitivity, specificity, and AUC values for detecting bone marrow in the appendicular skeleton were 86% (95% confidence interval [CI] 82-89%), 93% (95% CI 90-95%), and 0.95, respectively. • In scenarios where MRI availability is limited or is contraindicated, DECT could be an alternative to MRI for detecting bone marrow edema in the appendicular skeleton.

Diagnostic accuracy of dual-energy CT for detecting bone marrow edema in patients with acute knee injuries: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis evaluated the diagnostic accuracy of dual-energy CT (DECT) for detecting bone marrow edema (BME) in adult patients with acute knee injuries. METHODS: A systematic review of MEDLINE, EMBASE, Scopus, the Cochrane Library, and gray literature was performed from inception to January 31, 2020, using PRISMA-DTA guidelines. The review included studies assessing the diagnostic accuracy of DECT for detecting BME in at least 10 adult patients with acute knee injuries and with an MRI reference standard. Study details were independently extracted by two reviewers. Meta-analysis was performed using a bivariate mixed-effects regression model with subgroup analysis performed to evaluate for sources of variability. Risk of bias (ROB) was evaluated using the QUADAS-2 tool. RESULTS: Eight studies evaluating 267 patients between the ages of 25-54 with acute knee injuries undergoing DECT and MRI were included in analysis. Summary sensitivity, specificity, and AUROC values for BME were 84% (95% confidence interval (CI) 74-91%), 96% (95% CI 93-98%), and 0.97 (95% CI 0.95-0.98), respectively. Bone-based characterization was found to have lower specificity than region-based characterization (83% (57-95%) versus 97 (96-98%), p < 0.05), but no difference in sensitivity. No other statistical differences were identified amongst study subgroups to account for presumed variability amongst studies. Most studies were rated low risk for bias and applicability concerns. CONCLUSION: DECT is specific and accurate for detecting BME in adult patients with acute knee injuries and can be used as an alternative to MRI, particularly when MRI is contraindicated or unavailable.

Society for Vascular Surgery clinical practice guidelines of thoracic endovascular aortic repair for descending thoracic aortic aneurysms.

Thoracic aortic diseases, including disease of the descending thoracic aorta (DTA), are significant causes of death in the United States. Open repair of the DTA is a physiologically impactful operation with relatively high rates of mortality, paraplegia, and renal failure. Thoracic endovascular aortic repair (TEVAR) has revolutionized treatment of the DTA and has largely supplanted open repair because of lower morbidity and mortality. These Society for Vascular Surgery Practice Guidelines are applicable to the use of TEVAR for descending thoracic aortic aneurysm (TAA) as well as for other rarer pathologic processes of the DTA. Management of aortic dissections and traumatic injuries will be discussed in separate Society for Vascular Surgery documents. In general, there is a lack of high-quality evidence across all TAA diseases, highlighting the need for better comparative effectiveness research. Yet, large single-center experiences, administrative databases, and meta-analyses have consistently reported beneficial effects of TEVAR over open repair, especially in the setting of rupture. Many of the strongest recommendations from this guideline focus on imaging before, during, or after TEVAR and include the following: In patients considered at high risk for symptomatic TAA or acute aortic syndrome, we recommend urgent imaging, usually computed tomography angiography (CTA) because of its speed and ease of use for preoperative planning. Level of recommendation: Grade 1 (Strong), Quality of Evidence: B (Moderate). If TEVAR is being considered, we recommend fine-cut (≤0.25 mm) CTA of the entire aorta as well as of the iliac and femoral arteries. CTA of the head and neck is also needed to determine the anatomy of the vertebral arteries. Level of recommendation: Grade 1 (Strong), Quality of Evidence: A (High). We recommend routine use of three-dimensional centerline reconstruction software for accurate case planning and execution in TEVAR. Level of recommendation: Grade 1 (Strong), Quality of Evidence: B (Moderate). We recommend contrast-enhanced computed tomography scanning at 1 month and 12 months after TEVAR and then yearly for life, with consideration of more frequent imaging if an endoleak or other abnormality of concern is detected at 1 month. Level of recommendation: Grade 1 (Strong), Quality of Evidence: B (Moderate). Finally, based on our review, in patients who could undergo either technique (within the criteria of the device's instructions for use), we recommend TEVAR as the preferred approach to treat elective DTA aneurysms, given its reduced morbidity and length of stay as well as short-term mortality. Level of recommendation: Grade 1 (Strong), Quality of Evidence: A (High). Given the benefits of TEVAR, treatment using a minimally invasive approach is largely based on anatomic eligibility rather than on patient-specific factors, as is the case in open TAA repair. Thus, for isolated lesions of the DTA, TEVAR should be the primary method of repair in both the elective and emergent setting based on improved short-term and midterm mortality as well as decreased morbidity.

Verrucous esophageal carcinoma is a unique indolent subtype of squamous cell carcinoma: a systematic review and individual patient regression analysis.

BACKGROUND AND AIMS: Verrucous esophageal carcinoma (VEC) is a rare malignancy that presents a diagnostic challenge. We aim to characterize the clinical and genomic features, tumor behavior, and treatment outcomes of VEC to guide clinical practice. METHODS: We performed a systematic review of the literature and identified additional cases from Massachusetts General Hospital records and The Cancer Genome Atlas (TCGA). We obtained individual VEC patient data and analyzed publicly available clinicogenomic data from TCGA. We performed a regression analysis comparing cases of VEC to esophageal squamous cell carcinoma (ESCC) to identify factors influencing survival. RESULTS: A total of 135 patients were reported in 82 publications, and four unpublished cases from Massachusetts General Hospital (median age 65 years, 69% males, 48% smokers, 33% consumed alcohol). Symptoms were present at diagnosis in 95% of patients, most commonly dysphagia and weight loss. Median symptom onset to diagnosis time was 11.5 months with frequent misdiagnosis as Candida esophagitis. Among VEC cases with pathologic staging, lymph node metastases were rare (5%) compared to ESCC (40%). VEC was genomically characterized by enrichment of SMARCA4 missense mutations and a lack of pathogenic TP53 mutations. Despite its diagnostic elusiveness, in a multivariate regression analysis, VEC was detected at earlier stages (p = < 0.001) compared to ESCC, and advanced stage was the only significant factor affecting survival (p = 0.013). CONCLUSIONS: VEC is a rare, clinically and genomically distinct subtype of ESCC. Recognition and diagnosis of this lesion may allow the pursuit of curative and less morbid treatment strategies.

Anti-CD19 chimeric antigen receptor T-cell therapy in acute lymphocytic leukaemia: a systematic review and meta-analysis.

BACKGROUND: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has shown remarkable activity in patients with refractory or relapsed acute lymphocytic leukaemia. Various anti-CD19 CAR T-cell constructs have been trialled and responses vary widely among different studies. We aimed to systematically analyse the outcomes of patients with acute lymphocytic leukaemia treated with anti-CD19 CAR T cells and identify factors associated with differences in outcomes. METHODS: We did a systematic review and meta-analysis of published and unpublished clinical trials that reported data on the outcomes of adult or paediatric patients that were treated with anti-CD19 CAR T cells for relapsed or refractory B-cell acute lymphocytic leukaemia, reported between Jan 1, 2012, and April 14, 2020. Studies with two patients or fewer were excluded and summary data were extracted from the reports. The primary outcome was the number of patients who had complete remission at any time after anti-CD19 CAR T-cell infusion. This study is not registered in PROSPERO. FINDINGS: From 1160 studies, we identified 40 potentially appropriate studies, 35 (88%) of which met the eligibility criteria and were included in the final analysis (n=953 patients). The pooled complete remission was 80% (95% CI 75·5-84·8) and heterogeneity between studies was moderate (I2=56·96%). In the prespecified subgroup analyses, 195 (75% [95% CI 66·9-82·9, I2=35·22%]) of 263 patients in adult studies and 242 (81% [72·9-87·2, I2=54·45%]) of 346 patients in paediatric studies achieved complete remission, p=0·24. The pooled complete remission did not significantly differ with anti-CD19 CAR T-cell construct type or single-chain variable fragment clone, but was higher with autologous T-cell origin (727 [83%, 78·5-86·5, I2=44·34%] of 901 patients), compared with allogeneic T-cell origin (29 [55%, 30·6-79·0, I2=62·64%] of 52 patients; p=0·018). 242 (26% [95% CI 18·5-34·1]) of 854 patients developed grade 3 or worse cytokine release syndrome and 97 (12% [6·6-19·2]) of 532 developed grade 3 or worse neurotoxicity. There was no difference in the proportion of patients who achieved complete remission or who had cytokine release syndrome or neurotoxicity between different anti-CD19 CAR T-cell constructs. The risk of bias was assessed as low in 17 studies and moderate in 18 studies. INTERPRETATION: The high response rates after anti-CD19 CAR T-cell therapy can be used to guide the use of therapy in patients with relapsed or refractory acute lymphocytic leukaemia. Comparison studies are required to further determine differences in efficacy between different anti-CD19 CAR T-cell constructs in the setting of relapsed or refractory acute lymphocytic leukaemia. FUNDING: National Cancer Institute, National Comprehensive Cancer Network, Mayo Clinic K2R Research Pipeline, and Mayo Clinic Center for Individualized Medicine.

Diagnostic Performance of MRI in the Detection of Renal Lipid-Poor Angiomyolipomas: A Systematic Review and Meta-Analysis.

Background Lipid-poor angiomyolipomas (AMLs) are challenging to differentiate from other renal lesions at imaging and often necessitate biopsy or surgery. If sufficiently accurate, MRI may play a role as a replacement test for biopsy. Purpose To perform a systematic review to evaluate the diagnostic performance of MRI for lipid-poor AMLs in patients with renal masses. Materials and Methods A systematic review of MEDLINE, EMBASE, Scopus, the Cochrane Library, and the "gray literature" (conference proceedings) was performed without language restriction through July 18, 2019, with the assistance of a health sciences librarian. Original articles with more than 10 patients evaluating the diagnostic performance of MRI, with histopathologic findings used as the reference standard, for the diagnosis of lipid-poor AMLs in patients with renal masses were included. Studies including AMLs with macroscopic fat and studies with insufficient data were excluded. Patient, clinical, MRI, and diagnostic performance parameters were independently acquired by two authors. Meta-analysis was performed by using a random-effects or bivariate mixed-effects regression model depending on the number of studies. Risk of bias of individual studies was evaluated by using Quality Assessment of Diagnostic Accuracy Studies-2. Results Twenty-three studies with 2196 patients and 25 contingency tables were included. The pooled sensitivity, specificity, and area under the receiver operating characteristic curve were 83% (95% confidence interval [CI]: 72%, 90%), 90% (95% CI: 84%, 94%), and 0.93 (95% CI: 0.91, 0.95), respectively. Considerable variability was present for several variables, including MRI parameters; however, subgroup analysis did not identify MRI sequence or field strength as sources for variability. All studies were at high risk of bias for index test domain because no reported thresholds were prespecified. Conclusion MRI shows promising accuracy for detecting lipid-poor angiomyolipomas (area under the receiver operating characteristic curve, >0.9), indicating a potential role as a replacement test for biopsy in selected patients. Studies evaluating MRI accuracy with a pragmatic algorithm and prespecified threshold may be helpful to confirm this potential role in the management pathway. © RSNA, 2020 Online supplemental material is available for this article.

A Systematic Review and Meta-Analysis of Transcarotid Artery Revascularization with Dynamic Flow Reversal Versus Transfemoral Carotid Artery Stenting and Carotid Endarterectomy.

BACKGROUND: Transfemoral carotid artery stenting (TFCAS) was introduced as a less invasive option for carotid revascularization in patients at high risk for complications from carotid endarterectomy (CEA). The increased perioperative stroke and death risk of TFCAS has however prevented TFCAS from widespread acceptance as an alternative to CEA in high-risk patients. Recent research suggests that transcarotid artery revascularization (TCAR) may be associated with a low stroke and death risk and potentially meet the needs of patients at high surgical risk. We aimed to estimate the 30-day risk of stroke or death of TCAR and compare it to TFCAS and CEA. METHODS: We searched PubMed, Cochrane, Embase, and Scopus for studies of patients treated with TCAR. Meta-analysis was conducted when appropriate. A logistic-normal random-effects model with logit transformation was used to estimate the pooled event rates after TCAR. Pooled Mantel-Haenszel odds ratios (ORs) of events comparing TCAR to TFCAS and CEA were calculated using a fixed-effects model. Heterogeneity among studies was quantified with the chi-squared statistic of the likelihood ratio (LR) test that compares the random-effects and fixed-effects models. RESULTS: Nine nonrandomized studies evaluating 4012 patients who underwent TCAR were included. The overall 30-day risks after TCAR were stroke/death, 1.89% (95% confidence interval [CI]: 1.50, 2.37); stroke, 1.34% (95% CI: 1.02,1.75); death, 0.76% (95% CI: 0.56, 1.08); myocardial infarction (MI), 0.60% (95% CI: 0.23, 1.59); stroke/death/MI, 2.20% (95% CI: 1.31, 3.69); cranial nerve injury (CNI), 0.31% (95% CI: 0.12, 0.83). The failure rate of TCAR was 1.27% (95% CI: 0.32, 4.92). Two nonrandomized studies suggested that TCAR was associated with lower risk of stroke and death as compared with TFCAS (1.33% vs. 2.55%, OR: 0.52, 95% CI: 0.36, 0.74 and 0.76% vs. 1.46%, OR: 0.52, 95% CI: 0.32, 0.84, respectively). Four nonrandomized studies suggested that TCAR was associated with a lower risk of CNI (0.54% and 1.84%, OR: 0.52, 95% CI: 0.36, 0.74) than CEA, but no statistically significant difference in the 30-day risk of stroke, stroke/death, or stroke/death/MI. CONCLUSIONS: Among patients undergoing TCAR with dynamic flow reversal for carotid stenosis the 30-day risk of stroke or death was low. The perioperative stroke/death rate of TCAR was similar to that of CEA while CNI risk was lower. Larger prospective studies are needed to account for confounding factors and provide higher certainty.

Diagnostic accuracy of 99mTc-sestamibi SPECT/CT for detecting renal oncocytomas and other benign renal lesions: a systematic review and meta-analysis.

PURPOSE: The primary objectives of this systematic review and meta-analysis were to evaluate the diagnostic accuracy of 99mTc-sestamibi SPECT/CT for detecting renal oncocytoma versus (1) all other renal lesions and (2) chromophobe renal cell carcinoma (ChrRCC) alone. METHODS: A systematic review of MEDLINE, EMBASE, Scopus, the Cochrane Library, and the Gray Literature was performed. Original articles with > 5 patients evaluating oncocytomas versus other renal lesions with SPECT/CT using a pathological reference standard were included. Patient, clinical, imaging, and performance parameters were independently acquired by two reviewers. Meta-analysis was performed using a bivariate mixed-effects regression model. RESULTS: Four articles with a total of 117 renal lesions were included in analysis. The pooled and weighted sensitivity and specificity values of 99mTc-sestamibi SPECT/CT for detecting (1) renal oncocytoma versus other renal lesions were 92% (95% CI 72-98%) and 88% (95% CI 79-94%), respectively, and (2) 89% and 67%, respectively, for renal oncocytoma versus ChrRCC. The specificity for the detecting the oncocytoma-ChrRCC spectrum was 96% (95% CI 84-99%). The sensitivity and specificity for detecting benign versus malignant renal lesions were 86% (95% CI 66-95%) and 90% (95% CI 80-95%), and 88% and 95% when HOCTs were characterized as benign. All reporting studies used a cut-off tumor-to-background renal parenchyma radiotracer uptake ratio of > 0.6 for positive studies. CONCLUSION: 99mTc-sestamibi SPECT/CT demonstrates a high sensitivity and specificity for characterizing benign and low-grade renal lesions. This test can help improve the diagnostic confidence for patients with indeterminate renal masses being considered for active surveillance.

Submaximal angioplasty in the treatment of patients with symptomatic ICAD: a systematic review and meta-analysis.

INTRODUCTION: Management approaches for intracranial atherosclerosis include medical, surgical, or endovascular treatment. Among endovascular treatments, recent studies have stated that submaximal angioplasty (SA) may offer considerable benefits and be a promising alternative to aggressive medical therapyand/or stenting in the treatment of intracranial atherosclerotic disease (ICAD). OBJECTIVE: To investigate the rates of periprocedural and long-term cerebrovascular accidents, mortality, and restenosis in patients with symptomatic ICAD who were treated with SA. METHODS: An electronic database search was performed for relevant studies that reported clinical outcomes of patients with ICAD following SA. Outcomes of interest were incidence of transient ischemic attack, intracerebral hemorrhage, stroke, and mortality in the periprocedural period and at 1 year. The periprocedural period was defined as the time from SA until 30 days after the procedure. Technical success and restenosis rates after the procedure were also analyzed. RESULTS: A total of 19 studies with 777 patients were identified. The technical success rate was 93% (95% CI 85% to 98%). The incidence of 30-day and 1-year stroke (all types) was 3% (95% CI 1% to 5%) and 5% (95% CI 4% to 8%), respectively. Thirty-day and 1-year mortality was found to be 1% (95% CI 0% to 2%) and 2% (95% CI 0% to 4%), respectively. The combined incidence of stroke or death was 5% (95% CI 3% to 8%) at 30 days, and 9% (95% CI 7% to 12%) at 1 year. CONCLUSION: The findings suggest that SA might be a promising alternative treatment in the treatment of symptomatic ICAD due to its favorable technical profile, periprocedural safety, and long-term efficacy. A randomized clinical trial is warranted to compare the safety and efficacy of SA with 'gold standard' medical treatment.

Direct Oral Factor Xa Inhibitors for the Treatment of Acute Cancer-Associated Venous Thromboembolism: A Systematic Review and Network Meta-analysis.

OBJECTIVE: To explore the efficacy and safety of direct oral factor Xa inhibitors in the treatment of cancer-associated acute venous thromboembolism (VTE). PATIENTS AND METHODS: MEDLINE, CENTRAL (Cochrane Central Register of Controlled Trials), and Embase databases were searched for trials comparing direct oral anticoagulants (DOACs) to dalteparin for the management of cancer-associated acute VTE. Databases were searched from inception to September 19, 2018. A network meta-analysis using both frequentist and Bayesian methods was performed to analyze VTE recurrence and major and clinically relevant nonmajor bleeding. RESULTS: We identified 3 randomized controlled trials, at low risk of bias, that enrolled 1739 patients with cancer-associated VTE. Direct comparison revealed a lower rate of VTE recurrence in DOAC compared with dalteparin groups (odds ratio [OR], 0.48; 95% CI, 0.24-0.96; I2=46%). Indirect comparison suggested that apixaban had greater reduction in VTE recurrence compared with dalteparin (OR, 0.10; 95% CI, 0.01-0.82) but not rivaroxaban or edoxaban. Apixaban also had the highest probability of being ranked most effective. By direct comparisons, there was an increased likelihood of major bleeding in the DOAC group compared with dalteparin (OR, 1.70; 95% CI, 1.04-2.78). Clinically relevant nonmajor bleeding did not differ. Indirect estimates were imprecise. Subgroup analyses in gastrointestinal cancers suggested that dalteparin may have the lowest risk of bleeding, whereas estimates in urothelial cancer were imprecise. CONCLUSION: Direct oral anticoagulants appear to lower the risk of VTE recurrence compared with dalteparin while increasing major bleeding. Apixaban may be associated with the lowest risk of VTE recurrence compared with the other DOACs.