Neurobrucellosis Presenting with Motor Damage or Hearing Loss, and Use of Steroids are Associated with a Higher Risk of Sequelae or Relapse: A Systematic Review of Individual Participant Data.

BACKGROUND: Neurobrucellosis presents diverse clinical challenges and risks of long-term complications. OBJECTIVE: We aimed to assess the relationship between the duration of antibiotic therapy, clinical factors, and the outcome of neurobrucellosis with a case report combined with a systematic review of the literature. METHODS: We present a case of a 31 years-old man successfully treated at our Institution. We then searched Ovid MEDLINE, Embase and Scopus for articles that encompassed neurobrucellosis cases, duration of treatment, and outcome. The primary outcome was to assess an association between the duration of treatment and the risk of sequelae or relapses. Univariate, multivariate and sensitivity analysis were carried out to define which variables affect​ed​ the clinical outcome. Quality assessment was performed using a dedicated tool. RESULTS: A total of 123 studies were included, totaling 221 patients. Median duration of treatment was 4 months (IQR 3 - 6), 69% patients recovered without sequelae, 27% had sequelae. Additionally, five patients had a relapse, and 4 patients died. Multivariate analysis found that the duration of treatment, age, and the use of ceftriaxone were not associated with a higher risk of sequelae or relapses. A significant association was found for corticosteroids use (OR 0.39, 95% IC 0.16 - 0.96, p = 0.038), motor impairment (OR 0.29, 95% IC 0.14 - 0.62, p = 0.002), and hearing loss (OR 0.037, 95% IC 0.01 - 0.11, p < 0.001). CONCLUSIONS: This study highlights the variability in clinical presentations and treatment approaches for neurobrucellosis. Patients with factors indicating higher sequelae risk require meticulous follow-up.

Association between basic life support and survival in sports-related sudden cardiac arrest: a meta-analysis.

AIMS: To evaluate the association of basic life support with survival after sports-related sudden cardiac arrest (SR-SCA). METHODS AND RESULTS: In this systematic review and meta-analysis, a search of several databases from each database inception to 31 July 2021 without language restrictions was conducted. Studies were considered eligible if they evaluated one of three scenarios in patients with SR-SCA: (i) bystander presence, (ii) bystander cardiopulmonary resuscitation (CPR), or (iii) bystander automated external defibrillator (AED) use and provided information on survival. Risk of bias was evaluated using Risk of Bias in Non-randomized Studies of Interventions. The primary outcome was survival at the longest follow up. The meta-analysis was conducted using the random-effects model. The Grading of Recommendations Assessment, Development, and Evaluations (GRADE) approach was used to rate certainty in the evidence. In total, 28 non-randomized studies were included. The meta-analysis showed significant benefit on survival in all three groups: bystander presence [odds ratio (OR) 2.55, 95% confidence interval (CI) 1.48-4.37; I2 = 25%; 9 studies-988 patients], bystander CPR (OR 3.84, 95% CI 2.36-6.25; I2 = 54%; 23 studies-2523 patients), and bystander AED use (OR 5.25, 95% CI 3.58-7.70; I2 = 16%; 19 studies-1227 patients). The GRADE certainty of evidence was judged to be moderate. CONCLUSION: In patients with SR-SCA, bystander presence, bystander CPR, and bystander AED use were significantly associated with survival. These results highlight the importance of witness intervention and encourage countries to develop their first aid training policy and AED installation in sport settings.

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.

An artificial intelligence approach for predicting death or organ failure after hospitalization for COVID-19: development of a novel risk prediction tool and comparisons with ISARIC-4C, CURB-65, qSOFA, and MEWS scoring systems.

BACKGROUND: We applied machine learning (ML) algorithms to generate a risk prediction tool [Collaboration for Risk Evaluation in COVID-19 (CORE-COVID-19)] for predicting the composite of 30-day endotracheal intubation, intravenous administration of vasopressors, or death after COVID-19 hospitalization and compared it with the existing risk scores. METHODS: This is a retrospective study of adults hospitalized with COVID-19 from March 2020 to February 2021. Patients, each with 92 variables, and one composite outcome underwent feature selection process to identify the most predictive variables. Selected variables were modeled to build four ML algorithms (artificial neural network, support vector machine, gradient boosting machine, and Logistic regression) and an ensemble model to generate a CORE-COVID-19 model to predict the composite outcome and compared with existing risk prediction scores. The net benefit for clinical use of each model was assessed by decision curve analysis. RESULTS: Of 1796 patients, 278 (15%) patients reached primary outcome. Six most predictive features were identified. Four ML algorithms achieved comparable discrimination (P > 0.827) with c-statistics ranged 0.849-0.856, calibration slopes 0.911-1.173, and Hosmer-Lemeshow P > 0.141 in validation dataset. These 6-variable fitted CORE-COVID-19 model revealed a c-statistic of 0.880, which was significantly (P < 0.04) higher than ISARIC-4C (0.751), CURB-65 (0.735), qSOFA (0.676), and MEWS (0.674) for outcome prediction. The net benefit of the CORE-COVID-19 model was greater than that of the existing risk scores. CONCLUSION: The CORE-COVID-19 model accurately assigned 88% of patients who potentially progressed to 30-day composite events and revealed improved performance over existing risk scores, indicating its potential utility in clinical practice.

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.

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.

Clinical Presentation and Outcomes of Pregnant Women With Coronavirus Disease 2019: A Systematic Review and Meta-analysis.

BACKGROUND: Descriptions of coronavirus disease 2019 (COVID-19) have focused on the nonpregnant adult population. This study aims to describe the clinical characteristics and perinatal outcomes of COVID-19 in pregnancy. METHODS: We searched databases from December 2019 to 30 April 2020. Eligible studies reported clinical characteristics, radiological findings, and/or laboratory testing of pregnant women during infection. Data were pooled across studies using a random-effects model. RESULTS: Twenty-four studies (136 women) were included. The most common symptoms were fever (62.9%) and cough (36.8%). Laboratory findings included elevated C-reactive protein (57%) and lymphocytopenia (50%). Ground-glass opacity was the most common radiological finding (81.7%). Preterm birth rate was 37.7% and cesarean delivery rate was 76%. There was 1 maternal death. There were 2 fetal COVID-19 cases. CONCLUSIONS: The clinical picture in pregnant women with COVID-19 did not differ from the nonpregnant population; however, the rate of preterm birth and cesarean delivery are considerably higher than international averages.

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.

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 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 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 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.

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.

Diagnostic Accuracy of Limited MRI Protocols for Detecting Radiographically Occult Hip Fractures: A Systematic Review and Meta-Analysis.

OBJECTIVE. This systematic review and meta-analysis aimed to evaluate the diagnostic accuracy of limited MRI protocols for detecting radiographically occult proximal femoral fractures. MATERIALS AND METHODS. A systematic review of MEDLINE, Embase, Scopus, the Cochrane Library, and the gray literature through November 15, 2019, was performed. Original articles with 10 or more patients evaluating limited MRI protocols for the diagnosis of radiographically occult proximal femoral fractures compared with multiparametric MRI with or without clinical outcome as the reference standard were included in the analysis. Patient, clinical, MRI, and performance parameters were independently acquired by two reviewers. Meta-analysis was performed using a bivariate mixed-effects regression model. RESULTS. Eleven studies with 938 patients and 247 proximal femoral fractures met inclusion criteria, and five of these studies were included in the meta-analysis. The pooled and weighted summary sensitivity and specificity and the area under the summary ROC curve for limited MRI protocols in detecting radiographically occult hip fractures were 99% (95% CI, 91-100%), 99% (95% CI, 97-100%), and 1 (95% CI, 0.99-1), respectively. The aggregate sensitivity and specificity values for a single-plane T1-weighted sequence only, STIR sequence only, T1-weighted and STIR sequences, and T2-weighted sequence only were as follows: 97% (89/92) and 100% (76/76), 99% (126/127) and 99% (865/873), 100% (118/118) and 99% (867/874), and 86% (51/59) and 97% (137/141), respectively. Sensitivity was 100% (58/58) when images were acquired on 3-T scanners only and 99% (284/288) when interpreted only by certified radiologists. The mean scanning time for the limited MRI protocols was less than 5 minutes. CONCLUSION. Limited MRI protocols can be used as the standard of care in patients with a suspected but radiographically occult hip fracture. A protocol composed of coronal T1-weighted and STIR sequences is 100% sensitive.

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.

Natural History of Adrenal Incidentalomas With and Without Mild Autonomous Cortisol Excess: A Systematic Review and Meta-analysis.

Background: Adrenal incidentalomas are mostly benign nonfunctioning adrenal tumors (NFATs) or adenomas causing mild autonomous cortisol excess (MACE), but their natural history is unclear. Purpose: To summarize the follow-up data of adults with NFAT or MACE to determine the proportions of tumor growth, malignant transformation, and incident changes in hormone function; the prevalence of incident cardiometabolic comorbid conditions; and mortality. Data Sources: MEDLINE, Embase, Cochrane, and Scopus (January 1990 to February 2019) and bibliographies of identified articles, without language restriction. Study Selection: Studies that included 20 or more conservatively managed patients with NFAT or MACE and reported outcomes at baseline and after at least 12 months of follow-up. Data Extraction: Pairs of reviewers extracted outcomes and assessed methodological quality. Data Synthesis: Thirty-two studies reported outcomes of 4121 patients with NFAT or MACE, 61.5% of whom were women; the mean age was 60.2 years, and mean follow-up was 50.2 months. Mean tumor growth was 2 mm over 52.8 months. Clinically significant tumor enlargement (≥10 mm) occurred in 2.5% of patients, and none developed adrenal cancer. Clinically overt hormone excess was unlikely to develop (<0.1%) in patients with NFAT or MACE. Only 4.3% of patients with NFAT developed MACE, and preexisting MACE was unlikely to resolve (<0.1%). Hypertension, obesity, dyslipidemia, and type 2 diabetes were highly prevalent (60.0%, 42.0%, 33.7%, and 18.1% of patients, respectively) and were more likely to develop and worsen in MACE than NFAT. New cardiovascular events were more prevalent in MACE (15.5%) than NFAT (6.4%). Mortality was 11.2% and was similar between NFAT and MACE. Limitation: Evidence was scarce, and definitions of MACE and comorbid conditions were heterogeneous. Conclusion: During follow-up, NFAT and MACE do not show clinically relevant changes in size or hormonal function, but they may carry an increased risk for cardiometabolic comorbid conditions. Primary Funding Source: None.

Effects of Weight-Loss Medications on Cardiometabolic Risk Profiles: A Systematic Review and Network Meta-analysis.

BACKGROUND & AIMS: We performed a systematic review and network meta-analysis to evaluate the overall and comparative effects of weight-loss medications approved by the Food and Drug Administration for long-term use on cardiometabolic risk profiles of obese adults. METHODS: We performed a systematic literature review through February 28, 2017 to identify randomized clinical trials of the effects of Food and Drug Administration-approved weight-loss medications (ie, orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide) administered to obese adults for 1 year or more, compared with placebo or another active agent. Outcomes of interest included changes in blood glucose (fasting blood glucose [FBG] and hemoglobin A1c), cholesterol profile (low-density lipoprotein and high-density lipoproteins), blood pressure (BP; systolic/diastolic), and waist circumference (WC). We performed pair-wise and network meta-analyses with outcomes reported as weighted and standardized mean differences. Quality of evidence was rated using GRADE (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: In a meta-analysis of 28 randomized controlled trials (29,018 participants; median body mass index, 36.1 kg/m2), we associated weight-loss medications with a modest decrease in FBG (weighted mean difference, 4.0 mg/dL; 95% confidence interval, -4.4 to -3.6 mg/dL) and WC (weighted mean difference, reduction of 3.3 cm; 95% confidence interval, -3.5 to -3.1 cm), without clinically meaningful changes in systolic/diastolic BP or cholesterol profile vs placebo (standardized mean difference <0.2); effects varied among drugs. Phentermine-topiramate use was associated with a substantial decrease in WC and a modest decrease in FBG, hemoglobin A1c, and BP, and had minimal effect on cholesterol. Liraglutide use was associated with a substantial decrease in FBG, hemoglobin A1c, and WC, and a minimal effect on BP and cholesterol. Naltrexone-bupropion use was associated with moderate increase in high-density lipoprotein cholesterol, but had a minimal effect on FBG and WC. Orlistat use was associated with a decrease in low-density lipoprotein and high-density lipoprotein cholesterol. No drug improved all cardiometabolic risk factors. CONCLUSIONS: In a systematic review and network meta-analysis, we found Food and Drug Administration-approved weight-loss medications to have only modest positive effects on cardiometabolic risk profile. Further research is needed to evaluate the long-term cardiometabolic benefits of these medications. PROSPERO: CRD42016039486.

Predictors of Recurrent Hospitalizations and the Importance of These Hospitalizations for Subsequent Mortality After Incident Transient Ischemic Attack.

BACKGROUND: We examined predictors of recurrent hospitalizations and the importance of these hospitalizations for subsequent mortality after incident transient ischemic attacks (TIA) that have not yet been investigated. METHODS: Adults hospitalized for TIA from 2000 through 2017 were examined for recurrent hospitalizations, days, and percentage of time spent hospitalized and long-term mortality. RESULTS: Of 266 patients hospitalized for TIA, 122 died, 212 had 826 anycondition hospitalization (59 from TIA-related conditions) corresponding to 3384 inpatient days during 1693 person-years of follow-up. Of 42 patient-level characteristics, age greater than or equal to 65 years (Incidence rate ratio [IRR] 1.75, 95% confidence interval [CI] 1.19-2.55), current smoking (IRR 2.15, 95% CI 1.39-3.33), concurrent heart failure (IRR 1.81, 95% CI 1.17-2.80) or anemia (IRR 1.90, 95% CI 1.40-2.48), and no prescription statin (IRR 1.45, 95% CI 1.04-2.03, P = .0289) emerged as significant predictors of anycondition rehospitalization. All these variables except heart failure remained significant predictors of TIA-related rehospitalizations. All-cause mortality was significantly increased after each hospitalization from anycondition (hazard ratio [HR] 1.32, 95% CI 1.26-1.39), TIA-related condition (HR 1.72; 95% CI 1.28-2.30), and per each day (HR 1.05, 95% CI 1.04-1.05) and per 1% of follow-up time spent hospitalized from anycondition (HR 1.45, 95% CI 1.34-1.58). CONCLUSIONS: Older age, current tobacco smoking, concurrent heart failure or anemia, and no prescription statin, easily measured patient-level characteristics, identifies patients with TIA at high risk for recurrent hospitalizations and the burden of these hospitalizations predicts subsequent mortality.

Steroid Refractory Chronic Graft-Versus-Host Disease: Cost-Effectiveness Analysis.

Given the increasing incidence of chronic graft-versus-host disease (cGVHD) and its rapidly escalating costs due to many lines of drug treatments, we aimed to perform a meta-analysis to assess the comparative effectiveness of various treatment options. Using these results, we then conducted a cost-effectiveness analysis for the frequently utilized agents in steroid-refractory cGVHD. We searched for studies examining tacrolimus, sirolimus, rituximab, ruxolitinib, hydroxychloroquine, imatinib, bortezomib, ibrutinib, extracorporeal photopheresis, pomalidomide, and methotrexate. Studies with a median follow-up period shorter than 6 months and enrolling fewer than 5 patients were excluded. Meta-analysis for overall and organ system-specific GVHD response (overall response [ORR], complete response [CR], and partial response [PR]) was conducted for each intervention. Cost per CR and cost per CR + PR were calculated as the quotient of the 6-month direct treatment cost by CR and CR + PR. Forty-one studies involving 1047 patients were included. CR rates ranged from 7% to 30% with rituximab and methotrexate, respectively, and ORR ranged from 30% to 85% with tacrolimus and ruxolitinib, respectively. Cost per CR ranged from US$1,187,657 with ruxolitinib to US$680 with methotrexate. Cost per ORR ranged from US$453 for methotrexate to US$242,236 for ibrutinib. The most cost-effective strategy was methotrexate for all of the organ systems. Pomalidomide was found to be the least cost-effective treatment for eye, gastrointestinal, fascia/joint, skin, and oral GVHD, and imatinib was found to be the least cost-effective treatment for liver and extracorporeal photopheresis for lung GVHD. We observed huge cost-effectiveness differences among available agents. Attention to economic issues when treating cGVHD is important to recommend how treatments should be sequenced, knowing that many patients will cycle through available agents.

The cortisol stress response induced by surgery: A systematic review and meta-analysis.

OBJECTIVE: Surgery is a stressor that can be categorized by duration and severity and induces a systemic stress response that includes increased adrenal cortisol production. However, the precise impact of surgical stress on the cortisol response remains to be defined. DESIGN: We performed a systematic review and meta-analysis to assess the cortisol stress response induced by surgery and to stratify this response according to different parameters. METHODS: We conducted a comprehensive search in several databases from 1990 to 2016. Pairs of reviewers independently selected studies, extracted data and evaluated the risk of bias. Cortisol concentrations were standardized, pooled in meta-analysis and plotted over time. RESULTS: We included 71 studies reporting peri-operative serum cortisol measurements in 2953 patients. The cortisol response differed substantially between moderately/highly invasive and minimally invasive surgical procedures. Minimally invasive procedures did not show a peri-operative cortisol peak, whereas more invasive surgeries caused a cortisol surge that was more pronounced in older subjects, women and patients undergoing open surgery and general anaesthesia. The duration of the procedure and the use of etomidate for induction of anaesthesia did not affect the cortisol response. CONCLUSIONS: The peri-operative cortisol stress response is dynamic and influenced by patient-specific, surgical and anaesthetic features. However, the available evidence is derived from highly heterogeneous studies, with only two of 71 studies measuring cortisol by mass spectrometry, which currently prevents a precise and reproducible definition of this response.