Imaging assessment of spine infection.

This article comprehensively reviews current imaging concepts in spinal infection with primary focus on infectious spondylodiscitis (IS) as well as the less common entity of facet joint septic arthritis (FSA). This review encompasses the multimodality imaging appearances (radiographs, CT, MRI, and nuclear imaging) of spinal infection-both at initial presentation and during treatment-to aid the radiologist in guiding diagnosis and successful management. We discuss the pathophysiology of spinal infection in various patient populations (including the non-instrumented and postoperative spine) as well as the role of imaging-guided biopsy. We also highlight several non-infectious entities that can mimic IS (both clinically and radiologically) that should be considered during image interpretation to avoid misdiagnosis. These potential mimics include the following: Modic type 1 degenerative changes, acute Schmorl's node, neuropathic spondyloarthropathy, radiation osteitis, and inflammatory spondyloarthropathy (SAPHO syndrome).

Musculoskeletal trauma and artificial intelligence: current trends and projections.

Musculoskeletal trauma accounts for a significant fraction of emergency department visits and patients seeking urgent care, with a high financial cost to society. Diagnostic imaging is indispensable in the workup and management of trauma patients. However, diagnostic imaging represents a complex multifaceted system, with many aspects of its workflow prone to inefficiencies or human error. Recent technological innovations in artificial intelligence and machine learning have shown promise to revolutionize our systems for providing medical care to patients. This review will provide a general overview of the current state of artificial intelligence and machine learning applications in different aspects of trauma imaging and provide a vision for how such applications could be leveraged to enhance our diagnostic imaging systems and optimize patient outcomes.

Computed tomography-based body composition profile as a screening tool for geriatric frailty detection.

OBJECTIVE: To assess prevalence of CT imaging-derived sarcopenia, osteoporosis, and visceral obesity in clinically frail and prefrail patients and determine their association with the diagnosis of frailty. MATERIALS AND METHODS: This cross-sectional study was constructed using our institution's pelvic trauma registry and ambulatory database registry. The study included all elderly pelvic trauma patients and ambulatory outpatients between May 2016 and March 2020 who had a comprehensive geriatric assessment and CT abdomen/pelvis within 1 year from the date of the assessment. Patients were dichotomized in prefrail or frail groups. The study excluded patients with history of metastatic disease or malignancy requiring chemotherapy. RESULTS: The study cohort consisted of 151 elderly female and 65 male patients. Each gender population was subdivided into frail (114 female [75%], 51 male [78%]) and prefrail (37 female [25%], 14 male [22%]) patients. CT-imaging-derived diagnosis of osteoporosis (odds ratio, 2.5; 95% CI: 1.2-5.5) and sarcopenia (odds ratio, 2.6; 95% CI: 1.2-5.6) were associated with frailty in females, but did not reach statistical significance in males. BMI and subcutaneous adipose tissue at L3 level were statistically lower in the frail male group compared to the prefrail group. BMI showed strong correlation with the subcutaneous area at the L3 level in both genders (Spearman's coefficient of 0.8, p < 0.001). Hypoalbuminemia and visceral obesity were not associated with frailty in either gender. CONCLUSION: This proof-of-concept study demonstrates the feasibility of using CT-derived body-composition parameters as a screening tool for frailty, which can offer an opportunity for early medical intervention.

Nontraumatic Spinal Cord Compression: MRI Primer for Emergency Department Radiologists.

The occurrence of acute myelopathy in a nontrauma setting constitutes a medical emergency for which spinal MRI is frequently ordered as the first step in the patient's workup. The emergency department radiologist should be familiar with the common differential diagnoses of acute myelopathy and be able to differentiate compressive from noncompressive causes. The degree of spinal cord compression and presence of an intramedullary T2-hyperintense signal suggestive of an acute cord edema are critical findings for subsequent urgent care such as surgical decompression. Importantly, a delay in diagnosis may lead to permanent disability. In the spinal canal, compressive myelopathy can be localized to the epidural, intradural extramedullary, or intramedullary anatomic spaces. Effacement of the epidural fat and the lesion's relation to the thecal sac help to distinguish an epidural lesion from an intradural lesion. Noncompressive myelopathy manifests as an intramedullary T2-hyperintense signal without an underlying mass and has a wide range of vascular, metabolic, inflammatory, infectious, and demyelinating causes with seemingly overlapping imaging appearances. The differential diagnosis can be refined by considering the location of the abnormal signal intensity within the cord, the longitudinal extent of the disease, and the clinical history and laboratory findings. Use of a compartmental spinal MRI approach in patients with suspected nontraumatic spinal cord injury helps to localize the abnormality to an epidural, intradural extramedullary, or intramedullary space, and when combined with clinical and laboratory findings, aids in refining the diagnosis and determining the appropriate surgical or nonsurgical management.Online supplemental material is available for this article.©RSNA, 2019.

A simplified classification of proximal femoral fractures improves accuracy, confidence, and inter-reader agreement of hip fracture classification by radiology residents.

PURPOSE: To demonstrate the effect of teaching a simplified treatment-based classification of proximal femoral fractures on the accuracy, confidence, and inter-reader agreement of radiology residents. The authors hypothesize that these measures will improve after viewing an educational presentation. MATERIALS AND METHODS: Three radiology residents independently classified 100 operative proximal femoral fractures, both before and after viewing a 45-min educational video describing the simplified classification scheme, with a washout period of at least 12 weeks between sessions. Based on the gold standard established by consensus of two radiologists and an orthopedic trauma surgeon utilizing intraoperative fluoroscopic imaging, operative reports, and pre-procedural imaging, accuracy of classification was calculated for each reader before and after viewing the educational video. Reader confidence was recorded on a 0-10 scale, and inter-reader agreement was calculated with Fleiss's kappa. McNemar's test was used to compare accuracy, a paired t test was used to compare confidence, and the Z-test was used to compare kappa values after bootstrapping to determine the standard error of the mean. RESULTS: The study cohort included 60/100 females, with a mean age of 76.6 years. The pooled classification accuracy was initially 65%, which improved to 80% in the second reading session after viewing the educational video (p < 0.0001). Confidence improved from 6.9 initially to 8.6 (p < 0.0001). Inter-reader agreement improved from a kappa of 0.45 (moderate agreement) to 0.74 (substantial agreement) (p < 0.0001). CONCLUSIONS: A simplified treatment-based classification of proximal femoral fractures is easily taught to radiology residents and resulted in increased accuracy, increased inter-reader agreement, and increased reader confidence.

The Impact of Donor and Recipient Renal Dysfunction on Cardiac Allograft Survival: Insights Into Reno-Cardiac Interactions.

BACKGROUND: Renal dysfunction (RD) is a potent risk factor for death in patients with cardiovascular disease. This relationship may be causal; experimentally induced RD produces findings such as myocardial necrosis and apoptosis in animals. Cardiac transplantation provides an opportunity to investigate this hypothesis in humans. METHODS AND RESULTS: Cardiac transplantations from the United Network for Organ Sharing registry were studied (n = 23,056). RD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m(2). RD was present in 17.9% of donors and 39.4% of recipients. Unlike multiple donor characteristics, such as older age, hypertension, or diabetes, donor RD was not associated with recipient death or retransplantation (age-adjusted hazard ratio [HR] = 1.00, 95% confidence interval [CI] 0.94-1.07, P = .92). Moreover, in recipients with RD the highest risk for death or retransplantation occurred immediately posttransplant (0-30 day HR = 1.8, 95% CI 1.54-2.02, P < .001) with subsequent attenuation of the risk over time (30-365 day HR = 0.92, 95% CI 0.77-1.09, P = .33). CONCLUSIONS: The risk for adverse recipient outcomes associated with RD does not appear to be transferrable from donor to recipient via the cardiac allograft, and the risk associated with recipient RD is greatest immediately following transplant. These observations suggest that the risk for adverse outcomes associated with RD is likely primarily driven by nonmyocardial factors.

A combined-biomarker approach to clinical phenotyping renal dysfunction in heart failure.

BACKGROUND: Differentiating heart failure (HF) induced renal dysfunction (RD) from intrinsic kidney disease is challenging. It has been demonstrated that biomarkers such as B-type natriuretic peptide (BNP) or the blood urea nitrogen to creatinine ratio (BUN/creat) can identify high- vs low-risk RD. Our objective was to determine if combining these biomarkers could further improve risk stratification and clinical phenotyping of patients with RD and HF. METHODS AND RESULTS: A total of 908 patients with a discharge diagnosis of HF were included. Median values were used to define elevated BNP (>1296 pg/mL) and BUN/creat (>17). In the group without RD, survival was similar regardless of BNP and BUN/creat (n = 430, adjusted P = .52). Similarly, in patients with both a low BNP and BUN/creat, RD was not associated with mortality (n = 250, adjusted hazard ratio [HR] = 1.0, 95% confidence interval [CI] 0.6-1.6, P = .99). However, in patients with both an elevated BNP and BUN/creat those with RD had a cardiorenal profile characterized by venous congestion, diuretic resistance, hypotension, hyponatremia, longer length of stay, greater inotrope use, and substantially worse survival compared with patients without RD (n = 249, adjusted HR = 1.8, 95% CI 1.2-2.7, P = .008, P interaction = .005). CONCLUSIONS: In the setting of decompensated HF, the combined use of BNP and BUN/creat stratifies patients with RD into groups with significantly different clinical phenotypes and prognosis.

Cross-Residency Radiologic/Pathologic Correlation Curriculum: Teaching Correlation of Surgical Specimens With Imaging.

The College of American Pathologists expects pathologists to attain competency in radiologic/pathologic correlation, including correlation of histopathologic findings with imaging findings. While pathology residents appreciate the importance of radiologic/pathologic correlation, their lack of experience and confidence in interpreting imaging studies deters them from obtaining specimen radiographs and reviewing preoperative imaging studies. Formal training in this domain is lacking. A cross-residency curriculum was developed to help pathology residents build basic skills in the correlation of surgical specimens with preoperative imaging and specimen radiographs. Didactic sessions were prepared by 3 pairs of radiology and pathology residents with guidance from radiology and pathology attendings in the subspecialty areas of breast, musculoskeletal, and head and neck. The authors describe the development, implementation, and assessment of the curriculum. A total of 20 pathology residents attended the sessions, with 7 completing both the pre- and postintervention surveys. These residents gained confidence in their ability to interpret specimen radiographs and to select specimens to evaluate with radiography. They gained an appreciation of the importance of collaboration with radiologists in evaluating specimens and of viewing preoperative imaging studies to guide gross examination and dissection. They reported obtaining specimen radiographs and viewing preoperative imaging studies more frequently after attending the sessions. Innovative solutions such as this cross-residency educational initiative offer a potential solution to fulfill the radiologic/pathologic correlation competency standard for pathology residents and may be replicable by other residency programs and academic institutions.

Imaging of iatrogenic oesophageal injuries using optimized CT oesophageal leak protocol: pearls and pitfalls.

Iatrogenic injury to the oesophagus is a serious complication which is increasingly seen in clinical practice secondary to expansion and greater acceptability of surgical and endoscopic oesophageal procedures. Morbidity and mortality following such injury is high. This is mostly due to an inflammatory response to gastric contents in the mediastinum, and the negative intrathoracic pressures that may further draw out oesophageal contents into the mediastinum leading to mediastinitis. Subsequently, pulmonary complications such as pneumonia or abscess may ensue leading to rapid clinical deterioration. Optimized and timely cross-sectional imaging evaluation is necessary for early and aggressive management of these complications. The goal of this review is to make the radiologist aware of the importance of early and accurate identification of postoperative oesophageal injury using optimized CT imaging protocols and use of oral contrast. Specifically, it is critical to differentiate benign post-operative findings, such as herniated viscus or redundant anastomosis, from clinically significant postoperative complications as this helps guide appropriate management. Advantages and drawbacks of other diagnostic methods, such as contrast oesophagogram, are also discussed.

Familial dilated cardiomyopathy diagnosis is commonly overlooked at the time of transplant listing.

BACKGROUND: The prevalence and clinical characteristics of familial dilated cardiomyopathy (FDCM) among patients with end stage heart failure (ESHF) has yet to be elucidated. We sought to determine the prevalence of FDCM in ESHF in the United Network for Organ Sharing (UNOS) registry and compare this with center specific data from a large tertiary teaching hospital. Patients with a banked UNOS diagnosis of dilated cardiomyopathy (DCM) whose care originated at our center then underwent detailed pedigree analysis in order to determine the true prevalence of FDCM. METHODS AND RESULTS: A total of 16,091 patients with DCM from all centers were identified in the UNOS registry of whom 492 carried the diagnosis of FDCM (3.1%). Patients with the diagnosis of FDCM tended to be younger (42 versus 49 years old in idiopathic dilated cardiomyopathy (IDCM), p=0.001), were less likely to have diabetes (7.8% versus 16.5% in IDCM, p<0.0001), had slightly lower creatinine (1.2 versus 1.4 in IDCM, p=0.0001) and were more likely to have a panel reactive antibody level ≥ 20% (62.1% versus 44.7% in IDCM, p<0.0001). Consecutive living adult patients with ESHF were identified from the UNOS registry that had been treated at the Yale Center for Advanced Heart Failure (YCAHF). After excluding all diagnoses that did not include any form of non-ischemic DCM, 73 patients met the inclusion criteria. Center-specific UNOS data showed pre-pedigree analysis diagnosis of FDCM in 4.12% of patients (3 out of 73), consistent with that found in the UNOS database for all centers. However, after detailed family history and pedigree analysis, 19 (26%) of 73 patients were found to have FDCM, while the remaining 54 were found to have IDCM. Echocardiographic findings including mitral regurgitation, mitral valve annulus and left ventricular end diastolic dimension were not significantly different between groups when adjusting for multiple testing. CONCLUSIONS: The diagnosis of FDCM was missed in the majority of patients with end stage heart failure enrolled in the UNOS database, as sampled from a large, tertiary care teaching hospital in the United States. Echocardiographic findings are unlikely to aid in the differentiation between DCM and FDCM. Detailed pedigree analysis can successfully identify undiagnosed FDCM and should be encouraged prior to transplant listing as it has important implications for early detection and treatment of disease in family members.

Rapid and Highly Accurate Prediction of Poor Loop Diuretic Natriuretic Response in Patients With Heart Failure.

BACKGROUND: Removal of excess sodium and fluid is a primary therapeutic objective in acute decompensated heart failure and commonly monitored with fluid balance and weight loss. However, these parameters are frequently inaccurate or not collected and require a delay of several hours after diuretic administration before they are available. Accessible tools for rapid and accurate prediction of diuretic response are needed. METHODS AND RESULTS: Based on well-established renal physiological principles, an equation was derived to predict net sodium output using a spot urine sample obtained 1 or 2 hours after loop diuretic administration. This equation was then prospectively validated in 50 acute decompensated heart failure patients using meticulously obtained timed 6-hour urine collections to quantify loop diuretic-induced cumulative sodium output. Poor natriuretic response was defined as a cumulative sodium output of <50 mmol, a threshold that would result in a positive sodium balance with twice-daily diuretic dosing. Following a median dose of 3 mg (2-4 mg) of intravenous bumetanide, 40% of the population had a poor natriuretic response. The correlation between measured and predicted sodium output was excellent (r=0.91; P<0.0001). Poor natriuretic response could be accurately predicted with the sodium prediction equation (area under the curve =0.95, 95% confidence interval 0.89-1.0; P<0.0001). Clinically recorded net fluid output had a weaker correlation (r=0.66; P<0.001) and lesser ability to predict poor natriuretic response (area under the curve =0.76, 95% confidence interval 0.63-0.89; P=0.002). CONCLUSIONS: In patients being treated for acute decompensated heart failure, poor natriuretic response can be predicted soon after diuretic administration with excellent accuracy using a spot urine sample.

Hypochloremia and Diuretic Resistance in Heart Failure: Mechanistic Insights.

BACKGROUND: Recent epidemiological studies have implicated chloride, rather than sodium, as the driver of poor survival previously attributed to hyponatremia in heart failure. Accumulating basic science evidence has identified chloride as a critical factor in renal salt sensing. Our goal was to probe the physiology bridging this basic and epidemiological literature. METHODS AND RESULTS: Two heart failure cohorts were included: (1) observational: patients receiving loop diuretics at the Yale Transitional Care Center (N=162) and (2) interventional pilot: stable outpatients receiving ≥80 mg furosemide equivalents were studied before and after 3 days of 115 mmol/d supplemental lysine chloride (N=10). At the Yale Transitional Care Center, 31.5% of patients had hypochloremia (chloride ≤96 mmol/L). Plasma renin concentration correlated with serum chloride (r=-0.46; P<0.001) with no incremental contribution from serum sodium (P=0.49). Hypochloremic versus nonhypochloremic patients exhibited renal wasting of chloride (P=0.04) and of chloride relative to sodium (P=0.01), despite better renal free water excretion (urine osmolality 343±101 mOsm/kg versus 475±136; P<0.001). Hypochloremia was associated with poor diuretic response (odds ratio, 7.3; 95% confidence interval, 3.3-16.1; P<0.001). In the interventional pilot, lysine chloride supplementation was associated with an increase in serum chloride levels of 2.2±2.3 mmol/L, and the majority of participants experienced findings such as hemoconcentration, weight loss, reduction in amino terminal, pro B-type natriuretic peptide, increased plasma renin activity, and increased blood urea nitrogen to creatinine ratio. CONCLUSIONS: Hypochloremia is associated with neurohormonal activation and diuretic resistance with chloride depletion as a candidate mechanism. Sodium-free chloride supplementation was associated with increases in serum chloride and changes in several cardiorenal parameters. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02031354.

Evidence of Mild Liver Dysfunction Identifies Stable Heart Failure Outpatients with Reversible Renal Dysfunction.

BACKGROUND: In decompensated heart failure (HF), reversible renal dysfunction (RD) is more frequently observed in patients with mild liver dysfunction likely due to the shared pathophysiologic factors involved. The objective of this study was to determine if these findings also apply to stable HF outpatients. METHODS: Patients in the Beta-Blocker Evaluation of Survival Trial (BEST) were studied. Improvement in renal function (IRF) was defined as a 20% improvement in the estimated glomerular filtration rate from baseline to 3 months. RESULTS: Elevated bilirubin (BIL), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were significantly associated with signs of congestion or poor perfusion. IRF occurred in 12.0% of all patients and was more common in those with elevated BIL (OR = 1.5, p = 0.003), ALT (OR = 1.4, p = 0.01), and AST (OR = 1.4, p = 0.01). In a model containing all 3 liver parameters and baseline characteristics, including markers of congestion/poor perfusion, BIL (OR = 1.6, p = 0.001) and ALT (OR = 1.7, p < 0.001) were independently associated with IRF. CONCLUSIONS: Biochemical evidence of mild liver dysfunction is significantly associated with IRF in stable HF outpatients. Given the widespread availability and low cost of these markers, additional research is necessary to determine the utility of these parameters in identifying patients with reversible RD who may benefit from cardiorenal interventions.

Influence of age-related versus non-age-related renal dysfunction on survival in patients with left ventricular dysfunction.

Normal aging results in a predictable decrease in glomerular filtration rate (GFR), and low GFR is associated with worsened survival. If this survival disadvantage is directly caused by the low GFR, as opposed to the disease causing the low GFR, the risk should be similar regardless of the underlying mechanism. Our objective was to determine if age-related decreases in estimated GFR (eGFR) carry the same prognostic importance as disease-attributable losses in patients with ventricular dysfunction. We analyzed the Studies Of Left Ventricular Dysfunction limited data set (n = 6,337). The primary analysis focused on determining if the eGFR-mortality relation differed by the extent to which the eGFR was consistent with normal aging. Mean eGFR was 65.7 ml/min/1.73 m(2) (SD = 19.0). Across the range of age in the population (27 to 80 years), baseline eGFR decreased by 0.67 ml/min/1.73 m(2)/year (95% confidence interval [CI] 0.63 to 0.71). The risk of death associated with eGFR was strongly modified by the degree to which the low eGFR could be explained by aging (p for interaction <0.0001). For example, in a model incorporating the interaction, uncorrected eGFR was no longer significantly related to mortality (adjusted hazard ratio 1.0 per 10 ml/min/1.73 m(2), 95% CI 0.97 to 1.1, p = 0.53), whereas a disease-attributable decrease in eGFR above the median carried significant risk (adjusted hazard ratio 2.8, 95% CI 1.6 to 4.7, p <0.001). In conclusion, in the setting of left ventricular dysfunction, renal dysfunction attributable to normal aging had a limited risk for mortality, suggesting that the mechanism underlying renal dysfunction is critical in determining prognosis.

Diversity of envelope genes from an uncloned stock of SIVmac251.

AIDS vaccine and pathogenesis research will benefit from a more diverse array of cloned SIV challenge stocks from which to choose. Toward this end, 20 envelope genes were cloned from an extensively used, primary stock of uncloned SIVmac251. Each of the 20 clones had a unique sequence. Their translated sequences differed by as many as 26 amino acids from one another and by as many as 45 amino acids from the commonly used clone SIVmac239. Envelope sequences up to and including the membrane-spanning domain were exchanged into the infectious pathogenic SIVmac239 clone and virus stocks were produced by HEK293T cell transfection. Seventeen of the 20 recombinants were replication competent. The infectivities per ng p27 of the 17 new replication-competent recombinants in C8166-SEAP cells and in TZM-bl cells ranged from minus 32-fold to plus 7.6-fold relative to SIVmac239. A range of sensitivities to neutralization by sCD4 and by sera from SIV-infected macaques was observed but none was as sensitive to these neutralizing agents as SIVmac316, the highly macrophage-competent derivative of SIVmac239. Four strains that were most sensitive to sCD4 inhibition were also among the most sensitive to antibody-mediated neutralization. None of the new recombinant viruses replicated as well as SIVmac316 in primary alveolar macrophage cultures from rhesus monkeys but three of the strains did exhibit significant levels of delayed replication in these primary macrophages, reaching peak levels of virus production of ≥50 ng/ml p27 compared to 600-800 ng/ml p27 with SIVmac316. These new SIV clones are being contributed to the NIH AIDS Reagent Repository and are available to the scientific community.