Kristine M. Thomsen

Polyomavirus polymerase chain reaction as a surrogate marker of polyomavirus-associated nephropathy

Background. Polyomavirus-associated nephropathy (PVAN) is a significant cause of allograft loss after renal transplantation. A noninvasive assay that can guide the evaluation of PVAN would be of clinical value. We compared the utility of BK virus (BKV) polymerase chain reaction (PCR) and urine cytology in screening for concurrent PVAN. Methods. We used PCR to test urine and plasma samples from renal recipients simultaneously for BKV DNA. Additionally, we tested urine samples for decoy cells. Sample results were correlated with biopsy-proven PVAN. Receiver-operator characteristic curves were used to determine viral load thresholds associated with concurrent PVAN. Results. In this cross-sectional study, BKV viruria, viremia, and urinary decoy cells were detected in 24%, 9%, and 13% of renal recipients, respectively. Among 114 patients who had renal allograft biopsy, four (3.5%) were diagnosed with PVAN. Using pathology as gold standard for the diagnosis of PVAN, BKV viremia threshold of >1.6E+04 copies/mL had 100% sensitivity, 96% specificity, 50% positive predictive value, and 100% negative predictive value. A BKV viruria threshold of >2.5E+07 copies/mL had 100% sensitivity, 92% specificity, 31% positive predictive value, and 100% negative predictive value. In contrast, urine decoy cells had 25% sensitivity, 84% specificity, 5% positive predictive value, and 97% negative predictive value for the diagnosis of concurrent PVAN. Conclusion. BKV PCR may be a clinically useful noninvasive test to identify renal recipients with concurrent PVAN. BKV DNA >1.6E+04 copies/mL of plasma and >2.5E+07 copies/mL of urine were highly associated with concurrent PVAN whereas a negative PCR test makes the diagnosis of PVAN highly unlikely.

Beneficial Plasma Exchange Response in Central Nervous System Inflammatory Demyelination

BACKGROUND Plasma exchange (PLEX) is a beneficial rescue therapy for acute, steroid-refractory central nervous system inflammatory demyelinating disease (CNS-IDD). Despite the approximately 45% PLEX response rate reported among patients with CNS-IDD, determinants of interindividual differences in PLEX response are not well characterized. OBJECTIVE To perform an exploratory analysis of clinical, radiographic, and serological features associated with beneficial PLEX response. DESIGN Historical cohort study. SETTING Neurology practice, Mayo Clinic College of Medicine, Rochester, Minnesota. Patients All Mayo Clinic patients treated with PLEX between January 5, 1999, and November 12, 2007, for a steroid-refractory CNS-IDD attack. MAIN OUTCOME MEASURE The PLEX response in attack-related, targeted neurological deficit(s) assessed within the 6-month period following PLEX. RESULTS We identified 153 patients treated with PLEX for a steroid-refractory CNS-IDD, of whom 90 (59%) exhibited moderate to marked functional neurological improvement within 6 months following treatment. Pre-PLEX clinical features associated with a beneficial PLEX response were shorter disease duration (P = .02) and preserved deep tendon reflexes (P = .001); post-PLEX variables included a diagnosis of relapsing-remitting multiple sclerosis (P = .008) and a lower Expanded Disability Status Scale score (P < .001) at last follow-up. Plasma exchange was less effective for patients with multiple sclerosis who subsequently developed a progressive disease course (P = .046). Radiographic features associated with a beneficial PLEX response were presence of ring-enhancing lesions (odds ratio = 4.00; P = .03) and/or mass effect (odds ratio = 3.00; P = .02). No association was found between neuromyelitis optica-IgG serostatus and PLEX response. CONCLUSIONS We have identified clinical and radiographic features that may aid in identifying patients with fulminant, steroid-refractory CNS-IDD attacks who are more likely to respond to PLEX.

Perivenous demyelination: association with clinically defined acute disseminated encephalomyelitis and comparison with pathologically confirmed multiple sclerosis

Distinction between acute disseminated encephalomyelitis and acute multiple sclerosis is often clinically difficult. Perivenous demyelination is the pathological hallmark of acute disseminated encephalomyelitis, whereas confluent demyelination is the hallmark of acute multiple sclerosis. We investigated whether perivenous demyelination versus confluent demyelination distinguishes acute disseminated encephalomyelitis from multiple sclerosis. Patients with perivenous demyelination (n = 13; median age 43 years, range 5-67) on brain biopsy and/or autopsy, ascertained retrospectively, were compared with a cohort with confluent demyelination only (n = 91; 84% multiple sclerosis, 16% isolated syndrome at follow-up; median age 39 years, range 10-69). Clinical presentation, course and the International Paediatric Multiple Sclerosis Study Group clinical criteria for acute disseminated encephalomyelitis were assessed in both cohorts. Among the perivenous demyelination cohort, 10 patients had only perivenous demyelination and three also had confluent demyelination. All but one patient with perivenous demyelination only had a monophasic course, whereas two of three with both types had a relapsing course. The perivenous demyelination cohort was more likely than the confluent demyelination cohort to present with encephalopathy (P < 0.001), depressed level of consciousness (P < 0.001), headache (P < 0.001), meningismus (P = 0.04), cerebrospinal fluid pleocytosis (P = 0.04) or multifocal enhancing magnetic resonance imaging lesions (P < 0.001). A distinct pattern of cortical microglial activation and aggregation without associated cortical demyelination was found among six perivenous demyelination patients, all of whom had encephalopathy and four of whom had depressed level of consciousness. This pattern of cortical pathology was not observed in the confluent demyelination cohort, even in one patient with depressed level of consciousness. Clinical criteria were 80% sensitive and 91% specific for pathologically defined acute disseminated encephalomyelitis (perivenous demyelination), but misdiagnosed acute disseminated encephalomyelitis among 9% of patients with confluent demyelination and multiple sclerosis diagnosis at last follow-up. Perivenous demyelination is associated with meningoencephalopathic presentations and a monophasic course. Depressed level of consciousness is a more specific clinical criterion for pathologically confirmed acute disseminated encephalomyelitis than encephalopathy, which over-diagnosed acute disseminated encephalomyelitis among multiple sclerosis patients. A distinct pattern of cortical microglial activation without cortical demyelination may be the pathological correlate of depressed level of consciousness in acute disseminated encephalomyelitis. Although pathological evidence of perivenous demyelination may be superior to clinical criteria for diagnosing acute disseminated encephalomyelitis, the co-occurrence of perivenous and confluent demyelination in some individuals suggests pathogenic overlap between acute disseminated encephalomyelitis and multiple sclerosis and misclassification even with biopsy.

β-Lactam and Fluoroquinolone Combination Antibiotic Therapy for Bacteremia Caused by Gram-Negative Bacilli

ABSTRACT The role of combination antibiotic therapy with a beta-lactam and a fluoroquinolone for bacteremia caused by gram-negative bacilli, to our knowledge, has not been previously described. Much of the previous study of combination therapy has included beta-lactams and aminoglycosides. We conducted a large retrospective cohort study to evaluate 28-day all-cause mortality in patients with monomicrobial bacteremia due to aerobic gram-negative bacilli who received either a combination of beta-lactams and fluoroquinolones or beta-lactam monotherapy. We enrolled adult patients admitted to Mayo Clinic hospitals from 1 January 2001 to 31 October 2006 in the study. After stratification of patients by Pitt bacteremia scores, we used Cox regression models to estimate the hazard ratios (HR) for 28-day all-cause mortality after adjusting for the propensity to receive combination therapy. We identified 398 and 304 unique patients with bacteremia caused by gram-negative bacilli who received single and combination antibiotic therapy, respectively. In less severely ill patients with Pitt bacteremia scores of <4, combination therapy was associated with lower 28-day mortality than single therapy (4.2% [9 of 214] versus 8.8% [28 of 319]; adjusted HR, 0.44; 95% confidence interval [CI], 0.20 to 0.98; P = 0.044). In critically ill patients with Pitt bacteremia scores of ≥4, there was no difference in 28-day mortality between combination and single therapy (25.6% [23 of 90] versus 27.8% [22 of 79]; adjusted HR, 0.87; 95% CI, 0.47 to 1.62; P = 0.660). These findings were consistent for 14-day all-cause mortality. In this large cohort, we found for the first time that combination therapy with beta-lactams and fluoroquinolones was associated with a reduction in 28-day all-cause mortality among less severely ill patients with bacteremia caused by gram-negative bacilli.

Impact of analysis of frozen-section margin on reoperation rates in women undergoing lumpectomy for breast cancer: Evaluation of the National Surgical Quality Improvement Program data

BACKGROUND Reoperation for positive margins after lumpectomy for breast cancer is common. Intraoperative analysis of frozen-section (FS) margins permits immediate re-excision, avoiding reoperation. The aim of this study was to compare reoperation rates between an institution using routine FS analysis of all margins and the National Surgical Quality Improvement Program (NSQIP) data. METHODS We designed a retrospective cohort analysis comparing the NSQIP data from a FS single institution with the national NSQIP data from 2006 to 2010. Women undergoing lumpectomy for cancer were identified (N = 24,217), and reoperation rates were compared by the use of χ(2) analyses and multivariable logistic regression. During this time period, NSQIP did not differentiate between reoperations for complications or oncologic reasons. Reoperation rates for mastectomy patients (N = 21,734) and lumpectomy patients without cancer (N = 2,777) over the same time period were analyzed as controls, because reoperations after these procedures likely would be for reasons other than positive margins. RESULTS The 30-day reoperation rate after lumpectomy for cancer was greater nationally than at the FS institution (13.2% vs 3.6%, P < .001). Multivariable analysis showed that patients in the national NSQIP data set were over four times as likely to undergo reoperation as those at the FS institutions (odds ratio 4.19). The reoperation rates were similar between the two, both for patients undergoing mastectomy (4.7% vs 4.5%, P = .84) and those undergoing lumpectomy for benign diagnosis (2.9% vs 5.9%, P = .39). CONCLUSION Intraoperative FS margin analysis decreases the number of reoperations for patients undergoing breast conservation for breast cancer. This technique has important implications for patient satisfaction and cost of care.

Inferior vena cava filters in trauma patients: efficacy, morbidity, and retrievability.

BACKGROUND Thromboembolic events are potentially devastating sources of morbidity in trauma patients. With increasing experience and the introduction of retrievable devices, there has been a renewed interest in inferior vena cava (IVC) filters in trauma patients. METHODS The records for consecutive trauma patients undergoing IVC filter placement during the years 2001 to 2005 were reviewed, and clinical, demographic, and procedural data were evaluated for associations with thromboembolic events and device complications. RESULTS During the study years, 226 trauma patients had IVC filters inserted, and 140 of these patients (62%) had retrievable IVC filters placed. Six patients (3%) had a pulmonary embolism with the filter in place, and two patients (1%) had a pulmonary embolism after filter removal. The most common complication was thrombosis in 27 patients (12%), with clinically significant thrombus occurring in 15 patients (7%). There was no association between the type of filter (permanent or retrievable) or the brand of retrievable filter and thrombosis. Specific risk factors for thrombosis could not be identified. Retrievable filters were successfully removed in 61% of patients with retrievable filters. Technical success rate was 97% in those patients who underwent attempted removal. Removal was completed at a median of 21 days (range, 2-292 days). CONCLUSIONS Retrievable IVC filters in trauma patients are safe, but complications do occur with thrombosis being the most common. Retrieval has a high technical success rate when attempted. However, a significant number of trauma patients are lost to follow-up and this may impact the utilization of retrievable filters in this patient population.

Perioperative Cardiovascular Risk of Prior Coronary Stent Implantation Among Patients Undergoing Noncardiac Surgery

BACKGROUND Previous studies have observed high rates of perioperative cardiovascular events in patients with coronary stents undergoing noncardiac surgery (NCS). It is uncertain whether this finding reflects an independent association. OBJECTIVES The goal of this study was to assess the independent relationship between prior coronary stent implantation and the occurrence of perioperative major adverse cardiac and cerebrovascular events (MACCE) and bleeding and its relation with time from stenting to NCS. METHODS A total of 24,313 NCS cases at the Mayo Clinic (Rochester, Minnesota) from 2006 through 2011 were included in the study; 1,120 (4.6%) cases involved patients with coronary stents. MACCE was defined as death, myocardial infarction, cardiac arrest, or stroke. Age-adjusted odds ratios (aORs) were calculated after propensity adjustment for Revised Cardiac Risk Index factors and other conventional risk factors. RESULTS The 30-day MACCE rates were 3.7% and 1.5% in stented and unstented patients, respectively (p < 0.001). The risk of MACCE was largely related to the time from stent implantation to NCS, indicating substantially elevated risk in the first year after stenting (aOR: 2.59; 95% confidence interval [CI]: 1.36 to 4.94) but not thereafter (aOR: 0.89; 95% CI: 0.59 to 1.36). Bleeding displayed a similar pattern, indicating elevated risk in the first year after stenting (aOR: 2.23; 95% CI: 1.55 to 3.21) but not thereafter (aOR: 1.07; 95% CI: 0.89 to 1.28). Subgroup analysis in patients with known stent type found that the increased risk of both MACCE and bleeding >1 month after stent implantation was not limited to only those with drug-eluting stents. CONCLUSIONS This study found that prior coronary stent implantation is an independent risk factor for MACCE and bleeding when time from stenting to NCS is <1 year, both in patients with bare-metal and drug-eluting stents.

Risk Factors for 30-Day Unplanned Readmission and Major Perioperative Complications After Spine Fusion Surgery in Adults: A Review of the National Surgical Quality Improvement Program Database.

Study Design. Retrospective review of a prospective cohort. Objective. The aim of the study was to determine the patient characteristics and surgical procedure factors related to increased rates of 30-day unplanned readmission and major perioperative complications after spinal fusion surgery, and the association between unplanned readmission and major complications. Summary of Background Data. Reducing unplanned readmissions can reduce the cost of healthcare. Payers are implementing penalties for 30-day readmissions after discharge. There is limited data regarding the current rates and risk factors for unplanned readmission and major complications related to spinal fusion surgery. Methods. Spine fusion patients were identified using the 2012 and 2013 American College of Surgeons National Surgical Quality Improvement Program Participant User File. Rates of readmissions within 30 days after spine fusion surgery were calculated using the person-years method. Cox proportional hazards models were used to assess the independent associations of spine surgical procedure types, diagnoses, patient profiles, and major perioperative complications with unplanned related readmissions. Independent risk factors for major complications were assessed by multivariable logistic regression. Results. Of the 18,602 identified patients, there was a 5.2% overall major perioperative complication rate. There was a rate of 4.4% per 30 person-days for unplanned readmissions related to index surgery. Independent risk factors for both readmissions and major perioperative complications included combined anterior and posterior surgery, diagnosis of solitary tumor, older age, and higher American Society of Anesthesiologists class. Patients with deep/organ surgical site infection carried higher risk of having unplanned readmission, followed by pulmonary embolism, acute renal failure, and stroke/cerebral vascular accident with neurological deficit. Conclusion. This study provides benchmark rates of 30-day readmission based on diagnosis and procedure codes from a high-quality database for adult spinal fusion patients and showed increased rates of 30-day unplanned readmission and major perioperative complications for patients with specific risk factors. Targeted preoperative planning on modifiable risk factors with proportional reimbursement may promote higher-quality healthcare. Level of Evidence: 3

Evaluation for Clinical Predictors of Positive Temporal Artery Biopsy in Giant Cell Arteritis

PURPOSE To examine the clinical predictors of a positive temporal artery biopsy (TAB) among patients suspected of having giant cell arteritis. PATIENTS AND METHODS We conducted a retrospective study of all consecutive patients who underwent TAB by a single surgeon (K.L.R.) at the Department of Oral Maxillofacial Surgery from April 30, 2002, to June 29, 2006. The medical records were reviewed for the clinical symptoms, laboratory findings, biopsy results, and final diagnosis. The variables of interest as predictors of positive biopsy findings were analyzed using logistic regression analysis. RESULTS During the study period, 82 patients underwent TAB. Histologic evidence of arteritis was present in 22 patients (26.8%). Two (2.4%) were diagnosed with giant cell arteritis clinically but had negative TAB findings. The patients presenting with weight loss or jaw claudication were more likely to have a positive TAB finding (odds ratio 4.50, 95% confidence interval 1.45 to 13.93; and odds ratio 3.71, 95% confidence interval 1.28 to 10.76, respectively). No laboratory findings were predictive of a positive TAB finding. Prednisone use before TAB also was not associated with a decreased likelihood of a positive finding. CONCLUSIONS Patients suspected of having giant cell arteritis were more likely to have a positive TAB finding if they presented with weight loss or jaw claudication. In the present series, corticosteroid therapy before biopsy did not affect the rate of positive TAB findings.

Humoral Pattern II Multiple Sclerosis Pathology Not Associated With Neuromyelitis Optica IgG

The pathogenic relationship between neuromyelitis optica (NMO) and multiple sclerosis (MS) continues to be debated despite mounting evidence that these are distinct entities. 1, 2, 3 NMO-IgG, which targets the water channel protein aquaporin-4 (AQP4), is the first confirmed serum biomarker for any form of central nervous system inflammatory demyelinating disease and reliably distinguishes NMO from MS and other neurological diseases. Four immunopathological patterns (IP I-IV) have been described in early active MS lesions. 4 Some investigators have interpreted humoral MS IP II as having an immunopathogenic link with NMO because both share complement and immunoglobulin deposition and have a greater likelihood than other forms of MS to respond favorably to plasma exchange therapy.4,5 Here we report the NMO-IgG status of a cohort of patients with biopsy-proven early active lesions consistent with MS.