Isolated Ocular Mpox without Skin Lesions, United States.

We report a case of a 53-year-old HIV-negative patient in San Francisco, California, USA, with no classic mpox prodromal symptoms or skin lesions who experienced fulminant, vision-threatening scleritis, keratitis, and uveitis. Deep sequence analysis identified monkeypox virus RNA in the aqueous humor. We confirmed the virus on the cornea and sclera by PCR.

Discriminating Bacterial and Viral Infection Using a Rapid Host Gene Expression Test.

OBJECTIVES: Host gene expression signatures discriminate bacterial and viral infection but have not been translated to a clinical test platform. This study enrolled an independent cohort of patients to describe and validate a first-in-class host response bacterial/viral test. DESIGN: Subjects were recruited from 2006 to 2016. Enrollment blood samples were collected in an RNA preservative and banked for later testing. The reference standard was an expert panel clinical adjudication, which was blinded to gene expression and procalcitonin results. SETTING: Four U.S. emergency departments. PATIENTS: Six-hundred twenty-three subjects with acute respiratory illness or suspected sepsis. INTERVENTIONS: Forty-five-transcript signature measured on the BioFire FilmArray System (BioFire Diagnostics, Salt Lake City, UT) in ~45 minutes. MEASUREMENTS AND MAIN RESULTS: Host response bacterial/viral test performance characteristics were evaluated in 623 participants (mean age 46 yr; 45% male) with bacterial infection, viral infection, coinfection, or noninfectious illness. Performance of the host response bacterial/viral test was compared with procalcitonin. The test provided independent probabilities of bacterial and viral infection in ~45 minutes. In the 213-subject training cohort, the host response bacterial/viral test had an area under the curve for bacterial infection of 0.90 (95% CI, 0.84-0.94) and 0.92 (95% CI, 0.87-0.95) for viral infection. Independent validation in 209 subjects revealed similar performance with an area under the curve of 0.85 (95% CI, 0.78-0.90) for bacterial infection and 0.91 (95% CI, 0.85-0.94) for viral infection. The test had 80.1% (95% CI, 73.7-85.4%) average weighted accuracy for bacterial infection and 86.8% (95% CI, 81.8-90.8%) for viral infection in this validation cohort. This was significantly better than 68.7% (95% CI, 62.4-75.4%) observed for procalcitonin (p < 0.001). An additional cohort of 201 subjects with indeterminate phenotypes (coinfection or microbiology-negative infections) revealed similar performance. CONCLUSIONS: The host response bacterial/viral measured using the BioFire System rapidly and accurately discriminated bacterial and viral infection better than procalcitonin, which can help support more appropriate antibiotic use.

Endogenous Candida endophthalmitis: Who is really at risk?

OBJECTIVES: The Infectious Disease Society of America recommends that all patients with candidemia undergo a dilated retinal exam to exclude endogenous Candida endophthalmitis. Our objective was to determine if there are significant risk factors in candidemic patients for developing endogenous Candida endophthalmitis METHODS: We conducted a retrospective study of all candidemic patients at three academic medical centers between 2012 and 2017. We extracted risk factors for Candida endophthalmitis based on prior literature and compared them between patients with and without endophthalmitis. We then built a multivariate logistic regression model to assess which ones were significant. RESULTS: We found 771 patients with candidemia. 120 (15.6%) of these patients were diagnosed with Candida endophthalmitis. In our logistic regression analysis, central venous catheter presence (OR 8.35), intravenous drug use (OR 4.76), immunosuppression (OR 2.40), total parenteral nutrition recipient (OR 2.28), race (OR 1.65), age (OR 1.02), and gender (OR 0.57) were risk factors for developing Candida endophthalmitis. Additionally, Candida albicans was more likely to result in Candida endophthalmitis (OR 1.86). CONCLUSIONS: This cohort represents the largest study of risk factors for candidemic patients who developed endogenous Candida endophthalmitis. Based on our findings, clinicians should develop targeted and cost-effective strategies for endophthalmitis screening.

Validation of a host response test to distinguish bacterial and viral respiratory infection.

BACKGROUND: Distinguishing bacterial and viral respiratory infections is challenging. Novel diagnostics based on differential host gene expression patterns are promising but have not been translated to a clinical platform nor extensively tested. Here, we validate a microarray-derived host response signature and explore performance in microbiology-negative and coinfection cases. METHODS: Subjects with acute respiratory illness were enrolled in participating emergency departments. Reference standard was an adjudicated diagnosis of bacterial infection, viral infection, both, or neither. An 87-transcript signature for distinguishing bacterial, viral, and noninfectious illness was measured from peripheral blood using RT-PCR. Performance characteristics were evaluated in subjects with confirmed bacterial, viral, or noninfectious illness. Subjects with bacterial-viral coinfection and microbiologically-negative suspected bacterial infection were also evaluated. Performance was compared to procalcitonin. FINDINGS: 151 subjects with microbiologically confirmed, single-etiology illness were tested, yielding AUROCs 0•85-0•89 for bacterial, viral, and noninfectious illness. Accuracy was similar to procalcitonin (88% vs 83%, p = 0•23) for bacterial vs. non-bacterial infection. Whereas procalcitonin cannot distinguish viral from non-infectious illness, the RT-PCR test had 81% accuracy in making this determination. Bacterial-viral coinfection was subdivided. Among 19 subjects with bacterial superinfection, the RT-PCR test identified 95% as bacterial, compared to 68% with procalcitonin (p = 0•13). Among 12 subjects with bacterial infection superimposed on chronic viral infection, the RT-PCR test identified 83% as bacterial, identical to procalcitonin. 39 subjects had suspected bacterial infection; the RT-PCR test identified bacterial infection more frequently than procalcitonin (82% vs 64%, p = 0•02). INTERPRETATION: The RT-PCR test offered similar diagnostic performance to procalcitonin in some subgroups but offered better discrimination in others such as viral vs. non-infectious illness and bacterial/viral coinfection. Gene expression-based tests could impact decision-making for acute respiratory illness as well as a growing number of other infectious and non-infectious diseases.

A host gene expression approach for identifying triggers of asthma exacerbations.

RATIONALE: Asthma exacerbations often occur due to infectious triggers, but determining whether infection is present and whether it is bacterial or viral remains clinically challenging. A diagnostic strategy that clarifies these uncertainties could enable personalized asthma treatment and mitigate antibiotic overuse. OBJECTIVES: To explore the performance of validated peripheral blood gene expression signatures in discriminating bacterial, viral, and noninfectious triggers in subjects with asthma exacerbations. METHODS: Subjects with suspected asthma exacerbations of various etiologies were retrospectively selected for peripheral blood gene expression analysis from a pool of subjects previously enrolled in emergency departments with acute respiratory illness. RT-PCR quantified 87 gene targets, selected from microarray-based studies, followed by logistic regression modeling to define bacterial, viral, or noninfectious class. The model-predicted class was compared to clinical adjudication and procalcitonin. RESULTS: Of 46 subjects enrolled, 7 were clinically adjudicated as bacterial, 18 as viral, and 21 as noninfectious. Model prediction was congruent with clinical adjudication in 15/18 viral and 13/21 noninfectious cases, but only 1/7 bacterial cases. None of the adjudicated bacterial cases had confirmatory microbiology; the precise etiology in this group was uncertain. Procalcitonin classified only one subject in the cohort as bacterial. 47.8% of subjects received antibiotics. CONCLUSIONS: Our model classified asthma exacerbations by the underlying bacterial, viral, and noninfectious host response. Compared to clinical adjudication, the majority of discordances occurred in the bacterial group, due to either imperfect adjudication or model misclassification. Bacterial infection was identified infrequently by all classification schemes, but nearly half of subjects were prescribed antibiotics. A gene expression-based approach may offer useful diagnostic information in this population and guide appropriate antibiotic use.

The host response as a tool for infectious disease diagnosis and management.

INTRODUCTION: A century of advances in infectious disease diagnosis and treatment changed the face of medicine. However, challenges continue to develop including multi-drug resistance, globalization that increases pandemic risks, and high mortality from severe infections. These challenges can be mitigated through improved diagnostics, and over the past decade, there has been a particular focus on the host response. Since this article was originally published in 2015, there have been significant developments in the field of host response diagnostics, warranting this updated review. Areas Covered: This review begins by discussing developments in single biomarkers and pauci-analyte biomarker panels. It then delves into 'omics, an area where there has been truly exciting progress. Specifically, progress has been made in sepsis diagnosis and prognosis; differentiating viral, bacterial, and fungal pathogen classes; pre-symptomatic diagnosis; and understanding disease-specific diagnostic challenges in tuberculosis, Lyme disease, and Ebola. Expert Commentary: As 'omics have become faster, more precise, and less expensive, the door has been opened for academic, industry, and government efforts to develop host-based infectious disease classifiers. While there are still obstacles to overcome, the chasm separating these scientific advances from the patient's bedside is shrinking.

Immunogenicity of pulsatile-release PLGA microspheres for single-injection vaccination.

The World Health Organization's Expanded Programme on Immunization has led to a dramatic rise in worldwide vaccination rates over the past 40years, yet 19.4 million infants remain underimmunized each year. Many of these infants have received at least one vaccine dose but may remain unprotected because they did not receive subsequent booster doses due to logistical challenges. This study aimed to develop injectable controlled release microparticles with kinetics that mimic common vaccine dosing regimens consisting of large antigen doses administered periodically over the course of months in order to eliminate the need for boosters. Sixteen poly(lactic-co-glycolic acid) (PLGA) microsphere formulations containing bovine serum albumin (BSA) as a model vaccine antigen were screened in vitro to determine their respective release kinetics. Three formulations that exhibited desirable pulsatile release profiles were then selected for studying immunogenicity in mice. Two low-dose microsphere formulations induced peak anti-BSA IgG antibody titers of 13.9±1.3 and 13.7±2.2 log2 compared to 15.5±1.5 log2 for a series of three bolus injections delivered at 0, 4, and 8weeks with an equivalent cumulative dose. Similarly, high-dose formulations induced peak antibody titers that were 16.1±2.1 log2 compared to 17.7±2.2 log2 for controls. All three microparticle formulations studied in vivo induced peak antibody titers that were statistically similar to bolus controls. These results suggest that pulsatile antigen release from polymeric microparticles is a promising approach for single-injection vaccination, which could potentially reduce the logistical burden associated with immunization in the developing world.

The prevalence of undiagnosed pre-surgical cognitive impairment and its post-surgical clinical impact in elderly patients undergoing surgery for adult spinal deformity.

BACKGROUND: Pre-existing cognitive impairment (CI) is emerging as a predictor of poor post-operative outcomes in elderly patients. Little is known about impaired preoperative cognition and outcomes after elective spine surgery in this patient population. The purpose of this study was to assess the prevalence of neuro CI in elderly patients undergoing deformity surgery and its impact on postoperative outcomes. METHODS: Elderly subjects undergoing elective spinal surgery for correction of adult degenerative scoliosis were enrolled in this study. Pre-operative baseline cognition was assessed using the Saint Louis Mental Status (SLUMS) test. SLUMS consists of 11 questions, which can give a maximum of 30 points. Mild CI was defined as a SLUMS score between 21-26 points, while severe CI was defined as a SLUMS score of ≤20 points. Normal cognition was defined as a SLUMS score of ≥27 points. Complication rates, duration of hospital stay, and 30-day readmission rates were compared between patients with and without baseline CI. RESULTS: Eighty-two subjects were included in this study, with mean age of 73.26±6.08 years. Fifty-seven patients (70%) had impaired cognition at baseline. The impaired cognition group had the following outcomes: increased incidence of one or more postoperative complications (39% vs. 20%), higher incidence of delirium (20% vs. 8%), and higher rate of discharge institutionalization at skilled nursing or acute rehab facilities (54% vs. 30%). The length of hospital stay and 30-day hospital readmission rates were similar between both cohorts (5.33 vs. 5.48 days and 12.28% vs. 12%, respectively). CONCLUSIONS: CI is highly prevalent in elderly patients undergoing surgery for adult degenerative scoliosis. Impaired cognition before surgery was associated with higher rates of post-operative delirium, complications, and discharge institutionalization. CI assessments should be considered in the pre-operative evaluations of elderly patients prior to surgery.

Reduced Impact of Smoking Status on 30-Day Complication and Readmission Rates After Elective Spinal Fusion (≥3 Levels) for Adult Spine Deformity: A Single Institutional Study of 839 Patients.

BACKGROUND: Smoking status has been shown to affect postoperative outcomes after surgery. The aim of this study was to determine whether patients' smoking status impacts 30-day complication and readmission rates after elective complex spinal fusion (≥3 levels). METHODS: The medical records of 839 adult spinal deformity patients undergoing elective complex spinal fusion (≥3 levels) at a major academic institution from 2005 to 2015 were reviewed. We identified 124 (14.8%) smokers and 715 (85.2%) nonsmokers. Patient demographics, comorbidities, intraoperative and postoperative complications, and 30-day readmission rates were collected for each patient. The primary outcome investigated in this study was the rate of 30-day postoperative complication and readmission rates. RESULTS: Patient demographics and comorbidities were similar between both groups, including age, sex, and body mass index. Median [interquartile] number of fusion levels and operative time were similar between the cohorts (smoker: 5 [4-7] vs. nonsmoker: 5 [4-8], P = 0.58) and (smoker: 309.6 ± 157.9 minutes vs. nonsmoker: 287.5 ± 131.7 minutes, P = 0.16), respectively. Both cohorts had similar postoperative complication rates and lengths of hospital stay. There was no significant difference in 30-day readmission between the cohorts (smoker: 12.9% vs. nonsmoker: 10.8%, P = 0.48). There were no observed differences in 30-day complication rates, including pain (P = 0.46), UTI (P = 0.54), hardware failure (P = 0.36), wound dehiscence (P = 0.29), and wound drainage (P = 0.86). Smokers had greater rates of 30-day cellulitis (smoker: 1.6% vs. nonsmoker: 0.3%, P = 0.05) and DVT (smoker: 0.8% vs. nonsmoker: 0.0%, P = 0.02). CONCLUSIONS: Our study suggests that smoking does not significantly affect 30-day readmission rates after complex spinal surgery requiring ≥3 levels of fusion. Further studies are necessary to corroborate our findings.

Depression as an independent predictor of postoperative delirium in spine deformity patients undergoing elective spine surgery.

OBJECTIVE Depression is the most prevalent affective disorder in the US, and patients with spinal deformity are at increased risk. Postoperative delirium has been associated with inferior surgical outcomes, including morbidity and mortality. The relationship between depression and postoperative delirium in patients undergoing spine surgery is relatively unknown. The aim of this study was to determine if depression is an independent risk factor for the development of postoperative delirium in patients undergoing decompression and fusion for deformity. METHODS The medical records of 923 adult patients (age ≥ 18 years) undergoing elective spine surgery at a single major academic institution from 2005 through 2015 were reviewed. Of these patients, 255 (27.6%) patients had been diagnosed with depression by a board-certified psychiatrist and constituted the Depression group; the remaining 668 patients constituted the No-Depression group. Patient demographics, comorbidities, and intra- and postoperative complication rates were collected for each patient and compared between groups. The primary outcome investigated in this study was rate of postoperative delirium, according to DSM-V criteria, during initial hospital stay after surgery. The association between depression and postoperative delirium rate was assessed via multivariate logistic regression analysis. RESULTS Patient demographics and comorbidities other than depression were similar in the 2 groups. In the Depression group, 85.1% of the patients were taking an antidepressant prior to surgery. There were no significant between-group differences in intraoperative variables and rates of complications other than delirium. Postoperative complication rates were also similar between the cohorts, including rates of urinary tract infection, fever, deep and superficial surgical site infection, pulmonary embolism, deep vein thrombosis, urinary retention, and proportion of patients transferred to the intensive care unit. In total, 66 patients (7.15%) had an episode of postoperative delirium, with depressed patients experiencing approximately a 2-fold higher rate of delirium (10.59% vs 5.84%). In a multivariate logistic regression analysis, depression was an independent predictor of postoperative delirium after spine surgery in spinal deformity patients (p = 0.01). CONCLUSIONS The results of this study suggest that depression is an independent risk factor for postoperative delirium after elective spine surgery. Further studies are necessary to understand the effects of affective disorders on postoperative delirium, in hopes to better identify patients at risk.

Increased 30-Day Complication Rates Associated with Laminectomy in 874 Adult Patients with Spinal Deformity Undergoing Elective Spinal Fusion: A Single Institutional Study.

OBJECTIVE: Recent studies have reported that decompression with fusion leads to superior outcomes in correction of spinal deformity. The aim of this study was to determine if there is a difference in intraoperative and 30-day postoperative complication rates in patients undergoing spinal fusion with and without decompression. METHODS: Medical records of 874 adult (≥18 years old) patients with spinal deformity undergoing elective spinal fusion at a major academic institution from 2005 to 2015 were reviewed; 374 (42.8%) patients underwent laminectomy in addition to spinal fusion. The primary outcome investigated was the rate of intraoperative and 30-day complications. RESULTS: Patient demographics and comorbidities were similar between groups. The laminectomy cohort had significantly higher estimated blood loss (P < 0.0001), incidence of allogeneic blood transfusions (P = 0.0001), and rate of intraoperative durotomies (laminectomy cohort 10.4% vs. no-laminectomy cohort 3.1%; P < 0.0001). The laminectomy cohort had a significantly higher proportion of patients in the intensive care unit (28.6% vs. 17.7%; P < 0.001). There was no significant difference in 30-day readmission rate between cohorts (laminectomy cohort 13.0% vs. no-laminectomy cohort 9.8%; P = 0.13). Within 30 days after initial discharge, the laminectomy cohort had significantly higher rates of altered mental status (3.2% vs. 1.2%; P = 0.05), urinary tract infection (4.3% vs. 1.4%; P = 0.009), wound drainage (7.2% vs. 3.1%; P = 0.007), and instrumentation failure (1.1% vs. 0.0%; P = 0.03). CONCLUSIONS: Patients undergoing spinal fusion with laminectomy may have higher complication rates than patients undergoing spinal fusion alone.

Post-operative delirium is an independent predictor of 30-day hospital readmission after spine surgery in the elderly (≥65years old): A study of 453 consecutive elderly spine surgery patients.

In the last decade, costs of U.S. healthcare expenditures have been soaring, with billions of dollars spent on hospital readmissions. Identifying causes and risk factors can reduce soaring readmission rates and help lower healthcare costs. The aim of this is to determine if post-operative delirium in the elderly is an independent risk factor for 30-day hospital readmission after spine surgery. The medical records of 453 consecutive elderly (≥65years old) patients undergoing spine surgery at Duke University Medical Center from 2008 to 2010 were reviewed. We identified 17 (3.75%) patients who experienced post-operative delirium according to DSM-V criteria. Patient demographics, comorbidities, and post-operative complication rates were collected for each patient. Elderly patients experiencing post-operative delirium had an increased length of hospital stay (10.47days vs. 5.70days, p=0.009). Complication rates were similar between the cohorts with the post-operative delirium patients having increased UTI and superficial surgical site infections. In total, 12.14% of patients were re-admitted within 30-days of discharge, with post-operative delirium patients experiencing approximately a 4-fold increase in 30-day readmission rates (Delirium: 41.18% vs. No Delirium: 11.01%, p=0.002). In a multivariate logistic regression analysis, post-operative delirium is an independent predictor of 30-day readmission after spine surgery in the elderly (p=0.03). Elderly patients experiencing post-operative delirium after spine surgery is an independent risk factor for unplanned readmission within 30-days of discharge. Preventable measures and early awareness of post-operative delirium in the elderly may help reduce readmission rates.

Impact of Intraoperative Monitoring During Elective Complex Spinal Fusions (≥4 Levels) on 30-Day Complication and Readmission Rates: A Single-Institutional Study of 643 Adult Patients with Spinal Deformity.

OBJECTIVE: The aim of this study is to determine if there are differences in 30-day postoperative complication and readmission rates between patients with spinal deformity undergoing complex spinal fusion with and without intraoperative monitoring (IOM). METHODS: The medical records of 643 adult patients with spine deformity undergoing elective complex spinal fusion (≥4 levels) at a major academic institution from 2005 to 2015 were reviewed. We identified 122 cases (19%) that involved IOM including electromyography, somatosensory evoked potential, and/or transcranial motor evoked potential and 521 (81%) that did not (IOM, n = 122; no-IOM, n = 521). The primary outcome investigated was the rate of 30-day postoperative complications and readmission. RESULTS: Patient demographics and comorbidities were similar between both groups, including age, gender, body mass index, and smoking status. IOM cases had significantly increased operative time (IOM, 360.9 ± 153.8 minutes vs. no-IOM, 290.3 ± 127.1 minutes; P < 0.0001), with no differences in the incidences of spinal cord injury, nerve injury, and durotomy. Both cohorts had similar postoperative complications and length of hospital stay, with the no-IOM cohort having a greater incidence of intensive care unit transfer (no-IOM, 27.1% vs. IOM, 16.1%, P = 0.015). There was no significant difference in 30-day readmission between the cohorts (IOM, 8.2% vs. no-IOM, 12.3%; P = 0.27) or differences in sensorimotor deficits. Although the overall 30-day complication rate trended to be higher in the no-IOM cohort, these factors were not attributed to IOM use. CONCLUSIONS: Our study suggests that the use of IOM may not have a significant impact on overall surgical outcomes and 30-day readmission rates.

Posterolateral thoracic decompression with anterior column cage reconstruction versus decompression alone for spinal metastases with cord compression: analysis of perioperative complications and outcomes.

BACKGROUND: The optimal surgical strategy for patients with spinal metastases remains unknown. The aim of this study was to determine if performing an anterior column reconstruction to a posterolateral approach adds to perioperative complications. METHODS: A retrospective review of all adult patients with spinal metastases who had a posterolateral approach for resection between January 2000 and December 2008. Perioperative complications and functional outcomes were determined. RESULTS: A total of 23 patients met the study criteria. Eleven patients underwent a costotransversectomy (CT) approach with anterior column reconstruction while 12 patients had a transpedicular (TP) approach without anterior column reconstruction. The mean age was 55.9 and 59.3 years in the CT and TP groups, respectively. There was no intraoperative death in either group. One death attributed to sepsis occurred in the TP group. A total of 5 (45.5%) complications occurred in the CT group and 7 (58.3%) in the TP group (P=0.68). An improvement in American Spinal Injury Association (ASIA) impairment scale grades was observed in 3 (27.3%) patients in the CT group and 1 (8.3%) in TP group. ASIA grades remained the same in 8 (72.7%) patients in CT and 10 (83.3%) patients in TP groups. No patient worsened in the CT group whereas 1 (8.3%) patient in TP group worsened. The median survival was 12.2 months in the CT group and 19.0 months in the TP group (P=0.37). CONCLUSIONS: The addition of anterior column reconstruction does not appear to be associated with more operative or perioperative complications when compared to decompression alone. Anterior column reconstruction should not be aborted in fear of increasing perioperative complications.