Citations

Abstract Background Rapid blood culture diagnostics increase cost and have unclear benefit for patients with Gram-negative bacilli (GNB) bloodstream infections (BSIs). We conducted a multicenter, prospective randomized controlled trial (RAPIDS-GN), comparing outcomes of patients with GNB BSI who had blood culture testing with standard of care (SOC) culture and antibiotic susceptibility testing (AST) vs. rapid organism identification (ID) and phenotypic AST using the Accelerate Pheno System (AXDX). Methods Subjects with blood culture Gram stain showing GNB were randomized to receive SOC testing with antimicrobial stewardship review (AS) or AXDX plus SOC testing with AS, at two academic medical centers between October 2017 and October 2018. SOC testing included rapid MALDI-TOF mass spectrometry ID and agar dilution or broth microdilution AST. In a modified intention to treat analysis, subjects were excluded if: Gram stain was erroneous, culture was positive during off-hours, blood culture in the prior week had GNB, they were deceased/on comfort care, or admitted to a nonparticipating hospital. The primary outcome was time to first antibiotic modification within 72 hours after randomization. Subjects without antibiotic modifications were assigned a time of 72 hours. No censoring was observed. T-tests and Wilcoxon rank-sum tests were used for statistical analyses. Results Of 500 randomized subjects, 448 were included (226 SOC, 222 AXDX). Groups did not differ in baseline characteristics (Table 1). Median (IQR) hours to first antibiotic modification was faster in the AXDX vs. SOC group [8.6 (2.6, 27.6) vs. 14.9 (3.3, 41.1)], P = 0.02 (Figure 1). Median (IQR) hours to first Gram-negative antibiotic modification (including escalation and de-escalation) was faster in the AXDX than SOC group [17.4 (4.9, 72) vs. 42.1 (10.1, 72)], P < 0.001 (Figure 2). Groups did not differ in clinical outcomes (Table 2). Mean (S.D.) time to results was faster for AXDX than SOC for organism ID [2.7 (1.2) h vs. 15.6 (20.3) h, P < 0.001] and AST [13 (55.7) h vs. 54.6 (45.5) h, P < 0.001]. Conclusion In the largest trial to evaluate the clinical impact of a blood culture diagnostic for GNB BSI, we found that rapid organism ID and phenotypic AST led to faster changes in antibiotic therapy for Gram-negative bacteremia. Disclosures Ritu Banerjee, MD, PhD, Accelerate Diagnostics: Grant/Research Support; BioFire: Research Grant; Biomerieux: Research Grant; Roche: Research Grant Robin Patel, MD, ASM and IDSA: Other Financial or Material Support, Travel reimbursement, editor’s stipends; CD Diagnostics, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, ContraFect, TenNor Therapeutics Limited, Shionogi: Grant/Research Support; Curetis, Specific Technologies, NextGen Diagnostics, PathoQuest, Qvella: Consultant; NBME, Up-to-Date, the Infectious Diseases Board Review Course: Honorarium recipient, Other Financial or Material Support; Patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued: Other Financial or Material Support, Patents.

Susceptibility testing of the polymyxins (colistin and polymyxin B) is challenging for clinical laboratories. The Clinical and Laboratory Standards Institute (CLSI) Antimicrobial Susceptibility Testing Subcommittee evaluated two methods to enable accurate testing of these agents. These methods were a colistin broth disk elution (CBDE) and a colistin agar test (CAT), the latter of which was evaluated using two inoculum volumes, 1 μl (CAT-1) and 10 μl (CAT-10).

Background: Photopatch testing is important for diagnosing photoallergic contact dermatitis. Although results of photopatch testing have been presented from many European centers, there have been few reports of the results of photopatch testing in the United States. Objective: To review the Mayo Clinic’s recent experience with photopatch testing, identify common photoallergens, and compare our current and previous findings. Methods: We retrospectively reviewed records of patients who underwent photopatch testing at the Mayo Clinic between January 1, 2000, and December 31, 2005 (N=182). Results: Fifty-four patients (29.7%) had photoallergic contact reactions, and 29 (15.9%) had allergic contact reactions. The most common photoallergens were medications, sunscreen agents, fragrances, and antiseptics. Conclusion: Photopatch testing is the technique useful in identifying photoallergens. The series of allergens used must be constantly updated to reflect newly identified and outdated photoallergens. We present a 6-year experience with photopatch testing. Medications, sunscreen agents, fragrances, and antiseptics were the most frequently identified photoallergens.

Introduction Cutibacterium acnes is a recognized culprit for implant-associated infections, but positive cultures do not always indicate clinically relevant infection. Studies have shown a correlation between the β-hemolytic phenotype of C. acnes and its infectious capacity, but correlation with genetic phylotype has not been performed in literature. The purpose of this study is to evaluate β-hemolysis phenotype, genetic phylotype, and mid-term clinical outcomes of C. acnes isolated from orthopedic surgical sites. Methods Fifty-four C. acnes isolates previously obtained from surgical wounds of patients undergoing hip, knee, shoulder, or spine implant removal were re-cultured. There were 21 females and 33 males with an average age of 59 years (range, 18–84). Twenty-four were from clinically infected sites whereas 30 were considered contaminants. De novo β-hemolysis was analyzed and a retrospective chart review was performed to evaluate clinical outcomes at 7.1 years (range, 0.1–12.8). Results On Brucella agar with 5% rabbit blood, 46% of contaminant and 43% of infectious isolates were hemolytic. Type II phylotype was significantly more nonhemolytic regardless of infectious or contaminant status (p < 0.05). Type 1B correlated with a hemolytic-infectious phenotype and Type 1A with a hemolytic-contaminant phenotype but was not statistically significant. Conclusion The β-hemolytic profile of C. acnes did not correlate with phylotype or clinically relevant orthopedic infection.

Abstract Over 30% of patients with renal cell carcinoma (RCC) present with metastases, with median survival of 2 years. Kidney injury molecule 1 (KIM-1) is a cell-surface glycoprotein expressed by &gt;85% of RCC tumours and may serve as an early biomarker for RCC detection. Here we sought to determine if tumour KIM-1 plays a role in RCC cell extravasation and metastasis to lungs. Methods: We overexpressed KIM-1 in Renca cells (murine RCC) using stable transfection of an expression plasmid, or silenced endogenous KIM-1 in human 769-P and 786-O RCC cells using shRNA. We studied extravasation using the chorioallantoic membrane (CAM) model. We injected ~1x105 Renca or 769-P cells into blood vessels of chicken embryos (n=6), and measured percentage of cells that exited the capillary bed into surrounding spaces after 24 hours. To study lung metastasis, we injected ~5x105 Renca or 786-O cells intravenously through the tail vein of syngeneic BALB/c (n=10/group) or immune deficient Rag1-/- [BALB/c] (n=5/group) mice, and manually counted metastatic nodules in excised lungs after 17 days. Finally, we analyzed the publicly available Cancer Genome Atlas Illumina RNA-Seq dataset to determine if KIM-1 mRNA expression predicts overall survival in patients with clear cell RCC. Results: In CAM experiments, extravasation efficiency was significantly decreased in KIM-1pos 769-P cells compared to KIM-1neg 769-P cells (30.08% vs. 47.94%; p=0.0004), and in KIM-1pos Renca cells compared to KIM-1neg Renca cells (47.78% vs 60.73%; p=0.042). BALB/c mice injected with Kim-1pos Renca cells or Kim-1pos 786-O cells had significantly fewer lung metastases compared to mice injected with Kim-1neg Renca cells or Kim-1neg 786-O cells, respectively (257 vs 429, p=0.02; 131 vs 339 p=0.001). The inhibitory effect of KIM-1 expression in Renca and 786-O cells on numbers of lung metastases was similar in Rag1-/- mice, suggesting that the observed effects were not dependent on adaptive immunity. In the TCGA database, patients with the lowest vs. highest tertile of KIM-1 RCC expression has significantly higher mortality (unadjusted HR 1.82, 95% CI 1.23-2.70; p=0.0034). Conclusion: KIM-1 is a negative regulator of cell extravasation and inhibits the development of lung metastases in mice, and KIM-1 expression in human RCC may predict better survival. Deciphering the underlying mechanisms may lead to novel therapies. Citation Format: Jasper C. Lee, Marie A. Sarabusky, Audrey Champagne, Fabrice Lucien, Lakshman Gunaratnam. Kidney injury molecule-1 regulates metastasis in renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4604.

Background: Recent research has identified posterior tibial slope as a risk factor for anterior cruciate ligament (ACL) injury, due to increased forces on the ACL with this tibial anatomy. Biomechanical studies suggest that altering a patient’s posterior tibial slope may lower the risk of ACL injury. Due to the presence of an open physis, guided growth may be used to reduce the posterior tibia slope in this high risk skeletally immature population. The primary purpose of this study was to quantify and measure the posterior tibial slope in pediatric knees. Methods: Forty-four pediatric knee CT scans were analyzed using OsiriX, an imaging software. Specimens analyzed were between the ages of 2 and 12 years of age. The proximal tibial slope for each specimen was measured on CT scan sagittal slices at 2 locations: 1) At the medial tibial plateau at the mid region of the medial femoral condyle, as determined on a coronal slice through the femoral condyle; 2) At the lateral tibial plateau at the mid region of the lateral femoral condyle, as determined on the coronal slice through the femoral condyle. The measurement of the posterior tibial slope was determined by placing two lines parallel to the diaphysis of the tibia, one located in the middle of the diaphysis and one located at the most posterior aspect of the diaphysis. The most proximal aspect of both the medial and lateral tibial plateau were then identified and angle measurements were taken in reference to the parallel lines. The angle measurements were plotted graphically by age in order to account for variability in development within age groups. The anterior medial and lateral tibia plateau widths were measured by identifying the mid region of the respective plateaus. From this point, the distance between the top of the tibial plate and the physis was measured. Results: The average posterior tibial slope angle for the medial and lateral tibial plateau were (5.53° ± 4.17°) and (5.95° ± 3.96°) respectively. Independent samples t-test and ANOVA indicate the difference between the posterior tibial slope angle of the medial and lateral tibial plateau were not statistically significant (p < 0.05). When plotted graphically by age, a slight negative trend between age and posterior tibial slope was identified. As age increases, the medial and lateral posterior tibial slope decreases. The mean anterior medial tibial plateau width and lateral tibial plateau width were .99 cm and 1.19 cm respectively. Discussion/Conclusion: ACL primary and secondary injury occur at very high rates in the skeletally immature, especially in females at age 11 and older, and in males at age 13 and older. This data set offers some preliminary values for posterior tibial slope in patients without a history of ACL injury, allowing for comparisons to patients with ACL Injury. Increased tibial slope is a risk factor for ACL injury. In the skeletally immature, one option to alter the tibial slope is the use of guided growth with implants to slow the anterior growth of the proximal tibia, reducing the posterior slope of the tibia, and possibly lower the risk of ACL injury in this high-risk population. [Figure: see text][Figure: see text][Figure: see text][Figure: see text][Figure: see text][Table: see text][Table: see text]

Background: In skeletally immature patients, the MPFL femoral origin as near or below the physis in most age groups. Although MPFL reconstruction procedures that employ patella drill holes facilitate graft tension adjustment, recent research demonstrates significant risk of patella fractures if patella drill holes are utilized. For this reason, the use of patella drill holes may be best avoided, but this technical alteration makes graft tension fixation more challenging during MPFL reconstruction in the skeletally immature. The purpose of this study was to evaluate the feasibility of developing a physeal respecting femoral drill for the MPFL origin with surgical model simulation, which allows for graft tensioning during MPFL reconstruction. Methods: Pediatric cadaveric specimens (n=5) were dissected by a group of fellowship trained pediatric and/or sports orthopaedic surgeons, and these specimens were then subject to CT Scans for the creation of 3D models. Specimens, aged 7, 9, 10, 11 and 11 years, were used to develop surgical simulations. CT Scans were loaded into Osyrix, converted to appropriate file structure, and then 3D models were loaded into Blender (Stichting Blender Foundation, Buikslotermeerplein 161, 1025 ETAmsterdam, the Netherlands). These models were used to evaluate 3D models of the knee, with placement of medial femoral condyle drill holes starting at the MPFL femoral origin, and entering the joint just anterior to the PCL femoral origin. The anatomic goals of the surgical simulation include: 1. Place drill hole at the MPFL origin on the femur. 2 Enter the intercondylar notch region of the femur anterior to the PCL origin allowing for arthroscopic visualization. 3. avoiding the articular cartilage on the medial femoral condyle. 4. Avoid the femoral physis throughout the course of drilling from the femoral MPFL Origin point to the entry location into the intercondylar notch. In the specimens, a full length drill hole was placed with either a 4 or 5 mm drill hole. Results: All specimens were subject to the surgical modeling and simulated drill hole placement. In each case, a drill hole was successfully placed meeting all the goals of the simulation: 1. Starting Point at MPFL, 2. Exit point anterior the PCL origin, 3. Exit point posterior to the articular cartilage, and 4. Avoidance of direct physeal injury. Figures 1 and 2. Conclusion: Setting graft tension during MPFL reconstruction is one of the significant technical challenges during MPFL reconstruction, and appropriate graft position and tension may be the most critical elements of successful MPFL reconstruction. Historically, graft tension has been set on the patella, using drill holes for the MPFL attachment point on the patella, but this technique has been associated with patella fractures. In order to allow for adjustment of graft tension on the femoral side of the MPFL graft during surgical reconstruction, a surgical simulation was developed to confirm the anatomic appropriateness and safety of placement of femoral drill holes which allow for adjustment of graft tension. This surgical simulation model confirms that MPFL femoral origin anatomy can be reproduced with injury to the physis, the PCL, or the articular cartilage of the femoral condyle. This drill hole and graft can be visualized arthroscopically and allow for appropriate graft tensioning during the procedure. [Figure: see text][Figure: see text]

Background The recent introduction of high‐sensitivity cardiac troponin (hs‐cTn) assays has allowed clinicians to measure hs‐cTn before and after cardiac stress testing, but the hs‐cTn release pattern and potential utility in identifying inducible myocardial ischemia are unclear. We thus conducted a systematic review and meta‐analysis to improve our understanding of hs‐cTn release associated with exercise and pharmacological stress testing. Methods and Results Studies published between January 2008 and July 2016 that reported hs‐cTn change values (high‐sensitivity cardiac troponin T [hs‐cTnT] or high‐sensitivity cardiac troponin I [hs‐cTnI]) in relation to cardiac stress testing were searched and reviewed by 2 independent screeners. Primary outcomes were pooled estimates of absolute and relative hs‐cTn changes after cardiac stress test, stratified by the presence of inducible myocardial ischemia. This meta‐analysis included 11 studies (n=2432 patients). After exercise stress testing, hs‐cTnT increased by 0.5 ng/L or 11% (6 studies, n=406) and hs‐cTnI by 2.4 ng/L or 41% (4 studies, n=365) in patients with inducible myocardial ischemia versus hs‐cTnT by 1.1 ng/L or 18% (8 studies, n=629; P =0.29) and hs‐cTnI by 1.8 ng/L or 72% (4 studies, n=831; P =0.61) in patients who did not develop inducible myocardial ischemia. After pharmacological stress test, hs‐cTnT changed by −0.1 ng/L or −0.4% (6 studies, n=251) and hs‐cTnI by 2.4 ng/L or 32% (2 studies, n=108) in patients with inducible myocardial ischemia versus hs‐cTnT by 0.7 ng/L or 11% (5 studies, n=443, P =0.44) and hs‐cTnI by 1.7 ng/L or 38% (2 studies, n=116; P =0.62) in patients who did not develop inducible myocardial ischemia. Conclusions hs‐cTn rising patterns after exercise and pharmacological stress testing appear inconsistent and comparably small, and do not appear to be correlated with inducible myocardial ischemia.

Respiratory viral infections are associated with a wide range of acute syndromes and infectious disease processes in children and adults worldwide. Many viruses are implicated in these infections, and these viruses are spread largely via respiratory means between humans but also occasionally from animals to humans.