Derrick J. Chen

Drug confirmation by mass spectrometry: Identification criteria and complicating factors.

Drug confirmation by mass spectrometry coupled with chromatography is essential to toxicology, doping control, pain management, and workplace drug testing. High confidence in this technology is due to its superior specificity and sensitivity. However, there are challenges associated with drug confirmation, and proper setup and validation of these assays are important in assuring high-quality results. In this article, assay parameters required for drug confirmation are summarized based on recent scientific publications, various established guidelines, and our own practical experience. Factors affecting the result quality and correct results interpretation are critically reviewed. Several emerging technologies and their potential applications are briefly explored.

Cavernous angiomas in chronic epilepsy associated with focal cortical dysplasia.

Both cavernous angiomas and focal cortical dysplasia (FCD) are well recognized causes of pharmacoresistant epilepsy. Anecdotal cases of FCD adjacent to cavernous angiomas have been documented in the literature. This study systematically reviews a series of cavernous angiomas in epilepsy patients, looking for evidence of coexistent FCD. 146 patients were diagnosed with cavernous angiomas on resection specimens from January 1989 to May 2011; 18 cases also had epilepsy and had ample tissue excised to assess for FCD. FCD was classified according to criteria outlined by Palmini et al. [12]. Patients included 10 females (55.6%); the mean age of study patients was 38.5 years (range 21 - 51 years) at the time of resection. All patients had a history of epilepsy (median 11 years) prior to surgery. 17 cavernomas were located in the temporal lobe and 1 in the occipital lobe. Adjacent FCD was identified in 13 out of the 18 cases (72.2%): Type Ia (n = 8; 61.5%), Type Ib (n = 4; 30.8%), and Type IIa (n = 1; 7.7%). After resection, a majority of the patients experienced resolution of their epilepsy (n = 14; 77.8%). Of the 4 patients that did not experience seizure resolution, 2 had evidence of adjacent FCD (Type Ia = 1, Type Ib = 1) and 2 did not. FCD is frequently present in association with cavernous angiomas in patients with chronic epilepsy. The type of FCD seen adjacent to these lesions varies, but most are Palmini et al. Type I. Resection of the cavernous angiomas and adjacent FCD often results in a resolution of the epilepsy.

Semiquantitative histologic evaluation improves diagnosis of esophageal carcinoma cuniculatum on biopsy

Carcinoma cuniculatum, a unique variant of well-differentiated squamous cell carcinoma, has been only rarely reported in the esophagus. The present study was undertaken to determine if a previously observed common histologic pattern for carcinoma cuniculatum is diagnostically useful in esophageal mucosal biopsy specimens. Thirty-five esophageal mucosal biopsies obtained from 25 procedures in 11 patients with a resection-proven diagnosis of carcinoma cuniculatum were compared with 92 esophageal biopsies from 69 patients with benign diagnoses. All biopsies were assessed for the presence of hyperkeratosis, acanthosis, dyskeratosis, deep keratinization, intraepithelial neutrophils, neutrophilic microabscess, focal cytologic atypia, koilocyte-like cells, and keratin-filled cyst/burrows. Each feature, if present, was given one point, and the final histologic score was calculated for each biopsy by summing the points. The mean histologic score was 6.66 (s.d. 1.88) in biopsies from carcinoma cuniculatum vs a mean score of 1.93 (s.d. 1.75) for biopsies with benign diagnoses (P<0.0001). Using a cutoff value of 7 for carcinoma cuniculatum, 57% of biopsies (20/35) from 64% esophagogastroduodenoscopy procedures (16/25) in 91% patients (10/11) would be diagnostic, in comparison to the initial diagnostic rates of carcinoma of 9, 12, and 27%, respectively (P<0.0001 for all). None of the 92 benign biopsies showed a score of ≥7. Our results demonstrate that a semiquantitative histologic evaluation of mucosal biopsies taken from an esophageal mass greatly improves the diagnostic sensitivity from patients with carcinoma cuniculatum with 100% specificity. Larger studies are necessary to confirm the current findings.

Clinical significance of coryneform Gram-positive rods from blood identified by MALDI-TOF mass spectrometry and their susceptibility profiles – a retrospective chart review

With the advent of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), most Gram-positive rods (GPRs) are readily identified; however, their clinical relevance in blood cultures remains unclear. Herein, we assessed the clinical significance of GPRs isolated from blood and identified in the era of MALDI-TOF MS. A retrospective chart review of patients presenting to the Mayo Clinic, Rochester, MN, from January 1, 2013, to October 13, 2015, was performed. Any episode of a positive blood culture for a GPR was included. We assessed the number of bottles positive for a given isolate, time to positivity of blood cultures, patient age, medical history, interpretation of culture results by the healthcare team and whether infectious diseases consultation was obtained. We also evaluated the susceptibility profiles of a larger collection of GPRs tested in the clinical microbiology laboratory of the Mayo Clinic, Rochester, MN from January 1, 2013, to October 31, 2015. There were a total of 246 GPRs isolated from the blood of 181 patients during the study period. 56% (n = 101) were deemed contaminants by the healthcare team and were not treated; 33% (n = 59) were clinically determined to represent true bacteremia and were treated; and 8% (n = 14) were considered of uncertain significance, with patients prescribed treatment regardless. Patient characteristics associated with an isolate being treated on univariate analysis included younger age (P = 0.02), identification to the species level (P = 0.02), higher number of positive blood culture sets (P < 0.0001), lower time to positivity (P < 0.0001), immunosuppression (P = 0.03), and recommendation made by an infectious disease consultant (P = 0.0005). On multivariable analysis, infectious diseases consultation (P = 0.03), higher number of positive blood culture sets (P = 0.0005) and lower time to positivity (P = 0.03) were associated with an isolate being treated. 100, 83, 48 and 34% of GPRs were susceptible to vancomycin, meropenem, penicillin and ceftriaxone, respectively.

Comparison of turnaround time and total cost of HIV testing before and after implementation of the 2014 CDC/APHL Laboratory Testing Algorithm for diagnosis of HIV infection

BACKGROUND Updated recommendations for HIV diagnostic laboratory testing published by the Centers for Disease Control and Prevention and the Association of Public Health Laboratories incorporate 4th generation HIV immunoassays, which are capable of identifying HIV infection prior to seroconversion. OBJECTIVES The purpose of this study was to compare turnaround time and cost between 3rd and 4th generation HIV immunoassay-based testing algorithms for initially reactive results. STUDY DESIGN The clinical microbiology laboratory database at Mayo Clinic, Rochester, MN was queried for 3rd generation (from November 2012 to May 2014) and 4th generation (from May 2014 to November 2015) HIV immunoassay results. All results from downstream supplemental testing were recorded. Turnaround time (defined as the time of initial sample receipt in the laboratory to the time the final supplemental test in the algorithm was resulted) and cost (based on 2016 Medicare reimbursement rates) were assessed. RESULTS A total of 76,454 and 78,998 initial tests were performed during the study period using the 3rd generation and 4th generation HIV immunoassays, respectively. There were 516 (0.7%) and 581 (0.7%) total initially reactive results, respectively. Of these, 304 (58.9%) and 457 (78.7%) were positive by supplemental testing. There were 10 (0.01%) cases of acute HIV infection identified with the 4th generation algorithm. The most frequent tests performed to confirm an HIV-positive case using the 3rd generation algorithm, which were reactive initial immunoassay and positive HIV-1 Western blot, took a median time of 1.1 days to complete at a cost of

Does cumulative prostate cancer length (CCL) in prostate biopsies improve prediction of clinically insignificant cancer at radical prostatectomy in patients eligible for active surveillance

45.00. In contrast, the most frequent tests performed to confirm an HIV-positive case using the 4th generation algorithm, which included a reactive initial immunoassay and positive HIV-1/-2 antibody differentiation immunoassay for HIV-1, took a median time of 0.4 days and cost

In vitro evaluation of meropenem-vaborbactam against clinical CRE isolates at a tertiary care center with low KPC-mediated carbapenem resistance

63.25. Overall median turnaround time was 2.2 and 1.5 days, and overall median cost was

Clinical Utility of Broad-Range Fungal PCR

63.90 and

Phenotypic and Molecular Antimicrobial Susceptibility of Helicobacter pylori

72.50 for 3rd and 4th generation algorithms, respectively. CONCLUSIONS Both 3rd and 4th generation HIV immunoassays had similar total numbers of tests performed and positivity rates during the study period. A greater proportion of reactive 4th generation immunoassays were confirmed to be positive, and the 4th generation algorithm identified several cases of acute HIV infection that would have been missed by the 3rd generation algorithm. The 4th generation algorithm had a more rapid turnaround time but higher cost for confirmed positive HIV infections and overall, compared to the 3rd generation algorithm.

Syndromic and sporadic inflammatory/hyperplastic small-bowel polyps: a comparative study

To evaluate if cumulative prostate cancer length (CCL) on prostate needle biopsy divided by the number of biopsy cores (CCL/core) could improve prediction of insignificant cancer on radical prostatectomy (RP) in patients with prostate cancer eligible for active surveillance (AS).