Paenibacillus spp infection among infants with postinfectious hydrocephalus in Uganda: an observational case-control study.

BACKGROUND: Paenibacillus thiaminolyticus is a cause of postinfectious hydrocephalus among Ugandan infants. To determine whether Paenibacillus spp is a pathogen in neonatal sepsis, meningitis, and postinfectious hydrocephalus, we aimed to complete three separate studies of Ugandan infants. The first study was on peripartum prevalence of Paenibacillus in mother-newborn pairs. The second study assessed Paenibacillus in blood and cerebrospinal fluid (CSF) from neonates with sepsis. The third study assessed Paenibacillus in CSF from infants with hydrocephalus. METHODS: In this observational study, we recruited mother-newborn pairs with and without maternal fever (mother-newborn cohort), neonates (aged ≤28 days) with sepsis (sepsis cohort), and infants (aged ≤90 days) with hydrocephalus with and without a history of neonatal sepsis and meningitis (hydrocephalus cohort) from three hospitals in Uganda between Jan 13, 2016 and Oct 2, 2019. We collected maternal blood, vaginal swabs, and placental samples and the cord from the mother-newborn pairs, and blood and CSF from neonates and infants. Bacterial content of infant CSF was characterised by 16S rDNA sequencing. We analysed all samples using quantitative PCR (qPCR) targeting either the Paenibacillus genus or Paenibacillus thiaminolyticus spp. We collected cranial ultrasound and computed tomography images in the subset of participants represented in more than one cohort. FINDINGS: No Paenibacillus spp were detected in vaginal, maternal blood, placental, or cord blood specimens from the mother-newborn cohort by qPCR. Paenibacillus spp was detected in 6% (37 of 631 neonates) in the sepsis cohort and, of these, 14% (5 of 37 neonates) developed postinfectious hydrocephalus. Paenibacillus was the most enriched bacterial genera in postinfectious hydrocephalus CSF (91 [44%] of 209 patients) from the hydrocephalus cohort, with 16S showing 94% accuracy when validated by qPCR. Imaging showed progression from Paenibacillus spp-related meningitis to postinfectious hydrocephalus over 1-3 months. Patients with postinfectious hydrocephalus with Paenibacillus spp infections were geographically clustered. INTERPRETATION: Paenibacillus spp causes neonatal sepsis and meningitis in Uganda and is the dominant cause of subsequent postinfectious hydrocephalus. There was no evidence of transplacental transmission, and geographical evidence was consistent with an environmental source of neonatal infection. Further work is needed to identify routes of infection and optimise treatment of neonatal Paenibacillus spp infection to lessen the burden of morbidity and mortality. FUNDING: National Institutes of Health and Boston Children's Hospital Office of Faculty Development.

Building Perinatal Pathology Research Capacity in Sub-Saharan Africa.

Introduction: Over two million stillbirths and neonatal deaths occur in sub-Saharan Africa (sSA) annually. Despite multilateral efforts, reducing perinatal mortality has been slow. Although targeted pathologic investigation can often determine the cause of perinatal death, in resource-limited settings, stillbirths, early neonatal deaths, and placentas are rarely examined pathologically. However, the placenta is a key source of diagnostic information and is the main determinant of fetal growth and development in utero, influencing child health outcomes. Methods: In 2016, our collaborative intercontinental group began investigating infectious perinatal death and adverse child health outcomes in Uganda. We developed and initiated a 4-day combined didactic/practical curriculum to train health workers in placental collection, gross placental examination, and tissue sampling for histology. We also trained a local technician to perform immunohistochemistry staining. Results: Overall, we trained 12 health workers who performed gross placental assessment for > 1,000 placentas, obtaining > 5,000 formalin-fixed tissue samples for research diagnostic use. Median placental weights ranged from 425 to 456 g, and 33.3% of placentas were < 10th percentile in weight, corrected for gestational age. Acute chorioamnionitis (32.3%) and maternal vascular malperfusion (25.4%) were common diagnoses. Discussion: Through a targeted training program, we built capacity at a university-affiliated hospital in sSA to independently perform placental collection, gross pathologic examination, and placental tissue processing for histology and special stains. Our training model can be applied to other collaborative research endeavors in diverse resource-limited settings to improve research and clinical capacity and competency for diagnostics and management of stillbirth, neonatal death, and child health outcomes.

Cytomegalovirus infections in infants in Uganda: Newborn-mother pairs, neonates with sepsis, and infants with hydrocephalus.

OBJECTIVES: To estimate the prevalence of cytomegalovirus (CMV) infections among newborn-mother pairs, neonates with sepsis, and infants with hydrocephalus in Uganda. DESIGN AND METHODS: Three populations-newborn-mother pairs, neonates with sepsis, and infants (≤3 months) with nonpostinfectious (NPIH) or postinfectious (PIH) hydrocephalus-were evaluated for CMV infection at 3 medical centers in Uganda. Quantitative PCR (qPCR) was used to characterize the prevalence of CMV. RESULTS: The overall CMV prevalence in 2498 samples across all groups was 9%. In newborn-mother pairs, there was a 3% prevalence of cord blood CMV positivity and 33% prevalence of maternal vaginal shedding. In neonates with clinical sepsis, there was a 2% CMV prevalence. Maternal HIV seropositivity (adjusted odds ratio [aOR] 25.20; 95% confidence interval [CI] 4.43-134.26; p = 0.0001), residence in eastern Uganda (aOR 11.06; 95% CI 2.30-76.18; p = 0.003), maternal age <25 years (aOR 4.54; 95% CI 1.40-19.29; p = 0.02), and increasing neonatal age (aOR 1.08 for each day older; 95% CI 1.00-1.16; p = 0.05), were associated risk factors for CMV in neonates with clinical sepsis. We found a 2-fold higher maternal vaginal shedding in eastern (45%) vs western (22%) Uganda during parturition (n = 22/49 vs 11/50, the Fisher exact test; p = 0.02). In infants with PIH, the prevalence in blood was 24% and in infants with NPIH, it was 20%. CMV was present in the cerebrospinal fluid (CSF) of 13% of infants with PIH compared with 0.5% of infants with NPIH (n = 26/205 vs 1/194, p < 0.0001). CONCLUSIONS: Our findings highlight that congenital and postnatal CMV prevalence is substantial in this African setting, and the long-term consequences are uncharacterized.

Vaginal microbiome topic modeling of laboring Ugandan women with and without fever.

The composition of the maternal vaginal microbiome influences the duration of pregnancy, onset of labor, and even neonatal outcomes. Maternal microbiome research in sub-Saharan Africa has focused on non-pregnant and postpartum composition of the vaginal microbiome. Here we aimed to illustrate the relationship between the vaginal microbiome of 99 laboring Ugandan women and intrapartum fever using routine microbiology and 16S ribosomal RNA gene sequencing from two hypervariable regions (V1-V2 and V3-V4). To describe the vaginal microbes associated with vaginal microbial communities, we pursued two approaches: hierarchical clustering methods and a novel Grades of Membership (GoM) modeling approach for vaginal microbiome characterization. Leveraging GoM models, we created a basis composed of a preassigned number of microbial topics whose linear combination optimally represents each patient yielding more comprehensive associations and characterization between maternal clinical features and the microbial communities. Using a random forest model, we showed that by including microbial topic models we improved upon clinical variables to predict maternal fever. Overall, we found a higher prevalence of Granulicatella, Streptococcus, Fusobacterium, Anaerococcus, Sneathia, Clostridium, Gemella, Mobiluncus, and Veillonella genera in febrile mothers, and higher prevalence of Lactobacillus genera (in particular L. crispatus and L. jensenii), Acinobacter, Aerococcus, and Prevotella species in afebrile mothers. By including clinical variables with microbial topics in this model, we observed young maternal age, fever reported earlier in the pregnancy, longer labor duration, and microbial communities with reduced Lactobacillus diversity were associated with intrapartum fever. These results better defined relationships between the presence or absence of intrapartum fever, demographics, peripartum course, and vaginal microbial topics, and expanded our understanding of the impact of the microbiome on maternal and potentially neonatal outcome risk.

What's to Be Done About Laboratory Quality? Process Indicators, Laboratory Stewardship, the Outcomes Problem, Risk Assessment, and Economic Value: Responding to Contemporary Global Challenges.

OBJECTIVES: For 50 years, structure, process, and outcomes measures have assessed health care quality. For clinical laboratories, structural quality has generally been assessed by inspection. For assessing process, quality indicators (QIs), statistical monitors of steps in the clinical laboratory total testing, have proliferated across the globe. Connections between structural and process laboratory measures and patient outcomes, however, have rarely been demonstrated. METHODS: To inform further development of clinical laboratory quality systems, we conducted a selective but worldwide review of publications on clinical laboratory quality assessment. RESULTS: Some QIs, like seven generic College of American Pathologists Q-Tracks monitors, have demonstrated significant process improvement; other measures have uncovered critical opportunities to improve test selection and result management. The College of Pathologists of Australasia Key Indicator Monitoring and Management System has deployed risk calculations, introduced from failure mode effects analysis, as surrogate measures for outcomes. Showing economic value from clinical laboratory testing quality is a challenge. CONCLUSIONS: Clinical laboratories should converge on fewer (7-14) rather than more (21-35) process monitors; monitors should cover all steps of the testing process under laboratory control and include especially high-risk specimen-quality QIs. Clinical laboratory stewardship, the combination of education interventions among clinician test orderers and report consumers with revision of test order formats and result reporting schemes, improves test ordering, but improving result reception is more difficult. Risk calculation reorders the importance of quality monitors by balancing three probabilities: defect frequency, weight of potential harm, and detection difficulty. The triple approach of (1) a more focused suite of generic consensus quality indicators, (2) more active clinical laboratory testing stewardship, and (3) integration of formal risk assessment, rather than competing with economic value, enhances it.

Interpretive Diagnostic Error Reduction in Surgical Pathology and Cytology: Guideline From the College of American Pathologists Pathology and Laboratory Quality Center and the Association of Directors of Anatomic and Surgical Pathology.

CONTEXT: Additional reviews of diagnostic surgical and cytology cases have been shown to detect diagnostic discrepancies. OBJECTIVE: To develop, through a systematic review of the literature, recommendations for the review of pathology cases to detect or prevent interpretive diagnostic errors. DESIGN: The College of American Pathologists Pathology and Laboratory Quality Center in association with the Association of Directors of Anatomic and Surgical Pathology convened an expert panel to develop an evidence-based guideline to help define the role of case reviews in surgical pathology and cytology. A literature search was conducted to gather data on the review of cases in surgical pathology and cytology. RESULTS: The panel drafted 5 recommendations, with strong agreement from open comment period participants ranging from 87% to 93%. The recommendations are: (1) anatomic pathologists should develop procedures for the review of selected pathology cases to detect disagreements and potential interpretive errors; (2) anatomic pathologists should perform case reviews in a timely manner to avoid having a negative impact on patient care; (3) anatomic pathologists should have documented case review procedures that are relevant to their practice setting; (4) anatomic pathologists should continuously monitor and document the results of case reviews; and (5) if pathology case reviews show poor agreement within a defined case type, anatomic pathologists should take steps to improve agreement. CONCLUSIONS: Evidence exists that case reviews detect errors; therefore, the expert panel recommends that anatomic pathologists develop procedures for the review of pathology cases to detect disagreements and potential interpretive errors, in order to improve the quality of patient care.

Practices for Identifying and Rejecting Hemolyzed Specimens Are Highly Variable in Clinical Laboratories.

CONTEXT: Hemolysis is an important clinical laboratory quality attribute that influences result reliability. OBJECTIVE: To determine hemolysis identification and rejection practices occurring in clinical laboratories. DESIGN: We used the College of American Pathologists Survey program to distribute a Q-Probes-type questionnaire about hemolysis practices to Chemistry Survey participants. RESULTS: Of 3495 participants sent the questionnaire, 846 (24%) responded. In 71% of 772 laboratories, the hemolysis rate was less than 3.0%, whereas in 5%, it was 6.0% or greater. A visual scale, an instrument scale, and combination of visual and instrument scales were used to identify hemolysis in 48%, 11%, and 41% of laboratories, respectively. A picture of the hemolysis level was used as an aid to technologists' visual interpretation of hemolysis levels in 40% of laboratories. In 7.0% of laboratories, all hemolyzed specimens were rejected; in 4% of laboratories, no hemolyzed specimens were rejected; and in 88% of laboratories, some specimens were rejected depending on hemolysis levels. Participants used 69 different terms to describe hemolysis scales, with 21 terms used in more than 10 laboratories. Slight and moderate were the terms used most commonly. Of 16 different cutoffs used to reject hemolyzed specimens, moderate was the most common, occurring in 30% of laboratories. For whole blood electrolyte measurements performed in 86 laboratories, 57% did not evaluate the presence of hemolysis, but for those that did, the most common practice in 21 laboratories (24%) was centrifuging and visually determining the presence of hemolysis in all specimens. CONCLUSIONS: Hemolysis practices vary widely. Standard assessment and consistent reporting are the first steps in reducing interlaboratory variability among results.

Assessing Clinical Laboratory Quality: A College of American Pathologists Q-Probes Study of Prothrombin Time INR Structures, Processes, and Outcomes in 98 Laboratories.

CONTEXT: The anticoagulant warfarin has been identified as the second most frequent drug responsible for serious, disabling, and fatal adverse drug events in the United States, and its effect on blood coagulation is monitored by the laboratory test called international normalized ratio (INR). OBJECTIVE: To determine the presence of INR policies and procedures, INR practices, and completeness and timeliness of reporting critical INR results in participants' clinical laboratories. DESIGN: Participants reviewed their INR policies and procedure requirements, identified their practices by using a questionnaire, and studied completeness of documentation and timeliness of reporting critical value INR results for outpatients and emergency department patients. RESULTS: In 98 participating institutions, the 5 required policies and procedures were in place in 93% to 99% of clinical laboratories. Fifteen options for the allowable variations among duplicate results from different analyzers, 12 different timeliness goals for reporting critical values, and 18 unique critical value limits were used by participants. All required documentation elements were present in 94.8% of 192 reviewed INR validation reports. Critical value INR results were reported within the time frame established by the laboratory for 93.4% of 2604 results, but 1.0% of results were not reported. Although the median laboratories successfully communicated all critical results within their established time frames and had all the required validation elements based in their 2 most recent INR calculations, those participants at the lowest 10th percentile were successful in 80.0% and 85.7% of these requirements, respectively. CONCLUSIONS: Significant opportunities exist for adherence to INR procedural requirements and for practice patterns and timeliness goals for INR critical results' reporting.

Clinical Laboratory Quality Practices When Hemolysis Occurs.

CONTEXT: Hemolyzed specimens delay clinical laboratory results, proliferate unnecessary testing, complicate physician decisions, injure patients indirectly, and increase health care costs. OBJECTIVE: To determine quality improvement practices when hemolysis occurs. DESIGN: We used the College of American Pathologists (CAP) Survey Program to distribute a Q-Probes-type questionnaire about hemolysis practices to CAP Chemistry Survey participants. RESULTS: Of 3495 participants sent the questionnaire, 846 (24%) responded. Although 85%, 69%, and 55% of participants had written hemolysis policies for potassium, lactate dehydrogenase, and glucose, respectively, only a few (46%, 40%, and 40%) had standardized hemolysis reports between their primary and secondary chemistry analyzers for these 3 analytes. Most participants (70%) had not attempted to validate the manufacturers' hemolysis data for these 3 analytes; however, essentially all who tried, succeeded. Forty-nine percent of participants had taken corrective action to reduce hemolysis during the past year and used, on average, 2.4 different actions, with collection and distribution of hemolysis data to administrative leadership (57%), troubleshooting outliers (55%), retraining phlebotomist (53%), and establishment of quality improvement teams among the laboratory and at problem locations (37%) being the most common actions. When asked to assess their progress in reducing hemolysis, 70% noted slow to no progress, and 2% gave up on improvement. Upon measuring potassium, lactate dehydrogenase, and glucose, approximately 60% of participants used the same specimen flag for hemolysis as for lipemia and icterus. CONCLUSIONS: Hemolysis decreases the quality and increases the cost of health care. Practices for measuring, reporting, and decreasing hemolysis rates need improvement.

Correlation of High Body Mass Index With More Advanced Localized Prostate Cancer at Radical Prostatectomy Is Not Reflected in PSA Level and PSA Density but Is Seen in PSA Mass.

OBJECTIVES: Prostate cancer screening algorithms and preoperative nomograms do not include patients' body mass index (BMI). We evaluated outcomes at radical prostatectomy (RP) adjusted to BMI. METHODS: Serum prostate-specific antigen (PSA) levels, PSA mass, PSA density (PSAD), and RP findings were analyzed with respect to BMI in 4,926 men who underwent RP between 2005 and 2014. RESULTS: In total, 1,001 (20.3%) men were normal weight, 2,547 (51.7%) were overweight, and 1,378 (28%) were obese. Median PSA levels (ng/mL) were normal weight, 5.0; overweight, 5.1; and obese, 5.2 (P = .094). Median PSA mass increased with increasing BMI: 15.9 vs 17.4 vs 19.4 µg (P < .001). Median PSAD was not significantly different: 0.11 vs 0.11 vs 0.11 ng/mL/g (P = .084). Median prostate weight increased with increasing BMI: 44 vs 45 vs 49 g (P < .001). Median prostatectomy tumor volume increased with increasing BMI: 3.9 vs 4.7 vs 5.9 cm(3) (P < .001). Overweight and obese patients had a higher Gleason score and more locally advanced cancer (P < .001). Frequency of positive surgical margins increased with higher BMIs (P < .001). Frequency of lymph node metastasis did not differ significantly (P = .088). CONCLUSIONS: While BMI correlates with tumor volume, Gleason score, and extent of disease at RP, there is no routinely measured clinical parameter reflecting this. Only PSA mass highlights this correlation. Thus, BMI and potentially PSA mass should be taken into account in predictive algorithms pertaining to prostate cancer and its surgical treatment.

Seven Q-Tracks monitors of laboratory quality drive general performance improvement: experience from the College of American Pathologists Q-Tracks program 1999-2011.

CONTEXT: Many production systems employ standardized statistical monitors that measure defect rates and cycle times, as indices of performance quality. Clinical laboratory testing, a system that produces test results, is amenable to such monitoring. OBJECTIVE: To demonstrate patterns in clinical laboratory testing defect rates and cycle time using 7 College of American Pathologists Q-Tracks program monitors. DESIGN: Subscribers measured monthly rates of outpatient order-entry errors, identification band defects, and specimen rejections; median troponin order-to-report cycle times and rates of STAT test receipt-to-report turnaround time outliers; and critical values reporting event defects, and corrected reports. From these submissions Q-Tracks program staff produced quarterly and annual reports. These charted each subscriber's performance relative to other participating laboratories and aggregate and subgroup performance over time, dividing participants into best and median performers and performers with the most room to improve. Each monitor's patterns of change present percentile distributions of subscribers' performance in relation to monitoring durations and numbers of participating subscribers. Changes over time in defect frequencies and the cycle duration quantify effects on performance of monitor participation. RESULTS: All monitors showed significant decreases in defect rates as the 7 monitors ran variously for 6, 6, 7, 11, 12, 13, and 13 years. The most striking decreases occurred among performers who initially had the most room to improve and among subscribers who participated the longest. All 7 monitors registered significant improvement. Participation effects improved between 0.85% and 5.1% per quarter of participation. CONCLUSIONS: Using statistical quality measures, collecting data monthly, and receiving reports quarterly and yearly, subscribers to a comparative monitoring program documented significant decreases in defect rates and shortening of a cycle time for 6 to 13 years in all 7 ongoing clinical laboratory quality monitors.

Timeliness and accuracy of reporting preliminary blood culture results: a College of American Pathologists Q-probes study of 65 institutions.

CONTEXT: The speed and accuracy of preliminary blood culture reports impacts patient management and outcomes. OBJECTIVE: To evaluate the accuracy and timeliness of preliminary blood culture results among multiple laboratories. DESIGN: Q-Probes participants collected turnaround time (TAT) data on preliminary Gram stains, compared accuracy of up to 100 preliminary to final culture Gram stain results, and described blood culture laboratory practices. RESULTS: Sixty-four laboratories and 5031 blood cultures were evaluated. All participants used continuously monitoring blood culture systems. Median TAT from initial growth detection to notification of results was 45 minutes, with the longest component being preparation of Gram stains (median time = 25 minutes). Participants (N = 40) reporting a continuous schedule for processing blood cultures had significantly lower overall TAT (median= 37 minutes) compared with 15 participants with intermittent processing schedules (median= 124 minutes), P= .003. Time to complete Gram stain processing was lower (median time = 21 minutes) for 39 participants using continuous processing schedule compared with 14 others (median time= 67 minutes), P= .03. Goals for total TAT were used by 27 of 56 participants (48.2%). Having goals did not significantly affect TAT. A total of 4962 of 5021 Gram stain results (98.8%) agreed with final culture results. The highest discrepancy rates occurred among gram-positive bacilli (20 of 335; 6.0%) and mixed cultures (22 of 106; 20.8%). CONCLUSIONS: This study provides benchmarks for assessing blood culture quality performance. Timeliness and accuracy of preliminary blood culture reports were excellent. However, nearly one-third of laboratories did not process blood cultures continuously. This significantly prolonged reporting results, which could affect patient outcomes.

Do circulating tumor cells, exosomes, and circulating tumor nucleic acids have clinical utility? A report of the association for molecular pathology.

Diagnosing and screening for tumors through noninvasive means represent an important paradigm shift in precision medicine. In contrast to tissue biopsy, detection of circulating tumor cells (CTCs) and circulating tumor nucleic acids provides a minimally invasive method for predictive and prognostic marker detection. This allows early and serial assessment of metastatic disease, including follow-up during remission, characterization of treatment effects, and clonal evolution. Isolation and characterization of CTCs and circulating tumor DNA (ctDNA) are likely to improve cancer diagnosis, treatment, and minimal residual disease monitoring. However, more trials are required to validate the clinical utility of precise molecular markers for a variety of tumor types. This review focuses on the clinical utility of CTCs and ctDNA testing in patients with solid tumors, including somatic and epigenetic alterations that can be detected. A comparison of methods used to isolate and detect CTCs and some of the intricacies of the characterization of the ctDNA are also provided.

Twenty-five years of accomplishments of the College of American Pathologists Q-probes program for clinical pathology.

CONTEXT: During the past 25 years, the College of American Pathologists' (CAP) Q-Probes program has been available as a subscription program to teach laboratorians how to improve the quality of clinical laboratory services. OBJECTIVE: To determine the accomplishments of the CAP Q-Probes program. DESIGN: We reviewed Q-Probes participant information, study data and conclusions, author information, and program accomplishments. RESULTS: During this time 117 Q-Probes clinical pathology studies were conducted by 54 authors and coauthors, 42,899 laboratories enrolled from 24 countries, 98 peer-reviewed publications occurred and were cited more than 1600 times, and the studies were featured 59 times in CAP Today. The most frequent studies (19) focused on turnaround times for results or products at specific locations (emergency department, operating room, inpatients, outpatients), specific diseases (acute myocardial infarction, urinary tract), availability for specific events such as morning rounds or surgery, a specific result (positive blood cultures), and a method on how to use data for improvement (stat test outliers). Percentile ranking of study participants with better performance provided benchmarks for each study with attributes statistically defined that influenced improved performance. Other programs, such as an ongoing quality improvement program (Q-Tracks), a laboratory competency assessment program, a pathologist certification program, and an ongoing physician practice evaluation program (Evalumetrics), have been developed from Q-Probes studies. CONCLUSIONS: The CAP's Q-Probes program has made significant contributions to the medical literature and has developed a worldwide reputation for improving the quality of clinical pathology services worldwide.

Fifteen years' experience of a College of American Pathologists program for continuous monitoring and improvement.

CONTEXT: The Q-Tracks program, created in 1999, is a quality monitoring subscription service offered by the College of American Pathologists. OBJECTIVE: To establish benchmarks in quality metrics, monitor changes in performance over time, and identify practice characteristics associated with better performance. DESIGN: The Q-Tracks program provides ongoing study of multiple metrics offered in most laboratory disciplines. The design enables measuring the effects of process changes and comparisons with other participating laboratories. Each laboratory Q-Tracks monitor has a primary quality indicator and additional secondary indicators. RESULTS: To date, 19 Q-Tracks monitors have been offered, with 12 currently active monitors. Q-Tracks are primarily conducted in hospital-based laboratories in the United States, Canada, and 21 other countries. Common to most Q-Tracks monitors is a demonstration of performance improvement by subscribers with long-term participation. This finding was seen in preanalytic, turnaround time, and postanalytic measures. Q-Tracks monitors contribute to the overall demonstration and improvement of laboratory and hospital quality because they address core quality measures for the College of American Pathologists Laboratory Accreditation Program and multiple Joint Commission National Patient Safety Goals. CONCLUSIONS: The Q-Tracks program has established multiple benchmarks in most disciplines of the laboratory and has demonstrated significant performance improvement in benchmarks and individual laboratories over time.

Surgical pathology report defects: a College of American Pathologists Q-Probes study of 73 institutions.

CONTEXT: The rate of surgical pathology report defects is an indicator of quality and it affects clinician satisfaction. OBJECTIVE: To establish benchmarks for defect rates and defect fractions through a large, multi-institutional prospective application of standard taxonomy. DESIGN: Participants in a 2011 Q-Probes study of the College of American Pathologists prospectively reviewed all surgical pathology reports that underwent changes to correct defects and reported details regarding the defects. RESULTS: Seventy-three institutions reported 1688 report defects discovered in 360,218 accessioned cases, for an aggregate defect rate of 4.7 per 1000 cases. Median institutional defect rate was 5.7 per 1000 (10th to 90th percentile range, 13.5-0.9). Defect rates were higher in institutions with a pathology training program (8.5 versus 5.0 per 1000, P = .01) and when a set percentage of cases were reviewed after sign-out (median, 6.7 versus 3.8 per 1000, P = .10). Defect types were as follows: 14.6% misinterpretations, 13.3% misidentifications, 13.7% specimen defects, and 58.4% other report defects. Overall, defects were most often detected by pathologists (47.4%), followed by clinicians (22.0%). Misinterpretations and specimen defects were most often detected by pathologists (73.5% and 82.7% respectively, P < .001), while misidentifications were most often discovered by clinicians (44.6%, P < .001). Misidentification rates were lower when all malignancies were reviewed by a second pathologist before sign-out (0.0 versus 0.6 per 1000, P < .001), and specimen defect rates were lower when intradepartmental review of difficult cases was conducted after sign-out (0.0 versus 0.4 per 1000, P = .02). CONCLUSION: This study provides benchmarking data on report defects and defect fractions using standardized taxonomy.

Precursor lesions of mucinous carcinoma of the breast: analysis of 130 cases.

Mucinous mammary carcinoma (MC) is a tumor type with relatively favorable prognosis. Unlike the circumstances surrounding conventional invasive duct carcinoma, data are limited regarding precursor lesions for MC. This study characterizes patterns of mucinous ductal carcinoma in situ (DCIS) as a precursor lesion for MC. All slides from 130 cases of MC encountered between 2000 and 2011 at Henry Ford Hospital, Detroit, MI were reviewed to subclassify MC, identify DCIS, and explore transition patterns from DCIS to MC. Calponin, p63, chromogranin, synaptophysin, CD56, and MIB-1 immunostaining analyses were performed in 65 cases. Among 106 cases of pure (71 type A, 35 type B) and 24 cases of mixed MC, DCIS appeared in 88 (68%) specimens, with all but 4 showing luminal mucin accumulation. Dominant patterns of mucinous DCIS were cribriform/solid (66), cribriform and papillary (7), papillary (5), micropapillary (3), and flat (3). Fifty-seven (68%) cases of mucinous DCIS demonstrated transitions from DCIS to MC. Luminal mucinous distention, focal flattening and attenuation of the epithelium, and disruption of the duct wall resulting in a mucocele-like extravasation of malignant epithelia with escaping mucin was a transition pattern seen with all architectures of DCIS and in all types of MC. This was the only pattern of transition to type A MC. The epithelial outpouching, formation of a cleft with accumulation of mucin around the epithelium, and transition into mucin pools with floating tumor cell clusters was the second transition pattern that went from cribriform/solid DCIS to type B and mixed MC. DCIS preceding aggressive phenotypes of MC (type B and mixed) more often had a cribriform/solid architecture, higher nuclear grade, and higher Ki-67-labeling index (all P<0.05). In summary, mucinous DCIS is a precursor to MC with distinctive features that link patterns of DCIS with aggressive MC phenotypes. The 2 observed transitions between mucinous DCIS and MC suggest that pathogenesis of different types of MC is different correlating with less or more aggressive behavior of the latter.

Evaluation of a microarray-based assay for rapid identification of Gram-positive organisms and resistance markers in positive blood cultures.

Rapid identification of pathogens directly from positive blood cultures can play a major role in reducing patient mortality rates. We evaluated the performance of the Verigene Gram-Positive Blood Culture (BC-GP) assay (Nanosphere Inc., Northbrook, IL) for detection of commonly isolated Gram-positive organisms as well as associated resistance markers from positive blood cultures. Positive blood cultures (VersaTREK; Trek Diagnostic Systems, Independence, OH) from 203 patients with Gram-positive organism infections were analyzed using the BC-GP assay within 12 h for the detection of 12 different organisms, including staphylococci, streptococci, and enterococci, as well as for the presence of 3 resistance markers (mecA, vanA, and vanB). Results were compared to those of routine laboratory methods for identification and susceptibility testing. For identification of organisms and detection of resistance markers in 178 monomicrobial positive blood cultures, the BC-GP assay showed 94% and 97% concordance, respectively, with routine methods. After 25 polymicrobial cultures were included, the results showed 92% and 96% agreement for identification and resistance markers, respectively, for a total of 203 positive cultures. In 6/25 polymicrobial cultures, at least 1 isolate was not detected. Concordance levels for detection of major pathogens such Staphylococcus aureus (n = 45) and enterococci (n = 19) were 98% and 95%, respectively. Agreement levels for detection of resistance markers such as mecA and vanA/B were 92% and 100%, respectively. The BC-GP assay is capable of providing rapid identification of Gram-positive cocci as well as detection of resistance markers directly from positive blood cultures at least 24 to 48 h earlier than conventional methods.