High Clinical Impact of Broad-Range Fungal PCR in Suspected Fungal Sinusitis.

Broad-range fungal PCR is a powerful tool for identifying pathogens directly from patient specimens; however, reported estimates of clinical utility vary and costs discourage universal testing. We investigated the diagnostic and clinical utility of broad-range fungal PCR by examining 9 years of results from sinonasal specimens, hypothesizing that this anatomic location would identify immunocompromised patients at high risk for invasive fungal disease. We retrospectively identified 644 PCRs and 1,446 fungal cultures from sinus sites. To determine the relative performance of each testing modality, we performed chart review on 52 patients having specimens submitted for culture and PCR on the same day. Positivity rates were significantly higher for PCR (37.1%) than culture (13.7%) but similar for formalin-fixed and fresh tissues (42.3% versus 34.6%). Relative to culture, PCR had significantly faster turnaround time to both preliminary (94.5 versus 108.8 h) and final positive (137.9 versus 278.5 h) results. Among chart-reviewed patients, 88% were immunocompromised, 65% had proven or probable fungal disease, and testing sensitivities for culture and PCR (67.5% and 85.0%) were not statistically different. Nevertheless, PCR identified pathogens not recovered by culture in 14.9% of cases and informed clinical decision-making in 16.7% of all reviewed cases, and sensitivity of PCR combined with culture (90.0%) was higher than that of culture alone. We conclude that broad-range fungal PCR is frequently informative for patients at risk of serious fungal disease and is complementary to and has faster turnaround time than culture. Formalin-fixed tissue does not adversely affect diagnostic yield, but anatomic site may impact assay positivity rates.

Low Prevalence of Severe Acute Respiratory Syndrome Coronavirus 2 Among Pregnant and Postpartum Patients With Universal Screening in Seattle, Washington.

We found low prevalence of SARS-CoV-2 (2.7% [5/188]) among pregnant and postpartum patients with universal testing. Prevalence among symptomatic patients was similar under initial targeted screening (22.2% [4/18]) and universal approaches (19.1% [8/42]). Among 170 asymptomatic patients, 2 were positive or inconclusive, respectively; repeat testing at 24 hours was negative.

Expedited SARS-CoV-2 screening of donors and recipients supports continued solid organ transplantation.

Universal screening of potential organ donors and recipients for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now recommended prior to transplantation in the United States during the coronavirus disease 19 (COVID-19) pandemic. Challenges have included limited testing capacity, short windows of organ viability, brief lead time for notification of potential organ recipients, and the need to test lower respiratory donor specimens to optimize sensitivity. In an early U.S. epicenter of the outbreak, we designed and implemented a system to expedite this testing and the results here from the first 3 weeks. The process included a Laboratory Medicine designee for communication with organ recovery and transplant clinical staff, specialized sample labeling and handoff, and priority processing. Thirty-two organs recovered from 14 of 17 screened donors were transplanted vs 70 recovered from 23 donors during the same period in 2019. No pretransplant or organ donors tested positive for SARS-CoV-2. Median turnaround time from specimen receipt was 6.8 hours (donors), 6.5 hours (recipients): 4.5 hours faster than daily inpatient median. No organ recoveries or transplantations were disrupted by a lack of SARS-CoV-2 testing. Waitlist inactivations for COVID-19 precautions were reduced in our region. Systems that include specialized ordering pathways and adequate testing capacity can support continued organ transplantation, even in a SARS-CoV-2 hyperendemic area.

Detection of SARS-CoV-2 by bronchoscopy after negative nasopharyngeal testing: Stay vigilant for COVID-19.

PURPOSE: Real-time polymerase chain reaction (RT-PCR) detection of severe acute respiratory syndrome coronavirus (SARS-CoV-2) is required for diagnosis of coronavirus disease 2019 (COVID-19). Sensitivity of RT-PCR nasopharyngeal (NP) testing is presumed to be high, but there is no gold standard against which this has been determined. The objective was to determine whether lower respiratory tract infection (LRTI), detected in bronchoalveolar lavage fluid (BALF), occurs in the absence of upper respiratory tract infection with clinical testing of both specimen types. METHODS: Between March 26, 2020 and April 17, 2020 at the University of Washington Medical Center all patients with BALF specimens clinically tested for SARS-CoV-2 were identified. We assessed the proportion of patients with positive RT-PCR for SARS-CoV-2 in BALF after negative NP testing. We describe 3 cases with positive testing in BALF. RESULTS: Among 16 patients with BALF samples, 3 cases (19%) had SARS-CoV-2 detected in BALF. In Case 1, negative NP testing occurred early in the infection and respiratory symptoms may have been missed due to neurologic injury. In Case 2, outpatient diagnosis was aspiration pneumonia, but clinical suspicion remained high for COVID-19 at hospitalization based on epidemiological and clinical features. All 3 cases involved older adults (age >65 years), one of whom was immunosuppressed in the setting of lung transplantation (Case 3). CONCLUSIONS: These data demonstrate that SARS-CoV-2 LRTI occurs in the presence of negative NP testing. NP testing may underestimate the prevalence of COVID-19 and has implications for spread of SARS-CoV2 in the community and healthcare setting.

Measuring the rate of manual transcription error in outpatient point-of-care testing.

Many point-of-care laboratory tests are manually entered into the electronic health record by ambulatory clinic staff, but the rate of manual transcription error for this testing is poorly characterized. Using a dataset arising from a duplicated workflow that created a set of paired interfaced and manually entered point-of-care glucose measurements, we found that 260 of 6930 (3.7%) manual entries were discrepant from their interfaced result. Thirty-seven of the 260 (14.2%) errors were discrepant by more than 20% and included potentially dangerous mistranscriptions. An additional 37 (14.2%) errors were due to inclusion of non-numeric characters. Staff-entered result flags deviated from the result flag generated in the laboratory information system in 5121 of 6930 (73.9%) pairs. These data demonstrate that clinically significant discrepancies for clinic-entered point of care results occurred at a rate of approximately 5 per 1000 results and they underline the importance of interfacing instruments when feasible.

Transfusion support for transgender men of childbearing age.

BACKGROUND: To date, limited attention has been given to transgender recipients of blood components, particularly transgender men of childbearing age. Here, we highlight the essential information needed to provide transfusion support for this population. CASE REPORT: A 40-year-old transgender man, who retained his uterus and ovaries, presented with severe vaginal hemorrhage following biopsies for a cervical mass. He was admitted to the Gynecology unit and emergency blood was ordered. Because the patient was listed as male in the electronic health record (EHR), the transfusion service prepared uncrossmatched type O, RhD-positive red blood cells (RBC). After the sex/gender incongruence was recognized, the units were switched for Rh-negative. CONCLUSION: This case illustrates particular considerations when caring for transgender patients: gender/sex documentation, decision-making processes when gender/sex-specific care applies, and challenges to the pathology service.

Evidence-Based Validation of Hemolysis Index Thresholds by Use of Retrospective Clinical Data.

BACKGROUND: Semiquantitative hemolysis indices (HIs) are used by chemistry analyzers to measure sample integrity, but there is little standardization in HI reporting or validation of analyte-specific HI flagging. Additional methods of HI threshold validation are needed. METHODS: We retrospectively queried serum and plasma potassium measurements, HIs, and contemporaneous whole blood potassium measurements. Serum and plasma values were compared to whole blood values drawn within 6 h (n = 6422 pairs), and discrepancies between values were compared across HIs. We also retrieved orders of potassium-lowering medications occurring shortly after release of potassium results from hemolyzed samples. RESULTS: While nonhemolyzed samples showed high agreement, a significant percentage of released hemolyzed samples (36.1% of the most hemolyzed group) were discrepant by 1 mEq/L or more. In total, 15.5% of patients with an order from the hyperkalemia order set had the order after a hemolyzed value; the majority of those patients (42 of 46; 91.3%) received a potassium-lowering medication, most of whom did not have a redraw before drug administration. CONCLUSIONS: Retrospective review of discrepancies identified marked inconsistencies among higher HI samples and identified opportunities for improving the laboratory reporting policy, offering a clinical validation of the HI thresholds for potassium. Clinicians generally treated patients with hemolyzed samples, underscoring the importance of maintaining sample quality.

Pseudohypophosphatemia associated with high-dose liposomal amphotericin B therapy.

BACKGROUND: Hypophosphatemia is commonly observed in critically ill patients. Inorganic phosphorus is quantified by spectrophotometric measurement of a phosphomolybdate complex, a method with multiple documented interferents. Our clinical laboratory was contacted to investigate a case of asymptomatic hypophosphatemia in a patient receiving high-dose liposomal amphotericin B therapy (L-AMB). METHODS: In vitro experiments were performed by spiking L-AMB into residual plasma specimens. Phosphate was measured on the Beckman Coulter AU and Ortho Diagnostics Vitros instruments. RESULTS: When measured on the AU, phosphate in plasma with approximately 250mcg/mL of L-AMB demonstrated a median negative bias of 3.45mg/dL relative to unspiked samples. In contrast, Vitros phosphate measurements demonstrated excellent agreement for specimens with and without L-AMB (median bias -0.2mg/dL). CONCLUSIONS: High L-AMB concentrations induced a significant negative bias on phosphate measured by the AU assay, but did not affect the Vitros assay. Laboratorians and clinicians should be aware of this phenomenon in patients receiving L-AMB who develop unexplained hypophosphatemia.

Modelling the effects of blood component storage lesions on the quality of haemostatic resuscitation in massive transfusion for trauma.

BACKGROUND: All blood components undergo loss of potency during storage. These loss-of-potency storage lesions are important in trauma resuscitation because they reduce the haemostatic capacity of mixtures of components that attempt to reconstitute whole blood. Even red cell storage-related loss of potency, which averages 17% with modern additive solutions, is important because 6 units of red cells must be given to achieve the effect of 5 fully potent units. MATERIALS AND METHODS: Loss of potency of stored units of red blood cells, plasma, platelets, and cryoprecipitate were summed for dilutional, storage-related, pathogen reduction-related, and splenic sequestration-related causes and expressed as fractional plasma coagulation factor concentrations and platelet counts. RESULTS: Production of reconstituted whole blood from 1:1:1 unit ratios of red cells:plasma:platelets is associated with a 38% loss of plasma coagulation factor concentration and 56% loss of platelets. Storage losses of 17% for red cells, 10% for coagulation factors, and 30% for platelets are additive to pathogen reduction-related losses of 18% for coagulation factors and 30% for platelets. DISCUSSION: Component preparation and storage-related losses of potency for all blood components are serious problems for trauma resuscitation. Even red cell storage contributes to this problem and this can be made better in ways that can save many lives each year.

An Evaluation of Recurrent Diabetic Ketoacidosis, Fragmentation of Care, and Mortality Across Chicago, Illinois.

OBJECTIVE: A portion of patients with diabetes are repeatedly hospitalized for diabetic ketoacidosis (DKA), termed recurrent DKA, which is associated with poorer clinical outcomes. This study evaluated recurrent DKA, fragmentation of care, and mortality throughout six institutions in the Chicago area. RESEARCH DESIGN AND METHODS: A deidentified Health Insurance Portability and Accountability Act-compliant data set from six institutions (HealthLNK) was used to identify 3,615 patients with DKA (ICD-9 250.1x) from 2006 to 2012, representing 5,591 inpatient admissions for DKA. Demographic and clinical data were queried. Recurrence was defined as more than one DKA episode, and fragmentation of health care was defined as admission at more than one site. RESULTS: Of the 3,615 patients, 780 (21.6%) had recurrent DKA. Patients with four or more DKAs (n = 211) represented 5.8% of the total DKA group but accounted for 26.3% (n = 1,470) of the encounters. Of the 780 recurrent patients, 125 (16%) were hospitalized at more than one hospital. These patients were more likely to recur (odds ratio [OR] 2.96; 95% CI 1.99, 4.39; P < 0.0001) and had an average of 1.88-times the encounters than nonfragmented patients. Although only 13.6% of patients died of any cause during the study period, odds of death increased with age (OR 1.06; 95% CI 1.05, 1.07; P < 0.001) and number of DKA encounters (OR 1.28; 95% CI 1.04, 1.58; P = 0.02) after adjustment for age, sex, insurance, race, fragmentation, and DKA visit count. This study was limited by lack of medical record-level data, including comorbidities without ICD-9 codes. CONCLUSIONS: Recurrent DKA was common and associated with increased fragmentation of health care and increased mortality. Further research is needed on potential interventions in this unique population.