Rapid Testing Algorithm Performance in a Low-Prevalence Environment.

BACKGROUND: The performance of a statewide HIV rapid test algorithm (RTA) in a low-prevalence setting (0.71%) was examined for 3 years. METHODS: An initial rapid screening by HIV-1/2 Ag/Ab Combo test (RT#1) with Ab verification using a second, different rapid test (RT#2) was conducted. Clinic referral was immediate for antigen-only-positive screens. Antibody-positive screens were confirmed by RT#2. Specimens were collected following discordant RTA results (initially Ab-POS by RT#1, but negative on RT#2) and tested in accordance with the current Centers for Disease Control and Prevention/Association of Public Health Laboratories-based HIV diagnostic algorithm supplemented by a quantitative viral load whenever possible. RESULTS: Of 310,785 tests performed, 2400 preliminary positive screens were identified; 2191 (91.8%) confirmed by RT#2. Of 13 Determine Combo AG-POS results identified, only 1 confirmed positive. Of the remaining 196 discordant results, 182 (92.9%) were uninfected, including 13 with AG-POS/AB-POS results. Of 14 true positives (7.1%) identified after discordant RTA results, the average quantitative HIV-1 viral load was 277,385 copies/mL, but 5 (35.7%) of 14 had viral loads <1000 copies/mL. Among the 2191 "presumptive positive" by RTA, 3 false-positive (FP) RTAs were reported (both rapid tests having positive results, while the HIV-1/2 Ag/Ab assay and quantitative HIV-1 viral load showed negative results). CONCLUSIONS: The RTA was effective in predicting true-positive HIV test results and facilitating linkage to care. Discordant results were infrequent. Fingerstick DC Ag detection identified a single early infection. Many discordant cases that were subsequently positive were associated with viral loads <1000 copies/mL.

COVID-19 Vaccine Responses in Patients With Plasma Cell Dyscrasias After Complete Vaccination.

INTRODUCTION: Due to functional hypogammaglobulinemia, patients with multiple myeloma are at increased risk for infection and generally have poorer responses to vaccines. In this study, we examined antibody responses after complete COVID-19 vaccination in patients with plasma cell dyscrasias, most of whom were receiving treatment. PATIENTS AND METHODS: Real world study of consecutive patients with multiple myeloma and other plasma cell dyscrasias (PCD) were evaluated after complete vaccination with either the 2-shot mRNA vaccines from BioNTech and Moderna or the 1-shot adenoviral vector vaccine from Johnson & Johnson (J&J). Patients received vaccines 1-4 months before antibody testing without controlling for the type of vaccine or the timing of drug therapy. Patients with a clinical history or antibody evidence of prior infection were excluded. Antinucleocapsid and quantitative anti-spike antibody levels were measured with the Roche Elecys assay. RESULTS: Ninety-five percent of patients had detectable antibody responses. Multivariate analysis showed that higher age, ongoing anti-CD38 monoclonal antibody therapy and the J&J vaccine negatively affected quantitative response. A small number of ineffectively vaccinated patients receiving IVIG subsequently had detectable nucleocapsid and spike antibodies confirming the presence of the latter in currently administered IVIG. CONCLUSIONS: Nearly all PCD had detectable anti-spike antibodies after vaccination but age, anti-CD38 monoclonal antibody therapy, and the single-shot J&J vaccine negatively affected responses. In patients who received the J&J vaccine, second doses or heterologous mRNA vaccines should be tested. Quantitative antibody testing might make future management more rational, particularly in patients with poor responses.

Impact of Insurance Status on Survival Outcomes in Adults With Acute Lymphoblastic Leukemia (ALL): A Single-center Experience.

BACKGROUND: Socioeconomic factors including race, ethnicity, and poverty level have been associated with disparities in survival among adult patients with acute leukemia. Insurance status is also likely to affect survival outcomes in these patients but has not been well studied. We investigated the impact of insurance status at time of diagnosis on survival in adult patients with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Adult patients diagnosed with B-lineage ALL between January 1, 2007 and October 31, 2017 were included, with follow-up through January 19, 2018. Kaplan-Meier survival curves were used to estimate overall survival (OS) and progression-free survival (PFS) for the 2 groups. Cox proportional hazard regression methods were used for univariate and multivariate analyses. RESULTS: A total of 136 patients were included in the study, 29 without insurance and 107 with insurance at time of diagnosis. Patients without insurance were younger and more likely to be Hispanic or Latino compared with insured patients. When controlling for confounding variables, patients without insurance had worse PFS. There was no statistically significant difference in OS between the 2 groups. Hispanic or Latino ethnicity was associated with improved PFS and OS in multivariate analyses. CONCLUSIONS: Adult patients with ALL without health insurance at time of diagnosis had worse PFS when controlling for other relevant clinical factors. Lack of insurance may be an obstacle to timely, effective maintenance therapy in the outpatient setting. Further research is needed to understand how insurance status impacts survival and ways to mitigate any disparities.

Trends in Bone Marrow Sampling and Core Biopsy Specimen Adequacy in the United States and Canada: A Multicenter Study.

OBJECTIVES: To assess bone marrow (BM) sampling in academic medical centers. METHODS: Data from 6,374 BM samples obtained in 32 centers in 2001 and 2011, including core length (CL), were analyzed. RESULTS: BM included a biopsy (BMB; 93%) specimen, aspirate (BMA; 92%) specimen, or both (83%). The median (SD) CL was 12 (8.5) mm, and evaluable marrow was 9 (7.6) mm. Tissue contraction due to processing was 15%. BMB specimens were longer in adults younger than 60 years, men, and bilateral, staging, and baseline samples. Only 4% of BMB and 2% of BMB/BMA samples were deemed inadequate for diagnosis. BM for plasma cell dyscrasias, nonphysician operators, and ancillary studies usage increased, while bilateral sampling decreased over the decade. BM-related quality assurance programs are infrequent. CONCLUSIONS: CL is shorter than recommended and varies with patient age and sex, clinical circumstances, and center experience. While pathologists render diagnoses on most cases irrespective of CL, BMB yield improvement is desirable.

Evidence of both von Willebrand factor deposition and factor V deposition onto AL amyloid as the cause of a severe bleeding diathesis.

: Acquired coagulopathies are common; uncommonly, adsorption of coagulation factors from the circulation into the tissues by pathologic amyloid exceeds the body's ability to produce factor and results in acquired factor deficiency. When amyloidosis does cause a coagulopathy, it is most often acquired factor X deficiency, but there are rare reports of amyloidosis being associated with other acquired factor deficiencies. We investigated a case of a severe bleeding diathesis, the cause of which was combined acquired factor V deficiency and concomitant acquired von Willebrand syndrome. Studies revealed prolonged prothrombin time and activated partial thromboplastin time. Mixing patient plasma with normal plasma corrected both the prothrombin time and activated partial thromboplastin time. Assays showed decreased factor V activity of 27%; Ristocetin cofactor activity was decreased at 49%, but von Willebrand antigen was elevated at 213%. Multimer analysis was consistent with type 2 von Willebrand syndrome. Lymph node biopsy documented amyloid light chain type (AL) amyloidosis; extraction of protein from the lymph node documented AL lambda light chain amyloid. Marrow biopsy documented IgG lambda myeloma. Immunohistochemical staining of the lymph node, using investigational polyvalent antibodies, demonstrated that both von Willebrand factor and factor V were identifiable in areas of amyloid deposition, providing evidence that these coagulation factors were adsorbed to the amyloid protein, resulting in accelerated clearance from the circulation, previously reported to be the mechanism of cases of acquired factor X deficiency in the setting of amyloidosis. Although there are case reports of acquired von Willebrand syndrome because of amyloidosis and case reports of acquired factor V deficiency because of amyloidosis, this appears to be the first reported case of concomitant acquired von Willebrand syndrome and acquired factor V deficiency because of amyloidosis, and the first report of localization of both von Willebrand protein and factor V protein to AL amyloid as a cause of a severe bleeding diathesis.

Finding those at risk: acute HIV infection in Newark, NJ.

BACKGROUND: A screening strategy combining rapid HIV-1/2 (HIV) antibody testing with pooled HIV-1 RNA testing increases identification of HIV infections, but may have other limitations that restrict its usefulness to all but the highest incidence populations. OBJECTIVE: By combining rapid antibody detection and pooled nucleic acid amplification testing (NAAT) testing, we sought to improve detection of early HIV-1 infections in an urban Newark, NJ hospital setting. STUDY DESIGN: Pooled NAAT HIV-1 RNA testing was offered to emergency department patients and outpatients being screened for HIV antibodies by fingerstick-rapid HIV testing. For those negative by rapid HIV and agreeing to NAAT testing, pooled plasma samples were prepared and sent to the University of Washington where real-time reverse transcription-polymerase chain reaction (RT-PCR) amplification was performed. RESULTS: Of 13,226 individuals screened, 6381 had rapid antibody testing alone, and 6845 agreed to add NAAT HIV screening. Rapid testing identified 115 antibody positive individuals. Pooled NAAT increased HIV-1 case detection by 7.0% identifying 8 additional cases. Overall, acute HIV infection yield was 0.12%. While males represent only 48.1% of those tested by NAAT, all samples that screened positive for HIV-1 RNA were obtained from men. CONCLUSION: HIV-1 RNA testing of pooled, HIV antibody-negative specimens permits identification of recent infections. In Newark, pooled NAAT increased HIV-1 case detection and provided an opportunity to focus on treatment and prevention messages for those most at risk of transmitting infection. Although constrained by client willingness to participate in testing associated with a need to return to receive further results, use of pooled NAAT improved early infection sensitivity.

Use of a rapid HIV testing algorithm to improve linkage to care.

BACKGROUND: Awaiting definitive diagnosis before scheduling healthcare visits complicates HIV screening and referral. Clients screened by rapid tests as initially reactive often fail to return to receive definitive test results, are not linked to care and enter care late or not at all. OBJECTIVES: To evaluate statewide, (1) the accuracy of a single-visit, two test HIV rapid testing algorithm (RTA) and (2) its effect on referral to care for positive clients. STUDY DESIGN: A two-test RTA was implemented at 24 sites in New Jersey beginning in December 2008. All clients with a reactive rapid HIV test were offered a second rapid HIV test, and RTA results were compared with Western blot (WB). Referral to care occurred based upon two sequential positive rapid tests. RESULTS: The RTA program has screened 51,413 individuals obtaining 426 reactive rapid test results; 394 (92.5%) were reactive by a second rapid test, 32 (7.5%) had a negative second rapid test. Twenty-eight individuals refused WB testing. Of 369 RTA-positive individuals who have WB results, 368 (99.5%) were confirmed positive. Of RTA-positive clients, 290 (73.6%), including 25 (6.6%) who refused Western blot, were immediately referred for care including one individual with a false-positive RTA. CONCLUSIONS: The RTA reduced false positive results by 6.2% and agreed with WB results 99.5% of the time. Improved referral to care compared to traditional rapid HIV screening occurs when immediate referral is based on RTA verification of a preliminary positive rapid test. WB confirmation is not essential for effective screening and contributes to difficulties linking individuals to care.

PathMiner: a Web-based tool for computer-assisted diagnostics in pathology.

Large-scale, multisite collaboration has become indispensable for a wide range of research and clinical activities that rely on the capacity of individuals to dynamically acquire, share, and assess images and correlated data. In this paper, we report the development of a Web-based system, PathMiner , for interactive telemedicine, intelligent archiving, and automated decision support in pathology. The PathMiner system supports network-based submission of queries and can automatically locate and retrieve digitized pathology specimens along with correlated molecular studies of cases from "ground-truth" databases that exhibit spectral and spatial profiles consistent with a given query image. The statistically most probable diagnosis is provided to the individual who is seeking decision support. To test the system under real-case scenarios, a pipeline infrastructure was developed and a network-based test laboratory was established at strategic sites at the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Robert Wood Johnson University Hospital, the University of Pennsylvania School of Medicine, Hospital of the University of Pennsylvania, The Cancer Institute of New Jersey, and Rutgers University. The average five-class classification accuracy of the system was 93.18% based on a tenfold cross validation on a close dataset containing 3691 imaged specimens. We also conducted prospective performance studies with the PathMiner system in real applications in which the specimens exhibited large variations in staining characters compared with the training data. The average five-class classification accuracy in this open-set experiment was 87.22%. We also provide the comparative results with the previous literature and the PathMiner system shows superior performance.

Virtual microscopy and grid-enabled decision support for large-scale analysis of imaged pathology specimens.

Breast cancer accounts for about 30% of all cancers and 15% of cancer deaths in women. Advances in computer-assisted analysis hold promise for classifying subtypes of disease and improving prognostic accuracy. We introduce a grid-enabled decision support system for performing automatic analysis of imaged breast tissue microarrays. To date, we have processed more than 1,00,000 digitized specimens (1200 x 1200 pixels each) on IBM's World Community Grid (WCG). As a part of the Help Defeat Cancer (HDC) project, we have analyzed that the data returned from WCG along with retrospective patient clinical profiles for a subset of 3744 breast tissue samples, and have reported the results in this paper. Texture-based features were extracted from the digitized specimens, and isometric feature mapping was applied to achieve nonlinear dimension reduction. Iterative prototyping and testing were performed to classify several major subtypes of breast cancer. Overall, the most reliable approach was gentle AdaBoost using an eight-node classification and regression tree as the weak learner. Using the proposed algorithm, a binary classification accuracy of 89% and the multiclass accuracy of 80% were achieved. Throughout the course of the experiments, only 30% of the dataset was used for training.

High throughput analysis of breast cancer specimens on the grid.

Breast cancer accounts for about 30% of all cancers and 15% of all cancer deaths in women in the United States. Advances in computer assisted diagnosis (CAD) holds promise for early detecting and staging disease progression. In this paper we introduce a Grid-enabled CAD to perform automatic analysis of imaged histopathology breast tissue specimens. More than 100,000 digitized samples (1200 x 1200 pixels) have already been processed on the Grid. We have analyzed results for 3744 breast tissue samples, which were originated from four different institutions using diaminobenzidine (DAB) and hematoxylin staining. Both linear and nonlinear dimension reduction techniques are compared, and the best one (ISOMAP) was applied to reduce the dimensionality of the features. The experimental results show that the Gentle Boosting using an eight node CART decision tree as the weak learner provides the best result for classification. The algorithm has an accuracy of 86.02% using only 20% of the specimens as the training set.

Unusual forms of immature sporulating Coccidioides immitis diagnosed by fine-needle aspiration biopsy.

Coccidioidomycosis is an endemic infection acquired by inhalation of the spores (arthroconidia) of the thermally dimorphic fungus, Coccidioides immitis. The arthroconidia transform into spherical cells called mature spherules in the lung. Immature spherules and other atypical forms of immature C immitis have rarely been found in vivo. We report on a case that presented unusual forms of immature sporulating C immitis in a fine-needle aspiration specimen. A 36-year-old Chinese woman, living in New Jersey for the past 10 years, presented with fever, night sweats, hemoptysis, and an abnormal chest radiograph approximately 9 months after a brief vacation trip to the Grand Canyon in Arizona. She was treated with antibiotics for 4 weeks without improvement. Subsequent chest computed tomography showed a 3-cm cavitary lesion in the right lower lobe of the lung. Fine-needle aspiration biopsy revealed diverse morphologic forms of a fungus that was confirmed by culture as immature sporulating C immitis.