Publications by authors named "James M Crawford"

103 Publications

The Ethics of Artificial Intelligence in Pathology and Laboratory Medicine: Principles and Practice.

Acad Pathol 2021 Jan-Dec;8:2374289521990784. Epub 2021 Feb 16.

Department of Pathology, University of Michigan, Ann Arbor, MI, USA.

Growing numbers of artificial intelligence applications are being developed and applied to pathology and laboratory medicine. These technologies introduce risks and benefits that must be assessed and managed through the lens of ethics. This article describes how long-standing principles of medical and scientific ethics can be applied to artificial intelligence using examples from pathology and laboratory medicine.
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http://dx.doi.org/10.1177/2374289521990784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894680PMC
February 2021

Post-COVID-19 Cholangiopathy: A Novel Entity.

Am J Gastroenterol 2021 Jan 14. Epub 2021 Jan 14.

Division of Hepatology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, USA; Division of Infectious Diseases, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, USA; Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, USA; Department of Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, USA.

Introduction: Liver chemistry abnormalities are a frequent manifestation of coronavirus disease 2019 (COVID-19) but are usually transient and resolve with disease resolution.

Methods: We describe the clinical course and histologic features of 3 adults who developed prolonged and severe cholestasis during recovery from critical cardiopulmonary COVID-19.

Results: These patients had clinical and histologic features similar to secondary sclerosing cholangitis of the critically ill patient, but with unique histologic features including severe cholangiocyte injury and intrahepatic microangiopathy suggestive of direct hepatic injury from COVID-19.

Discussion: We believe that these cases constitute a novel severe post-COVID-19 cholangiopathy with potential for long-term hepatic morbidity.
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http://dx.doi.org/10.14309/ajg.0000000000001154DOI Listing
January 2021

Estimating the predictive value of negative severe acute respiratory coronavirus virus 2 (SARS-CoV-2) results: A prospective study.

Infect Control Hosp Epidemiol 2020 Dec 10:1-3. Epub 2020 Dec 10.

Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York.

We performed a prospective study of 501 patients, regardless of symptoms, admitted to the hospital, to estimate the predictive value of a negative nasopharyngeal swab for severe acute respiratory coronavirus virus 2 (SARS-CoV-2). At a positivity rate of 10.2%, the estimated negative predictive value (NPV) was 97.2% and the NPV rose as prevalence decreased during the study.
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http://dx.doi.org/10.1017/ice.2020.1362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783084PMC
December 2020

Metal-Organic Framework HKUST-1 Promotes Methane Hydrate Formation for Improved Gas Storage Capacity.

ACS Appl Mater Interfaces 2020 Nov 13;12(47):53510-53518. Epub 2020 Nov 13.

Chemical and Biological Engineering Department, Colorado School of Mines, Golden, Colorado 80401, United States.

The large demand of natural gas consumption requires an effective technology to purify and store methane, the main component of natural gas. Metal-organic frameworks and gas hydrates are highly appealing materials for the efficient storage of industrially relevant gases, including methane. In this study, the methane storage capacity of the combination of methane hydrates and HKUST-1, a copper-based metal-organic framework, was studied using high pressure differential scanning calorimetry. The results show a synergistic effect, as the addition of HKUST-1 promoted hydrate growth, thus increasing the amount of water converted to hydrate from 5.9 to 87.2% and the amount of methane stored, relative to the amount of water present, from 0.55 to 8.1 mmol/g. The success of HKUST-1 as a promoter stems mainly from its large surface area, high thermal conductivity, and hydrophilicity. These distinctive properties led to a kinetically favorable decrease in hydrate growth induction period by 4.4 h upon the addition of HKUST-1. Powder X-ray diffraction and nitrogen isotherm suggests that the hydrate formation occurs primarily on the surface of HKUST-1 rather than within the pores. Remarkably, the HKUST-1 crystals show no significant changes in terms of structural integrity after many cycles of hydrate formation and dissociation, which results in the material having a long life cycle. These results confirm the beneficial role of HKUST-1 as a promoter for gas hydrate formation to increase methane gas storage capacity.
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http://dx.doi.org/10.1021/acsami.0c15675DOI Listing
November 2020

3D Printed Alternative to the Standard Synthetic Flocked Nasopharyngeal Swabs Used for COVID-19 testing.

Clin Infect Dis 2020 Sep 10. Epub 2020 Sep 10.

University of South Florida, Morsani College of Medicine, Tampa, FL.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, can be detected in respiratory samples by Real-time Reverse Transcriptase (RT)-PCR or other molecular methods. Accessibility of diagnostic testing for COVID-19 has been limited by intermittent shortages of supplies required for testing, including flocked nasopharyngeal (FLNP) swabs.

Methods: We developed a 3D-printed nasopharyngeal (3DP) swab as a replacement of the FLNP swab. The performance of 3DP and FLNP swabs were compared in a clinical trial of symptomatic patients at three clinical sites (n=291) using three SARS-CoV-2 EUA tests: a modified version of the CDC Real-time Reverse Transcriptase (RT)-PCR Diagnostic Panel and two commercial automated formats, Roche Cobas and NeuMoDx.

Results: The cycle threshold (C(t)) values from the gene targets and the RNase P gene control in the CDC assay showed no significant differences between swabs for both gene targets (p=0.152 and p=0.092), with the RNase P target performing significantly better in the 3DP swabs (p & 0.001). The C(t) values showed no significant differences between swabs for both viral gene targets in the Roche cobas assay (p=0.05 and p=0.05) as well as the NeuMoDx assay (p=0.401 and p=0.484). The overall clinical correlation of COVID-19 diagnosis between all methods was 95.88% (Kappa 0.901).

Conclusions: 3DP swabs were equivalent to standard FLNP in three testing platforms for SARS-CoV-2. Given the need for widespread testing, 3DP swabs printed on-site are an alternate to FLNP that can rapidly scale in response to acute needs when supply chain disruptions affect availability of collection kits.
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http://dx.doi.org/10.1093/cid/ciaa1366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499529PMC
September 2020

Reevaluation of the US Pathologist Workforce Size.

JAMA Netw Open 2020 07 1;3(7):e2010648. Epub 2020 Jul 1.

Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston.

Importance: There is currently no national organization that publishes its data that serves as the authoritative source of the pathologist workforce in the US. Accurate physician numbers are needed to plan for future health care service requirements.

Objective: To assess the accuracy of current pathologist workforce estimates in the US by examining why divergency appears in different published resources.

Design, Setting, And Participants: This study examined the American Board of Pathology classification for pathologist primary specialty and subspecialties and analyzed previously published reports from the following data sources: the Association of American Medical Colleges (AAMC), the Accreditation Council for Graduate Medical Education (ACGME), a 2013 College of American Pathologists (CAP) report, a commercially available version of the American Medical Assoication (AMA) Physician Masterfile, and an unpublished data summary from June 10, 2019.

Main Outcomes And Measures: Number of physicians classified as pathologists.

Results: The most recent AAMC data from 2017 (published in 2018) reported 12 839 physicians practicing "anatomic/clinical pathology," which is a subset of the whole. In comparison, the current AMA Physician Masterfile, which is not available publicly, listed 21 292 active pathologists in June 2019. The AMA Physician Masterfile includes all pathologists in 15 subspecialized training areas as identified by the ACGME. By contrast, AAMC's data, which derive from the AMA Physician Masterfile data, only count physicians primarily associated with 3 general categories of pathologists and 1 subspecialty category (ie, chemical pathology). Thus, the AAMC pathology workforce estimate does not include those whose principal work is in 11 subspecialty areas, such as blood banking or transfusion medicine, cytopathology, hematopathology, or microbiology. An additional discrepancy relates to the ACGME residency (specialties) and fellowship (subspecialties) training programs in which pathologists with training in dermatopathology appear as dermatologists and pathologists with training in molecular genetic pathology appear as medical geneticists.

Conclusions And Relevance: This analysis found that most sources reported only select categories of the pathologist workforce rather than the complete workforce. The discordant nature of reporting may pertain to other medical specialties that have undergone increased subspecialization during the past 2 decades (eg, surgery and medicine). Reconsideration of the methods for determining the pathologist workforce and for all workforces in medicine appears to be needed.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.10648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366184PMC
July 2020

Rapid Emergence of SARS-CoV-2 in the Greater New York Metropolitan Area: Geolocation, Demographics, Positivity Rates, and Hospitalization for 46 793 Persons Tested by Northwell Health.

Clin Infect Dis 2020 12;71(12):3204-3213

Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, Hempstead, New York, USA.

Background: In March 2020, the greater New York metropolitan area became an epicenter for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The initial evolution of case incidence has not been well characterized.

Methods: Northwell Health Laboratories tested 46 793 persons for SARS-CoV-2 from 4 March through 10 April. The primary outcome measure was a positive reverse transcription-polymerase chain reaction test for SARS-CoV-2. The secondary outcomes included patient age, sex, and race, if stated; dates the specimen was obtained and the test result; clinical practice site sources; geolocation of patient residence; and hospitalization.

Results: From 8 March through 10 April, a total of 26 735 of 46 793 persons (57.1%) tested positive for SARS-CoV-2. Males of each race were disproportionally more affected than females above age 25, with a progressive male predominance as age increased. Of the positive persons, 7292 were hospitalized directly upon presentation; an additional 882 persons tested positive in an ambulatory setting before subsequent hospitalization, a median of 4.8 days later. Total hospitalization rate was thus 8174 persons (30.6% of positive persons). There was a broad range (>10-fold) in the cumulative number of positive cases across individual zip codes following documented first caseincidence. Test positivity was greater for persons living in zip codes with lower annual household income.

Conclusions: Our data reveal that SARS-CoV-2 incidence emerged rapidly and almost simultaneously across a broad demographic population in the region. These findings support the premise that SARS-CoV-2 infection was widely distributed prior to virus testing availability.
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http://dx.doi.org/10.1093/cid/ciaa922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454448PMC
December 2020

Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area.

JAMA 2020 05;323(20):2052-2059

Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York.

Importance: There is limited information describing the presenting characteristics and outcomes of US patients requiring hospitalization for coronavirus disease 2019 (COVID-19).

Objective: To describe the clinical characteristics and outcomes of patients with COVID-19 hospitalized in a US health care system.

Design, Setting, And Participants: Case series of patients with COVID-19 admitted to 12 hospitals in New York City, Long Island, and Westchester County, New York, within the Northwell Health system. The study included all sequentially hospitalized patients between March 1, 2020, and April 4, 2020, inclusive of these dates.

Exposures: Confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by positive result on polymerase chain reaction testing of a nasopharyngeal sample among patients requiring admission.

Main Outcomes And Measures: Clinical outcomes during hospitalization, such as invasive mechanical ventilation, kidney replacement therapy, and death. Demographics, baseline comorbidities, presenting vital signs, and test results were also collected.

Results: A total of 5700 patients were included (median age, 63 years [interquartile range {IQR}, 52-75; range, 0-107 years]; 39.7% female). The most common comorbidities were hypertension (3026; 56.6%), obesity (1737; 41.7%), and diabetes (1808; 33.8%). At triage, 30.7% of patients were febrile, 17.3% had a respiratory rate greater than 24 breaths/min, and 27.8% received supplemental oxygen. The rate of respiratory virus co-infection was 2.1%. Outcomes were assessed for 2634 patients who were discharged or had died at the study end point. During hospitalization, 373 patients (14.2%) (median age, 68 years [IQR, 56-78]; 33.5% female) were treated in the intensive care unit care, 320 (12.2%) received invasive mechanical ventilation, 81 (3.2%) were treated with kidney replacement therapy, and 553 (21%) died. As of April 4, 2020, for patients requiring mechanical ventilation (n = 1151, 20.2%), 38 (3.3%) were discharged alive, 282 (24.5%) died, and 831 (72.2%) remained in hospital. The median postdischarge follow-up time was 4.4 days (IQR, 2.2-9.3). A total of 45 patients (2.2%) were readmitted during the study period. The median time to readmission was 3 days (IQR, 1.0-4.5) for readmitted patients. Among the 3066 patients who remained hospitalized at the final study follow-up date (median age, 65 years [IQR, 54-75]), the median follow-up at time of censoring was 4.5 days (IQR, 2.4-8.1).

Conclusions And Relevance: This case series provides characteristics and early outcomes of sequentially hospitalized patients with confirmed COVID-19 in the New York City area.
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http://dx.doi.org/10.1001/jama.2020.6775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177629PMC
May 2020

Targeting potential drivers of COVID-19: Neutrophil extracellular traps.

J Exp Med 2020 06;217(6)

Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.

Coronavirus disease 2019 (COVID-19) is a novel, viral-induced respiratory disease that in ∼10-15% of patients progresses to acute respiratory distress syndrome (ARDS) triggered by a cytokine storm. In this Perspective, autopsy results and literature are presented supporting the hypothesis that a little known yet powerful function of neutrophils-the ability to form neutrophil extracellular traps (NETs)-may contribute to organ damage and mortality in COVID-19. We show lung infiltration of neutrophils in an autopsy specimen from a patient who succumbed to COVID-19. We discuss prior reports linking aberrant NET formation to pulmonary diseases, thrombosis, mucous secretions in the airways, and cytokine production. If our hypothesis is correct, targeting NETs directly and/or indirectly with existing drugs may reduce the clinical severity of COVID-19.
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http://dx.doi.org/10.1084/jem.20200652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161085PMC
June 2020

Canal of Hering loss is an initiating step for primary biliary cholangitis (PBC): A hypothesis.

Med Hypotheses 2020 Mar 16;140:109680. Epub 2020 Mar 16.

Department of Cellular Pathology, Royal Free Hospital, London, UK.

The origin and initiating features of PBC remain obscure despite decades of study. However, recent papers have demonstrated loss of canals of Hering (CoH) to be the earliest histologic change in liver biopsy specimens from patients with primary biliary cholangitis (PBC). We posit that CoH loss prior to significant inflammation or evidence of bile duct injury might be a very early, perhaps even an initiating lesion of PBC. As a potential target of inflammatory or toxic injury, CoH loss may initiate rather than follow the cascade of events leading to duct injury and loss and their sequelae. Toxins may be exogenous in origin, such as environmental toxins or drug exposures, or endogenous, resulting from genetic or epigenetic alterations in canalicular bile transporters upstream from the CoH. In turn, this hypothesis suggests that loss of CoH would lead to altered bile flow and composition injurious to downstream bile ducts, because bile composition has not been modulated by normal CoH physiologic functions or because, in the absence of CoH, canalicular fluid flow into the biliary tree is disrupted interfering with soluble trophic factors important for bile duct integrity. Regardless of the pathogenic mechanism causing CoH loss, only following such loss would the characteristic diagnostic findings of PBC become evident: damage to downstream interlobular and sub-lobular bile ducts. To the extent that the causal mechanisms for CoH loss can be identified, clinical identification (as through early identification of CoH loss) and intervention (depending on the inciting cause) may offer promise for treatment of this enigmatic disease.
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http://dx.doi.org/10.1016/j.mehy.2020.109680DOI Listing
March 2020

The Value Proposition for Pathologists: A Population Health Approach.

Acad Pathol 2020 Jan-Dec;7:2374289519898857. Epub 2020 Jan 14.

Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.

The transition to a value-based payment system offers pathologists the opportunity to play an increased role in population health by improving outcomes and safety as well as reducing costs. Although laboratory testing itself accounts for a small portion of health-care spending, laboratory data have significant downstream effects in patient management as well as diagnosis. Pathologists currently are heavily engaged in precision medicine, use of laboratory and pathology test results (including autopsy data) to reduce diagnostic errors, and play leading roles in diagnostic management teams. Additionally, pathologists can use aggregate laboratory data to monitor the health of populations and improve health-care outcomes for both individual patients and populations. For the profession to thrive, pathologists will need to focus on extending their roles outside the laboratory beyond the traditional role in the analytic phase of testing. This should include leadership in ensuring correct ordering and interpretation of laboratory testing and leadership in population health programs. Pathologists in training will need to learn key concepts in informatics and data analytics, health-care economics, public health, implementation science, and health systems science. While these changes may reduce reimbursement for the traditional activities of pathologists, new opportunities arise for value creation and new compensation models. This report reviews these opportunities for pathologist leadership in utilization management, precision medicine, reducing diagnostic errors, and improving health-care outcomes.
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http://dx.doi.org/10.1177/2374289519898857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961144PMC
January 2020

Northwell Health Laboratories: The 10-Year Outcomes After Deciding to Keep the Lab.

Arch Pathol Lab Med 2019 12 17;143(12):1517-1530. Epub 2019 May 17.

Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York.

Context.—: Northwell Health Laboratories were established in 1997, serving the Northwell Health system. In 2008, the health system considered minority entry into a joint venture with a commercial laboratory. Based on arguments made by Northwell laboratory leadership, the decision was made to retain full ownership of the laboratory.

Objective.—: To evaluate the 10-year outcomes of the 2008 decision and assess the value of a fully integrated laboratory service line for a regional health network.

Design.—: Ten-year outcomes were analyzed including financial, volume, and value-based activities.

Results.—: First, a fully integrated laboratory service line was created, with unified medical and managerial leadership. Second, Core Laboratory volumes and revenues grew at annualized rates of 4.5% and 16.0%, respectively. Third, hospital-based laboratory costs were held either constant, or grew in accordance with strategic clinical programs. Fourth, laboratory services were able to provide leadership in innovative system clinical programming and value-based payment programs. Fifth, the laboratories became a regional asset, forming a joint venture affiliation with New York City Health + Hospitals, and supporting distressed hospitals in Brooklyn, New York. Lastly, Northwell Health Laboratories have become a reputational asset through leadership in 2 consortia: The Compass Group and Project Santa Fe.

Conclusions.—: The 10-year outcomes have exceeded projections made in 2008, validating the decision to retain the laboratories as a wholly owned system asset. The laboratories are now well positioned for leading innovation in patient care and for helping to drive a favorable posture for the health system under new payment models for health care.
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http://dx.doi.org/10.5858/arpa.2018-0569-SADOI Listing
December 2019

Gross Dissection Time Values of Pathologists' Assistants Using Standardized Metrics.

Am J Clin Pathol 2019 05;151(6):598-606

Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine of Medicine at Hofstra/Northwell, Hempstead, NY.

Objectives: A validated and objective method to quantify the gross dissection time of pathologists' assistants (PAs) does not exist. We propose a method to calculate standardized work units (dissection time values [DTVs]) to monitor PA productivity.

Methods: The Current Procedural Terminology system specifies six levels of specimen complexity encompassing 176 unique specimen types. Using our institutional dictionary, we designated all specimen types into a priori five levels of complexity based on expected dissection time. We hypothesized that expected time could be matched prospectively with the actual measured dissection time for all specimens. Dissection time data were collected prospectively for 12,775 specimens at two tertiary academic medical centers, and work effort was converted to a numeric DTV equivalent (number of minutes to dissect single specimen/420 minutes in a working day).

Results: For 44 of 155 specimen types, measured dissection time for the five "levels" was lower than expected dissection (P < .0001). Accordingly, those 44 specimen types were reclassified to a lower level.

Conclusions: A numeric standard of the work effort for dissection time for 155 specimen types was developed, validated, and then used prospectively to monitor grossing efficiency of PA workforce.
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http://dx.doi.org/10.1093/ajcp/aqz007DOI Listing
May 2019

The Role of the Pathologist in Population Health.

Arch Pathol Lab Med 2019 05 6;143(5):610-620. Epub 2018 Nov 6.

From the Policy Roundtable, College of American Pathologists, Washington, DC (Dr Gross); Clinical Informatics, College of American Pathologists, Northfield, Illinois (Ms Kennedy); the Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Lake Success, New York (Drs Kothari and Crawford); Eastern Great Lakes Pathology, Amherst, New York (Dr Scamurra); the Division of Laboratory Medicine, Geisinger Medical Laboratories, Danville, Pennsylvania (Dr Wilkerson); and the Department of Pathology, Wake Forest School of Medicine, Winston-Salem, North Carolina (Dr Cohen).

Context.—: As part of its value-based care initiative, the College of American Pathologists has pursued research to better understand the role pathologists can have in population health.

Objectives.—: To answer the following questions: (1) what is the impact of population health and population health management on pathologists; (2) what roles are pathologists playing in population health management; (3) is population health something that pathologists in both larger and smaller settings can engage in; (4) are pathologists in a position to analyze laboratory data for population health, and, if so, what are the key information sources those pathologists must access; and (5) what steps can a pathologist take to become involved in population health?

Design.—: We conducted 10 semistructured interviews with pathologists and other medical laboratory leaders who have been active in population health. These interviews were supplemented with a review of the medical literature.

Results.—: Pathologists have demonstrated that laboratory data can provide unique value-added contributions to improving the health of populations. These contributions are not limited to pathologists in large, integrated settings. However, pathologists need to be proactive to contribute to health systems' population health efforts and may need to both enhance their own skills and the quality of their data to maximize the value of their contributions.

Conclusions.—: Although not necessarily a definitive summary of the roles that pathologists are playing in population health, this article identifies some of the promising and innovative activities occurring among pathologists and laboratorians.
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http://dx.doi.org/10.5858/arpa.2018-0223-CPDOI Listing
May 2019

Evidence-Based Alignment of Pathology Residency With Practice: Methodology and General Consideration of Results.

Acad Pathol 2018 Jan-Dec;5:2374289518790501. Epub 2018 Aug 21.

American Board of Pathology, Tampa, FL, USA.

Few medical specialties engage in ongoing, organized data collection to assess how graduate medical education in their disciplines align with practice. Pathology educators, the American Board of Pathology, and major pathology organizations undertook an evidence-based, empirical assessment of what all pathologists need to learn in categorical residency. Two challenges were known when we commenced and we encountered 2 others during the project; all were ultimately satisfactorily addressed. Initial challenges were (1) ensuring broad representation of the new-in-practice pathologist experience and (2) adjusting for the effect on this experience of subspecialty fellowship(s) occurring between residency and practice. Additional challenges were (3) needing to assess and quantify degree and extent of subspecialization in different practice settings and (4) measuring changing practice responsibilities with increasing time in practice. We instituted annual surveys of pathologists who are relatively new (<10 years) in practice and a survey of physician employers of new pathologists. The purpose of these surveys was to inform (1) the American Board of Pathology certification process, which needs to assess the most critical knowledge, judgment, and skills required by newly practicing pathologists, and (2) pathology graduate medical education training requirements, which need to be both efficient and effective in graduating competent practitioners. This article presents a survey methodology to evaluate alignment of graduate medical education training with the skills needed for new-in-practice physicians, illustrates an easily interpreted graphical format for assessing survey data, and provides high-level results showing consistency of findings between similar populations of respondents, and between new-in-practice physicians and physician-employers.
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http://dx.doi.org/10.1177/2374289518790501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6104218PMC
August 2018

Histology of portal vascular changes associated with idiopathic non-cirrhotic portal hypertension: nomenclature and definition.

Histopathology 2019 Jan 17;74(2):219-226. Epub 2018 Oct 17.

Section of Gastroenterology and Hepatology, Geisel School of Medicine at Dartmouth College, Hanover, NH, USA.

Idiopathic non-cirrhotic portal hypertension (INCPH) is a rare vascular liver disease that has attracted new interest in recent years. It is characterised by clinical signs of portal hypertension in the absence of cirrhosis or severe fibrosis and any known cause of portal hypertension. As much uncertainty exists about INCPH pathophysiology, and no definite diagnostic tests are available, liver biopsy is an essential tool for achieving a definite diagnosis. Unfortunately, the histological diagnosis of INCPH is not always straightforward, as the characteristic lesions are unevenly distributed, vary greatly in their severity, are often very subtle, and are not all necessarily present in a single case. Furthermore, specifically for the characteristic portal vessel changes observed in INCPH, the terminology and definition are ambiguous, which adds complexity to the already complex clinicopathological scenario. An international study group of liver pathologists and hepatologists pursued a consensus on nomenclature for the portal vascular lesions of INCPH. Such standardisation may assist pathologists in the recognition of such lesions, and will possibly facilitate further advancement in this field.
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http://dx.doi.org/10.1111/his.13738DOI Listing
January 2019

Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer.

Cancer Discov 2018 09 31;8(9):1112-1129. Epub 2018 May 31.

Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.

Pancreatic cancer is the most lethal common solid malignancy. Systemic therapies are often ineffective, and predictive biomarkers to guide treatment are urgently needed. We generated a pancreatic cancer patient-derived organoid (PDO) library that recapitulates the mutational spectrum and transcriptional subtypes of primary pancreatic cancer. New driver oncogenes were nominated and transcriptomic analyses revealed unique clusters. PDOs exhibited heterogeneous responses to standard-of-care chemotherapeutics and investigational agents. In a case study manner, we found that PDO therapeutic profiles paralleled patient outcomes and that PDOs enabled longitudinal assessment of chemosensitivity and evaluation of synchronous metastases. We derived organoid-based gene expression signatures of chemosensitivity that predicted improved responses for many patients to chemotherapy in both the adjuvant and advanced disease settings. Finally, we nominated alternative treatment strategies for chemorefractory PDOs using targeted agent therapeutic profiling. We propose that combined molecular and therapeutic profiling of PDOs may predict clinical response and enable prospective therapeutic selection. New approaches to prioritize treatment strategies are urgently needed to improve survival and quality of life for patients with pancreatic cancer. Combined genomic, transcriptomic, and therapeutic profiling of PDOs can identify molecular and functional subtypes of pancreatic cancer, predict therapeutic responses, and facilitate precision medicine for patients with pancreatic cancer. .
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http://dx.doi.org/10.1158/2159-8290.CD-18-0349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125219PMC
September 2018

Acute-on-chronic liver failure 2018: a need for (urgent) liver biopsy?

Expert Rev Gastroenterol Hepatol 2018 Jun 14;12(6):565-573. Epub 2018 Jun 14.

u Institute of Liver Studies , King's College Hospital and King's College , London , England.

Introduction: 'Acute-on-Chronic-Liver Failure (ACLF)' entered hepatology practice by the end of the 20th century. Although we lack precise and universally agreed definitions, acute decompensation of chronic liver disease with jaundice and deranged clotting, multi-organ failure and high, short-term mortality are hallmarks of the syndrome. Timely recognition and and treatment, including urgent liver transplantation, may save the life of certain patients. The diagnosis and management are mostly based on clinical features, but some have suggested to incorporate histopathology (liver biopsy). This may add to the differentiation between acute and chronic disease, primary and concomitant etiologies, and identify prognostic determinants. Areas covered: A review of the literature on ACLF and the outcome of the discussions at a topical international meeting on specific histopathological aspects of diagnosis and prognosis of the syndrome. Expert commentary: There is a lack of standardized descriptions of histopathological features and there is limited prospective experience with the role of pathology of ACLF. It is important for the clinical hepatologist to understand the potential and limitations of (transjugular) liver biopsy in ACLF and for the pathologist to help address the clinical question and recognise the histopathological features that help to characterize ACLF, both in terms of diagnosis and prognosis.
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http://dx.doi.org/10.1080/17474124.2018.1481388DOI Listing
June 2018

Improving American Healthcare Through "Clinical Lab 2.0": A Project Santa Fe Report.

Acad Pathol 2017 Jan-Dec;4:2374289517701067. Epub 2017 Apr 18.

TriCore Laboratories, Albuquerque, NM, USA.

Project Santa Fe was established both to provide thought leadership and to help develop the evidence base for the valuation of clinical laboratory services in the next era of American healthcare. The participants in Project Santa Fe represent major regional health systems that can operationalize laboratory-driven innovations and test their valuation in diverse regional marketplaces in the United States. We provide recommendations from the inaugural March 2016 meeting of Project Santa Fe. Specifically, in the transition from volume-based to value-based health care, clinical laboratories are called upon to provide programmatic leadership in reducing total cost of care through optimization of time-to-diagnosis and time-to-effective therapeutics, optimization of care coordination, and programmatic support of wellness care, screening, and monitoring. This call to action is more than working with industry stakeholders on the basis of our expertise; it is providing leadership in creating the programs that accomplish these objectives. In so doing, clinical laboratories can be effectors in identifying patients at risk for escalation in care, closing gaps in care, and optimizing outcomes of health care innovation. We also hope that, through such activities, the evidence base will be created for the new value propositions of integrated laboratory networks. In the very simplest sense, this effort to create "Clinical Lab 2.0" will establish the impact of laboratory diagnostics on the full 100% spend in American healthcare, not just the 2.5% spend attributed to in vitro diagnostics. In so doing, our aim is to empower regional and local laboratories to thrive under new models of payment in the next era of American health care delivery.
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http://dx.doi.org/10.1177/2374289517701067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5497901PMC
April 2017

Strengths of the Northwell Health Laboratory Service Line: Maintaining Performance During Threatened Interruptions in Service.

Acad Pathol 2016 Jan-Dec;3:2374289516650961. Epub 2016 Jun 16.

Department of Pathology and Laboratory Medicine, Hofstra Northwell School of Medicine, Manhasset, NY, USA.

From 2009 to 2015, the laboratories of the 19-hospital North Shore-LIJ Health System experienced 5 threatened interruptions in service and supported 2 regional health-care providers with threatened interruptions in their laboratory service. We report our strategies to maintain laboratory performance during these events, drawing upon the strengths of our integrated laboratory service line. Established in 2009, the laboratory service line has unified medical and administrative leadership and system-wide divisional structure, quality management, and standardization of operations and procedures. Among many benefits, this governance structure enabled the laboratories to respond to a series of unexpected events. Specifically, at our various service sites, the laboratories dealt with pandemic (2009), 2 floods (2010, 2012), 2 fires (2010, 2015), and laboratory floor subsidence (2013). We were also asked to provide support for a regional physician network facing abrupt loss of testing services from closure of another regional clinical laboratory (2010) and to intervene for a non-health system hospital threatened with closure owing to noncompliance of laboratory operations (2012). In all but a single instance, patient care was served without interruption in service. In the last instance, fire interrupted laboratory services for 30 minutes. We conclude that in a large integrated health system, threats to continuous laboratory operations are not infrequent when measured on an annual basis. While most threats are from external physical circumstances, some emanate from unexpected administrative events. A strong laboratory governance mechanism that includes unified medical and administrative leadership across the entirety of the laboratory service line enables successful responses to these threats.
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http://dx.doi.org/10.1177/2374289516650961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5497918PMC
June 2016

Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer.

J Exp Med 2017 03 23;214(3):579-596. Epub 2017 Feb 23.

Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724.

Pancreatic stellate cells (PSCs) differentiate into cancer-associated fibroblasts (CAFs) that produce desmoplastic stroma, thereby modulating disease progression and therapeutic response in pancreatic ductal adenocarcinoma (PDA). However, it is unknown whether CAFs uniformly carry out these tasks or if subtypes of CAFs with distinct phenotypes in PDA exist. We identified a CAF subpopulation with elevated expression of α-smooth muscle actin (αSMA) located immediately adjacent to neoplastic cells in mouse and human PDA tissue. We recapitulated this finding in co-cultures of murine PSCs and PDA organoids, and demonstrated that organoid-activated CAFs produced desmoplastic stroma. The co-cultures showed cooperative interactions and revealed another distinct subpopulation of CAFs, located more distantly from neoplastic cells, which lacked elevated αSMA expression and instead secreted IL6 and additional inflammatory mediators. These findings were corroborated in mouse and human PDA tissue, providing direct evidence for CAF heterogeneity in PDA tumor biology with implications for disease etiology and therapeutic development.
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http://dx.doi.org/10.1084/jem.20162024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339682PMC
March 2017

Amending HIV Drugs: A Novel Small-Molecule Approach To Target Lupus Anti-DNA Antibodies.

J Med Chem 2016 10 20;59(19):8859-8867. Epub 2016 Sep 20.

Department of Research, Mayo Clinic , 13400 East Shea Boulevard, Scottsdale, Arizona 85259, United States.

Systemic lupus erythematosus is an autoimmune disease that can affect numerous tissues and is characterized by the production of nuclear antigen-directed autoantibodies (e.g., anti-dsDNA). Using a combination of virtual and ELISA-based screens, we made the intriguing discovery that several HIV-protease inhibitors can function as decoy antigens to specifically inhibit the binding of anti-dsDNA antibodies to target antigens such as dsDNA and pentapeptide DWEYS. Computational modeling revealed that HIV-protease inhibitors comprised structural features present in DWEYS and predicted that analogues containing more flexible backbones would possess preferred binding characteristics. To address this, we reduced the internal amide backbone to improve flexibility, producing new small-molecule decoy antigens, which neutralize anti-dsDNA antibodies in vitro, in situ, and in vivo. Pharmacokinetic and SLE model studies demonstrated that peptidomimetic FISLE-412,1 a reduced HIV protease inhibitor analogue, was well-tolerated, altered serum reactivity to DWEYS, reduced glomeruli IgG deposition, preserved kidney histology, and delayed SLE onset in NZB/W F1 mice.
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http://dx.doi.org/10.1021/acs.jmedchem.6b00694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5592695PMC
October 2016

Fulminant Colitis Following Rituximab Therapy.

Gastroenterol Hepatol (N Y) 2016 Jan;12(1):58-60

Hofstra School of Medicine, North Shore-Long Island Jewish Health System, Hempstead, New York.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865788PMC
January 2016

A Required Rotation in Clinical Laboratory Management for Pathology Residents: Five-Year Experience at Hofstra Northwell School of Medicine.

Acad Pathol 2016 Jan-Dec;3:2374289516644621. Epub 2016 May 3.

Department of Pathology and Laboratory Medicine, Hofstra Northwell School of Medicine, Lake Success, NY, USA.

Leadership and management training during pathology residency have been identified repeatedly by employers as insufficient. A 1-month rotation in clinical laboratory management (CLM) was created for third-year pathology residents. We report on our experience and assess the value of this rotation. The rotation was one-half observational and one-half active. The observational component involved being a member of department and laboratory service line leadership, both at the departmental and institutional level. Observational participation enabled learning of both the content and principles of leadership and management activities. The active half of the rotation was performance of a project intended to advance the strategic trajectory of the department and laboratory service line. In our program that matriculates 4 residents per year, 20 residents participated from April 2010 through December 2015. Their projects either activated a new priority area or helped propel an existing strategic priority forward. Of the 16 resident graduates who had obtained their first employment or a fellowship position, 9 responded to an assessment survey. The majority of respondents (5/9) felt that the rotation significantly contributed to their ability to compete for a fellowship or their first employment position. The top reported benefits of the rotation included people management; communication with staff, departmental, and institutional leadership; and involvement in department and institutional meetings and task groups. Our 5-year experience demonstrates both the successful principles by which the CLM rotation can be established and the high value of this rotation to residency graduates.
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http://dx.doi.org/10.1177/2374289516644621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5497904PMC
May 2016

The Authors' Reply.

Am J Clin Pathol 2016 Jan;145(1):143-4

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January 2016

Role of aetiology in the progression, regression, and parenchymal remodelling of liver disease: implications for liver biopsy interpretation.

Histopathology 2016 Jun 28;68(7):953-67. Epub 2016 Apr 28.

Section of Gastroenterology and Hepatology, Dartmouth Medical School, Hanover, NH, USA.

Clinicopathological concepts on acute and chronic liver disease have evolved rapidly during the last few years, with advances in general and specific treatment options and improved patient outcomes. The old paradigm of 'irreversibility' of cirrhosis had been challenged in major ways, and the validity of the usage of the term 'cirrhosis' has come into question. This paper addresses aetiology-based clinicopathological concepts and features that may deserve attention because they may determine disease outcome and, specifically, patterns of regression and remodelling. A variety of therapeutic interventions may influence remaining disease features after elimination of damaging agents (virus, alcohol, etc.), and determine the final clinical outcome including the risk of hepatocellular carcinoma (HCC). New concepts create new responsibilities and opportunities for the pathologist to contribute to the understanding of liver pathology and communicate this with clinical colleagues and researchers.
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http://dx.doi.org/10.1111/his.12957DOI Listing
June 2016

Laboratory Critical Values Should Support Effective Clinical Decision Making.

Am J Clin Pathol 2016 Jan;145(1):142-3

Hofstra North ShoreLIJ School of MedicineHempstead, NY.

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http://dx.doi.org/10.1093/ajcp/aqv089DOI Listing
January 2016

The Pathologist Workforce in the United States: II. An Interactive Modeling Tool for Analyzing Future Qualitative and Quantitative Staffing Demands for Services.

Arch Pathol Lab Med 2015 Nov;139(11):1413-30

From the Department of Pathology, Duke University Medical Center, Durham, North Carolina (Dr Robboy); The Smart Cube, Noida, India (Mr Gupta); the Department of Pathology and Laboratory Medicine, North Shore-Long Island Jewish Health System, Manhasset, New York (Dr Crawford); the Department of Pathology, Huntsman Cancer Hospital, University of Utah, Salt Lake City (Dr Cohen); the Department of Pathology, George Washington University, Washington, DC (Dr Karcher); the Department of Pathology, University of Vermont College of Medicine, Burlington (Dr Leonard); the Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts (Dr Magnani); Novis Consulting, Lee, New Hampshire (Dr Novis); the Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York (Dr Prystowsky); the Department of Pathology and Genomic Medicine, The Methodist Hospital, Houston, Texas (Dr Powell); Policy Roundtable, College of American Pathologists, Washington, DC (Dr Gross); the Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston (Dr Black-Schaffer).

Context: Pathologists are physicians who make diagnoses based on interpretation of tissue and cellular specimens (surgical/cytopathology, molecular/genomic pathology, autopsy), provide medical leadership and consultation for laboratory medicine, and are integral members of their institutions' interdisciplinary patient care teams.

Objective: To develop a dynamic modeling tool to examine how individual factors and practice variables can forecast demand for pathologist services.

Design: Build and test a computer-based software model populated with data from surveys and best estimates about current and new pathologist efforts.

Results: Most pathologists' efforts focus on anatomic (52%), laboratory (14%), and other direct services (8%) for individual patients. Population-focused services (12%) (eg, laboratory medical direction) and other professional responsibilities (14%) (eg, teaching, research, and hospital committees) consume the rest of their time. Modeling scenarios were used to assess the need to increase or decrease efforts related globally to the Affordable Care Act, and specifically, to genomic medicine, laboratory consolidation, laboratory medical direction, and new areas where pathologists' expertise can add value.

Conclusions: Our modeling tool allows pathologists, educators, and policy experts to assess how various factors may affect demand for pathologists' services. These factors include an aging population, advances in biomedical technology, and changing roles in capitated, value-based, and team-based medical care systems. In the future, pathologists will likely have to assume new roles, develop new expertise, and become more efficient in practicing medicine to accommodate new value-based delivery models.
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http://dx.doi.org/10.5858/arpa.2014-0559-OADOI Listing
November 2015

Standards for Clinical Grade Genomic Databases.

Arch Pathol Lab Med 2015 Nov;139(11):1400-12

From the Department of Laboratory Medicine and Pathology, University of Minnesota Medical Center, Minneapolis (Dr Yohe); the Department of Pathology and Laboratory Medicine and the Department of Biomedical Informatics, Emory University, Atlanta, Georgia (Dr Carter); the Department of Pathology, Washington University School of Medicine, St. Louis, Missouri (Dr Pfeifer); the Department of Pathology and Laboratory Medicine, Hofstra North Shore-Long Island Jewish School of Medicine, Hempstead, New York (Dr Crawford); the Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha (Dr Cushman-Vokoun); the MAWD Pathology Group, North Kansas City, Missouri (Dr Caughron); and the Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington (Dr Leonard).

Context: Next-generation sequencing performed in a clinical environment must meet clinical standards, which requires reproducibility of all aspects of the testing. Clinical-grade genomic databases (CGGDs) are required to classify a variant and to assist in the professional interpretation of clinical next-generation sequencing. Applying quality laboratory standards to the reference databases used for sequence-variant interpretation presents a new challenge for validation and curation.

Objectives: To define CGGD and the categories of information contained in CGGDs and to frame recommendations for the structure and use of these databases in clinical patient care.

Design: Members of the College of American Pathologists Personalized Health Care Committee reviewed the literature and existing state of genomic databases and developed a framework for guiding CGGD development in the future.

Results: Clinical-grade genomic databases may provide different types of information. This work group defined 3 layers of information in CGGDs: clinical genomic variant repositories, genomic medical data repositories, and genomic medicine evidence databases. The layers are differentiated by the types of genomic and medical information contained and the utility in assisting with clinical interpretation of genomic variants. Clinical-grade genomic databases must meet specific standards regarding submission, curation, and retrieval of data, as well as the maintenance of privacy and security.

Conclusion: These organizing principles for CGGDs should serve as a foundation for future development of specific standards that support the use of such databases for patient care.
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http://dx.doi.org/10.5858/arpa.2014-0568-CPDOI Listing
November 2015