Attitudes and Beliefs of Pathology Residents Regarding the Subspecialty of Clinical Chemistry: Results of a Survey.

CONTEXT: -Previous studies suggest that training in pathology residency programs does not adequately prepare pathology residents to become competent in clinical chemistry. OBJECTIVES: -To define the beliefs of pathology residents in the United States regarding their preparation for practicing clinical chemistry in their career, their attitude toward the discipline, and the attractiveness of clinical chemistry as a career. DESIGN: -The residents of all pathology residency programs in the United States were given the opportunity to participate in an online survey. RESULTS: -Three hundred thirty-six pathology residents responded to the survey. Analysis of the survey results indicates that pathology residents are more likely to believe that their income may be lower if they select a career that has a clinical chemistry focus and that their faculty do not value clinical chemistry as much as the anatomic pathology part of the residency. Residents also report that clinical chemistry is not as enjoyable as anatomic pathology rotations during residency or preferable as a sole career path. A large proportion of residents also believe that they will be slightly prepared or not prepared to practice clinical chemistry by the end of their residency and that they do not have enough background and/or time to learn clinical chemistry during their residency programs to be able to practice this specialty effectively post graduation. CONCLUSIONS: -Our survey results suggest that many pathology residents do not have a positive attitude toward clinical chemistry and do not experience a supportive learning environment with an expectation that they will become competent in clinical chemistry with a residency alone.

A bundled care approach to patients with idiopathic pulmonary fibrosis improves transplant-free survival.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease with poor prognosis and limited therapeutic options. The 2011 ATS/ERS/JRS/ALAT consensus statement provided a number of recommendations for the management of IPF patients. The primary objective of this study was to determine if "bundling" these recommendations in the management of patients with IPF impacts clinical outcomes. METHODS: We conducted a single center, retrospective cohort study of 284 patients diagnosed with IPF. The proposed bundle of care (BOC) components were: (1) visits to a specialized interstitial lung diseases clinic with evaluation of pulmonary function tests at least twice yearly; (2) referral to pulmonary rehabilitation yearly; (3) timed walk test yearly; (4) echocardiogram yearly; and (5) gastroesophageal reflux therapy. Each component of the BOC was given a score of "1" per year of follow up, and the average sum of the scores (ranging from 0 to 5) was determined for the entire period of follow-up (BOCS), as well as during the first year of follow-up (BOCY1). The primary outcome measure was transplant-free survival. RESULTS: Age, gender, smoking status, BMI, %FVC, %DLCO did not differ between levels of BOCS and BOCY1. Lowest BOCS (≤1) was associated with a lower transplant-free survival independent of age and %FVC compared to patients with the highest BOCS (>4) (HR 2.274, CI 1.12-4.64, p = 0.024). Lower BOCY1 was associated with a higher risk for transplant or death independent of age and %FVC in comparison to patients with highest BOCY1 (≤1 vs. >4, HR 2.23, p = 0.014; >1 to 2 vs. >4, HR 1.87, p = 0.011; >2 to 3 vs. >4, HR 1.72, p = 0.019). CONCLUSION: IPF patients with higher BOC scores had improved transplant-free survival. Prospective studies are needed to confirm these findings and determine the best strategies for the management of patients with IPF.

The pathology milestones and the next accreditation system.

CONTEXT: In the late 1990s, the Accreditation Council for Graduate Medical Education developed the Outcomes Project and the 6 general competencies with the intent to improve the outcome of graduate medical education in the United States. The competencies were used as the basis for developing learning goals and objectives and tools to evaluate residents' performance. By the mid-2000s the stakeholders in resident education and the general public felt that the Outcomes Project had fallen short of expectations. OBJECTIVE: To develop a new evaluation method to track trainee progress throughout residency using benchmarks called milestones. A change in leadership at the Accreditation Council for Graduate Medical Education brought a new vision for the accreditation of training programs and a radically different approach to the evaluation of residents. DATA SOURCES: The Pathology Milestones Working Group reviewed examples of developing milestones in other specialties, the literature, and the Accreditation Council for Graduate Medical Education program requirements for pathology to develop pathology milestones. The pathology milestones are a set of objective descriptors for measuring progress in the development of competency in patient care, procedural skill sets, medical knowledge, practice-based learning and improvement, interpersonal and communication skills, professionalism, and systems-based practice. CONCLUSIONS: The milestones provide a national standard for evaluation that will be used for the assessment of all residents in Accreditation Council for Graduate Medical Education-accredited pathology training programs.

Pathologist workforce in the United States: I. Development of a predictive model to examine factors influencing supply.

CONTEXT: Results of prior pathology workforce surveys have varied between a state of equilibrium and predictions of shortage. OBJECTIVE: To assess the current and future supply of pathologists, and apply a dynamic modeling tool for assessing the effects of changing market forces and emerging technologies on the supply of pathologists' services through 2030. DESIGN: Data came from various sources, including the literature, College of American Pathologists' internal data, and primary research through custom-developed surveys for the membership and for pathology practice managers RESULTS: Through 2010, there were approximately 18 000 actively practicing pathologists in the United States (5.7 per 100 000 population), approximately 93% of whom were board certified. Our model projects that the absolute and per capita numbers of practicing pathologists will decrease to approximately 14 000 full-time equivalent (FTE) pathologists or 3.7 per 100 000 in the coming 2 decades. This projection reflects that beginning in 2015, the numbers of pathologists retiring will increase precipitously, and is anticipated to peak by 2021. Including all types of separation, the net pathologist strength will begin falling by year 2015. Unless workforce entry or exit rates change, this trend will continue at least through 2030. These changes reflect the closure of many training programs 2 to 4 decades ago and the substantially decreased number of graduating residents. CONCLUSIONS: This comprehensive analysis predicts that pathologist numbers will decline steadily beginning in 2015. Anticipated population growth in general and increases in disease incidence owing to the aging population, to be presented in a companion article on demand, will lead to a net deficit in excess of more than 5700 FTE pathologists. To reach the projected need in pathologist numbers of nearly 20 000 FTE by 2030 will require an increase from today of approximately 8.1% more residency positions. We believe a pathologist shortage will negatively impact both patient access to laboratory services and health care providers' abilities to deliver more effective health care to their patient populations.

Pathology graduate medical education (overview from 2006-2010).

Graduate medical education of pathologists has undergone considerable changes since 2006. The "Outcome Project" and reduction of basic anatomic pathology/clinical pathology training to 4 years are major changes. With implementation of the 80-hour week, it now takes 16,000 hours to train a pathologist who is competent to sit for the American Board of Pathology examination and practice independently. Reduction of the training time from 5 to 4 years has produced a perception (or reality) of mandatory fellowships. Changes are discussed, and trends are updated. Recent data is compared with data reported by the author in 2001 and 2006, and is updated through 2010.

2008 ACLPS panel discussion on resident education in clinical pathology.

A curriculum in clinical pathology (CP) was developed under the auspices of the Academy of Clinical Laboratory Physicians and Scientists (ACLPS) in 2006. At the 2008 ACLPS meeting in Philadelphia, PA, a panel was convened to address the current challenges in resident education and how to overcome them. Current challenges include the heterogeneity of the discipline (which requires analytical, medical, and managerial knowledge), the diverse repertoire of clinical laboratory testing, and the need to better integrate the resident into the work flow of the laboratory, especially with respect to clinical consultation. Recommendations of the panel include the incorporation of active learning, clinical consultation, and competency assessment into CP resident training. A summary of the panel discussion is presented herein.

A comparison between whites and blacks with severe multi-organ iron overload identified in 16,152 autopsies.

BACKGROUND & AIMS: Little is known about differences in the prevalence of severe iron overload at death in whites and blacks. We evaluated data and samples from 16,152 autopsies (8484 whites, 7668 blacks) performed at a single university hospital. METHODS: Cases of severe multi-organ iron overload were identified by review of autopsy protocols and Perls-stained tissue specimens, analysis of hepatocyte and Kupffer cell iron levels, and measurement of liver tissue iron concentrations. RESULTS: We analyzed autopsy data from 10,345 adults (age > or =21 years), 1337 children (1-20 years), and 4470 infants (<1 year). Iron overload without reports of excessive exogenous iron was observed in 18 adults; the prevalence in whites and blacks was 0.0019 and 0.0015, respectively (P = .6494). Twenty-nine adults and 2 children had iron overload with reports of excessive exogenous iron. In adults, the prevalences of iron overload with reports of excessive exogenous iron in whites and blacks were 0.0040 and 0.0013, respectively (P = .0107). Among adults, the prevalence of cirrhosis was 6-fold greater in those with iron overload. In adults with severe iron overload, 67% without reports of excessive exogenous iron and 14% with reports of excessive exogenous iron died of hepatic failure or cardiomyopathy caused by siderosis. The overall prevalence of deaths caused by severe iron overload in whites and blacks was 0.0021 and 0.0009, respectively (P = .0842). CONCLUSIONS: The prevalence of severe iron overload without reports of excessive exogenous iron did not differ significantly between whites and blacks. The prevalence of iron overload with reports of excessive exogenous iron was greater in whites. Hepatic failure and cardiomyopathy were common causes of death in severe iron overload cases.

Proposed research training guidelines for residents in laboratory medicine.

It is expected that the role of the clinical pathologist will evolve from the more passive role of managing testing facilities to one of active service provider, using powerful molecular, cell biologic, and biochemical tools. The scope of knowledge required to be an effective physician scientist or an accomplished practicing clinical pathologist, however, cannot be acquired through clinical training alone and requires dedicated, structured research learning time. The goal of this article is to consider mechanisms that effectively integrate research training and scholarly activity into residency education in laboratory medicine/clinical pathology. The proposed curricula are purposely unstructured to allow maximum flexibility for training programs to meet the needs and career goals of individual residents.

Assessing resident competency in laboratory medicine.

Validation of the competence of laboratory medicine (LM) residents for independent practice and to sit for the examination in clinical pathology rests with the program director. Assessing knowledge and basic skills were the primary measure of residents until 2000. The Accreditation Council of Graduate Medical Education and the ABMS launched the Outcome Project in 2000 as a response to the public. A shift in emphasis from "process" to a more "outcomes driven" assessment came with the Outcome Project. As of July 2006, the training of LM residents must incorporate the six competencies of the Outcome Project within each resident experience (rotation). In this article, comparison of historic and current methods of assessing residents is noted. Current and future outcomes and the pivotal role of consultation in LM are noted.

Pathology graduate medical education (overview from 1926 to 2005).

Postgraduate training of pathologists in the United States dates from 1926. From 1926 to 1936, certification was developed as a measure of competence for the public. In 2000, competence was redefined by the Accreditation Council for Graduate Medical Education (ACGME) Outcome Project for all physicians-in-training as mastering "the six competencies." These consist of (1) patient care, (2) medical knowledge, (3) practice-based learning and improvement, (4) interpersonal and communication skills, (5) professionalism, and (6) systems-based practice. The Outcome Project emerged in parallel with the American Board of Medical Specialties' Maintenance of Certification Project for all physicians. Outcome measures and benchmarks are the methods by which competence in medical practice will be measured for the public. Trends in pathology graduate medical education previously reported in 2001 (Hum Path 2001;32[7]:671-676) are updated through 2005 and reviewed. Demographic data regarding number and size of programs, curricula initiatives for pathology, changes in assessment, and outcomes information on certificates issued are discussed. Factors shaping pathology residency training are reviewed, as well as future trends that will impact training curricula.

Curriculum content and evaluation of resident competency in clinical pathology (laboratory medicine): a proposal.

Ten years have passed since the Graylyn Conference Report on Laboratory Medicine Clinical Pathology training was issued. Over that period, the Accreditation Council for Graduate Medical Education substantially revised the requirements for training programs; the American Board of Pathology amended both the requirements and the periods needed for certification; and the discipline itself, along with the broader discipline of pathology, evolved significantly. Recently, a curriculum proposal in anatomical pathology was published as a potential template to be used by training programs to help meet these new and evolving needs. Toward the same end, the Academy of Clinical Laboratory Physicians and Scientists has now developed a template for a curriculum in clinical pathology (laboratory medicine), taking into account newly designated and revised areas of residency core competency, the alterations in training requirements promulgated by the Accreditation Council for Graduate Medical Education and American Board of Pathology, and the rapidly developing nature of the discipline itself. The proposed clinical pathology curriculum defines goals and objectives for training, provides guidelines for instructional methods, and gives examples of how outcomes can be assessed. This curriculum is presented as a potentially helpful outline for use by pathology residency training programs.

Curriculum content and evaluation of resident competency in clinical pathology (laboratory medicine): a proposal.

Ten years have passed since the Graylyn Conference Report on Laboratory Medicine/Clinical Pathology training was issued. During that period, the Accreditation Council for Graduate Medical Education (ACGME) substantially revised the requirements for training programs, the American Board of Pathology (ABP) amended the requirements and the time needed for certification, and the discipline itself along with the broader discipline of pathology, evolved significantly. Recently, a curriculum proposal in anatomic pathology was published as a potential template to be used by training programs to help meet these new and evolving needs. Toward the same end, the Academy of Clinical Laboratory Physicians and Scientists has developed a template for a curriculum in clinical pathology (laboratory medicine), taking into account newly designated and revised areas of residency core competency, the alterations in training requirements promulgated by the ACGME and ABP, and the rapidly developing nature of the discipline itself The proposed clinical pathology curriculum defines goals and objectives for training, provides guidelines for instructional methods, and gives examples of how outcomes can be assessed. This curriculum is presented as a potentially helpful outline for use by pathology residency training programs.

Curriculum content and evaluation of resident competency in clinical pathology (laboratory medicine): a proposal.

Ten years have passed since the Graylyn Conference Report on Laboratory Medicine/Clinical Pathology training was issued. Over that time period, the Accreditation Council for Graduate Medical Education (ACGME) substantially revised the requirements for training programs, the American Board of Pathology (ABP) amended both the requirements and the time periods needed for certification, and the discipline itself, along with the broader discipline of pathology, evolved significantly. Recently, a curriculum proposal in anatomic pathology was published as a potential template to be used by training programs to help meet these new and evolving needs. Toward the same end, the Academy of Clinical Laboratory Physicians and Scientists has now developed a template for a curriculum in clinical pathology (laboratory medicine), taking into account newly designated and revised areas of residency core competency, the alterations in training requirements promulgated by the ACGME and ABP, and the rapidly developing nature of the discipline itself. The proposed clinical pathology curriculum defines goals and objectives for training, provides guidelines for instructional methods, and gives examples of how outcomes can be assessed. This curriculum is presented as a potentially helpful outline for use by pathology residency training programs.

Loss of fibroblast Thy-1 expression correlates with lung fibrogenesis.

Fibroblasts consist of heterogeneous subpopulations that have distinct roles in fibrotic responses. Previously we reported enhanced proliferation in response to fibrogenic growth factors and selective activation of latent transforming growth factor (TGF)-beta in fibroblasts lacking cell surface expression of Thy-1 glycoprotein, suggesting that Thy-1 modulates the fibrogenic potential of fibroblasts. Here we report that compared to controls Thy-1-/- C57BL/6 mice displayed more severe histopathological lung fibrosis, greater accumulation of lung collagen, and increased TGF-beta activation in the lungs 14 days after intratracheal bleomycin. The majority of cells demonstrating TGF-beta activation and myofibroblast differentiation in bleomycin-induced lesions were Thy-1-negative. Histological sections from patients with idiopathic pulmonary fibrosis demonstrated absent Thy-1 staining within fibroblastic foci. Normal lung fibroblasts, in both mice and humans, were predominantly Thy-1-positive. The fibrogenic cytokines interleukin-1 and tumor necrosis factor-alpha induced loss of fibroblast Thy-1 surface expression in vitro, which was associated with Thy-1 shedding, Smad phosphorylation, and myofibroblast differentiation. These results suggest that fibrogenic injury promotes loss of lung fibroblast Thy-1 expression, resulting in enhanced fibrogenesis.

Pelvic trauma in rapidly fatal motor vehicle accidents.

OBJECTIVE: To study the incidence and nature of pelvic fractures in rapidly fatal automobile accidents. DESIGN: Retrospective. SETTING: County Medical Examiner's Office. PATIENTS: The files of 255 consecutive motor vehicle accident fatalities examined at the Jefferson County Coroner/Medical Examiner's office (study period 1996-1998) were reviewed. We correlated this information with our previous findings, derived from a review of 392 such cases (study period 1994-1996). RESULTS: Approximately 25% of decedents involved in rapidly fatal automobile accidents sustained pelvic fractures. In 93% of the cases, postmortem radiographs were available and suitable for scoring according to the Orthopaedic Trauma Association nomenclature. The distribution of pelvic fractures by type was type A, 16%; type B, 32%; and type C, 52%, with the most common pelvic fracture being type C1 (26%). Additionally, pedestrians and motorcyclists were twice as likely to sustain a pelvic fracture, and the severity of pelvic fracture type seemed to correlate with increasing speed of the automobile. No correlation between drug use or direction of impact and incidence or type of pelvic fracture was observed. Compared with published studies on survivors of automobile accidents, our data suggest that pelvic injuries may tend to be more severe in victims who do not survive to hospitalization. CONCLUSIONS: Our data indicate that current estimates about the mortality of pelvic fractures may be faulty due to exclusion of victims who fail to survive to hospitalization. This series suggests that an appreciation of the full spectrum of pelvic ring disruptions requires collaboration between orthopaedic surgeons and forensic pathologists.

Pulmonary transplantation for advanced bronchioloalveolar carcinoma.

BACKGROUND: No effective therapy is currently available for the diffuse stage of bronchioloalveolar carcinoma. OBJECTIVE: We tested the hypothesis that total lung replacement with standard lung transplantation techniques would provide curative therapy. METHODS: Nine patients aged 31 to 58 years with bronchioloalveolar carcinoma were entered in the study. Five patients initially had bilateral diffuse tumor. Four patients had recurrence in the contralateral lung after pulmonary resection. RESULTS: Between 1993 and 1998, all 9 patients underwent transplantation (2 single-lung and 7 bilateral transplants, 1 reoperative single-lung transplant, and 1 reoperative bilateral transplant). Two patients had mediastinal node metastasis (level 7) at the time of transplantation, and 1 of these had a frankly invasive adenocarcinoma. Of the 8 patients with pure bronchioloalveolar carcinoma, 6 had recurrent pulmonary tumor after transplantation. In 2 of these patients the tumor was localized and could be resected with left lower lobectomy in one case and left pneumonectomy in the other. One is alive 89 months after transplantation; the other died 82 months after transplantation. Four other patients had a diffuse pattern of pulmonary recurrence. Two died of progressive pulmonary failure; 1 of these had retransplantation with recurrence. A third patient died of cerebral edema shortly after bilateral retransplantation. The other patient is alive with recurrence 39 months after transplantation and has bronchiolitis obliterans. Two patients without recurrence are well with unrestricted performance levels 87 and 76 months after transplantation. CONCLUSIONS: Transplantation produces a powerful palliative outcome in patients with advanced bronchioloalveolar carcinoma, but the recurrence rate is high. Transplantation for this indication remains controversial.

Nitric oxide-dependent generation of reactive species in sickle cell disease. Actin tyrosine induces defective cytoskeletal polymerization.

The intermittent vascular occlusion occurring in sickle cell disease (SCD) leads to ischemia-reperfusion injury and activation of inflammatory processes including enhanced production of reactive oxygen species and increased expression of inducible nitric-oxide synthase (NOS2). Appreciating that impaired nitric oxide-dependent vascular function and the concomitant formation of oxidizing and nitrating species occur in concert with increased rates of tissue reactive oxygen species production, liver and kidney NOS2 expression, tissue 3-nitrotyrosine (NO(2)Tyr) formation and apoptosis were evaluated in human SCD tissues and a murine model of SCD. Liver and kidney NOS2 expression and NO(2)Tyr immunoreactivity were significantly increased in SCD mice and humans, but not in nondiseased tissues. TdT-mediated nick end-label (TUNEL) staining showed apoptotic cells in regions expressing elevated levels of NOS2 and NO(2)Tyr in all SCD tissues. Gas chromatography mass spectrometry analysis revealed increased plasma protein NO(2)Tyr content and increased levels of hepatic and renal protein NO(2)Tyr derivatives in SCD (21.4 +/- 2.6 and 37.5 +/- 7.8 ng/mg) versus wild type mice (8.2 +/- 2.2 and 10 +/- 1.2 ng/mg), respectively. Western blot analysis and immunoprecipitation of SCD mouse liver and kidney proteins revealed one principal NO(2)Tyr-containing protein of 42 kDa, compared with controls. Enzymatic in-gel digestion and MALDI-TOF mass spectrometry identified this nitrated protein as actin. Electrospray ionization and fragment analysis by tandem mass spectrometry revealed that 3 of 15 actin tyrosine residues are nitrated (Tyr(91), Tyr(198), and Tyr(240)) at positions that significantly modify actin assembly. Confocal microscopy of SCD human and mouse tissues revealed that nitration led to morphologically distinct disorganization of filamentous actin. In aggregate, we have observed that the hemoglobin point mutation of sickle cell disease that mediates hemoglobin polymerization defects is translated, via inflammatory oxidant reactions, into defective cytoskeletal polymerization.

Spatial mapping of pulmonary and vascular nitrotyrosine reveals the pivotal role of myeloperoxidase as a catalyst for tyrosine nitration in inflammatory diseases.

Nitrotyrosine (NO(2)Tyr) formation is a hallmark of acute and chronic inflammation and has been detected in a wide variety of human pathologies. However, the mechanisms responsible for this posttranslational protein modification remain elusive. While NO(2)Tyr has been considered a marker of peroxynitrite (ONOO(-)) formation previously, there is growing evidence that heme-protein peroxidase activity, in particular neutrophil-derived myeloperoxidase (MPO), significantly contributes to NO(2)Tyr formation in vivo via the oxidation of nitrite (NO(2)(-)) to nitrogen dioxide (.NO(2)). Coronary arteries from a patient with coronary artery disease, liver and lung tissues from a sickle cell disease patient, and an open lung biopsy from a lung transplant patient undergoing rejection were analyzed immunohistochemically to map relative tissue distributions of MPO and NO(2)Tyr. MPO immunodistribution was concentrated along the subendothelium in coronary tissue and hepatic veins as well as in the alveolar epithelial compartment of lung tissue from patients with sickle cell disease or acute rejection. MPO immunoreactivity strongly colocalized with NO(2)Tyr formation, which was similarly distributed in the subendothelial and epithelial regions of these tissues. The extracellular matrix protein fibronectin (FN), previously identified as a primary site of MPO association in vascular inflammatory reactions, proved to be a major target protein for tyrosine nitration, with a strong colocalization of MPO, NO(2)Tyr, and tissue FN occurring. Finally, lung tissue from MPO(-/-) mice, having tissue inflammatory responses stimulated by intraperitoneal zymosan administration, revealed less subendothelial NO(2)Tyr immunoreactivity than tissue from wild-type mice, confirming the significant role that MPO plays in catalyzing tissue nitration reactions. These observations reveal that (i) sequestration of neutrophil-derived MPO in vascular endothelial and alveolar epithelial compartments is an important aspect of MPO distribution and action in vivo, (ii) MPO-catalyzed NO(2)Tyr formation occurs in diverse vascular and pulmonary inflammatory pathologies, and (iii) extracellular matrix FN is an important target of tyrosine nitration in these inflammatory processes.