bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute Antibody-Mediated Rejection of Renal Transplant: Pathogenetic and Diagnostic Considerations
Authors: Truong Luan D. , Barrios Roberto , Adrogue Horacio E. , Gaber Lillian W. 
Published: February 2021

AbstractContext.—Acute antibody-mediated rejection (AMR) has emerged recently as an important cause of graft failure.Objective.—To review the pathogenetic, clinicopathologic, and diagnostic considerations of AMR.Data Sources.—Review of literature and the authors' experience.Conclusions.—Acute antibody-mediated rejection is mediated by antibodies specific for donor antigens, which bind to target antigens and activate the complement system, culminating in tissue injury. The clinical manifestation of AMR is not specific, and transplant biopsy is needed for diagnosis. The glomeruli show thrombosis or neutrophils or mononuclear leukocytes in capillary lumens. The tubulointerstitial compartment shows edema, hemorrhage, necrosis, mild inflammation, and neutrophils or mononuclear leukocytes in the peritubular capillary lumens. The blood vessels show thrombosis, thrombotic microangiopathy, fibrinoid necrosis, or transmural vasculitis. Strong staining for C4d in the peritubular capillaries is characteristic. A definitive diagnosis of AMR requires (1) morphologic evidence of acute tissue injury, (2) immunopathologic evidence for antibody action, and (3) serologic evidence of circulating donor-specific antibodies. Acute antibody-mediated rejection should be suspected if some but not all 3 criteria are met. Since effective treatment is currently available, accurate and timely diagnosis of AMR is essential.
Pulmonary Infections in Transplantation Pathology
Authors: Stewart Susan 
Published: February 2021

Abstract
Context.—Pulmonary infections are common and often life-threatening in solid organ and stem cell transplant recipients. Understanding their pathology is critical to making improvements in care and survival as well as in surgical techniques, immunosuppression management, prophylaxis, and treatment. Pulmonary infections are particularly common and serious in the susceptible population of lung transplant recipients.
Objective.—To summarize recent updates in the field for opportunistic infections and some common pathogens, and to consider the role of the diagnostic pulmonary histopathologist as well as advances in molecular diagnosis.
Data Sources.—This work is based on a selected review of the relevant medical and scientific literature, with emphasis on lung transplantation experience gained during 2 decades of practice.
Conclusions.—Pulmonary infections in transplant recipients present a diagnostic challenge and are a continuing source of mortality and morbidity despite improvement in prophylaxis and treatment. Accurate diagnosis requires multidisciplinary input from clinicians, radiologists, and pathology disciplines as well as complementary molecular methods.
Effect of Indian Ayurvedic Medicine Ashwagandha on Measurement of Serum Digoxin and 11 Commonly Monitored Drugs Using Immunoassays: Study of Protein Binding and Interaction With Digibind
Authors: Dasgupta Amitava , Peterson Amanda , Wells Alice , Actor Jeffrey K. 
Published: February 2021

Abstract
Context.—Ashwagandha, a popular Ayurvedic medicine, is now available in the United States. Alkaloids found in this herb have structural similarity with digoxin.
Objective.—To study potential interference of Ashwagandha with serum digoxin measurement by immunoassays. Potential interference was also investigated with immunoassays for 11 other commonly monitored drugs. In addition, interaction of components of Ashwagandha with the Fab fragment of antidigoxin antibody (Digibind) was investigated.
Design.—Two different brands of liquid extract and 1 dry powdered form of Ashwagandha were used for this investigation. Aliquots of drug-free serum were supplemented with various concentrations of Ashwagandha and apparent digoxin concentrations were measured by 3 digoxin immunoassays. Mice were fed with Ashwagandha and apparent digoxin concentrations were measured 1 and 3 hours after feeding. Potential interference of Ashwagandha with immunoassays of 11 other drugs was also investigated. Interaction of components of Ashwagandha with Digibind was studied in vitro.
Results.—Significant apparent digoxin concentrations were observed both in vitro and in vivo using the fluorescence polarization immunoassay of digoxin, whereas the Beckman and the microparticle enzyme immunoassay digoxin assay demonstrated minimal interference. Immunoassays of 11 other drugs tested were unaffected. When Ashwagandha extract was added to a serum pool containing digoxin, falsely elevated digoxin value was observed with fluorescence polarization immunoassay, but values were falsely lowered when measured by the microparticle enzyme immunoassay. Digibind neutralized digoxin-like immunoreactive components of Ashwagandha in vitro.
Conclusions.—Components of Ashwagandha interfered with serum digoxin measurements using immunoassays. Digibind neutralized free digoxin-like immunoreactive components of Ashwagandha.
Expanding the Pathologic Spectrum of Immunoglobulin Light Chain Proximal Tubulopathy
Authors: Kapur Umesh , Barton Kevin , Fresco Raoul , Leehy David J. , Picken Maria M. 
Published: February 2021

AbstractContext.—In plasma cell dyscrasias, involvement of the distal tubules is frequent and well characterized. In contrast, proximal tubules have only rarely been reported to show diagnostic pathology such as intracytoplasmic crystals.Objective.—To look for additional morphologic features that might be helpful in the diagnosis of proximal tubulopathy associated with an underlying plasma cell dyscrasia.Design.—We examined patients presenting with nonspecific renal symptoms who were found to have light chain restriction limited to proximal tubular epithelium by immunofluorescence. We correlated these results with light microscopy, electron microscopy, and the clinical findings.Results.—By immunofluorescence, 5 patients had light chain restriction in proximal tubular epithelium. By light microscopy, only 1 patient had focal rhomboid crystals in the proximal tubular epithelium; all other biopsies failed to show any discernible pathology within the proximal tubules or elsewhere in the kidney. By electron microscopy, proximal tubules from 2 patients showed crystals with a latticelike structure, whereas the remaining 3 patients had only prominent phagolysosomes. However, by immunoelectron microscopy, the lysosomal content showed light chain restriction (in 2 cases studied). Post–kidney biopsy, all patients were diagnosed with multiple myeloma or plasma cell dyscrasia. One patient developed renal failure and had recurrence of crystals in the allograft.Conclusions.—Light chain proximal tubulopathy may be associated with the presence of crystals or with the presence of phagolysosomes with light chain restriction as the sole abnormality. Both κ and λ light chains may be involved. The prognosis is variable and the pathology may recur in transplants.
Prognostic Significance of CD44, Platelet-Derived Growth Factor Receptor α, and Cyclooxygenase 2 Expression in Renal Cell Carcinoma
Authors: Tawfik Ossama W. , Kramer Brandan , Shideler Barbara , Danley Marsha , Kimler Bruce F. , Holzbeierlein Jeffrey 
Published: February 2021

AbstractContext.—Pathologic stage is the main prognostic factor for predicting outcome in renal cell carcinoma (RCC). Because of its unreliability in predicting tumor progression, other factors are needed to provide additional prognostic information.Objective.—The expression of CD44, cyclooxygenase 2, and platelet-derived growth factor receptor α (PDGFR-α) was evaluated as a potential prognostic factor for survival in patients with RCC.Design.—Sixty-two patients (42 men and 20 women; median age, 61 years), undergoing partial (10 cases) or radical (55 cases) nephrectomy for RCC were retrospectively analyzed by immunohistochemical analysis for CD44, cyclooxygenase 2, and PDGFR-α expression. Impact of various factors on disease-specific and overall survival was calculated using Cox proportional hazards models.Results.—There was a gradual increase in CD44 and cyclooxygenase 2 expression with increasing RCC nuclear grade. In contrast, PDGFR-α expression showed no consistent relationship with nuclear grade. On univariate analysis, metastasis at time of surgery (P &lt; .001), tumor size (P = .004), pathologic stage group (P = .001), and nuclear grade (P = .004) were correlated with disease-specific survival. On multivariate analysis, only the presence of metastasis at diagnosis (P &lt; .001) was significant. For overall survival, metastasis (P &lt; .001), tumor size (P = .02), pathologic stage group (P = .01), nuclear grade (P = .003), and PDGFR-α (P = .03) were significant on univariate analysis. Only metastasis (P = .001) and PDGFR-α (P = .03) were significant on multivariate analysis.Conclusions.—When combined with other variables, PDGFR-α expression in RCC may provide additional predictive value related to the patient's overall survival. However, CD44 and cyclooxygenase 2 do not seem to be independent prognostic indicators in predicting outcomes for patients with RCC.
Effects of a Pneumatic Tube System on Routine and Novel Hematology and Coagulation Parameters in Healthy Volunteers
Authors: Kratz Alexander , Salem Raneem O. , Van Cott Elizabeth M. 
Published: February 2021

Abstract
Context.—Technologic advances affecting analyzers used in clinical laboratories have changed the methods used to obtain many laboratory measurements, and many novel parameters are now available. The effects of specimen transport through a pneumatic tube system on laboratory results obtained with such modern instruments are unclear.
Objective.—To determine the effects of sample transport through a pneumatic tube system on routine and novel hematology and coagulation parameters obtained on state-of-the-art analyzers.
Design.—Paired blood samples from 33 healthy volunteers were either hand delivered to the clinical laboratory or transported through a pneumatic tube system.
Results.—No statistically significant differences were observed for routine complete blood cell count and white cell differential parameters or markers of platelet activation, such as the mean platelet component, or of red cell fragmentation. When 2 donors who reported aspirin intake were excluded from the analysis, there was a statistically, but not clinically, significant impact of transport through the pneumatic tube system on the mean platelet component. There were no statistically significant differences for prothrombin time, activated partial thromboplastin time, waveform slopes for prothrombin time or activated partial thromboplastin time, fibrinogen, or fibrin monomers.
Conclusions.—Although further study regarding the mean platelet component may be required, transport through a pneumatic tube system has no clinically significant effect on hematology and coagulation results obtained with certain modern instruments in blood samples from healthy volunteers.
The Origin of Reference Intervals
Authors: Friedberg Richard C. , Souers Rhona , Wagar Elizabeth A. , Stankovic Ana K. , Valenstein Paul N. 
Published: February 2021

Abstract
Context.—Standards have been developed for establishing reference intervals, but little is known about how intervals are determined in practice, interlaboratory variation in intervals, or errors that occur while setting reference intervals.
Objectives.—To determine (1) methods used by clinical laboratories to establish reference intervals for 7 common analytes, (2) variation in intervals, and (3) factors that contribute to establishment of “outlier” intervals.
Design.—One hundred sixty-three clinical laboratories provided information about their reference intervals for potassium, calcium, magnesium, thyroid-stimulating hormone, hemoglobin, platelet count, and activated partial thromboplastin time.
Results.—Approximately half the laboratories reported conducting an internal study of healthy individuals to validate reference intervals for adults. Most laboratories relied on external sources to establish reference intervals for pediatric patients. There was slight variation in intervals used by the central 80% of study laboratories, but some laboratories outside the central 80% had surprisingly low and high limits for their reference intervals. In some cases the intervals used by 2 laboratories had no overlap. For example, one laboratory considered a hemoglobin of 13.8 g/dL in a woman to be “low” while another considered the same value to be “high.” Three percent of reference intervals contained a limit that qualified as an “outlier” using standard statistical tests; we could not identify any practice associated with adoption of outlier intervals.
Conclusions.—Many laboratories adopt reference intervals from manufacturers without on-site testing of healthy individuals. Reference intervals used by facilities that forgo on-site testing are not statistically different from intervals validated with on-site studies.
Epithelioid Cell Clusters With an Extensive Lymphoid Background
Authors: Zarka Matthew A. 
Published: February 2021

Abstract
Context.—Fine-needle aspiration of salivary gland lesions can be particularly challenging for pathologists. There are numerous neoplasms that occur in this area and several cytologic variations of each specific lesion.
Objective.—To present and discuss a practical pattern recognition approach to fine-needle aspiration diagnosis, which includes categorizing lesions that share a certain overall cytologic architectural pattern, followed by identifying unique cellular characteristics that are specific to a certain lesion. An extensive discussion of one cytologic common pattern of salivary gland lesions, “epithelioid cell clusters with an extensive lymphoid background,” is presented. The pathologic entities that fall under this architectural pattern group are discussed, with an emphasis on neoplasms.
Data Sources.—Published literature and personal experience.
Conclusions.—A practical cytologic architectural pattern method can aid the pathologist in rendering a correct diagnosis when evaluating salivary gland lesions. One common pattern in salivary gland cytopathology is epithelioid cell clusters with an extensive lymphoid background. This pattern is often associated with Warthin tumor; however, other benign and malignant entities fall under this diagnostic group. Unique cytologic features separate these lesions into their respective diagnostic category.
Anti–Interleukin 8 Autoantibody:Interleukin 8 Immune Complexes Visualized by Laser Confocal Microscopy in Injured Lung
Authors: Allen Timothy Craig , Fudala Rafal , Sandra E Nash , Kurdowska Anna 
Published: February 2021

AbstractContext.—Anti–interleukin 8 autoantibody:interleukin 8 (anti–IL-8 autoantibody:IL-8) complexes are present in lung fluids of patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS), and levels of these complexes correlate with progression to and the outcome of ARDS. FcγRIIa, an immunoglobulin G (IgG) receptor, mediates proinflammatory activity of the complexes.Objective.—To evaluate lung tissues from patients with ARDS for presence of anti–IL-8 autoantibody:IL-8 complexes and to establish whether the complexes associate with FcγRIIa.Design.—Lung tissue sections from 3 patients with ARDS and sections of normal lung tissues from 3 patients were stained with antibodies against IL-8 and IgG to detect immune complexes and with antibody against FcγRIIa. In some experiments, sections were blocked with anti-Fcγ RIIa antibody before staining. Samples were analyzed using confocal microscopy.Results.—Interleukin 8 costained with IgG and FcγRIIa in lung tissues from patients with ARDS but not in control tissues, suggesting that anti–IL-8 autoantibody:IL-8 complexes are deposited in lungs of patients with ARDS via FcγRIIa. Further, colocalization between IL-8 and FcγRIIa could be blocked by anti-FcγRIIa.Conclusions.—Our data demonstrate that anti–IL-8 autoantibody:IL-8 complexes are present in lung tissues of patients with ARDS, and are attached to FcγRIIa.
The Medicolegal Aspect of Error in Pathology: A Search of Jury Verdicts and Settlements
Authors: Kornstein Michael J. , Byrne Sean P. 
Published: February 2021

Abstract
Context.—Identifying medical errors is a topic of current attention. Among the various approaches is the study of medical malpractice cases.
Objective.—To identify the most common medical errors involving the practice of pathology from a medicolegal perspective by analysis of published jury verdict and settlement reports.
Design.—Search approximately 50 publications that gather jury verdict and settlement information using LexisNexis, an on-line searchable archive, for pathology-related cases.
Results.—One hundred seventy-one legal cases were identified from 1988 through 2005. Nearly one-half involved surgical pathology; among the remainder, cytology cases slightly outnumbered those pertaining to clinical pathology. Among the surgical pathology cases and overall, based on this database, the most common reason for a medical malpractice lawsuit related to pathology was the alleged missed diagnosis of melanoma on a skin biopsy specimen. Less commonly, the surgical pathology cases involved breast biopsy specimens, gynecological specimens, lung, genitourinary system, technical or preanalytic errors (eg, mixed-up specimens), soft tissue, hematopathology, head and neck, gastrointestinal/hepatobiliary system, or thyroid. Among the 48 cases related to cytology, 37 involved false-negative Papanicolaou smears. Less common were cases related to fine-needle aspirates of the breast or thyroid or cytology specimens of the lung. Among the 36 cases involving clinical pathology, 32 related to the blood bank—usually transfusion-acquired human immunodeficiency virus infection.
Conclusions.—These data are in agreement with other publications as to the most frequent causes of medical malpractice allegations related to pathology. As these issues are addressed, the number of errors should decrease. Studying the jury verdict and settlements data may provide additional insight into medical errors and patient safety.
Metastatic Renal Cell Carcinoma to Hemangioblastoma in von Hippel-Lindau Disease
Authors: Polydorides Alexandros D. , Rosenblum Marc K. , Edgar Mark A. 
Published: February 2021

Abstract
A case of metastatic renal cell carcinoma (RCC) to a capillary hemangioblastoma (HAB) of the central nervous system in a 52-year-old woman with von Hippel-Lindau (vHL) syndrome is described. We review the literature on metastatic RCC to HAB, summarize the histologic and immunohistochemical features that can distinguish between the 2 tumors, and comment on the significance of such a finding in terms of the clinical diagnosis of vHL. We found the expression of CAM 5.2, RCC antigen, and CD10 to be strong in RCC and absent in HAB and, conversely, staining with Leu-7, neural cell adhesion molecule, and inhibin-α was present in HAB but weak or absent in RCC. These antibodies can be used to differentiate these entities, provided one is astute in recognizing the possibility of their coexistence.
Disseminated Coccidioidomycosis in Pregnancy
Authors: Hooper Jody E. , Lu Qun , Pepkowitz Samuel H. 
Published: February 2021

Abstract
Coccidioidomycosis is a fungal infection contracted through the inhalation of airborne spores, which are most frequently present in desert areas of the southwestern United States and Mexico. Primary immune response to infection is by TH1, a subset of helper T cells. Although pulmonary symptoms are most common, hematogenous systemic spread can also occur. Pregnancy is a well-noted risk factor for disseminated Coccidioides infection. The objective of this review is to provide an overview of coccidioidomycosis and to review immunologic and hormonal factors that increase risk of dissemination in pregnancy. Dissemination may occur more frequently in pregnant patients than in nonpregnant women because of shifts in T-cell immunity, changes in cytokine production, and increased hormone levels. There is disagreement regarding the precise incidence of systemic spread in pregnancy, but most sources agree that risk is substantially increased and vigilance must be high in patients with exposures in endemic areas.
Noninfectious Complications of Blood Transfusion
Authors: Eder Anne F. , Chambers Linda A. 
Published: February 2021

AbstractContext.—Serious noninfectious complications are far more likely to occur than viral disease transmission from blood component transfusion.Objective.—To compile a comprehensive list of the noninfectious risks of transfusion, examples of published risk estimates, and summaries of recent information regarding cause, prevention, or management of noninfectious transfusion risks.Data Sources.—Information was obtained from peer-reviewed English-language medical journal publications since 1990.Conclusions.—Early complications, although potentially more serious, usually occur less frequently (&lt;1 in 1000 transfusions) than late complications, which often affect more than 1% of recipients. Areas of active investigation and discussion include acute hemolytic reactions, transfusion-related acute lung injury, red cell alloimmunization, platelet transfusion refractoriness, and transfusion immunosuppression. Continued effort toward research and education to promote recognition and prevention of noninfectious complications associated with blood components is warranted.
Pathogen Inactivation: The Definitive Safeguard for the Blood Supply
Authors: Bryant Barbara J. , Klein Harvey G. 
Published: February 2021

Abstract
Context.—Pathogen inactivation provides a proactive approach to cleansing the blood supply. In the plasma fractionation and manufacturing industry, pathogen inactivation technologies have been successfully implemented resulting in no transmission of human immunodeficiency, hepatitis C, or hepatitis B viruses by US-licensed plasma derivatives since 1985. However, these technologies cannot be used to pathogen inactivate cellular blood components. Although current blood donor screening and disease testing has drastically reduced the incidence of transfusion-transmitted diseases, there still looms the threat to the blood supply of a new or reemerging pathogen. Of particular concern is the silent emergence of a new agent with a prolonged latent period in which asymptomatic infected carriers would donate and spread infection.
Objective.—To review and summarize the principles, challenges, achievements, prospective technologies, and future goals of pathogen inactivation of the blood supply.
Data Sources.—The current published English-language literature from 1968 through 2006 and a historical landmark article from 1943 are integrated into a review of this subject.
Conclusions.—The ultimate goal of pathogen inactivation is to maximally reduce the transmission of potential pathogens without significantly compromising the therapeutic efficacy of the cellular and protein constituents of blood. This must be accomplished without introducing toxicities into the blood supply and without causing neoantigen formation and subsequent antibody production. Several promising pathogen inactivation technologies are being developed and clinically tested, and others are currently in use. Pathogen inactivation offers additional layers of protection from infectious agents that threaten the blood supply and has the potential to impact the safety of blood transfusions worldwide.