Effectiveness of combined plasma cell therapy and costimulation blockade based desensitization regimen in heart transplant candidates.

BACKGROUND: Desensitization is one of the strategies to reduce antibodies and facilitate heart transplantation in highly sensitized patients. We describe our center's desensitization experience with combination of plasma cell (PC) depletion therapy (with proteasome inhibitor or daratumumab) and costimulation blockade (with belatacept). METHODS: We reviewed five highly sensitized patients who underwent desensitization therapy with plasma cell depletion and costimulation blockade. We evaluated the response to therapy by measuring the changes in cPRA, average MFI, and number of positive beads > 5000MFI. RESULTS: Five patients, mean age of 56 (37-66) years with average cPRA of 98% at 5000 MFI underwent desensitization therapy. After desensitization, mean cPRA decreased from 98% to 70% (p = .09), average number of beads > 5000 MFI decreased from 59 to 37 (p = .15), and average MFI of beads > 5000 MFI decreased from 16713 to 13074 (p = .26). CONCLUSION: Combined PC depletion and CoB could be a reasonable strategy for sustained reduction in antibodies in highly sensitized patients being listed for heart transplantation.

Taxonomic assessment of Alligator Snapping Turtles (Chelydridae: Macrochelys), with the description of two new species from the southeastern United States.

The Alligator Snapping Turtle, Macrochelys temminckii, is a large, aquatic turtle limited to river systems that drain into the Gulf of Mexico. Previous molecular analyses using both mitochondrial and nuclear DNA suggested that Macrochelys exhibits significant genetic variation across its range that includes three distinct genetic assemblages (western, central, and eastern = Suwannee). However, no taxonomic revision or morphological analyses have been conducted previously. In this study, we test previous hypotheses of distinct geographic assemblages by examining morphology, reanalyzing phylogeographic genetic structure, and estimating divergence dating among lineages in a coalescent framework using Bayesian inference. We reviewed the fossil record and discuss phylogeographic and taxonomic implications of the existence of three distinct evolutionary lineages. We measured cranial (n=145) and post-cranial (n=104) material on field-captured individuals and museum specimens. We analyzed 420 base pairs (bp) of mitochondrial DNA sequence data for 158 Macrochelys. We examined fossil Macrochelys from ca. 15-16 million years ago (Ma) to the present to better assess historical distributions and evaluate named fossil taxa. The morphological and molecular data both indicate significant geographical variation and suggest three species-level breaks among genetic lineages that correspond to previously hypothesized genetic assemblages. The holotype of Macrochelys temminckii is from the western lineage. Therefore, we describe two new species as Macrochelys apalachicolae sp. nov. from the central lineage and Macrochelys suwanniensis sp. nov. from the eastern lineage (Suwannee River drainage). Our estimates of divergence times suggest that the most recent common ancestor (MRCA) of M. temminckii (western) and M. apalachicolae (central) existed 3.2-8.9 Ma during the late Miocene to late Pliocene, whereas M. temminckii-M. apalachicolae and M. suwanniensis last shared a MRCA 5.5-13.4 Ma during the mid-Miocene to early Pliocene. Examination of fossil material revealed that the fossil taxon M. floridana is actually a large Chelydra. Our taxonomic revision of Macrochelys has conservation and management implications in Florida, Georgia, and Alabama.

Silvopastoral systems benefit invertebrate biodiversity on tropical livestock farms in Caquetá, Colombia.

In the Colombian Amazon, there has been long-term and sustained loss of primary forest threatening biodiversity and climate change mitigation. Silvopastoral practices that integrate trees into livestock production could help address both local economic and wider environmental challenges.We aimed to assess the effects of silvopastoral practices on invertebrate communities on smallholder farms in Caquetá, Colombia. Using sweep nets and malaise trapping, invertebrate communities were compared between traditional pasture, silvopasture and forest edge habitats.Invertebrate communities collected using sweep nets were contrasting among habitat types, communities were significantly different between traditional pasture and forest edge habitats and diversity and evenness were greatest in forest edges compared to traditional pastures. It appears that silvopasture areas, by supporting similar invertebrate assemblages to both traditional pasture and forest edges, may be acting as an intermediate habitat.When individual invertebrate orders were compared, Lepidoptera and Coleoptera were found in greater abundance in the forest edge habitats, while Hemiptera were more abundant in traditional pasture. Hemipterans are often pests of forage plants in pasture systems and these differences in abundance may have implications for ecosystem services and disservices.Silvopastoral approaches cannot replace the unique biodiversity supported by native forests but could deliver benefits for invertebrate conservation and ecosystem services if integrated into landscapes.

Resumen: En la Amazonía colombiana ha habido una pérdida sostenida y a largo plazo de bosque primario que amenaza la biodiversidad y la mitigación del cambio climático. Las prácticas silvopastoriles que integran los árboles en la producción ganadera podrían ayudar a abordar tanto los desafíos económicos locales como los ambientales.Nuestro objetivo fue evaluar los efectos de las prácticas silvopastoriles en comunidades de invertebrados en pequeñas fincas en Caquetá, Colombia. Las comunidades de invertebrados se compararon entre las pasturas nativas, el sistema silvopastoril y los hábitats del borde del bosque mediante el uso redes entomológicas de barrido y trampas Malaise.Las comunidades de invertebrados recolectadas usando redes entomológicas de barrido contrastaban entre los tipos de hábitat. Las comunidades eran significativamente diferentes entre las pasturas nativas y el borde de bosque. Pareciera que las áreas de silvopastoreo, al soportar conjuntos de invertebrados similares tanto a las pasturas nativas como a los bordes del bosque, pueden estar actuando como un hábitat intermedio.Cuando se compararon los órdenes individuales de invertebrados, los lepidópteros y los coleópteros se encontraron en mayor abundancia en los hábitats del borde del bosque, mientras que los hemípteros eran más abundantes en las pasturas nativas. Los hemípteros son a menudo plagas de plantas forrajeras en sistemas de pastoreo y estas diferencias en abundancia pueden tener implicaciones y perjuicios para los servicios ecosistémicos.Los sistemas silvopastoriles no pueden reemplazar la biodiversidad única apoyada por los bosques nativos, pero podrían ofrecer beneficios para la conservación de invertebrados y los servicios ecosistémicos si se integran en los paisajes.

A new species of Glabellula Bezzi, 1902 (Diptera: Mythicomyiidae: Glabellulinae) from Colombia, and an updated key to South American species.

Glabellula Bezzi, 1902 has a cosmopolitan distribution and is a poorly studied group in the Neotropical Region, and completely unknown in Colombia. One new species of Glabellula is described from Colombia, namely Glabellula antioquensis sp. nov. (type-locality: Buriticá, La Angelina). Illustrations and a dichotomous key to the South American species are presented.

Two new species of Asymphyloptera Collin (Diptera: Empididae: Clinocerinae) from Colombia, with an updated key to males of New World species.

The genus Asymphyloptera is recorded from Colombia for the first time, with the description of two new species from Parque Natural Regional Cerro Pramo de Miraflores: A. miraflorensis sp. nov. and A. tama sp. nov. The two species are illustrated, and an updated key and distribution map for all New World species are presented.

First records of Pieza Evenhuis, 2002 (Diptera: Mythicomyiidae: Mythicomyiinae) from Colombia, with description of a new species from arid zones of a Tropical dry forest.

Pieza Evenhuis, 2002 has a New World distribution and is a poorly studied group in the Neotropical Region, and completely unknown in Colombia. We recorded for the first time the genus Pieza in Colombia with two species, namely Pieza rafaeli Mendes et al., 2019 and we described Pieza globosa sp. nov. (type-locality: Sabanalarga, Boca de Niquia) from arid zones of a Tropical dry forest. Illustrations and a distribution map are presented.

Open removal models with temporary emigration and population dynamics to inform invasive animal management.

Removal sampling data are the primary source of monitoring information for many populations (e.g., invasive species, fisheries). Population dynamics, temporary emigration, and imperfect detection are common sources of variation in monitoring data and are key parameters for informing management. We developed two open robust-design removal models for simultaneously modeling population dynamics, temporary emigration, and imperfect detection: a random walk linear trend model (estimable without ancillary information), and a 2-age class informed population model (InfoPM, closely related to integrated population models) that incorporated prior information for age-structured vital rates and relative juvenile availability. We applied both models to multiyear, removal trapping time-series of a large invasive lizard (Argentine black and white tegu, Salvator merianae) in three management areas of South Florida to evaluate the effectiveness of management programs. Although estimates of the two models were similar, the InfoPMs generally returned more precise estimates, partitioned dynamics into births, deaths, net migration, and provided a decision support tool to predict population dynamics under different effort scenarios while accounting for uncertainty. Trends in tegu superpopulation abundance estimates were increasing in two management areas despite generally high removal rates. However, tegu abundance appeared to decline in the Core management area, where trapping density was the highest and immigration the lowest. Finally, comparing abundance predictions of no-removal scenarios to those estimated in each management area suggested significant population reductions due to management. These results suggest that local tegu population control via systematic trapping may be feasible with high enough trap density and limited immigration; and highlights the value of these trapping programs. We provided the first estimates of tegu abundance, capture probabilities, and population dynamics, which is critical for effective management. Furthermore, our models are applicable to a wide range of monitoring programs (e.g., carcass recovery or removal point-counts).

Waitlist and post-transplant outcomes in patients listed with intra-aortic balloon pump for heart transplant: United Network for Organ Sharing registry.

BACKGROUND: Intra-aortic balloon pump as bridge-to-transplant (BTT) has been used successfully in patients with refractory cardiogenic shock. However, the waitlist mortality in this population is high and predictors of waitlist mortality in this population are not known. We sought to identify predictors for waitlist mortality in patients listed with intra-aortic balloon pump and risk factors for 1-year mortality after heart transplant in this population. METHODS: We identified patients listed for heart transplantation with intra-aortic balloon pump in the United Network for Organ Sharing data set from 1994 to 2015. Univariable and multivariable Cox proportional hazards models were used to identify predictors of waitlist mortality and 1-year post-transplant mortality. RESULTS: From 1945 patients listed with intra-aortic balloon pump, 67.5% (N = 1313) were alive at 1 year and waitlist mortality was 32.5% (N = 632). We found that higher pulmonary vascular resistance, need for inotropes, and need for mechanical ventilation were associated with higher waitlist mortality. Mechanical ventilation and dialysis prior to transplantation were important predictors of 1-year post-transplant mortality. CONCLUSION: Predictors of mortality such as high pulmonary vascular resistance, dialysis dependence, inotrope, and ventilator dependence in patients listed with intra-aortic balloon pump can help us identify those patients that are at high risk of dying prior to a heart transplantation.

The Undergraduate Training in Genomics (UTRIG) Initiative: early & active training for physicians in the genomic medicine era.

Genomic medicine is transforming patient care. However, the speed of development has left a knowledge gap between discovery and effective implementation into clinical practice. Since 2010, the Training Residents in Genomics (TRIG) Working Group has found success in building a rigorous genomics curriculum with implementation tools aimed at pathology residents in postgraduate training years 1-4. Based on the TRIG model, the interprofessional Undergraduate Training in Genomics (UTRIG) Working Group was formed. Under the aegis of the Undergraduate Medical Educators Section of the Association of Pathology Chairs and representation from nine additional professional societies, UTRIG's collaborative goal is building medical student genomic literacy through development of a ready-to-use genomics curriculum. Key elements to the UTRIG curriculum are expert consensus-driven objectives, active learning methods, rigorous assessment and integration.

Squamous Cell Carcinoma of the Lung.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.

Genetic Mutations and Multifactorial Inheritance: Dilated Cardiomyopathy.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.

Pathology Course Director Perspectives of a Recent LCME Experience: Preparation in an Integrated Curriculum With the Revised Standards.

Preparation for a Liaison Committee of Medical Education (LCME) accreditation site visit is a daunting task for any medical school, particularly for medical schools that have adopted integrated curricula. The LCME accreditation is the standard that all US and Canadian allopathic medical schools must meet in order for the school to award the degree of medical doctor. The Uniformed Services University of the Health Sciences (USU) recently underwent a full-scale LCME accreditation visit that was conducted under the newly revised LCME standards and elements. The site visit occurred just 5 years after our school began implementing a totally revised, organ system-based curriculum. Preparing for a critical, high-stakes site visit shortly after transitioning to a totally revised, integrated module-based preclerkship curriculum presented an array of new challenges that required a major modification to the type of preparation, communication, and collaboration that traditionally occurs between course directors and departmental chairs. These included the need to ensure accurate, timely communication of curricular details to different levels of the academic administration, particularly as it related to the execution of self-directed learning (SDL). Preparation for our site visit, did, however, provide a novel opportunity to highlight the unique educational experiences associated with the study of pathology, as pathology traverses both clinical and basic sciences. Sharing these experiences may be useful to other programs that are either undergoing or who are preparing to undergo an accreditation visit and may also aid in a broader communication of the highlights or initiatives of educational activities.

New record of Blepharicnema splendens (Diptera, Calliphoridae, Luciliini) and range expansion in Caquetá, Colombia

Blepharicnema splendens is a dipteran with occurrence restricted to the Neotropical Andean mountain forests from 1,400 to 2,500 masl. We surveyed the species using Van Someren-Rydon traps with decaying fish as bait in four sites (veredas) in the Eastern Cordillera, in the Municipality of Florencia, Caquetá, Colombia. A total of 221 individuals were collected in the four localities. The Vereda Las Brisas had the highest abundance, with 104 specimens (45.4%), followed by El Vergel, 76 (33.2%), Tarqui, 46 (20.1%) and Los Lirios, 2 (0.9%). The record of this species in the mountainous ecosystems of the Department of Caquetá expands the known distribution of B. splendens and adds to the incipient knowledge on the diversity of Diptera in this region. (AU)

Transmyocardial revascularization to enhance myocardial vasculogenesis and hemodynamic function.

OBJECTIVE: A significant number of patients have coronary artery disease that is not amenable to traditional revascularization. Prospective, randomized clinical trials have demonstrated therapeutic benefits with transmyocardial laser revascularization in this cohort. The molecular mechanisms underlying this therapy, however, are poorly understood. The focus of this study was evaluation of the proposed vasculogenic mechanisms involved in transmyocardial laser revascularization. METHODS: Male Yorkshire pigs (30-35 kg, n = 25) underwent left thoracotomy and placement of ameroid constrictors around the proximal left circumflex coronary artery. During the next 4 weeks, a well-defined region of myocardial ischemia developed, and the animals underwent a redo left thoracotomy. The animals were randomly assigned to sham treatment (thoracotomy only, control, n = 11) or transmyocardial laser revascularization of hibernating myocardium with a holmium:yttrium-aluminum-garnet laser (n = 14). After an additional 4 weeks, the animals underwent median sternotomy, echocardiographic analysis of wall motion, and hemodynamic analysis with an ascending aortic flow probe and pulmonary artery catheter. The hearts were explanted for molecular analysis. RESULTS: Molecular analysis demonstrated statistically significant increases in the proangiogenic proteins nuclear factor kappaB (42 +/- 27 intensity units vs 591 +/- 383 intensity units, P = .03) and angiopoietin 1 (0 +/- 0 intensity units vs 241 +/- 87 intensity units, P = .003) relative to sham control values with transmyocardial laser revascularization within the ischemic myocardium. There were also increases in vasculogenesis (18.8 +/- 8.7 vessels/high-power field vs 31.4 +/- 10.2 vessels/high-power field, P = .02), and perfusion (0.028 +/- 0.009 microm3 blood/microm3 tissue vs 0.044 +/- 0.004 microm3 blood/microm3 tissue, P = .01). Enhanced myocardial viability was demonstrated by increased myofilament density (40.7 +/- 8.5 cardiomyocytes/high-power field vs 50.8 +/- 7.5 cardiomyocytes/high-power field, P = .03). Regional myocardial function within the treated territory demonstrated augmented contractility. Global hemodynamic function was significantly improved relative to the control group with transmyocardial laser revascularization (cardiac output 2.1 +/- 0.2 L/min vs 2.7 +/- 0.2 L/min, P = .007, mixed venous oxygen saturation 64.7% +/- 3.6% vs 76.1% +/- 3.4%, P = .008). CONCLUSION: Transmyocardial laser revascularization with the holmium-YAG laser enhances perfusion, with resultant improvement in myocardial contractility.

The morphologic spectrum of infantile lobar emphysema: a study of 33 cases.

Infantile lobar emphysema (ILE) is a relatively uncommon entity characterised by radiologic pulmonary lobar overinflation. The spectrum of underlying pathology in ILE has not been previously detailed. We have reviewed thirty-three cases of ILE accessioned to the Armed Forces Institute of Pathology, Washington D.C., since 1970. Seventeen (51.5%) presented in the first week of life, 27 (81.8%) presented within the first six months, and an additional six cases presented beyond six months including three beyond 18 months of age. Upper lobe involvement occurred in 96.9% cases and multiple lobes were involved in six cases. Nine infants had polyalveolar (hyperplastic) lobes determined on the basis of radial alveolar counts (RACs), while 21 were considered to be "classic ILE" since these showed lobar hyperexpansion without any other abnormality. RACs in infants with classic ILE remained fairly constant irrespective of age unlike a progressive increase seen in normal age-matched controls, suggesting a post-partum arrest of acinar development in ILE. Additional findings included serpiginous bronchioles resembling those seen in extralobar sequestration in two cases, bronchopulmonary dysplasia in two cases, and one case each showing "cystic alveoli" and peripheral subpleural cysts. ILE thus seems to be a composite of various pathologies resulting in a single clinical entity. We hypothesise that the timing of an inciting functional or anatomic bronchial obstruction during in-utero lung development determines morphologic variation in ILE.

Neuroblastoma, ganglioneuroblastoma, and ganglioneuroma: radiologic-pathologic correlation.

Neuroblastoma, ganglioneuroblastoma, and ganglioneuroma are tumors of the sympathetic nervous system that arise from primitive sympathogonia and are referred to collectively as neuroblastic tumors. They arise wherever sympathetic tissue exists and may be seen in the neck, posterior mediastinum, adrenal gland, retroperitoneum, and pelvis. The three tumors differ in their degree of cellular and extracellular maturation; immature tumors tend to be aggressive and occur in younger patients (median age, just under 2 years), whereas mature tumors occur in older children (median age, approximately 7 years) and tend to behave in a benign fashion. The most benign tumor is the ganglioneuroma, which is composed of gangliocytes and mature stroma. Ganglioneuroblastoma is composed of both mature gangliocytes and immature neuroblasts and has intermediate malignant potential. Neuroblastoma is the most immature, undifferentiated, and malignant tumor of the three. Neuroblastoma, however, may have a relatively benign course, even when metastatic. Thus, these neuroblastic tumors vary widely in their biologic behavior. Features such as DNA content, tumor proto-oncogenes, and catecholamine synthesis influence prognosis, and their presence or absence aids in categorizing patients as high, intermediate, or low risk. Treatment consists of surgery and, usually, chemotherapy. Despite recent advances in treatment, including bone marrow transplantation, neuroblastoma remains a relatively lethal tumor, accounting for 10% of pediatric cancers but 15% of cancer deaths in children.