An ISHLT consensus statement on strategies to prevent and manage hemocompatibility related adverse events in patients with a durable, continuous-flow ventricular assist device.

Life expectancy of patients with a durable, continuous-flow left ventricular assist device (CF-LVAD) continues to increase. Despite significant improvements in the delivery of care for patients with these devices, hemocompatability-related adverse events (HRAEs) are still a concern and contribute to significant morbility and mortality when they occur. As such, dissemination of current best evidence and practices is of critical importance. This ISHLT Consensus Statement is a summative assessment of the current literature on prevention and management of HRAEs through optimal management of oral anticoagulant and antiplatelet medications, parenteral anticoagulant medications, management of patients at high risk for HRAEs and those experiencing thrombotic or bleeding events, and device management outside of antithrombotic medications. This document is intended to assist clinicians caring for patients with a CF-LVAD provide the best care possible with respect to prevention and management of these events.

Biomimetic biodegradable artificial antigen presenting cells synergize with PD-1 blockade to treat melanoma.

Biomimetic materials that target the immune system and generate an anti-tumor responses hold promise in augmenting cancer immunotherapy. These synthetic materials can be engineered and optimized for their biodegradability, physical parameters such as shape and size, and controlled release of immune-modulators. As these new platforms enter the playing field, it is imperative to understand their interaction with existing immunotherapies since single-targeted approaches have limited efficacy. Here, we investigate the synergy between a PLGA-based artificial antigen presenting cell (aAPC) and a checkpoint blockade molecule, anti-PD1 monoclonal antibody (mAb). The combination of antigen-specific aAPC-based activation and anti-PD-1 mAb checkpoint blockade induced the greatest IFN-γ secretion by CD8+ T cells in vitro. Combination treatment also acted synergistically in an in vivo murine melanoma model to result in delayed tumor growth and extended survival, while either treatment alone had no effect. This was shown mechanistically to be due to decreased PD-1 expression and increased antigen-specific proliferation of CD8+ T cells within the tumor microenvironment and spleen. Thus, biomaterial-based therapy can synergize with other immunotherapies and motivates the translation of biomimetic combinatorial treatments.

Gene delivery polymer structure-function relationships elucidated via principal component analysis.

Principal component analysis was applied to a biomaterial library of poly(beta-amino ester)s, useful for non-viral gene delivery, to elucidate chemical parameters that drive biological function. Correlative relationships and principal components were analyzed between 24 physico-chemical polymer properties and 3 cell-based functional variables in human glioblastoma cells (transfection, uptake, and viability).

Gene delivery to human adult and embryonic cell-derived stem cells using biodegradable nanoparticulate polymeric vectors.

Gene delivery to stem cells holds great potential for tissue regeneration and delivery of therapeutic proteins. The major barrier is the lack of safe and efficient delivery methods. Here, we report enhanced gene delivery systems for human stem cells using biodegradable polymeric vectors. A library of poly (beta-amino esters) end-modified derivatives was developed and optimized for high transfection efficiency and low cytotoxicity for three human stem cell lines including human mesenchymal stem cells (hMSCs), human adipose-derived stem cells (hADSCs) and human embryonic stem cell-derived cells (hESCds). In the presence of 10% serum, leading end-modified C32 polymeric vectors exhibited significantly high transfection efficiency in hMSCs (27+/-2%), hADSCs (24+/-3%) and hESCds (56+/-11%), with high cell viability (87-97%) achieved in all cell types. Our results show that poly(beta-amino esters) as a class, and end-modified versions of C32 in particular, are efficient polymeric vectors for gene delivery to both adult and embryonic-derived stem cells.

Development of a novel gene delivery scaffold utilizing colloidal gold-polyethylenimine conjugates for DNA condensation.

We have developed a novel gene delivery scaffold based on DNA plasmid condensation with colloidal gold/polyethylenimine conjugates. This scaffold system was designed to enable systematic study of the relationships between DNA complex physical properties and transfection efficiency. Using an enhanced green fluorescent protein-coding reporter plasmid and a Chinese hamster ovary cell line, we have measured the transfection efficiencies of our complexes using flow cytometry and their cytotoxicities using the trypan blue assay. We have also assayed complex particle morphologies using atomic force microscopy, photon correlation spectroscopy, and a novel plasmon absorbance peak position analysis. We achieved comparable rates of transfection relative to the commonly used polycationic condensation agents calcium phosphate and LipofectAMINE, with comparably low cytotoxicities. In addition, by manipulating colloidal gold concentration, we could partially decouple complex physical properties including charge ratio, size, DNA loading, and polyethylenimine concentration. Our morphological analyses showed that complexes with a diameter of a few hundred nanometers and a charge ratio of approximately 8 perform best in our transfection efficiency assays. The use of colloidal gold as a component in our delivery system provides a versatile system for manipulating complex properties and morphology as well as a convenient scaffold for planned ligand conjugation studies.

Does low phosphorus supply limit seedling establishment and tree growth in groves of ectomycorrhizal trees in a central African rainforest?

• In a forest grove at Korup dominated by the ectomycorrhizal species Microberlinia bisulcata , an experiment tested whether phosphorus (P) was a limiting nutrient. • P-fertilization of seven subplots 1995-97 was compared with seven controls. It led to large increases in soil P concentrations. Trees were measured in 1995 and 2000. M. bisulcata and four other species were transplanted into the treatments, and a wild cohort of M. bisulcata seedlings was followed in both. Leaf litter fall from trees and seedlings were analysed for nutrients. • Growth of trees was not affected by added P. Transplanted seedlings survived better in the controls than added-P subplots: they did not grow better with added-P. M. bisulcata wildlings survived slightly better in the added-P subplots in yr 1 but not later. Litter fall and transplanted survivors had much higher concentrations of P (not N) in the added-P than control subplots. • Under current conditions, it appears that P does not limit growth of trees or hinder seedling establishment, especially of M. bisculcata , in these low-P grove soils.

Pseudoporphyria.

Pseudoporphyria is the term used to describe a photodistributed bullous disorder with clinical and histologic features of porphyria cutanea tarda, but without accompanying biochemical porphyrin abnormalities. Medications, chronic renal failure/dialysis, excessive sun exposure and UVA radiation have all been reported to cause pseudoporphyria. Recognition, diagnosis, and appropriate management of pseudoporphyria are discussed.

Xerosis in hypothyroidism: a potential role for the use of topical thyroid hormone in euthyroid patients.

Xerosis is an extraordinarily common problem in dermatology. Despite the knowledge of well recognized aggravating factors, its etiology is an enigma, and the management of the condition is often suboptimal. Dry skin may be a manifestation of hypothyroidism. The nature of this association is reviewed, culminating in the speculation that topical thyroid hormone may represent a useful modality in euthyroid patients with xerosis or other disorders of keratinization.

Shade and leaf loss affect establishment of grove-forming ectomycorrhizal rain forest tree species.

• The poor regeneration of Microberlinia bisulcata in groves in Korup, Central Africa was investigated in the forest to highlight factors that interact with light. • Survival and growth of nursery-grown seedlings of M. bisulcata with four other species in each of two 1-yr trials were recorded after transplantation into quadrats differing in PAR. Total mass was predicted for PAR treatments in nursery trials reported separately. • Plant mass was strongly dependent on PAR for all species. At low PAR, across species, plant mass was positively related to seed mass. Forest : nursery mass ratios decreased with increasing PAR; M. bisulcata had the lowest ratios of all species at high PAR. Leaf weight ratio declined more steeply with increasing PAR in the forest than in the nursery and this was particularly marked for M. bisulcata. • Herbivory was the most probable cause of leaf loss. Forest : nursery ratios were negatively correlated with species' abundances in the forest. Besides its small seed size and shade intolerance, M. bisulcata is highly susceptible to leaf loss when illuminated. Opportunities for seedling release are thus very low.

Light and seed size affect establishment of grove-forming ectomycorrhizal rain forest tree species.

• Regeneration of the dominant ectomycorrhizal tree Microberlinia bisulcata in groves in Korup, Central Africa, is very poor. The hypothesis was tested that this species is more shade intolerant than other co-occurring species. • In two 1-yr trials, each with M. bisulcata and four other species at a nursery close to Korup, growth was measured under five PAR levels, with ± added P and ± watering in the dry season. In parallel experiments the effects of PAR with two R : FR ratios were investigated. • Increasing PAR had a consistent effect on the rates of increase in plant mass and on changes in the other variables. Doubling soil P, watering and halving the R : FR ratio had almost no effect. However, across species, mass at low PAR and relative growth rate related positively and negatively, respectively, to seed mass. • One contributing factor for the poor recruitment of M. bisulcata is therefore its low survival and slow growth at low PAR, due to its small seed size. The two codominant ectomycorrhizal grove species of Tetraberlinia, with larger seeds, were less affected by low PAR.

Localized whirlpool folliculitis in a football player.

Pseudomonas aeruginosa folliculitis occurs in patients exposed to contaminated water. Most out-breaks are associated with whirlpools. The infection is characterized by follicular, erythematous papules and pustules located on immersed body surfaces. Most reported cases are the result of recreational water use, occur in a diffuse pattern, and are devoid of green pustular pigment changes. The case described occurred in a football player after whirlpool treatment for an ankle strain. Green pustules and a localized affected area are unusual aspects of this case.

Linear childhood discoid lupus erythematosus following the lines of Blaschko: a case report with review of the linear manifestations of lupus erythematosus.

Seventeen cases of childhood discoid lupus erythematosus (DLE) have been previously reported in the literature. We describe the first reported case of childhood linear DLE following the lines of Blaschko. The clinical and histologic characteristics of childhood DLE are discussed and a review of the linear manifestations of childhood LE is presented.

Postmortem MR imaging of lobar cerebral infarction with pathologic and in vivo correlation.

Postmortem magnetic resonance (MR) imaging features of different types of lobar cerebral infarction are correlated with the findings in gross and histologic specimens. The postmortem findings are also correlated with in vivo findings in similar cases selected from teaching files. In acute infarction, white matter vasogenic edema leads to high signal intensity on T2-weighted images and blurring of the gray-white matter junction. Petechial hemorrhage in the cortex results in inhomogeneous signal intensity on T2-weighted images. In laminar necrosis, the hyperintense cortex on T1-weighted images is due not to hemorrhage but possibly to necrosis and the presence of lipid-laden macrophages. In subacute infarction, cortical edema and necrosis may cause the gyral pattern of enhancement. Meningeal inflammation and early fibrosis are probably responsible for meningeal enhancement. In chronic infarction, gliosis and cystic malacia are responsible for the increased signal intensity of white matter on T2-weighted images. Knowledge of the pathologic features of cerebral infarction helps in understanding the MR imaging findings.

Ultrasonography in the detection of aneuploidy in the first trimester.

Ultrasonography has been used increasingly in the first trimester to identify fetal anomalies as early as possible in gestation. First trimester sonographic screening may detect a greater proportion of aneuploid fetuses than sonography performed later in pregnancy, and it may allow determination of potential markers for prediction of chromosomal anomalies.

Fetal echocardiography in multiple gestations.

We reviewed fetal echocardiograms from 36 multiple gestations from 20 weeks gestation to term. Seven sets of twins plus one set of triplets were referred because of a suspect cardiac anomaly in one fetus; heart disease was confirmed in one fetus of six sets of twins and in one triplet. Six sets were referred because of extracardiac malformations and heart disease was confirmed in two sets (including both twins in one set). The remaining case was detected in a patient sent for evaluation of karyotypic abnormality. Thus 11 fetal cardiac defects were detected in ten pregnancies. Chromosomes were abnormal in three of the anomalous fetuses. Two sets discordant for heart disease were monochorionic. Intervention, including a change in the planned location of delivery, or maternal digitalization for fetal congestive failure, occurred in six. We conclude that fetal echocardiography is feasible and useful in appropriate multiple gestations. Although often ethically complex, the information gained can be applied to patient management.

Diagnosis and significance of cystic hygroma in the first trimester.

Thirty cases of cervical cystic hygroma were diagnosed in the first trimester of pregnancy. Karyotype analysis was available in 29 (97 per cent). Fifteen (52 per cent) had a chromosomal abnormality. The ultrasound appearance was described as posterior cervical, lateral cervical, or cervical hygroma with hydrops. Of the 14 euploid embryos, six were electively aborted, two are undelivered, and six have been delivered as phenotypically normal infants. In cases in which the chromosomes were normal and the pregnancy continued, all lesions resolved by 18 weeks.

Saphenous vein rupture pressure, rupture stress, and carotid endarterectomy vein patch reconstruction.

Early postoperative patch rupture is a catastrophic complication of carotid endarterectomy reconstruction with greater saphenous vein. Mechanical determinants of saphenous vein rupture were identified by structural measurements and the results applied to carotid endarterectomy patch geometry. Diameter and rupture pressure was measured in fresh saphenous vein segments from the ankle, knee, or thigh in 157 patients undergoing bypass operations. Circumferential hoop rupture stress was calculated and the results were applied to 157 carotid endarterectomy reconstructions. All vein ruptures were in the cylindric axis. The mean vein diameter was 4.58 mm. The mean vein rupture pressure was 2873 mm Hg (3.78 atm). Vein diameter was larger in the thigh than in the ankle or knee (p less than 0.01), but there was no significant difference in rupture pressure between veins from the three locations. Women had a smaller vein diameter than had men at all locations (p less than 0.01). There was a positive linear correlation between vein diameter and rupture pressure. The mean maximum diameter of curvature of 157 carotid endarterectomy reconstructions with a vein patch was 13.3 mm. Multiple random applications of the 157 veins to 157 carotid diameters predicted a mean patch rupture pressure of 1087 mm Hg (1.43 atm), 1163 mm Hg (1.53 atm) for men, and 866 mm Hg (1.14 atm) for women. Predicted vein patch rupture pressures less than 300 mm Hg were found in 5.7% of cases (8.8% women and 1.2% men). Only 0.6% of patients (1.8% women and 0% men) had a predicted rupture pressure less than 200 mm Hg. No veins with a diameter greater than or equal to 4.0 mm had a predicted patch rupture pressure less than 300 mm Hg. These results suggest that small-diameter saphenous veins have a higher risk of rupture when used as a carotid patch.

A comparison of transvaginal and abdominal ultrasound in visualizing the first trimester conceptus.

Ultrasound visualization of the first trimester embryo was compared using abdominal and transvaginal sonography. The parameters evaluated included the ability to obtain biometry, the ability to visualize detailed internal anatomy, and a subjective assessment of the overall image clarity. In 120 patients studied, transvaginal sonography was superior to abdominal sonography in obtaining biometric measurements in 51 cases (43%) and for visualizing internal anatomy in 45 cases (38%); also the image clarity of transvaginal sonography was subjectively better in 75 cases (63%). Vaginal sonography was superior to abdominal sonography in gestations less than or equal to 10 weeks, in obese patients, and in patients with retroverted uteri. The major difficulty encountered with transvaginal sonography was the limited maneuverability of the probe to generate specific views. Vaginal sonography can be a valuable tool in imaging the first trimester fetus, complementing, not replacing, abdominal sonography.