HLA-DR-DQ associations, combined with PLASMIC score, are reliable predictors of acquired thrombotic thrombocytopenic purpura (aTTP) and aid in differentiating aTTP from other thrombotic microangiopathies.

BACKGROUND: Thrombotic microangiopathies (TMA) are a group of disorders with overlapping clinical features that require urgent intervention. Treatment is based on the recognition of the TMA type, which is often challenging. The aim of this study was to identify specific HLA associations with different TMA types to aid rapid diagnosis and appropriate treatment, since the HLA assay can be completed within five hours. METHODS: All 86 consecutive patients who presented to the University of Arkansas for Medical Sciences between May 2013 and January 2021 with a presumptive diagnosis of TMA were included in this study. HLA typing was performed and correlated with other clinical and laboratory studies. RESULTS: In comparison with other types of TMA, patients with acquired thrombotic thrombocytopenic purpura (aTTP) showed increased frequencies of HLA-DRB1*11, HLA-DQB1*03:01/19, HLA-DRB1*08 and HLA-DRB3. Combining the presence of these HLA associations with a PLASMIC score of 6 or more achieved a higher positive predictive value (90%) for identifying aTTP than the PLASMIC score alone (69%). In comparison with other TMA types, patients with aTTP showed decreased frequencies of HLA-DRB4, HLA-DRB1*07, HLA-DQB1*02. The HLA-DRB1*07/DQB1*02 was not observed in any aTTP patients (negative predictive value: 100%), and thus the presence of this haplotype essentially rules out aTTP. Further, HLA-DRB1*11/DQB1*03:01/19 was absent in atypical hemolytic uremic syndrome patients. CONCLUSION: HLA alleles can be used as an adjunct for the rapid assessment of TMA and can help to differentiate it from other primary and secondary forms of TMA, allowing for earlier definitive therapy.

Acoustic Activation Imaging With Intravenous Perfluoropropane Nanodroplets Results in Selective Bioactivation of the Risk Area.

BACKGROUND: Acoustically activatable perfluoropropane droplets (PD) can be formulated from commercially available microbubble preparations. Diagnostic transthoracic ultrasound frequencies have resulted in acoustic activation (AA) predominately within myocardial infarct zones (IZ). OBJECTIVE: We hypothesized that the AA area following acute coronary ischemia/reperfusion (I/R) would selectively enhance the developing scar zone, and target bioeffects specifically to this region. METHODS: We administered intravenous PD in 36 rats and 20 pigs at various stages of myocardial scar formation (30 minutes, 1 day, and 7 days post I/R) to determine what effect infarct age had on the AA within the IZ. This was correlated with histology, myeloperoxidase activity, and tissue nitrite activity. RESULTS: The degree of AA within the IZ in rats was not associated with collagen content, neutrophil infiltration, or infarct age. AA within 24 hours of I/R was associated with increased nitric oxide utilization selectively within the IZ (P < .05 compared with remote zone). The spatial extent of AA in pigs correlated with infarct size only when performed before sacrifice at 7 days (r = .74, P < .01). CONCLUSIONS: Acoustic activation of intravenous PD enhances the developing scar zone following I/R, and results in selective tissue nitric oxide utilization.

US regulatory considerations for low field magnetic resonance imaging systems.

Although there has been a resurgence of interest in low field magnetic resonance imaging (MRI) systems in recent years, low field MRI is not a new concept. FDA has a long history of evaluating the safety and effectiveness of MRI systems encompassing a wide range of field strengths. Many systems seeking marketing authorization today include new technological features (such as artificial intelligence), but this does not fundamentally change the regulatory paradigm for MR systems. In this review, we discuss some of the US regulatory considerations for low field magnetic resonance imaging (MRI) systems, including applicability of existing laws and regulations and how the U.S. Food and Drug Administration (FDA) evaluates low field MRI systems for market authorization. We also discuss regulatory considerations in the review of low field MRI systems incorporating novel AI technology. We foresee that MRI systems of all field strengths intended for general diagnostic use will continue to be evaluated for marketing clearance by the metric of substantial equivalence set forth in the premarket notification pathway.

Thermal and Acoustic Stabilization Of Volatile Phase-Change Contrast Agents Via Layer-By-Layer Assembly.

OBJECTIVE: Phase-change contrast agents (PCCAs) are perfluorocarbon nanodroplets (NDs) that have been widely studied for ultrasound imaging in vitro, pre-clinical studies, and most recently incorporated a variant of PCCAs, namely a microbubble-conjugated microdroplet emulsion, into the first clinical studies. Their properties also make them attractive candidates for a variety of diagnostic and therapeutic applications including drug-delivery, diagnosis and treatment of cancerous and inflammatory diseases, as well as tumor-growth tracking. However, control over the thermal and acoustic stability of PCCAs both in vivo and in vitro has remained a challenge for expanding the potential utility of these agents in novel clinical applications. As such, our objective was to determine the stabilizing effects of layer-by-layer assemblies and its effect on both thermal and acoustic stability. METHODS: We utilized layer-by-layer (LBL) assemblies to coat the outer PCCA membrane and characterized layering by measuring zeta potential and particle size. Stability studies were conducted by; 1) incubating the LBL-PCCAs at atmospheric pressure at 37∘C and 45∘C followed by; 2) ultrasound-mediated activation at 7.24 MHz and peak-negative pressures ranging from 0.71 - 5.48 MPa to ascertain nanodroplet activation and resultant microbubble persistence. The thermal and acoustic properties of decafluorobutane gas-condensed nanodroplets (DFB-NDs) layered with 6 and 10 layers of charge-alternating biopolymers, (LBL6NDs and LBL10NDs) respectively, were studied and compared to non-layered DFB-NDs. Half-life determinations were conducted at both 37∘C and 45∘C with acoustic droplet vaporization (ADV) measurements occurring at 23∘C. DISCUSSION: Successful application of up to 10 layers of alternating positive and negatively charged biopolymers onto the surface membrane of DFB-NDs was demonstrated. Two major claims were substantiated in this study; namely, (1) biopolymeric layering of DFB-NDs imparts a thermal stability up to an extent; and, (2) both LBL6NDs and LBL10NDs did not appear to alter particle acoustic vaporization thresholds, suggesting that the thermal stability of the particle may not necessarily be coupled with particle acoustic vaporization thresholds. CONCLUSION: Results demonstrate that the layered PCCAs had higher thermal stability, where the half-lifes of the LBLxNDs are significantly increased after incubation at 37∘C and 45∘C. Furthermore, the acoustic vaporization profiles the DFB-NDs, LBL6NDs, and LBL10NDs show that there is no statistically significant difference between the acoustic vaporization energy required to initiate acoustic droplet vaporization.

Acute and Post-Acute COVID-19 Outcomes Among Immunologically Naïve Adults During Delta Versus Omicron Waves

II.ImportanceThe U.S. arrival of the Omicron variant led to a rapid increase in SARS-CoV-2 infections. While numerous studies report characteristics of Omicron infections among vaccinated individuals and/or persons with a prior history of infection, comprehensive data describing infections among immunologically naive adults is lacking. ObjectiveTo examine COVID-19 acute and post-acute clinical outcomes among a well-characterized cohort of unvaccinated and previously uninfected adults who contracted SARS-CoV-2 during the Omicron (BA.1/BA.2) surge, and to compare outcomes with infections that occurred during the Delta wave. DesignA prospective cohort undergoing high-resolution symptom and virologic monitoring between June 2021 and September 2022 SettingMultisite recruitment of community-dwelling adults in 8 U.S. states ParticipantsHealthy, unvaccinated adults between 30 to 64 years of age without an immunological history of SARS-CoV-2 who were at high-risk of infection were recruited. Participants were followed for up to 48 weeks, submitting regular COVID-19 symptom surveys and nasal swabs for SARS-CoV-2 PCR testing. Exposure(s)Omicron (BA.1/BA.2 lineages) versus Delta SARS-CoV-2 infection, defined as a positive PCR that occurred during a period when the variant represented [≥]50% of circulating SARS-CoV-2 variants in the participants geographic region. Main Outcome(s) and Measure(s)The main outcomes examined were the prevalence and severity of acute ([≤]28 days post-onset) and post-acute ([≥]5 weeks post-onset) symptoms. ResultsAmong 274 immunologically naive participants, 166 (61%) contracted SARS-CoV-2. Of these, 137 (83%) and 29 (17%) infections occurred during the Omicron- and Delta-predominant periods, respectively. Asymptomatic infections occurred among 6.7% (95% CI: 3.1%, 12.3%) of Omicron cases and 0.0% (95% CI: 0.0%, 11.9%) of Delta cases. Healthcare utilization among Omicron cases was 79% (95% CI: 43%, 92%, P =0.001) lower relative to Delta cases. Relative to Delta, Omicron infections also experienced a 56% (95% CI: 26%, 74%, P =0.004) and 79% (95% CI: 54%, 91%, P <0.001) reduction in the risk and rate of post-acute symptoms, respectively. Conclusions and RelevanceThese findings suggest that among previously immunologically naive adults, few Omicron (BA.1/BA.2) and Delta infections are asymptomatic, and relative to Delta, Omicron infections were less likely to seek healthcare and experience post-acute symptoms. KEY POINTSO_ST_ABSQuestionC_ST_ABSWhat are acute and post-acute outcomes among previously uninfected and unvaccinated adults who contracted Omicron (BA.1/BA.2), and how do these compare with Delta infections? FindingsIn this prospective cohort of 274 immunologically naive adults, 166 (61%) contracted SARS-CoV-2, with 9 (5.5%) asymptomatic infections. Compared with Delta, Omicron infections experienced a 79% relative reduction in healthcare utilization, and 56% and 79% relative reductions in the risk and rate of post-acute symptoms ([≥]5-weeks), respectively. MeaningThese findings suggest among immunologically naive adults, few infections are asymptomatic, and relative to Delta, Omicron infections have lower likelihoods of severe illness and post-acute symptoms.

Platelet-Dependent Inflammatory Dysregulation in Patients with Stages 4 or 5 Chronic Kidney Disease: A Mechanistic Clinical Study.

Background: Chronic kidney disease (CKD) is characterized by dysregulated inflammation that worsens with CKD severity. The role of platelets in modulating inflammation in stage 4 or 5 CKD remains unexplored. We investigated whether there are changes in platelet-derived thromboinflammatory markers in CKD with dual antiplatelet therapy (DAPT; aspirin 81 mg/d plus P2Y12 inhibitor). Methods: In a mechanistic clinical trial, we compared platelet activation markers (aggregation and surface receptor expression), circulating platelet-leukocyte aggregates, leukocyte composition (monocyte subtypes and CD11b surface expression), and plasma cytokine profile (45 analytes) of non-CKD controls (n=26) and CKD outpatients (n=48) with a glomerular filtration rate (GFR) <30 ml/min per 1.73 m2 on 2 weeks of DAPT. Results: Patients with CKD demonstrated a reduced mean platelet count, elevated mean platelet volume, reduced platelet-leukocyte aggregates, reduced platelet-bound monocytes, higher total non-classic monocytes in the circulation, and higher levels of IL-1RA, VEGF, and fractalkine (all P<0.05). There were no differences in platelet activation markers between CKD and controls. Although DAPT reduced platelet aggregation in both groups, it had multifaceted effects on thromboinflammatory markers in CKD, including a reduction in PDGF levels in all CKD individuals, reductions in IL-1ß and TNF-α levels in select CKD individuals, and no change in a number of other cytokines. Significant positive correlations existed for baseline IL-1ß, PDGF, and TNF-α levels with older age, and for baseline TNF-α levels with presence of diabetes mellitus and worse albuminuria. Mean change in IL-1ß and PDGF levels on DAPT positively correlated with younger age, mean change in TNF-α levels with higher GFR, and mean changes in PDGF, and TRAIL levels correlated with worse albuminuria. Minimum spanning trees plot of cytokines showed platelet-derived CD40L had a large reduction in weight factor after DAPT in CKD. Additionally, platelet-derived IL-1ß and PDGF were tightly correlated with other cytokines, with IL-1ß as the hub cytokine. Conclusions: Attenuated interactions between platelets and leukocytes in the CKD state coincided with no change in platelet activation status, an altered differentiation state of monocytes, and heightened inflammatory markers. Platelet-derived cytokines were one of the central cytokines in patients with CKD that were tightly correlated with others. DAPT had multifaceted effects on thromboinflammation, suggesting that there is platelet-dependent and -independent inflammation in stage 4 or 5 CKD.

Development of ACE2 autoantibodies after SARS-CoV-2 infection.

BACKGROUND: Activation of the immune system is implicated in the Post-Acute Sequelae after SARS-CoV-2 infection (PASC) but the mechanisms remain unknown. Angiotensin-converting enzyme 2 (ACE2) cleaves angiotensin II (Ang II) resulting in decreased activation of the AT1 receptor and decreased immune system activation. We hypothesized that autoantibodies against ACE2 may develop after SARS-CoV-2 infection, as anti-idiotypic antibodies to anti-spike protein antibodies. METHODS AND FINDINGS: We tested plasma or serum for ACE2 antibodies in 67 patients with known SARS-CoV-2 infection and 13 with no history of infection. None of the 13 patients without history of SARS-CoV-2 infection and 1 of the 20 outpatients that had a positive PCR test for SARS-CoV-2 had levels of ACE2 antibodies above the cutoff threshold. In contrast, 26/32 (81%) in the convalescent group and 14/15 (93%) of patients acutely hospitalized had detectable ACE2 antibodies. Plasma from patients with antibodies against ACE2 had less soluble ACE2 activity in plasma but similar amounts of ACE2 protein compared to patients without ACE2 antibodies. We measured the capacity of the samples to inhibit ACE2 enzyme activity. Addition of plasma from patients with ACE2 antibodies led to decreased activity of an exogenous preparation of ACE2 compared to patients that did not have antibodies. CONCLUSIONS: Many patients with a history of SARS-CoV-2 infection have antibodies specific for ACE2. Patients with ACE2 antibodies have lower activity of soluble ACE2 in plasma. Plasma from these patients also inhibits exogenous ACE2 activity. These findings are consistent with the hypothesis that ACE2 antibodies develop after SARS-CoV-2 infection and decrease ACE2 activity. This could lead to an increase in the abundance of Ang II, which causes a proinflammatory state that triggers symptoms of PASC.

Views of Black women patients with obesity on desired and undesired weight-focused clinical encounters.

Non-Hispanic Black women have the highest rates of overweight/obesity of any group in the United States. To date, few interventions have worked to reduce overweight/obesity in this population. This study investigated the views of Black women with overweight and obesity treated in a primary care setting regarding desired and undesired verbal and non-verbal behaviours by providers in provider-patient clinical encounters focused on losing weight, maintaining weight loss, and/or obesity. Two focus groups and an individual interview (n = 15) were conducted. Qualitative data analysis yielded five distinct themes, with 11 codes (listed in parenthesis): (a) desired weight-focused discussions (codes: Discussing weight loss with patients and discussing weight-loss maintenance with patients), (b) desired weight-focused support (codes: Supporting patients experiencing weight loss and supporting patients experiencing weight gain), (c) undesired weight-focused discussions (codes: Things to avoid during weight loss discussions and things to avoid during weight gain discussions), (d) desired attitudes and behaviours during weight-focused discussions (codes: Show caring and understanding and encourage behaviour change for weight loss), and (e) building physician-patient rapport (codes: Enable patients to feel respected by doctors, enable patients to feel comfortable with doctors and enable patients to trust their doctors). The qualitative approach employed in this study generates a deep understanding not only of the experiences of Black women patients but also of potential strategies that physicians could employ to succeed in their discussions with patients regarding healthy weight achievement and maintenance.

Epitope Analysis Aids in Transplant Decision Making by Determining the Clinical Relevance of Apparent Pre-Transplant Donor Specific Antibodies (DSA).

Pre-transplantation work-up on a patient with end stage renal disease using Single Antigen Bead (SAB) testing showed significant anti-HLA-B*44:02 (>5,000 MFI) and anti-HLA-B*44:03 (>1,000 MFI) antibodies, with persistence on quarterly testing. No significant Class II anti-HLA antibodies were present. The patient received a potential offer from a living unrelated-donor expressing HLA-B*44:02. Based on the presence of anti-HLA-B*44:02 antibody, the crossmatch (XM) was predicted to be positive. However, the actual fluorescence cytometry crossmatch (FCXM) was negative. FCXM and Complement Dependent Cytotoxicity-XM (CDC-XM) studies with three surrogate donors who expressed HLA-B*44:02 (and no other potential confounding HLA types) were also negative. Additional assays were performed for detecting anti-HLA antibodies. Immucor® LSA® SAB analyses also revealed presence of anti-HLA-B*44:02 and anti-HLA-B*44:03 antibodies. However, One Lambda® Antigen Trays, C1q analysis, and iBeads®, did not detect elevated anti-HLA-B*44:02 and/or anti-HLA-B*44:03 antibodies. An extensive evaluation of all exposed and non-exposed epitopes expressed by the patient and the donor was performed to identify the non-shared epitopes between them. The donor specific antibody (DSA) pattern detected would be expected to conform to non-shared epitopes; however, non-shared "exposed" epitopes were not present in the DSA antibody pattern. Whereas, the apparent DSA antibody pattern consisted of antibodies to "non-exposed" epitopes. Altogether, it was concluded that the anti-HLA-B*44:02 antibody detected by SAB testing was directed against some denatured component(s) (non-exposed) of the HLA antigen attached to the SAB, and would not be clinically significant. The patient received the transplant and the post-transplant course has been uneventful for greater than 5 years. This case emphasizes: (1) A significant number of SAB may have denatured HLA molecules attached to them (2) The DSA and non-DSA anti-HLA antibody patterns should be evaluated for the expected epitope components to determine the clinical relevance. Additional testing should be considered to help with these analyses (3) The FCXM remains the "gold standard" for making the final decision to transplant, since the "stringent" use of a "predicted" positive XM using apparent DSA detected by SAB analysis may exclude XM-compatible donors.

Evaluation of Apparatus Used to Test Liquid through Protective Materials: Comparison of a Modified Dot-Blot Apparatus to the ASTM Penetration Cell.

Personal protective equipment (PPE), such as gowns used in the latest Ebola outbreak in Western Africa, are critical in preventing the spread of deadly diseases. Appropriate test systems and test soils are needed to adequately evaluate PPE. ASTM F903, Standard Test Method for Resistance of Materials Used in Protective Clothing to Penetration by Liquid, has been used for decades to test fabrics' resistance to liquid penetration. However, this test apparatus requires at least 60 mL of test solutions, is labor intensive, and has problems with leakage around the gaskets. We compared the F903 test apparatus to a modified dot-blot apparatus to evaluate the visual penetration of a blood test soil. A series of commercially available gowns and drapes were tested in each apparatus. Using blood test soil at 2 psi, there was no statistically significant difference between the two methods except for in one gown. By comparing this gown in the ASTM test apparatus with and without a screen, the particular screen selected did not account for the difference between the dot-blot and F903 apparatuses; however, it is conceivable that a particular screen/fabric combination could account for this difference. The modified dot-blot apparatus was evaluated using three different test solutions: blood, vomit, and a labeled protein (goat anti-rabbit immunoglobulin G-horseradish peroxidase [GaR IgG-HRP]) in a blood test soil solution. This testing revealed significant difference in penetration for some of the PPE garments. The modified dot-blot had several large advantages over the ASTM apparatus-over six times less specimen volume and no edge or gasket leakage. In addition, nitrocellulose can be easily incorporated into the modified dot-blot apparatus, enabling the trapping of viruses and proteins that penetrate PPE-thus permitting the use of antibodies to quickly and sensitively detect penetration.

Optimization of Phase-Change Contrast Agents for Targeting MDA-MB-231 Breast Cancer Cells.

Breast cancer remains a leading cause of death for women throughout the world. Recent advances in medical imaging technologies and tumor targeting agents signify vast potential for progress toward improved management of this global problem. Phase-change contrast agents (PCCAs) are dynamic imaging agents with practical applications in both the research and clinical settings. PCCAs possess characteristics that allow for cellular uptake where they can be converted from liquid-phase PCCAs to gaseous microbubbles via ultrasound energy. Previously, we reported successful internalization of folate-targeted PCCAs in MDA-MB-231 breast cancer cells followed by ultrasound-mediated activation to produce internalized microbubbles. This study examines the binding, internalization and activation of folate-receptor targeted PCCAs in MDA-MB-231 breast cancer cells as a function of gaseous core compositions, incubation time and ultrasound exposure period. In vitro results indicate that internalization and ultrasound-mediated activation of PCCAs were significantly greater using a 50:50 mixture of decafluorobutane:dodecafluoropentane compared with other core compositions: 50:50 octafluoropropane:decafluorobutane (p < 0.0001), decafluorobutane (p < 0.04) and dodecafluoropentane (p < 0.0001). Furthermore, it was found that PCCAs composed of perfluorocarbons with higher boiling points responded with greater activation efficiency when exposed to 12 s of ultrasound exposure as opposed to 4 s of ultrasound exposure. When evaluating different incubation times, it was found that incubating the PCCAs with breast cancer cells for 60 min did not produce significantly greater internalization and activation compared with incubation for 10 min; this was concluded after comparing the number of microbubbles present per cell before ultrasound versus post-ultrasound, and finding a ratio of intracellular microbubbles post-ultrasound/pre-ultrasound, 3.46 versus 3.14, respectively. The data collected in this study helps illustrate further optimization of folate-receptor targeted PCCAs for breast cancer targeting and imaging.

Endothelial vascular cell adhesion molecule 1 is a marker for high-risk carotid plaques and target for ultrasound molecular imaging.

BACKGROUND: Molecular imaging of carotid plaque vulnerability to atheroembolic events is likely to lead to improvements in selection of patients for carotid endarterectomy (CEA). The aims of this study were to assess the relative value of endothelial inflammatory markers for this application and to develop molecular ultrasound contrast agents for their imaging. METHODS: Human CEA specimens were obtained prospectively from asymptomatic (30) and symptomatic (30) patients. Plaques were assessed by semiquantitative immunohistochemistry for vascular cell adhesion molecule 1 (VCAM-1), lectin-like oxidized low-density lipoprotein receptor 1, P-selectin, and von Willebrand factor. Established small peptide ligands to each of these targets were then synthesized and covalently conjugated to the surface of lipid-shelled microbubble ultrasound contrast agents, which were then evaluated in a flow chamber for binding kinetics to activated human aortic endothelial cells under variable shear conditions. RESULTS: Expression of VCAM-1 on the endothelium of CEA specimens from symptomatic patients was 2.4-fold greater than that from asymptomatic patients (P < .01). Expression was not significantly different between groups for P-selectin (P = .43), von Willebrand factor (P = .59), or lectin-like oxidized low-density lipoprotein receptor 1 (P = .99). Although most plaques from asymptomatic patients displayed low VCAM-1 expression, approximately one in five expressed high VCAM-1 similar to plaques from symptomatic patients. In vitro flow chamber experiments demonstrated that VCAM-1-targeted microbubbles bind cells that express VCAM-1, even under high-shear conditions that approximate those found in human carotid arteries, whereas binding efficiency was lower for the other agents. CONCLUSIONS: VCAM-1 displays significantly higher expression on high-risk (symptomatic) vs low-risk (asymptomatic) carotid plaques. Ultrasound contrast agents bearing ligands for VCAM-1 can sustain high-shear attachment and may be useful for identifying patients in whom more aggressive treatment is warranted.

Surface orientation effects on bending properties of surgical mesh are independent of tensile properties.

INTRODUCTION: Current mechanical testing of surgical mesh focuses primarily on tensile properties even though implanted devices are not subjected to pure tensile loads. Our objective was to determine the flexural (bending) properties of surgical mesh and determine if they correlate with mesh tensile properties. METHODS: The flexural rigidity values of 11 different surgical mesh designs were determined along three textile directions (machine, cross-machine, and 45° to machine; n = 5 for each) using ASTM D1388-14 while tracking surface orientation. Tensile testing was also performed on the same specimens using ASTM D882-12. Linear regressions were performed to compare mesh flexural rigidity to mesh thickness, areal mass density, filament diameter, ultimate tensile strength, and maximum extension. RESULTS: Of 33 mesh specimen groups, 30 had significant differences in flexural rigidity values when comparing surface orientations (top and bottom). Flexural rigidity and mesh tensile properties also varied with textile direction (machine and cross-machine). There was no strong correlation between the flexural and tensile properties, with mesh thickness having the best overall correlation with flexural rigidity. CONCLUSIONS: Currently, surface orientation is not indicated on marketed surgical mesh, and a single mesh may behave differently depending on the direction of loading. The lack of correlation between flexural stiffness and tensile properties indicates the need to examine mesh bending stiffness to provide a more comprehensive understanding of surgical mesh mechanical behaviors. Further investigation is needed to determine if these flexural properties result in the surgical mesh behaving mechanically different depending on implantation direction. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 854-862, 2018.

Enteropatía asociada a olmesartán: atención a un fenómeno iatrogénico emergente / Olmesartan-associated enteropathy: attention to an emerging iatrogenic phenomenon

El olmesartán es un antagonista del receptor tipo 1 de la angiotensina II utilizado habitualmente en el tratamiento de pacientes con hipertensión arterial. Recientemente se han descrito varios casos de enteropatía sprue-like asociados al uso de este fármaco, con afectación clínica importante y total remisión tras la retirada del mismo. Se presenta el caso de un varón de 64 años, con antecedentes de hipertensión arterial en tratamiento con olmesartan-amlodipino con clínica de diarrea y pérdida de peso severas, atrofia vellositaria en biopsia duodenal sin criterios de enfermedad celiaca y remisión completa del cuadro tras la supresión del olmesartán. Basado en los hallazgos del caso clínico presentado, se revisan las manifestaciones clínicas e histopatológicas así como el curso evolutivo de una posible causa de enteropatía farmacológica recientemente descrita (AU)

Olmesartan is an angiotensin II type 1 receptor blocker commonly used in the treatment of hypertension. Several cases of sprue-like enteropathy associated with the use of this drug have been described which, even with important signs and limitations for the patient, present a full recovery after discontinuing the use of olmesartan. The case of a 64 year-old patient is presented, diagnosed with hypertension, under treatment with olmesartan- amlodipine, with chronic diarrhoea and villous atrophy on intestinal biopsies without diagnostic criteria for celiac disease and with complete remission after suspending discontinuing the use of olmesartan. Based on the clinical features presented by the case reported, the clinical and anatomopathological findings are described as well as the evolution of drug-induced enteropathy (AU)

Percent cPRA (Calculated Panel Reactive Antibody) Value Predicts Percent of Positive Platelet Crossmatches.

BACKGROUND: Platelet refractoriness or lack of platelet increase after platelet transfusion is seen in patients receiving chronic platelet transfusion support. Antibodies may develop against human platelet antigens (HPA) and/or against HLA class I antigens. Crossmatch (XM) compatible platelets or HLA-identical or HLA-compatible platelets are typically used to manage transfusion refractoriness. We aimed to determine if percent calculated Panel Reactive Antibody (% cPRA) against class I HLA antigens could predict percent positive platelet XM when looking for compatible transfusion products. METHODS: A retrospective review of all platelet XM performed at our institution between 2008-2012 was performed, and patient characteristics recorded. For each patient, the percentage of all positive platelet XM performed was calculated and compared with the corresponding % cPRA levels against class I HLA antigens. RESULTS: Mean and median % positive platelet XM for all 50 patients tested in the period 2008-2012 were 61% and 60% (range 0-100%), respectively. Mean and median % cPRA levels were 66% and 68% (range 0-100%), respectively. No correlation was seen between age, sex, race, or diagnosis and positive platelet XM results. CONCLUSION: The results of our study indicate that the % cPRA correlates well with the % positive platelet XM. Thus, a higher % cPRA alerts the blood bank that additional platelets will be required for XM and/or that it would be beneficial to request HLA-identical or compatible units.

Optically and acoustically triggerable sub-micron phase-change contrast agents for enhanced photoacoustic and ultrasound imaging.

We demonstrate a versatile phase-change sub-micron contrast agent providing three modes of contrast enhancement: 1) photoacoustic imaging contrast, 2) ultrasound contrast with optical activation, and 3) ultrasound contrast with acoustic activation. This agent, which we name 'Cy-droplet', has the following novel features. It comprises a highly volatile perfluorocarbon for easy versatile activation, and a near-infrared optically absorbing dye chosen to absorb light at a wavelength with good tissue penetration. It is manufactured via a 'microbubble condensation' method. The phase-transition of Cy-droplets can be optically triggered by pulsed-laser illumination, inducing photoacoustic signal and forming stable gas bubbles that are visible with echo-ultrasound in situ. Alternatively, Cy-droplets can be converted to microbubble contrast agents upon acoustic activation with clinical ultrasound. Potentially all modes offer extravascular contrast enhancement because of the sub-micron initial size. Such versatility of acoustic and optical 'triggerability' can potentially improve multi-modality imaging, molecularly targeted imaging and controlled drug release.