Diagnostic accuracy of magnetic resonance imaging in the evaluation of pulmonary infections in immunocompromised patients

Purpose: To evaluate the accuracy of magnetic resonance imaging (MRI) for diagnosing pulmonary infections in immunocompromised adults. Material and methods: Computed tomography (CT) and MRI chest were performed in 35 immuno-compromised patients suspected of pulmonary infection. The MRI sequences that were performed included axial and coronal T2 half-Fourier acquisition single-shot turbo spin-echo (HASTE), spectrally attenuated inversion recovery (SPAIR), true fast imaging with steady-state free precession (TRUFI), and three-dimensional fast low angle shot (3D FLASH) using breath-hold and respiratory triggered BLADE (proprietary name for periodically rotated overlapping parallel lines with enhanced reconstruction). The presence of nodules, consolidations, and ground-glass opacities was evaluated. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for MRI using CT scan as a reference standard. Results: The sensitivity of MRI in nodule detection was 50% overall and 75% for nodules measuring more than 5 mm. Consolidation was detected with 100% sensitivity. Sensitivity and PPV for the detection of ground-glass opacities (GGOs) were 77.7% and 53.8%, respectively. T2 HASTE axial had the fewest image artefacts. Respiratory triggered MR pulse sequence did not add any significant diagnostic information as compared to the non-respiratory triggered MR pulse sequences. Conclusions: Sensitivity for detecting small nodules and GGOs on MR is poor; CT scan remains the imaging modality of choice for the evaluation of pulmonary infections in immunocompromised patients. However, MRI can be used in the follow-up imaging of these patients

Large animal model species in pluripotent stem cell therapy research and development for retinal diseases: a systematic review

Aim: Retinal cell therapy modalities, in the category of advanced therapy medicinal products (ATMPs), are being developed to target several retinal diseases. Testing in large animal models (LAMs) is a crucial step in translating retinal ATMPs into clinical practice. However, challenges including budgetary and infrastructure constraints can hinder LAM research design and execution. Here, to facilitate the comparison of the various LAMs in pluripotent retinal cell therapy research, we aimed to systematically evaluate the species distribution, reported scientific utility, and methodology of a range of LAMs. Methods: A systematic search using the words retina, stem cell, transplantation, large animal, pig, rabbit, dog, and nonhuman primate was conducted in the PubMed, Embase, Science Direct and GoogleScholar databases in February 2023. Results: We included 22 studies involving pluripotent stem cells (induced pluripotent stem cells or human embryonic stem cells) in LAMs, including non-human primates (NHP), pigs, dogs, and rabbits. Nearly half of the studies utilized wild-type animal models. In other studies, retinal degeneration features were simulated via laser, chemical, or genetic insult. Transplants were delivered subretinally, either as cell suspensions or pre-formed monolayers (with or without biodegradable scaffolding). The transplanted cells dose per eye varied widely (40,000 – 4,000,000 per dose). Cells were delivered via vitrectomy surgery in 15 studies and by an “ab externo” approach in one study. Structural outcomes were assessed using confocal scanning laser ophthalmoscopy imaging. Functional outcomes included multifocal electroretinogram and, in one case, a measure of visual acuity. Generally, cell suspension transplants exhibited low intraretinal incorporation, while monolayer transplants incorporated more efficiently. Immune responses posed challenges for allogeneic transplants, suggesting that autologous iPSC-derived transplants may be required to decrease the likelihood of rejection. Conclusion: The use of appropriate LAMs helps to advance the development of retinal ATMPs. The anatomical similarity of LAM and human eyes allows the implementation of clinically-relevant surgical techniques. While the FDA Modernization Act 2.0 has provided a framework to consider alternative methods including tissue-on-a-chip and human cell culture models for pharmacologic studies, LAM testing remains useful for cell and tissue replacement studies to inform the development of clinical trial protocols

Clay minerals as the key to the sequestration of carbon in soils

Results from earlier laboratory and field experiments were interrogated for the possibilities of sequestration, or longterm accumulation, of carbon from excess greenhouse gases in the atmosphere. In the laboratory study, samples of three (top) soils dominated by kaolinite and illite (together), smectite, and allophane were examined for the adsorption and desorption of dissolved organic carbon (DOC). Adsorption and desorption of DOC were carried out on clay fractions extracted physically and after first native organic matter and then iron oxides were removed chemically. Labeled organic material was added to the soils to assess the priming effect of organic carbon (OC). In the field, changes in OC were measured in sandy soils that had been amended by additions of clay for between 3 and 17 years, both through incorporation of exogenous clay and delving of in situ clay. The laboratory experiments demonstrated that a portion of DOC was held strongly in all soils. The amount of DOC adsorbed depended on clay mineral types, including Fe oxides. Much adsorbed DOC was lost by desorption in water and a substantial amount of native OC was lost on priming with new OC. Addition of clay to soils led to increased OC. Therefore, addition of clay to soil may enhance net sequestration of C. Organic carbon close to mineral surfaces or within microaggregates is held most strongly. Carbon sequestration may occur in subsoils with unsaturated mineral surfaces. However, incorporation of carbon into macroaggregates from enhanced plant growth might be most effective in removing excess carbon from the atmosphere, albeit over the short-term

Improving outcome over time of percutaneous coronary interventions in unstable angina

AbstractOBJECTIVEThis study was performed to evaluate the recent changes in the outcome of coronary interventions in patients with unstable angina (UA).BACKGROUNDAn early invasive strategy has not been shown to be superior to conservative treatment in patients with UA. Earlier studies had utilized older technology. Interventional approaches have changed in the recent past, but to our knowledge, no large studies have addressed the impact of these changes on the outcome of coronary interventions.METHODSWe analyzed the in-hospital and intermediate-term outcome in 7,632 patients with UA who underwent coronary interventions in the last two decades. The study population was divided into three groups: group 1, n = 2,209 who had coronary intervention from 1979 to 1989; group 2, n = 2,212 with interventions from 1990 to 1993; and group 3, n = 3,211 treated from 1994 to 1998.RESULTSGroup 2 and 3 patients were older and sicker compared with group 1 patients. The clinical success improved significantly in group 3 (94.1%) compared with group 2 (87%) and group 1 (76.5%) (p < 0.001). There was a significant reduction in in-hospital mortality, Q-wave myocardial infarction and need for emergency bypass surgery in group 3 compared with the earlier groups. One-year event-free survival was also significantly higher in the recent group compared with the earlier groups: 77% in group 3, 70% in group 2 and 74% in group 1 (p < 0.001). With the use of multivariate models to adjust for clinical and angiographic variables, treatment during the most recent era was found to be independently associated with improved in-hospital and intermediate-term outcomes.CONCLUSIONSThere has been significant improvement in the in-hospital and intermediate-term outcome of coronary interventions in patients with UA in recent years; newer trials comparing conservative and invasive strategies are therefore needed

Solid lipid nanoparticles for ocular delivery of isoniazid: evaluation, proof of concept and in vivo safety & kinetics

Aim: Evaluation of solid lipid nanoparticles (SLNs) for ocular delivery of isoniazid (INH). Materials & methods: INH-SLNs were characterized for morphological, thermal, crystalline and nuclear magnetic resonance properties. In vitro release and ex vivo corneal permeability of INH-SLNs was also evaluated. Proof-of-concept uptake studies were performed in corneal and conjunctival cell lines and in vivo in rat eye using fluorescein-labeled SLNs. Antimycobacterial activity of INH-SLNs was confirmed. In vivo aqueous humor pharmacokinetics, toxicity and tolerance was performed in rabbit/rat eye. Results: INH-SLNs showed extended release (48 h), enhanced corneal permeability (1.6-times), five-times lower MIC, significant in vitro and in vivo uptake of fluorescein-labeled SLNs, 4.2-times ocular bioavailability (area under the curve) and in vivo acute and repeat dose safety. Conclusion: INH-SLNs are an effective ocular delivery system

Clinical Prediction Model Suitable for Assessing Hospital Quality for Patients Undergoing Carotid Endarterectomy

Background: Assessing hospital quality in the performance of carotid endarterectomy (CEA) requires appropriate risk adjustment across hospitals with varying case mixes. The aim of this study was to develop and validate a prediction model to assess the risk of in‐hospital stroke or death after CEA that could aid in the assessment of hospital quality. Methods and Results: Patients from National Cardiovascular Data Registry (NCDR)'s Carotid Artery Revascularization and Endarterectomy (CARE) Registry undergoing CEA without acute evolving stroke from 2005 to 2013 were included. In‐hospital stroke or death was modeled using hierarchical logistic regression with 20 candidate variables and accounting for hospital‐level clustering. Internal validation was achieved with bootstrapping; model discrimination and calibration were assessed. A total of 213 (1.7%) primary end point events occurred during 12 889 procedures. Independent predictors of stroke or death included age, prior peripheral artery disease, diabetes mellitus, prior coronary artery disease, having a symptomatic carotid lesion, having a contralateral carotid occlusion, or having New York Heart Association Class III or IV heart failure. The model was well calibrated and demonstrated moderate discriminative ability (c‐statistic 0.65). The NCDR CEA score was then developed to support simple, prospective risk quantification in the clinical setting. Conclusions: The NCDR CEA score, comprising 7 clinical variables, predicts in‐hospital stroke or death after CEA. This model can be used to estimate hospital risk‐adjusted outcomes for CEA and to assist with the assessment of hospital quality

Quantitative trait loci mapping reveals the complexity of adult plant resistance to leaf rust in spring wheat ‘Copio’

The spring wheat (Triticum aestivum L.) line ‘Copio’ has exhibited high level of adult plant resistance (APR) to the leaf rust (Puccinia triticina) pathogen in Mexico during field evaluations. To elucidate the genetic basis of leaf rust resistance in Copio, 176 F4-derived F6-recombinant inbred lines (RILs) from a cross of wheat lines ‘Apav’ and Copio were phenotyped in the field for two seasons in the United States and Mexico. A total of 762 genotyping-by-sequencing (GBS) single nucleotide polymorphic (SNP) markers were used to develop linkage maps. Composite interval mapping identified seven quantitative trait loci (QTL), all contributed by Copio. Three QTL on chromosome arms 1BL (QLr.umn-1B), 2AS (QLr.umn-2A), and 3BS (QLr.umn-3B) were consistently expressed across all four environments. The QTL on 1BL represents Lr46, which is a pleiotropic APR gene, while the QTL on 2AS is colocated to the Lr37 gene in the 2NS/2AS translocation fragment. The QTL on 3BS, mapped to the Sr2/Yr30/Lr27 genomic region, is more likely to be a unique locus conferring APR to leaf rust races because all phenotyping environments had Lr27 virulent pathotypes. Moreover, the functionality of Lr27 is complimented by Lr31 on chromosome 4BS, which is lacking in both parents. Marker haplotypes identified seven RILs carrying a combination of resistance alleles at all three loci. This combination reduced leaf rust coefficient of infection up to 52 and 36% in the Mexican and U.S. environments, respectively. This study reports the complex genetic mechanism of APR to leaf rust in Copio and its importance as a potential resistance source for gene pyramiding through recombination breeding

A Total of 1,007 Percutaneous Coronary Interventions Without Onsite Cardiac Surgery Acute and Long-Term Outcomes

ObjectivesWe sought to compare clinical outcomes of elective percutaneous coronary intervention (PCI) and primary PCI for ST-segment elevation myocardial infarction (STEMI) at a community hospital without onsite cardiac surgery to those at a tertiary center with onsite cardiac surgery.BackgroundDisagreement exists about whether hospitals with cardiac catheterization laboratories, but without onsite cardiac surgery, should develop PCI programs. Primary PCI for STEMI at hospitals without onsite cardiac surgery have achieved satisfactory outcomes; however, elective PCI outcomes are not well defined.MethodsA total of 1,007 elective PCI and primary PCI procedures performed from March 1999 to August 2005 at the Immanuel St. Joseph’s Hospital–Mayo Health System (ISJ) in Mankato, Minnesota, were matched one-to-one with those performed at St. Mary’s Hospital (SMH) in Rochester, Minnesota. Strict protocols were followed for case selection and PCI program requirements. Clinical outcomes (in-hospital procedural success, death, any myocardial infarction, Q-wave myocardial infarction, and emergency coronary artery bypass surgery) and follow-up survival were compared between groups.ResultsAmong 722 elective PCIs, procedural success was 97% at ISJ compared with 95% at SMH (p = 0.046). Among 285 primary PCIs for STEMI, procedural success was 93% at ISJ and 96% at SMH (p = 0.085). No patients at ISJ undergoing PCI required emergent transfer for cardiac surgery. Survival at two years’ follow-up by treatment location was similar for patients with elective PCI and primary PCI.ConclusionsSimilar clinical outcomes for elective PCI and primary PCI were achieved at a community hospital without onsite cardiac surgery compared with those at a tertiary center with onsite cardiac surgery using a prospective, rigorous protocol for case selection and PCI program requirements