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BACKGROUND: The optimisation of patients in primary care is a prime opportunity to manage patient care within the community and reduce the burden of referrals on secondary care. This paper presents a quality improvement clinical programme taking place within an NHS Primary Care Network as part of the wider Leicester Leicestershire Rutland integrated chronic kidney disease programme. METHOD: Patients are optimised to guidelines from the National Institute for Health and Care Excellence, by a primary care clinical team who are supported by nephrology consultants and nephrology pharmacists. Multidisciplinary team meetings take place with secondary care specialists and primary care staff. Learning is passed to the community clinicians for better patient treatment locally. RESULTS: A total of 526 patients were reviewed under this project.The total number of referrals to secondary care which were discharged following first outpatient appointment, reduced from 42.9% to 10%. This reduction of 32.9% represents the optimisation of patient cases through this quality improvement project. Patients can be optimised and managed within the community, reducing the number of unnecessary referrals to secondary care. CONCLUSION: This programme has the potential to offer significant improvement in patient outcomes when expanded to a larger patient base. Medicine management and the use of clinical staff are optimised in both primary and secondary care.
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Atención Primaria de Salud , Mejoramiento de la Calidad , Insuficiencia Renal Crónica , Humanos , Insuficiencia Renal Crónica/terapia , Derivación y Consulta , Grupo de Atención al PacienteRESUMEN
Glitches, spin-up events in neutron stars, are of prime interest, as they reveal properties of nuclear matter at subnuclear densities. We numerically investigate the glitch mechanism due to vortex unpinning using analogies between neutron stars and dipolar supersolids. We explore the vortex and crystal dynamics during a glitch and its dependence on the supersolid quality, providing a tool to study glitches from different radial depths of a neutron star. Benchmarking our theory against neutron-star observations, our work will open a new avenue for the quantum simulation of stellar objects from Earth.
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BACKGROUND: There is a need to investigate mechanisms of phenotypic plasticity in marine invertebrates as negative effects of climate change, like ocean acidification, are experienced by coastal ecosystems. Environmentally-induced changes to the methylome may regulate gene expression, but methylome responses can be species- and tissue-specific. Tissue-specificity has implications for gonad tissue, as gonad-specific methylation patterns may be inherited by offspring. We used the Pacific oyster (Crassostrea gigas) - a model for understanding pH impacts on bivalve molecular physiology due to its genomic resources and importance in global aquaculture- to assess how low pH could impact the gonad methylome. Oysters were exposed to either low pH (7.31 ± 0.02) or ambient pH (7.82 ± 0.02) conditions for 7 weeks. Whole genome bisulfite sequencing was used to identify methylated regions in female oyster gonad samples. C- > T single nucleotide polymorphisms were identified and removed to ensure accurate methylation characterization. RESULTS: Analysis of gonad methylomes revealed a total of 1284 differentially methylated loci (DML) found primarily in genes, with several genes containing multiple DML. Gene ontologies for genes containing DML were involved in development and stress response, suggesting methylation may promote gonad growth homeostasis in low pH conditions. Additionally, several of these genes were associated with cytoskeletal structure regulation, metabolism, and protein ubiquitination - commonly-observed responses to ocean acidification. Comparison of these DML with other Crassostrea spp. exposed to ocean acidification demonstrates that similar pathways, but not identical genes, are impacted by methylation. CONCLUSIONS: Our work suggests DNA methylation may have a regulatory role in gonad and larval development, which would shape adult and offspring responses to low pH stress. Combined with existing molluscan methylome research, our work further supports the need for tissue- and species-specific studies to understand the potential regulatory role of DNA methylation.
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Crassostrea , Metilación de ADN , Animales , Crassostrea/metabolismo , ADN/metabolismo , Ecosistema , Femenino , Homeostasis , Concentración de Iones de Hidrógeno , Océanos y Mares , Agua de Mar/químicaRESUMEN
BACKGROUND: Allergy to bites of blood-sucking insects, including biting midges, can affect both human and veterinary patients. Horses are often suffering from an IgE-mediated allergic dermatitis caused by bites of midges (Culicoides spp). With the aim to improve allergen immunotherapy (AIT), numerous Culicoides allergens have been produced as recombinant (r-) proteins. This study aimed to test a comprehensive panel of differently expressed Culicoides r-allergens on a cohort of IBH-affected and control horses using an allergen microarray. METHODS: IgE levels to 27 Culicoides r-allergens, including 8 previously unpublished allergens, of which 11 were expressed in more than one expression system, were determined in sera from 347 horses. ROC analyses were carried out, cut-offs selected using a specificity of 95% and seropositivity rates compared between horses affected with insect bite hypersensitivity (IBH) and control horses. The combination of r-allergens giving the best performing test was determined using logistic regression analysis. RESULTS: Seropositivity was significantly higher in IBH horses compared with controls for 25 r-allergens. Nine Culicoides r-allergens were major allergens for IBH with seven of them binding IgE in sera from > 70% of the IBH-affected horses. Combination of these top seven r-allergens could diagnose > 90% of IBH-affected horses with a specificity of > 95%. Correlation between differently expressed r-allergens was usually high (mean = 0.69, range: 0.28-0.91). CONCLUSION: This microarray will be a powerful tool for the development of component-resolved, patient-tailored AIT for IBH and could be useful for the study of allergy to biting midges in humans and other species.
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Ceratopogonidae , Enfermedades de los Caballos , Hipersensibilidad , Mordeduras y Picaduras de Insectos , Alérgenos , Animales , Caballos , Humanos , Hipersensibilidad/veterinaria , Inmunoglobulina E , Mordeduras y Picaduras de Insectos/veterinaria , Análisis por MicromatricesRESUMEN
Withering syndrome (WS), a serious disease affecting abalone Haliotis spp., is caused by infection from an intracellular Rickettsia-like organism (WS-RLO). Diagnosis of the disease currently relies on a combination of histological examination and molecular methods (in situ hybridization, standard PCR, and sequence analysis). However, these techniques only provide a semi-quantitative assessment of bacterial load. We created a real-time quantitative PCR (qPCR) assay to specifically identify and enumerate bacterial loads of WS-RLO in abalone tissue, fecal, and seawater samples based on 16S rDNA gene copy numbers. The qPCR assay designed to detect DNA of the WS-RLO was validated according to standards set by the World Organisation for Animal Health. Standard curves derived from purified plasmid dilutions were linear across 7 logs of concentration, and efficiencies ranged from 90.2 to 97.4%. The limit of detection was 3 gene copies per reaction. Diagnostic sensitivity was 100% and specificity was 99.8%. The qPCR assay was robust, as evidenced by its high level of repeatability and reproducibility. This study has shown for the first time that WS-RLO DNA can be detected and quantified in abalone tissue, fecal, and seawater samples. The ability to detect and quantify RLO gene copies in a variety of materials will enable us to better understand transmission dynamics in both farmed and natural environments.
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Gastrópodos/microbiología , Reacción en Cadena de la Polimerasa/métodos , Rickettsia/aislamiento & purificación , Animales , Interacciones Huésped-Patógeno , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Livestock facilities are widely regarded as reservoirs of infectious disease, owing to their abundance in particulate matter (PM) and microbial bioaerosols. Over the past decade, bioaerosol studies have increasingly utilised high throughput sequencing (HTS) to achieve superior throughput, taxonomic resolution, and the detection of unculturable organisms. However, the prevailing focus on amplicon sequencing has limited the identification of viruses and microbial taxa at the species-level. Herein, a literature search was conducted to identify methods capable of overcoming the aforementioned limitations. Screening 1531 international publications resulted in 29 eligible for review. Metagenomics capable of providing rich insights were identified in only three instances. Notably, long-read sequencing was not utilised for metagenomics. This review also identified that sample collection methods lack a uniform approach, highlighted by the differences in sampling equipment, flow rates and durations. Further heterogeneity was introduced by the unique sampling conditions, which makes it challenging to ground new findings within the established literature. For instance, winter was associated with increased microbial abundance and antimicrobial resistance, yet less alpha diversity. Researchers implementing metagenomics into the livestock environment should consider season, the microclimate, and livestock growth stage as influential upon their findings. Considering the increasing accessibility of long-read sequencing, future research should explore its viability within a novel uniform testing protocol for bioaerosol emissions.
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Aerosoles , Microbiología del Aire , Monitoreo del Ambiente , Ganado , Aerosoles/análisis , Animales , Monitoreo del Ambiente/métodos , Metagenómica/métodos , Material Particulado/análisis , Crianza de Animales Domésticos/métodos , Genómica , Contaminantes Atmosféricos/análisisRESUMEN
BACKGROUND: Severe asthma (SA) in horses, resembling human asthma, is a prevalent, debilitating allergic respiratory condition marked by elevated allergen-specific immunoglobulin E (IgE) against environmental proteins; however, research exploring the exposome's influence on IgE profiles is currently limited but holds paramount significance for diagnostic and therapeutic developments. ANIMALS: Thirty-five sports horses were analyzed, consisting of environmentally matched samples from France (5 SA; 6 control), the United States (6 SA; 6 control), and Canada (6 SEA; 6 control). METHODS: This intentional cross-sectional study investigated the sensitization profiles of SA-affected and healthy horses via serological antigen microarray profiling. Partial least square-discriminant analysis (PLS-DA) was used to identify and rank the importance of allergens for class separation (ie, affected/non-affected) as variable influence of projection (VIP), and allergen with commonality internationally established via frequency analysis. RESULTS: PLS-DA models showed high discriminatory power in predicting SA in horses from Canada (area under the curve [AUC] 0.995) and France (AUC 0.867) but poor discriminatory power in horses from the United States (AUC 0.38). Hev b 5.0101, Cyn D, Der p 2, and Rum cr were the only shared allergens across all geographical groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Microarray profiling can identify specific allergenic components associated with SA in horses, while mathematical modeling of this data can be used for disease classification, highlighting the variability of sensitization profiles between geographical locations and emphasizing the importance of local exposure to the prevalence of different allergens. Frequency scoring analysis can identify important variables that contribute to the classification of SA across different geographical regions.
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Asma , Enfermedades de los Caballos , Hipersensibilidad , Humanos , Animales , Caballos , Estudios Transversales , Asma/veterinaria , Asma/diagnóstico , Alérgenos , Hipersensibilidad/veterinaria , Inmunoglobulina E , Enfermedades de los Caballos/diagnósticoRESUMEN
Importance: Systematic reviews of medical imaging diagnostic test accuracy (DTA) studies are affected by between-study heterogeneity due to a range of factors. Failure to appropriately assess the extent and causes of heterogeneity compromises the interpretability of systematic review findings. Objective: To assess how heterogeneity has been examined in medical imaging DTA studies. Evidence Review: The PubMed database was searched for systematic reviews of medical imaging DTA studies that performed a meta-analysis. The search was limited to the 40 journals with highest impact factor in the radiology, nuclear medicine, and medical imaging category in the InCites Journal Citation Reports of 2021 to reach a sample size of 200 to 300 included studies. Descriptive analysis was performed to characterize the imaging modality, target condition, type of meta-analysis model used, strategies for evaluating heterogeneity, and sources of heterogeneity identified. Multivariable logistic regression was performed to assess whether any factors were associated with at least 1 source of heterogeneity being identified in the included meta-analyses. Methodological quality evaluation was not performed. Data analysis occurred from October to December 2022. Findings: A total of 242 meta-analyses involving a median (range) of 987 (119-441â¯510) patients across a diverse range of disease categories and imaging modalities were included. The extent of heterogeneity was adequately described (ie, whether it was absent, low, moderate, or high) in 220 studies (91%) and was most commonly assessed using the I2 statistic (185 studies [76%]) and forest plots (181 studies [75%]). Heterogeneity was rated as moderate to high in 191 studies (79%). Of all included meta-analyses, 122 (50%) performed subgroup analysis and 87 (36%) performed meta-regression. Of the 242 studies assessed, 189 (78%) included 10 or more primary studies. Of these 189 studies, 60 (32%) did not perform meta-regression or subgroup analysis. Reasons for being unable to investigate sources of heterogeneity included inadequate reporting of primary study characteristics and a low number of included primary studies. Use of meta-regression was associated with identification of at least 1 source of variability (odds ratio, 1.90; 95% CI, 1.11-3.23; P = .02). Conclusions and Relevance: In this systematic review of assessment of heterogeneity in medical imaging DTA meta-analyses, most meta-analyses were impacted by a moderate to high level of heterogeneity, presenting interpretive challenges. These findings suggest that, despite the development and availability of more rigorous statistical models, heterogeneity appeared to be incomplete, inconsistently evaluated, or methodologically questionable in many cases, which lessened the interpretability of the analyses performed; comprehensive heterogeneity assessment should be addressed at the author level by improving personal familiarity with appropriate statistical methodology for assessing heterogeneity and involving biostatisticians and epidemiologists in study design, as well as at the editorial level, by mandating adherence to methodologic standards in primary DTA studies and DTA meta-analyses.
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Diagnóstico por Imagen , Revisiones Sistemáticas como Asunto , Humanos , Diagnóstico por Imagen/estadística & datos numéricos , Diagnóstico por Imagen/normas , Diagnóstico por Imagen/métodos , Metaanálisis como Asunto , Pruebas Diagnósticas de Rutina/estadística & datos numéricos , Pruebas Diagnósticas de Rutina/normasRESUMEN
Background: Malaria remains a major cause of morbidity in sub-Saharan Africa. Undetected asymptomatic falciparum malaria results in a large transmission reservoir and there is evidence of increasing non-falciparum malaria as malaria is controlled in Africa, both resulting in challenges for malaria control programs. Methods: We performed quantitative real time PCR for 4 malaria species in 4,596 individuals from the 2014-2015 Rwanda Demographic Health Survey. Bivariate models were used to determine species-specific associations with risk factors. Results: Asymptomatic falciparum malaria, P. ovale spp., and P. malariae infection had broad spatial distribution across Rwanda. P. vivax infection was rare. Overall infection prevalence was 23.6% (95%CI [21.7%, 26.0%]), with falciparum and non-falciparum at 17.6% [15.9%, 19.0%] and 8.3% [7.0%, 10.0%], respectively. Parasitemias tended to be low and mixed species infections were common, especially where malaria transmission was the highest. Falciparum infection was associated with socio-econiomic status, rural residence and low altitude. Few risk factors were associated with non-falciparum malaria. Conclusions: Asymptomatic falciparum malaria and non-falciparum malaria are common and widely distributed across Rwanda. Continued molecular monitoring of Plasmodium spp. is needed to monitor these threats to malaria control in Africa.
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Nonbacterial thrombotic endocarditis (NBTE) describes a cluster of noninfectious heart valve lesions and is histologically characterised by the presence of sterile platelet and fibrin-rich aggregates. Risk factors include hypercoagulable states such as active malignancy, autoimmune disorders, and prothrombotic haematological conditions. NBTE involving bioprosthetic heart valves is exceedingly rare. We present a case of a 73-year-old man with a bioprosthetic aortic valve and no NBTE risk factors who developed right-sided homonymous hemianopia during an admission for decompensated congestive cardiac failure. After detailed clinical work-up including brain MRI, the man was diagnosed with acute ischemic cardioembolic stroke involving the left posterior cerebral artery territory. He subsequently underwent successful bioprosthetic aortic valve replacement with histologic examination of the explant supporting diagnosis of NBTE. Evidence of new neurological deficit or disturbance in patients with prosthetic heart valves should prompt investigation for cardioembolic stroke. Whilst rare, NBTE should be considered as a differential diagnosis for cardioembolic stroke, even in patients without predisposing systemic disease.
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BACKGROUND: Diagnostic neuroimaging plays an essential role in guiding clinical decision-making in the management of patients with cerebral aneurysms. Imaging technologies for investigating cerebral aneurysms constantly evolve, and clinicians rely on the published literature to remain up to date. Reporting guidelines have been developed to standardise and strengthen the reporting of clinical evidence. Therefore, it is essential that radiological diagnostic accuracy studies adhere to such guidelines to ensure completeness of reporting. Incomplete reporting hampers the reader's ability to detect bias, determine generalisability of study results or replicate investigation parameters, detracting from the credibility and reliability of studies. OBJECTIVE: The purpose of this systematic review was to evaluate adherence to the Standards for Reporting of Diagnostic Accuracy Studies (STARD) 2015 reporting guideline amongst imaging diagnostic accuracy studies for cerebral aneurysms. METHODS: A systematic search for cerebral aneurysm imaging diagnostic accuracy studies was conducted. Journals were cross examined against the STARD 2015 checklist and their compliance with item numbers was recorded. RESULTS: The search yielded 66 articles. The mean number of STARD items reported was 24.2 ± 2.7 (71.2% ± 7.9%), with a range of 19 to 30 out of a maximum number of 34 items. CONCLUSION: Taken together, these results indicate that adherence to the STARD 2015 guideline in cerebral aneurysm imaging diagnostic accuracy studies was moderate. Measures to improve compliance include mandating STARD 2015 adherence in instructions to authors issued by journals.
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Aneurisma Intracraneal , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Control de Calidad , Reproducibilidad de los Resultados , Adhesión a Directriz , Neuroimagen , Proyectos de InvestigaciónRESUMEN
Delineating the relative influence of genotype and the environment on DNA methylation is critical for characterizing the spectrum of organism fitness as driven by adaptation and phenotypic plasticity. In this study, we integrated genomic and DNA methylation data for two distinct Olympia oyster (Ostrea lurida) populations while controlling for within-generation environmental influences. In addition to providing the first characterization of genome-wide DNA methylation patterns in the oyster genus Ostrea, we identified 3,963 differentially methylated loci between populations. Our results show a clear coupling between genetic and epigenetic patterns of variation, with 27% of variation in interindividual methylation differences explained by genotype. Underlying this association are both direct genetic changes in CpGs (CpG-SNPs) and genetic variation with indirect influence on methylation (mQTLs). When comparing measures of genetic and epigenetic population divergence at specific genomic regions this relationship surprisingly breaks down, which has implications for the methods commonly used to study epigenetic and genetic coupling in marine invertebrates.
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Metilación de ADN , Genoma , Animales , Genética de Población , Epigénesis Genética , Invertebrados/genética , Islas de CpGRESUMEN
Malaria programs rely upon a variety of diagnostic assays, including rapid diagnostic tests (RDTs), microscopy, polymerase chain reaction (PCR), and bead-based immunoassays (BBA), to monitor malaria prevalence and support control and elimination efforts. Data comparing these assays are limited, especially from high-burden countries like the Democratic Republic of the Congo (DRC). Using cross-sectional and routine data, we compared diagnostic performance and Plasmodium falciparum prevalence estimates across health areas of varying transmission intensity to illustrate the relevance of assay performance to malaria control programs. Data and samples were collected between March-June 2018 during a cross-sectional household survey across three health areas with low, moderate, and high transmission intensities within Kinshasa Province, DRC. Samples from 1,431 participants were evaluated using RDT, microscopy, PCR, and BBA. P. falciparum parasite prevalence varied between diagnostic methods across all health areas, with the highest prevalence estimates observed in Bu (57.4-72.4% across assays), followed by Kimpoko (32.6-53.2%), and Voix du Peuple (3.1-8.4%). Using latent class analysis to compare these diagnostic methods against an "alloyed gold standard," the most sensitive diagnostic method was BBA in Bu (high prevalence) and Voix du Peuple (low prevalence), while PCR diagnosis was most sensitive in Kimpoko (moderate prevalence). RDTs were consistently the most specific diagnostic method in all health areas. Among 9.0 million people residing in Kinshasa Province in 2018, the estimated P. falciparum prevalence by microscopy, PCR, and BBA were nearly double that of RDT. Comparison of malaria RDT, microscopy, PCR, and BBA results confirmed differences in sensitivity and specificity that varied by endemicity, with PCR and BBA performing best for detecting any P. falciparum infection. Prevalence estimates varied widely depending on assay type for parasite detection. Inherent differences in assay performance should be carefully considered when using community survey and surveillance data to guide policy decisions.
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Tanner crab (Chionoecetes bairdi) is an economically important species that is threatened by ocean warming and bitter crab disease, which is caused by an endoparasitic dinoflagellate, Hematodinium. Little is known about disease transmission or its link to host mortality, or how ocean warming will affect pathogenicity or host susceptibility. To provide a transcriptomic resource for the Tanner crab, we generated a suite of RNA-seq libraries encompassing pooled hemolymph samples from crab displaying differing infection statuses and maintained at different temperatures (ambient (7.5ËC), elevated (10ËC), or decreased (4ËC)). After assembling a transcriptome and performing a multifactor differential gene expression analysis, we found genes influenced by temperature in relation to infection and detected some of those genes over time at the individual level using RNA-seq data from one crab. Biological processes associated with those genes include lipid storage, transcription, response to oxidative stress, cell adhesion, and morphogenesis. Alteration in lipid storage and transcription provide insight into how temperature impacts energy allocation in Hematodinium infected crabs. Alteration in expression patterns in genes associated with morphogenesis could suggest that hemocytes were changing morphology and/or type in response to temperature. This project provides insight into how Hematodinium infection could influence crab physiology as oceans warm.
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Braquiuros , Dinoflagelados , Animales , Braquiuros/genética , Dinoflagelados/genética , Hemocitos , Océanos y Mares , Alimentos MarinosRESUMEN
BACKGROUND: Microbial communities are ubiquitous throughout ecosystems and are commensal with hosts across taxonomic boundaries. Environmental and species-specific microbiomes are instrumental in maintaining ecosystem and host health, respectively. The introduction of pathogenic microbes that shift microbiome community structure can lead to illness and death. Understanding the dynamics of microbiomes across a diversity of environments and hosts will help us to better understand which taxa forecast survival and which forecast mortality events. RESULTS: We characterized the bacterial community microbiome in the water of a commercial shellfish hatchery in Washington state, USA, where the hatchery has been plagued by recurring and unexplained larval mortality events. By applying the complementary methods of metagenomics and metaproteomics we were able to more fully characterize the bacterial taxa in the hatchery at high (pH 8.2) and low (pH 7.1) pH that were metabolically active versus present but not contributing metabolically. There were shifts in the taxonomy and functional profile of the microbiome between pH and over time. Based on detected metagenomic reads and metaproteomic peptide spectral matches, some taxa were more metabolically active than expected based on presence alone (Deltaproteobacteria, Alphaproteobacteria) and some were less metabolically active than expected (e.g., Betaproteobacteria, Cytophagia). There was little correlation between potential and realized metabolic function based on Gene Ontology analysis of detected genes and peptides. CONCLUSION: The complementary methods of metagenomics and metaproteomics contribute to a more full characterization of bacterial taxa that are potentially active versus truly metabolically active and thus impact water quality and inter-trophic relationships.
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BACKGROUND: Insect bite hypersensitivity (IBH) is an IgE-mediated allergic dermatitis in horses incited by salivary allergens from Culicoides spp. IBH does not occur in Iceland, as the causative agents are absent, however a high prevalence is seen in horses exported to Culicoides-rich environments. AIMS: To study the natural course of sensitization to Culicoides allergens and identify the primary sensitizing allergen(s) in horses exported from Iceland utilizing a comprehensive panel of Culicoides recombinant (r-) allergens. METHOD: IgE microarray profiling to 27 Culicoides r-allergens was conducted on 110 serological samples from horses imported to Switzerland from Iceland that subsequently developed IBH or remained healthy. Furthermore, a longitudinal study of 31 IBH horses determined IgE profiles the summer preceding first clinical signs of IBH (TIBH-1), the summer of first clinical signs (TIBH) and the following summer (TIBH+1). In a group of Icelandic horses residing in Sweden, effects of origin (born in Iceland or Sweden) and duration of IBH (<4 years, 4-7 years, >7 years) on Culicoides-specific IgE was evaluated. Sero-positivity rates and IgE levels were compared. RESULTS: At TIBH, horses were sensitized to a median of 11 r-allergens (range = 0-21), of which nine were major allergens. This was significantly higher than TIBH-1 (3, 0-16), as well as the healthy (1, 0-14) group. There was no significant increase between TIBH and TIBH+1(12, 0-23). IBH-affected horses exported from Iceland had a significantly higher degree of sensitization than those born in Europe, while duration of IBH did not significantly affect degree of sensitization. CONCLUSION: Significant sensitization is only detected in serum the year of first clinical signs of IBH. Horses become sensitized simultaneously to multiple Culicoides r-allergens, indicating that IgE-reactivity is due to co-sensitization rather than cross-reactivity between Culicoides allergens. Nine major first sensitizing r-allergens have been identified, which could be used for preventive allergen immunotherapy.
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Alérgenos/inmunología , Ceratopogonidae/inmunología , Dermatitis Atópica/inmunología , Enfermedades de los Caballos/inmunología , Caballos/inmunología , Mordeduras y Picaduras de Insectos/inmunología , Animales , Reacciones Cruzadas , Dermatitis Atópica/sangre , Enfermedades de los Caballos/sangre , Islandia , Inmunoglobulina E/sangre , Mordeduras y Picaduras de Insectos/sangre , Estudios Longitudinales , Análisis por Matrices de Proteínas/métodos , Estaciones del Año , Suecia , SuizaRESUMEN
Heart disease represents a significant public health burden and is associated with considerable morbidity and mortality at the level of the individual. Current therapies for pathologies such as myocardial infarction, cardiomyopathy and heart failure are unable to repair damaged tissue to an extent that provides restoration of function approaching that of the pre-diseased state. Novel approaches to repair and regenerate the injured heart include cell therapy and the use of exogenous factors. Improved understanding of the role of growth factors in endogenous cardiac repair processes has motivated the investigation of their potential as therapeutic agents for cardiac pathology. Despite the disappointing performance of other growth factors in historical clinical trials, insulin-like growth factor 1 (IGF-1), neuregulin and platelet-derived growth factor (PDGF) have recently emerged as new candidate therapies. These growth factors elicit tissue repair through anti-apoptotic, pro-angiogenic and fibrosis-modulating mechanisms and have produced clinically significant functional improvement in preclinical studies. Early human trials suggest that IGF-1 and neuregulin are well tolerated and yield dose-dependent benefit, warranting progression to later phase studies. However, outstanding challenges such as short growth factor serum half-life and insufficient target-organ specificity currently necessitate the development of novel delivery strategies.
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PURPOSE: Cardiac pathologies remain a dominant cause of morbidity and mortality within the community. The drive to develop therapies capable of repairing damaged heart tissue to achieve clinically significant restoration of function has motivated the pursuit of novel approaches such as cell therapy. To this end, evidence of therapeutic benefits achieved by using mesenchymal stem cells (MSCs) has captured considerable interest despite a relative lack of information regarding the mechanisms involved. This narrative review synthesizes and interprets the current literature describing mechanisms by which MSCs can elicit cardiac repair, thereby directing attention to avenues of further inquiry. METHODS: OVID versions of MEDLINE and EMBASE were searched for studies describing the role of MSCs in mammalian cardiac repair. Additional studies were sourced from the reference lists of relevant articles and other personal files. FINDINGS: MSCs elicit cardiac repair in a range of in vitro systems and animal models of diseases such as myocardial infarction and heart failure. Important mechanisms include the preservation of myocardial contractility, the promotion of angiogenesis, and the modulation of fibrosis. Exposing in vitro MSCs to a microenvironment reflective of that encountered in the injured heart seems to potentiate these therapeutic mechanisms. IMPLICATIONS: Promising results in animal studies warrant continuation of clinical MSC cardiac therapy studies. Paracrine functions of MSCs seem to be the dominant mechanism of cardiac repair over direct cellular effects. Although integral, the MSC secretome remains poorly defined. In addition, most of the mechanistic data within the literature have been derived from animal MSC research, necessitating more human MSC-based work.
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Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/citología , Infarto del Miocardio/terapia , Animales , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Fibroblastos/citología , Corazón/fisiopatología , Humanos , Células Musculares/citologíaRESUMEN
STUDY DESIGN: Retrospective radiographic study. OBJECTIVES: T1 slope is an important parameter of sagittal spinal balance. However, the T1 superior endplate can be difficult to visualize on radiographs due to overlying anatomical structures. C7 slope has been proposed as a potential substitute for T1 slope when the T1 superior endplate is not well visualized. The objective of this study was 2-fold: (1) to assess the correlation between C7 and T1 slopes on upright cervical spine radiographs and (2) to evaluate the interrater reliability of C7 slope. METHODS: Cervical spine radiographs taken between December 2017 and June 2018 at a single institution were reviewed. Two observers measured upper C7 slope, lower C7 slope, and T1 slope. The correlations between upper and lower C7 slope and T1 slope were evaluated, and linear regression analyses were performed. Interrater reliability of C7 slope was also assessed. RESULTS: In this cohort of 152 patients, there was a strong correlation between upper C7 slope and T1 slope (r = 0.91, P < .001), as well as between lower C7 slope and T1 slope (r = 0.90, P < .001). T1 slope could be estimated from the linear regression equation, T1 slope = 0.87 × C7 slope + 7, with an overall model fit of R 2 = 0.8. There was strong interrater reliability for upper (intraclass correlation coefficient [ICC] = 0.95, P < .001) and lower C7 slope (ICC = 0.96, P < .001). CONCLUSIONS: Both the upper and lower C7 slope are strongly correlated with T1 slope and can be used as a substitute to estimate T1 slope when the superior endplate of T1 is not well visualized.
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OBJECTIVE: The purpose of this study was to identify predictors of 30-day postoperative pulmonary complications after open reduction and internal fixation (ORIF) of vertebral fractures. METHODS: We performed a retrospective study using the American College of Surgeons National Surgical Quality Improvement Program database from 2010 to 2014. Adult patients who underwent ORIF of vertebral fractures were included and divided into 2 groups based on the occurrence of 30-day postoperative pulmonary complications. Baseline patient and operative characteristics were compared between the 2 groups. Multivariate regression (MVR) analysis was performed to identify independent risk factors for pulmonary complications. RESULTS: A total of 900 patients were included in our cohort. The overall 30-day pulmonary complication rate was 5.67%. Patients who had a pulmonary complication after vertebral ORIF were more often men and more often had diabetes, functional dependence, American Society of Anesthesiologists score classification of 3 or higher, pulmonary comorbidity, renal comorbidity, and preoperative anemia. The pulmonary complication group also had a higher incidence of 30-day mortality, prolonged hospitalization, pneumonia, cardiac complications, urinary tract infection, blood transfusion, and sepsis. The MVR analysis found that pulmonary comorbidity (odds ratio [OR], 5.3; 95% confidence interval [CI], 2.5-11.5; P < 0.001), diabetes (OR, 2.1; 95% CI, 1.0-4.2; P = 0.037), partial or dependent functional status (OR, 4.7; 95% CI, 2.2-10.2; P < 0.001), and cervical spine involvement (OR, 3.6; 95% CI, 1.7-8.0; P = 0.001) were independent predictors of pulmonary complications. CONCLUSIONS: Early identification of risk factors for postoperative pulmonary complications is important in the evaluation of patients with vertebral fractures for surgical decision-making, preoperative optimization, and subsequent postoperative care to improve patient outcomes and minimize morbidity.