Determining the value of the abdominal core health quality collaborative to support regulatory decisions.

PURPOSE: The study objective is to document value created by real-world evidence from the Abdominal Core Health Quality Collaborative (ACHQC) for regulatory decisions. The ACHQC is a national effort that generates data on hernia repair techniques and devices. METHODS: Two retrospective cohort evaluations compared cost and time of ACHQC analyses to traditional postmarket studies. The first analysis was based on 25 reports submitted to the European Medicines Agency of 20 mesh products for post-market surveillance. A second analysis supported label expansion submitted to the Food and Drug Administration, Center for Devices and Radiological Health for a robotic-assisted surgery device to include ventral hernia repair. Estimated costs of counterfactual studies, defined as studies that might have been done if the registry had not been available, were derived from a model described in the literature. Return on investment, percentage of cost savings, and time savings were calculated. RESULTS: 45,010 patients contributed to the two analyses. The cost and time differences between individual 25 ACHQC analyses (41,112 patients) and traditional studies ranged from $1.3 to $2.2 million and from 3 to 4.8 years, both favoring use of the ACHQC. In the second label expansion analysis (3,898 patients), the estimated return on investment ranged from 11 to 461% with time savings of 5.1 years favoring use of the ACHQC. CONCLUSIONS: Compared to traditional postmarket studies, use of ACHQC data can result in cost and time savings when used for appropriate regulatory decisions in light of key assumptions.

Initial Experiences with Amyloid-Related Imaging Abnormalities in Patients Receiving Aducanumab Following Accelerated Approval.

Aducanumab is the first FDA-approved amyloid-lowering immunotherapy for Alzheimer's disease. There is little real-world data to guide management of amyloid-related imaging abnormalities (ARIA), a potentially serious side-effect which requires surveillance with magnetic resonance imaging. We report our experiences in managing ARIA in patients receiving aducanumab at the Butler Hospital Memory and Aging Program during the year following FDA approval. We followed the Appropriate Use Recommendations for aducanumab to guide patient selection, detection, and management of ARIA (1). ARIA-E occurred in 6 out of 24 participants treated; all APOE-ε4 carriers. Treatment was discontinued in 4 cases of moderate-severe ARIA-E, temporarily held in 1 moderate case, and dosed through in 1 mild case (mean duration = 3 months, range, 1-6 months). No participants required hospitalization or high dose corticosteroids. Participants on anticoagulation were excluded and no macrohemorrhages occurred. These data support the measured approaches to treatment outlined in the Appropriate Use Recommendations.

Vaccine third dose and cancer patients: necessity or luxury?

The current state of the SARS-CoV-2 pandemic is an equilibrium between expanding vaccine coverage on the one hand, and emergence of variants of concern which compromise vaccine effectiveness and enhance viral transmission on the other. Inequity in vaccine distribution, primarily an ethical issue, challenges this equilibrium, as industrialized countries prepare to administer a third booster dose to their population. Solid tumor cancer patients typically respond well to initial full vaccination and someone could argue that they should not be prioritized for an adjuvant third dose, since protection from severe disease has largely been achieved with the two-dose regimen. Nevertheless, their immune status is dynamic and not all of them exhibit an adequate immune response. A booster third dose is necessary for the inadequate responders, while it will result in better protection of all patients from mild disease as well, which if presented could have ominous consequences due to their overall frailty, and their need to adhere to strict therapeutic schemes. International scientific and public health communities should develop approaches that allow for wide immediate vaccination coverage of the developing world, in parallel with administration of adjuvant doses to solid tumor cancer patients (and other at-risk categories) of the developed nations, in order to avoid prolonging the pandemic, which will be prospectively against cancer patients' best interest.

Asc-Seurat: analytical single-cell Seurat-based web application.

BACKGROUND: Single-cell RNA sequencing (scRNA-seq) has revolutionized the study of transcriptomes, arising as a powerful tool for discovering and characterizing cell types and their developmental trajectories. However, scRNA-seq analysis is complex, requiring a continuous, iterative process to refine the data and uncover relevant biological information. A diversity of tools has been developed to address the multiple aspects of scRNA-seq data analysis. However, an easy-to-use web application capable of conducting all critical steps of scRNA-seq data analysis is still lacking. We present Asc-Seurat, a feature-rich workbench, providing an user-friendly and easy-to-install web application encapsulating tools for an all-encompassing and fluid scRNA-seq data analysis. Asc-Seurat implements functions from the Seurat package for quality control, clustering, and genes differential expression. In addition, Asc-Seurat provides a pseudotime module containing dozens of models for the trajectory inference and a functional annotation module that allows recovering gene annotation and detecting gene ontology enriched terms. We showcase Asc-Seurat's capabilities by analyzing a peripheral blood mononuclear cell dataset. CONCLUSIONS: Asc-Seurat is a comprehensive workbench providing an accessible graphical interface for scRNA-seq analysis by biologists. Asc-Seurat significantly reduces the time and effort required to analyze and interpret the information in scRNA-seq datasets.

[Intravitreal ganciclovir as an additional therapy option in acute retinal necrosis]. / Intravitreales Ganciclovir als additive Therapieoption bei akuter retinaler Nekrose.

Acute retinal necrosis (ARN) is a rare viral inflammatory disease, characterized by uveitis, retinal vasculitis, and necrosis in the late stages. Therapeutic management is based on the clinical findings. The positive outcome in our patient (VA 0.6) indicates that, beside the management of retinal detachment and lens opacification, additional intravitreal injections of 2 mg ganciclovir may achieve better results than systemic/topical antiviral application alone.

Identification and Expression Profile of Two Putative Odorant-Binding Proteins from the Neotropical Brown Stink Bug, Euschistus heros (Fabricius) (Hemiptera: Pentatomidae).

This work presents the first identification of putative odorant-binding proteins (OBPs) from a member of the Pentatomidae, i.e. the brown stink bug Euschistus heros (Fabricius), an important pest of soybean in Brazil. Antennae from both sexes of E. heros adults (12 days old and unmated) were used to construct a cDNA library, from which two transcripts encoding putative E. heros OBPs (EherOBPs) were identified. The expression levels of EherOBP1 and EherOBP2 were found to be higher in male antennae than in female and there was difference in expression in legs, wings, and abdomens of the two sexes. The histolocalization of EherOBP1 and EherOBP2 transcripts in antennae also showed a sexual dimorphism in the chemoreception system, with different expression sites in the antennal segments between males and females, occurring predominantly at the base of the sensillum. The implications of these findings for stink bug chemoreception are discussed.

Socio-economic, industrial and cultural parameters of pig-borne infections.

The pork-processing industry has been possibly the fastest growing sector of the food industry in recent years. Specialization, genetic homogenization of the pig population, high density of the breeding population, reduced human-animal interactions, slaughter at a lower age and increased international trade of live animals and pork are parameters that affect, positively or negatively, the emergence of novel pig-borne pathogens, many of which are pig-specific, and many of which have significant zoonotic potential, as observed in recent outbreaks of Nipah virus and Streptococcus suis in Southeast Asia and China, respectively. Numerous other pathogens are transmitted to humans through direct contact with or consumption of pig products, and globalization trends in trade and human population movements have resulted in outbreaks of pig-borne diseases even in Muslim countries and in Israel, where pork consumption is religiously prohibited. The role of pigs as potential reservoirs of antibiotic-resistant pathogens or genes encoding resistance, and the role of feral pigs as a reservoir of zoonotic disease, are scientific fields in direct need of further research.

Targeted cell reprogramming produces analgesic chromaffin-like cells from human mesenchymal stem cells.

Transplantation of allogeneic adrenal chromaffin cells demonstrated the promise of favorable outcomes for pain relief in patients. However, there is a very limited availability of suitable human adrenal gland tissues, genetically well-matched donors in particular, to serve as grafts. Xenogeneic materials, such as porcine and bovine adrenal chromaffin cells, present problems; for instance, immune rejection and possible pathogenic contamination are potential issues. To overcome these challenges, we have tested the novel approach of cell reprogramming to reprogram human bone marrow (BM)-derived mesenchymal stem cells (hMSCs) using cellular extracts of porcine chromaffin cells. We produced a new type of cell, chromaffin-like cells, generated from the reprogrammed hMSCs, which displayed a significant increase in expression of human preproenkephalin (hPPE), a precursor for enkephalin opioid peptides, compared to the inherent expression of hPPE in naive hMSCs. The resultant chromaffin-like cells not only expressed the key molecular markers of adrenal chromaffin cells, such as tyrosine hydroxylase (TH) and methionine enkephalin (Met-enkephalin), but also secreted opioid peptide Met-enkephalin in culture. In addition, intrathecal injection of chromaffin-like cells in rats produced significant analgesic effects without using immunosuppressants. These results suggest that analgesic chromaffin-like cells can be produced from an individual's own tissue-derived stem cells by targeted cell reprogramming and also that these chromaffin-like cells may serve as potential autografts for chronic pain management.

Comparative study of LbL and crosslinked pH sensitive PEGylated LbL microspheres: synthesis, characterization and biological evaluation.

In this report, the fabrication of hollow, pH-sensitive microspheres using the layer by layer method is being demonstrated. The process is based on the coating of colloidal silica templates with polyelectrolyte layers, followed by dissolution of the core using a buffer system of hydrofluoric acid and ammonium fluoride. With this buffer system, the template can be dissolved in mild pH conditions, where the polymeric layers are still stable. The resulting microspheres show pH dependent properties, where they swell and dissolve at a certain pH value. In order to improve the nanocontainers properties, such as solubility and cytotoxicity a second specimen of microspheres was fabricated by coating the fabricated microspheres with one layer of poly(acrylic acid) and one layer of methoxy-polyethylene glycol amine, and then these additional layers were crosslinked by carbodiimide chemistry. Loading and release properties of the fabricated microspheres have been studied in order to investigate their behavior as a function of pH and ionic strength. These novel microspheres have potential application in the fields of drug delivery, diagnostics and life sciences.

Diagnosis of chronic brucellar meningitis and meningoencephalitis: the results of the Istanbul-2 study.

No detailed data exist in the literature on the accurate diagnosis of chronic brucellar meningitis or meningoencephalitis. A multicentre retrospective chart review was performed at 19 health centres to determine sensitivities of the diagnostic tests. This study included 177 patients. The mean values of CSF biochemical test results were as follows: CSF protein, 330.64 ± 493.28 mg/dL; CSF/ blood-glucose ratio, 0.35 ± 0.16; CSF sodium, 140.61 ± 8.14 mMt; CSF leucocyte count, 215.99 ± 306.87. The sensitivities of the tests were as follows: serum standard tube agglutination (STA), 94%; cerebrospinal fluid (CSF) STA, 78%; serum Rose Bengal test (RBT), 96%; CSF RBT, 71%; automated blood culture, 37%; automated CSF culture, 25%; conventional CSF culture, 9%. The clinician should use every possible means to diagnose chronic neurobrucellosis. The high seropositivitiy in brucellar blood tests must facilitate the use of blood serology. Although STA should be preferred over RBT in CSF in probable neurobrucellosis other than the acute form of the disease, RBT is not as weak as expected. Moreover, automated culture systems should be applied when CSF culture is needed.

Radiographic signs of static carpal instability with distal end radius fractures: is current treatment adequate?

Patients presenting with distal end radius fractures may have concomitant carpal instability due to disruption of the scapholunate ligament. This study examined the incidence of static radiographic signs of carpal instability in patients with distal radial fractures before and after fracture treatment. We performed a retrospective radiographic study of 141 patients presenting to Central Middlesex Hospital, London between January 2002-May 2004 with distal end radius fractures. We used abnormal scapholunate angle as the primary indicator of possible carpal dissociation. Abnormal scapholunate angles were noted in 39% of patients at presentation and 35% of patients after treatment with no statistically significant intra-patient variability. Persistent static radiographic signs of carpal instability are high in this subset of patients. The long-term morbidity of persistent wrist instability may be avoided by early radiological diagnosis with clinical correlation to identify carpal ligament injuries and initiate treatment that addresses both the bony and ligamentous components of the injury.

Identification of genes encoding hypothetical proteins in open-reading frame expressed sequence tags from mammalian stages of Trypanosoma cruzi.

Approximately 50% of the predicted protein-coding genes of the Trypanosoma cruzi CL Brener strain are annotated as hypothetical or conserved hypothetical proteins. To further characterize these genes, we generated 1161 open-reading frame expressed sequence tags (ORESTES) from the mammalian stages of the VL10 human strain. Sequence clustering resulted in 435 clusters, consisting of 339 singletons and 96 contigs. Significant matches to the T. cruzi predicted gene database were found for ~94% contigs and ~69% singletons. These included genes encoding surface proteins, known to be intensely expressed in the parasite mammalian stages and implicated in host cell invasion and/or immune evasion mechanisms. Among 151 contigs and singletons with similarity to predicted hypothetical protein-coding genes and conserved hypothetical protein-coding genes, 83% showed no match with T. cruzi EST and/or proteome databases. These ORESTES are the first experimental evidence that the corresponding genes are in fact transcribed. Sequences with no significant match were searched against several T. cruzi and National Center for Biotechnology Information non-redundant sequence databases. The ORESTES analysis indicated that 124 predicted conserved hypothetical protein-coding genes and 27 predicted hypothetical protein-coding genes annotated in the CL Brener genome are transcribed in the VL10 mammalian stages. Six ORESTES annotated as hypothetical protein-coding genes showing no match to EST and/or proteome databases were confirmed by Northern blot in VL10. The generation of this set of ORESTES complements the T. cruzi genome annotation and suggests new stage-regulated genes encoding hypothetical proteins.

Epidemiological and clinical aspects of human Brucella suis infection in Polynesia.

High brucellosis seroprevalence rates in domestic swine herds have been reported in Wallis and Futuna Islands and are associated with a significant burden of human infection by Brucella suis, a species that is rarely incriminated in human disease. Between 2003 and 2010, seven patients had a positive blood culture for B. suis biovar 1, 11 symptomatic patients had a positive Rose Bengal test (RBT) and a positive serum agglutination test (SAT) and three asymptomatic cases were found to be positive for RBT, SAT or ELISA IgM (after systematic screening of 52 family members of 15 index cases). Overall, Brucella infection was diagnosed in 21 people, corresponding to a mean annual incidence of 19 cases/100 000 inhabitants. Compared to series of patients infected with other more commonly encountered Brucella spp. such as B. melitensis and B. abortus, clinical presentation and percentage and distribution of complications were similar, apart from a marked observation of significantly increased median alanine aminotransferase levels, 20 times greater than upper normal rates, but not accompanied by any particular hepatic pathology. Wallis and Futuna, where people live in close proximity to animals and where the cultural significance of pig-raising precludes the implementation of adequate veterinary preventive measures, thus represents one of the few known B. suis foci worldwide and allows for evaluation of the peculiarities of this infection.

The socio-ecology of zoonotic infections.

The resurgence of infectious diseases of zoonotic origin observed in recent years imposes a major morbidity/mortality burden worldwide, and also a major economic burden that extends beyond pure medical costs. The resurgence and epidemiology of zoonoses are complex and dynamic, being influenced by varying parameters that can roughly be categorized as human-related, pathogen-related, and climate/environment-related; however, there is significant interplay between these factors. Human-related factors include modern life trends such as ecotourism, increased exposure through hunting or pet owning, and culinary habits, industrialization sequelae such as farming/food chain intensification, globalization of trade, human intrusion into ecosystems and urbanization, significant alterations in political regimes, conflict with accompanying breakdown of public health and surveillance infrastructure, voluntary or involuntary immigration, loosening of border controls, and hierarchy issues in related decision-making, and scientific advances that allow easier detection of zoonotic infections and evolution of novel susceptible immunocompromised populations. Pathogen-related factors include alterations in ecosystems and biodiversity that influence local fauna synthesis, favouring expansion of disease hosts or vectors, pressure for virulence/resistance selection, and genomic variability. Climate/environment-related factors, either localized or extended, such as El Niño southern oscillation or global warming, may affect host-vector life cycles through varying mechanisms. Emerging issues needing clarification include the development of predictive models for the infectious disease impact of environmental projects, awareness of the risk imposed on immunocompromised populations, recognition of the chronicity burden for certain zoonoses, and the development of different evaluations of the overall stress imposed by a zoonotic infection on a household, and not strictly a person.

Decreasing trends of ultrasonographic prevalence of cystic echinococcosis in a rural Greek area.

Greece is considered as one of the endemic European countries for cystic echinococcosis (CE). We evaluated the prevalence trends of CE in the rural area of Trikala, Central Greece, through ultrasound records for the period 2001-2008. Of the 47,045 total number of abdominal ultrasound tests performed in the period 2001-2008, a total of 153 individuals had abdominal CE. Despite this generally high figure, significantly lower prevalence rates were noted during the second half of the study period. The implementation of a national campaign for CE control, started in 1984, has led to decreasing annual detection rates of CE in Central Greece.

Reappearance of viral hemorrhagic fever with renal syndrome in northwestern Greece.

BACKGROUND: Minor outbreaks of viral hemorrhagic fever (VHF) with renal failure have occurred in northwestern Greece over past decades. However, during the most recent decade, there has been a paucity of human cases despite the detection of hantavirus in rodents of this area. CASE REPORTS: We present herein the cases of two patients with VHF, arising in the same area, hospitalized for a short period of time. One patient presented with renal failure, while severe hepatic involvement was predominant in the other. Significantly high ELISA antibody titers for hantavirus established the diagnosis. Supportive treatment led to a successful outcome in both cases. We further discuss the difficulties in differential diagnosis of VHF from other zoonoses with similar endemicity, such as leptospirosis. CONCLUSIONS: Awareness of the continuing presence of VHF in rural Greece is needed, and a rapid diagnosis is important for the correct therapeutic approach. Continuous surveillance for such diseases, at both the animal (rodents) and human level, is warranted.