Review: The Role of Dual-Energy Computed Tomography in Detecting Monosodium Urate Deposits in Vascular Tissues.

PURPOSE OF REVIEW: To highlight novel findings in the detection of monosodium urate deposits in vessels using dual energy computed tomography, and to discuss the potential clinical implications for gout and hyperuricemia patients. RECENT FINDINGS: Gout is an independent risk factor for cardiovascular disease. However, classical risk calculators do not take into account these hazards, and parameters to identify patients at risk are lacking. Monosodium urate measured by dual energy computed tomography is a well-established technology for the detection and quantification of monosodium urate deposits in peripheral joints and tendons. Recent findings also suggest its applicability to identify vascular urate deposits. Dual energy computed tomography is a promising tool for detection of cardiovascular monosodium urate deposits in gout patients, to better delineate individuals at increased risk for cardiovascular disease.

Glucocorticoid treatment influences prostate cancer cell growth and the tumor microenvironment via altered glucocorticoid receptor signaling in prostate fibroblasts.

Despite significant therapeutic advances in recent years, treatment of metastatic prostate cancer (PCa) remains palliative, owing to the inevitable occurrence of drug resistance. There is increasing evidence that epithelial glucocorticoid receptor (GR) signaling and changes in the tumor-microenvironment (TME) play important roles in this process. Since glucocorticoids (GCs) are used as concomitant medications in the course of PCa treatment, it is essential to investigate the impact of GCs on stromal GR signaling in the TME. Therefore, general GR mRNA and protein expression was assessed in radical prostatectomy specimens and metastatic lesions. Elevated stromal GR signaling after GC treatment resulted in altered GR-target gene, soluble protein expression, and in a morphology change of immortalized and primary isolated cancer-associated fibroblasts (CAFs). Subsequently, these changes affected proliferation, colony formation, and 3D-spheroid growth of multiple epithelial PCa cell models. Altered expression of extra-cellular matrix (ECM) and adhesion-related proteins led to an ECM remodeling. Notably, androgen receptor pathway inhibitor treatments did not affect CAF viability. Our findings demonstrate that GC-mediated elevated GR signaling has a major impact on the CAF secretome and the ECM architecture. GC-treated fibroblasts significantly influence epithelial tumor cell growth and must be considered in future therapeutic strategies.

Impact of Dual-Energy Computed Tomography (DECT) Postprocessing Protocols on Detection of Monosodium Urate (MSU) Deposits in Foot Tendons of Cadavers.

OBJECTIVE: To evaluate two different dual-energy computed tomography (DECT) post-processing protocols for the detection of MSU deposits in foot tendons of cadavers with verification by polarizing light microscopy as the gold standard. MATERIAL AND METHODS: A total of 40 embalmed cadavers (15 male; 25 female; median age, 82 years; mean, 80 years; range, 52-99; SD ± 10.9) underwent DECT to assess MSU deposits in foot tendons. Two postprocessing DECT protocols with different Hounsfield unit (HU) thresholds, 150/500 (=established) versus 120/500 (=modified). HU were applied to dual source acquisition with 80 kV for tube A and 140 kV for tube B. Six fresh cadavers (4 male; 2 female; median age, 78; mean, 78.5; range 61-95) were examined by DECT. Tendon dissection of 2/6 fresh cadavers with positive DECT 120 and negative DECT 150 studies were used to verify MSU deposits by polarizing light microscopy. RESULTS: The tibialis anterior tendon was found positive in 57.5%/100% (DECT 150/120), the peroneus tendon in 35%/100%, the achilles tendon in 25%/90%, the flexor halluces longus tendon in 10%/100%, and the tibialis posterior tendon in 12.5%/97.5%. DECT 120 resulted in increased tendon MSU deposit detection, when DECT 150 was negative, with an overall agreement between DECT 150 and DECT 120 of 80% (p = 0.013). Polarizing light microscope confirmed MSU deposits detected only by DECT 120 in the tibialis anterior, the achilles, the flexor halluces longus, and the peroneal tendons. CONCLUSION: The DECT 120 protocol showed a higher sensitivity when compared to DECT 150.

Single-Center Experience in Detecting Influenza Virus, RSV and SARS-CoV-2 at the Emergency Department.

Reverse transcription polymerase chain reaction (RT-PCR) on respiratory tract swabs has become the gold standard for sensitive and specific detection of influenza virus, respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this retrospective analysis, we report on the successive implementation and routine use of multiplex RT-PCR testing for patients admitted to the Internal Medicine Emergency Department (ED) at a tertiary care center in Western Austria, one of the hotspots in the early coronavirus disease 2019 (COVID-19) pandemic in Europe. Our description focuses on the use of the Cepheid® Xpert® Xpress closed RT-PCR system in point-of-care testing (POCT). Our indications for RT-PCR testing changed during the observation period: From the cold season 2016/2017 until the cold season 2019/2020, we used RT-PCR to diagnose influenza or RSV infection in patients with fever and/or respiratory symptoms. Starting in March 2020, we used the RT-PCR for SARS-CoV-2 and a multiplex version for the combined detection of all these three respiratory viruses to also screen subjects who did not present with symptoms of infection but needed in-hospital medical treatment for other reasons. Expectedly, the switch to a more liberal RT-PCR test strategy resulted in a substantial increase in the number of tests. Nevertheless, we observed an immediate decline in influenza virus and RSV detections in early 2020 that coincided with public SARS-CoV-2 containment measures. In contrast, the extensive use of the combined RT-PCR test enabled us to monitor the re-emergence of influenza and RSV detections, including asymptomatic cases, at the end of 2022 when COVID-19 containment measures were no longer in place. Our analysis of PCR results for respiratory viruses from a real-life setting at an ED provides valuable information on the epidemiology of those infections over several years, their contribution to morbidity and need for hospital admission, the risk for nosocomial introduction of such infection into hospitals from asymptomatic carriers, and guidance as to how general precautions and prophylactic strategies affect the dynamics of those infections.

Prevalence of Monosodium Urate (MSU) Deposits in Cadavers Detected by Dual-Energy Computed Tomography (DECT).

BACKGROUND: Dual-energy computed tomography (DECT) allows direct visualization of monosodium urate (MSU) deposits in joints and soft tissues. PURPOSE: To describe the distribution of MSU deposits in cadavers using DECT in the head, body trunk, and feet. MATERIALS AND METHODS: A total of 49 cadavers (41 embalmed and 8 fresh cadavers; 20 male, 29 female; mean age, 79.5 years; SD ± 11.3; range 52-95) of unknown clinical history underwent DECT to assess MSU deposits in the head, body trunk, and feet. Lens, thoracic aorta, and foot tendon dissections of fresh cadavers were used to verify MSU deposits by polarizing light microscopy. RESULTS: 33/41 embalmed cadavers (80.5%) showed MSU deposits within the thoracic aorta. 11/41 cadavers (26.8%) showed MSU deposits within the metatarsophalangeal (MTP) joints and 46.3% of cadavers demonstrated MSU deposits within foot tendons, larger than and equal to 5 mm. No MSU deposits were detected in the cranium/intracerebral vessels, or the coronary arteries. Microscopy used as a gold standard could verify the presence of MSU deposits within the lens, thoracic aorta, or foot tendons in eight fresh cadavers. CONCLUSIONS: Microscopy confirmed the presence of MSU deposits in fresh cadavers within the lens, thoracic aorta, and foot tendons, whereas no MSU deposits could be detected in cranium/intracerebral vessels or coronary arteries. DECT may offer great potential as a screening tool to detect MSU deposits and measure the total uric acid burden in the body. The clinical impact of this cadaver study in terms of assessment of MSU burden should be further proven.

Quantity of IgG response to SARS-CoV-2 spike glycoprotein predicts pulmonary recovery from COVID-19.

The CovILD study is a prospective, multicenter, observational cohort study to systematically follow up patients after coronavirus disease-2019 (COVID-19). We extensively evaluated 145 COVID-19 patients at 3 follow-up visits scheduled for 60, 100, and 180 days after initial confirmed diagnosis based on typical symptoms and a positive reverse transcription-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We employed comprehensive pulmonary function and laboratory tests, including serum concentrations of IgG against the viral spike (S) glycoprotein, and compared the results to clinical data and chest computed tomography (CT). We found that at the 60 day follow-up, 131 of 145 (90.3%) participants displayed S-specific serum IgG levels above the cut-off threshold. Notably, the highly elevated IgG levels against S glycoprotein positively correlated with biomarkers of immune activation and negatively correlated with pulmonary function and the extent of pulmonary CT abnormalities. Based on the association between serum S glycoprotein-specific IgG and clinical outcome, we generated an S-specific IgG-based recovery score that, when applied in the early convalescent phase, accurately predicted delayed pulmonary recovery after COVID-19. Therefore, we propose that S-specific IgG levels serve as a useful immunological surrogate marker for identifying at-risk individuals with persistent pulmonary injury who may require intensive follow-up care after COVID-19.

The International Consensus on ANA Patterns (ICAP) in 2021-The 6th Workshop and Current Perspectives.

The establishment of the International Consensus on ANA Patterns (ICAP) in 2014-2015 was welcomed by members of the medical community as a significant improvement in guiding harmonization of ANA test interpretation and reporting. In the subsequent years, several itinerant meetings and continuous interaction with the community contributed to disseminate the ICAP harmonization on the immunofluorescence patterns observed in the indirect immunofluorescence assay on HEp-2 cells (HEp-2 IFA) and to promote progressive improvement in the classification of HEp-2 IFA patterns. The 6th ICAP Workshop was held in person on September 6, 2021 as a satellite meeting of the 15th Dresden Symposium on Autoantibodies. This article summarizes the major discussions at the meeting as well as outlining the current plans for the ICAP committee.

How to report the antinuclear antibodies (anti-cell antibodies) test on HEp-2 cells: guidelines from the ICAP initiative.

Results of the anti-nuclear antibodies-indirect immunofluorescence assay (anti-cell antibodies test) on HEp-2 cell substrates should be communicated to clinicians in a standardized way, adding value to laboratory findings and helping with critical clinical decisions. This paper proposes a test report based on the practices informed by 118 laboratories in 68 countries, with recommendations from the International Consensus on ANA Patterns (ICAP) group. Major focus is placed on the report format containing endpoint titers, immunofluorescence patterns together with anti-cell (AC) nomenclature, remarks on follow-up or reflex testing, and possible other autoantibody associations. ISO 15,189 directives were integrated into the test report. Special situations addressed include serum screening dilutions and endpoint titers, relevance of immunofluorescence patterns with special attention to cytoplasmic patterns, mixed and compound patterns, and how to report different titers corresponding to multiple patterns or autoantibodies in the same sample. This paper suggests a subtitle for the HEp-2-IIFA, namely anti-cell antibodies test, which could gradually substitute the original outdated ANA nomenclature. This ICAP pro forma report represents a further step in harmonizing the way relevant clinical information could be provided by laboratories.

Taxonomy notes and new occurrence data of four species of atyid shrimp (Crustacea: Decapoda: Atyidae) in Vietnam, all described from China.

BACKGROUND: Freshwater shrimp of the family Atyidae De Haan, 1849 have been studied in Vietnam for more than a century. A total of 24 species of atyid shrimps from the genera Caridina H. Milne Edwards, 1837, Neocaridina Kubo, 1938, Atyopsis Chace, 1983 have been recorded from Vietnam. With 22 species, the majority are from the genus Caridina. In 2013, Karge and Klotz mentioned the occurrence of four yet undescribed species belonging to Paracaridina Liang, Guo & Tang, 1999 in Vietnam without taxonomic details.In general, studies of freshwater atyids in Vietnam are limited and most Vietnamese taxa await a taxonomic revision. The available data do not fully reflect their estimated species diversity in the country and distribution data are deficient. Here, we focus on four species of atyid shrimps from two genera, viz. Caridinacantonensis Yu, 1938, C.lanceifrons Yu, 1936, C.serrata Stimpson, 1860 and Neocaridinapalmata (Shen, 1948), all described from China and have been reported to occur in Vietnam. The previous reports on the occurrence of these species in Vietnam are largely unreliable due to taxonomic confusion. To contribute to the knowledge of these taxa, we provide the first verified distribution records of the four species in the country with some taxonomic remarks. NEW INFORMATION: This study shows the first taxonomically-verified distribution data of four atyid shrimp species originally described from China, but also reported from Vietnam, albeit under various species names and, in some cases, erroneously. These data allow the first meaningful discussion of the distribution in light of the reproductive strategy of these four species and, in conjunction with the taxonomic remarks, will contribute to the knowledge of these taxa. As a result of this research and data from previous studies, we now consider all four species as widespread and non-endemic, but land-locked (with a complete freshwater life cycle). In Vietnam, all four species are confined to the northern half of the country. Beyond Vietnam, we provide the first records for Caridinalanceifrons from southern Thailand, which suggests a major sampling gap in Indochina.

Lake Poso's shrimp fauna revisited: the description of five new species of the genus Caridina (Crustacea, Decapoda, Atyidae) more than doubles the number of endemic lacustrine species.

Lake Poso, an ancient lake system on the Indonesian island Sulawesi, harbours an endemic species flock of six, four lacustrine and two riverine species of the freshwater shrimp genus Caridina. In this study, five new lacustrine species are described, bringing the total to eleven species altogether. The number of lacustrine species is more than doubled to nine species compared to the last taxonomic revision in 2009. One of them, Caridina mayamareenae Klotz, Wowor & von Rintelen, sp. nov., even represents the first case of an atyid shrimp associated with freshwater snails which is morphologically adapted to living in shells. An integrative approach was used by providing a combination of morphological, ecological, and molecular data. Based on standard morphological characters, distribution, substrate preferences, and colouration of living specimens in the field, five distinct undescribed species could be distinguished. To support our species-hypothesis based on the mitochondrial genes 16S and COI, a molecular phylogeny was used for all eleven species from Lake Poso. All species form a well-supported monophyletic group, but only four morphospecies consistently correspond to mtDNA clades - a possible reason could be introgressive hybridisation, incomplete lineage sorting, or not yet fixed species boundaries. These results are discussed further in the context of adaptive radiation, which turned out to be more diverse than previously described. Finally, yet importantly, subjecting all new species to similar threats and to the same IUCN category and criterion than the previously described species from the lake is recommended.

Overcoming limitations in the availability of swabs systems used for SARS-CoV-2 laboratory diagnostics.

The diagnosis of COVID-19 relies on the direct detection of SARS-CoV-2 RNA in respiratory specimens by RT-PCR. The pandemic spread of the disease caused an imbalance between demand and supply of materials and reagents needed for diagnostic purposes including swab sets. In a comparative effectiveness study, we conducted serial follow-up swabs in hospitalized laboratory-confirmed COVID-19 patients. We assessed the diagnostic performance of an in-house system developed according to recommendations by the US CDC. In a total of 96 serial swabs, we found significant differences in the accuracy of the different swab systems to generate a positive result in SARS-CoV-2 RT-PCR, ranging from around 50 to 80%. Of note, an in-house swab system was superior to most commercially available sets as reflected by significantly lower Ct values of viral genes. Thus, a simple combination of broadly available materials may enable diagnostic laboratories to bypass global limitations in the supply of swab sets.

Quality and best practice in medical laboratories: specific requests for autoimmunity testing.

Special conditions associated with laboratory autoimmune testing are not well compatible with recent developments in regulatory frameworks such as EN/ISO 15189 accreditation or in vitro diagnostic medical device regulation (IVD-R). In addition, international recommendations, guidelines and disease criteria are poorly defined with respect to requirements on autoantibody testing. Laboratory specialists from Austria, Belgium, Croatia, Estonia, Finland, France, Germany, Greece, Hungary, Italy, Norway, Poland, Portugal, South Africa, Spain, Sweden, Switzerland, and The Netherlands collected information, reported national experience, and identified quality issues in relation to autoantibody testing that require consensus on interpretation of the regulatory frameworks and guidelines. This process has been organized by the European Autoimmunity Standardisation Initiative (EASI). By identifying the critical items and looking for a consensus, our objective was to define a framework for, in particular, EN/ISO accreditation purposes. Here, we present a review of current publications and guidelines in this field to unify national guidelines and deliver in this way a European handout on quality control and accreditation for laboratories involved in autoantibody testing. We focus on quality items that can be checked during accreditation visits. Despite various local varieties, we encountered an overwhelming dedication to quality assurance in all contributing countries.

Clinical relevance of HEp-2 indirect immunofluorescent patterns: the International Consensus on ANA patterns (ICAP) perspective.

The indirect immunofluorescence assay (IIFA) on HEp-2 cells is widely used for detection of antinuclear antibodies (ANA). The dichotomous outcome, negative or positive, is integrated in diagnostic and classification criteria for several systemic autoimmune diseases. However, the HEp-2 IIFA test has much more to offer: besides the titre or fluorescence intensity, it also provides fluorescence pattern(s). The latter include the nucleus and the cytoplasm of interphase cells as well as patterns associated with mitotic cells. The International Consensus on ANA Patterns (ICAP) initiative has previously reached consensus on the nomenclature and definitions of HEp-2 IIFA patterns. In the current paper, the ICAP consensus is presented on the clinical relevance of the 29 distinct HEp-2 IIFA patterns. This clinical relevance is primarily defined within the context of the suspected disease and includes recommendations for follow-up testing. The discussion includes how this information may benefit the clinicians in daily practice and how the knowledge can be used to further improve diagnostic and classification criteria.

The complex study of complexes: The first well-supported phylogeny of two species complexes within genus Caridina (Decapoda: Caridea: Atyidae) sheds light on evolution, biogeography, and habitat.

Atyid shrimps, a key component of tropical freshwater ecosystems, face multiple anthropogenic threats and thus need special attention. With more than 300 described species, the genus Caridina is the most speciose of all the Caridea infra-order. Caridina spp. occupy diverse habitats in tropical freshwaters of the Indo-West Pacific region. Several species complexes have been recognized, based on common morphological features, but little is known about how well these morphological characteristics align with phylogenetic characteristics. Furthermore, no phylogeny of the genus Caridina published so far has provided well-resolved and supported relationships among different species, thus impeding the possibility of proposing evolutionary hypotheses. In this study we used next generation sequencing (NGS) to provide new insights into the phylogenetic relationships among the genus Caridina, focusing on two complexes: 'Caridina nilotica' and 'Caridina weberi'. We collected 92 specimens belonging to these two groups from most of their known geographical range, representing 50 species, for which we sequenced seven mitochondrial genes and two nuclear markers using ion torrent NGS. We performed a phylogenetic analysis, which yielded the first well-supported tree for the genus Caridina. On this tree were mapped the geographic ranges and the habitats used by the different species, and a time calibration was tested. We found the driving factors that most likely account for separation of clades are differences in habitat and to a lesser extent geography. This work provides new insights into the taxonomy of this group and identifies opportunities for further studies in order to fill knowledge gaps that currently impede the management and conservation of atyid species.

Effects of Antitumor Necrosis Factor Therapy on Osteoprotegerin, Neopterin, and sRANKL Concentrations in Patients with Rheumatoid Arthritis.

BACKGROUND: Rheumatoid arthritis is a systemic autoimmune disease characterized by joint erosions, progressive focal bone loss, and chronic inflammation. METHODS: 20 female patients with moderate-to-severe rheumatoid arthritis were treated with anti-TNF-antibody adalimumab in addition to concomitant antirheumatic therapies. Patients were assessed for overall disease activity using the DAS28 score, and neopterin, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) concentrations as well as osteoprotegerin (OPG) and soluble receptor activator of NF-κB ligand (sRANKL) concentrations were determined before therapy and at week 12. Neopterin as well as OPG and sRANKL were determined by commercial ELISAs. RESULTS: Before anti-TNF therapy patients presented with high disease activity and elevated concentrations of circulating inflammatory markers. OPG concentrations correlated with neopterin (rs = 0.494, p = 0.027), but not with DAS28. OPG concentrations and disease activity scores declined during anti-TNF-treatment (both p < 0.02). Patients who achieved remission (n = 7) or showed a good response according to EULAR criteria (n = 13) presented with initially higher baseline OPG levels, which subsequently decreased significantly during treatment (p = 0.018 for remission, p = 0.011 for good response). CONCLUSIONS: Adalimumab therapy was effective in modifying disease activity and reducing proinflammatory and bone remodelling cascades.