Objective:Cartilaginous tumors of the larynx are rare, representing less than 1% of all laryngeal tumors. Chondromas are benign mesenchymal tumors characterized by a slow-paced growth, primarily originated in the cricoid cartilage, followed by the thyroid, arytenoid, and epiglottic cartilages. This scoping review aims to understand the extent of evidence on the epidemiology, clinical characteristics, morbidity, and recurrence of the laryngeal chondroma (LC).Data sources:MEDLINE (Ovid), Embase (Elsevier), Web of Science (Clarivate), Cochrane Central Register of Controlled Trials and Systematic Reviews, Lilacs, Scopus, and Google Scholar databases.Review methods:The scoping review was conducted from 1816 to 2023, for observational studies describing LC. Titles and abstracts were screened for relevance, followed by an evaluation of the full text for eligibility. The data were collected from the qualifying articles, and a narrative summary of the outcomes was prepared.Results:One hundred and nineteen studies met the inclusion criteria. Ninety-four case reports, 22 case series, and 3 cohorts. Two hundred and four participants with a diagnosis of LC were described. Male:female ratio was 2.8:1. The most common localization was the cricoid (113; 47.08%), followed by the thyroid (45; 18.75%), and the arytenoid cartilage (27; 11.25%). Dyspnea (78.85%) and hoarseness (74.28%) were the most reported symptoms. The recurrence rate was 11.25%, and complications were uncommon following the resection.Conclusion:This scoping review found a low-frequency rate over all the cartilaginous laryngeal tumors. Most patients were treated with resection, with a low rate of malignancy conversion. This population has low attributable mortality, morbidity, and recurrence according to the current literature.

Approximately 5 million dengue virus-infected patients progress to a potentially life-threatening severe dengue (SD) infection annually. To identify the immune features and temporal dynamics underlying SD progression, we performed deep immune profiling by mass cytometry of PBMCs collected longitudinally from SD progressors (SDp) and uncomplicated dengue (D) patients. While D is characterized by early activation of innate immune responses, in SDp there is rapid expansion and activation of IgG-secreting plasma cells and memory and regulatory T cells. Concurrently, SDp, particularly children, demonstrate increased proinflammatory NK cells, inadequate expansion of CD16+ monocytes, and high expression of the FcγR CD64 on myeloid cells, yet a signature of diminished antigen presentation. Syndrome-specific determinants include suppressed dendritic cell abundance in shock/hemorrhage versus enriched plasma cell expansion in organ impairment. This study reveals uncoordinated immune responses in SDp and provides insights into SD pathogenesis in humans with potential implications for prediction and treatment.

Severe dengue (SD) is a major cause of morbidity and mortality. To define dengue virus (DENV) target cells and immunological hallmarks of SD progression in children's blood, we integrated two single-cell approaches capturing cellular and viral elements: virus-inclusive single-cell RNA sequencing (viscRNA-Seq 2) and targeted proteomics with secretome analysis and functional assays. Beyond myeloid cells, in natural infection, B cells harbor replicating DENV capable of infecting permissive cells. Alterations in cell type abundance, gene and protein expression and secretion as well as cell-cell communications point towards increased immune cell migration and inflammation in SD progressors. Concurrently, antigen-presenting cells from SD progressors demonstrate intact uptake yet impaired interferon response and antigen processing and presentation signatures, which are partly modulated by DENV. Increased activation, regulation and exhaustion of effector responses and expansion of HLA-DR-expressing adaptive-like NK cells also characterize SD progressors. These findings reveal DENV target cells in human blood and provide insight into SD pathogenesis beyond antibody-mediated enhancement.

To define the clinical and anatomical factors associated with dyskinesias following thalamic infarction, we performed neurological examination and three-dimensional brain magnetic resonance imaging for 23 patients with thalamic infarction. We measured the total volumes and the largest diameters of the lesions on axial and coronal images. Using the atlas of human thalamus, we investigated the damaged thalamic nuclei. We compared the means of the volumes and the largest diameters of the lesions, and the frequencies of damaged thalamic nuclei between patients with and without thalamic dyskinesias. Seven (two pseudochoreoathetosis and five dystonia) of the 23 patients with thalamic infarction developed dyskinesias. No specific neurological deficits at the onset of stroke predicted the development of dyskinesias. The mean volume of the lesions of patients with dyskinesias (739 mm(3)) was significantly larger than that of those without dyskiensias (92.9 mm(3)). The means of the largest axial (11.6 mm) and coronal (10.8 mm) diameters were significantly larger in patients with dyskinesias, compared to those (axial, 7.1 mm; coronal, 6.4 mm) of patients without dyskinesias. Patients with dyskinesias had damage in the centromedian (CM) thalamic nucleus more frequently compared to those without dyskinesias. Patients with a large thalamic infarction involving the CM nucleus are more likely to develop dyskinesias.

AbstractSevere dengue (SD) is a major cause of morbidity and mortality impacting approximately 5 million of the 400 million people infected with dengue virus (DENV) annually. To define DENV target cells and immunological hallmarks of SD progression in children’s blood, we integrated virus-inclusive single cell RNA-Seq 2 (viscRNA-Seq 2) with functional assays. Beyond myeloid cells, in natural infection, B cells harbor replicating DENV capable of infecting permissive cells. Alterations in cell type abundance, gene and protein expression and secretion, and cell-cell communications point towards increased migration and inflammation in SD progressors (SDp). Concurrently, antigen presenting cells from SDp demonstrate intact uptake, yet impaired interferon responses and antigen presentation, in part DENV-modulated. Increased activation, regulation, and exhaustion of effector responses and expansion of HLA-DR-expressing, possibly compensatory, adaptive-like NK cells also characterize SDp. These findings reveal DENV target cells in the human blood and provide insight into SD pathogenesis beyond antibody-mediated enhancement.

IntroductionFlaviviridae family belongs to the Spondweni serocomplex, which is mainly transmitted by vectors from the Aedes genus. Zika virus (ZIKV) is part of this genus. It was initially reported in Brazil in December 2014 as an unknown acute generalized exanthematous disease and was subsequently identified as ZIKV infection. ZIKV became widespread all over Brazil and was linked with potential cases of microcephaly.Case reportWe report a case of a 28-year-old Colombian woman, who came to the Obstetric Department with an assumed conglomerate of fetal abnormalities detected via ultrasonography, which was performed at 29.5 weeks of gestation. The patient presented with multiple abnormalities, which range from a suggested Arnold–Chiari malformation, compromising the lateral and third ventricles, liver calcifications, bilateral pyelocalic dilatations, other brain anomalies, and microcephaly. At 12 weeks of gestation, the vertical transmission of ZIKV was suspected. At 38.6 weeks of gestation, the newborn was delivered, with the weight in the 10th percentile (3,180 g), height in the 10th percentile (48 cm), and cephalic circumference under the 2nd percentile (31 cm). Due to the physical findings, brain magnetic resonance imaging (MRI) was performed, revealing a small and deviated brain stem, narrowing of the posterior fossa, a giant posterior fossa cyst with ventricular dilatation, a severe cortical and white matter thinning, cerebellar vermis with hypoplasia, and superior and lateral displacement of the cerebellum. In addition, hydrocephalus was displayed by the axial sequence, and the cerebral cortex was also compromised with lissencephaly. Schizencephaly was found with left frontal open-lip, and no intracranial calcifications were found. Two novel heterozygous nonsense mutations were identified using whole-exome sequencing, and both are located in exon 8 under the affection of ZIKV congenital syndrome (CZS) that produced a premature stop codon resulting in the truncation of the cyclin-dependent kinase 5 regulatory subunit-associated protein 2 (CDK5RAP2) protein.ConclusionWe used molecular and microbiological assessments to report the initial case of vertically transmitted ZIKV infection with congenital syndrome associated with a neurological syndrome, where a mutation in the CDK5RAP2 gene was also identified. The CDK5RAP2 gene encodes a pericentriolar protein that intervenes in microtubule nucleation and centriole attachment. Diallelic mutation has previously been associated with primary microcephaly.

BACKGROUND:Vector-borne diseases are a public health problem in Colombia, where dengue virus infection is hyperendemic. The introduction of other arboviruses, such as chikungunya and Zika in the last three years, has aggravated the situation. Mobile health (mHealth) offers new strategies for strengthening health care and surveillance systems promoting the collection, delivery, and access of health information to professionals, researchers, and patients. Assessing mobile application performance has been a challenge in low- and middle-income countries due to the difficulty of implementing these technologies in different clinical settings. In this study, we evaluate the usability and acceptability of a mobile application, FeverDX, as a support tool in the management of patients with febrile syndrome and suspected arboviruses infection by general practitioners from Colombia. METHODS:A pilot implementation study was conducted to evaluate the usability and acceptability of FeverDX using the modified version of the Mobile Application Rating Scale (uMARS). The evaluation form included 25 questions regarding quantity and quality of information, engagement, functionality, aesthetics, impact, and acceptability by healthcare workers. Each item uses a 5-point scale (1-Inadequate, 2-Poor, 3-Acceptable, 4-Good, 5-Excellent). A global score was obtained for the evaluation form test by determining the median scores of each subsection. A descriptive statistical analysis of the data obtained was performed. RESULTS:Between December 2016 and January 2017, a total of 20 general practitioners from the Emergency room and hospitalization areas evaluated FeverDX. Less than half (9/20) of the evaluators had a comprehensive knowledge of the Colombian Ministry of Health's guidelines for the diagnosis and management of arboviruses, and evaluators partially (4/9) or completely (5/9) agreed that the content of the application follows the management guidelines. On uMARS scale, FeverDX excelled regarding impact (median 5; IQR = 5-5), functionality (median 5; IQR = 4.8-5), and information and scientific basis (median 4; IQR = 4-4). FeverDX scored well regarding user feedback (median 4; IQR = 4-4.5), design and aesthetics (median 4; IQR = 4-4.3), and subjective assessment of quality (median 4.5; IQR = 4.3-4.8). CONCLUSIONS:FeverDX, a mobile application, is a novel mHealth strategy to strengthen care processes and facilitate the detection and reporting of notifiable surveillance diseases. It could improve adherence to clinical practice guidelines for the management and prevention of prevalent diseases as arboviruses in healthcare settings. Although this pilot study used a small sample size, FeverDx performed adequately in a simulated emergency consultation. Further implementation studies are needed to increase the reliability of mHealth technologies in different scenarios.

Introduction: Aeromonas species are renowned enteric pathogens with virulence determinants linked to human diseases, such as gastroenteritis, skin, soft-tissue and muscle infections, and septicemia. A recent concern of resistance in this organism has emerged, especially the presence carbapenemases. Herein we describe a case series of emerging carbapenem-resistant Aeromonas species infection in our hospital in Cali, Colombia. Materials and methods: Cases from 2012 to 2018 are reported. Clinical data was abstracted from the clinical charts and laboratory information. Phenotypic detection of resistance was identified using the VITEK (R) 2 system (BioMerieux) and broth microdilution MicroScan WalkAway plus System (Beckman Coulter). CARBA NP-test and multiplex qPCR assay was performed in 11 isolates to identify genes encoding carbapenemases (bla(KPC), bla(VIM), bla(IMP) and bla(NDM)). Results: 21 cases of Aeromonas infection in hospitalized patients with phenotypic resistance to carbapenems were studied. The median age was 50 years, 55% (12/21) were male, and 67% (14/21) were healthcare-associated infections (HAI). Aeromonas hydrophila was the most common species (19/21). Forty-three percent (9/21) of the patients were immunocompromised. The mortality was 33% (7/21), and in patients with bacteremia was 100%. Most patients received empirical treatment with meropenem and failed to this treatment. PCR amplification tests showed negative results for the carbapenemases analyzed. Conclusion: Emerging phenotypic carbapenem-resistant infection has been seen in our hospital, most as HAI. High mortality was found, especially in immunocompromised patients and in those who failled empirical treatment with carbapenems. As the main carbapenemases tested were negative, carbapenem-resistant could be attributed to an intrinsic metallo-beta-lactamase, CphA encoded by the cphA gene, possible hyperproduction of ampC beta-lactamase and/or porins expression. (C) 2019 Sociedade Brasileira de Infectologia. Published by Elsevier Espana, S.L.U.

Dengue fever is the most prevalent arbovirus infection among humans, and tropical regions are hyperendemic for this infection. The number of solid organ transplant recipients is continuously increasing, and there are few data regarding the clinical course and outcomes of dengue infection among this population. We report on a retrospective case series of solid organ transplant recipients with dengue virus infection from 2001 to 2018 at Fundación Valle del Lili in Cali, Colombia. A total of 20 patients were included. The median age was 50.5 years (interquartile range [IQR] = 31-63.5 years) and 65% were female. Regarding the clinical course, 75% of patients had at least one warning sign, 45% were managed in the intensive care unit, and 30% had severe dengue. The median of time from transplant and dengue infection was 27.6 months (IQR = 3.82-59.12 months), and three patients had the disease in the first month after the transplant. All patients were discharged, and none of them had graft rejection. Dengue is an endemic disease in our region and represents a threat among solid organ transplantation recipients. All patients had a full recovery after the infection, suggesting that timely and effective management of patients and the access to high-complexity services could prevent fatal cases.

There is a need to identify biomarkers predictive of severe dengue. Single-cohort transcriptomics has not yielded generalizable results or parsimonious, predictive gene sets. We analyzed blood samples of dengue patients from seven gene expression datasets (446 samples, five countries) using an integrated multi-cohort analysis framework and identified a 20-gene set that predicts progression to severe dengue. We validated the predictive power of this 20-gene set in three retrospective dengue datasets (84 samples, three countries) and a prospective Colombia cohort (34 patients), with an area under the receiver operating characteristic curve of 0.89, 100% sensitivity, and 76% specificity. The 20-gene dengue severity scores declined during the disease course, suggesting an infection-triggered host response. This 20-gene set is strongly associated with the progression to severe dengue and represents a predictive signature, generalizable across ages, host genetic factors, and virus strains, with potential implications for the development of a host response-based dengue prognostic assay.

Dengue virus (DENV) infection can result in severe complications. Yet, the understanding of the molecular correlates of severity is limited, partly due to difficulties in defining the peripheral blood mononuclear cells (PBMCs) that are associated with DENV in vivo. Additionally, there are currently no biomarkers predictive of progression to severe dengue (SD). Bulk transcriptomics data are difficult to interpret because blood consists of multiple cell types that may react differently to infection. Here we applied virus-inclusive single cell RNA-seq approach (viscRNA-Seq) to profile transcriptomes of thousands of single PBMCs derived early in the course of disease from six dengue patients and four healthy controls, and to characterize distinct DENV-associated leukocytes. Multiple genes, particularly interferon response genes, were upregulated in a cell-specific manner prior to progression to SD. Expression of MX2 in naive B cells and CD163 in CD14 + CD16 + monocytes was predictive of SD. The majority of DENV-associated cells in the blood of two patients who progressed to SD were naive IgM B cells expressing the CD69 and CXCR4 receptors and antiviral genes, followed by monocytes. Bystander uninfected B cells also demonstrated immune activation, and plasmablasts from two patients exhibited antibody lineages with convergently hypermutated heavy chain sequences. Lastly, assembly of the DENV genome revealed diversity at unexpected genomic sites. This study presents a multi-faceted molecular elucidation of natural dengue infection in humans and proposes biomarkers for prediction of SD, with implications for profiling any tissue and viral infection, and for the development of a dengue prognostic assay. Significance A fraction of the 400 million people infected with dengue annually progresses to severe dengue (SD). Yet, there are currently no biomarkers to effectively predict disease progression. We profiled the landscape of host transcripts and viral RNA in thousands of single blood cells from dengue patients prior to progressing to SD. We discovered cell-type specific immune activation and candidate predictive biomarkers. We also revealed preferential virus association with specific cell populations, particularly naive B cells and monocytes. We then explored immune activation of bystander cells, clonality and somatic evolution of adaptive immune repertoires, and viral genomics. This multi-faceted approach could advance understanding of pathogenesis of any viral infection, map an atlas of infected cells and promote the development of prognostics.

Abstract Background There is an urgent need for the identification of biomarkers predictive of severe dengue. Single cohort transcriptomic studies have not yielded a parsimonious gene set predictive of severe dengue. We hypothesized that integration of gene expression data from heterogeneous patient populations with dengue infection would yield a set of conserved genes that is predictive of severe dengue and generalizable across cohorts. Methods Ten dengue gene expression datasets were identified in publicly available microarray repositories. A novel integrated multicohort platform was used to detect differentially expressed gene transcripts between uncomplicated and severe dengue patients and validate the identified putative signature in silico and prospectively in a new cohort of 34 dengue patients in Colombia. Dengue diagnosis was made by NS1 antigen and anti-DENV IgM antibody and confirmed by RT-PCR assays, ELISA, and IgG avidity measurements. The expression level of the signature genes was measured via microfluidic qRT-PCR assays in blood samples collected longitudinally during the course of illness. Results Using the multicohort analysis to analyze 446 peripheral blood samples of patients with dengue infection from 7 publicly available gene expression datasets, we identified a 20 gene set that predicts the development of severe dengue. We in silico validated the diagnostic power of this gene set to separate severe dengue from dengue with or without warning signs in 3 independent datasets composed of 84 samples with a global area under the ROC curve (AUC) of 0.80 [95% CI 0.68–0.88]. We prospectively validated the gene set in a new cohort composed of 34 dengue patients from Colombia with an AUC of 0.89 [95% CI 0.81–0.97]. The severity scores measured in patients with severe dengue progressively declined in longitudinal samples. Conclusion Our data indicate that the identified 20 gene signature predicts the development of severe dengue in patients prior to its onset and suggest that dengue infection itself triggers this host response. These findings may provide new insight into the pathogenesis of severe dengue and have implications for the development of a prognostic molecular assay to identify patients at risk to develop severe dengue. Disclosures T. E. Sweeney, Inflammatix, Inc.: Employee and Shareholder, Salary. P. Khatri, Inflammatix, Inc: Scientific Advisor and Shareholder, Licensing agreement or royalty.

Abstract Background Severe microcirculatory changes are involved in the pathophysiological mechanisms that lead to irreversible final stages of dengue shock. We report our experience of the evaluation of sublingual microcirculation in adult patients with severe dengue Methods Adults patients with severe dengue (by WHO 2009 criteria) were included. Dengue diagnostics was made by positive serology for IgM / IgG, antigen NS1 or PCR. Sublingual Microcirculation (SM) was evaluated by Sidestream Dark Field imaging. Microvascular flow index (MFI), proportion of small-perfused vessels (%SVP), heterogeneity index (HI) and Total Vascular Density were calculated. All patients received Fluids Challenge (FC) at hospital admission. Results SM was assessed in 10 patients. The median age was 65 years [IQR: 34–70], 60% were male. Eight patients were admitted to the ICU, of which 63% required invasive ventilatory and vasoactive support. One patient died. After the fluid challenge, the median of the %SVP was 94 [IR: 97 – 77], the median of the MFI was 2.82 [IR: 2, 85 – 2, 14]. There were not significant differences in %SVP and MFI among the patients who survived. In the deceased patient, the %SVP with continuous flow was 59, 18% and the MFI was 1, 45; these values were significantly decreased compared with patients who survived. A significant negative correlation between hematocrit and %SVP, and MFI was found. Conclusion Initial fluid challenge, that identifies and treats volume depletion, could correct microcirculation abnormalities evaluated by SDF imaging. However, in the patient who did not respond to this challenge, significant alterations of the MFI and the %SVP were evidenced. There is a need for more studies to improve our understanding of the role of microcirculation evaluation in these patients. Disclosures All authors: No reported disclosures.